theophylline (Rx)

Brand and Other Names:Theo 24, Theochron, more...Elixophyllin, aminophylline, Uniphyl
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

capsule, extended-release (24 hours)

  • 100mg
  • 200mg
  • 300mg
  • 400mg

tablet, extended release (12 hours)

  • 100mg
  • 200mg
  • 300mg
  • 450mg

tablet, extended-release (24 hours)

  • 400mg
  • 600mg

oral elixir

  • 80mg/15mL

intravenous solution

  • 400mg/250mL D5W
  • 400mg/500mL D5W
  • 800mg/500mL D5W

Acute Bronchospasm

Loading

  • Patients not currently taking theophylline: 5-7 mg/kg IV/PO; not to exceed 25 mg/min IV  
  • Aminophylline: 6-7 mg/kg IV infused over 20 minutes

Maintenance

  • 0.4-0.6 mg/kg/hr IV or 4.8-7.2 mg/kg PO (extended release) q12hr to maintain levels 10-15 mg/L  
  • Smokers: 0.79 mg/kg/hr IV for next 12 hours after loading dose, then 0.63 mg/kg/hr or 5 mg/kg PO (extended release) q8hr
  • Coadmininstration with drugs that decrease theophylline clearance (eg, cimetidine, ciprofloxacin, and erythromycin and other macrolides): 0.2-0.3 mg/kg/hr IV or PO (extended release) q12-24hr
  • Congestive heart failure: 0.39 mg/kg/hr IV for next 12 hours after loading dose, then 0.08-0.16 mg/kg/hr

Dosage Modifications

Hepatic impairment: After loading dose, 0.39 mg/kg/hr IV for next 12 hours, then 0.08-0.16 mg/kg/hr  

Dosing Considerations

For PO loading, use immediate-release theophylline

If patient is already taking theophylline, give smaller loading dose

Use ideal body weight to calculate dose

1 mg/kg results in 2 mg/L (34.4 mmol/L) increase in serum theophylline

Therapeutic range: 10-20 mg/L (172-344 mmol/L)

Aminophylline

  • All dosages expressed as aminophylline; use ideal body weight (theophylline distributes poorly into body fat) to calculate dose; individualize dose based on steady-state serum concentrations
  • If administering aminophylline, increase dose by 25% (aminophylline is approximately 79-86% theophylline)
  • Treatment of asthma and acute COPD exacerbations with aminophylline is not recommended by current clinical practice guidelines

Dosage Forms & Strengths

capsule, extended-release (24 hours)

  • 100mg
  • 200mg
  • 300mg
  • 400mg

tablet, extended-release (12 hours)

  • 100mg
  • 200mg
  • 300mg
  • 450mg

tablet, extended-release (24 hours)

  • 400mg
  • 600mg

oral elixir

  • 80mg/15mL

intravenous solution

  • 400mg/250mL D5W
  • 400mg/500mL D5W
  • 800mg/500mL D5W

Bronchospasm

Loading

  • No theophylline administered in previous 24 hours: 5-7 mg/kg IV/PO; IV infused over 20-30 minutes  

Maintenance

  • 1.5-6 months: 0.5 mg/kg/hr IV or 10 mg/kg/day PO in divided doses  
  • 6-12 months: 0.6-0.7 mg/kg/hr IV or 12-18 mg/kg/day PO in divided doses
  • 1-9 years: 1 mg/kg/hr IV or 8 mg/kg PO (extended release) q8hr
  • 9-12 years: 0.8-0.9 mg/kg/hr IV or 6.4 mg/kg PO (extended release) q8hr
  • 12-16 years: 0.7 mg/kg/hr IV or 5.6 mg/kg PO (extended release) q8hr

Neonatal Apnea

Loading: 4-5 mg/kg PO/IV once  

Maintenance: 3-6 mg/kg/day PO/IV divided q8hr

Dosing Considerations

If administering aminophylline, increase dose by 20-25% (aminophylline is approximately 79-86% theophylline)

Use ideal body weight to calculate dose

1 mg/kg results in 2 mg/L (34.4 mmol/L) increase in serum theophylline

Acute Bronchospasm

After loading dose, 0.47 mg/kg/hr IV for next 12 hours, then 0.24 mg/kg/hr  

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Interactions

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            Contraindicated (3)

            • dipyridamole

              theophylline decreases effects of dipyridamole by pharmacodynamic antagonism. Contraindicated. May produce false negative results in dipyridamole thallium imaging tests. Separate by 24 hr.

