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.secobarbitalMonitor Closely (2)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.secukinumabMonitor Closely (1)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.siltuximabMonitor Closely (1)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.smokingMonitor Closely (1)smoking will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.somapacitanMonitor Closely (2)somapacitan will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates somapacitan will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substratessomatrogonMonitor Closely (2)somatrogon will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates somatrogon will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substratessomatropinMonitor Closely (2)somatropin will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrates somatropin will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substratessotalolMonitor Closely (1)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.St John's WortSerious - Use Alternative (1)St John's Wort will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.stiripentolMonitor Closely (2)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.tazemetostatMonitor Closely (1)tazemetostat will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.teclistamabMonitor Closely (1)teclistamab will increase the level or effect of theophylline by altering metabolism. Use Caution/Monitor. Teclistamab causes release of cytokines that may suppress activity of CYP450 enzymes, resulting in increased exposure of CYP substrates. Monitor for increased concentrations or toxicities of sensitive CYP substrates. Adjust dose of CYP substrate drug as needed. tecovirimatMonitor Closely (1)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.teduglutideMonitor Closely (1)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 ethylMonitor Closely (1)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.teriflunomideMonitor Closely (1)teriflunomide decreases levels of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.tesamorelinMonitor Closely (1)theophylline will decrease the level or effect of tesamorelin by altering metabolism. Modify Therapy/Monitor Closely. Monitor theophylline levelsthyroid desiccatedMinor (1)thyroid desiccated decreases levels of theophylline by increasing elimination. Minor/Significance Unknown.ticlopidineMinor (1)ticlopidine increases levels of theophylline by decreasing metabolism. Minor/Significance Unknown.timololMonitor Closely (1)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 useMonitor Closely (1)tobacco use will decrease the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.topiramateMonitor Closely (1)topiramate will decrease the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.trofinetideMonitor Closely (1)trofinetide will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).tucatinibSerious - Use Alternative (1)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.ustekinumabMonitor Closely (1)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.vemurafenibMonitor Closely (1)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.verapamilMonitor Closely (2)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.voriconazoleMonitor Closely (1)voriconazole will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.voxelotorSerious - Use Alternative (1)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.zafirlukastMonitor Closely (1)zafirlukast will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)theophylline decreases levels of zafirlukast by unknown mechanism. Minor/Significance Unknown.zileutonMonitor Closely (1)zileuton will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. 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 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 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 concentrationPregnancy 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. 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 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 BRAND FORM. UNIT PRICE PILL IMAGE Theo-24 oral- 400 mg capsuleTheo-24 oral- 100 mg capsuleTheo-24 oral- 200 mg capsuleTheo-24 oral- 300 mg capsuleTheo-24 oral- 200 mg capsuleTheo-24 oral- 400 mg capsuleTheo-24 oral- 300 mg capsuletheophylline oral- 400 mg tablettheophylline oral- 80 mg/15 mL solutiontheophylline oral- 450 mg tablettheophylline oral- 300 mg tablettheophylline oral- 200 mg tablettheophylline oral- 600 mg tablettheophylline oral- 400 mg tablettheophylline oral- 300 mg tablettheophylline oral- 600 mg tablettheophylline oral- 400 mg tablettheophylline oral- 450 mg tablettheophylline oral- 300 mg tablettheophylline oral- 80 mg/15 mL solutiontheophylline oral- 450 mg tablettheophylline oral- 300 mg tablettheophylline oral- 450 mg tablettheophylline oral- 100 mg tablettheophylline oral- 80 mg/15 mL elixirtheophylline oral- 600 mg tablettheophylline oral- 80 mg/15 mL solutionCopyright © 2010 First DataBank, Inc.Print Patient Educationtheophylline 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