Skip to Content

Aminophylline

Pronunciation

Pronunciation

(am in OFF i lin)

Index Terms

  • Theophylline Ethylenediamine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous, as dihydrate:

Generic: 25 mg/mL (10 mL, 20 mL)

Tablet, Oral, as dihydrate:

Generic: 100 mg [DSC], 200 mg [DSC]

Pharmacologic Category

  • Phosphodiesterase Enzyme Inhibitor, Nonselective

Pharmacology

Causes bronchodilatation, diuresis, CNS and cardiac stimulation, and gastric acid secretion by blocking phosphodiesterase which increases tissue concentrations of cyclic adenine monophosphate (cAMP) which in turn promote catecholamine stimulation of lipolysis, glycogenolysis, and gluconeogenesis and induce release of epinephrine from adrenal medulla cells

Absorption

Theophylline: Oral: Rapid and complete

Distribution

Theophylline: 0.45 L/kg based on ideal body weight

Metabolism

Theophylline: Children >1 year and Adults: Hepatic; involves CYP1A2, 2E1, and 3A4; forms active metabolites (caffeine and 3-methylxanthine)

Excretion

Theophylline: Children >3 months and Adults: Urine (10% as unchanged drug)

Time to Peak

Oral: 1-2 hours; IV: Within 30 minutes

Half-Life Elimination

Theophylline: Highly variable and dependent upon age, liver function, cardiac function, lung disease, and smoking history

Premature infants, postnatal age 3-15 days: 30 hours (range: 17-43 hours)

Premature infants, postnatal age 25-57 days: 20 hours (range: 9.4-30.6 hours)

Children 1-4 yrs: 3.4 hours (range: 1.2-5.6 hours); 6-17 years: 3.7 hours (range: 1.5-5.9 hours)

Adults 16-60 years with asthma, nonsmoking, otherwise healthy: 8.7 hours (range: 6.1-12.8 hours)

Protein Binding

Theophylline: 40%, primarily to albumin

Special Populations: Hepatic Function Impairment

Theophylline clearance is decreased 50% or more in patients with hepatic insufficiency.

Special Populations: Elderly

Clearance is decreased by an average of 30% in healthy patients older than 60 years of age compared with younger adults.

Special Populations: Children

Clearance is very low in neonates and reaches max values by 1 year of age, remains relatively constant until about 9 years of age, and then slowly decreases by approximately 50% to adult values at about 16 years of age.

Special Populations Note

Concurrent illness: Theophylline clearance is decreased in patients with acute pulmonary edema, heart failure, cor pulmonale, fever, hypothyroidism, liver disease (eg, acute hepatitis, cirrhosis), reduced renal function in infants younger than 3 months of age, sepsis with multiorgan failure, and shock.

Smoking: Theophylline clearance is increased by smoking (ie, marijuana or tobacco), approximately 50% in young adult smokers and 80% in elderly tobacco smokers. Cessation of smoking for 1 week causes a reduction in theophylline clearance by 40%.

Special risk patients: Pharmacokinetics vary widely among similar patients and cannot be predicted by age, sex, body weight, or other demographic parameters. However, a prolonged half-life may occur in patients with heart failure, liver dysfunction, alcoholism, and respiratory infection patients.

Use: Labeled Indications

Treatment of symptoms and reversible airway obstruction due to asthma or other chronic lung diseases (eg, emphysema, chronic bronchitis)

Note: The 2007 National Heart, Lung, and Blood Institute Asthma Guidelines and the 2015 Global Initiative for Asthma Guidelines (GINA) recommend against aminophylline IV for the treatment of asthma exacerbations because of poor efficacy and safety concerns (GINA, 2015; NAEPP, 2007).

Use: Unlabeled

Reversal of adenosine-, dipyridamole-, or regadenoson-induced adverse reactions (eg, angina, hypotension) during nuclear cardiac stress testing

Contraindications

Hypersensitivity to theophylline, ethylenediamine, or any component of the formulation

Canadian labeling: Additional contraindications (not in U.S. labeling): Coronary artery disease where cardiac stimulation might prove harmful; patients with peptic ulcer disease

Dosing: Adult

Note: Doses should be individualized based on peak serum concentrations and should be based on ideal body weight. Theophylline dose is 80% of aminophylline dose. The treatment of asthma exacerbations with aminophylline is not supported or recommended by current clinical practice guidelines (GINA, 2015; NAEPP, 2007).

