Usage
Aminophylline, a combination of theophylline and ethylenediamine, is primarily prescribed for the treatment of respiratory conditions like asthma, chronic bronchitis, emphysema, and chronic obstructive pulmonary disease (COPD). It is categorized as a bronchodilator and a xanthine derivative. Its mechanism of action involves relaxing the smooth muscles in the airways, leading to bronchodilation and improved airflow to the lungs. It also exhibits some anti-inflammatory effects. Although less common, it may also be used to treat apnea of prematurity (in neonates) and occasionally for paroxysmal dyspnea associated with left heart failure.
Alternate Names
Aminophylline is sometimes referred to as aminophylline hydrate. Brand names for theophylline, the active component of aminophylline, include Theo-24, Theochron, Elixophyllin, and Uniphyl. Aminophylline itself is also available as a generic medication and under various brand names internationally.
How It Works
Pharmacodynamics: Aminophylline acts as a nonselective phosphodiesterase inhibitor, increasing intracellular cyclic adenosine monophosphate (cAMP). This leads to smooth muscle relaxation in the bronchi, resulting in bronchodilation. Theophylline also antagonizes adenosine receptors, which further contributes to bronchodilation and may have anti-inflammatory effects.
Pharmacokinetics: Aminophylline is well-absorbed orally. It is metabolized primarily in the liver by the cytochrome P450 enzyme system, specifically CYP1A2 and CYP3A4, and is eliminated primarily through renal excretion. The half-life of theophylline varies significantly, from about 3.5 hours in young children to 9 hours in healthy adults and can be prolonged in patients with liver disease, heart failure, and in neonates.
Mode of Action: Theophylline, the active component of aminophylline, works by inhibiting phosphodiesterases, enzymes that break down cAMP. Increased cAMP levels lead to bronchial smooth muscle relaxation and bronchodilation. Theophylline also inhibits adenosine receptors, which can cause bronchoconstriction.
Elimination Pathways: Theophylline is primarily metabolized by the liver and excreted by the kidneys.
Dosage
Aminophylline dosage must be individualized and closely monitored based on serum theophylline levels and clinical response. Dosages are calculated using ideal body weight (IBW) or lean body mass, especially in obese patients.
Standard Dosage
Adults:
- Loading Dose (for patients not currently taking theophylline): 5-7 mg/kg (of aminophylline) IV or orally over 20-30 minutes (maximum infusion rate: 25 mg/min). If using aminophylline hydrate, 6 mg/kg IV.
- Maintenance Dose: 0.4-0.6 mg/kg/hour IV or 4.8-7.2 mg/kg orally (extended-release) every 12 hours. Adjust to maintain serum theophylline levels within the therapeutic range (10-20 mcg/mL).
Children:
- Dosage is complex and varies with age and weight. Consult pediatric dosing guidelines and monitor serum levels closely.
- Consider:
- 1.5-6 months: 0.5 mg/kg/hr IV or 10 mg/kg/day PO divided every 8 hours
- 6-12 months: 0.6-0.7 mg/kg/hr IV or 12-18 mg/kg/day PO divided every 8 hours
- 1-9 years: 1 mg/kg/hr IV or 8 mg/kg PO (extended release) every 8 hours
- 9-12 years: 0.8-0.9 mg/kg/hr IV or 6.4 mg/kg PO (extended release) every 8 hours
- 12-16 years: 0.7 mg/kg/hr IV or 5.6 mg/kg PO (extended release) every 8 hours
- Pediatric Safety Considerations: Children are more susceptible to theophylline toxicity. Closely monitor serum levels and watch for signs of adverse effects.
Special Cases:
- Elderly Patients: Start with lower doses (e.g., 0.3 mg/kg/hour IV maintenance) due to decreased clearance.
- Patients with Renal Impairment: Dose adjustment may be necessary depending on the severity of impairment. Consult specific renal dosing recommendations.
- Patients with Hepatic Dysfunction: Significant dose reduction is required due to reduced clearance. Close monitoring is crucial.
- Patients with Comorbid Conditions: Consider dose adjustments for conditions like congestive heart failure, cor pulmonale, or other conditions affecting theophylline clearance.
Clinical Use Cases
- Intubation: Aminophylline is not typically used during intubation itself, but it might be administered to manage bronchospasm after intubation.
- Surgical Procedures: Aminophylline is generally not administered during surgical procedures.
- Mechanical Ventilation: Aminophylline can be used to facilitate weaning from mechanical ventilation, typically with a lower dose regimen (e.g., 200 mg aminophylline bid). Serum levels should be monitored.
- Intensive Care Unit (ICU) Use: Dose is titrated to therapeutic range and usually given via IV infusion.
- Emergency Situations: Use loading doses as appropriate in acute asthma exacerbations and emergencies. Titrate and monitor serum levels.
