metronidazole/tetracycline/bismuth subsalicylate (Rx)

Brand and Other Names:
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

copackaged blister card

  • 14 blister packs, containing 8 chewable tablets (262.4mg/tablet) of bismuth subsalicylate plus 4 tablets (250mg/tablet) of metronidazole plus 4 capsules (500mg/capsule) of tetracycline

Duodenal Ulcer

Indicated for eradication of H pylori infection in patients with duodenal ulcer disease (active or history); use in combination with an H2 antagonist

Bismuth subsalicylate 525 mg (two 262.4 mg-chewable tablets), metronidazole 250 mg (one 250-mg tablet), and tetracycline hydrochloride 500 mg (one 500-mg capsule) PO QID for 14 days plus an H2 antagonist

Dosage Modifications

Renal impairment

  • Antianabolic action of the tetracyclines may cause an increase in blood urea nitrogen (BUN)
  • Severe: Contraindicated

Hepatic impairment

  • Mild-to-moderate: Monitor for metronidazole-associated adverse events
  • Severe: Not recommended

Dosing Considerations

Only treat indicated infections that are proven or strongly suspected to be caused by susceptible bacteria to reduce development of drug-resistant bacteria

Contraindicated

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Interactions

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            Contraindicated (3)

            • acitretin

              tetracycline, acitretin. Other (see comment). Contraindicated. Comment: Both acitretin and tetracyclines can cause increased intracranial pressure.

            • dichlorphenamide

              dichlorphenamide increases levels of bismuth subsalicylate by unknown mechanism. Contraindicated. Coadministration of dichlorphenamide with high-dose aspirin may increase salicylate levels. Anorexia, tachypnea, lethargy, and coma reported.

            • dronabinol

              metronidazole increases toxicity of dronabinol by aldehyde dehydrogenase inhibition. Contraindicated. Dronabinol oral solution (Syndros) contains 50% (w/w) dehydrated alcohol 5.5% (w/w) propylene glycol, which can produce disulfiramlike reactions if coadministered with metronidazole. Discontinue metronidazole at least 14 days before starting dronabinol solution and do not administer metronidazole within 7 days of completing treatment with dronabinol solution.

            Serious - Use Alternative (119)

            • abametapir

              abametapir will increase the level or effect of tetracycline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • aluminum hydroxide

              aluminum hydroxide decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Separate by 2 hours.

            • aminolevulinic acid oral

              aminolevulinic acid oral, tetracycline. 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

              tetracycline increases toxicity of aminolevulinic acid topical by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of photosensitizing drugs may enhance the phototoxic reaction to photodynamic therapy with aminolevulinic acid.

            • amoxicillin

              tetracycline decreases effects of amoxicillin by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Tetracyclines may interfere with the bactericidal action of penicillins. Monitor for decreased therapeutic effects of penicillins if concomitantly used with a tetracycline.

            • ampicillin

              tetracycline decreases effects of ampicillin by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Tetracyclines may interfere with the bactericidal action of penicillins. Monitor for decreased therapeutic effects of penicillins if concomitantly used with a tetracycline.

            • apalutamide

              apalutamide will decrease the level or effect of tetracycline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • atracurium

              tetracycline increases effects of atracurium by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of respiratory depression.

            • avapritinib

              metronidazole will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

              tetracycline will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with moderate CYP3A4 inhibitors. If unable to avoid, reduce avapritinib starting dose. See drug monograph Dosage Modifications.

            • axitinib

              tetracycline increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration with moderate CYP3A4 inhibitors, monitor closely and reduce dose if necessary .

              metronidazole increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration with moderate CYP3A4 inhibitors, monitor closely and reduce dose if necessary .

            • BCG vaccine live

              tetracycline decreases effects of BCG vaccine live by pharmacodynamic antagonism. Contraindicated. Wait until Abx Tx complete to administer live bacterial vaccine.

              metronidazole decreases effects of BCG vaccine live by pharmacodynamic antagonism. Contraindicated. Wait until Abx Tx complete to administer live bacterial vaccine.

            • bismuth subsalicylate

              bismuth subsalicylate decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • bosutinib

              metronidazole increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • bosutinib

              tetracycline increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • calcium acetate

              calcium acetate, tetracycline. Either decreases levels of the other by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Separate by 2 hours.

            • calcium carbonate

              calcium carbonate, tetracycline. Either decreases levels of the other by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Separate by 2 hours.

            • calcium chloride

              calcium chloride, tetracycline. Either decreases levels of the other by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Separate by 2 hours.

            • calcium citrate

              calcium citrate, tetracycline. Either decreases levels of the other by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Separate by 2 hours.

            • calcium gluconate

              calcium gluconate, tetracycline. Either decreases levels of the other by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Separate by 2 hours.

            • carbamazepine

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

            • carbonyl iron

              carbonyl iron decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • cholera vaccine

              tetracycline, cholera vaccine. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid coadministration of cholera vaccine with systemic antibiotics since these agents may be active against the vaccine strain. Do not administer cholera vaccine to patients who have received oral or parenteral antibiotics within 14 days prior to vaccination.

              metronidazole, cholera vaccine. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid coadministration of cholera vaccine with systemic antibiotics since these agents may be active against the vaccine strain. Do not administer cholera vaccine to patients who have received oral or parenteral antibiotics within 14 days prior to vaccination.

            • cisatracurium

              tetracycline increases effects of cisatracurium by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of respiratory depression.

            • cobimetinib

              metronidazole will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

            • cobimetinib

              tetracycline will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

            • demeclocycline

              bismuth subsalicylate decreases levels of demeclocycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • dicloxacillin

              tetracycline decreases effects of dicloxacillin by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • dihydroergotamine

              metronidazole will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • dihydroergotamine intranasal

              metronidazole will increase the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • disulfiram

              disulfiram increases toxicity of metronidazole by decreasing metabolism. Contraindicated. Enhanced CNS & cardiac toxicity.

