hydrocodone/ibuprofen (Rx)

Brand and Other Names:Ibudone, Reprexain, more...Vicoprofen

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

hydrocodone/ibuprofen

tablet: Schedule II

  • 5mg/200mg
  • 7.5mg/200mg
  • 10mg/200mg

Analgesia

Short-term (generally less than 10 days) management of acute pain

Lowest effective dose for the shortest duration consistent with individual patient treatment goals

Usual dose: 5-7.5 mg/200 mg PO q4-6 hr PRN; not to exceed 5 tabs/24hr

Renal Impairment

Not recommended in patients with advanced renal disease

Renal disease or impairment; increased risk of renal toxicity and injury may occur

Administration

Not indicated for the treatment of chronic conditions such as osteoarthritis or rheumatoid arthritis

Extra caution and reduced dosages should be used when treating the elderly

Elderly or debilitated patients may experience increased risk of gastrointestinal injury, including fatal events; increased risk of renal toxicity and injury; respiratory depression

Dosage Forms & Strengths

hydrocodone/ibuprofen

tablet: Schedule II

  • 5mg/200mg
  • 7.5mg/200mg
  • 10mg/200mg

Analgesia

<16 years: Safety and efficacy not established

≥16 years

  • Short-term (generally <10 days) management of acute pain
  • Lowest effective dose for the shortest duration consistent with individual patient treatment goals
  • Usual dose: 5-7.5 mg/200 mg PO q4-6 hr PRN; not to exceed 5 tabs/24hr
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Interactions

Interaction Checker

and hydrocodone/ibuprofen

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            Contraindicated (1)

            • alvimopan

              alvimopan, hydrocodone. receptor binding competition. Contraindicated. Alvimopan is contraindicated in opioid tolerant patients (ie, those who have taken therapeutic doses of opioids for >7 consecutive days immediately prior to taking alvimopan). Patients recently exposed to opioids are expected to be more sensitive to the effects of alvimopan and therefore may experience abdominal pain, nausea and vomiting, and diarrhea. No significant interaction is expected with concurrent use of opioid analgesics and alvimopan in patients who received opioid analgesics for 7 or fewer consecutive days prior to alvimopan.

            Serious - Use Alternative (154)

            • acrivastine

              acrivastine and hydrocodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • alfentanil

              hydrocodone, alfentanil. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • alprazolam

              hydrocodone, alprazolam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • aminolevulinic acid oral

              aminolevulinic acid oral, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

            • aminolevulinic acid topical

              ibuprofen, aminolevulinic acid topical. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

            • amisulpride

              amisulpride and hydrocodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • amobarbital

              hydrocodone, amobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

              amobarbital will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • apixaban

              ibuprofen and apixaban both increase anticoagulation. Avoid or Use Alternate Drug.

            • arbaclofen

              hydrocodone, arbaclofen. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • aripiprazole

              hydrocodone, aripiprazole. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • asenapine

              hydrocodone, asenapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • asenapine transdermal

              asenapine transdermal and hydrocodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • aspirin

              ibuprofen decreases effects of aspirin by Other (see comment). Avoid or Use Alternate Drug. Comment: Ibuprofen decreases the antiplatelet effects of low-dose aspirin by blocking the active site of platelet cyclooxygenase. Administer ibuprofen 8 h before aspirin or at least 2-4 h after aspirin. The effect of other NSAIDs on aspirin is not established.

              ibuprofen increases toxicity of aspirin by anticoagulation. Avoid or Use Alternate Drug. increases risk of bleeding.

            • aspirin rectal

              ibuprofen decreases effects of aspirin rectal by Other (see comment). Avoid or Use Alternate Drug. Comment: Ibuprofen decreases the antiplatelet effects of aspirin by blocking the active site of platelet cyclooxygenase. The effect of other NSAIDs on aspirin is not established.

            • aspirin/citric acid/sodium bicarbonate

              ibuprofen decreases effects of aspirin/citric acid/sodium bicarbonate by Other (see comment). Avoid or Use Alternate Drug. Comment: Ibuprofen decreases the antiplatelet effects of aspirin by blocking the active site of platelet cyclooxygenase. The effect of other NSAIDs on aspirin is not established.

            • atracurium

              hydrocodone, atracurium. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • avapritinib

              avapritinib and hydrocodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • baclofen

              hydrocodone, baclofen. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • benazepril

              ibuprofen, benazepril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, hydrocodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

              benzhydrocodone/acetaminophen and hydrocodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • bremelanotide

              bremelanotide will decrease the level or effect of hydrocodone by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

            • brexpiprazole

              brexpiprazole and hydrocodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • brimonidine

              brimonidine and hydrocodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • brivaracetam

              brivaracetam and hydrocodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • buprenorphine

              buprenorphine decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients. .

              hydrocodone, buprenorphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • buprenorphine buccal

              buprenorphine buccal decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients. .

            • buprenorphine subdermal implant

              buprenorphine subdermal implant decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients. .

              buprenorphine subdermal implant and hydrocodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • buprenorphine transdermal

              buprenorphine transdermal decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients. .

              hydrocodone, buprenorphine transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

              buprenorphine transdermal and hydrocodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • buprenorphine, long-acting injection

              buprenorphine, long-acting injection decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients. .

              buprenorphine, long-acting injection and hydrocodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • buspirone

              hydrocodone, buspirone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • butabarbital

              hydrocodone, butabarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • butalbital

              hydrocodone, butalbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • butorphanol

              butorphanol decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients.

              hydrocodone, butorphanol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • calcium/magnesium/potassium/sodium oxybates

              hydrocodone, calcium/magnesium/potassium/sodium oxybates. Either increases levels of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • captopril

              ibuprofen, captopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • cariprazine

              hydrocodone, cariprazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • carisoprodol

              hydrocodone, carisoprodol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • chloral hydrate

              hydrocodone, chloral hydrate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • chlordiazepoxide

              hydrocodone, chlordiazepoxide. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • chlorpromazine

              hydrocodone, chlorpromazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • chlorzoxazone

              hydrocodone, chlorzoxazone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • cisatracurium

              hydrocodone, cisatracurium. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • clonazepam

              hydrocodone, clonazepam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • clonidine

              clonidine, hydrocodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

            • clorazepate

              hydrocodone, clorazepate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • clozapine

              hydrocodone, clozapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • codeine

              hydrocodone, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • cyclobenzaprine

              hydrocodone, cyclobenzaprine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • dantrolene

              hydrocodone, dantrolene. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • desflurane

              hydrocodone, desflurane. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • dexmedetomidine

              hydrocodone, dexmedetomidine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • diazepam

              hydrocodone, diazepam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • diazepam intranasal

              diazepam intranasal, hydrocodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • doxylamine

              hydrocodone, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • enalapril

              ibuprofen, enalapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • erdafitinib

              ibuprofen will increase the level or effect of erdafitinib by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration with strong CYP2C9 inhibitors, monitor closely for adverse reactions and consider decreasing dose accordingly. If strong CYP2C9 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.

            • estazolam

              hydrocodone, estazolam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • eszopiclone

              hydrocodone, eszopiclone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • ethanol

              hydrocodone, ethanol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • etomidate

              hydrocodone, etomidate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • fentanyl

              hydrocodone, fentanyl. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • fentanyl intranasal

              hydrocodone, fentanyl intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • fentanyl transdermal

              hydrocodone, fentanyl transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • fentanyl transmucosal

              hydrocodone, fentanyl transmucosal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • fexinidazole

              fexinidazole will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fluphenazine

              hydrocodone, fluphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • flurazepam

              hydrocodone, flurazepam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • fosinopril

              ibuprofen, fosinopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • haloperidol

              hydrocodone, haloperidol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • hydromorphone

              hydrocodone, hydromorphone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • iloperidone

              hydrocodone, iloperidone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • isocarboxazid

              isocarboxazid increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

            • isoflurane

              hydrocodone, isoflurane. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • ivosidenib

              ivosidenib will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • ketamine

              hydrocodone, ketamine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • ketorolac

              ibuprofen, ketorolac. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.

            • ketorolac intranasal

              ibuprofen, ketorolac intranasal. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.

            • levorphanol

              hydrocodone, levorphanol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • linezolid

              linezolid increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.

            • lisinopril

              ibuprofen, lisinopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • lorazepam

              hydrocodone, lorazepam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • loxapine

              hydrocodone, loxapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • loxapine inhaled

              hydrocodone, loxapine inhaled. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • lurasidone

              hydrocodone, lurasidone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • meperidine

              hydrocodone, meperidine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • meprobamate

              hydrocodone, meprobamate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • metaxalone

              hydrocodone, metaxalone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • methadone

              hydrocodone, methadone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • methocarbamol

              hydrocodone, methocarbamol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • methohexital

              hydrocodone, methohexital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • methotrexate

              ibuprofen increases levels of methotrexate by decreasing renal clearance. Avoid or Use Alternate Drug. Concomitant administration of NSAIDs with high dose methotrexate has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and GI toxicity. NSAIDs may reduce tubular secretion of methotrexate and enhance toxicity. .

