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Aminophylline: Drug information

Aminophylline: Drug information
(For additional information see "Aminophylline: Patient drug information" and see "Aminophylline: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Pharmacologic Category
  • Phosphodiesterase Enzyme Inhibitor, Nonselective
Dosing: Adult

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 theophylline concentrations. Theophylline dose is ~80% of aminophylline dose.

Reversible airflow obstruction, acute refractory symptoms

Reversible airflow obstruction, acute refractory symptoms: Note: Routine use of aminophylline is not recommended for the treatment of acute asthma exacerbations or chronic obstructive pulmonary disease exacerbations (Ref). Optimal regimen, dose, and therapeutic concentrations are uncertain; refer to institutional protocol.

Loading dose: Note: Doses presented are intended to achieve a serum theophylline concentration of ~10 mcg/mL.

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 theophylline concentrations.

Adults ≤60 years of age: Continuous infusion: IV: 0.5 mg/kg/hour; maximum dose: 1,125 mg/day unless serum theophylline concentrations 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 theophylline concentrations 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 theophylline concentrations 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 theophylline 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 during nuclear cardiac stress testing, reversal

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 (Ref).

IV: 50 to 250 mg administered over 30 to 60 seconds, repeat as necessary (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

Initial: 0.25 mg/kg/hour; maximum dose: 500 mg/day unless serum theophylline concentrations indicate need for larger dose. Use with caution and monitor serum theophylline concentrations frequently.

Dosing: Older Adult

Refer to adult dosing. Maximum dose: 500 mg/day unless serum theophylline concentrations indicate need for a larger dose.

Dosing: Pediatric

(For additional information see "Aminophylline: Pediatric drug information")

Note: All dosages expressed as aminophylline; use ideal body weight to calculate dose; adjust dose based on steady-state serum concentrations. Theophylline dose is ~80% of aminophylline dose.

Reversible airflow obstruction, acute symptoms

Reversible airflow obstruction, acute symptoms: Note: The treatment of asthma exacerbations with aminophylline is not supported or recommended by current clinical practice guidelines (Ref).

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.

Dosing: Kidney Impairment: Pediatric

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.

Dosing: Hepatic Impairment: Pediatric

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.

Adverse Reactions

The following adverse drug reactions are derived from product labeling unless otherwise specified.

Frequency not defined:

Gastrointestinal: Diarrhea, nausea, vomiting

Genitourinary: Diuresis (transient)

Nervous system: Headache, insomnia, irritability, restlessness, seizure, tremor

Postmarketing:

Dermatologic: Allergic skin reaction (Thompson 1984), erythema multiforme (Thompson 1984), exfoliative dermatitis (Thompson 1984), skin photosensitivity (Thompson 1984)

Hypersensitivity: Anaphylaxis (Thompson 1984), angioedema (Thompson 1984)

Contraindications

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.

Warnings/Precautions

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 concentration 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 theophylline concentration measurement should be limited to ~25% increase of the previous infusion rate or daily dose.

Dosage Forms: US

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)

Generic Equivalent Available: US

Yes

Pricing: US

Solution (Aminophylline Intravenous)

25 mg/mL (per mL): $1.72

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.

Dosage Forms: Canada

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

Solution, Injection:

Generic: 50 mg/mL ([DSC])

Solution, Intravenous, as dihydrate:

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

Administration: Adult

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 (Ref).

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

Extravasation management: If extravasation occurs, stop infusion immediately; leave needle/cannula in place temporarily but do NOT flush the line; gently aspirate extravasated solution, then remove needle/catheter; elevate extremity; apply dry, warm compresses; initiate hyaluronidase antidote (Ref).

Hyaluronidase: Intradermal or SUBQ: Inject a total of 1 mL (15 units/mL) as 5 separate 0.2 mL injections (using a tuberculin syringe) around the site of extravasation; if IV catheter remains in place, administer IV through infiltrated catheter; may repeat in 30 to 60 minutes if no resolution (Ref).

Administration: Pediatric

IV: For IV administration only. Infusion time is based on indication:

Apnea of prematurity: Neonates: Infuse dose over 15 to 30 minutes (Ref).

Reversible airflow obstruction, acute symptoms: Infants, Children, and Adolescents: Infuse loading dose over 30 minutes (Ref).

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 (Ref); elevate extremity.

Usual Infusion Concentrations: Adult

IV infusion: 250 mg in 250 mL (concentration: 1 mg/mL) of D5W or NS

Usual Infusion Concentrations: Pediatric

IV infusion: 1 mg/mL.

Use: Labeled Indications

Reversible airflow obstruction: Treatment of acute exacerbations of symptoms and reversible airflow obstruction due to asthma or other chronic lung diseases (eg, emphysema, chronic bronchitis) as an adjunct to inhaled beta-2 selective agonists and systemically administered corticosteroids.

Use: Off-Label: Adult

Dipyridamole- or regadenoson-induced adverse reactions during nuclear cardiac stress testing, reversal

Medication Safety Issues
Sound-alike/look-alike issues:

Aminophylline may be confused with amitriptyline, ampicillin

Metabolism/Transport Effects

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

Drug Interactions

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.