Acute symptoms: Manufacturer’s labeling:

Loading dose: Oral, IV:

Patients not currently receiving aminophylline or theophylline: Aminophylline 5.7 mg/kg (equivalent to theophylline 4.6 mg/kg) administered IV or theophylline 5 mg/kg administered orally.

Patients currently receiving aminophylline or theophylline: A loading dose is not recommended without first obtaining a serum theophylline concentration in patients who have received aminophylline or theophylline within the past 24 hours. The loading dose should be calculated as follows:

Dose = (desired serum theophylline concentration - measured serum theophylline concentration) (Vd)

Acute symptoms: Manufacturer’s labeling:

Maintenance dose: IV: Note: To achieve a target theophylline concentration of 10 mcg/mL unless otherwise noted. Lower initial doses may be required in patients with reduced theophylline clearance. Dosage should be adjusted according to serum level measurements during the first 12- to 24-hour period.

Adults 16-60 years (otherwise healthy, nonsmokers): 0.51 mg/kg/hour (equivalent to theophylline 0.4 mg/kg/hour); maximum daily dose: aminophylline 1139 mg/day (equivalent to theophylline 900 mg/day) unless serum levels indicate need for larger dose

Adults >60 years: 0.38 mg/kg/hour (equivalent to theophylline 0.3 mg/kg/hour); maximum daily dose: aminophylline 507 mg/day (equivalent to theophylline 400 mg/day) unless serum levels indicate need for larger dose

Dosage adjustment for cardiac decompensation, cor pulmonale, hepatic dysfunction, sepsis with multiorgan failure, shock: 0.25 mg/kg/hour (equivalent to theophylline 0.2 mg/kg/hour); maximum daily dose: aminophylline 507 mg/day (equivalent to theophylline 400 mg/day) unless serum levels indicate need for larger dose

Dosage adjustment after serum theophylline measurement:

Within normal limits: Asthma: 5-15 mcg/mL: Maintain dosage if tolerated. Recheck serum theophylline concentration at 24-hour intervals (for acute IV dosing) or at 6- to 12-month intervals (for oral dosing). Finer adjustments in dosage may be needed for some patients. If levels ≥15 mcg/mL, consider 10% dose reduction to improve safety margin.

Too high:

20-24.9 mcg/mL: Decrease dose by ~25%. Recheck serum theophylline concentrations (see "Note").

25-30 mcg/mL: Skip next dose (oral) or stop infusion for 12 hours (children) or 24 hours (adults) and decrease subsequent doses by ~25%. Recheck serum theophylline concentrations (see "Note").

>30 mcg/mL: Stop dosing and treat overdose; if resumed, decrease subsequent doses by 50%. Recheck serum theophylline concentrations (see "Note").

Too low: <9.9 mcg/mL: If tolerated, but symptoms remain, increase dose by ~25%. Recheck serum theophylline concentrations (see "Note").

Note: Recheck serum theophylline levels after 3 days when using oral dosing, or after 12 hours (children) or 24 hours (adults) when dosing intravenously. Patients maintained with oral therapy may be reassessed at 6- to 12-month intervals.

Chronic conditions: Oral: Note: Increase dose only if tolerated. Consider lowering dose or using a slower titration if caffeine-like adverse events occur. Smaller doses given more frequently may be used in patients with a more rapid metabolism to prevent breakthrough symptoms which could occur due to low trough concentration prior to the next dose.

Adults 16-60 years without risk factors for impaired theophylline clearance:

Aminophylline 380 mg/day (equivalent to theophylline 300 mg/day) in divided doses every 6-8 hours for 3 days;

Then increase to 507 mg/day (equivalent to theophylline 400 mg/day) in divided doses every 6-8 hours for 3 days

Maintenance dose: 760 mg/day (equivalent to theophylline 600 mg/day) in divided doses every 6-8 hours

Dose adjustment in patients with risk factors for impaired theophylline clearance and patients in whom monitoring serum theophylline levels is not feasible: Do not exceed a dose of aminophylline 507 mg/day (equivalent to theophylline 400 mg/day)

Reversal of adenosine-, dipyridamole-, or regadenoson-induced adverse reactions (eg, angina, hypotension) during nuclear cardiac stress testing (off-label use): IV: 50-250 mg administered over 30-60 seconds, repeat as necessary. Note: Since adenosine-induced side effects are short lived after discontinuation of the infusion, aminophylline administration is only very rarely required (ASNC [Henzlova 2016]).

