Caffeine concentrations are usually undetectable in adults regardless of renal function. In neonates, caffeine may accumulate to concentrations that approximate the unmetabolized Theophylline concentration and thus, exert a pharmacologic effect. Both the N-demethylation and hydroxylation pathways of Theophylline biotransformation are capacity-limited.

Accurate prediction of dose-dependency of Theophylline metabolism in patients a priori is not possible, but patients with very high initial clearance rates i. Since little Theophylline is excreted unchanged in the urine and since active metabolites of Theophylline i.

In contrast, the large fraction of the Theophylline dose excreted in the urine as unchanged Theophylline and caffeine in neonates requires careful attention to dose reduction and frequent monitoring of serum Theophylline concentrations in neonates with reduced renal function See WARNINGS.

Serum Concentrations at Steady-State: After multiple doses of Theophylline, steady-state is reached in hours average 40 hours in adults.

The difference between peak and trough concentrations is larger in patients with more rapid Theophylline clearance. Special Populations See Table I for mean clearance and half-life values: Gender differences in Theophylline clearance are relatively small and unlikely to be of clinical significance. Significant reduction in Theophylline clearance, however, has been reported in women on the 20th day of the menstrual cycle and during the third trimester of pregnancy. Pharmacokinetic differences in Theophylline clearance due to race have not been studied.

Only a small fraction, e. The extent of reduction in Theophylline clearance in patients with CHF appears to be directly correlated to the severity of the cardiac disease. Since Theophylline clearance is independent of liver blood flow, the reduction in clearance appears to be due to impaired hepatocyte function rather than reduced perfusion. Tobacco and marijuana smoking appears to increase the clearance of Theophylline by induction of metabolic pathways.

Use of nicotine gum has been shown to have no effect on Theophylline clearance. Fever, regardless of its underlying cause, can decrease the clearance of Theophylline. The magnitude and duration of the fever appear to be directly correlated to the degree of decrease of Theophylline clearance. Children with rapid rates of Theophylline clearance i. Other factors associated with decreased Theophylline clearance include the third trimester of pregnancy, sepsis with multiple organ failure, and hypothyroidism.

Other factors associated with increased Theophylline clearance include hyperthyroidism and cystic fibrosis. Theophylline has also been shown to reduce the need for short courses of daily oral prednisone to relieve exacerbations of airway obstruction that are unresponsive to bronchodilators in asthmatics. In patients with chronic obstructive pulmonary disease COPD , clinical studies have shown that Theophylline decreases dyspnea, air trapping, the work of breathing, and improves contractility of diaphragmatic muscles with little or no improvement in pulmonary function measurements.

Theophylline extended-release tablets are indicated for the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, e. Theophylline extended-release tablets are contraindicated in patients with a history of hypersensitivity to Theophylline or other components in the product. Theophylline should be used with extreme caution in patients with the following clinical conditions due to the increased risk of exacerbation of the concurrent condition: Active peptic ulcer disease Cardiac arrhythmias not including bradyarrhythmias Conditions that Reduce Theophylline Clearance: There are several readily identifiable causes of reduced Theophylline clearance.

If the total daily dose is not appropriately reduced in the presence of these risk factors, severe and potentially fatal Theophylline toxicity can occur. Careful consideration must be given to the benefits and risks of Theophylline use and the need for more intensive monitoring of serum Theophylline concentrations in patients with the following risk factors: Cessation of Smoking Drug Interactions: Adding a drug that inhibits Theophylline metabolism e. Whenever a patient receiving Theophylline develops nausea or vomiting, particularly repetitive vomiting, or other signs or symptoms consistent with Theophylline toxicity even if another cause may be suspected , additional doses of Theophylline should be withheld and a serum Theophylline concentration measured immediately.

Increases in the dose of Theophylline should not be made in response to an acute exacerbation of symptoms of chronic lung disease since Theophylline provides little added benefit to inhaled beta2 -selective agonists and systemically administered cortico-steroids in this circumstance and increases the risk of adverse effects. A peak steady-state serum Theophylline concentration should be measured before increasing the dose in response to persistent chronic symptoms to ascertain whether an increase in dose is safe.

As the rate of Theophylline clearance may be dose-dependent i. Careful consideration of the various interacting drugs and physiologic conditions that can alter Theophylline clearance and require dosage adjustment should occur prior to initiation of Theophylline therapy, prior to increases in Theophylline dose, and during follow up see WARNINGS.