            • febuxostat

              febuxostat increases levels of theophylline by decreasing metabolism. Contraindicated.

            • riociguat

              theophylline, riociguat. Either increases effects of the other by additive vasodilation. Contraindicated. Coadministration of nonspecific PDE-5 inhibitors (eg, dipyridamole, theophylline) and guanylate cyclase stimulators (eg, riociguat) is contraindicated due to risk of additive hypotension.

            Serious - Use Alternative (31)

            • abametapir

              abametapir will increase the level or effect of theophylline 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.

              abametapir will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP1A2 substrates. If not feasible, avoid use of abametapir.

            • allopurinol

              allopurinol increases levels of theophylline by decreasing metabolism. Avoid or Use Alternate Drug.

            • apalutamide

              apalutamide will decrease the level or effect of theophylline 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.

            • bremelanotide

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

            • bupropion

              theophylline increases toxicity of bupropion by unspecified interaction mechanism. Avoid or Use Alternate Drug. May lower seizure threshold; keep bupropion dose as low as possible.

            • carbamazepine

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

              theophylline decreases levels of carbamazepine by increasing metabolism. Avoid or Use Alternate Drug.

            • ceritinib

              ceritinib increases levels of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concurrent use of CYP3A substrates known to have narrow therapeutic indices or substrates primarily metabolized by CYP3A during treatment with ceritinib; if use of these medications is unavoidable, consider dose.

            • cimetidine

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

            • ciprofloxacin

              ciprofloxacin will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Concomitant use of theophylline and ciprofloxacin has decreased theophylline clearance and increased plasma levels and symptoms of toxicity. Serious and fatal reactions have included cardiac arrest, seizure, status epilepticus, and respiratory failure. If concomitant use cannot be avoided, monitor theophylline levels and adjust dosage as needed.

              ciprofloxacin will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Concomitant use of theophylline and ciprofloxacin has decreased theophylline clearance and increased plasma levels and symptoms of toxicity. Serious and fatal reactions have included cardiac arrest, seizure, status epilepticus, and respiratory failure. If concomitant use cannot be avoided, monitor theophylline levels and adjust dosage as needed.

            • clarithromycin

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

            • erythromycin base

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

            • erythromycin ethylsuccinate

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

            • erythromycin lactobionate

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

            • erythromycin stearate

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

            • fexinidazole

              fexinidazole will increase the level or effect of theophylline 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.

            • fluvoxamine

              fluvoxamine will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • givosiran

              givosiran will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP1A2 substrates with givosiran. If unavoidable, decrease the CYP1A2 substrate dosage in accordance with approved product labeling.

            • idelalisib

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

            • ivosidenib

              ivosidenib will decrease the level or effect of theophylline 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.

            • ketoconazole

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

            • lonafarnib

              lonafarnib will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

            • metoclopramide intranasal

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

            • nefazodone

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

            • pefloxacin

              pefloxacin will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • regadenoson

              theophylline decreases effects of regadenoson by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid methylxanthines for 12 hours before regadenoson administration.

            • rifabutin

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

            • rifampin

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

            • rucaparib

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

            • St John's Wort

              St John's Wort will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • tucatinib

              tucatinib will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • voxelotor

              voxelotor will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            Monitor Closely (147)

            • acebutolol

              acebutolol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

            • activated charcoal

              activated charcoal decreases levels of theophylline by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • adenosine

              theophylline decreases effects of adenosine by pharmacodynamic antagonism. Use Caution/Monitor.

