THEOLIXIR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for THEOLIXIR (THEOLIXIR).
Theophylline is a xanthine derivative that acts as a competitive nonselective phosphodiesterase inhibitor, increasing intracellular cyclic AMP levels, and as an antagonist at adenosine receptors (A1 and A2 subtypes), leading to bronchodilation, anti-inflammatory effects, and stimulation of respiratory drive.
| Metabolism | Hepatic metabolism via CYP1A2, CYP2E1, and CYP3A4. Approximately 10% excreted unchanged in urine. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 10% of elimination; the remainder is hepatically metabolized, with 80% excreted in urine as metabolites (1-methyluric acid and 3-methylxanthine) and less than 10% in feces. |
| Half-life | Terminal elimination half-life is 3–5 hours in adults (nonsmokers), but prolonged to 6–8 hours in neonates, elderly, and patients with hepatic cirrhosis or heart failure. Smoking (tobacco or marijuana) reduces half-life to 1–2 hours due to enzyme induction. |
| Protein binding | Approximately 40% bound to albumin (primarily), with some binding to alpha-1-acid glycoprotein; binding is reduced in neonates and patients with hypoalbuminemia. |
| Volume of Distribution | 0.3–0.7 L/kg; approximates total body water. Higher Vd in neonates (0.8 L/kg) due to increased extracellular fluid. Clinically, loading dose calculation uses Vd = 0.5 L/kg. |
| Bioavailability | Oral immediate-release: 96–100% (virtually complete); sustained-release formulations: 80–100% (dependent on formulation and food effects). |
| Onset of Action | Oral immediate-release: 15–30 minutes; oral sustained-release: 1–2 hours; intravenous: 1–2 minutes. |
| Duration of Action | Immediate-release oral: 4–6 hours; sustained-release oral: 8–12 hours (based on dosing interval). Duration is dose-dependent and variable due to metabolism differences. |
Oral: 200-400 mg every 6 hours (maximum 1600 mg/day) as sustained-release tablets or liquid. Inhalation: Not applicable.
| Dosage form | ELIXIR |
| Renal impairment | No adjustment required for GFR >30 mL/min. For GFR 10-30 mL/min: reduce dose by 50% and increase interval to every 12 hours. For GFR <10 mL/min: give 200 mg every 12-24 hours. |
| Liver impairment | Child-Pugh A: no change. Child-Pugh B: reduce dose by 50% (maximum 800 mg/day). Child-Pugh C: reduce dose by 75% (maximum 400 mg/day) or increase interval to every 12-24 hours. |
| Pediatric use | Oral: Initial 5 mg/kg/dose every 6 hours; titrate to target serum concentration of 5-15 mcg/mL. Maximum: 20 mg/kg/day or 800 mg/day, whichever lower. |
| Geriatric use | Start at lowest adult dose (200 mg every 6 hours) and monitor serum levels; decreased clearance may necessitate lower maintenance doses. Maximum daily dose 800 mg. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for THEOLIXIR (THEOLIXIR).
| Breastfeeding | Theophylline is excreted into breast milk with M/P ratio approximately 0.6-0.7. Average infant dose ~1.5% of maternal weight-adjusted dose. Considered compatible with breastfeeding; observe infant for irritability or sleep disturbance, especially with maternal doses >800 mg/day or high serum levels. |
| Teratogenic Risk | Theophylline (active ingredient in THEOLIXIR) is not a major human teratogen. First trimester: Limited data show no consistent association with major malformations. Second/Third trimesters: Fetal tachycardia and jitteriness may occur at maternal therapeutic levels; toxicity can cause neonatal irritability, vomiting, and apnea. Risk of preterm labor or low birth weight not established. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to theophylline or any component of the formulation","Pre-existing cardiac arrhythmias (especially tachyarrhythmias)"]
| Precautions | ["Narrow therapeutic index; serum levels should be monitored to avoid toxicity","Risk of seizures, arrhythmias, and death at high concentrations","Caution in patients with hepatic impairment, congestive heart failure, pulmonary edema, or fever","Potential for drug interactions with CYP1A2 inhibitors/inducers"] |
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| Fetal Monitoring | Monitor maternal serum theophylline levels (therapeutic range 5-15 mcg/mL) to avoid toxicity. Assess fetal heart rate for tachycardia. Monitor neonatal for signs of theophylline toxicity (irritability, vomiting, jitteriness) if used near term. |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies show no impairment at clinically relevant doses. |