            • methyl aminolevulinate

              ibuprofen, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

            • methylene blue

              methylene blue increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

            • metoclopramide intranasal

              hydrocodone, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

            • midazolam

              hydrocodone, midazolam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • moexipril

              ibuprofen, moexipril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • molindone

              hydrocodone, molindone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • morphine

              hydrocodone, morphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • nalbuphine

              nalbuphine decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients.

              hydrocodone, nalbuphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • naproxen

              ibuprofen will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Avoid or Use Alternate Drug. Therapeutic duplication

              ibuprofen and naproxen both increase anticoagulation. Avoid or Use Alternate Drug. Therapeutic duplication

              ibuprofen and naproxen both increase serum potassium. Avoid or Use Alternate Drug. Therapeutic duplication

            • olanzapine

              hydrocodone, olanzapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • olopatadine intranasal

              hydrocodone and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • orphenadrine

              hydrocodone, orphenadrine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • oxaprozin

              ibuprofen will increase the level or effect of oxaprozin by acidic (anionic) drug competition for renal tubular clearance. Avoid or Use Alternate Drug. Therapeutic duplication

              ibuprofen and oxaprozin both increase anticoagulation. Avoid or Use Alternate Drug. Therapeutic duplication

              ibuprofen and oxaprozin both increase serum potassium. Avoid or Use Alternate Drug. Therapeutic duplication

            • oxazepam

              hydrocodone, oxazepam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • oxycodone

              hydrocodone, oxycodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • oxymorphone

              hydrocodone, oxymorphone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • ozanimod

              ozanimod and hydrocodone both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

            • paliperidone

              hydrocodone, paliperidone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • pancuronium

              hydrocodone, pancuronium. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • pemetrexed

              ibuprofen increases levels of pemetrexed by unspecified interaction mechanism. Avoid or Use Alternate Drug. Especially in pts. w/mild moderate renal insufficiency. D/C NSAIDs 2 5 d before and 2 d after pemetrexed administration.

            • pentazocine

              pentazocine decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients.

              hydrocodone, pentazocine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • pentobarbital

              hydrocodone, pentobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • perindopril

              ibuprofen, perindopril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • perphenazine

              hydrocodone, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • pexidartinib

              ibuprofen and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

            • phenelzine

              phenelzine increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

            • phenobarbital

              hydrocodone, phenobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • pimavanserin

              hydrocodone, pimavanserin. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • pimozide

              hydrocodone, pimozide. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • pretomanid

              ibuprofen, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

            • primidone

              hydrocodone, primidone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • procarbazine

              procarbazine increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

            • prochlorperazine

              hydrocodone, prochlorperazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • propofol

              hydrocodone, propofol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • quazepam

              hydrocodone, quazepam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • quetiapine

              hydrocodone, quetiapine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • quinapril

              ibuprofen, quinapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • ramelteon

              hydrocodone, ramelteon. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • ramipril

              ibuprofen, ramipril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • rasagiline

              rasagiline increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

            • remifentanil

              hydrocodone, remifentanil. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • risperidone

              hydrocodone, risperidone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • rocuronium

              hydrocodone, rocuronium. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • secobarbital

              hydrocodone, secobarbital. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • selegiline

              selegiline increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

            • selegiline transdermal

              selegiline transdermal increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

            • selinexor

              selinexor, hydrocodone. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

            • sevoflurane

              hydrocodone, sevoflurane. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • siponimod

              ibuprofen will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

            • sodium oxybate

              hydrocodone, sodium oxybate. Either increases levels of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • succinylcholine

              hydrocodone, succinylcholine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • sufentanil

              hydrocodone, sufentanil. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • sufentanil SL

              hydrocodone, sufentanil SL. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

              sufentanil SL, hydrocodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • suvorexant

              hydrocodone, suvorexant. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • tacrolimus

              ibuprofen, tacrolimus. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Concomitant administration increases risk of nephrotoxicity.

            • tapentadol

              hydrocodone, tapentadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • tasimelteon

              hydrocodone, tasimelteon. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • temazepam

              hydrocodone, temazepam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • thioridazine

              hydrocodone, thioridazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

            • thiothixene

              hydrocodone, thiothixene. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • tramadol

              tramadol, hydrocodone. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

              hydrocodone, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • trandolapril

              ibuprofen, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • tranylcypromine

              tranylcypromine increases toxicity of hydrocodone by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

            Monitor Closely (374)

            • acebutolol

              acebutolol and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of acebutolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • aceclofenac

              aceclofenac and ibuprofen both increase anticoagulation. Use Caution/Monitor.

              aceclofenac and ibuprofen both increase serum potassium. Use Caution/Monitor.

            • acemetacin

              acemetacin and ibuprofen both increase anticoagulation. Use Caution/Monitor.

              acemetacin and ibuprofen both increase serum potassium. Use Caution/Monitor.

            • agrimony

              ibuprofen and agrimony both increase anticoagulation. Use Caution/Monitor.

            • albuterol

              ibuprofen increases and albuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • alfalfa

              ibuprofen and alfalfa both increase anticoagulation. Use Caution/Monitor.

            • alfuzosin

              ibuprofen decreases effects of alfuzosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • aliskiren

              ibuprofen will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • almotriptan

              hydrocodone, almotriptan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • alosetron

              hydrocodone, alosetron. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • alteplase

              ibuprofen and alteplase both increase anticoagulation. Use Caution/Monitor. Potential for increased risk of bleeding, caution is advised.

            • American ginseng

              ibuprofen and American ginseng both increase anticoagulation. Use Caution/Monitor.

            • amikacin

              ibuprofen increases levels of amikacin by decreasing renal clearance. Use Caution/Monitor. Interaction mainly occurs in preterm infants.

            • amiloride

              amiloride and ibuprofen both increase serum potassium. Modify Therapy/Monitor Closely.

            • amiodarone

              amiodarone will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • amitriptyline

              hydrocodone, amitriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • amoxapine

              hydrocodone, amoxapine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • amphetamine

              hydrocodone, amphetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • antithrombin alfa

              antithrombin alfa and ibuprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • antithrombin III

              antithrombin III and ibuprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • apalutamide

              apalutamide will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • arformoterol

              ibuprofen increases and arformoterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • argatroban

              argatroban and ibuprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • artemether/lumefantrine

              artemether/lumefantrine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • asenapine

              asenapine and hydrocodone both increase sedation. Use Caution/Monitor.

              ibuprofen decreases effects of asenapine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

              asenapine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • aspirin

              aspirin and ibuprofen both increase anticoagulation. Use Caution/Monitor.

              aspirin and ibuprofen both increase serum potassium. Use Caution/Monitor.

            • atazanavir

              atazanavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • aspirin rectal

              aspirin rectal and ibuprofen both increase anticoagulation. Use Caution/Monitor.

              aspirin rectal and ibuprofen both increase serum potassium. Use Caution/Monitor.

            • aspirin/citric acid/sodium bicarbonate

              aspirin/citric acid/sodium bicarbonate and ibuprofen both increase anticoagulation. Use Caution/Monitor.

              aspirin/citric acid/sodium bicarbonate and ibuprofen both increase serum potassium. Use Caution/Monitor.

            • atenolol

              atenolol and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of atenolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • azficel-T

              azficel-T, ibuprofen. Other (see comment). Use Caution/Monitor. Comment: Patients taking NSAIDS may experience increased bruising or bleeding at biopsy and/or injection sites. Concomitant use of NSAIDs is not recommended.

            • azilsartan

              ibuprofen, azilsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              ibuprofen decreases effects of azilsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • belzutifan

              belzutifan will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

            • bemiparin

              bemiparin and ibuprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • benazepril

              benazepril, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • bendroflumethiazide

              ibuprofen increases and bendroflumethiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • betaxolol

              betaxolol and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of betaxolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • betrixaban

              ibuprofen, betrixaban. Either increases levels of the other by anticoagulation. Use Caution/Monitor.

            • bimatoprost

              bimatoprost, ibuprofen. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

            • bisoprolol

              bisoprolol and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of bisoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • bivalirudin

              bivalirudin and ibuprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • bosentan

              bosentan will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • brexanolone

              brexanolone, hydrocodone. Either increases toxicity of the other by sedation. Use Caution/Monitor.

            • budesonide

              ibuprofen, budesonide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • bumetanide

              ibuprofen increases and bumetanide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              ibuprofen decreases effects of bumetanide by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • bupropion

              bupropion will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              hydrocodone, bupropion. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • candesartan

              candesartan and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of candesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              candesartan, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • captopril

              captopril, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • carbamazepine

              carbamazepine will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

              ibuprofen will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor plasma levels when used concomitantly

            • carbenoxolone

              ibuprofen increases and carbenoxolone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • celecoxib

              celecoxib will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • carvedilol

              carvedilol and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of carvedilol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • celecoxib

              celecoxib and ibuprofen both increase anticoagulation. Use Caution/Monitor.

              celecoxib and ibuprofen both increase serum potassium. Use Caution/Monitor.