            • amifampridine

              theophylline 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.

            • amobarbital

              amobarbital will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

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

            • aprepitant

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

            • armodafinil

              armodafinil will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

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

            • artemether/lumefantrine

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

            • atazanavir

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

            • atenolol

              atenolol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

            • betaxolol

              betaxolol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

            • bisoprolol

              bisoprolol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

            • blinatumomab

              blinatumomab increases levels of theophylline by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

            • bosentan

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

            • brodalumab

              brodalumab, theophylline. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, brodalumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of brodalumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • budesonide

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

            • butabarbital

              butabarbital will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

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

            • butalbital

              butalbital will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

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

            • cannabidiol

              cannabidiol, theophylline. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Owing to the potential for both CYP1A2 induction and inhibition with the coadministration of CYP1A2 substrates and cannabidiol, consider reducing dosage adjustment of CYP1A2 substrates as clinically appropriate.

            • carbamazepine

              carbamazepine will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • carvedilol

              carvedilol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

            • celiprolol

              celiprolol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

            • cenobamate

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

              cenobamate, theophylline. Either increases effects of the other by sedation. Use Caution/Monitor.

            • cigarette smoking

              cigarette smoking will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • cimetidine

              cimetidine will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • cobicistat

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

            • conivaptan

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

            • cortisone

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

            • crizotinib

              crizotinib increases levels of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of crizotinib with CYP3A substrates with narrow therapeutic indices should be avoided.

            • crofelemer

              crofelemer increases levels of theophylline 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.

            • dabrafenib

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

            • darifenacin

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

            • darunavir

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

            • dasatinib

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

            • deferasirox

              deferasirox will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Avoid the concomitant use of theophylline with deferasirox. If you must co-administer theophylline and deferasirox, monitor theophylline concentration and consider theophylline dose modification.

            • deflazacort

              theophylline and deflazacort both decrease serum potassium. Use Caution/Monitor.

            • dexamethasone

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

            • DHEA, herbal

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

            • dichlorphenamide

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

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

            • diltiazem

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

            • doxapram

              doxapram, theophylline. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Increased skeletal muscle activity, agitation, hyperactivity.

            • dronedarone

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

            • dulaglutide

              dulaglutide, theophylline. Other (see comment). Use Caution/Monitor. Comment: Dulaglutide slows gastric emptying and may impact absorption of concomitantly administered oral medications; be particularly cautious when coadministered with drugs that have a narrow therapeutic index.

            • dupilumab

              dupilumab, theophylline. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, dupilumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of dupilumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • efavirenz

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

            • elagolix

              elagolix decreases levels of theophylline 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 theophylline 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, theophylline. 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.

            • erythromycin base

              erythromycin base will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • esmolol

              esmolol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

            • ethinylestradiol

              ethinylestradiol will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • etravirine

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

            • fedratinib

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

            • ferric maltol

              ferric maltol, theophylline. Either increases levels of the other by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ferric maltol with certain oral medications may decrease the bioavailability of either ferric maltol and some oral drugs. For oral drugs where reductions in bioavailability may cause clinically significant effects on its safety or efficacy, separate administration of ferric maltol from these drugs. Duration of separation may depend on the absorption of the medication concomitantly administered (eg, time to peak concentration, whether the drug is an immediate or extended release product).

            • fexinidazole

              fexinidazole will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • fluconazole

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

            • fludrocortisone

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

            • fosamprenavir

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

            • fosphenytoin

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

            • grapefruit

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

            • green tea

              green tea increases levels of theophylline by decreasing renal clearance. Use Caution/Monitor. Due to caffeine content.

            • griseofulvin

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

            • guselkumab

              guselkumab, theophylline. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • hydrocortisone

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

            • iloperidone

              iloperidone increases levels of theophylline 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.

            • indacaterol, inhaled

              theophylline, indacaterol, inhaled. serum potassium. Use Caution/Monitor. Combination may increase risk of hypokalemia.