Dosage Adjustments
Adjust doses based on serum theophylline levels, clinical response, age, and the presence of comorbid conditions that influence drug metabolism (e.g., heart failure, liver disease). Smokers typically require higher doses. Consult specific dosing guidelines for various scenarios and patient populations.
Side Effects
Common Side Effects:
Nausea, vomiting, headache, insomnia, irritability, nervousness, diarrhea, abdominal discomfort, tremors.
Rare but Serious Side Effects:
Seizures, cardiac arrhythmias (tachycardia, extrasystoles), circulatory failure, hyperglycemia, albuminuria, hematemesis.
Long-Term Effects:
Chronic use can potentially lead to gastrointestinal issues, cardiovascular problems, and dependence.
Adverse Drug Reactions (ADR):
Severe allergic reactions (anaphylaxis), Stevens-Johnson syndrome (rare), toxic epidermal necrolysis (rare).
Contraindications
- Hypersensitivity to theophylline or ethylenediamine.
- Active peptic ulcer disease.
- Uncontrolled seizure disorders.
- Acute porphyria.
Drug Interactions
- CYP450 Interactions: Theophylline metabolism is affected by CYP1A2 and CYP3A4 inducers (e.g., rifampin, phenobarbital) and inhibitors (e.g., cimetidine, erythromycin, ciprofloxacin, fluconazole).
- Other Drug Interactions: Interacts with many other medications including but not limited to: lithium, beta-blockers, adenosine, benzodiazepines, some antibiotics. Consult comprehensive drug interaction resources for detailed information.
- Lifestyle Factors: Smoking (increases clearance), alcohol (may decrease clearance), and certain foods (e.g., charcoal-broiled meats, high-protein diets) can affect theophylline levels.
Pregnancy and Breastfeeding
Theophylline is classified as Pregnancy Category C. It crosses the placenta and is present in breast milk. Weigh the benefits against the risks for both mother and fetus/infant. Use during pregnancy or breastfeeding only if clearly needed and under close medical supervision.
Drug Profile Summary
- Mechanism of Action: Nonselective phosphodiesterase inhibitor, increasing cAMP, causing bronchodilation; adenosine receptor antagonist.
- Side Effects: Nausea, vomiting, headache, insomnia, seizures, arrhythmias.
- Contraindications: Hypersensitivity, active peptic ulcer, uncontrolled seizures.
- Drug Interactions: CYP1A2 and CYP3A4 inhibitors/inducers, numerous drug interactions.
- Pregnancy & Breastfeeding: Category C; use with caution.
- Dosage: Individualized based on serum levels and clinical response. See detailed dosage section above.
- Monitoring Parameters: Serum theophylline levels, ECG, blood pressure, heart rate, renal and liver function tests.
Popular Combinations
Theophylline may be used in combination with inhaled corticosteroids and beta-agonists in the management of asthma and COPD.
Precautions
- Monitor serum theophylline levels, especially when initiating therapy and making dose adjustments.
- Closely observe patients with cardiac, liver, or renal disease.
- Avoid abrupt discontinuation.
- Counsel patients about potential side effects and drug interactions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Aminophylline + Theophylline?
A: Dosing is highly individualized. Refer to detailed dosage section above. Serum levels are crucial in guiding dosage.
Q2: What are the common side effects?
A: Common side effects include nausea, vomiting, headache, insomnia, and gastrointestinal disturbances.
A: Seizures, cardiac arrhythmias, and circulatory failure require urgent medical intervention.
Q4: What are the contraindications to Aminophylline + Theophylline use?
A: Contraindications include hypersensitivity to theophylline or ethylenediamine, active peptic ulcer disease, and uncontrolled seizure disorders.
Q5: What are the key drug interactions?
A: Numerous drugs can interact, including CYP1A2 and CYP3A4 inhibitors/inducers (e.g., cimetidine, erythromycin, ciprofloxacin, rifampin), lithium, and certain antibiotics. Consult comprehensive drug interaction resources.
Q6: Can Aminophylline + Theophylline be used in pregnant or breastfeeding women?
A: It’s a Pregnancy Category C drug. Use only if clearly needed and under close medical supervision due to potential risks to the fetus/infant.
Q7: How is Aminophylline + Theophylline administered?
A: It can be given intravenously or orally. For IV administration, dilute appropriately and infuse slowly, especially for loading doses. Various oral formulations exist, including immediate-release and extended-release tablets and liquids.
Q8: What are the important monitoring parameters for patients on Aminophylline + Theophylline?
A: Monitor serum theophylline levels, ECG, blood pressure, and heart rate. Renal and liver function tests may be indicated in certain patients.
Q9: What is the therapeutic range for serum theophylline levels?
A: The generally accepted therapeutic range is 10-20 mcg/mL, although lower levels may be effective in some individuals.
Q10: Can aminophylline be used to wean patients off mechanical ventilation?
A: Yes, a lower intermittent dosing strategy may be utilized. Serum levels should be monitored and the patient’s clinical status closely observed.