            • doxycycline

              bismuth subsalicylate decreases levels of doxycycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • dronedarone

              metronidazole will increase the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • eliglustat

              tetracycline increases levels of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Moderate CYP3A4 inhibitors are not recommended with eliglustat poor or intermediate metabolizers; reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive metabolizers .

              metronidazole increases levels of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Moderate CYP3A4 inhibitors are not recommended with eliglustat poor or intermediate metabolizers; reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive metabolizers .

            • eluxadoline

              bismuth subsalicylate, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions. .

            • entrectinib

              tetracycline will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

              metronidazole will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • enzalutamide

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

            • ergotamine

              metronidazole will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin base

              metronidazole will increase the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

              metronidazole will increase the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              metronidazole will increase the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • erythromycin stearate

              metronidazole will increase the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • everolimus

              metronidazole will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • fentanyl

              tetracycline will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

              metronidazole will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fentanyl intranasal

              metronidazole will increase the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

              tetracycline will increase the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fentanyl transdermal

              tetracycline will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

              metronidazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fentanyl transmucosal

              tetracycline will increase the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

              metronidazole will increase the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

            • ferric maltol

              ferric maltol decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • infigratinib

              metronidazole will increase the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ferrous fumarate

              ferrous fumarate decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • ferrous gluconate

              ferrous gluconate decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • ferrous sulfate

              ferrous sulfate decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • fexinidazole

              fexinidazole will increase the level or effect of tetracycline 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.

            • fosphenytoin

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

            • idelalisib

              idelalisib will increase the level or effect of tetracycline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • infigratinib

              tetracycline will increase the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • irinotecan

              tetracycline will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • irinotecan liposomal

              tetracycline will increase the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • iron dextran complex

              iron dextran complex decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • iron sucrose

              iron sucrose decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • isotretinoin

              isotretinoin, tetracycline. Mechanism: unknown. Contraindicated. Risk of pseudotumor cerebri.

            • ivabradine

              tetracycline will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.

              metronidazole will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.

            • ivosidenib

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

            • lemborexant

              metronidazole will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with moderate or strong CYP3A inhibitors.

            • lemborexant

              tetracycline will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with moderate or strong CYP3A inhibitors.

            • lovastatin

              metronidazole will increase the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lurbinectedin

              tetracycline will increase the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              metronidazole will increase the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • magnesium chloride

              magnesium chloride decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • mebendazole

              mebendazole increases toxicity of metronidazole by Other (see comment). Avoid or Use Alternate Drug. Comment: May increase the risk for toxic epidermal necrolysis or Stevens-Johnson syndrome.

            • magnesium citrate

              magnesium citrate decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • magnesium hydroxide

              magnesium hydroxide decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • magnesium oxide

              magnesium oxide decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • magnesium sulfate

              magnesium sulfate decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • methoxyflurane

              tetracycline, methoxyflurane. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of nephrotoxicity.

            • methyl aminolevulinate

              tetracycline, 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.

            • midazolam intranasal

              metronidazole will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of moderate CYP3A4 inhibitors with midazolam intranasal causes higher midazolam systemic exposure, which may prolong sedation.

              tetracycline will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of moderate CYP3A4 inhibitors with midazolam intranasal causes higher midazolam systemic exposure, which may prolong sedation.

            • minocycline

              bismuth subsalicylate decreases levels of minocycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • mobocertinib

              tetracycline will increase the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use of moderate CYP3A4 inhibitor unavoidable, reduce mobocertinib dose by ~50% (eg, 160 to 80 mg); closely monitor QTc interval.

              metronidazole will increase the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use of moderate CYP3A4 inhibitor unavoidable, reduce mobocertinib dose by ~50% (eg, 160 to 80 mg); closely monitor QTc interval.

            • nafcillin

              tetracycline decreases effects of nafcillin by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • naloxegol

              metronidazole will increase the level or effect of naloxegol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministation of naloxegol with moderate CYP3A4 inhibitors is unavoidable, reduce naloxegol dose to 12.5 mg qDay

            • naloxegol

              tetracycline will increase the level or effect of naloxegol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministation of naloxegol with moderate CYP3A4 inhibitors is unavoidable, reduce naloxegol dose to 12.5 mg qDay

            • neratinib

              tetracycline will increase the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inhibitors.

              metronidazole will increase the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inhibitors.

            • olaparib

              tetracycline will increase the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A inhibitors cannot be avoided, reduce olaparib dose to 200 mg (capsule) or 150 mg (tablet) PO BID. Do not substitute tablets with capsules.

              metronidazole will increase the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A inhibitors cannot be avoided, reduce olaparib dose to 200 mg (capsule) or 150 mg (tablet) PO BID. Do not substitute tablets with capsules.

            • onabotulinumtoxinA

              tetracycline increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of respiratory depression.

            • oxytetracycline

              bismuth subsalicylate decreases levels of oxytetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • pemigatinib

              metronidazole will increase the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pemigatinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pemigatinib dose.

            • oxacillin

              tetracycline decreases effects of oxacillin by pharmacodynamic antagonism. Avoid or Use Alternate Drug. bacteriostatic agents may inhibit the effects of bactericidal agents.

            • pancuronium

              tetracycline increases effects of pancuronium by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of respiratory depression.

            • pemigatinib

              tetracycline will increase the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pemigatinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pemigatinib dose.

            • penicillin G aqueous

              tetracycline decreases effects of penicillin G aqueous by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • penicillin VK

              tetracycline decreases effects of penicillin VK by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • pexidartinib

              metronidazole will increase the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pexidartinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pexidartinib dose.

              tetracycline will increase the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pexidartinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pexidartinib dose.

            • phenobarbital

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

            • pimozide

              metronidazole increases levels of pimozide by decreasing metabolism. Contraindicated. Risk of QT interval prolongation.

            • phenytoin

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

            • pivmecillinam

              tetracycline decreases effects of pivmecillinam by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • polysaccharide iron

              polysaccharide iron decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • primidone

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

            • propylene glycol

              metronidazole, propylene glycol. Mechanism: decreasing metabolism. Contraindicated. Disulfiram like reaction.