            • indinavir

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

            • interferon alfa 2b

              interferon alfa 2b increases levels of theophylline by decreasing metabolism. Use Caution/Monitor. Greater risk of interaction in smokers.

            • interferon alfa n3

              interferon alfa n3 increases levels of theophylline by decreasing metabolism. Use Caution/Monitor. Greater risk of interaction in smokers.

            • interferon gamma 1b

              interferon gamma 1b increases levels of theophylline by decreasing metabolism. Use Caution/Monitor. Greater risk of interaction in smokers.

            • iodine (radioactive)

              iodine (radioactive) increases levels of theophylline by decreasing elimination. Use Caution/Monitor.

            • isoniazid

              isoniazid will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

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

            • istradefylline

              istradefylline will increase the level or effect of theophylline 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.

            • itraconazole

              itraconazole will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • ixekizumab

              ixekizumab, theophylline. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, ixekizumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of ixekizumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • labetalol

              labetalol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

            • lapatinib

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

            • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

              levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will increase the level or effect of theophylline by decreasing metabolism. Use Caution/Monitor. Combined oral contraceptives containing EE may inhibit the metabolism and increase plasma concentrations of cyclosporine.

            • lumefantrine

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

            • marijuana

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

            • methimazole

              methimazole increases levels of theophylline by decreasing elimination. Use Caution/Monitor.

            • methotrexate

              methotrexate increases levels of theophylline by unknown mechanism. Use Caution/Monitor. Methotrexate may decrease the clearance of theophylline. Theophylline levels should be monitored when used concomitantly with methotrexate.

            • methylprednisolone

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

            • metoprolol

              metoprolol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

            • metronidazole

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

            • mexiletine

              mexiletine will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • miconazole vaginal

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

            • midazolam intranasal

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

            • mitotane

              mitotane decreases levels of theophylline 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.

            • modafinil

              modafinil will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

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

            • nadolol

              nadolol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

            • nebivolol

              nebivolol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

            • nelfinavir

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

            • nevirapine

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

            • nifedipine

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

            • nilotinib

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

            • nilutamide

              nilutamide will increase the level or effect of theophylline by decreasing metabolism. Use Caution/Monitor.

            • obeticholic acid

              obeticholic acid will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. CYP1A2 substrates that have a narrow therapeutic index should be monitored closely and the dose adjusted accordingly.

            • olodaterol inhaled

              theophylline and olodaterol inhaled both decrease serum potassium. Use Caution/Monitor.

            • osilodrostat

              osilodrostat will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • oxcarbazepine

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

            • pantoprazole

              pantoprazole increases toxicity of theophylline by Other (see comment). Use Caution/Monitor. Comment: Prolonged use of proton pump inhibitors can cause hypochlorhydria, which in turn causes peristalsis in small intestine to increase and peristalsis in the proximal colon to decrease; monitor for toxicity.

            • peginterferon alfa 2a

              peginterferon alfa 2a will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • peginterferon alfa 2b

              peginterferon alfa 2b increases levels of theophylline by unknown mechanism. Use Caution/Monitor. Alpha interferons may decrease the clearance of theophylline resulting in increased plasma concentrations.

            • penbutolol

              penbutolol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

            • pentobarbital

              pentobarbital will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

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

            • phenobarbital

              phenobarbital will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

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

            • phenytoin

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

            • pindolol

              pindolol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

            • pipemidic acid

              pipemidic acid will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • posaconazole

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

            • prednisone

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

            • primidone

              primidone will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

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

            • propranolol

              propranolol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

            • propylthiouracil

              propylthiouracil increases levels of theophylline by decreasing elimination. Use Caution/Monitor.

            • quinupristin/dalfopristin

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

            • rabeprazole

              rabeprazole increases toxicity of theophylline by Other (see comment). Use Caution/Monitor. Comment: Prolonged use of proton pump inhibitors can cause hypochlorhydria, which in turn causes peristalsis in small intestine to increase and peristalsis in the proximal colon to decrease; monitor for toxicity.