            • celiprolol

              celiprolol and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of celiprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • cenobamate

              cenobamate will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • ceritinib

              ceritinib will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • chloramphenicol

              chloramphenicol will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • chloroquine

              chloroquine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • chlorothiazide

              ibuprofen increases and chlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • chlorpropamide

              ibuprofen increases effects of chlorpropamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • chlorthalidone

              ibuprofen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • choline magnesium trisalicylate

              ibuprofen and choline magnesium trisalicylate both increase anticoagulation. Use Caution/Monitor.

              ibuprofen and choline magnesium trisalicylate both increase serum potassium. Use Caution/Monitor.

            • cimetidine

              cimetidine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • cinnamon

              ibuprofen and cinnamon both increase anticoagulation. Use Caution/Monitor.

            • ciprofloxacin

              ibuprofen, ciprofloxacin. Other (see comment). Modify Therapy/Monitor Closely. Comment: Mechanism: unknown. Increased risk of CNS stimulation and seizures with high doses of fluoroquinolones.

            • citalopram

              citalopram, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. If possible, avoid concurrent use.

              hydrocodone, citalopram. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • clarithromycin

              clarithromycin will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • clomipramine

              clomipramine, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. Clomipramine inhib. serotonin uptake by platelets.

            • clobazam

              hydrocodone, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

            • clomipramine

              hydrocodone, clomipramine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • clopidogrel

              clopidogrel, ibuprofen. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Clopidogrel and NSAIDs both inhibit platelet aggregation.

            • cobicistat

              cobicistat will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • conivaptan

              conivaptan will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • cordyceps

              ibuprofen and cordyceps both increase anticoagulation. Use Caution/Monitor.

            • cortisone

              ibuprofen, cortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • cyclopenthiazide

              ibuprofen increases and cyclopenthiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • cyclosporine

              ibuprofen, cyclosporine. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis, increasing the risk of nephrotoxicity.

            • dabigatran

              dabigatran and ibuprofen both increase anticoagulation. Use Caution/Monitor. Caution is advised, both drugs have the potential to cause bleeding. Concomitant use may increase risk of bleeding.

            • dabrafenib

              dabrafenib will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • dalteparin

              dalteparin and ibuprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • daridorexant

              hydrocodone and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • darifenacin

              darifenacin will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • darunavir

              darunavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • deferasirox

              deferasirox, ibuprofen. Other (see comment). Use Caution/Monitor. Comment: Combination may increase GI bleeding, ulceration and irritation. Use with caution.

            • defibrotide

              defibrotide increases effects of ibuprofen by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Defibrotide may enhance effects of platelet inhibitors.

            • deflazacort

              ibuprofen, deflazacort. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • desipramine

              hydrocodone, desipramine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • desvenlafaxine

              desvenlafaxine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              hydrocodone, desvenlafaxine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • dexamethasone

              dexamethasone will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

              ibuprofen, dexamethasone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • dextroamphetamine

              hydrocodone, dextroamphetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • dichlorphenamide

              dichlorphenamide, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis.

            • dichlorphenamide

              dichlorphenamide and hydrocodone both decrease serum potassium. Use Caution/Monitor.

            • diclofenac

              diclofenac and ibuprofen both increase anticoagulation. Use Caution/Monitor.

              diclofenac and ibuprofen both increase serum potassium. Use Caution/Monitor.

            • difelikefalin

              difelikefalin and hydrocodone both increase sedation. Use Caution/Monitor.

            • diflunisal

              diflunisal and ibuprofen both increase anticoagulation. Use Caution/Monitor.

              diflunisal and ibuprofen both increase serum potassium. Use Caution/Monitor.

            • digoxin

              ibuprofen and digoxin both increase serum potassium. Use Caution/Monitor.

            • diphenhydramine

              diphenhydramine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • dobutamine

              ibuprofen increases and dobutamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dong quai

              ibuprofen and dong quai both increase anticoagulation. Use Caution/Monitor.

            • dopexamine

              ibuprofen increases and dopexamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • doxazosin

              ibuprofen decreases effects of doxazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • doxepin

              hydrocodone, doxepin. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • dronabinol

              ibuprofen will increase the level or effect of dronabinol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Dronabinol is a CYP2C9 substrate.

            • dronedarone

              dronedarone will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • drospirenone

              drospirenone and ibuprofen both increase serum potassium. Modify Therapy/Monitor Closely.

            • duloxetine

              duloxetine, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

              duloxetine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              hydrocodone, duloxetine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • edoxaban

              edoxaban, ibuprofen. Either increases toxicity of the other by anticoagulation. Modify Therapy/Monitor Closely. Both drugs have the potential to cause bleeding, monitor closely. Promptly evaluate any signs or symptoms of blood loss.

            • efavirenz

              efavirenz will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • efavirenz

              efavirenz will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • elagolix

              elagolix decreases levels of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • eletriptan

              hydrocodone, eletriptan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • eltrombopag

              eltrombopag increases levels of ibuprofen by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.

            • eluxadoline

              ibuprofen increases levels of eluxadoline by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. As a precautionary measure due to incomplete information on the metabolism of eluxadoline, use caution when coadministered with strong CYP2C9/10 inhibitors.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

              elvitegravir/cobicistat/emtricitabine/tenofovir DF, ibuprofen. Either increases toxicity of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine and tenofovir with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • emtricitabine

              emtricitabine, ibuprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • encorafenib

              encorafenib, hydrocodone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • enalapril

              enalapril, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • enoxaparin

              enoxaparin and ibuprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • enzalutamide

              enzalutamide will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • ephedrine

              ibuprofen increases and ephedrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epinephrine

              ibuprofen increases and epinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epinephrine racemic

              ibuprofen increases and epinephrine racemic decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epoprostenol

              ibuprofen and epoprostenol both increase anticoagulation. Use Caution/Monitor.

            • eprosartan

              eprosartan and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of eprosartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              eprosartan, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • escitalopram

              escitalopram, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

              hydrocodone, escitalopram. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • esketamine intranasal

              esketamine intranasal, hydrocodone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

            • esmolol

              esmolol and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of esmolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • ethacrynic acid

              ibuprofen increases and ethacrynic acid decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • etodolac

              etodolac and ibuprofen both increase anticoagulation. Use Caution/Monitor.

              etodolac and ibuprofen both increase serum potassium. Use Caution/Monitor.

            • etravirine

              etravirine will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • fedratinib

              fedratinib will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fennel

              ibuprofen and fennel both increase anticoagulation. Use Caution/Monitor.

            • fenoprofen

              fenoprofen and ibuprofen both increase anticoagulation. Use Caution/Monitor.

              fenoprofen and ibuprofen both increase serum potassium. Use Caution/Monitor.

            • feverfew

              ibuprofen and feverfew both increase anticoagulation. Use Caution/Monitor.

            • fish oil triglycerides

              fish oil triglycerides will increase the level or effect of ibuprofen by anticoagulation. Use Caution/Monitor. Prolonged bleeding reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. Periodically monitor bleeding time in patients receiving fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.

            • flibanserin

              hydrocodone, flibanserin. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • fludrocortisone

              ibuprofen, fludrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • fluoxetine

              fluoxetine, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

              hydrocodone, fluoxetine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

              fluoxetine will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • flurbiprofen

              flurbiprofen and ibuprofen both increase anticoagulation. Use Caution/Monitor.

              flurbiprofen and ibuprofen both increase serum potassium. Use Caution/Monitor.

            • fluvoxamine

              fluvoxamine and hydrocodone both increase serotonin levels. Use Caution/Monitor. If concomitant use warranted, carfully observe patient, particularly during treatment initiation and dose adjustment

            • fluvoxamine

              fluvoxamine, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding; SSRIs inhib. srotonin uptake by platelets.

            • fondaparinux

              fondaparinux and ibuprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • formoterol

              ibuprofen increases and formoterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • forskolin

              ibuprofen and forskolin both increase anticoagulation. Use Caution/Monitor.

            • fosamprenavir

              fosamprenavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • fosinopril

              fosinopril, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • frovatriptan

              hydrocodone, frovatriptan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • furosemide

              ibuprofen increases and furosemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • gabapentin

              gabapentin, hydrocodone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • gabapentin enacarbil

              gabapentin enacarbil, hydrocodone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • ganaxolone

              hydrocodone and ganaxolone both increase sedation. Use Caution/Monitor.

            • garlic

              ibuprofen and garlic both increase anticoagulation. Use Caution/Monitor.

            • gemifloxacin

              gemifloxacin, ibuprofen. Other (see comment). Modify Therapy/Monitor Closely. Comment: Increased risk of CNS stimulation and seizures with high doses of fluoroquinolones.