Monitoring Serum Theophylline Concentrations: Consider therapy modification Formoterol: Theophylline Derivatives may enhance the hypokalemic effect of Formoterol. Theophylline Derivatives may decrease the serum concentration of Fosphenytoin. Seek alternatives when possible. Consider therapy modification Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics.

Guanethidine may enhance the hypertensive effect of Sympathomimetics. Theophylline Derivatives may enhance the hypokalemic effect of Indacaterol. Monitor therapy Iobenguane I Sympathomimetics may diminish the therapeutic effect of Iobenguane I Specifically, the risk for seizures may be increased. Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants.

Consider therapy modification Iomeprol: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Consider therapy modification Iopamidol: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Consider therapy modification Isoniazid: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid.

Specific dose adjustment recommendations are not presently available. Consider therapy modification Lithium: Theophylline Derivatives may decrease the serum concentration of Lithium.

Monitor therapy Macrolide Antibiotics: Consider therapy modification Methotrexate: May decrease the serum concentration of Theophylline. Metreleptin may increase the serum concentration of Theophylline.

Consider therapy modification Obeticholic Acid: Theophylline Derivatives may enhance the hypokalemic effect of Olodaterol. Theophylline Derivatives may diminish the neuromuscular-blocking effect of Pancuronium. Pancuronium dosage adjustment may be necessary to induce paralysis in patients receiving concomitant theophylline derivatives.

Monitor closely for adverse effects e. Consider therapy modification Pefloxacin: Monitor therapy Peginterferon Alfa-2b: Theophylline Derivatives may decrease the serum concentration of Phenytoin. Consider therapy modification Propafenone: Monitor therapy Protease Inhibitors: Ciprofloxacin and enoxacin are of greatest concern. Consider therapy modification Regadenoson: Theophylline may diminish the vasodilatory effect of Regadenoson.

Consider therapy modification Riociguat: Theophylline Derivatives may enhance the hypotensive effect of Riociguat. Tedizolid may enhance the tachycardic effect of Sympathomimetics.

Consider therapy modification Thyroid Products: May increase the metabolism of Theophylline Derivatives. Consider alternatives to such combinations whenever possible, particularly if the CYP1A2 substrate has a relatively narrow therapeutic index. Consider therapy modification Zafirlukast: Theophylline Derivatives may decrease the serum concentration of Zafirlukast. Zafirlukast may increase the serum concentration of Theophylline Derivatives. If theophylline is added to existing zileuton therapy, use a lower starting dose.

Monitor for increased serum concentrations and effects of theophylline. Theophylline may decrease triiodothyronine. Adverse Reactions Frequency not defined. Adverse events observed at therapeutic serum levels. Cardiac flutter, tachycardia Central nervous system: Hypercalcemia with concomitant hyperthyroid disease Gastrointestinal: Gastroesophageal reflux aggravation , gastrointestinal ulcer aggravation , nausea, vomiting Genitourinary: The concurrent administration of caffeine to patients taking aminophyllinemay produce excessive caffeine-like side effects, such as nausea, irritability or nervousness.

Moderate Caffeine is a CNS stimulant. Major Aminophylline is expected to decrease plasma concentrations of carbamazepine via 3A4 induction. Also, aminophylline is primarily metabolized in the liver by the CYP1A2 isoenzyme. Carbamazepine can stimulate the hepatic metabolism of aminophylline if used concurrently. Aminophylline doses may need to be increased if carbamazepine is added. More importantly, serious aminophylline toxicity can result if carbamazepine is discontinued and the dose of aminophylline is not correspondingly decreased.

Major Theophylline is expected to decrease plasma concentrations of carbamazepine via 3A4 induction. Theophylline is primarily metabolized in the liver by the CYP1A2 isoenzyme. Carbamazepine can stimulate the hepatic metabolism of theophylline if used concurrently. Theophylline doses may need to be increased if carbamazepine is added. More importantly, serious theophylline toxicity can result if carbamazepine is discontinued and the dose of theophylline is not correspondingly decreased.

Major Avoid the use of ceritinib, a time-dependent inhibitor of CYP3A4, with CYP3A4 substrates that have a narrow therapeutic index, such as theophylline, aminophylline as theophylline exposure may be increased. If co-administration is unavoidable, consider a theophylline dose reduction and monitor for theophylline toxicity. Major Charcoal exerts a nonspecific effect, and many medications can be adsorbed by activated charcoal.