            • rifampin

              rifampin will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • rifapentine

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

            • ritonavir

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

            • rufinamide

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

            • sarilumab

              sarilumab, theophylline. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.

            • secobarbital

              secobarbital will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

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

            • secukinumab

              secukinumab, theophylline. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, secukinumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of secukinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • siltuximab

              siltuximab, theophylline. Other (see comment). Use Caution/Monitor. Comment: CYP450 activity in the liver is down regulated by infection and inflammation stimuli including cytokines (eg, IL-6); inhibition of IL-6 by siltuximab may restore CYP450 enzymatic activity; caution if coadministered with CYP substrates that have a narrow therapeutic index.

            • smoking

              smoking will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • sotalol

              sotalol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

            • stiripentol

              stiripentol, theophylline. affecting hepatic enzyme CYP1A2 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP1A2 inhibitor and inducer. Monitor CYP1A2 substrates coadministered with stiripentol for increased or decreased effects. CYP1A2 substrates may require dosage adjustment.

              stiripentol, theophylline. 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.

            • tazemetostat

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

            • tecovirimat

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

            • teduglutide

              teduglutide increases levels of theophylline by Other (see comment). Use Caution/Monitor. Comment: Teduglutide may increase absorption of concomitant PO medications; caution with with drugs requiring titration or those with a narrow therapeutic index; dose adjustment may be necessary.

            • telotristat ethyl

              telotristat ethyl will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.

            • teriflunomide

              teriflunomide decreases levels of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • tesamorelin

              theophylline will decrease the level or effect of tesamorelin by altering metabolism. Modify Therapy/Monitor Closely. Monitor theophylline levels

            • timolol

              timolol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

            • tobacco use

              tobacco use will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • topiramate

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

            • ustekinumab

              ustekinumab, theophylline. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

            • vemurafenib

              vemurafenib decreases levels of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Concomitant use of vemurafenib with agents with narrow therapeutic windows is not recommended as vemurafenib may alter their concentrations. If coadministration cannot be avoided, use caution and consider dose reduction of concomitant CYP1A2 substrate drug.

            • verapamil

              verapamil will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

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

            • voriconazole

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

            • zafirlukast

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

            • zileuton

              zileuton will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            Minor (25)

            • amiodarone

              amiodarone increases levels of theophylline by decreasing metabolism. Minor/Significance Unknown.

            • cetirizine

              theophylline increases levels of cetirizine by decreasing elimination. Minor/Significance Unknown.

            • cilostazol

              theophylline increases levels of cilostazol by decreasing metabolism. Minor/Significance Unknown.

            • clarithromycin

              clarithromycin increases levels of theophylline by decreasing metabolism. Minor/Significance Unknown.

            • clinafloxacin

              clinafloxacin increases levels of theophylline by decreasing metabolism. Minor/Significance Unknown.

            • dexlansoprazole

              dexlansoprazole increases toxicity of theophylline by Other (see comment). Minor/Significance Unknown. Comment: Prolonged use of proton pump inhibitors can cause hypochlorhydria, which in turn causes peristalsis in small intestine to increase and peristalsis in the proximal colon to decrease; monitor for toxicity.

            • disulfiram

              disulfiram increases levels of theophylline by decreasing metabolism. Minor/Significance Unknown.

            • elderberry

              elderberry increases effects of theophylline by decreasing metabolism. Minor/Significance Unknown.

            • esomeprazole

              esomeprazole increases toxicity of theophylline by Other (see comment). Minor/Significance Unknown. Comment: Prolonged use of proton pump inhibitors can cause hypochlorhydria, which in turn causes peristalsis in small intestine to increase and peristalsis in the proximal colon to decrease; monitor for toxicity.

            • lansoprazole

              lansoprazole increases levels of theophylline by decreasing metabolism. Minor/Significance Unknown.

              lansoprazole increases toxicity of theophylline by Other (see comment). Minor/Significance Unknown. Comment: Prolonged use of proton pump inhibitors can cause hypochlorhydria, which in turn causes peristalsis in small intestine to increase and peristalsis in the proximal colon to decrease; monitor for toxicity.