Dosing: Geriatric

Adults >60 years: Refer to adult dosing. Do not exceed a dose of aminophylline 507 mg/day (equivalent to theophylline 400 mg/day)

Dosing: Pediatric

Note: Doses should be individualized based on peak serum concentrations and should be based on ideal body weight. Theophylline dose is 79% of aminophylline dose. The treatment of asthma exacerbations with aminophylline is not supported or recommended by current clinical practice guidelines (GINA, 2015; NAEPP, 2007).

Acute symptoms: Manufacturer’s labeling:

Loading dose: Oral, IV: Refer to adult dosing.

Acute symptoms: Manufacturer’s labeling:

Maintenance dose: IV: Note: To achieve a target theophylline concentration of 10 mcg/mL unless otherwise noted. Lower initial doses may be required in patients with reduced theophylline clearance. Dosage should be adjusted according to serum level measurements during the first 12- to 24-hour period.

Infants 6-52 weeks: Dose (mg/kg/hour) = [(0.008 x age in weeks) + 0.21] divided by 0.79 (equivalent to theophylline: Dose (mg/kg/hour) = [(0.008 x age in weeks) + 0.21])

Children 1-9 years: 1.01 mg/kg/hour (equivalent to theophylline 0.8 mg/kg/hour)

Children 9-12 years: 0.89 mg/kg/hour (equivalent to theophylline 0.7 mg/kg/hour)

Adolescents 12-16 years (cigarette or marijuana smokers): 0.89 mg/kg/hour (equivalent to theophylline 0.7 mg/kg/hour)

Adolescents 12-16 years (nonsmokers): 0.63 mg/kg/hour (equivalent to theophylline 0.5 mg/kg/hour); maximum daily dose: aminophylline 1139 mg/day (equivalent to theophylline 900 mg/day) unless serum levels indicate need for larger dose

Adolescents >16 years: Refer to adult dosing.

Dosage adjustment for cardiac decompensation, cor pulmonale, hepatic dysfunction, sepsis with multiorgan failure, shock: Refer to adult dosing.

Dosage adjustment after serum theophylline measurement:

Within normal limits: Asthma: 5-15 mcg/mL: Maintain dosage if tolerated. Recheck serum theophylline concentration at 24-hour intervals (for acute IV dosing) or at 6- to 12-month intervals (for oral dosing). Finer adjustments in dosage may be needed for some patients. If levels ≥15 mcg/mL, consider 10% dose reduction to improve safety margin.

Too high:

20-24.9 mcg/mL: Decrease dose by ~25%. Recheck serum theophylline concentrations (see "Note").

25-30 mcg/mL: Skip next dose (oral) or stop infusion for 12 hours and decrease subsequent doses by ~25%. Recheck serum theophylline concentrations (see "Note").

>30 mcg/mL: Stop dosing and treat overdose; if resumed, decrease subsequent doses by 50%. Recheck serum theophylline concentrations (see "Note").

Too low: <9.9 mcg/mL: If tolerated, but symptoms remain, increase dose by ~25%. Recheck serum theophylline concentrations (see "Note").

Note: Recheck serum theophylline levels after 3 days when using oral dosing, or after 12 hours when dosing intravenously. Patients maintained with oral therapy may be reassessed at 6- to 12-month intervals.

Chronic conditions: Oral: Note: Increase dose only if tolerated. Consider lowering dose or using a slower titration if caffeine-like adverse events occur. Smaller doses given more frequently may be used in patients with a more rapid metabolism to prevent breakthrough symptoms which could occur due to low trough concentration prior to the next dose.

Children 1-15 years and <45 kg without risk factors for impaired theophylline clearance:

Aminophylline 15.2-17.7 mg/kg/day (equivalent to theophylline 12-14 mg/kg/day) in divided doses every 4-6 hours for 3 days, maximum daily dose: aminophylline 380 mg/day (equivalent to theophylline 300 mg/day);

Then increase to 20.3 mg/kg/day (equivalent to theophylline 16 mg/kg/day) in divided doses every 4-6 hours for 3 days, maximum dose: aminophylline 507 mg/day (equivalent to theophylline 400 mg/day)

Maintenance dose: 25.3 mg/kg/day (equivalent to theophylline 20 mg/kg/day) in divided doses every 4-6 hours, maximum dose: aminophylline 760 mg/day (equivalent to theophylline 600 mg/day)

Note: Dose adjustment in patients with risk factors for impaired theophylline clearance and patients in whom monitoring serum theophylline levels is not feasible: Do not exceed a dose of aminophylline 20.3 mg/kg/day (equivalent to theophylline 16 mg/kg/day). Maximum dose: Aminophylline 507 mg/day (equivalent to theophylline 400 mg/day)

Children >45 kg without risk factors for impaired theophylline clearance: Refer to adult dosing.

