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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for UNI-DUR (UNI-DUR).
| Breastfeeding | Excreted in human milk; M/P ratio not established. Potential for serious adverse reactions in nursing infants. Decision to discontinue nursing or drug based on importance to mother. |
| 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 |
■ 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 component. Concurrent use with ephedrine or other xanthines. Active seizure disorder (relative). Uncontrolled cardiac arrhythmias. Severe hepatic impairment.
| 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). |
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| 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. |