When taken as a dietary supplement for flatulence or other purposes, activated charcoal will decrease the effectiveness of other regularly taken medications e. Activated charcoal repeat dosing is an important therapeutic adjunct in severe theophylline drug overdoses; repeat doses also increase the elimination of the drug.

Major Note that charcoal exerts a nonspecific effect, and many medications can be adsorbed by activated charcoal. Activated charcoal is an important therapeutic adjunct in theophylline drug overdoses, but otherwise should be avoided in non-emergent use. Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: Cimetidine inhibits the CYP1A2 isoenzyme and not only reduces the hepatic metabolism of aminophylline, but a reduction in the renal clearance of theophylline may occur via competition for renal tubular secretion.

However, the hepatic-based interaction is more significant. In patients receiving aminophylline, an alternative to cimetidine should be considered when possible. Alternatively, if concomitant therapy is necessary, patients should be monitored closely for increased effects of theophylline and the need for aminophylline dosage adjustments. The Beers criteria recommends that this drug combination be avoided in older adults.

Cimetidine inhibits the CYP1A2 isoenzyme and not only reduces the hepatic metabolism of theophylline, but a reduction in the renal clearance of theophylline may occur via competition for renal tubular secretion. In patients receiving theophylline, an alternative to cimetidine should be considered when possible. Alternatively, if concomitant therapy is necessary, patients should be monitored closely for increased effects of theophylline and the need for theophylline dosage adjustments. Major Avoid coadministration of ciprofloxacin and aminophylline due to the potential for increased and prolonged plasma exposure of theophylline.

Monitor theophylline concentrations and adjust dosage as appropriate if concurrent administration cannot be avoided. Serious and fatal reactions have occurred in patients receiving concurrent ciprofloxacin and theophylline. These reactions have included cardiac arrest, seizure, status epilepticus, and respiratory failure. Although similar serious adverse reactions have been reported in patients receiving theophylline alone, the possibility that these reactions may be potentiated by ciprofloxacin cannot be eliminated.

Major Avoid coadministration of ciprofloxacin and theophylline due to the potential for increased and prolonged plasma exposure of theophylline. Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: Moderate Colesevelam may decrease the absorption of oral aminophylline. To minimize potential for interactions, consider administering oral aminophylline at least 1 hour before or at least 4 hours after colesevelam.

Moderate Colesevelam may decrease the absorption of oral theophylline. To minimize potential for interactions, consider administering oral theophylline at least 1 hour before or at least 4 hours after colesevelam. Moderate Caution is warranted when darunavir is administered with theophylline; aminophylline as there is a potential for elevated theophylline concentrations. Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: Higher dosages of aminophylline might be required.

If these drugs are used together, therapeutic drug monitoring should be considered. Higher dosages of theophylline might be required. Moderate Use dichlorphenamide and theophylline, aminophylline together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including theophylline, aminophylline. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment.

If hypokalemia occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy. Moderate Diltiazem may inhibit the cytochrome P metabolism of aminophylline. Since the therapeutic range is narrow for aminophylline, it is prudent to monitor aminophylline serum concentrations during diltiazem therapy. Moderate Diltiazem may inhibit the cytochrome P metabolism of theophylline. Since the therapeutic range is narrow for theophylline, it is prudent to monitor theophylline serum concentrations during diltiazem therapy.

Major Aminophylline is a prodrug of theophylline. Disulfiram inhibits the hepatic hydroxylation and demethylation of theophylline, thereby increasing the serum levels of theophylline and increasing the risk for theophylline toxicity.

Patients should be monitored for theophylline toxicity if disulfiram is added to aminophylline therapy. If aminophylline is added after disulfiram is begun and disulfiram is later discontinued, subtherapeutic theophylline serum concentrations can result. In addition, some preparations of aminophylline elixir may contain significant amounts of ethanol, which can cause reactions with disulfiram; read labels carefully.

Major Disulfiram inhibits the hepatic hydroxylation and demethylation of theophylline, thereby increasing the serum levels of theophylline and increasing the risk for theophylline toxicity. Patients should be monitored for theophylline toxicity if disulfiram is added to theophylline therapy. If theophylline is added after disulfiram is begun and disulfiram is later discontinued, subtherapeutic theophylline serum concentrations can result.