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

Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Amisulpride (Oral). 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

ARIPiprazole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Asenapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Asenapine. Specifically, the risk of seizures may be increased. 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

Benperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Benperidol. Specifically, the risk of seizures may be increased. 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

Blonanserin: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Blonanserin. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Brexpiprazole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Broccoli: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor therapy

Bromperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Bromperidol. Specifically, the risk of seizures may be increased. 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

Cariprazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Clarithromycin: May increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

Clothiapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

CloZAPine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk of seizures may be increased. 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

DroPERidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of DroPERidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Elranatamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

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

Flupentixol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

FluPHENAZine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of FluPHENAZine. Specifically, the risk of seizures may be increased. 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

Glofitamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy

Haloperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Iloperidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iloperidone. Specifically, the risk of seizures may be increased. 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

Leniolisib: May increase the serum concentration of CYP1A2 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination

Levothyroxine: May enhance the adverse/toxic effect of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Levothyroxine may enhance the therapeutic effect of Sympathomimetics. Sympathomimetics may enhance the therapeutic effect of Levothyroxine. Risk C: Monitor therapy

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Consider initial dose reductions of sympathomimetic agents, and closely monitor for enhanced blood pressure elevations, in patients receiving linezolid. Risk D: Consider therapy modification

Lithium: Theophylline Derivatives may decrease the serum concentration of Lithium. Risk C: Monitor therapy

Loxapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Loxapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Lumateperone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Lurasidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

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

Methotrimeprazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Methotrimeprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Molindone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Mosunetuzumab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). 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

OLANZapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of OLANZapine. Specifically, the risk of seizures may be increased. 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

Paliperidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

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

Periciazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Perphenazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Perphenazine. Specifically, the risk of seizures may be increased. 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

Pimozide: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Pipamperone [INT]: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Pipamperone [INT]. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor therapy

Prochlorperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Promazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

QUEtiapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

QuiNINE: May decrease the serum concentration of Theophylline Derivatives. Theophylline Derivatives may increase the serum concentration of QuiNINE. 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

RisperiDONE: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Ritlecitinib: May increase the serum concentration of CYP1A2 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Ritonavir: May decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

Sertindole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sertindole. Specifically, the risk of seizures may be increased. 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

Sulpiride: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sulpiride. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

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

Talquetamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Teclistamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

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

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

Thioridazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Thiothixene: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Thiothixene. Specifically, the risk of seizures may be increased. 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

Trifluoperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Trifluoperazine. Specifically, the risk of seizures may be increased. 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

Ziprasidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Food Interactions

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.

Pregnancy Considerations

Aminophylline is a complex of theophylline and ethylenediamine. Theophylline crosses the placenta. Refer to Theophylline monograph for additional information.

Breastfeeding Considerations

Aminophylline is a complex of theophylline and ethylenediamine. Theophylline is present in breast milk.

Maternal use of aminophylline is considered compatible with breastfeeding (WHO 2002). Refer to Theophylline monograph for additional information.

Monitoring Parameters

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 serum concentrations: Serum theophylline concentrations should be monitored after initiation of therapy and 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 change in patient’s treatment regimen that may alter theophylline clearance (eg, fever >102°F or sustained for 24 hours or more, hepatitis, or drugs that are added or discontinued); changes in fluid balance; electrolyte concentrations, acid-base balance during prolonged therapy.

Loading dose: Measure serum theophylline concentrations 30 minutes after the end of an IV loading dose in patients who have not received theophylline in the previous 24 hours to determine the need for an additional loading (serum theophylline concentration <10 mcg/mL) or to delay starting the maintenance IV infusion (serum theophylline concentration >20 mcg/mL).

Continuous infusion: Measure serum theophylline concentrations one half-life (eg, ~4 hours in children 1 to 9 years of age or 8 hours in nonsmoking, otherwise healthy adults) after starting a continuous infusion, then every 12 to 24 hours for duration of infusion; measure more frequently in acutely ill patients.

Monitor infusion site.

Reference Range

Therapeutic serum trough concentration:

Note: Therapeutic goal may vary depending on acuity and severity of the patient, as well as disease state (Barnes 2013).

Children: 5 to 15 mcg/mL.

Adults: 5 to 15 mcg/mL (Barnes 2013).

Toxic concentration: >20 mcg/mL.

Mechanism of Action

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.

