UNI-DUR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for UNI-DUR (UNI-DUR).
UNI-DUR (theophylline) inhibits phosphodiesterase enzymes, leading to increased intracellular cAMP levels. This causes bronchodilation, anti-inflammatory effects (reduced eosinophil infiltration, decreased cytokine release), and enhanced diaphragmatic contractility. It also acts as a weak adenosine receptor antagonist.
| Metabolism | Theophylline is primarily metabolized in the liver by cytochrome P450 enzymes CYP1A2 (major) and CYP2E1, CYP3A4 (minor). It undergoes N-demethylation and oxidation to form metabolites (1-methylxanthine, 3-methylxanthine, 1,3-dimethyluric acid). Approximately 10% is excreted unchanged in urine. |
| Excretion | Primarily renal (70-80%) as unchanged drug and metabolites; 10-15% fecal. |
| Half-life | Terminal elimination half-life 24-36 hours; prolonged in renal impairment (up to 90 hours). |
| Protein binding | 95% bound to albumin. |
| Volume of Distribution | Vd 0.2-0.3 L/kg; indicates distribution primarily in extracellular fluid. |
| Bioavailability | Oral: 85-95% (immediate-release); 70-80% (extended-release). |
| Onset of Action | Oral: 2-4 hours; IV: 5-15 minutes. |
| Duration of Action | Oral: 12-24 hours; IV: 6-12 hours. Extended-release formulation provides sustained effect over 24 hours. |
| Molecular Weight | 225.29 |
200-400 mg orally every 12 hours; maximum 800 mg daily.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR 30-50 mL/min: 200 mg every 12 hours; GFR <30 mL/min: 200 mg every 24 hours; hemodialysis: 200 mg after dialysis. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 200 mg every 12 hours; Child-Pugh C: 200 mg every 24 hours. |
| Pediatric use | 5-10 mg/kg orally every 12 hours; maximum 400 mg daily. |
| Geriatric use | Initiate at 200 mg every 12 hours; increase cautiously, monitor renal function. |
| 1st trimester | Insufficient human data; animal studies not available. Avoid use in first trimester unless benefit outweighs risk. |
| 2nd trimester | Limited data; use only if clearly needed. May cause fetal tachycardia or uterine hyperstimulation. |
| 3rd trimester | Avoid use in late pregnancy due to risk of delay in labor or preterm contractions. May cause fetal tachycardia. |
Clinical note
Comprehensive clinical and safety monograph for UNI-DUR (UNI-DUR).
| Placental transfer | Extensive placental transfer; crosses rapidly and achieves fetal concentrations similar to maternal levels. |
| Breastfeeding | Excreted into breast milk in small amounts; limited data. Use with caution in lactating women, especially with premature infants or those with compromised renal function. |
■ FDA Black Box Warning
WARNING: Life-threatening adverse events, including seizures, cardiac arrhythmias, and respiratory arrest, can occur with theophylline toxicity. Serum theophylline levels must be monitored closely, and dosing adjusted to maintain therapeutic range (5-15 mcg/mL). Concurrent use with other xanthines (e.g., caffeine) is contraindicated.
| Serious Effects |
Hypersensitivity to theophylline or any componentSeizure disorders not controlled by medicationActive peptic ulcer diseaseSevere cardiac arrhythmias
| Precautions | Therapeutic drug monitoring required due to narrow therapeutic index. Caution in patients with hepatic impairment, heart failure, pneumonia, elderly, and fever (prolonged half-life). Drug interactions with CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine) and inducers (e.g., smoking, rifampin). Seizure risk at high levels. Cardiotoxicity (atrial/ventricular arrhythmias). |
| Food/Dietary | Food does not affect absorption significantly; however, consistent dietary caffeine intake may increase side effects. A high-protein, low-carbohydrate diet can decrease theophylline clearance; avoid drastic dietary changes. |
Loading safety data…
| Lactation Rating |
| L3 (Moderately Safe) |
| Teratogenic Risk | Pregnancy Category C. First trimester: no adequate studies, potential risk based on animal data. Second and third trimesters: may cause fetal harm including decreased uterine blood flow, growth restriction, and premature labor inhibition. Avoid use unless benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and uterine contractions; fetal heart rate and growth via ultrasound; assess for signs of preterm labor or placental insufficiency. |
| Fertility Effects | No adequate studies on fertility. Animal studies show no impairment, but potential hormonal effects may theoretically affect fertility. Advise caution in women attempting conception. |
| Clinical Pearls | UNI-DUR (theophylline extended-release) requires monitoring of serum theophylline concentrations to maintain efficacy and avoid toxicity; therapeutic range is 5-15 mcg/mL. Avoid use in patients with active peptic ulcer disease or seizure disorders. Dosage adjustments needed in hepatic impairment, heart failure, and with concurrent use of drugs that affect CYP1A2 and CYP3A4. |
| Patient Advice | Take UNI-DUR exactly as prescribed, at the same time each day, with or without food. · Do not crush or chew the tablets; swallow whole. · Avoid smoking and limit caffeine intake as they can alter theophylline levels. · Report symptoms of toxicity such as nausea, vomiting, insomnia, palpitations, or seizures. · Do not change brands or formulations without consulting your healthcare provider. |