In addition, some preparations of theophylline elixir contain significant amounts of ethanol, which can cause reactions with disulfiram; read labels carefully. Major Use caution if coadministration of dronabinol with theophylline, aminophylline is necessary, and monitor for increased theophylline levels and theophylline-related adverse effects.

Dronabinol is highly bound to plasma proteins, and may displace and increase the free fraction of other concomitantly administered protein-bound drugs; caution is recommended with other drugs with a narrow therapeutic index.

Additionally, however, increased theophylline metabolism has been reported with smoking of marijuana; the interaction is similar in effect to that of smoking tobacco, which may substantially decrease theophylline serum concentrations. Because dronabinol, THC is a synthetic analog of a naturally occurring substance found in marijuana, this interaction may also theoretically occur with dronabinol.

However, it is also probable that compounds produced via the smoking process i. Although the concomitant administration of dronedarone and CYP3A substrates may result in increased exposure of the substrate, data from clinical studies indicate dronedarone does not increase the steady state aminophylline exposure. Although the concomitant administration of dronedarone and CYP3A substrates may result in increased exposure of the substrate, data from clinical studies indicate dronedarone does not increase the steady state theophylline exposure.

Moderate Serum concentrations of theophylline may be increased during concurrent administration with ethinyl estradiol. This interaction occurs from the inhibition of methylxanthine oxidation in the liver. The resulting increased half life and decreased clearance may necessitate a decrease in theophylline dosage.

Minor Serum concentrations of aminophylline may be increased during concurrent administration with ethinyl estradiol. The resulting increased half life and decreased clearance may necessitate a decrease in aminophylline dosage.

Drospirenone; Ethinyl Estradiol; Levomefolate: Moderate Close monitoring of theophylline levels is advisable during concurrent use of duloxetine and theophylline.

Moderate Coadministration of dupilumab may result in altered exposure to theophylline. Thus, the formation of CYP enzymes could be normalized during dupilumab administration. Monitor theophylline concentrations if dupilumab is initiated or discontinued in a patient taking theophylline; theophylline dose adjustments may be needed. Major Dyphylline is a xanthine derivative and should not be administered with other methylxanthines e. Adverse effects such as diarrhea, tremors, insomnia, seizures, or cardiac arrhythmias are also possible when excessive dosages of methylxanthine drugs are taken.

The efficacy and safety of aminophylline if used in combination with echinacea are unknown. Monitor for changes in efficacy or toxicity if aminophylline is used in combination with echinacea, until more data are available.

The efficacy and safety of theophylline if used in combination with echinacea are unknown. Monitor for changes in efficacy or toxicity if theophylline is used in combination with echinacea, until more data are available. Moderate Administering theophylline, aminophylline with elbasvir; grazoprevir may result in elevated theophylline plasma concentrations. If these drugs are used together, closely monitor for signs of adverse events. Moderate Aminophylline used concurrently with inhaled general anesthetics may increase the risk of cardiac arrhythmias.

Moderate Theophylline used concurrently with inhaled general anesthetics may increase the risk of cardiac arrhythmias. When ketamine and theophylline are given concurrently a clinically significant reduction in the seizure threshold is observed. Ethinyl Estradiol; Ethynodiol Diacetate: Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: Ethinyl Estradiol; Norethindrone Acetate: Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: Ethinyl Estradiol; Norethindrone; Ferrous fumarate: Medications that cause induction of hepatic CYP enzymes, such as phenytoin, ethotoin, or fosphenytoin, may increase the hepatic oxidative metabolism of theophylline or aminophylline.

Theophylline doses may need to be increased if hydantoin anticonvulsants are added. More importantly, serious theophylline toxicity can result if any of these drugs are discontinued and the dose of theophylline is not correspondingly decreased.

Also, theophylline may inhibit the oral absorption of phenytoin. Minor Aminophylline is a prodrug of theophylline, and is primarily metabolized in the liver by the CYP1A2 isoenzyme. In general, famotidine does not interact with aminophylline and does not affect theophylline levels in most patients.

One small study documented a significant decrease in theophylline clearance after therapy with famotidine. Be alert for any evidence of interaction, and monitor the patients aminophylline therapy as per standard of care or if side effects are reported. In general, famotidine does not interact with theophylline and does not affect theophylline levels in most patients.