Pharmacokinetics (Adult Data Unless Noted)

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])

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

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%.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Carena | Euphyllin | Phyllocontin;
  • (AR) Argentina: Aminofilin | Aminofilina northia;
  • (AT) Austria: Euphyllin | Mundiphyllin;
  • (BD) Bangladesh: Aminocardol | Aminomal | Aminophyllinum | Cardophylin | Euphylin | Filin | Larnox | Restophyllin;
  • (BE) Belgium: Aminoslow | Euphyllin;
  • (BG) Bulgaria: Aminophyllinum | Euphyllin | Novphyllin;
  • (BR) Brazil: Aminofil | Aminofilin | Aminofilina | Aminoima | Aminoliv | Aminotil | Asmafin | Asmapen | Asmofilin | Asmoquinol | Furp aminofilina | Minoton | Pulmodilat | Unifilin;
  • (CH) Switzerland: Escophyllin;
  • (CL) Chile: Aminofilina;
  • (CN) China: A mi kang | Phyllocontin;
  • (CO) Colombia: Aminofilina;
  • (CZ) Czech Republic: Aminophyllinum | Euphylin | Farophyllin | Pharophyllin | Syntophyllin;
  • (DE) Germany: Aminophyllin;
  • (DK) Denmark: Teofylamin;
  • (DO) Dominican Republic: Aminofilina | Aminofilina larjan | Aminomal;
  • (EC) Ecuador: Aminofilina | Eufilina;
  • (EE) Estonia: Aminophyllinum | Euphyllin | Euphyllinum;
  • (EG) Egypt: Minophylline-n;
  • (FI) Finland: Aminocont | Aminofylline;
  • (FR) France: Aminophylline PCH | Planphylline;
  • (GB) United Kingdom: Aminophylline kent | Amnivent | Cardophylin | Norphyllin | Pecram | Phyllocontin continus;
  • (HK) Hong Kong: Neophyllin;
  • (HR) Croatia: Aminophyllinum Lek;
  • (HU) Hungary: Aminophyllin | Aminophyllinum | Diaphyllin;
  • (ID) Indonesia: Aminofillin | Decafil | Erphafillin | Phyllocontin continus;
  • (IE) Ireland: Phyllocontin continus;
  • (IN) India: Aminophyllin | Minophyl | Phyllocontin;
  • (IT) Italy: Aminofil bil | Aminofillina | Aminomal | Aminomal r | Aminophilline | Tefamin;
  • (JO) Jordan: Euphyllin;
  • (JP) Japan: Aminophylline abbott | Aminophylline fujisawa | Aminophylline merck hoei | Aminophylline Nichiiko | Aminophylline Nipro | Aminophylline towa | Aminophylline Tsuruhara | Anephyllin | Apnission | Kyophyllin | Microfillin | Neophyllin | Nichfylin | Novophyllin | Theocardin v;
  • (KE) Kenya: Aminomal r;
  • (KR) Korea, Republic of: Aminophylline huons | Ascontin | Daihan aminophylline | Pediatric asthcontin continus;
  • (KW) Kuwait: Phyllocontin;
  • (LB) Lebanon: Aminofil;
  • (LT) Lithuania: Aminophyllinum | Eufilinas | Euphylin | Euphyllin | Farophyllin | Novphyllin | Pharophyllin | Sophafyllin | Syntophyllin;
  • (LU) Luxembourg: Euphyllin;
  • (LV) Latvia: Aminophyllinum | Eifilins | Euphyllin | Farophyllin | Novphyllin | Pharophyllin | Syntophyllin;
  • (MX) Mexico: Aminofilina | Aminofilina gi | Amofilin | Mino tec;
  • (NG) Nigeria: Macdech | Shree aminophylline | Vinco aminophylline;
  • (NO) Norway: Aminofyllin amdipharm | Aminophylline life;
  • (PE) Peru: Aminofilina;
  • (PH) Philippines: Hizon aminophylline | Theofil;
  • (PK) Pakistan: Aminofil | Aminophylin | Amphyll | Asmolin | Broncophylline | Phyllocontin | Retaphyline;
  • (PL) Poland: Aminophylinum | Aminophyllinum | Euphyllin darnitsa | Farophyllin | Syntophyllin;
  • (PT) Portugal: Aminofilina | Aminofilina Braun | Aminofilina Gestafarma | Aminomal | Filotempo;
  • (RO) Romania: Aminofilin | Aminofilina | Aminofilina arena | Aminofilina bioeel;
  • (RU) Russian Federation: Aminophyllin | Aminophylline escom | Eufillin | Euphyllin | Euphyllin darnitsa | Euphylline;
  • (SA) Saudi Arabia: Euphyllin;
  • (SE) Sweden: Teofyllamin Meda;
  • (SI) Slovenia: Aminophyllin;
  • (SK) Slovakia: Aminophyllinum | Pharophyllin;
  • (TH) Thailand: Amino Patar | Asmalia | Fileen;
  • (TR) Turkey: Aminocardol | Carena | Lafiline | Tecar;
  • (TW) Taiwan: Aminophyllin | Anpillin | Asiphylline | Cotranlin | Phyllocontin;
  • (UA) Ukraine: Aminophyllin | Euphylline;
  • (UG) Uganda: Ago amin | Nest;
  • (UY) Uruguay: Aminofilina | Larjanfilina;
  • (VE) Venezuela, Bolivarian Republic of: Aminofilina;
  • (ZA) South Africa: Aminophyllin | Aminophyllin fresenius | Aminophylline searle | Merck-aminophylline | Micro theophyl ethylenediamine | Mylan aminophylline | Norstan-Ted | Phyllocontin | Sabax aminophylline;
  • (ZM) Zambia: Aramino
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