NEOTHYLLINE
Clinical safety rating
cautionComprehensive clinical and safety monograph for NEOTHYLLINE (NEOTHYLLINE).
Neothyphylline is a bronchodilator that acts as a competitive antagonist at adenosine A1 and A2 receptors, and also inhibits phosphodiesterase (PDE3 and PDE4), leading to increased intracellular cAMP levels and subsequent relaxation of bronchial smooth muscle.
| Metabolism | Primarily hepatic via CYP1A2, with minor contributions from CYP2E1 and CYP3A4. |
| Excretion | Renal excretion accounts for approximately 70-80% of elimination, primarily as unchanged drug; hepatic metabolism accounts for 20-30%; biliary/fecal excretion is negligible (<2%). |
| Half-life | Terminal elimination half-life is 3-5 hours in adults with normal renal function; prolonged to 12-24 hours in severe renal impairment (CrCl <10 mL/min); in neonates, half-life is 15-30 hours. |
| Protein binding | 40-50% bound to albumin; low protein binding reduces risk of drug interactions. |
| Volume of Distribution | 0.3-0.5 L/kg; approximates total body water; indicates distribution into interstitial and intracellular fluids. |
| Bioavailability | Oral: 90-100% (well absorbed); Rectal: 80-90% (variable). |
| Onset of Action | Oral: 15-30 minutes; Intravenous: 1-2 minutes; Rectal: 30-60 minutes. |
| Duration of Action | Oral: 4-6 hours; Intravenous: 2-4 hours; Rectal: 3-5 hours. Duration may be extended in hepatic or renal impairment. |
| Molecular Weight | 180.16 |
150-300 mg orally every 6-8 hours; maximum 1200 mg/day.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 30-50 mL/min: 50% of normal dose every 8 hours; GFR 10-29 mL/min: 25% of normal dose every 12 hours; GFR <10 mL/min: avoid use. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | 6-12 mg/kg/day orally divided every 6-8 hours; maximum 400 mg/day. |
| Geriatric use | Start at lower end of adult dosing, monitor for toxicity; consider dose reduction by 25-50% due to age-related changes. |
| 1st trimester | Use only if clearly needed; no well-controlled studies in pregnant women. Theophylline crosses the placenta and may cause fetal tachycardia. |
| 2nd trimester | Use with caution; monitor maternal serum levels closely. Dose adjustments may be necessary due to changes in clearance during pregnancy. |
| 3rd trimester | Use with caution; neonatal effects (e.g., irritability, jitteriness) may occur if maternal levels are high. Consider tapering before delivery. |
Clinical note
Comprehensive clinical and safety monograph for NEOTHYLLINE (NEOTHYLLINE).
| Placental transfer | Theophylline readily crosses the placenta, achieving fetal serum levels comparable to maternal levels. |
| Breastfeeding | Theophylline is excreted into breast milk in small amounts (approximately 10% of maternal serum level). Irritability and insomnia have been reported in nursing infants. Use with caution, monitor infant for signs of stimulation, and consider timing feeds to avoid peak milk concentrations. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Insufficient human data. Animal studies show no teratogenicity at clinically relevant doses. Risk cannot be excluded; use only if benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal serum theophylline levels (therapeutic 5-15 mcg/mL), heart rate, and respiratory status. Fetal heart rate monitoring may be considered. |
| Fertility Effects | No known adverse effects on fertility based on limited data. |
■ FDA Black Box Warning
No FDA black box warning reported.
| Serious Effects |
Hypersensitivity to theophylline or any componentActive seizure disorder (unless controlled by other therapy)Peptic ulcer disease (active)Hyperthyroidism (untreated or inadequately controlled)
| Precautions | Monitor serum theophylline levels; reduce dose in patients with hepatic impairment, congestive heart failure, or acute febrile illness; risk of seizures at high concentrations; caution with concurrent use of CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) or inducers (smoking, rifampin). |
| Food/Dietary | Avoid excessive dietary caffeine (coffee, tea, cola, chocolate) as it may increase theophylline side effects. Charcoal-broiled foods may increase metabolism of theophylline, potentially reducing efficacy. St. John's wort may decrease theophylline levels. |
| Clinical Pearls | Neothyline (theophylline) has a narrow therapeutic index; monitor serum levels (target 5-15 mcg/mL). Use with caution in patients with heart failure, liver disease, or fever, as clearance is reduced. Cimetidine, ciprofloxacin, and erythromycin increase levels. Smoking induces metabolism requiring higher doses. Seizures or arrhythmias may occur at toxic levels. |
| Patient Advice | Take exactly as prescribed; do not change dose without consulting your doctor. · Avoid consuming large amounts of caffeine (coffee, tea, chocolate, cola) as it may increase side effects. · Inform your doctor about all medications you take, especially antibiotics, heart medications, or seizure drugs. · Watch for signs of toxicity: nausea, vomiting, insomnia, restlessness, rapid heartbeat, or seizures. Seek immediate help if these occur. · Do not smoke or stop smoking suddenly, as it may affect how this drug works in your body. |
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