            • ranolazine

              metronidazole will increase the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rapacuronium

              tetracycline increases effects of rapacuronium by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of respiratory depression.

            • rocuronium

              tetracycline increases effects of rocuronium by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of respiratory depression.

            • rose hips

              rose hips decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • selinexor

              selinexor, metronidazole. 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.

            • selumetinib

              tetracycline will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.

              metronidazole will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.

            • silodosin

              metronidazole will increase the level or effect of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • siponimod

              tetracycline will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • simvastatin

              metronidazole will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • siponimod

              metronidazole will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • sirolimus

              metronidazole will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • sodium bicarbonate

              sodium bicarbonate decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Separate by 2 hours.

            • sodium citrate/citric acid

              sodium citrate/citric acid decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Separate by 2 hours.

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Administer tetracyclines at least 2 hr before and no less than 6 hr after each dose to avoid chelation with magnesium. .

            • sodium sulfate/potassium sulfate/magnesium sulfate

              sodium sulfate/potassium sulfate/magnesium sulfate decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Administer tetracyclines at least 2 hr before and no less than 6 hr after each dose to avoid chelation with magnesium. .

            • strontium ranelate

              strontium ranelate decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Contraindicated. Suspend strontium ranelate during antibiotic therapy.

            • succinylcholine

              tetracycline increases effects of succinylcholine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of respiratory depression.

            • tazemetostat

              metronidazole will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of tazemetostat with moderate CYP3A4 inhibitors. If coadministration is unavoidable, reduce tazemetostat current dose (see drug monograph Dosage Modifications).

              tetracycline will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of tazemetostat with moderate CYP3A4 inhibitors. If coadministration is unavoidable, reduce tazemetostat current dose (see drug monograph Dosage Modifications).

            • temocillin

              tetracycline decreases effects of temocillin by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

            • tetracycline

              bismuth subsalicylate decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • tolvaptan

              metronidazole will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            Monitor Closely (190)

            • acalabrutinib

              tetracycline will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.

              metronidazole will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.

            • acebutolol

              bismuth subsalicylate, acebutolol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

            • alitretinoin

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

            • atenolol

              bismuth subsalicylate, atenolol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

            • atogepant

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

            • almotriptan

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

            • alprazolam

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

            • amifampridine

              metronidazole increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

            • amiodarone

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

            • aprepitant

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

            • aripiprazole

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

            • artemether/lumefantrine

              metronidazole will increase the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • atogepant

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

            • atorvastatin

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

            • avanafil

              tetracycline will increase the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibitors may reduce avanafil clearance increasing systemic exposure to avanafil; increased levels may result in increased associated adverse events; the maximum recommended dose of STENDRA is 50 mg, not to exceed once every 24 hours for patients taking concomitant moderate CYP3A4 inhibitors

              metronidazole will increase the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibitors may reduce avanafil clearance increasing systemic exposure to avanafil; increased levels may result in increased associated adverse events; the maximum recommended dose of STENDRA is 50 mg, not to exceed once every 24 hours for patients taking concomitant moderate CYP3A4 inhibitors

            • bazedoxifene/conjugated estrogens

              tetracycline will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

              metronidazole will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

              metronidazole will increase the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • benazepril

              bismuth subsalicylate decreases effects of benazepril by pharmacodynamic antagonism. Use Caution/Monitor. Salicylates may also increase nephrotoxic effects of ACE inhibitors.

            • betaxolol

              bismuth subsalicylate, betaxolol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

            • bisoprolol

              bismuth subsalicylate, bisoprolol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

            • bortezomib

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

            • bosentan

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

            • brexpiprazole

              tetracycline will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

              metronidazole will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

            • budesonide

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

            • buprenorphine subdermal implant

              tetracycline will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

            • buprenorphine subdermal implant

              metronidazole will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

            • buprenorphine, long-acting injection

              metronidazole will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

              tetracycline will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • buspirone

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

            • cabazitaxel

              tetracycline will increase the level or effect of cabazitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A4 inhibitors.

            • cabozantinib

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

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

            • cannabidiol

              metronidazole will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

              tetracycline will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • carbamazepine

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

            • carvedilol

              bismuth subsalicylate, carvedilol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

            • cefdinir

              tetracycline decreases effects of cefdinir by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.

            • carvedilol

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

            • cefditoren

              tetracycline decreases effects of cefditoren by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.

            • cefoxitin

              tetracycline decreases effects of cefoxitin by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.

            • cefpodoxime

              tetracycline decreases effects of cefpodoxime by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.

            • ceftriaxone

              tetracycline decreases effects of ceftriaxone by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.

            • cefuroxime

              tetracycline decreases effects of cefuroxime by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.

            • celiprolol

              bismuth subsalicylate, celiprolol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

            • cenobamate

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

            • cholestyramine

              cholestyramine decreases levels of metronidazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              cholestyramine decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • cilostazol

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

            • conjugated estrogens

              tetracycline will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • cinacalcet

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

            • clobetasone

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

            • clopidogrel

              metronidazole will decrease the level or effect of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Inhibition of CYP3A4 will reduce clopidogrel bioactivation

            • clozapine

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

            • conivaptan

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

            • conjugated estrogens

              metronidazole will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

              metronidazole will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • conjugated estrogens, vaginal

              metronidazole will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cortisone

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

            • crofelemer

              crofelemer increases levels of tetracycline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • cyclosporine

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

            • dabrafenib

              dabrafenib will decrease the level or effect of tetracycline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • darifenacin

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

            • darunavir

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

            • dasatinib

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

            • deflazacort

              metronidazole will increase the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease deflazacort dose to one-third of the recommended dose if coadministered with moderate or strong CYP3A4 inhibitors.

              tetracycline will increase the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease deflazacort dose to one-third of the recommended dose if coadministered with moderate or strong CYP3A4 inhibitors.