            • gentamicin

              ibuprofen increases and gentamicin decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ginger

              ibuprofen and ginger both increase anticoagulation. Use Caution/Monitor.

            • ginkgo biloba

              ibuprofen and ginkgo biloba both increase anticoagulation. Use Caution/Monitor.

            • glimepiride

              ibuprofen increases effects of glimepiride by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • glipizide

              ibuprofen increases effects of glipizide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • glyburide

              ibuprofen increases effects of glyburide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

              ibuprofen increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

            • grapefruit

              grapefruit will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • green tea

              green tea, ibuprofen. Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of bleeding.

            • haloperidol

              haloperidol will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • heparin

              heparin and ibuprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • horse chestnut seed

              ibuprofen and horse chestnut seed both increase anticoagulation. Use Caution/Monitor.

            • hydralazine

              ibuprofen decreases effects of hydralazine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • hydrochlorothiazide

              ibuprofen increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • hydrocortisone

              ibuprofen, hydrocortisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • ibrutinib

              ibrutinib will increase the level or effect of ibuprofen by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

            • idelalisib

              idelalisib will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • imatinib

              imatinib, ibuprofen. Either increases toxicity of the other by Other (see comment). Modify Therapy/Monitor Closely. Comment: Imatinib may cause thrombocytopenia; bleeding risk increased when imatinib is coadministered with anticoagulants, NSAIDs, platelet inhibitors, and thrombolytic agents.

              imatinib will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              imatinib will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

              imatinib will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • imipramine

              hydrocodone, imipramine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • indapamide

              ibuprofen increases and indapamide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • indinavir

              indinavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • indomethacin

              ibuprofen and indomethacin both increase anticoagulation. Use Caution/Monitor.

              ibuprofen and indomethacin both increase serum potassium. Use Caution/Monitor.

            • irbesartan

              irbesartan and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of irbesartan by pharmacodynamic antagonism. Use Caution/Monitor. Antihypertensive effect of angiotensin receptor blockers may be attenuated by NSAIDs; monitor renal function and blood pressure periodically.

              irbesartan, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • isoniazid

              isoniazid will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • isoproterenol

              ibuprofen increases and isoproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • istradefylline

              istradefylline will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • ketoconazole

              ketoconazole will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • ketoprofen

              ibuprofen and ketoprofen both increase anticoagulation. Use Caution/Monitor.

              ibuprofen and ketoprofen both increase serum potassium. Use Caution/Monitor.

            • ketorolac

              ibuprofen and ketorolac both increase anticoagulation. Use Caution/Monitor.

              ibuprofen and ketorolac both increase serum potassium. Use Caution/Monitor.

            • ketorolac intranasal

              ibuprofen and ketorolac intranasal both increase anticoagulation. Use Caution/Monitor.

              ibuprofen and ketorolac intranasal both increase serum potassium. Use Caution/Monitor.

            • labetalol

              labetalol and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of labetalol by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs diminish antihypertensive effects of beta-blockers.

            • lacosamide

              ibuprofen increases levels of lacosamide by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Consider decreasing lacosamide dose when coadministered with strong CYP2C9 inhibitors.

            • larotrectinib

              larotrectinib will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lasmiditan

              lasmiditan, hydrocodone. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

            • latanoprost

              latanoprost, ibuprofen. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

            • latanoprostene bunod ophthalmic

              latanoprostene bunod ophthalmic, ibuprofen. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

            • lemborexant

              lemborexant, hydrocodone. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

            • lenacapavir

              lenacapavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

            • lesinurad

              ibuprofen will increase the level or effect of lesinurad by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

            • letermovir

              letermovir increases levels of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression.

            • levalbuterol

              ibuprofen increases and levalbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • levofloxacin

              levofloxacin, ibuprofen. Other (see comment). Modify Therapy/Monitor Closely. Comment: Risk of CNS stimulation/seizure. Mechanism: Displacement of GABA from receptors in brain.

            • levoketoconazole

              levoketoconazole will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • levomilnacipran

              levomilnacipran, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. SNRIs may further impair platelet activity in patients taking antiplatelet or anticoagulant drugs.

              hydrocodone, levomilnacipran. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • lisdexamfetamine

              hydrocodone, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • lisinopril

              lisinopril, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • lithium

              ibuprofen increases levels of lithium by decreasing renal clearance. Use Caution/Monitor.

            • lopinavir

              lopinavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • lorcaserin

              hydrocodone, lorcaserin. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • lorlatinib

              lorlatinib will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lornoxicam

              ibuprofen and lornoxicam both increase anticoagulation. Use Caution/Monitor.

              ibuprofen and lornoxicam both increase serum potassium. Use Caution/Monitor.

            • losartan

              losartan and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of losartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              losartan, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Ibuprofen it a substrate of CYP2C9. Lumacaftor has the potential to induce CYP2C9 substrates.

            • lumefantrine

              lumefantrine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • lurasidone

              lurasidone, hydrocodone. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

            • maprotiline

              hydrocodone, maprotiline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • maraviroc

              maraviroc will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • marijuana

              marijuana will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • meclofenamate

              meclofenamate and ibuprofen both increase anticoagulation. Use Caution/Monitor.

              meclofenamate and ibuprofen both increase serum potassium. Use Caution/Monitor.

            • mefenamic acid

              ibuprofen and mefenamic acid both increase anticoagulation. Use Caution/Monitor.

              ibuprofen and mefenamic acid both increase serum potassium. Use Caution/Monitor.

            • melatonin

              melatonin increases effects of ibuprofen by anticoagulation. Use Caution/Monitor. Melatonin may decrease prothrombin time.

            • meloxicam

              ibuprofen and meloxicam both increase anticoagulation. Use Caution/Monitor.

              ibuprofen and meloxicam both increase serum potassium. Use Caution/Monitor.

            • mesalamine

              mesalamine, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive nephrotoxicity.

            • metaproterenol

              ibuprofen increases and metaproterenol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • methamphetamine

              hydrocodone, methamphetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • methyclothiazide

              ibuprofen increases and methyclothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • methylphenidate

              hydrocodone, methylphenidate. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • methylprednisolone

              ibuprofen, methylprednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • metolazone

              ibuprofen increases and metolazone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • metoprolol

              metoprolol and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of metoprolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • midazolam intranasal

              midazolam intranasal, hydrocodone. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

            • mifepristone

              mifepristone will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • milnacipran

              milnacipran, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

              hydrocodone, milnacipran. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • mipomersen

              mipomersen, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

            • mirtazapine

              hydrocodone, mirtazapine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • mistletoe

              ibuprofen increases and mistletoe decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • mitotane

              mitotane will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • moexipril

              moexipril, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • moxifloxacin

              moxifloxacin, ibuprofen. Other (see comment). Modify Therapy/Monitor Closely. Comment: Increased risk of CNS stimulation and seizures with high doses of fluoroquinolones.

            • moxisylyte

              ibuprofen decreases effects of moxisylyte by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • mycophenolate

              ibuprofen will increase the level or effect of mycophenolate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • nabumetone

              ibuprofen and nabumetone both increase anticoagulation. Use Caution/Monitor.

              ibuprofen and nabumetone both increase serum potassium. Use Caution/Monitor.

            • nadolol

              nadolol and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of nadolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • nafcillin

              nafcillin will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • naratriptan

              hydrocodone, naratriptan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • nebivolol

              nebivolol and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • nefazodone

              nefazodone, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

              nefazodone will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

              hydrocodone, nefazodone. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • nelfinavir

              nelfinavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • nettle

              ibuprofen increases and nettle decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nevirapine

              nevirapine will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • nicardipine

              nicardipine will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • nilotinib

              nilotinib will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • nirmatrelvir/ritonavir

              nirmatrelvir/ritonavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Careful monitoring of hydrocodone therapeutic and adverse effects (including potentially fatal respiratory depression) recommended when coadministered. Reduce hydrocodone dose if necessary.

            • norepinephrine

              ibuprofen increases and norepinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nortriptyline

              hydrocodone, nortriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • oliceridine

              oliceridine, hydrocodone. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • olmesartan

              olmesartan and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of olmesartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              olmesartan, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • ospemifene

              ibuprofen increases levels of ospemifene by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              ibuprofen, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • panax ginseng

              ibuprofen and panax ginseng both increase anticoagulation. Use Caution/Monitor.

            • parecoxib

              ibuprofen and parecoxib both increase serum potassium. Use Caution/Monitor.

              parecoxib will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              ibuprofen and parecoxib both increase anticoagulation. Use Caution/Monitor.

            • paroxetine

              paroxetine, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

              hydrocodone, paroxetine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

              paroxetine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • pau d'arco

              ibuprofen and pau d'arco both increase anticoagulation. Use Caution/Monitor.

            • pegvisomant

              hydrocodone will decrease the level or effect of pegvisomant by unknown mechanism. Use Caution/Monitor. Prescribing information describes higher pegvisomant doses are required to control insulinlike growth factor levels when coadministered with opioids.

