Note: All dosages expressed as aminophylline. Dose should be individualized based on serum concentrations. Due to longer half-life compared to older patients, the time to achieve steady-state serum concentration is prolonged in neonates; obtain serum theophylline concentration after 48 to 72 hours of therapy (usually 72 hours in neonates); repeat values should be obtained 3 days after each change in dosage or weekly if on a stabilized dosage.
Apnea of prematurity: Limited data available: Note: Caffeine citrate is the preferred agent to treat apnea of prematurity (AAP [Eichenwald 2016]).
Preterm neonates:
Loading dose: IV: 5 to 8 mg/kg/dose (Armanian 2014; Hochwald 2002; Jones 1979; Shivakumar 2017; Tey 2016; Wongsiridej 2021; Ye 2019); in one trial of 61 neonates (birth weight: ≤1,500 g), a loading dose of 8 mg/kg/dose achieved targeted theophylline serum concentrations in more patients compared to a loading dose of 6 mg/kg/dose (Hochwald 2002). Begin maintenance dose 8 to 12 hours following loading dose (al-Omran 1997).
Maintenance: IV: Initial: 2 to 6 mg/kg/day divided every 8 to 12 hours; reported range: 2 to 9 mg/kg/day; increased dosages may be indicated as liver metabolism increases; monitor serum concentrations and adjust to achieve targeted concentrations (al-Omran 1997; Armanian 2014; Hochwald 2002; Shivakumar 2017; Skouroliakou 2009; Tey 2016; Wongsiridej 2021; Ye 2019).
Dosing adjustment in renal impairment: Dose reduction and frequent monitoring of serum theophylline concentrations are required in neonates with decreased renal function; 50% of dose is excreted unchanged in the urine of neonates.
Note: All dosages expressed as aminophylline; use ideal body weight to calculate dose; adjust dose based on steady-state serum concentrations. Aminophylline 0.8 mg = Theophylline (anhydrous) 1 mg.
Reversible airflow obstruction, acute symptoms: Note: The treatment of asthma exacerbations with aminophylline is not supported or recommended by current clinical practice guidelines (GINA 2021; NAEPP 2007).
Infants, Children, and Adolescents:
Loading dose:
Patients who have not received aminophylline or theophylline in the previous 24 hours: IV: 5.7 mg/kg/dose.
Patients who have received aminophylline or theophylline in the previous 24 hours: Obtain serum theophylline concentration prior to administering a loading dose. The loading dose should be calculated as follows:
Dose = (C desired – C measured) (Vd)
C desired = desired serum theophylline concentration
C measured = measured serum theophylline concentration
Maintenance dose: Note: Dosing presented is to achieve a target theophylline concentration of 10 mcg/mL. Lower initial doses may be required in patients with reduced theophylline clearance. Dosage should be adjusted according to serum concentration measurements during the first 12- to 24-hour period.
Infants 4 to 6 weeks: IV: 1.9 mg/kg/dose every 12 hours.
Infants 6 to 52 weeks: Continuous IV infusion: Dose (mg/kg/hour) = [(0.008 × age in weeks) + 0.21] divided by 0.8.
Children 1 to <9 years: Continuous IV infusion: 1 mg/kg/hour.
Children 9 to <12 years: Continuous IV infusion: 0.9 mg/kg/hour.
Adolescents 12 to <16 years (otherwise healthy, nonsmokers): Continuous IV infusion: 0.6 mg/kg/hour; maximum dose: 1,125 mg/day unless serum concentrations indicate need for larger dose.
Adolescents 12 to <16 years (cigarette or marijuana smokers): Continuous IV infusion: 0.9 mg/kg/hour.
Adolescents ≥16 years (otherwise healthy, nonsmokers): Continuous IV infusion: 0.5 mg/kg/hour; maximum dose: 1,125 mg/day unless serum concentrations indicate need for larger dose.
Patients with cardiac decompensation, cor pulmonale, sepsis with multiorgan failure, or shock: Infants, Children, and Adolescents: Continuous IV infusion: Initial: 0.25 mg/kg/hour; maximum dose: 500 mg/day unless serum concentrations indicate need for larger dose.
Dosage adjustment based on serum theophylline concentrations:
Infants, Children, and Adolescents: Note: Recheck serum theophylline concentrations in 12 hours (ages 1 month to <16 years) or 24 hours (ages ≥16 years) after dose adjustment; concentrations should also be evaluated if adverse effects occur or conditions altering theophylline clearance are present (eg, sustained fever, drug interactions). Adjust dose based on the following serum concentration results:
<9.9 mcg/mL: If tolerated, but symptoms are not controlled, increase infusion rate by ~25%. Recheck serum theophylline concentrations.