            • levocetirizine

              theophylline increases levels of levocetirizine by decreasing elimination. Minor/Significance Unknown.

            • levothyroxine

              levothyroxine decreases levels of theophylline by increasing elimination. Minor/Significance Unknown.

            • liothyronine

              liothyronine decreases levels of theophylline by increasing elimination. Minor/Significance Unknown.

            • lithium

              theophylline decreases levels of lithium by increasing renal clearance. Minor/Significance Unknown.

            • omeprazole

              omeprazole will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

              omeprazole increases toxicity of theophylline by Other (see comment). Minor/Significance Unknown. Comment: Prolonged use of proton pump inhibitors can cause hypochlorhydria, which in turn causes peristalsis in small intestine to increase and peristalsis in the proximal colon to decrease; monitor for toxicity.

            • pentoxifylline

              pentoxifylline increases levels of theophylline by decreasing metabolism. Minor/Significance Unknown.

            • phytoestrogens

              phytoestrogens increases levels of theophylline by decreasing metabolism. Minor/Significance Unknown.

              phytoestrogens increases levels of theophylline by decreasing elimination. Minor/Significance Unknown.

            • propafenone

              propafenone increases levels of theophylline by decreasing renal clearance. Minor/Significance Unknown.

            • pyrantel pamoate

              pyrantel pamoate increases levels of theophylline by unspecified interaction mechanism. Minor/Significance Unknown.

            • pyridoxine

              theophylline decreases levels of pyridoxine by altering metabolism. Minor/Significance Unknown.

            • pyridoxine (Antidote)

              theophylline decreases levels of pyridoxine (Antidote) by altering metabolism. Minor/Significance Unknown.

            • ribociclib

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

            • thyroid desiccated

              thyroid desiccated decreases levels of theophylline by increasing elimination. Minor/Significance Unknown.

            • ticlopidine

              ticlopidine increases levels of theophylline by decreasing metabolism. Minor/Significance Unknown.

            • zafirlukast

              theophylline decreases levels of zafirlukast by unknown mechanism. Minor/Significance Unknown.

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            Adverse Effects

            Frequency Not Defined

            Peak serum concentration <20 mcg/mL

            • Central nervous system excitement, headache, insomnia, irritability, restlessness, seizure
            • Diarrhea, nausea, vomiting
            • Diuresis (transient)
            • Exfoliative dermatitis
            • Skeletal muscle tremors
            • Tachycardia, flutter
            • Hypercalcemia (with concomitant hyperthyroid disease)
            • Difficulty urinating (elderly males with prostatism)

            Peak serum concentration >30 mcg/mL

            • Acute myocardial infarction
            • Seizures (resistant to anticonvulsants)
            • Urinary retention
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            Warnings

            Contraindications

            Hypersensitivity

            Cautions

            Patients, who develop CNS abnormalities, reported (rarely) to experience nonconvulsive status epilepticus

            Theophylline clearance may decrease in patients with congestive heart failure, acute pulmonary edema, hepatic disease, cor pulmonale, acute hepatitis, hypothyroidism, cirrhosis, fever, or sepsis with multiorgan failure and shock; severe and potentially fatal toxicity may occur if reduced theophylling clearance occurs

            Avoid extravasation; vesicant; ensure proper placement of catherer prior to and during infusion

            Use with caution in patients with hyperthyroidism, seizure disorder, peptic ulcer, or cardiovascular disease

            Some dosage forms may contain propylene glycol; use caution; seizures, hyperosmolality, lactic acidosis, and respiratory depression reported associated with use of large amounts of propylene glycol

            Measure serum levels and withhold subsequent doses if patient develops signs and symptoms of theophylline toxicity

            Use caution in patients with cardiac arrhythmia, excluding bradyarrhythmia; use may exacerbate arrhythmia