            • pegaspargase

              pegaspargase increases effects of ibuprofen by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.

            • peginterferon alfa 2b

              peginterferon alfa 2b decreases levels of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. When patients are administered peginterferon alpha-2b with CYP2C9 substrates, the therapeutic effect of these drugs may be altered.

            • penbutolol

              penbutolol and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of penbutolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • pentobarbital

              pentobarbital will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • perindopril

              perindopril, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • perphenazine

              perphenazine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • phenindione

              phenindione and ibuprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • phenobarbital

              phenobarbital will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • phenoxybenzamine

              ibuprofen decreases effects of phenoxybenzamine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • phentolamine

              ibuprofen decreases effects of phentolamine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • phenytoin

              phenytoin will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression.

            • phytoestrogens

              ibuprofen and phytoestrogens both increase anticoagulation. Use Caution/Monitor.

            • pindolol

              pindolol and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of pindolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • pirbuterol

              ibuprofen increases and pirbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • piroxicam

              ibuprofen and piroxicam both increase anticoagulation. Use Caution/Monitor.

              ibuprofen and piroxicam both increase serum potassium. Use Caution/Monitor.

            • pivmecillinam

              pivmecillinam, ibuprofen. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

              pivmecillinam, ibuprofen. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • posaconazole

              posaconazole will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • potassium acid phosphate

              ibuprofen and potassium acid phosphate both increase serum potassium. Modify Therapy/Monitor Closely.

            • potassium chloride

              ibuprofen and potassium chloride both increase serum potassium. Modify Therapy/Monitor Closely.

            • potassium citrate

              ibuprofen and potassium citrate both increase serum potassium. Modify Therapy/Monitor Closely.

            • potassium iodide

              potassium iodide and ibuprofen both increase serum potassium. Use Caution/Monitor.

            • pralatrexate

              ibuprofen increases levels of pralatrexate by decreasing renal clearance. Use Caution/Monitor. NSAIDs may delay pralatrexate clearance, increasing drug exposure. Adjust the pralatrexate dose as needed.

            • prasugrel

              ibuprofen, prasugrel. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Chronic use of NSAIDs with prasugrel may increase bleeding risk.

            • prazosin

              ibuprofen decreases effects of prazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • prednisolone

              ibuprofen, prednisolone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • prednisone

              ibuprofen, prednisone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of GI ulceration.

            • pregabalin

              pregabalin, hydrocodone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • primidone

              primidone will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • probenecid

              ibuprofen will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • propafenone

              propafenone will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • propranolol

              propranolol and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of propranolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • protamine

              protamine and ibuprofen both increase anticoagulation. Modify Therapy/Monitor Closely.

            • protriptyline

              hydrocodone, protriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • quinacrine

              quinacrine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • quinapril

              quinapril, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • quinidine

              quinidine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • ramipril

              ramipril, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • ranolazine

              ranolazine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • reishi

              ibuprofen and reishi both increase anticoagulation. Use Caution/Monitor.

            • remimazolam

              remimazolam, hydrocodone. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

            • reteplase

              ibuprofen and reteplase both increase anticoagulation. Use Caution/Monitor. Potential for increased risk of bleeding, caution is advised.

            • ribociclib

              ribociclib will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifabutin

              rifabutin will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • rifampin

              rifampin will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • rifapentine

              rifapentine will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

            • ritonavir

              ritonavir will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              ritonavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • rivaroxaban

              rivaroxaban, ibuprofen. Other (see comment). Use Caution/Monitor. Comment: NSAIDs are known to increase bleeding. Bleeding risk may be increased when NSAIDs are used concomitantly with rivaroxaban. Monitor for signs/symptoms of blood loss.

            • rivastigmine

              rivastigmine increases toxicity of ibuprofen by pharmacodynamic synergism. Use Caution/Monitor. Monitor patients for symptoms of active or occult gastrointestinal bleeding.

            • rizatriptan

              hydrocodone, rizatriptan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • rucaparib

              rucaparib will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • sacubitril/valsartan

              sacubitril/valsartan and ibuprofen both increase serum potassium. Use Caution/Monitor.

              sacubitril/valsartan, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

              ibuprofen decreases effects of sacubitril/valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

            • safinamide

              hydrocodone, safinamide. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • salicylates (non-asa)

              ibuprofen and salicylates (non-asa) both increase anticoagulation. Use Caution/Monitor.

              ibuprofen and salicylates (non-asa) both increase serum potassium. Use Caution/Monitor.

            • salmeterol

              ibuprofen increases and salmeterol decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • salsalate

              ibuprofen and salsalate both increase anticoagulation. Use Caution/Monitor.

              ibuprofen and salsalate both increase serum potassium. Use Caution/Monitor.

            • saquinavir

              saquinavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • saw palmetto

              saw palmetto increases toxicity of ibuprofen by unspecified interaction mechanism. Use Caution/Monitor. May increase risk of bleeding.

            • secobarbital

              secobarbital will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May also enhance CNS depressant effect of hydrocodone

            • sertraline

              sertraline, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

              sertraline will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              hydrocodone, sertraline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • Siberian ginseng

              ibuprofen and Siberian ginseng both increase anticoagulation. Use Caution/Monitor.

            • St John's Wort

              St John's Wort will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution when discontinuing CYP3A4 inducers that are coadministered with hydrocodone; plasma concentrations of hydrocodone may increase and can result in potentially fatal respiratory depression

              hydrocodone, St John's Wort. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • silodosin

              ibuprofen decreases effects of silodosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • sodium picosulfate/magnesium oxide/anhydrous citric acid

              ibuprofen, sodium picosulfate/magnesium oxide/anhydrous citric acid. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May be associated with fluid and electrolyte imbalances.

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of ibuprofen by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

            • sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol

              ibuprofen, sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol. Other (see comment). Use Caution/Monitor. Comment: Caution when bowel preps are used with drugs that cause SIADH or NSAIDs; increased risk for water retention or electrolyte imbalance.

            • sodium sulfate/potassium sulfate/magnesium sulfate

              sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of ibuprofen by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

            • sotalol

              sotalol and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of sotalol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • sparsentan

              ibuprofen and sparsentan both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Coadministration of NSAIDS, including selective COX-2 inhibitors, may result in deterioration of kidney function (eg, possible kidney failure). Monitor for signs of worsening renal function with concomitant use with NSAIDs.

            • spironolactone

              spironolactone and ibuprofen both increase serum potassium. Modify Therapy/Monitor Closely.

            • stiripentol

              stiripentol, hydrocodone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

              stiripentol, hydrocodone. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

            • succinylcholine

              ibuprofen and succinylcholine both increase serum potassium. Use Caution/Monitor.

            • sulfasalazine

              ibuprofen and sulfasalazine both increase anticoagulation. Use Caution/Monitor.

              ibuprofen and sulfasalazine both increase serum potassium. Use Caution/Monitor.

            • sulindac

              ibuprofen and sulindac both increase anticoagulation. Use Caution/Monitor.

              ibuprofen and sulindac both increase serum potassium. Use Caution/Monitor.

            • sumatriptan

              hydrocodone, sumatriptan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • sumatriptan intranasal

              hydrocodone, sumatriptan intranasal. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • tafluprost

              tafluprost, ibuprofen. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

            • tazemetostat

              tazemetostat will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will decrease the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • telmisartan

              telmisartan and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of telmisartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              telmisartan, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • temocillin

              temocillin, ibuprofen. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

              temocillin, ibuprofen. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • tenecteplase

              ibuprofen and tenecteplase both increase anticoagulation. Use Caution/Monitor. Potential for increased risk of bleeding, caution is advised.

            • tenofovir DF

              tenofovir DF, ibuprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of tenofovir DF with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

            • terazosin

              ibuprofen decreases effects of terazosin by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            • terbinafine

              ibuprofen will increase the level or effect of terbinafine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

            • terbutaline

              ibuprofen increases and terbutaline decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • thioridazine

              thioridazine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

            • ticagrelor

              ticagrelor, ibuprofen. Either increases effects of the other by anticoagulation. Use Caution/Monitor. Increased risk of bleeding with use of ticagrelor and chronic NSAID use. .

            • ticarcillin

              ticarcillin, ibuprofen. Either increases levels of the other by plasma protein binding competition. Use Caution/Monitor.

              ticarcillin, ibuprofen. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

            • ticlopidine

              ticlopidine will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

              ticlopidine increases toxicity of ibuprofen by anticoagulation. Use Caution/Monitor.

            • timolol

              timolol and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of timolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • tipranavir

              tipranavir will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              tipranavir will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • tobramycin inhaled

              tobramycin inhaled and ibuprofen both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Avoid concurrent or sequential use to decrease risk for ototoxicity

            • tolazamide

              ibuprofen increases effects of tolazamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • tolbutamide

              ibuprofen increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor. Risk of hypoglycemia.