10 to 14.9 mcg/mL: Maintain infusion rate if tolerated and symptoms controlled. Recheck serum concentrations at 24-hour intervals. If symptoms not controlled, consider additional medications for management.
15 to 19.9 mcg/mL: Consider 10% reduction in infusion rate to improve safety margin even if dose is tolerated.
20 to 24.9 mcg/mL: Decrease infusion rate by ~25%. Recheck serum concentrations.
25 to 30 mcg/mL: Stop infusion for 12 hours (ages 1 month to <16 years) or 24 hours (ages ≥16 years) and decrease subsequent infusion rate by at least 25% even if no adverse effects are present. Recheck serum concentrations.
>30 mcg/mL: Stop infusion and treat overdose; if resumed, decrease subsequent infusion rate by at least 50%. Recheck serum concentrations.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function: IV:
Infants 1 to 3 months: There are no specific dosage adjustments provided in the manufacturer's labeling; consider dose reduction and frequent monitoring of serum theophylline concentrations.
Infants >3 months, Children, and Adolescents: No adjustment necessary.
Infants, Children, and Adolescents: Continuous IV infusion: Initial maintenance infusion: 0.25 mg/kg/hour; maximum dose: 500 mg/day unless serum concentrations indicate need for larger dose. Use with caution and monitor serum theophylline concentrations frequently.
(For additional information see "Aminophylline: Drug information")
Note: All dosages expressed as aminophylline; use ideal body weight to calculate dose (theophylline has limited distribution into body fat); individualize dose based on steady-state serum concentrations. Theophylline dose is ~80% of aminophylline dose.
Reversible airflow obstruction, acute symptoms: Note: Routine use of aminophylline is not recommended for the treatment of acute asthma exacerbations or chronic obstructive pulmonary disease exacerbations (GINA 2022; GOLD 2022).
Loading dose:
Patients who have not received aminophylline or theophylline in the previous 24 hours: IV: 5.7 mg/kg.
Patients who have received aminophylline or theophylline in the previous 24 hours: Note: Loading dose should not be given before obtaining a serum theophylline concentration.
Calculate loading dose based on serum theophylline concentrations, as follows:
IV: Loading dose = (desired serum theophylline concentration − measured serum theophylline concentration) * (Vd); where Vd = 0.5 L/kg [Example: (10 mcg/mL (desired) – 5 mcg/mL (measured)) * 0.5 L/kg * 70 kg = 175 mg loading dose].
Maintenance dose: Note: Dosing presented is to achieve a target theophylline concentration of 10 mcg/mL. Lower initial doses may be required in patients with reduced theophylline clearance. Adjust dose according to serum level measurements.
Adults ≤60 years of age: Continuous infusion: IV: 0.5 mg/kg/hour; maximum dose: 1,125 mg/day unless serum levels indicate need for larger dose.
Adults >60 years of age: Continuous infusion: IV: 0.38 mg/kg/hour; maximum dose: 500 mg/day unless serum levels indicate need for larger dose.
Cardiac decompensation, cor pulmonale, sepsis with multiorgan failure, and shock: Continuous infusion: IV: 0.25 mg/kg/hour; maximum dose: 500 mg/day unless serum levels indicate need for larger dose.
Dosage adjustment based on serum theophylline concentrations: Note: Recheck serum theophylline concentration 24 hours after dosage adjustment.
<9.9 mcg/mL: If dosage is tolerated but symptoms are not controlled, increase infusion rate ~25%.
10 to 14.9 mcg/mL: Maintain infusion rate if dosage is tolerated and symptoms controlled. Recheck serum concentrations at 24-hour intervals. If symptoms are not controlled and dosage is tolerated, consider adding additional medications to treatment regimen.
15 to 19.9 mcg/mL: Consider 10% dose reduction in infusion rate to improve safety margin even if dose is tolerated.
20 to 24.9 mcg/mL: Decrease infusion rate by 25% even if no adverse effects present.
25 to 30 mcg/mL: Stop infusion for 24 hours and decrease subsequent infusion rate at least 25%. If symptomatic, stop infusion and consider whether overdose treatment is indicated.
>30 mcg/mL: Stop infusion and treat overdose; if resumed, decrease subsequent infusion rate at least 50%.