            Use with caution in patients with cystic fibrosis; increased theophylline clearance may occur

            Use with caution in patients with seizure disorders; use may exacerbate seizure disorder

            Do not increase dose in response to acute exacerbation of symptoms unless steady state serum theophylline concentration of <10 mcg//mL

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            Pregnancy & Lactation

            Pregnancy category: C

            Lactation: Theophylline is excreted into breast milk and may cause irritability or other signs of mild toxicity in nursing human infants; serious adverse effects in infant are unlikely unless mother has toxic serum theophylline concentration

            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

            Theophylline relaxes smooth muscles of respiratory tract and suppresses the response of the airways to stimuli

            May increase tissue concentration of cyclic adenine monophosphate (cAMP) by inhibiting 2 isoenzymes of phosphodiesterase (PDE III and, to a lesser extent, PDE IV), which ultimately induces release of epinephrine from the adrenal medulla cells

            Absorption

            Onset: Variable

            Duration: Variable

            Peak plasma time: 1-2 hr

            Peak plasma concentration: 10 mcg/mL

            Distribution

            Protein bound: 40-55%

            Vd: 0.3-0.7 L/kg

            Metabolism

            Metabolized in liver by CYP1A2 and CYP3A4

            Metabolites: 1,3-Dimethyluric acid, 1-methyluric acid, 3-methylxanthine

            Elimination

            Half-life: Nonsmoker, 8 hr; smoker, 4-5 hr

            Clearance: 1.45 mL/min/kg

            Excretion: Urine

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            Administration

            IV Incompatibilities

            Additive: Clindamycin, dobutamine, epinephrine, erythromycin, meperdine, morphine, norepinephrine, vancomycin, vitamins B and C

            Y-site: Amiodarone, dobutamine, fenoldopam

            Not specified: Carbenicillin, tetracycline

            IV Compatibilities

            Additive: Calcium gluconate, dopamine, esmolol, heparin, hydrocortisone, hydroxyzine, lidocaine, nitroglycerin, pentobarbital, potassium chloride, sodium bicarbonate, verapamil

            Syringe: Heparin, pentobarbital

            Y-site: Ampicillin, cefazolin, esmolol, heparin, potassium chloride, vitamins B and C

            Not specified: Diazepam

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Theo-24 oral
            -
            400 mg capsule
            Theo-24 oral
            -
            300 mg capsule
            Theo-24 oral
            -
            200 mg capsule
            Theo-24 oral
            -
            100 mg capsule
            Theo-24 oral
            -
            200 mg capsule
            Theo-24 oral
            -
            300 mg capsule
            Theo-24 oral
            -
            400 mg capsule
            theophylline oral
            -
            80 mg/15 mL elixir
            theophylline oral
            -
            400 mg tablet
            theophylline oral
            -
            600 mg tablet
            theophylline oral
            -
            200 mg tablet
            theophylline oral
            -
            600 mg tablet
            theophylline oral
            -
            400 mg tablet
            theophylline oral
            -
            300 mg tablet
            theophylline oral
            -
            80 mg/15 mL solution
            theophylline oral
            -
            80 mg/15 mL solution
            theophylline oral
            -
            450 mg tablet
            theophylline oral
            -
            300 mg tablet
            theophylline oral
            -
            600 mg tablet
            theophylline oral
            -
            450 mg tablet
            theophylline oral
            -
            100 mg tablet
            theophylline oral
            -
            400 mg tablet

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            theophylline oral

            THEOPHYLLINE SUSTAINED-RELEASE - ORAL

            (thee-OF-i-lin)

            COMMON BRAND NAME(S): Uniphyl

            USES: Theophylline is used to treat lung diseases such as asthma and COPD (bronchitis, emphysema). It must be used regularly to prevent wheezing and shortness of breath. This medication belongs to a class of drugs known as xanthines. It works by relaxing the muscles around the airways so that they open up and you can breathe more easily. It also decreases the lungs' response to irritants. Controlling symptoms of breathing problems can decrease time lost from work or school.This medication must be used regularly to be effective. It does not work right away and should not be used to relieve sudden breathing problems. If sudden shortness of breath occurs, use your quick-relief inhaler as prescribed.