            • tolfenamic acid

              ibuprofen and tolfenamic acid both increase anticoagulation. Use Caution/Monitor.

              ibuprofen and tolfenamic acid both increase serum potassium. Use Caution/Monitor.

            • tolmetin

              ibuprofen and tolmetin both increase anticoagulation. Use Caution/Monitor.

              ibuprofen and tolmetin both increase serum potassium. Use Caution/Monitor.

            • tolvaptan

              ibuprofen and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • torsemide

              ibuprofen increases and torsemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • trandolapril

              trandolapril, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • travoprost ophthalmic

              travoprost ophthalmic, ibuprofen. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

            • trazodone

              trazodone, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

              hydrocodone, trazodone. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • triamcinolone acetonide injectable suspension

              ibuprofen, triamcinolone acetonide injectable suspension. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Concomitant use of NSAIDS and corticosteroids increases the risk of gastrointestinal side effects. .

            • trimipramine

              hydrocodone, trimipramine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • triamterene

              triamterene and ibuprofen both increase serum potassium. Modify Therapy/Monitor Closely.

            • valoctocogene roxaparvovec

              ibuprofen and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.

            • valsartan

              valsartan and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • venlafaxine

              venlafaxine, ibuprofen. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of upper GI bleeding. SSRIs inhib. serotonin uptake by platelets.

              venlafaxine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

              hydrocodone, venlafaxine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • vitamin K1 (phytonadione)

              ibuprofen increases and vitamin K1 (phytonadione) decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • voriconazole

              voriconazole will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

            • voclosporin

              voclosporin, ibuprofen. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

            • vorapaxar

              ibuprofen, vorapaxar. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive antiplatelet effect may occur.

            • vortioxetine

              ibuprofen, vortioxetine. Either increases effects of the other by anticoagulation. Use Caution/Monitor.

            • warfarin

              ibuprofen, warfarin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Drugs with antiplatelet properties may increase anticoagulation effect of warfarin.

            • zanubrutinib

              ibuprofen, zanubrutinib. Either increases effects of the other by anticoagulation. Modify Therapy/Monitor Closely. Zanubrutinib-induced cytopenias increases risk of hemorrhage. Coadministration of zanubritinib with antiplatelets or anticoagulants may further increase this risk.

            • zolmitriptan

              hydrocodone, zolmitriptan. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • zotepine

              ibuprofen decreases effects of zotepine by pharmacodynamic antagonism. Use Caution/Monitor. NSAIDs decrease prostaglandin synthesis.

            Minor (106)

            • aceclofenac

              aceclofenac will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • acemetacin

              acemetacin will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • acetazolamide

              acetazolamide will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • acyclovir

              ibuprofen will increase the level or effect of acyclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • adefovir

              ibuprofen increases levels of adefovir by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • alendronate

              ibuprofen, alendronate. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of GI ulceration.

            • aminohippurate sodium

              ibuprofen will increase the level or effect of aminohippurate sodium by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • amiodarone

              amiodarone will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • amobarbital

              amobarbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • anamu

              ibuprofen and anamu both increase anticoagulation. Minor/Significance Unknown.

            • anastrozole

              anastrozole will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • aspirin

              aspirin will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • aspirin rectal

              aspirin rectal will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • aspirin/citric acid/sodium bicarbonate

              aspirin/citric acid/sodium bicarbonate will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • balsalazide

              ibuprofen will increase the level or effect of balsalazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • bendroflumethiazide

              bendroflumethiazide will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • bosentan

              bosentan will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • butabarbital

              butabarbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • butalbital

              butalbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • carbamazepine

              carbamazepine will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • cefadroxil

              cefadroxil will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefamandole

              cefamandole will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefdinir

              cefdinir will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cefpirome

              cefpirome will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ceftibuten

              ceftibuten will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • celecoxib

              celecoxib will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cephalexin

              cephalexin will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • chlorothiazide

              chlorothiazide will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • chlorpropamide

              ibuprofen will increase the level or effect of chlorpropamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • chlorthalidone

              chlorthalidone will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • choline magnesium trisalicylate

              ibuprofen will increase the level or effect of choline magnesium trisalicylate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cimetidine

              cimetidine will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • creatine

              creatine, ibuprofen. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction) Combination may have additive nephrotoxic effects.

            • cyclopenthiazide

              cyclopenthiazide will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • cyclophosphamide

              cyclophosphamide will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • danshen

              ibuprofen and danshen both increase anticoagulation. Minor/Significance Unknown.

            • devil's claw

              ibuprofen and devil's claw both increase anticoagulation. Minor/Significance Unknown.

            • diclofenac

              diclofenac will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • diclofenac topical

              diclofenac topical, ibuprofen. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Although low, there is systemic exposure to diclofenac topical; theoretically, concomitant administration with systemic NSAIDS or aspirin may result in increased NSAID adverse effects.

            • diflunisal

              diflunisal will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • digoxin

              ibuprofen increases levels of digoxin by decreasing renal clearance. Minor/Significance Unknown.

            • disulfiram

              disulfiram will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • eplerenone

              ibuprofen decreases effects of eplerenone by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

            • etodolac

              etodolac will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • etravirine

              etravirine will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • felbamate

              felbamate will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • fenoprofen

              fenoprofen will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • feverfew

              ibuprofen decreases effects of feverfew by pharmacodynamic antagonism. Minor/Significance Unknown.

            • fluconazole

              fluconazole will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • flurbiprofen

              flurbiprofen will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • furosemide

              ibuprofen decreases effects of furosemide by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

            • ganciclovir

              ibuprofen will increase the level or effect of ganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • gentamicin

              ibuprofen increases levels of gentamicin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

            • hydrochlorothiazide

              hydrochlorothiazide will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • imidapril

              ibuprofen decreases effects of imidapril by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

            • indapamide

              indapamide will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • indomethacin

              ibuprofen will increase the level or effect of indomethacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ketoconazole

              ketoconazole will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • ketoprofen

              ibuprofen will increase the level or effect of ketoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ketorolac

              ibuprofen will increase the level or effect of ketorolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ketorolac intranasal

              ibuprofen will increase the level or effect of ketorolac intranasal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • leflunomide

              leflunomide will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • levoketoconazole

              levoketoconazole will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • lornoxicam

              ibuprofen will increase the level or effect of lornoxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • meclofenamate

              meclofenamate will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • mefenamic acid

              ibuprofen will increase the level or effect of mefenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • meloxicam

              ibuprofen will increase the level or effect of meloxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • mesalamine

              ibuprofen will increase the level or effect of mesalamine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • methyclothiazide

              methyclothiazide will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • metolazone

              metolazone will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • metronidazole

              metronidazole will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • miconazole vaginal

              miconazole vaginal will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • nabumetone

              ibuprofen will increase the level or effect of nabumetone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • nateglinide

              nateglinide will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • neomycin PO

              ibuprofen increases levels of neomycin PO by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

            • nilotinib

              nilotinib will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • noni juice

              ibuprofen and noni juice both increase serum potassium. Minor/Significance Unknown.

            • ofloxacin

              ofloxacin, ibuprofen. Other (see comment). Minor/Significance Unknown. Comment: Risk of CNS stimulation/seizure. Mechanism: Displacement of GABA from receptors in brain.

            • parecoxib

              ibuprofen will increase the level or effect of parecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • paromomycin

              ibuprofen increases levels of paromomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

            • pentobarbital

              pentobarbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • phenobarbital

              phenobarbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • piroxicam

              ibuprofen will increase the level or effect of piroxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • primidone

              primidone will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • rifampin

              rifampin will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • rifapentine

              rifapentine will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • rose hips

              rose hips will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • salicylates (non-asa)

              ibuprofen will increase the level or effect of salicylates (non-asa) by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • salsalate

              ibuprofen will increase the level or effect of salsalate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • secobarbital

              secobarbital will decrease the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • streptomycin

              ibuprofen increases levels of streptomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

            • sulfamethoxazole

              sulfamethoxazole will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • sulfasalazine

              ibuprofen will increase the level or effect of sulfasalazine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • sulindac

              ibuprofen will increase the level or effect of sulindac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • tobramycin

              ibuprofen increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.

            • tolfenamic acid

              ibuprofen will increase the level or effect of tolfenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • tolmetin

              ibuprofen will increase the level or effect of tolmetin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • treosulfan

              treosulfan decreases effects of ibuprofen by Mechanism: unspecified interaction mechanism. Minor/Significance Unknown.

            • triamterene

              triamterene, ibuprofen. Other (see comment). Minor/Significance Unknown. Comment: Risk of acute renal failure. Mechanism: NSAIDs decrease prostaglandin synthesis, which normally protect against nephrotoxicity.

              ibuprofen increases toxicity of triamterene by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis, increasing the risk of nephrotoxicity.

            • valganciclovir

              ibuprofen will increase the level or effect of valganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • valproic acid

              valproic acid will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • vancomycin

              ibuprofen increases levels of vancomycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in neonates.