Be alert for any evidence of interaction, and monitor the patients theophylline therapy as per standard of care or if side effects are reported. Moderate Use caution if febuxostat and aminophylline are used concurrently. Aminophylline is converted to the active form, theophylline, in the body. By inhibiting xanthine oxidase, febuxostat alters theophylline metabolism. These changes were not considered statistically significant. An approximately fold increase in the amount of 1-methylxanthine a major metabolite of theophylline excreted in the urine was also noted.

Since the long-term safety of exposure to 1-methylxanthine in humans is unknown, use with caution when coadministering febuxostat with aminophylline.

Moderate Use caution if febuxostat and theophylline are used concurrently. Since the long-term safety of exposure to 1-methylxanthine in humans is unknown, use with caution when coadministering febuxostat with theophylline. Moderate Fluconazole may increase the serum concentrations of aminophylline.

Serum aminophylline concentrations should be monitored closely if fluconazole is added. Moderate Fluconazole may increase the serum concentrations of theophylline. Serum theophylline concentrations should be monitored closely if fluconazole is added. Aminophylline is metabolized by this enzyme. If aminophylline is co-administered with fluvoxamine, the aminophylline daily dosage should be reduced and plasma aminophylline concentrations should be monitored.

Patients should report any increase in methylxanthine-induced side effects, like tremor, nausea, or vomiting promptly. Theophylline is metabolized by this enzyme. If theophylline is co-administered with fluvoxamine, the theophylline daily dosage should be reduced and plasma theophylline concentrations should be monitored. Moderate Concomitant use of glycerol phenylbutyrate and theophylline may result in decreased exposure of theophylline. Monitor for decreased efficacy of theophylline during coadministration.

Moderate If golimumab is initiated or discontinued in a patient taking aminophylline, monitor the theophylline concentration; aminophylline dose adjustment may be needed. The formation of CYP enzymes may be suppressed by increased concentrations of cytokines e. Thus, it is expected that the formation of CYP enzymes could be normalized during golimumab receipt.

Clinically relevant drug interactions may occur with CYP substrates that have a narrow therapeutic index such as aminophylline. Moderate If golimumab is initiated or discontinued in a patient taking theophylline, monitor the theophylline concentration; theophylline dose adjustment may be needed.

Major Some green tea products contain caffeine. Concurrent administration of aminophylline with caffeine can produce excessive CNS stimulation such as nervousness, irritability, tremors, or insomnia. Caffeine-like side effects, such as headache and nausea, may also increase.

It is recommended that dietary caffeine consumption be controlled during aminophylline administration and minimized if possible. Decreased elimination of both caffeine and theophylline may explain some of these reactions; decreased elimination has been demonstrated in healthy men on theophylline consuming dietary caffeine.

Concurrent administration of theophylline with caffeine can produce excessive CNS stimulation such as nervousness, irritability, tremors, or insomnia. Major Caffeine and, to a small extent, theophylline are active constituents of guarana. The concurrent administration of guarana to patients taking theophylline may produce excessive caffeine-like side effects, such as nausea, irritability or nervousness.

Adverse effects such as tremors, insomnia, seizures, or cardiac arrhythmias are also possible when excessive dosages of guarana are taken concurrently with theophylline.

Patients taking theophylline should avoid medications or dietary supplements containing guarana. Patients may also need to limit their intake of guarana-containing beverages to avoid caffeine-like side effects. Severe Use of halothane in a patient taking aminophylline is not recommended due to an increased risk of ventricular arrhythmias. Halothane sensitizes the myocardial conduction system to catecholamines, and aminophylline increases the release of endogenous catecholamines.

Severe Use of halothane in a patient taking theophylline is not recommended due to an increased risk of ventricular arrhythmias. Halothane sensitizes the myocardial conduction system to catecholamines, and theophylline increases the release of endogenous catecholamines. If aminophylline is being initiated in a patient who is already taking a drug that inhibits its clearance, the dose required to achieve a therapeutic serum theophylline concentration will be smaller. Patients should be closely monitored for toxicity.

Serum theophylline concentrations should be monitored. Because propranolol is non-selective, the beta-2 blocking activity may reduce the effectiveness of aminophylline and other treatments for asthma or COPD.

Discontinuation of a concomitant drug that inhibits aminophylline clearance will result in decreased serum theophylline concentrations, unless the aminophylline dose is appropriately increased. If theophylline is being initiated in a patient who is already taking a drug that inhibits its clearance, the dose of theophylline required to achieve a therapeutic theophylline concentration will be smaller.