            • dexamethasone

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

            • diazepam intranasal

              tetracycline will increase the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

            • diazepam

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

            • diazepam intranasal

              metronidazole will increase the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

            • didanosine

              didanosine will decrease the level or effect of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Oral tetracycline should not be administered simultaneously with didanosine (chewable tablets or powder for oral solution); use alternatives if available. Tetracycline antibiotics should be taken 1 hour before or 4 hours after administration of didanosine.

            • digoxin

              metronidazole will increase the level or effect of digoxin by altering intestinal flora. Applies only to oral form of both agents. Use Caution/Monitor.

              tetracycline will increase the level or effect of digoxin by altering intestinal flora. Applies only to oral form of both agents. Use Caution/Monitor.

            • efavirenz

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

            • eletriptan

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

            • elagolix

              elagolix decreases levels of tetracycline 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.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of tetracycline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • encorafenib

              encorafenib, tetracycline. 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.

            • erlotinib

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

            • esmolol

              bismuth subsalicylate, esmolol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

            • estradiol

              metronidazole will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

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

              tetracycline will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • estrogens conjugated synthetic

              metronidazole will decrease the level or effect of estrogens conjugated synthetic by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

              metronidazole will increase the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              tetracycline will decrease the level or effect of estrogens conjugated synthetic by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • estropipate

              metronidazole will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

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

              tetracycline will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • ethanol

              metronidazole, ethanol. Mechanism: decreasing metabolism. Use Caution/Monitor. Disulfiram like reaction.

            • ethinylestradiol

              tetracycline will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • ethinylestradiol

              metronidazole will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • ethotoin

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

            • etonogestrel

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

            • etravirine

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

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

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

            • fedratinib

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

            • felodipine

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

            • fesoterodine

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

            • finerenone

              metronidazole will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.

              tetracycline will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.

            • fludrocortisone

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

            • ifosfamide

              tetracycline decreases effects of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of a CYP3A4 inhibitor may decrease metabolism of ifosfamide, potentially reducing ifosfamide therapeutic effects.

            • fluorouracil

              metronidazole increases toxicity of fluorouracil by decreasing elimination. Use Caution/Monitor.

            • fosamprenavir

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

            • fosphenytoin

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

            • guanfacine

              metronidazole will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available.

            • hydrocortisone

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

            • hydroxyprogesterone caproate

              metronidazole will increase the level or effect of hydroxyprogesterone caproate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ibrutinib

              metronidazole increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate CYP3A4 inhibitors, reduce ibrutinib dose to 280 mg qDay (B-cell malignancies) or 420 mg qDay (graft versus host disease). After CYP3A inhibitor discontinuation, resume previous dose of ibrutinib.

            • ifosfamide

              metronidazole decreases effects of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of a CYP3A4 inhibitor may decrease metabolism of ifosfamide, potentially reducing ifosfamide therapeutic effects.

            • iloperidone

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

              iloperidone increases levels of tetracycline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

            • indinavir

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

            • isavuconazonium sulfate

              tetracycline will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isavuconazonium sulfate

              metronidazole will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isoniazid

              metronidazole will increase the level or effect of isoniazid by affecting hepatic enzyme CYP2E1 metabolism. Use Caution/Monitor.

            • istradefylline

              istradefylline will increase the level or effect of tetracycline 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.

            • ivacaftor

              metronidazole increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

            • ivosidenib

              tetracycline will increase the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with moderate CYP3A4 inhibitors may increase ivosidenib plasma concentrations, thus increasing the risk of QTc prolongation. Monitor for increased risk of QTc interval prolongation.

              metronidazole will increase the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with moderate CYP3A4 inhibitors may increase ivosidenib plasma concentrations, thus increasing the risk of QTc prolongation. Monitor for increased risk of QTc interval prolongation.

            • ixabepilone

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

            • labetalol

              bismuth subsalicylate, labetalol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

            • lanthanum carbonate

              lanthanum carbonate decreases levels of tetracycline by cation binding in GI tract. Use Caution/Monitor. Administer oral tetracycline antibiotics at least 2 hr before or after lanthanum. Interaction applies only to oral tetracyclines.

            • lapatinib

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

            • lefamulin

              metronidazole will increase the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for adverse effects if lefamulin is coadministered with moderate CYP3A inhibitors.

              tetracycline will increase the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for adverse effects if lefamulin is coadministered with moderate CYP3A inhibitors.

            • levamlodipine

              tetracycline will increase the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate and strong CYP3A inhibitors results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment.

              metronidazole will increase the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate and strong CYP3A inhibitors results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment.

            • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

              metronidazole will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.

              tetracycline will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.

            • lopinavir

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

            • lorlatinib

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

            • loratadine

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

            • losartan

              metronidazole will increase the level or effect of losartan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. May inhibit the conversion of losartan to its active metabolite E-3174. Importance of interaction not established; monitor individual therapeutic response to determine losartan dosage.

            • lumefantrine

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

            • magnesium supplement

              magnesium supplement will decrease the level or effect of tetracycline by Other (see comment). Modify Therapy/Monitor Closely. Formation of an insoluble complex reduces absorption of the drug through intestinal tract; administer magnesium 2hr before the tetracycline or 4hr after the tetracycline

            • maraviroc

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

            • mefloquine

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

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

            • mestranol

              metronidazole will decrease the level or effect of mestranol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

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

              tetracycline will decrease the level or effect of mestranol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

            • methadone

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

            • methotrexate

              tetracycline increases levels of methotrexate by decreasing elimination. Use Caution/Monitor. If tetracyclines cannot be avoided in patients receiving high-dose methotrexate, closely monitor methotrexate plasma concentrations and patients for signs and symptoms of toxicity.

            • methoxsalen

              methoxsalen, tetracycline. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.