Dosing: Renal Impairment

Oral: IV:

Children >3 months, Adolescents, and Adults: No dosage adjustment necessary.

Infants 1 to 3 months: Consider dose reduction and frequent monitoring of serum theophylline concentrations.

Dosing: Hepatic Impairment

Oral: Infants, Children, Adolescents, and Adults: No dosage adjustment provided in manufacturer’s labeling. However, dose reduction and frequent monitoring of serum theophylline concentration are required in patients with decreased hepatic function (eg, cirrhosis, acute hepatitis, cholestasis). Maximum daily dose: aminophylline 507 mg/day (equivalent to theophylline 400 mg/day)

IV: Infants, Children, Adolescents, and Adults: Initial: 0.25 mg/kg/hour (equivalent to theophylline 0.2 mg/kg/hour); maximum daily dose: aminophylline 507 mg/day (equivalent to theophylline 400 mg/day) unless serum concentrations indicate need for larger dose. Use with caution and monitor serum theophylline concentrations frequently.

Administration

Tablet: If dose is missed, administer the next dose at the scheduled time (do not make up missed dose).

IV: For IV administration only (IM use is not recommended). Loading doses should be administered IV over 30 minutes. Infusion rate should not exceed 21 mg/hour (equivalent to theophylline 17 mg/hour) in patients with cor pulmonale, cardiac decompensation, liver dysfunction, patients >60 years of age, or patients taking medications which reduce theophylline clearance.

For reversal of adenosine-, dipyridamole-, or regadenoson-induced adverse events during nuclear cardiac stress testing, administer IV undiluted over 30-60 seconds, repeat as necessary. Since adenosine-induced side effects are short lived after discontinuation of the infusion, aminophylline administration is only very rarely required.

Vesicant; ensure proper needle or catheter placement prior to and during IV infusion. Avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave needle/cannula in place); gently aspirate extravasated solution (do NOT flush the line); initiate hyaluronidase antidote; remove needle/cannula; apply dry cold compresses (Hurst, 2004); elevate extremity.

Hyaluronidase: Intradermal or SubQ: Inject a total of 1 mL (15 units/mL) as five separate 0.2 mL injections (using a 25-gauge needle) into area of extravasation at the leading edge in a clockwise manner (MacCara, 1983; Zenk, 1981).

Compatibility

Stable in dextran 6% in D5W, dextran 6% in NS, D5LR, D5NS, D51/2NS, D51/4NS, D5W, D10W, D20W, LR, 1/2NS, NS.

Y-site administration: Incompatible with amiodarone, ciprofloxacin, dobutamine, fenoldopam, hydralazine, isoproterenol, ondansetron, TrophAmine®, vinorelbine, warfarin.

Compatibility in syringe: Incompatible with ceftriaxone, dimenhydrinate, doxapram, potassium phosphate.

Storage

Solution: Vials should be stored at room temperature of 20°C to 25°C (68°F to 77°F). Protect from light. Do not use solutions if discolored or if crystals are present.

Tablet: Store at room temperature of 20°C to 25°C (68°F to 77°F). Protect from light and moisture.

Drug Interactions

Abiraterone Acetate: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy

Acebrophylline: May enhance the stimulatory effect of Theophylline Derivatives. Avoid combination

Adalimumab: May decrease the serum concentration of Theophylline Derivatives. Monitor therapy

Adenosine: Theophylline Derivatives may diminish the therapeutic effect of Adenosine. Consider therapy modification

Alcohol (Ethyl): May increase the serum concentration of Aminophylline. Monitor therapy

Allopurinol: May increase the serum concentration of Theophylline Derivatives. Monitor therapy

Antithyroid Agents: May increase the serum concentration of Theophylline Derivatives. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Barbiturates: May decrease the serum concentration of Theophylline Derivatives. Monitor therapy

Benzodiazepines: Theophylline Derivatives may diminish the therapeutic effect of Benzodiazepines. Consider therapy modification

Beta-Blockers (Beta1 Selective): May diminish the bronchodilatory effect of Theophylline Derivatives. Management: Monitor for reduced theophylline efficacy during concomitant use with any beta-blocker. Beta-1 selective agents are less likely to antagonize theophylline than nonselective agents, but selectivity may be lost at higher doses. Monitor therapy

Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Theophylline Derivatives. Consider therapy modification

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

Cannabis: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy

CarBAMazepine: May decrease the serum concentration of Theophylline Derivatives. Theophylline Derivatives may decrease the serum concentration of CarBAMazepine. Management: Seek alternatives to this combination when possible. If these agents are used together, monitor closely for decreased serum concentrations/therapeutic effects of both medications. Consider therapy modification

Cimetidine: May decrease the metabolism of Theophylline Derivatives. Consider therapy modification

CYP1A2 Inducers (Strong): May increase the metabolism of CYP1A2 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP1A2 Inhibitors (Moderate): May decrease the metabolism of CYP1A2 Substrates. Monitor therapy

CYP1A2 Inhibitors (Strong): May decrease the metabolism of CYP1A2 Substrates. Consider therapy modification

Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy

Deferasirox: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy

Disulfiram: May increase the serum concentration of Theophylline Derivatives. Monitor therapy

Doxofylline: Theophylline Derivatives may enhance the adverse/toxic effect of Doxofylline. Avoid combination

Estrogen Derivatives: May increase the serum concentration of Theophylline Derivatives. Monitor therapy

Febuxostat: May increase serum concentrations of the active metabolite(s) of Theophylline Derivatives. Specifically, concentrations of 1-methylxanthine, a metabolite of unknown clinical importance, may become elevated. Monitor therapy

FluvoxaMINE: May decrease the metabolism of Theophylline Derivatives. Consider therapy modification

Formoterol: Theophylline Derivatives may enhance the adverse/toxic effect of Formoterol. Theophylline Derivatives may enhance the hypokalemic effect of Formoterol. Monitor therapy

Fosphenytoin: May decrease the serum concentration of Theophylline Derivatives. Theophylline Derivatives may decrease the serum concentration of Fosphenytoin. Management: Seek alternatives when possible. If used together, monitor for decreased concentrations/effects of phenytoin or theophylline if the other agent is initiated/dose increased, or increased concentrations/effects if the other is discontinued/dose decreased. Consider therapy modification

Indacaterol: Theophylline Derivatives may enhance the adverse/toxic effect of Indacaterol. Theophylline Derivatives may enhance the hypokalemic effect of Indacaterol. Monitor therapy

Interferons: May decrease the metabolism of Theophylline Derivatives. Monitor therapy

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

Isoniazid: May increase the serum concentration of Theophylline Derivatives. Monitor therapy

Isoproterenol: May decrease the serum concentration of Theophylline Derivatives. Monitor therapy

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: 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: May decrease the metabolism of Theophylline Derivatives. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin; Telithromycin. Consider therapy modification

Methotrexate: May increase the serum concentration of Theophylline Derivatives. Monitor therapy

Mexiletine: May decrease the metabolism of Theophylline Derivatives. Consider therapy modification

Obeticholic Acid: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy

Olodaterol: Theophylline Derivatives may enhance the adverse/toxic effect of Olodaterol. Theophylline Derivatives may enhance the hypokalemic effect of Olodaterol. Monitor therapy

Pancuronium: Theophylline Derivatives may enhance the adverse/toxic effect of Pancuronium. Theophylline Derivatives may diminish the neuromuscular-blocking effect of Pancuronium. Management: Pancuronium dosage adjustment may be necessary to induce paralysis in patients receiving concomitant theophylline derivatives. Monitor closely for adverse effects (e.g., cardiac effects) with concomitant use of these agents. Consider therapy modification

Peginterferon Alfa-2b: May increase the serum concentration of CYP1A2 Substrates. Monitor therapy

Pentoxifylline: May increase the serum concentration of Theophylline Derivatives. Monitor therapy

Phenytoin: May decrease the serum concentration of Theophylline Derivatives. Theophylline Derivatives may decrease the serum concentration of Phenytoin. Management: Seek alternatives when possible. If used together, monitor for decreased concentrations/effects of phenytoin or theophylline if the other agent is initiated/dose increased, or increased concentrations/effects if the other is discontinued/dose decreased. Consider therapy modification

Propafenone: May increase the serum concentration of Theophylline Derivatives. Monitor therapy

Protease Inhibitors: May decrease the serum concentration of Theophylline Derivatives. Exceptions: Fosamprenavir. Monitor therapy

QuiNINE: May increase the serum concentration of Theophylline Derivatives. Monitor therapy

