RESPORAL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RESPORAL (RESPORAL).
RESPORAL contains theophylline, a methylxanthine that inhibits phosphodiesterase (PDE) isoenzymes, leading to increased intracellular cAMP and cGMP levels. It also antagonizes adenosine receptors, resulting in bronchodilation and anti-inflammatory effects.
| Metabolism | Primarily hepatic via cytochrome P450 enzymes, including CYP1A2, CYP2E1, and CYP3A4. Approximately 90% of theophylline is metabolized in the liver. |
| Excretion | Renal excretion accounts for 70% of elimination (30% unchanged), biliary/fecal 20%, and 10% metabolized. |
| Half-life | Terminal half-life is 12 hours (range 10-14 h), supporting twice-daily dosing in most patients. |
| Protein binding | 95% bound to albumin. |
| Volume of Distribution | Vd 0.5 L/kg, indicating moderate tissue distribution. |
| Bioavailability | Oral: 80%; inhaled: 25% (due to local deposition and first-pass metabolism). |
| Onset of Action | Oral: 30-60 minutes; IV: immediate; inhaled: 5-15 minutes. |
| Duration of Action | Oral: 12 hours; IV: 6-8 hours; inhaled: 4-6 hours. |
| Molecular Weight | 387.43 |
2 mg orally twice daily
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR 30-59 mL/min: 1 mg orally twice daily; GFR <30 mL/min: 1 mg orally once daily |
| Liver impairment | Child-Pugh Class A: 2 mg orally twice daily; Class B: 1 mg orally twice daily; Class C: not recommended |
| Pediatric use | Weight <30 kg: 1 mg orally twice daily; Weight ≥30 kg: 2 mg orally twice daily |
| Geriatric use | Age ≥65 years: 1 mg orally twice daily; monitor for renal function and adjust dose accordingly |
| 1st trimester | Avoid use in first trimester due to potential teratogenicity. |
| 2nd trimester | Use only if clearly needed; limited human data. |
| 3rd trimester | Risk of neonatal respiratory depression if used near term. |
Clinical note
Comprehensive clinical and safety monograph for RESPORAL (RESPORAL).
| Placental transfer | Crosses placenta with fetal levels approximately 50-70% of maternal levels. |
| Breastfeeding | Excreted in breast milk in low amounts; monitor infant for respiratory depression. |
| Lactation Rating | L3 |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to resporalSevere hepatic impairmentConcurrent use with MAOIs
| Precautions | Cardiovascular toxicity: arrhythmias, hypotension, tachycardia; risk increases with serum levels >20 mcg/mL., Seizures: may occur at toxic concentrations, especially in patients with pre-existing seizure disorders or conditions that lower seizure threshold., Gastrointestinal effects: nausea, vomiting, and diarrhea; may be signs of toxicity., Drug interactions: caution with drugs that inhibit (e.g., cimetidine, ciprofloxacin, fluvoxamine) or induce (e.g., rifampin, phenobarbital, carbamazepine) CYP1A2., Metabolic effects: hypokalemia, hyperglycemia, and metabolic acidosis in overdose., Hepatic impairment: reduce dose in patients with hepatic insufficiency., Pregnancy: use only if clearly needed; crosses placenta. |
| Food/Dietary | Avoid grapefruit and grapefruit juice, as they may increase drug levels by CYP3A4 inhibition. |
Loading safety data…
| Teratogenic Risk | First trimester: Limited data; animal studies show no teratogenicity at clinically relevant doses. Second/third trimesters: Associated with decreased uterine blood flow; avoid use unless benefit outweighs risk. Peripartum: May cause transient respiratory depression in neonates if used near term. |
| Fetal Monitoring | Monitor fetal heart rate and uterine activity during prolonged use. Assess neonatal respiratory status post-delivery if used near term. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies show no impairment. |
| Clinical Pearls | RESPORAL (a proposed H1-receptor antagonist for allergic rhinitis) requires dose adjustment in renal impairment (CrCl <30 mL/min). Onset of action is 1-3 hours; maximal effect at steady state (2 days). Monitor for sedation in elderly or hepatic impairment. Avoid concurrent CNS depressants. |
| Patient Advice | Take once daily at the same time; may cause drowsiness initially. · Avoid driving or operating heavy machinery until you know how this medication affects you. · Do not consume alcohol or take other sedating medications. · If you have kidney or liver disease, inform your doctor before starting. · Store at room temperature, away from moisture and heat. |