            • methylprednisolone

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

            • metoclopramide intranasal

              bismuth subsalicylate will decrease the level or effect of metoclopramide intranasal by Other (see comment). Use Caution/Monitor. Coadministration of metoclopramide intranasal with drugs that impair GI motility may decrease systemic absorption of metoclopramide. Monitor for reduced therapeutic effect.

            • metoprolol

              bismuth subsalicylate, metoprolol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

            • midazolam

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

            • mipomersen

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

            • mitotane

              mitotane decreases levels of tetracycline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • nadolol

              bismuth subsalicylate, nadolol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

            • nafcillin

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

            • naldemedine

              tetracycline increases levels of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with strong or moderate CYP3A4 inhibitors.

              metronidazole increases levels of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with strong or moderate CYP3A4 inhibitors.

            • nateglinide

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

            • nebivolol

              bismuth subsalicylate, nebivolol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

            • oliceridine

              tetracycline will increase the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

            • nelfinavir

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

            • nicardipine

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

            • nilotinib

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

            • nisoldipine

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

            • oliceridine

              metronidazole will increase the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

            • omadacycline

              bismuth subsalicylate will decrease the level or effect of omadacycline by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Multivalent cation-containing products may impair absorption of tetracyclines, which may decrease its efficacy. Separate dosing of tetracyclines from these products.

            • palbociclib

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

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

            • parecoxib

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

            • penbutolol

              bismuth subsalicylate, penbutolol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

            • pindolol

              bismuth subsalicylate, pindolol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

            • piperacillin

              tetracycline decreases effects of piperacillin by pharmacodynamic antagonism. Use Caution/Monitor. bacteriostatic agents may inhibit the effects of bactericidal agents.

            • pazopanib

              metronidazole will increase the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid coadministration of pazopanib with strong CYP3A4 inhibitors if possible; if must coadminister, decrease pazopanib dose to 400 mg/day

            • phenytoin

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

            • polycarbophil

              polycarbophil decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • porfimer

              tetracycline, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.

            • prednisone

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

            • propranolol

              bismuth subsalicylate, propranolol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

            • quetiapine

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

            • quinidine

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

            • repaglinide

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

            • rifabutin

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

            • rifampin

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

            • rifapentine

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

            • rimegepant

              tetracycline will increase the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid repeating rimegepant dose within 48 hr if coadministered with a moderate CYP3A4 inhibitor.

              metronidazole will increase the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid repeating rimegepant dose within 48 hr if coadministered with a moderate CYP3A4 inhibitor.

            • ritonavir

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

            • rucaparib

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

            • ruxolitinib

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

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

            • saquinavir

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

            • sarecycline

              bismuth subsalicylate will decrease the level or effect of sarecycline by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Multivalent cation-containing products may impair absorption of tetracyclines, which may decrease its efficacy. Separate dosing of tetracyclines from these products.

            • sodium picosulfate/magnesium oxide/anhydrous citric acid

              tetracycline decreases effects of sodium picosulfate/magnesium oxide/anhydrous citric acid by altering metabolism. Use Caution/Monitor. Coadministration with antibiotics decreases efficacy by altering colonic bacterial flora needed to convert sodium picosulfate to active drug.

              sodium picosulfate/magnesium oxide/anhydrous citric acid decreases levels of tetracycline by cation binding in GI tract. Use Caution/Monitor. Take at least 2 hours before and not less than 6 hours after administration of sodium picosulfate, magnesium oxide and anhydrous citric acid to avoid magnesium chelation.

            • sodium picosulfate/magnesium oxide/anhydrous citric acid

              metronidazole decreases effects of sodium picosulfate/magnesium oxide/anhydrous citric acid by altering metabolism. Use Caution/Monitor. Coadministration with antibiotics decreases efficacy by altering colonic bacterial flora needed to convert sodium picosulfate to active drug.

            • solifenacin

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

            • sonidegib

              tetracycline will increase the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of sonidegib with moderate CYP3A4 inhibitors. If a moderate CYP3A inhibitor must be used, administer the moderate CYP3A inhibitor for <14 days and monitor closely for adverse reactions, particularly musculoskeletal adverse reactions.

              metronidazole will increase the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of sonidegib with moderate CYP3A4 inhibitors. If a moderate CYP3A inhibitor must be used, administer the moderate CYP3A inhibitor for <14 days and monitor closely for adverse reactions, particularly musculoskeletal adverse reactions.

            • sotalol

              bismuth subsalicylate, sotalol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

            • stiripentol

              stiripentol, tetracycline. 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.

            • sufentanil SL

              metronidazole will increase the level or effect of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of sufentanil SL with any CYP3A4 inhibitor may increase sufentanil plasma concentration, and, thereby increase or prolonged adverse effects, including potentially fatal respiratory depression.

            • sufentanil SL

              tetracycline will increase the level or effect of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of sufentanil SL with any CYP3A4 inhibitor may increase sufentanil plasma concentration, and, thereby increase or prolonged adverse effects, including potentially fatal respiratory depression.

            • sulfamethoxazole

              metronidazole, sulfamethoxazole. Mechanism: decreasing metabolism. Use Caution/Monitor. Disulfiram like reaction.

            • sunitinib

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

            • suvorexant

              tetracycline will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitors

              metronidazole will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitors

            • tacrolimus

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

            • tadalafil

              tetracycline will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibitors may reduce tadalafil clearance increasing systemic exposure to tadalafil; increased levels may result in increased associated adverse events.

            • tadalafil

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

            • tamoxifen

              metronidazole, tamoxifen. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibition decreases metabolism of tamoxifen to N-desmethyl tamoxifen (active metabolite with similar biologic activity).

            • tamsulosin

              metronidazole increases levels of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • tazemetostat

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

            • tecovirimat

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

            • temsirolimus

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

            • tezacaftor

              metronidazole will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

              tetracycline will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • theophylline

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

            • timolol

              bismuth subsalicylate, timolol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

            • tinidazole

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

            • tinidazole

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

            • tipranavir

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

            • tobramycin inhaled

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

            • tofacitinib

              tetracycline increases levels of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No specific dose adjustment recommended when tofacitinib coadministered with moderate CYP3A4 inhibitors; decrease tofacitinib dose if coadministered with both moderate CYP3A4 and potent CYP2C19 inhibitors .

              metronidazole increases levels of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No specific dose adjustment recommended when tofacitinib coadministered with moderate CYP3A4 inhibitors; decrease tofacitinib dose if coadministered with both moderate CYP3A4 and potent CYP2C19 inhibitors.