Quinolone Antibiotics: May decrease the metabolism of Theophylline Derivatives. Ciprofloxacin and enoxacin are of greatest concern. Theophylline/quinolone therapy might augment the seizure-producing potential of each of the individual agents. Exceptions: Gemifloxacin; LevoFLOXacin (Systemic); Lomefloxacin; Moxifloxacin (Systemic); Nalidixic Acid; Sparfloxacin. Consider therapy modification

Regadenoson: Aminophylline may diminish the vasodilatory effect of Regadenoson. Consider therapy modification

Riociguat: Theophylline Derivatives may enhance the hypotensive effect of Riociguat. Avoid combination

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Teriflunomide: May decrease the serum concentration of CYP1A2 Substrates. Monitor therapy

Thiabendazole: May decrease the metabolism of Theophylline Derivatives. Consider therapy modification

Thiopental: Aminophylline may diminish the therapeutic effect of Thiopental. Monitor therapy

Thyroid Products: May increase the metabolism of Theophylline Derivatives. Monitor therapy

Ticlopidine: May decrease the metabolism of Theophylline Derivatives. Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Vemurafenib: May increase the serum concentration of CYP1A2 Substrates. Management: 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. Monitor therapy

Zileuton: May increase the serum concentration of Aminophylline. Management: Reduce aminophylline dose by 50% upon initiation of zileuton therapy. If aminophylline is added to existing zileuton therapy, use a lower starting dose. Monitor for increased theophylline serum concentrations and effects. Consider therapy modification

Test Interactions

Plasma glucose, uric acid, free fatty acids, total cholesterol, HDL, HDL/LDL ratio, and urinary free cortisol excretion may be increased by theophylline. Theophylline may decrease triiodothyronine.

Adverse Reactions

Frequency not defined. Adverse events observed at therapeutic serum levels:

Cardiovascular: Cardiac flutter, tachycardia

Central nervous system: Behavioral changes (children), headache, insomnia, irritability, restlessness, seizure

Dermatologic: Allergic skin reaction, exfoliative dermatitis

Gastrointestinal: Diarrhea, nausea, vomiting

Genitourinary: Diuresis (transient)

Neuromuscular & skeletal: Tremor

Warnings/Precautions

Concerns related to adverse effects:

• Extravasation: Vesicant; ensure proper catheter or needle position prior to and during infusion. Avoid extravasation.

• Theophylline toxicity: If a patient develops signs and symptoms of theophylline toxicity (eg, persistent, repetitive vomiting), a serum level should be measured and subsequent doses held. Theophylline clearance may be decreased in patients with acute pulmonary edema, congestive heart failure, cor pulmonale, fever, hepatic disease, acute hepatitis, cirrhosis, hypothyroidism, sepsis with multiorgan failure, and shock; clearance may also be decreased in neonates, infants <3 months of age with decreased renal function, infants <1 year of age, the elderly >60 years, and patients following cessation of smoking.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with hypertension or cardiac arrhythmias (excluding bradyarrhythmias).

• Hyperthyroidism: Use with caution in patients with hyperthyroidism.

• Peptic ulcer disease: Use with caution in patient with peptic ulcer disease (use is contraindicated in the Canadian labeling).

• Seizure disorder: Use with caution in patients with a history of seizure disorder.

Other warnings/precautions:

• Dosage adjustments: Due to potential saturation of theophylline clearance at serum levels within (or in some patients less than) the therapeutic range, dosage adjustment should be made in small increments (maximum: 25% dose increase).

• Monitoring: Due to wide interpatient variability, theophylline serum level measurements must be used to optimize therapy and prevent serious toxicity.

Monitoring Parameters

Monitor heart rate; CNS effects (insomnia, irritability); respiratory rate (COPD patients often have resting controlled respiratory rates in low 20s); arterial or capillary blood gases (if applicable)

Theophylline levels: Serum theophylline levels should be monitored prior to making dose increases; in the presence of signs or symptoms of toxicity; or when a new illness, worsening of a present illness, or medication changes occur that may change theophylline clearance

IV loading dose: Measure serum concentrations 30 minutes after the end of an IV loading dose

IV infusion: Measure serum concentrations one half-life after starting a continuous infusion, then every 12-24 hours

Pregnancy Risk Factor

C

Pregnancy Considerations

Refer to Theophylline monograph.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience agitation or polyuria. Have patient report immediately to prescriber tachycardia, abnormal heartbeat, fast breathing, severe dizziness, passing out, severe anxiety, nausea, vomiting, severe diarrhea, severe headache, confusion, insomnia, seizures, or tremors (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Hide