Dipyridamole- or regadenoson-induced adverse reactions (eg, angina, hypotension) during nuclear cardiac stress testing, reversal (off-label use): Note: Since adenosine-induced side effects are short lived after discontinuation of the infusion, aminophylline administration is only very rarely required (ASNC [Henzlova 2016]).
IV: 50 to 250 mg administered over 30 to 60 seconds, repeat as necessary (ASNC [Henzlova 2016]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
Initial: 0.25 mg/kg/hour; maximum dose: 500 mg/day unless serum concentrations indicate need for larger dose. Use with caution and monitor serum theophylline concentrations frequently.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous, as dihydrate [preservative free]:
Generic: 25 mg/mL (10 mL, 20 mL)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Generic: 50 mg/mL (10 mL)
Solution, Intravenous, as dihydrate:
Generic: 25 mg/mL (10 mL, 20 mL)
IV: For IV administration only. Infusion time is based on indication:
Apnea of prematurity: Neonates: Infuse dose over 15 to 30 minutes (Bhatt-Mehta 1995).
Reversible airflow obstruction, acute symptoms: Infants, Children, and Adolescents: Infuse loading dose over 30 minutes (manufacturer's labeling).
Vesicant; ensure proper needle or catheter placement prior to and during IV infusion. Avoid extravasation. 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 (see Management of Drug Extravasations for more details); remove needle/cannula; apply dry cold compresses (Hurst 2004; Reynolds 2014); elevate extremity.
IV: For IV administration only. Loading doses should be administered IV over 30 minutes. In patients with cor pulmonale, cardiac decompensation, hepatic impairment, patients >60 years of age, or patients taking medications that reduce theophylline clearance, the initial maintenance infusion rate should not exceed 21 mg/hour.
Off-label use: For reversal of adenosine-, dipyridamole-, or regadenoson-induced adverse events during nuclear cardiac stress testing, administer IV undiluted over 30 to 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 (ASNC [Henzlova 2016]).
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; Reynolds 2014); elevate extremity.
Hyaluronidase: Intradermal or SUBQ: Inject a total of 1 to 1.7 mL (15 units/mL) as five separate 0.2 to 0.3 mL injections (using a 25-gauge needle) into area of extravasation at the leading edge in a clockwise manner (MacCara 1983; Reynolds 2014; Zenk 1981).
IV infusion: 1 mg/mL.
Store at 20°C to 25°C (68°F to 77°F) in original carton. Protect from light. Do not use if discolored or if crystals are present.
Treatment of acute exacerbation symptoms and reversible airflow obstruction associated with asthma, chronic obstructive pulmonary disease (COPD), or other chronic lung diseases as an adjunct to inhaled beta-2 selective agonists and systemically administered corticosteroids (FDA approved in pediatric patients [age not specified] and adults); has also been used for treatment of apnea of prematurity.
Note: The 2007 National Heart, Lung, and Blood Institute Asthma Guidelines and the 2021 Global Initiative for Asthma Guidelines recommend against aminophylline for the treatment of asthma exacerbations because of poor efficacy and safety concerns (GINA 2021; NAEPP 2007).
Aminophylline may be confused with amitriptyline, ampicillin
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined. Adverse events observed at therapeutic serum levels:
Central nervous system: Headache, insomnia, irritability, restlessness, seizure
Dermatologic: Allergic skin reaction, exfoliative dermatitis
Gastrointestinal: Diarrhea, nausea, vomiting
Genitourinary: Diuresis (transient)
Neuromuscular & skeletal: Tremor
Hypersensitivity to aminophylline, theophylline, ethylenediamine, or any component of the formulation.
Canadian labeling: Additional contraindications (not in US labeling): Coronary artery disease where cardiac stimulation might prove harmful; peptic ulcer disease.
Concerns related to adverse effects:
• Extravasation: Vesicant; ensure proper catheter or needle position prior to and during infusion. Avoid extravasation.
• Theophylline toxicity: Severe and potentially fatal theophylline toxicity may occur if reduced theophylline clearance occurs. Theophylline clearance may be decreased in patients with acute pulmonary edema, heart failure, cor pulmonale, fever (≥102°F for ≥24 hours or lesser temperature elevations for longer periods), hepatic disease, acute hepatitis, cirrhosis, hypothyroidism, sepsis with multiorgan failure, shock, neonates (term and premature), infants <3 months of age with decreased renal function, infants <1 year, elderly >60 years, and patients following cessation of smoking. Consider benefits versus risks and the need for more intensive monitoring in these patients; reduced dosing may be required. If a patient develops signs and symptoms of theophylline toxicity (eg, nausea or persistent, repetitive vomiting), a serum theophylline level should be measured immediately and subsequent doses withheld.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with cardiac arrhythmias (excluding bradyarrhythmias); use may exacerbate arrhythmias.
