NEOTHYLLINE
Clinical safety rating: caution
Comprehensive 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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NEOTHYLLINE (NEOTHYLLINE).
| Breastfeeding | Excreted into breast milk; M/P ratio unknown. Use with caution, monitor infant for irritability or poor feeding. |
| 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. |
■ FDA Black Box Warning
No FDA black box warning reported.
| Serious Effects |
Hypersensitivity to neothyphylline or other xanthines; active seizure disorder; uncontrolled arrhythmias; porphyria.
| 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). |
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| Fertility Effects | No known adverse effects on fertility based on limited data. |