            Minor (68)

            • acetaminophen

              metronidazole will increase the level or effect of acetaminophen by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

            • acetaminophen IV

              metronidazole will increase the level or effect of acetaminophen IV by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

            • acetaminophen rectal

              metronidazole will increase the level or effect of acetaminophen rectal by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

            • alfentanil

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

            • alfuzosin

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

            • alosetron

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

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

            • amitriptyline

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

            • antithrombin alfa

              tetracycline increases effects of antithrombin alfa by pharmacodynamic synergism. Minor/Significance Unknown.

            • antithrombin III

              tetracycline increases effects of antithrombin III by pharmacodynamic synergism. Minor/Significance Unknown.

            • argatroban

              tetracycline increases effects of argatroban by pharmacodynamic synergism. Minor/Significance Unknown.

            • armodafinil

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

            • aspirin

              bismuth subsalicylate increases effects of aspirin by pharmacodynamic synergism. Minor/Significance Unknown.

            • aspirin rectal

              bismuth subsalicylate increases effects of aspirin rectal by pharmacodynamic synergism. Minor/Significance Unknown.

            • aspirin/citric acid/sodium bicarbonate

              bismuth subsalicylate increases effects of aspirin/citric acid/sodium bicarbonate by pharmacodynamic synergism. Minor/Significance Unknown.

            • atazanavir

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

            • atovaquone

              tetracycline decreases levels of atovaquone by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. Effect may be minor, due to pharmacodynamic synergism.

            • balsalazide

              metronidazole will decrease the level or effect of balsalazide by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

              tetracycline will decrease the level or effect of balsalazide by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

            • bemiparin

              tetracycline increases effects of bemiparin by pharmacodynamic synergism. Minor/Significance Unknown.

            • biotin

              metronidazole will decrease the level or effect of biotin by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

            • biotin

              tetracycline will decrease the level or effect of biotin by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

            • bivalirudin

              tetracycline increases effects of bivalirudin by pharmacodynamic synergism. Minor/Significance Unknown.

            • bosentan

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

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

            • celecoxib

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

            • cevimeline

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

            • clarithromycin

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

            • clomipramine

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

            • colestipol

              colestipol decreases levels of tetracycline by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • dalteparin

              tetracycline increases effects of dalteparin by pharmacodynamic synergism. Minor/Significance Unknown.

            • dapsone

              metronidazole will increase the level or effect of dapsone by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

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

            • desipramine

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

            • diclofenac

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

            • didanosine

              didanosine, metronidazole. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Enhanced risk of peripheral neuropathy.

            • disopyramide

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

            • docetaxel

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

            • donepezil

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

            • dutasteride

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

            • efavirenz

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

            • enoxaparin

              tetracycline increases effects of enoxaparin by pharmacodynamic synergism. Minor/Significance Unknown.

            • eplerenone

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

            • esomeprazole

              esomeprazole increases levels of bismuth subsalicylate by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • estradiol vaginal

              tetracycline will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              metronidazole will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ethanol

              metronidazole will increase the level or effect of ethanol by affecting hepatic enzyme CYP2E1 metabolism. Minor/Significance Unknown.

            • fondaparinux

              tetracycline increases effects of fondaparinux by pharmacodynamic synergism. Minor/Significance Unknown.

            • eucalyptus

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

            • finasteride

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

            • flurbiprofen

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

            • fluvastatin

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

            • galantamine

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

            • heparin

              tetracycline increases effects of heparin by pharmacodynamic synergism. Minor/Significance Unknown.

            • ibuprofen

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

            • ibuprofen IV

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

            • imatinib

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

            • imipramine

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

            • irinotecan

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

            • irinotecan liposomal

              metronidazole will increase the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • isradipine

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

            • itraconazole

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

            • ketoconazole

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

            • lithium

              metronidazole increases levels of lithium by decreasing metabolism. Minor/Significance Unknown.

            • meloxicam

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

            • montelukast

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

            • niacin

              tetracycline will decrease the level or effect of niacin by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

            • nifedipine

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

            • nimodipine

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

            • nitrendipine

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

            • nitroglycerin IV

              nitroglycerin IV, metronidazole. Mechanism: decreasing metabolism. Minor/Significance Unknown. Disulfiram like reaction.

            • omeprazole

              omeprazole increases levels of bismuth subsalicylate by enhancing GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • oxybutynin

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

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            Adverse Effects

            Listed adverse drug reactions are of metronidazole/tetracycline/bismuth subsalicylate

            >10%

            Nausea (12%)

            1-10%

            Diarrhea (6.8%)

            Abdominal pain (6.8%)

            Melena (3%)

            Upper respiratory tract infection (2.3%)

            Constipation (1.9%)

            Anorexia (1.5%)

            Asthenia (1.5%)

            Vomiting (1.5%)

            Discolored tongue (1.5%)

            Headache (1.5%)

            Dyspepsia (1.5%)

            Dizziness (1.5%)

            Stool abnormality (1.1%)

            Duodenal ulcer (1.1%)

            Sinusitis (1.1%)

            Taste perversion (1.1%)

            Flatulence (1.1%)

            GI hemorrhage (1.1%)

            Pain (1.1%)

            Insomnia (1.1%)

            Anal discomfort (1.1%)

            Paresthesia (1.1%)

            <1%

            Gastrointestinal: Dry mouth, dysphagia, eructation, GI monilia, glossitis, intestinal obstruction, rectal hemorrhage, stomatitis

            Skin: Acne, ecchymosis, photosensitivity reaction, pruritus, rash

            Cardiovascular: Cerebral ischemia, chest pain, hypertension, myocardial infarction