            • voriconazole

              voriconazole will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • willow bark

              ibuprofen will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • zafirlukast

              zafirlukast will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

            • ziconotide

              ziconotide, hydrocodone. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.

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            Adverse Effects

            >10%

            Dizziness

            Drowsiness

            Constipation

            Nausea

            Vomiting

            Diarrhea

            Dyspepsia

            Flatulence

            Hypotension

            1-10%

            Syncope

            Agitation, depression, dizziness, dysphoria, euphoria

            Faintness, mental clouding, restlessness, sedation, weakness

            Cholinergic effects

            Flushing, sweating, urticaria

            Respiratory depression

            Headache, fatigue, lightheadedness, tinnitus

            Erythematous macular rashes

            Erythema multiforme, exfoliative dermatitis, toxic epidermal necrolysis, photosensitivity

            GI bleeding, GI ulceration

            Neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia

            Jaundice

            Acute renal failure, decreased creatinine clearance, elevations in BUN

            <1%

            Bronchitis

            Asthma

            Cystitis

            Cough

            Dysphagia

            Abnormal dreams

            Decreased libido

            Myalgia

            Neuralgia

            Pulmonary congestion

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            Warnings

            Black Box Warnings

            Addiction, abuse, and misuse

            • Long-acting hydrocodone exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death
            • Assess each patient’s risk prior to prescribing, and monitor all patients regularly for the development of these behaviors or conditions

            Life-threatening respiratory depression

            • Serious, life-threatening, or fatal respiratory depression may occur
            • Monitor for respiratory depression, especially during initiation or following a dose increase
            • Instruct patients to swallow capsules/tablets whole; crushing, chewing, or dissolving the extended-release dosage forms can cause rapid release and absorption of a potentially fatal dose of hydrocodone

            Accidental exposure

            • Accidental consumption of even 1 dose of hydrocodone, especially by children, can result in a fatal overdose of hydrocodone

            Neonatal opioid withdrawal syndrome

            • For patients who require opioid therapy while pregnant, be aware that infants may require treatment for neonatal opioid withdrawal syndrome
            • Prolonged maternal use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening and requires management according to protocols developed by neonatology experts

            Interaction with CNS depressants

            • Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death
            • Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate
            • Limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation
            • Coingestion of with alcohol may increase hydrocodone plasma levels and result in a potentially fatal overdose (alters release of drug from capsule)

            Interaction with CYP3A4 inhibitors

            • Initiation of CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of hydrocodone

            Cardiovascular Risk

            • NSAIDs may increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal
            • Risk may increase with duration of use
            • Patients with risk factors for or existing cardiovascular disease may be at greater risk
            • NSAIDs are contraindicated for perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (increased risk of MI & stroke)

            Gastrointestinal Risk

            • NSAIDs increase risk of serious GI adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal
            • GI adverse events may occur at any time during use and without warning symptoms
            • Elderly patients are at greater risk for serious GI events

            Contraindications

            Coronary artery bypass graft (CABG) surgery, treatment of peri-operative pain; increased incidence of myocardial infarction and stroke

            Relative: bleeding disorder, duodenal/gastric/peptic ulcer, stomatitis, SLE, ulcerative colitis, upper GI disease, late pregnancy (may cause premature closure of ductus), urticaria, or allergic-type reactions following aspirin or other nonsteroidal anti-inflammatory agents

            Significant respiratory depression

            Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment

            Known or suspected gastrointestinal obstruction, including paralytic ileus

            Known hypersensitivity (e.g., anaphylactic reactions, serious skin reactions) to hydrocodone, ibuprofen, or any components of the drug product.

            Patients known to be hypersensitive to other opioids may exhibit cross-sensitivity

            History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs

            Cautions

            Hydrocodone may cause spasm of sphincter of Oddi; opioids maycause increases in serum amylase; monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms

            Hydrocodone may increase frequency of seizures in patients with seizure disorders, and may increase risk of seizures occurring in other clinical settings associated with seizures; monitor patients with a history of seizure disorders for worsened seizure control during therapy

            Avoid use of mixed agonist/antagonist (eg, pentazocine, nalbuphine, and butorphanol) or partial agonist (eg, buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic; in these patients, mixed agonist/antagonist and partial agonist analgesics may reduce analgesic effect and/or precipitate withdrawal symptoms; when discontinuing therapy in a physically-dependent patient, gradually taper the dosage; do not abruptly discontinue therapy in these patients

            Therapy may impair mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery; warn patients not to drive or operate dangerous machinery unless they are tolerant to effects of this drug and know how they will react to the medication

            Increases in serum potassium concentration, including hyperkalemia, reported with use of NSAIDs, even in some patients without renal impairment; in patients with normal renal function, those effects have been attributed to a hyporeninemic-hypoaldosteronism state

            Ibuprofen has been associated with anaphylactic reactions in patients with and without known hypersensitivity to ibuprofen and in patients with aspirin-sensitive asthma; seek emergency help if an anaphylactic reaction occurs

            A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs; because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, this drug is contraindicated in patients with this form of aspirin sensitivity; when used in patients with pre-existing asthma (without known aspirin sensitivity), monitor patients for changes in signs and symptoms of asthma

            NSAIDs, including ibuprofen, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal; these serious events may occur without warning. inform patients about signs and symptoms of serious skin reactions, and to discontinue use at first appearance of skin rash or any other sign of hypersensitivity; this drug is contraindicated in patients with previous serious skin reactions to NSAIDs

            Aseptic meningitis with fever and coma has been observed on rare occasions in patients on ibuprofen therapy; although more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients who do not have an underlying chronic disease; if signs or symptoms of meningitis develop, possibility of being related to ibuprofen should be considered

            Pharmacological activity of this drug combination in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections

            Blurred or diminished vision, scotomata, and changes in color vision reported with oral ibuprofen; discontinue therapy if a patient develops such complaints, and refer the patient for an ophthalmologic examination that includes central visual fields and color vision testing

            Hypertension

            • Therapy, can lead to new onset or worsening of pre-existing hypertension, either of which may contribute to increased incidence of CV events; patients taking angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs; monitor blood pressure (BP) during initiation of NSAID treatment and throughout the course of therapy

            Addiction, abuse and misuse

            • Therapy exposes users to the risks of addiction, abuse, and misuse; although risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed this drug; addiction can occur at recommended dosages and if drug is misused or abused
            • Risks of addiction are increased in patients with personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depression)
            • The potential for these risks should not, however, prevent proper management of pain in any given patient; patients at increased risk may be prescribed opioid-containing products such as this drug, but use in such patients necessitates intensive counseling about risks and proper use of this drug along with intensive monitoring for signs of addiction, abuse, and misuse
            • Opioids are sought by drug abusers and people with addiction disorders, and are subject to criminal diversion; consider these risks when prescribing or dispensing this medication
            • Strategies to reduce these risks include prescribing drug in the smallest appropriate quantity and advising patient on proper disposal of unused drug; contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product

            Adrenal insufficiency

            • Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure
            • If adrenal insufficiency is suspected, confirm diagnosis with diagnostic testing as soon as possible; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers
            • Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency; the information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency

            Severe hypotension

            • This drug may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients; there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics)
            • Monitor these patients for signs of hypotension after initiating or titrating the dosage; in patients with circulatory shock, this drug may cause vasodilation that can further reduce cardiac output and blood pressure; avoid use in patients with circulatory shock

            Increased cranial pressure, brain tumors, head injury, or impaired consciousness

            • In patients who may be susceptible to intracranial effects of CO2 retention (eg, those with evidence of increased intracranial pressure or brain tumors), this drug may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure
            • Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy; opioids may also obscure the clinical course in a patient with a head injury; avoid use in patients with impaired consciousness or coma

            Life-threatening respiratory depression

            • Serious, life-threatening, or fatal respiratory depression reported with use of opioids, even when used as recommended; respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death
            • Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on patient’s clinical status; carbon dioxide (CO2 ) retention from opioid-induced respiratory depression can exacerbate sedating effects of opioids
            • While serious, life-threatening, or fatal respiratory depression can occur at any time during use of this medication, the risk is greatest during initiation of therapy or following a dosage increase
            • Monitor patients closely for respiratory depression, especially within first 24-72 hours of initiating therapy with and following dosage increases
            • To reduce risk of respiratory depression, proper dosing and titration of this drug are essential; overestimating dosage when converting patients from another opioid product can result in fatal overdose with first dose
            • Accidental ingestion of even one dose of this drug, especially by children, can result in respiratory depression and death due to overdose

            Life-threatening respiratory depression in patients with chronic pulmonary disease

            • Use in patients with acute or severe bronchial asthma in an unmonitored setting or absence of resuscitative equipment contraindicated
            • Treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages
            • Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients; monitor such patients closely, particularly when initiating and titrating this drug and when is given concomitantly with other drugs that depress respiration; alternatively, consider use of non-opioid analgesics in these patients