            HOW TO USE: Take this medication by mouth as directed by your doctor, usually once or twice daily. Since different manufacturers have different ways to take this medication, ask your doctor or pharmacist about the best time(s) to take your brand of theophylline and if you should take the drug with or without food.Do not crush or chew the capsules or tablets. Doing so can release all of the drug at once, increasing the risk of side effects. Also, do not split the tablets unless they have a score line and your doctor or pharmacist tells you to do so. Swallow the whole or split tablet without crushing or chewing.The dosage is based on your medical condition, response to treatment, age, weight, lab tests (theophylline blood levels), and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products). To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully.Certain diets (such as high protein/low carbohydrate or high carbohydrate/low protein) may change the effect of theophylline. Tell your doctor if you have any major changes in your diet. Your doctor may need to adjust your dose.Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time(s) each day. Keep taking this medication even if you feel well. Do not increase your dose, take this drug more often, or stop taking it without first consulting your doctor.Get medical help right away if your asthma symptoms worsen or if you are using your quick-relief inhaler more than usual or more often than prescribed.

            SIDE EFFECTS: Nausea/vomiting, stomach/abdominal pain, headache, trouble sleeping, diarrhea, irritability, restlessness, nervousness, shaking, or increased urination may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: nausea/vomiting that doesn't stop, fast/slow/irregular heartbeat, muscle cramps, fainting, confusion, dizziness.Get medical help right away if you have any very serious side effects, including: seizures.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before using theophylline, tell your doctor or pharmacist if you are allergic to it; or to other xanthine drugs (such as aminophylline, oxtriphylline, caffeine); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: stomach/intestinal ulcer, seizures, thyroid disease, heart problems (such as heart failure, irregular heartbeat), liver disease, high blood pressure.If you get sick or have a fever while taking this medication, tell your doctor right away. The dose of your medicine may need to be adjusted.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Older adults may be more sensitive to the side effects of this drug, especially fast/irregular heartbeat, or trouble sleeping. Careful monitoring of side effects and drug blood levels is recommended.Children may be more sensitive to the side effects of this drug. Careful monitoring of side effects and drug blood levels is recommended.During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor. Changes in your body during the last 3 months of pregnancy may affect the amount of this drug in your blood. Your doctor should carefully monitor the amount of drug in your blood, as well as any side effects, so that your dose may be changed if needed.This drug passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.A product that may interact with this drug is: riociguat.Other medications can affect the removal of theophylline from your body, which may affect how theophylline works. Examples include cimetidine, disulfiram, fluvoxamine, interferon, mexiletine, propranolol, rifampin, drugs used to treat seizures (such as carbamazepine, phenytoin), St. John's wort, ticlopidine, viloxazine, among others.Cigarette/marijuana (cannabis) smoking decreases blood levels of this medication. Tell your doctor if you smoke or if you have recently stopped smoking.Caffeine and alcohol can increase the side effects of this medication. Avoid drinking large amounts of beverages containing alcohol or caffeine (such as coffee, tea, colas), eating large amounts of chocolate, or taking nonprescription products that contain caffeine.Theophylline is very similar to aminophylline and oxtriphylline. Do not take medications containing aminophylline or oxtriphylline while using theophylline.This medication may interfere with certain lab tests (such as blood sugar, cholesterol, uric acid, dipyridamole-thallium imaging tests), possibly causing false test results. Make sure lab personnel and all your doctors know you use this drug.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: nausea/vomiting that doesn't stop, seizures, muscle cramps, fast/irregular heartbeat, mental/mood changes (such as agitation, confusion), vomit that looks like coffee grounds.

            NOTES: Do not share this medication with others.Lab and/or medical tests (such as theophylline blood levels) should be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.

            MISSED DOSE: If you miss a dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

            Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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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.