Aminophylline

• Approved Indications:
• Treatment and prevention of bronchospasm associated with reversible airway obstruction in conditions such as asthma, chronic bronchitis, and emphysema (chronic obstructive pulmonary disease, COPD).
• Adjunct therapy in acute exacerbations of asthma and COPD to improve airway patency.
• Management of apnea of prematurity in neonates when other treatments are ineffective.
• Off-label/Clinically Accepted Uses:
• Occasionally used in status asthmaticus refractory to first-line bronchodilators.
• May be used to enhance respiratory muscle contractility in respiratory failure.
• Some use in chronic bronchitis or emphysema patients with reversible airway obstruction.

• Adults:
• Initial IV loading dose: 5–6 mg/kg administered over 20–30 minutes.
• Maintenance IV infusion: 0.5–0.9 mg/kg/hour adjusted according to serum levels.
• Oral dosing: Usually 200–400 mg every 6–8 hours, adjusted based on therapeutic response and serum concentration.
• Pediatrics:
• Loading dose IV: 5–6 mg/kg over 20–30 minutes.
• Maintenance dose IV: 0.5–1 mg/kg/hour continuous infusion.
• Oral dose: 5–6 mg/kg/day divided into 3–4 doses; adjust according to serum levels.
• Elderly:
• Initiate with lower doses due to altered metabolism; close serum level monitoring recommended.
• Renal and Hepatic Impairment:
• Dosage adjustments necessary; metabolism may be reduced, leading to accumulation and toxicity risk.
• Administration Routes:
• Intravenous infusion for rapid onset in acute settings.
• Oral tablets or solution for maintenance therapy.
• Monitoring:
• Regular serum theophylline level monitoring (therapeutic range 10–20 mcg/mL) to avoid toxicity.
• Monitor vital signs and clinical respiratory status frequently.

Aminophylline is a compound of theophylline and ethylenediamine that, once in the body, dissociates to release theophylline. Theophylline acts primarily by inhibiting phosphodiesterase enzymes (mainly PDE3 and PDE4), leading to increased intracellular cyclic AMP (cAMP) levels. Elevated cAMP causes relaxation of bronchial smooth muscle, resulting in bronchodilation. Additionally, it antagonizes adenosine receptors, which contributes to bronchodilation and reduced inflammatory mediator release. The net effect is airway smooth muscle relaxation, improved airflow, and enhanced diaphragmatic contractility.

• Absorption:
• Well absorbed orally with peak plasma levels occurring within 1 to 2 hours; IV administration produces immediate levels.
• Distribution:
• Distributed widely throughout body tissues and fluids; volume of distribution approximately 0.5 L/kg.
• Crosses the blood-brain barrier and placenta; present in breast milk.
• Metabolism:
• Primarily metabolized by hepatic cytochrome P450 enzymes, mainly CYP1A2 and CYP3A4.
• Elimination:
• Mainly excreted as metabolites in urine; less than 10% excreted unchanged.
• Half-life:
• Approximately 7–9 hours in healthy adults; can be prolonged in elderly, liver disease, congestive heart failure, and smokers (who metabolize faster).
• Bioavailability:
• Oral bioavailability approximately 90%.

• Pregnancy:
• FDA pregnancy category C. Animal studies have shown adverse effects at high doses; limited human data. Use only if clearly needed and benefits outweigh risks.
• Lactation:
• Theophylline passes into breast milk in small amounts; generally considered compatible with breastfeeding but monitor infant for side effects.
• Caution advised in pregnancy and lactation due to limited human data.

• Bronchodilator
• Methylxanthine Derivative

• Known hypersensitivity to aminophylline, theophylline, or related methylxanthines.
• Active peptic ulcer disease (relative contraindication due to increased acid secretion).
• Severe cardiac arrhythmias, including ventricular fibrillation.
• Seizure disorders (use with caution).
• Concomitant use of other methylxanthines (to avoid toxicity).

• Narrow therapeutic index requiring careful serum level monitoring to avoid toxicity.
• Toxicity risk increased by hepatic impairment, congestive heart failure, fever, and drug interactions.
• Use caution in patients with cardiac disease; may precipitate arrhythmias.
• Avoid abrupt discontinuation in chronic use to prevent rebound bronchospasm.
• Monitor for signs of overdose: nausea, vomiting, seizures, arrhythmias.
• Use with caution in seizure disorders and in patients with active peptic ulcer disease.
• Smoking induces metabolism and may reduce therapeutic levels.

• Common:
• Gastrointestinal: nausea, vomiting, abdominal discomfort.
• Central nervous system: headache, insomnia, irritability, tremor.
• Cardiovascular: palpitations, tachycardia.
• Serious/Rare:
• Severe arrhythmias, including ventricular tachycardia and fibrillation.
• Seizures, especially in overdose.
• Hypotension.
• Allergic reactions such as rash or urticaria.

• Enzyme Inducers (reduce aminophylline levels):
• Rifampin, carbamazepine, phenytoin, phenobarbital, smoking (induction of CYP1A2).
• Enzyme Inhibitors (increase levels and toxicity risk):
• Cimetidine, fluoroquinolones (ciprofloxacin), macrolides (erythromycin), allopurinol, oral contraceptives.
• Other Interactions:
• Concomitant use with other methylxanthines increases risk of toxicity.
• Beta-agonists may have additive cardiovascular effects.
• Caution with sympathomimetic agents due to increased risk of arrhythmias.
• Food and Alcohol:
• High-protein, low-carb diets may increase clearance.
• Alcohol can affect metabolism variably; caution advised.

• Recent guidelines emphasize the limited role of aminophylline/theophylline in asthma management due to narrow therapeutic index and availability of safer alternatives.
• Continued use primarily reserved for refractory cases or where inhaled therapy is insufficient or unavailable.
• Therapeutic drug monitoring recommended to optimize dosing and minimize toxicity.
• EMA and FDA recommend caution and thorough monitoring due to potential serious adverse effects.

• Store at controlled room temperature between 20°C and 25°C.
• Protect from light and moisture.
• Keep container tightly closed.
• Avoid excessive heat and freezing.
• Oral solutions should be stored according to manufacturer instructions and discarded after recommended period.