ATNAA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ATNAA (ATNAA).
Atropine is a competitive antagonist of muscarinic acetylcholine receptors (M1, M2, M3, M4, M5), blocking the effects of parasympathetic nervous system. Pralidoxime is an acetylcholinesterase reactivator; it displaces the phosphoryl group from the inhibited enzyme, allowing restoration of cholinesterase activity.
| Metabolism | Atropine: Hepatic metabolism via CYP2D6 and CYP3A4, with approximately 30-50% excreted unchanged in urine. Pralidoxime: Primarily renal excretion as unchanged drug and metabolites; minimal hepatic metabolism. |
| Excretion | Renal: predominantly as metabolites and unchanged drug; approximately 50-70% of atropine and up to 97% of pralidoxime are excreted renally. Biliary/fecal: minor route for atropine (<5%). |
| Half-life | Atropine: 2-4 hours in adults (prolonged in elderly and children). Pralidoxime: 1.2-2.6 hours (shorter due to rapid renal clearance). Clinical context: half-lives are extended in organophosphate poisoning due to altered distribution. |
| Protein binding | Atropine: 14-22% bound (primarily to albumin). Pralidoxime: negligible (<10% bound, mainly to albumin). |
| Volume of Distribution | Atropine: 1.5-3.5 L/kg (large due to extensive tissue distribution including CNS). Pralidoxime: 0.3-0.8 L/kg (limited distribution, primarily extracellular). |
| Bioavailability | Intramuscular (IM): Atropine ~50-80% (due to incomplete absorption); pralidoxime ~80-100%. Oral: Atropine ~10-50% (fist-pass metabolism); pralidoxime ~20-40% (erratic absorption). |
| Onset of Action | Intravenous (IV): Immediate (within 1-2 minutes). Intramuscular (IM): Within 5-10 minutes. Auto-injector (IM): 5-10 minutes. Onset may be delayed in severe poisoning due to poor perfusion. |
| Duration of Action | Atropine: 2-6 hours (clinical effects may persist longer due to prolonged receptor binding). Pralidoxime: 1-3 hours. Duration is dose-dependent and shorter in severe poisoning. |
Initial dose: 0.4 mg (1 mL) IV/IM/SC, repeated every 2-3 minutes as needed. Subsequent doses: 2 mg (5 mL) IV/IM/SC if opioid-induced respiratory depression recurs.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment. GFR does not significantly alter clearance; use standard dosing. |
| Liver impairment | No specific Child-Pugh based adjustments. However, in severe hepatic impairment, monitor for prolonged effect; dose reductions not routinely recommended. |
| Pediatric use | Weight-based: 0.01-0.02 mg/kg IV/IM/SC per dose, repeated every 2-3 minutes as needed. Maximum initial dose: 2 mg. For neonatal abstinence: 0.01-0.02 mg/kg IV every 3-5 minutes. |
| Geriatric use | No specific dose adjustment. Elderly may have increased sensitivity; use lowest effective dose and monitor for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ATNAA (ATNAA).
| Breastfeeding | Atropine is excreted into human milk with a relative infant dose <10% of maternal weight-adjusted dose; specific M/P ratio not established. Pralidoxime excretion unknown. Risk of anticholinergic effects (dry mouth, constipation, tachycardia) in nursing infant. Benefit of treatment for maternal organophosphate poisoning outweighs potential infant risk. Discontinue breastfeeding temporarily during administration and pump and discard milk for 24 hours post-dose. |
| Teratogenic Risk | ATNAA (atropine and pralidoxime chloride) is pregnancy category C. First trimester: Limited human data; animal studies not available. Potential for dose-dependent fetal tachycardia and reduced uteroplacental blood flow due to atropine's anticholinergic effects. Second and third trimesters: Atropine crosses placenta; may cause fetal tachycardia and possible decreased amniotic fluid volume. Pralidoxime has low placental transfer; no known teratogenicity in animal studies. Use only for life-threatening organophosphate poisoning. |
■ FDA Black Box Warning
None. However, use with caution in patients with asthma, glaucoma, and cardiovascular disease. Not recommended for routine use in organophosphate poisoning without atropine.
| Serious Effects |
Hypersensitivity to any component. Atropine is contraindicated in narrow-angle glaucoma, obstructive uropathy, and myasthenia gravis (unless treating cholinergic crisis). Pralidoxime is contraindicated in severe renal impairment (unless life-threatening emergency).
| Precautions | May cause tachycardia, hypertension, and ventricular arrhythmias; use with caution in coronary artery disease. Atropine may exacerbate angle-closure glaucoma and produce blurred vision. Pralidoxime may cause muscle weakness and respiratory depression. Monitor cardiac function. |
| Food/Dietary | No known food interactions. |
Loading safety data…
| Fetal Monitoring | Continuous maternal ECG and heart rate monitoring; fetal heart rate monitoring if viable gestational age; uterine activity monitoring for preterm labor; maternal oxygen saturation; serial maternal serum acetylcholinesterase and RBC cholinesterase levels; signs of organophosphate toxicity recurrence. |
| Fertility Effects | No human studies on fertility. Animal studies not available. Atropine may affect menstrual cycle regulation via anticholinergic effects on hypothalamic-pituitary-ovarian axis. Pralidoxime has no known effect on fertility. Recovery of organophosphate-induced ovarian toxicity may be required for fertility restoration. |
| Clinical Pearls | ATNAA (atropine and pralidoxime chloride) auto-injector is used for nerve agent or organophosphate poisoning. Administer immediately after suspected exposure. Can repeat dosing if symptoms persist. Monitor for atropine toxicity (tachycardia, hyperthermia, delirium). Pralidoxime is most effective if given within 24 hours. |
| Patient Advice | Inject into outer thigh through clothing if necessary. · After injection, seek emergency medical help immediately. · May cause blurred vision, dry mouth, and confusion. · Do not use for asthma or allergic reactions. · Keep auto-injector accessible and check expiration date. |