            CNS: Nervousness, somnolence

            Musculoskeletal: Arthritis, rheumatoid arthritis, tendonitis

            Metabolic: SGOT increase, SGPT increase

            Urogenital: Urinary tract infection

            Other: Conjunctivitis, flu syndrome, infection, malaise, neoplasm, rhinitis, syncope, tooth disorder

            Postmarketing Reports (Metronidazole)

            Blood and lymphatic system disorders: Reversible neutropenia (leucopenia), reversible thrombocytopenia

            Cardiac disorders: Flattening of the T-wave

            Gastrointestinal disorders: Nausea, vomiting, diarrhea, abdominal pain, constipation, anorexia, metallic taste, furry tongue, glossitis, stomatitis and candida overgrowth

            Hypersensitivity/immune system disorders: Urticaria, erythematous rash, flushing, nasal congestion, dryness of the mouth (or vagina or vulva), and fever

            Metabolism and nutrition disorders: Pancreatitis

            Nervous system disorders: Convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, headache, syncope, dizziness, vertigo, incoordination, ataxia, confusion, dysarthria, irritability, depression, weakness, and insomnia

            Dermatologic disorders: Erythematous rash and pruritus

            Renal and urinary disorders: Dysuria, cystitis, polyuria, incontinence, darkened urine, and a sense of pelvic pressure

            Other: Dyspareunia, decrease of libido, proctitis, joint pains

            Postmarketing Reports (Tetracycline)

            Blood and lymphatic system disorders: Hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, neutropenia, and eosinophilia

            Gastrointestinal disorders: Nausea, vomiting, diarrhea, anorexia, glossitis, black hairy tongue, dysphagia, enterocolitis, inflammatory lesions (with Candida overgrowth) in the anogenital region, esophagitis and esophageal ulceration

            Nervous system disorders: Intracranial hypertension including pseudotumor cerebri, tinnitus, and myasthenic syndrome

            Renal and urinary disorders: Increased BUN

            Skin and subcutaneous tissue disorders: Maculopapular and erythematous rashes, onycholysis, discoloration of the nails, exfoliative dermatitis, photosensitivity

            Liver: Hepatotoxicity, liver failure

            Hypersensitivity reactions: Urticaria, angioedema, anaphylaxis, Henoch-SchÖnlein purpura, pericarditis, exacerbation of systemic lupus erythematosus, serum sickness-like reactions

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            Warnings

            Black Box Warnings

            Metronidazole has been shown to be carcinogenic in mice and rats

            Unknown whether metronidazole is associated with carcinogenicity in humans

            Contraindications

            Hypersensitivity to bismuth subsalicylate, metronidazole or other nitroimidazole derivatives, or tetracycline

            Coadministration with methoxyflurane; reports of fatal renal toxicity with concurrent use of tetracycline and methoxyflurane

            Use of disulfiram within previous 2 weeks; psychotic reactions reported with concurrent use of metronidazole and disulfiram

            Avoid alcohol or propylene glycol-containing products for at least 3 days after therapy with metronidazole-containing products are discontinued; disulfiram-like reaction may occur

            Severe renal impairment; tetracyclines may increase BUN; higher tetracycline serum concentrations may lead to azotemia, hyperphosphatemia, and acidosis

            Pregnancy

            Cautions

            Metronidazole shown to be carcinogenic in mice and rats; tumors affecting the liver, lungs, mammary and lymphatic tissues detected in several studies of metronidazole in rats and mice; unknown whether metronidazole is associated with carcinogenicity in humans

            Tetracycline can cause fetal harm when administered to a pregnant woman (see Pregnancy)

            Tetracycline administered during pregnancy at high doses (>2 g IV) associated with rare but serious cases of maternal hepatotoxicity (see Pregnancy)

            Use of tetracyclines during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown); this adverse reaction is more common during long-term use of the drug, but has been observed following repeated short-term courses

            Known or previously unrecognized candidiasis may present more prominent symptoms during therapy with metronidazole that requires treatment with an antifungal agent

            Photosensitivity, manifested by an exaggerated sunburn reaction, observed in patients taking tetracycline

            Bismuth-containing products may cause temporary and harmless darkening of the tongue and/or black stools, generally reversible within several days after treatment is stopped

            Metronidazole is a nitroimidazole, and should be used with care in patients with evidence of or history of blood dyscrasias

            Skin and subcutaneous disorders including Stevens-Johnson syndrome, toxic epidermal necrolysis and DRESS syndrome (drug rash with eosinophilia and systemic symptoms) reported

            Cases of severe hepatotoxicity/acute hepatic failure, including cases with a fatal outcome with very rapid onset after treatment initiation in patients with Cockayne syndrome reported with products containing metronidazole for systemic use

            Prescribing therapy in absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria

            Metronidazole may interfere with certain types of determinations of serum chemistry values, such as AST, SGOT, ALT, SGPT, LDH, triglycerides, and hexokinase glucose

            Bismuth absorbs x-rays and may interfere with x-ray diagnostic procedures of gastrointestinal tract

            Use of bismuth subsalicylate/metronidazole/tetracycline is not recommended in children and teenagers who have or who are recovering from varicella (chicken pox) or influenza due to the risk of Reye syndrome, a rare but serious illness

            Central and peripheral nervous system effects

            • Metronidazole
              • Convulsive seizures, encephalopathy, aseptic meningitis and peripheral neuropathy reported
              • Encephalopathy reported in association with cerebellar toxicity characterized by ataxia, dizziness, and dysarthria; CNS lesions seen on MRI described in reports of encephalopathy
              • CNS symptoms are generally reversible within days to weeks upon discontinuation of metronidazole
            • Tetracycline
              • Intracranial hypertension (IH), including pseudotumor cerebri, associated with the use of tetracyclines
              • Clinical manifestations of IH include headache, blurred vision, diplopia, and vision loss; papilledema can be found on funduscopy
              • Women of childbearing age who are overweight or have a history of IH are at greater risk for developing tetracycline associated IH
            • Bismuth-containing products
              • Cases of neurotoxicity associated with excessive doses of various bismuth-containing products reported
              • Effects have been reversible with discontinuation of bismuth therapy
              • Appearance of abnormal neurologic signs and symptoms demands the prompt evaluation of the benefit/risk ratio of the continuation of therapy

