AQUAPHYLLIN
Clinical safety rating
cautionComprehensive clinical and safety monograph for AQUAPHYLLIN (AQUAPHYLLIN).
Phosphodiesterase-3 (PDE3) inhibitor with additional adenosine receptor antagonism and weak inhibition of phosphodiesterase-4 (PDE4). Increases intracellular cAMP and cGMP, leading to bronchodilation and anti-inflammatory effects.
| Metabolism | Primarily hepatic via CYP1A2, with minor contributions from CYP3A4 and CYP2E1. |
| Excretion | Renal: 90-95% unchanged; biliary/fecal: <5%. |
| Half-life | Terminal elimination half-life: 3-5 hours in healthy adults; prolonged to 8-12 hours in neonates and up to 30 hours in cirrhosis. |
| Protein binding | Approximately 40% bound to albumin. |
| Volume of Distribution | 0.3-0.5 L/kg, indicating distribution primarily in extracellular fluid. |
| Bioavailability | Oral: 85-95%; intramuscular: 75-90%. |
| Onset of Action | Intravenous: 15-30 minutes; oral: 30-60 minutes; intramuscular: 30-45 minutes. |
| Duration of Action | Intravenous: 4-6 hours; oral: 4-6 hours; duration may be prolonged in renal impairment. |
| Molecular Weight | 180.16 |
300 mg orally every 6 hours as needed for acute asthma exacerbation; for chronic maintenance, 300 mg orally every 8 hours.
| Dosage form | SYRUP |
| Renal impairment | No adjustment required. |
| Liver impairment | In Child-Pugh Class B or C, reduce dose by 50% and monitor serum theophylline levels. |
| Pediatric use | Loading dose: 5 mg/kg orally. Maintenance: 4 mg/kg orally every 6 hours for children 1-9 years; 3 mg/kg orally every 6 hours for children 10-16 years. Maximum daily dose: 24 mg/kg. |
| Geriatric use | Use lower initial dose (e.g., 200 mg orally every 8 hours) and titrate slowly; monitor serum theophylline levels due to decreased clearance. |
| 1st trimester | Theophylline crosses the placenta. Use only if clearly needed; risk of teratogenicity not definitively established in humans, but associated with fetal tachycardia and irritability. |
| 2nd trimester | Monitor maternal serum levels closely; dose adjustments may be needed due to changes in clearance. Increased risk of neonatal toxicity if maternal levels high. |
| 3rd trimester | Avoid near term if possible; neonatal theophylline withdrawal (apnea, irritability) and toxicity (tachycardia, jitteriness) can occur. Use lowest effective dose. |
Clinical note
Comprehensive clinical and safety monograph for AQUAPHYLLIN (AQUAPHYLLIN).
| Placental transfer | Theophylline readily crosses the placenta; fetal serum concentrations approximate maternal levels. Cord blood concentrations are similar to maternal concentrations. |
| Breastfeeding | Theophylline is excreted into breast milk with a milk:plasma ratio of ~0.6-0.9. Infant serum levels may reach therapeutic levels if maternal dose high. Monitor for irritability, insomnia, or tachycardia in the infant. American Academy of Pediatrics considers compatible with breastfeeding, but caution advised. |
| Lactation Rating | L3 (Moderately Safe) – potential for infant toxicity; use with caution and monitor infant effects. |
| Teratogenic Risk | Theophylline (Aquaphyllin) is pregnancy category C. First trimester: No well-controlled studies; risk cannot be ruled out. Second/third trimesters: Increased risk of neonatal apnea, tachycardia, and jitteriness due to transplacental passage. Maternal toxicity at high doses may cause fetal hypoxia. |
| Fetal Monitoring | Monitor maternal serum theophylline levels (target 5-15 mcg/mL), heart rate, and signs of toxicity (nausea, tachycardia, arrhythmias). Fetal monitoring: heart rate and growth. Neonatal surveillance for jitteriness, tachycardia, and feeding intolerance after delivery. |
| Fertility Effects | No direct evidence of impaired fertility. Theophylline may affect uterine contractility and has been used off-label in tocolysis, but no specific fertility impact documented. Standard effects of asthma control on fertility apply. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to theophylline or any component of the formulationExisting arrhythmia requiring suppressionSeizure disorder (unless adequately controlled with anticonvulsants)
| Precautions | Cardiovascular events: arrhythmias, tachycardia, hypotension, Seizures in patients with history of seizure disorder, Significant drug interactions with CYP1A2 inhibitors (e.g., cimetidine, fluoroquinolones) and inducers (e.g., smoking, rifampin), Overdose risk: narrow therapeutic index, monitor serum levels |
| Food/Dietary | Avoid large amounts of caffeine (coffee, tea, cola, chocolate) as it may increase theophylline levels and risk of toxicity. High-protein, low-carbohydrate diets may decrease theophylline metabolism; low-protein, high-carbohydrate diets may increase metabolism. Consistent dietary habits are recommended. Charcoal-broiled meats may increase metabolism. |
| Clinical Pearls | Aquaphyllin (theophylline) has a narrow therapeutic index; serum levels should be maintained between 5-15 mcg/mL for optimal bronchodilation. Monitor for toxicity (nausea, vomiting, tremor, tachycardia) especially in patients with hepatic impairment, heart failure, or concurrent use of CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine). Smoking induces theophylline metabolism requiring higher doses. Use with caution in elderly and patients with seizure disorders. |
| Patient Advice | Take exactly as prescribed; do not change dose without consulting your doctor. · Avoid consuming large amounts of caffeine-containing foods or beverages (coffee, tea, cola, chocolate) as they may increase side effects. · Report symptoms of toxicity such as persistent nausea, vomiting, rapid or irregular heartbeat, or seizures immediately. · Do not stop taking this medication abruptly; taper under medical supervision. · Inform your doctor of all medications you take, including over-the-counter drugs and herbal supplements. · If you smoke, tell your doctor; changes in smoking habits may require dose adjustment. · Store at room temperature away from moisture and heat. |
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