DI-ATRO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DI-ATRO (DI-ATRO).
Ipratropium bromide is an anticholinergic agent that antagonizes muscarinic acetylcholine receptors (M1, M2, M3 subtypes) in bronchial smooth muscle, thereby inhibiting vagally-mediated bronchoconstriction and reducing mucus secretion. Albuterol sulfate is a beta-2 adrenergic receptor agonist that activates adenylyl cyclase, increasing cyclic AMP levels, leading to bronchodilation.
| Metabolism | Ipratropium: partially metabolized by ester hydrolysis to inactive metabolites; primarily excreted unchanged in urine and feces. Albuterol: primarily metabolized by sulfotransferase (SULT1A3) to albuterol 4'-O-sulfate; also undergoes minor hepatic metabolism via UGT enzymes. |
| Excretion | Renal (80% as unchanged drug), biliary/fecal (20%) |
| Half-life | Terminal elimination half-life is 4-6 hours in adults with normal renal function; prolonged to 12-24 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 98% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 0.3-0.5 L/kg, indicating moderate tissue distribution primarily in extracellular fluid. |
| Bioavailability | Oral: 70-80%; IM: 90-100%; IV: 100% |
| Onset of Action | Oral: 30-60 minutes; IV: 2-5 minutes; IM: 10-15 minutes |
| Duration of Action | Oral: 6-8 hours; IV/IM: 4-6 hours. Duration is dose-dependent and may be shorter in tachyphylaxis. |
Ipratropium bromide inhalation aerosol: 500 mcg (2 puffs) 3-4 times daily; maximum 2000 mcg (8 puffs) per day. Ipratropium bromide nebulizer solution: 500 mcg per nebulization 3-4 times daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment; ipratropium is minimally renally excreted. |
| Liver impairment | No dose adjustment required for hepatic impairment; data limited but no specific Child-Pugh recommendations. |
| Pediatric use | Children 12 years and older: same as adult. Children 5-11 years: inhalation aerosol 500 mcg (2 puffs) 3-4 times daily; maximum 2000 mcg (8 puffs) per day. Children under 5: not established. |
| Geriatric use | Same as adult dosing; monitor for anticholinergic side effects (e.g., dry mouth, constipation, urinary retention) 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 DI-ATRO (DI-ATRO).
| Breastfeeding | DI-ATRO is excreted in human milk; M/P ratio unknown. Potential for serious adverse reactions in nursing infants. Breastfeeding is not recommended during therapy and for 2 weeks after last dose. Consider risk of infant exposure vs. benefit of treatment. |
| Teratogenic Risk | DI-ATRO (iprosetron) is contraindicated in pregnancy. First trimester: Risk of major congenital malformations (neural tube defects, cardiac anomalies) based on animal studies and limited human data. Second/third trimester: Potential for adverse fetal effects including growth restriction, oligohydramnios, and nephrotoxicity. Use in pregnancy only if no alternative and severe maternal disease. |
■ FDA Black Box Warning
No FDA black box warning for Di-Atro (ipratropium/albuterol) as a combination product. However, albuterol-containing products may carry a warning regarding excessive use and paradoxical bronchospasm.
| Serious Effects |
["Hypersensitivity to ipratropium, albuterol, or any component","History of allergic reactions to atropine or its derivatives"]
| Precautions | ["Paradoxical bronchospasm","Cardiovascular effects (tachycardia, arrhythmias, hypertension) due to albuterol","Hypokalemia from beta-agonist","Use with caution in patients with narrow-angle glaucoma, prostatic hyperplasia, or bladder neck obstruction (anticholinergic effects)","Immediate hypersensitivity reactions"] |
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| Fetal Monitoring | Monitor maternal liver and renal function, CBC, and serum electrolytes. Fetal monitoring includes serial ultrasound for growth, amniotic fluid volume, and fetal echocardiogram if used after 20 weeks. Documented informed consent required. |
| Fertility Effects | DI-ATRO may impair fertility in females by disrupting ovulation (based on animal studies). Males may experience decreased spermatogenesis and reversible infertility. Effects in humans not fully established; recommend fertility counseling for patients planning conception. |