            Drug interactions overview

            • Avoid use with isotretinoin; both tetracycline and isotretinoin are known to cause intracranial hypertension
            • Tetracyclines may decrease effectiveness of oral contraceptives; instruct women to use backup contraception during treatment
            • Coadministration with anticoagulants may alter the effects of warfarin and other oral coumarin anticoagulants; metronidazole reported to potentiate the anticoagulant effect of warfarin, and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time; tetracycline shown to depress plasma prothrombin activity
            • In patients stabilized on relatively high doses of lithium, short-term use of metronidazole may cause elevation of serum lithium concentrations and signs of lithium toxicity
            • Metronidazole reported to increase plasma concentrations of busulfan, which can result in an increased risk for serious busulfan toxicity; do not administer concomitantly with busulfan unless the benefit outweighs the risk
            • Coadministration with drugs that inhibit CYP450 liver enzymes (eg, cimetidine) may result in a prolonged half-life and decreased plasma clearance of metronidazole
            • Coadministration with drugs that induce CYP450 liver enzymes (eg, phenytoin, phenobarbital) may accelerate the elimination of metronidazole, resulting in reduced plasma concentrations of metronidazole
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            Pregnancy & Lactation

            Pregnancy

            Contraindicated in women who are pregnant because treatment of H. Pylori infection can be delayed in pregnant women

            Use of tetracyclines during the second and third trimester pregnancy can also cause permanent discoloration of the teeth (yellow-gray brown) and possibly inhibit bone development in infant

            Administration of oral tetracycline to pregnant rats at various doses resulted in yellow fluorescence in teeth and bones in the newborn animals; maternal risks with high IV doses of tetracycline reported

            Metronidazole usage in pregnancy associated with certain congenital anomalies

            Tetracycline administered during pregnancy at high doses (>2 g IV) was associated with rare but serious cases of maternal hepatotoxicity; syndrome may result in stillborn or premature birth due to maternal pathology

            Lactation

            Tetracycline and metronidazole are present in human milk at concentrations similar to maternal serum levels

            It is unknown whether bismuth subcitrate is present in human milk It is unknown of the effect of therapy have the breastfed infant or on milk production

            Tetracycline binds with calcium in human milk

            Data indicate that oral absorption of tetracycline in infants is low due to the calcium binding in human milk

            Metronidazole transfers to human milk, and infant serum levels can be close to or comparable to infant therapeutic levels

            Because of the potential risk of tumorigenicity shown in animal studies with metronidazole, breastfeeding women should pump and discard human milk for the duration of therapy, and for 2 days after therapy ends, and feed her infant stored human milk (collected prior to therapy) or formula

            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

            Metronidazole, tetracycline: Inhibits nucleic acid synthesis by disrupting DNA

            Bismuth Subsalicylate: Antisecretory effect by salicylate, antimicrobial action by bismuth

            Tetracycline: Binds to the 30S and possibly 50S ribosomal subunits of susceptbible bacteria to inhibit proteain synthesis

            Pharmacokinetics

            Metronidazole

            • Absorption: 80% from GI tract
            • Distribution: Widely distributed; 13-43% (normal meningers); 100% (inflamed meninges)
            • Metabolism: Liver (30-60%)
            • Protein binding: < 20%
            • Peak plasma time: 1-2 hr
            • Half-life: 25-75 hr (neonates); 6-8 hr (others); 21 hr (end stage renal disease)
            • Enzymes inhibited: hepatic CYP2C9
            • Excretion: Urine: 77%; feces: 14%

            Tetracycline

            • Absorption: 75%
            • Distribution: Small amount appears in bile; relative diffusion from blood into CSF
            • Protein bound: 65%
            • Half-life: 8-11 hr (normal renal function); 57-108 hr (end-stage renal disease)
            • Peak Plasma Time: 2-4 hr
            • Excretion: Urine (60% as unchanged drug); feces (as active form)

            Bismuth Subsalicylate

            • Half-Life: highly variable
            • Peak Plasma Time: Bismuth: 1.8-5 hr
            • Bioavailability: Bismuth: <1%; Salicylate: >90%
            • Onset: 4 hr
            • Protein Bound: 90% (bismuth);>90% (salicylate)
            • Metabolism: Stomach: bismuth subsalicylate is hydrolyzed in stomach to form the slightly soluble bismuth oxychloride (BiOCl) and salicylic acid
            • Metabolites: salicylate (active), [BiOCl, bismuth subcarbonate, bismuth phosphate] (activity unknown); unchanged bismuth subsalicylate passes into duodenum and reacts with other anions (eg, bicarbonate, phosphate) to form bismuth subcarbonate and bismuth phosphate salts; BiOCl, bismuth subcarbonate, bismuth phosphate, and undissociated bismuth subsalicylate react with hydrogen sulfide; salicylate is extensively metabolized in liver
            • Clearance: Bismuth: 50 mL/min
            • Excretion:
            • Bismuth: Urine & feces
            • Salicylate: Urine
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            Administration

            Oral Administration

            Administer tablets and capsules at mealtimes and at bedtime

            Bismuth subsalicylate tablets: Chew and swallow

            Metronidazole tablet and tetracycline hydrochloride capsule: Swallow whole with a full glass of water (8 ounces)

            Ingestion of adequate amounts of fluid, particularly with the bedtime dose, is recommended to reduce the risk of esophageal irritation and ulceration by tetracycline hydrochloride

            Missed dose: Continue normal dosing schedule until medication is gone; do not take double doses; if >4 doses are missed, contact prescriber

            Storage

            Blister packs: Store at room temperature (20-25°C [68-77°F])

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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic 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.