Because propranolol is non-selective, the beta-2 blocking activity may reduce the effectiveness of theophylline and other treatments for asthma or COPD. Discontinuation of a concomitant drug that inhibits theophylline clearance will result in decreased theophylline concentrations, unless the theophylline dose is appropriately increased. Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: Moderate In vitro studies indicate that hydroxyprogesterone increases the metabolic rate of CYP1A2 isoenzymes.

The metabolism of drugs metabolized by CYP1A2, such as theophylline, aminophylline may be increased during treatment with hydroxyprogesterone. Major Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with theophylline, aminophylline, a CYP3A substrate, as theophylline, aminophylline toxicities may be significantly increased. Moderate Generalized seizures have occurred in patients who were receiving imipenem-cilastatin concomitantly with aminophylline.

The mechanism of this interaction is not known. Patients should be monitored for signs of CNS toxicity during coadministration. Moderate Generalized seizures have occurred in patients who were receiving imipenem-cilastatin concomitantly with theophylline. Moderate The formation of CYP enzymes may be suppressed by increased concentrations of cytokines e. Thus, it is expected that the formation of CYP enzymes could be normalized during infliximab receipt. If infliximab is initiated or discontinued in a patient taking theophylline, monitor the theophylline concentration; theophylline dose adjustment may be needed.

Minor Influenza virus vaccine has been reported to inhibit the clearance of medications metabolized by cytochrome P including theophylline or aminophylline.

The use of these medications should not prohibit influenza immunization if indicated. However, because an occasional predisposed patient may experience an increase in the effects of theophylline or aminophylline, monitoring for theophylline toxicity may be warranted; a temporary dosage adjustment may be needed if an interaction occurs.

Major Interferons, when administered systemically, may decrease the clearance of aminophylline resulting in increased plasma levels. Until additional information is available,interferons should be used cautiously in patients receiving aminophylline. Monitor theophylline concentrations and for signs and symptoms of toxicity. Major Interferons, when administered systemically, may decrease the clearance of theophylline resulting in increased plasma levels.

Until additional information is available,interferons should be used cautiously in patients receiving theophylline. Major Use of medications that lower the seizure threshold, such as aminophylline, should be carefully evaluated when considering intrathecal iopamidol.

Some physicians discontinue these drugs at least 48 hours before and for at least 24 hours after intrathecal use. Major Use of medications that lower the seizure threshold, such as theophylline, should be carefully evaluated when considering intrathecal iopamidol.

Moderate Concomitant use of isavuconazonium with theophylline, aminophylline may result in increased serum concentrations of theophylline. Theophylline and aminophylline are substrates of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme.

Caution and close monitoring are advised if these drugs are used together. Minor Isoniazid, INH may reduce aminophylline clearance. Although data regarding this drug interaction are conflicting, it appears that this can be explained by the duration of isoniazid administration. Larger doses of isoniazid and longer duration of isoniazid administration are more likely to affect aminophylline pharmacokinetics.

At least one patient developed aminophylline toxicity as a result of this interaction with isoniazid. Minor Isoniazid, INH may reduce theophylline clearance. Larger doses of isoniazid and longer duration of isoniazid administration are more likely to affect theophylline pharmacokinetics.

At least one patient developed theophylline toxicity as a result of this interaction with isoniazid. Major Rifampin is a potent inducer of the cytochrome P hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of aminophylline. Dosages of aminophylline may need to be adjusted while the patient is receiving rifampin. Major Rifampin is a potent inducer of the cytochrome P hepatic enzyme system and can reduce the plasma concentrations and possibly the efficacy of theophylline.

Dosages of theophylline may need to be adjusted while the patient is receiving rifampin. Major Although beta2-agonists are commonly used with theophylline, the combination of isoproterenol and theophylline could potentially increase cardiac adverse reactions such as cardiac arrhythmias. If isoproterenol and theophylline are used together, theophylline serum concentrations should be closely monitored. Minor Use caution when administering ivacaftor and theophylline, aminophylline concurrently.

Co-administration can theoretically increase theophylline or aminophylline exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined. Moderate When ketamine and theophylline are given concurrently a clinically significant reduction in the seizure threshold is observed.

This combination may also increase the risk of cardiac arrhythmias.

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