            Neonatal opioid withdrawal syndrome

            • Prolonged use of therapy during pregnancy can result in withdrawal in the neonate; neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
            • Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly; advise pregnant women using opioids for a prolonged period of risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available

            Cardiovascular thrombotic events

            • Increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI), and stroke, which can be fatal reported; it is unclear that the risk for CV thrombotic events is similar for all NSAIDs
            • The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease; however, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate
            • Some observational studies found that this increased risk of serious CV thrombotic events began as early as first weeks of treatment; the increase in CV thrombotic risk has been observed most consistently at higher doses
            • To minimize potential risk for an adverse CV event in NSAID-treated patients, use lowest effective dose for shortest duration possible; physicians and patients should remain alert for development of such events, throughout entire treatment course, even in absence of previous CV symptoms; patients should be informed about symptoms of serious CV events and steps to take if they occur
            • There is no consistent evidence that concurrent use of aspirin mitigates increased risk of serious CV thrombotic events associated with NSAID use; the concurrent use of aspirin and an NSAID, such as ibuprofen, increases risk of serious gastrointestinal (GI) events
            • Avoid use in patients with a recent MI unless benefits are expected to outweigh risk of recurrent CV thrombotic events; if this drug is used in patients with a recent MI, monitor patients for signs of cardiac ischemia

            Gastrointestinal bleeding, ulceration, and perforation

            • NSAIDs, including ibuprofen, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of esophagus, stomach, small intestine, or large intestine, which can be fatal; these serious adverse events can occur at any time, with or without warning symptoms, in patients treated with this drug
            • Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic; upper GI ulcers, gross bleeding, or perforation caused by NSAIDs reported in patients treated for one year; however, even short-term NSAID therapy is not without risk
            • Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who used NSAIDs have increased risk for developing a GI bleed compared to patients without these risk factors
            • Other factors that increase risk for GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status
            • Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients; additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding
            • Strategies to minimize the GI risks in NSAID-treated patients:
              • Use lowest effective dosage for shortest possible duration
              • Avoid administration of more than one NSAID at a time
              • Avoid use in patients at higher risk unless benefits are expected to outweigh increased risk of bleeding
              • For high risk patients, as well as those with active GI bleeding, consideralternate therapies other than NSAIDs
              • Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy
              • If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue therapy until a serious GI adverse event ruled out
              • In setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding

            Hepatotoxicity

            • Elevations of ALT or AST (three or more times the upper limit of normal [ULN]) reported in NSAID-treated patients in clinical trials with NSAIDS; in addition, rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure reported
            • Elevations of ALT or AST (<3X ULN) may occur; inform patients of warning signs and symptoms of hepatotoxicity (eg, nausea, fatigue,lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and “flulike” symptoms)
            • If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash, etc), discontinue therapy immediately, and perform a clinical evaluation of patient

            Heart failure and edema

            • Randomized controlled trials have demonstrated approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients
            • In a Danish National Registry study of patients with heart failure,NSAID use increased risk of MI, hospitalization for heart failure, and death; additionally, fluid retention and edema reported in some patients treated with NSAIDs
            • Use of this medication may blunt the CV effects of several therapeutic agents used to treat these medical conditions (eg, diuretics, ACE inhibitors, or angiotensin receptor blockers[ARBs])
            • Avoid use in patients with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure; if this drug is used in patients with severe heart failure, monitor patients for signs of worsening heart failure

            Renal toxicity and hyperkalemia

            • Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury; renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion; in these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation
            • Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or angiotensin receptor blockers (ARBs), and the elderly; discontinuation of NSAID therapy was usually followed by recovery to pretreatment state
            • No information is available from controlled clinical studies regarding use of this medication in patients with advanced renal disease; the renal effects of this drug may hasten the progression of renal dysfunction in patients with pre-existing renal disease
            • Correct volume status in dehydrated or hypovolemic patients prior to initiating this medication; monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use
            • Avoid use in patients with advanced renal disease unless benefits are expected to outweigh risk of worsening renal function; if used in patients with advanced renal disease, monitor patients for signs of worsening renal function

            Hematologic toxicity

            • Anemia has occurred in NSAID-treated patients; this may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis
            • If treated patient treated has any signs or symptoms of anemia, monitor hemoglobin or hematocrit; NSAID-containing products, may increase risk of bleeding events
            • Co-morbid conditions such as coagulation disorders, concomitant use of warfarin, other anticoagulants, antiplatelet agents (eg, aspirin), serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs) may increase risk; monitor these patients for signs of bleeding

            Drug interaction overview

            • Concomitant use or discontinuation of CYP3A4 inhibitors and inducers
              • Concomitant use of this medication with a CYP3A4 inhibitor, such as macrolide antibiotics (eg, erythromycin), azole-antifungal agents (eg, ketoconazole), and protease inhibitors (eg, ritonavir), may increase plasma concentrations of hydrocodone and prolong opioid adversereactions, which may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose is achieved
              • Similarly, discontinuation of a CYP3A4 inducer, such asrifampin, carbamazepine, and phenytoin, in treated patients may increase hydrocodone plasma concentrations and prolong opioid adverse reactions
              • When using this medication with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in treated patients, monitor patients closely at frequent intervals and consider dosage reduction until stable drug effects are achieved
              • Concomitant use of this drug with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease hydrocodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to hydrocodone
              • When using this drug with CYP3A4 inducers or discontinuing CYP3A4inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur
            • Benzodiazepines or other CNS depressants
              • Profound sedation, respiratory depression, coma, and death may result from concomitant use of this drug with benzodiazepines or other CNS depressants (eg, non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol)
              • Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate
              • Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases risk of drug-related mortality compared to use of opioid analgesics alone; because of similar pharmacological properties, it is reasonable to expect similar risk with concomitant use of other CNS depressant drugs with opioid analgesics
              • If decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe lowest effective dosages and minimum durations of concomitant use; in patients already receiving an opioid analgesic, prescribe a lower initial dose of benzodiazepine or other CNS depressant than indicated in absence of an opioid, and titrate based on clinical response
              • If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of opioid analgesic, and titrate based on clinical response
              • Follow patients closely for signs and symptoms of respiratory depression and sedation; advise both patients and caregivers about risks of respiratory depression and sedation when this drug is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs)
              • Advise patients not to drive or operate heavy machinery until effects of concomitant use of benzodiazepine or other CNS depressant have been determined; screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of risk for overdose and death associated with use of additional CNS depressants including alcohol and illicit drugs

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            Pregnancy & Lactation

            Pregnancy

            Prolonged use of opioid analgesics during pregnancy can cause neonatal opioid withdrawal syndrome; there are no available data in pregnant women to inform a drug associated risk for major birth defects and miscarriage; published studies with morphine use during pregnancy have not reported a clear association with opioids and major birth defects

            Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth; the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of drug by newborn; observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly

            Lactation

            Drug is present in breast milk; published lactation studies report variable concentrations of drug in breast milk with administration of immediate-release formulation to nursing mothers in early postpartum period

            The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy; capsules and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

            Monitor infants exposed to drug through breast milk for excess sedation and respiratory depression; withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast- feeding is stopped

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Hydrocodone: Binds to opiate receptors in the CNS, which in turn produces generalized CNS depression and alters perception and response to pain

            Ibuprofen: Inhibits synthesis of prostaglandins in body tissues by inhibiting cyclooxygenase; at least 2 isoenzymes, cyclooxygenase-1 (COX-1) & -2 (COX-2); has antipyretic, anti-inflammatory, and analgesic properties

            Metabolism

            Hydrocodone: by liver (O-demethylation, N-demethylation, 6-keto reduction); hepatic P450 enzyme CYP2D6

            Ibuprofen: rapid hepatic oxidation to inactive metabolites: (+)-2-[4'-(2-hydroxy-2-methylpropyl) phenyl] propionic acid (metabolite A), (+)-2-[4'-(2-carboxypropyl) phenyl] propionic acid (metabolite B)

            Elimination

            Excretion

            • Hydrocodone: Mainly urine
            • Ibuprofen: Urine 50-60% (<10% unchanged)

            Half-Life

            • Hydrocodone: 3.3-4.4 hr
            • Ibuprofen: 2-4 hr

            Absorption

            Onset: 0.5 hr (ibuprofen)

            Bioavailability 80-90% (ibuprofen)

            Vd: 0.12 L/kg (ibuprofen)

            Protein Bound: 90-99% (ibuprofen)

            Peak Plasma Time

            • Hydrocodone: 1.3 hr
            • Ibuprofen: 2 hr

            Duration

            • Hydrocodone: 4-8 hr
            • Ibuprofen: 4-6 hr

            Pharmacogenomics

            Hydrocodone is metabolized to Hydromorphone via CYP2D6; CYP2D6 poor metabolizers may not achieve adequate analgesia

            Ultra-rapid metabolizers (up to 7% of Caucasians and up to 30% of Asian and African populations) may have increased toxicity due to rapid conversion

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            Formulary

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
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            Code Definition
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.