• Cystic fibrosis: Use with caution in patients with cystic fibrosis; increased theophylline clearance may occur.
• Hepatic impairment: Use with caution in patients with hepatic impairment (eg, cirrhosis, acute hepatitis, cholestasis); risk of severe and potentially fatal theophylline toxicity is increased. Theophylline clearance is decreased ≥50% in these patients. Dose reduction and frequent monitoring of serum theophylline concentrations are required.
• Hyperthyroidism: Use with caution in patients with hyperthyroidism; increased theophylline clearance may occur.
• Peptic ulcer disease: Use with caution in patients with active peptic ulcer disease; use may exacerbate peptic ulcer.
• Seizure disorder: Use with caution in patients with seizure disorders; use may exacerbate seizure disorder.
Special populations:
• Older adult: Use extreme caution in the elderly; these patients are at greater risk of serious theophylline toxicity.
• Pediatric: Select dose with caution and with frequent monitoring of concentrations (especially <1 year); rate of clearance is highly variable in these patients.
Other warnings/precautions:
• Appropriate use: Do not increase dose in response to acute exacerbation of symptoms unless steady state serum theophylline concentration is <10 mcg/mL. As the rate of theophylline clearance may be dose-dependent, an increase in dose based upon a subtherapeutic serum concentration measurement should be limited to ~25% increase of the previous infusion rate or daily dose.
Substrate of CYP1A2 (major), CYP2C9 (minor), CYP2D6 (minor), CYP2E1 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program
Acebrophylline: May enhance the stimulatory effect of Theophylline Derivatives. Risk X: Avoid combination
Adalimumab: May decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Adenosine: Theophylline Derivatives may diminish the therapeutic effect of Adenosine. Management: Consider alternatives to this combination if possible. Theophylline may decrease adenosine efficacy and higher adenosine doses may be required. When using adenosine for diagnostic studies, discontinue theophylline derivatives 5 half-lives prior to test. Risk D: Consider therapy modification
Alcohol (Ethyl): May increase the serum concentration of Aminophylline. Risk C: Monitor therapy
Allopurinol: May increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy
Antipsychotic Agents: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Antithyroid Agents: May increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Barbiturates: May decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Benzodiazepines: Theophylline Derivatives may diminish the therapeutic effect of Benzodiazepines. Risk C: Monitor therapy
Beta2-Agonists: May enhance the adverse/toxic effect of Theophylline Derivatives. Specifically, sympathomimetic effects may be increased. Theophylline Derivatives may enhance the hypokalemic effect of Beta2-Agonists. Risk C: Monitor therapy
Beta-Blockers (Beta1 Selective): May diminish the bronchodilatory effect of Theophylline Derivatives. Risk C: Monitor therapy
Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Theophylline Derivatives. Risk C: Monitor therapy
Broccoli: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor therapy
BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor therapy
Cambendazole: May increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Cannabis: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: 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. Risk D: Consider therapy modification
Clarithromycin: May increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Risk D: Consider therapy modification
CYP1A2 Inducers (Moderate): May decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
CYP1A2 Inhibitors (Moderate): May increase the serum concentration of Theophylline Derivatives. Management: Consider avoidance of this combination. If coadministration is necessary, monitor for increased theophylline serum concentrations and toxicities when combined. Theophylline dose reductions will likely be required. Risk D: Consider therapy modification
CYP1A2 Inhibitors (Strong): May increase the serum concentration of Theophylline Derivatives. Management: Consider avoidance of this combination. If coadministration is necessary, consider an empiric theophylline dose reduction to one-third of the original theophylline dose. Monitor for increased theophylline serum concentrations and toxicities when combined. Risk D: Consider therapy modification
CYP1A2 Inhibitors (Weak): May increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Doxofylline: Theophylline Derivatives may enhance the adverse/toxic effect of Doxofylline. Risk X: Avoid combination
Erythromycin (Systemic): May increase the serum concentration of Theophylline Derivatives. Theophylline Derivatives may decrease the serum concentration of Erythromycin (Systemic). Management: Consider alternatives to this combination. If combined, monitor for increased serum concentrations/toxic effects of theophylline derivatives.Theophylline derivative dose reductions may be needed. Also monitor for reduced erythromycin efficacy. Risk D: Consider therapy modification
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. Risk C: Monitor therapy
Filgotinib: May increase the serum concentration of CYP1A2 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Fluconazole: May increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Formoterol: Theophylline Derivatives may enhance the adverse/toxic effect of Formoterol. Theophylline Derivatives may enhance the hypokalemic effect of Formoterol. Risk C: 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. Risk D: Consider therapy modification
Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy
Indacaterol: Theophylline Derivatives may enhance the adverse/toxic effect of Indacaterol. Theophylline Derivatives may enhance the hypokalemic effect of Indacaterol. Risk C: Monitor therapy
Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: 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 antiseizure drugs. Risk D: Consider therapy modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Isoniazid: May increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Isoproterenol: May decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Ketamine: May enhance the adverse/toxic effect of Theophylline Derivatives. Specifically, the risk for seizures may be increased. Risk C: Monitor therapy
Kratom: May enhance the adverse/toxic effect of Sympathomimetics. Risk X: Avoid combination
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. Risk D: Consider therapy modification
Lithium: Theophylline Derivatives may decrease the serum concentration of Lithium. Risk C: Monitor therapy
Methotrexate: May increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Nirmatrelvir and Ritonavir: May decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Norfloxacin: May increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Olodaterol: Theophylline Derivatives may enhance the adverse/toxic effect of Olodaterol. Theophylline Derivatives may enhance the hypokalemic effect of Olodaterol. Risk C: Monitor therapy
Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy
Pacritinib: May increase the serum concentration of CYP1A2 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Pancuronium: Theophylline Derivatives may enhance the adverse/toxic effect of Pancuronium. Theophylline Derivatives may diminish the neuromuscular-blocking effect of Pancuronium. Risk C: Monitor therapy
Pentoxifylline: May increase the serum concentration of Theophylline Derivatives. Risk C: 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. Risk D: Consider therapy modification
QuiNINE: Theophylline Derivatives may increase the serum concentration of QuiNINE. QuiNINE may decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Regadenoson: Aminophylline may enhance the neuroexcitatory and/or seizure-potentiating effect of Regadenoson. Aminophylline may diminish the vasodilatory effect of Regadenoson. Management: Avoid using aminophylline or other methylxanthines (eg, caffeine) for at least 12 hours prior to the administration of regadenoson. Aminophylline may be administered after regadenoson to diminish adverse events. Monitor for seizures. Risk D: Consider therapy modification
RifAMPin: May decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Riociguat: Theophylline Derivatives may enhance the hypotensive effect of Riociguat. Risk X: Avoid combination
Ritonavir: May decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor therapy
Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy
Sulfinpyrazone: May decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Telithromycin: May increase the serum concentration of Theophylline Derivatives. Management: Consider separating administration of telithromycin and theophylline derivatives by at least one hour to prevent gastrointestinal adverse effects. Monitor for theophylline toxicities and consider monitoring of serum theophylline levels. Risk D: Consider therapy modification
Thiopental: Aminophylline may diminish the therapeutic effect of Thiopental. Risk C: Monitor therapy
Thyroid Products: May increase the metabolism of Theophylline Derivatives. Risk C: Monitor therapy
Tobacco (Smoked): May decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Verapamil: May increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Viloxazine: May increase the serum concentration of Theophylline Derivatives. Risk X: Avoid combination
Zafirlukast: Theophylline Derivatives may decrease the serum concentration of Zafirlukast. Zafirlukast may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
Ethanol: Ethanol may decrease theophylline clearance. Management: Monitor theophylline concentrations, particularly when alcohol consumption patterns change.
Food: Theophylline clearance is increased and half-life decreased by low carbohydrate/high protein diets, parenteral nutrition, and daily consumption of charcoal-broiled beef; a high carbohydrate/low protein diet can decrease the clearance and prolong the half-life of theophylline. Management: Avoid extremes of dietary protein and carbohydrate intake.
Aminophylline is a complex of theophylline and ethylenediamine. Theophylline crosses the placenta. Refer to Theophylline monograph for additional information.
Serum theophylline concentrations, heart rate, respiratory rate, number and severity of apnea spells (when used for apnea of prematurity); arterial or capillary blood gases (if applicable); pulmonary function tests. Monitor infusion site.
Therapeutic concentrations:
Asthma: 5 to 15 mcg/mL.
Apnea of prematurity: 6 to 12 mcg/mL; goal concentration is reduced due to decreased protein binding and higher free fraction.
|
Dosage Form |
When to Obtain SampleA |
|---|---|
|
AThe time to achieve steady-state serum concentration is prolonged in patients with longer half-lives (eg, infants and adults with cardiac or liver failure; see theophylline half-life table). In these patients, serum theophylline concentrations should be drawn after 48 to 72 hours of therapy; may need to obtain concentrations prior to steady-state to assess the patient's current progress or evaluate potential toxicity. | |
|
IV bolus |
30 min after end of 30-min infusion |
|
Continuous IV infusion |
12 to 24 h after initiation of infusion |
Theophylline has two distinct actions; smooth muscle relaxation (ie, bronchodilation) and suppression of the response of the airways to stimuli (ie, non-bronchodilator prophylactic effects). Bronchodilation is mediated by inhibition of two isoenzymes, phosphodiesterase (PDE III and, to a lesser extent, PDE IV) while non-bronchodilation effects are mediated through other molecular mechanisms. Theophylline increases the force of contraction of diaphragmatic muscles through enhancement of calcium uptake through adenosine-mediated channels.
Theophylline:
Distribution: Theophylline: ~0.45 L/kg based on ideal body weight; distributes poorly into body fat; Vd may increase in premature neonates, hepatic cirrhosis, acidemia (uncorrected), elderly, and third trimester of pregnancy.
Protein binding: Theophylline: ~40%, primarily to albumin; decreased in neonates (due to a greater percentage of fetal albumin), hepatic cirrhosis, acidemia (uncorrected), elderly, third trimester of pregnancy.
Metabolism: Theophylline: Hepatic via demethylation (CYP 1A2) and hydroxylation (CYP 2E1 and 3A4); forms active metabolites (caffeine and 3-methylxanthine)
Half-life elimination: Theophylline: Highly variable and dependent upon age, hepatic function, cardiac function, lung disease, and smoking history
Premature infants, postnatal age 3 to 15 days: 30 hours (range: 17 to 43 hours)
Premature infants, postnatal age 25 to 57 days: 20 hours (range: 9.4 to 30.6 hours)
Term infants, postnatal age 1 to 2 days: 25.7 hours (range: 25 to 26.5 hours)
Term infants, postnatal age 3 to 30 weeks: 11 hours (range: 6 to 29 hours)
Children 1 to 4 years: 3.4 hours (range: 1.2 to 5.6 hours)
Children and Adolescents 6 to 17 years: 3.7 hours (range: 1.5 to 5.9 hours)
Adults ≥18 years to ≤60 years (asthma, nonsmoking, otherwise healthy): 8.7 hours (range: 6.1 to 12.8 hours)
Elderly >60 years (nonsmoking, healthy): 9.8 hours (range: 1.6 to 18 hours)
Clearance: Certain conditions may significantly alter theophylline clearance; severe and potentially fatal theophylline toxicity may occur if reduced theophylline clearance occurs.
Decreased theophylline clearance: Neonates and infants; elderly >60 years; acute pulmonary edema, cor pulmonale; fever (≥102°F for ≥24 hours or lesser temperature elevations for longer periods); heart failure; hepatic impairment (eg, cirrhosis, acute hepatitis, cholestasis); hypothyroidism; patients following cessation of smoking; sepsis with multiple organ failure; shock; third trimester of pregnancy.
Increased theophylline clearance: Hyperthyroidism; cystic fibrosis; smoking (ie, marijuana or tobacco).
Time to peak, serum: Within 30 minutes
Excretion: Theophylline: Urine (~50% as unchanged drug [Neonates]; ~10% as unchanged drug [Infants >3 months, Adolescents, and Adults])
Altered kidney function: Clearance is decreased in infants <3 months with decreased renal function.
Hepatic function impairment: Clearance is decreased by ≥50% in patients with hepatic impairment (eg, cirrhosis, acute hepatitis, cholestasis).
Pediatric: 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. Renal excretion of unchanged theophylline in neonates amounts to about 50% of the dose, compared to about 10% in children older than three months and in adults.
Older adult: Clearance is decreased by an average of 30% in patients >60 years.
Sex: Significant reduction in theophylline clearance has been reported in women on the 20th day of the menstrual cycle and during the third trimester of pregnancy.
Smoking: Clearance is increased by smoking (ie, marijuana or tobacco) by ~50% in young adult and ~80% in elderly tobacco smokers. Cessation of smoking for 1 week causes a reduction in theophylline clearance by ~40%.
Each mg/kg of theophylline administered as a bolus will increase the serum theophylline concentration by an average of 2 mcg/mL.
Solution (Aminophylline Intravenous)
25 mg/mL (per mL): $1.65
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
