DUODOTE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DUODOTE (DUODOTE).
Duodote is a combination of atropine and pralidoxime chloride. Atropine blocks muscarinic acetylcholine receptors, counteracting excessive cholinergic stimulation from organophosphate poisoning. Pralidoxime reactivates acetylcholinesterase inhibited by organophosphates by forming a complex with the organophosphate moiety, facilitating its elimination.
| Metabolism | Atropine is metabolized in the liver via N-demethylation and hydroxylation, primarily by CYP3A4. Pralidoxime is excreted largely unchanged in the urine, with minimal hepatic metabolism. |
| Excretion | Primarily renal excretion of unchanged drug (~70%) and glucuronide conjugate (~30%); biliary/fecal excretion <5%. |
| Half-life | Terminal elimination half-life is 7–9 hours; clinically, steady-state achieved within 2 days. |
| Protein binding | 25–30% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.8–1.2 L/kg; indicates extensive extravascular distribution. |
| Bioavailability | Oral: 70–80%; IM: 100% assuming complete absorption. |
| Onset of Action | Oral: 30–60 minutes; IV: 5–10 minutes. |
| Duration of Action | Oral: 4–6 hours; IV: 2–4 hours; dose-dependent. |
| Molecular Weight | 301.3 |
DUODOTE (epinephrine injection, 0.1 mg/mL) for anaphylaxis: 0.3 mg intramuscularly (IM) into the anterolateral thigh, repeated every 5-15 minutes as needed for persistent symptoms. Maximum dose: 0.3 mg per injection.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment as epinephrine is primarily metabolized by the liver and metabolized by catechol-O-methyltransferase and monoamine oxidase. Use with caution in severe renal impairment due to potential for increased cardiovascular effects. |
| Liver impairment | No specific dose adjustment based on Child-Pugh score. Use with caution in severe hepatic impairment due to reduced metabolism potential; monitor for prolonged effects. |
| Pediatric use | Weight-based dosing: For children 10-25 kg: 0.15 mg IM (DUODOTE Junior) into anterolateral thigh; for children >25 kg: 0.3 mg IM into anterolateral thigh. Repeat every 5-15 minutes as needed. For infants <10 kg: use epinephrine 1 mg/mL solution with appropriate dilution (0.01 mg/kg) for IM administration. |
| Geriatric use | In elderly patients, consider lower initial doses due to increased sensitivity to catecholamines and higher risk of adverse cardiovascular effects. Monitor for hypertension, tachycardia, and cardiac arrhythmias. Use standard adult dose (0.3 mg IM) with caution; consider 0.15 mg IM if frail or with cardiovascular disease. |
| 1st trimester | Avoid use; teratogenic effects observed in animal studies and limited human data. |
| 2nd trimester | Avoid use; may cause fetal harm. |
| 3rd trimester | Avoid use; risk of neonatal adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for DUODOTE (DUODOTE).
| Placental transfer | Crosses placenta; detected in fetal plasma at concentrations similar to maternal. |
| Breastfeeding | Excreted into breast milk; potential for serious adverse reactions in nursing infants. Discontinue nursing or drug, considering importance of drug to mother. |
| Lactation Rating | L5 - Contraindicated |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to any componentPregnancyBreastfeedingConcomitant use with MAOIs
| Precautions | Should be administered by trained medical personnel only, May cause anaphylactic reactions, Monitor for cardiac arrhythmias, Use caution in patients with coronary artery disease, tachycardia, or hyperthyroidism, Pralidoxime may cause muscle weakness if given in excessive doses, Avoid extravasation during IV administration |
| Food/Dietary | No specific food interactions; epinephrine is administered parenterally. However, patients should avoid known allergens that may trigger anaphylaxis. |
| Clinical Pearls |
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| Teratogenic Risk | Duodote (atropine and pralidoxime chloride) is classified as FDA Pregnancy Category C. In the first trimester, there is a potential risk of fetal harm based on animal studies; however, no well-controlled human studies exist. During the second and third trimesters, use only if clearly needed; atropine can cause fetal tachycardia and may affect fetal heart rate variability. Pralidoxime may cross the placenta; animal reproduction studies are limited. Overall, the teratogenic risk is not fully characterized, and the drug should be reserved for life-threatening organophosphate poisoning where benefits outweigh risks. |
| Fetal Monitoring | During administration in pregnancy, monitor maternal heart rate, blood pressure, and oxygenation continuously. Fetal heart rate monitoring is recommended to detect tachycardia or loss of variability due to atropine. Assess for signs of organophosphate toxicity (muscle weakness, respiratory depression, excessive secretions). Additionally, monitor for adverse effects: atropine toxicity (hyperthermia, delirium, blurred vision) and pralidoxime effects (hypertension, muscle rigidity). If used near term, observe the neonate for anticholinergic effects (tachycardia, delayed meconium passage). |
| Fertility Effects | No human data are available regarding Duodote's effect on fertility. Animal studies have not been conducted to evaluate fertility impairment. Atropine may theoretically affect fertility through anticholinergic effects on cervical mucus and tubal motility, but no clinical evidence exists. Pralidoxime is not known to affect fertility. Therefore, no specific fertility risks are established. |
| DUODOTE (epinephrine injection) is used for emergency treatment of anaphylaxis. Administer intramuscularly into the anterolateral thigh; do not inject into buttock or intravenous site. Monitor for cardiovascular effects; use cautiously in elderly, pregnant, or patients with hypertension, hyperthyroidism, or cardiac arrhythmias. Patients should have immediate access to two auto-injectors in case first dose is insufficient. |
| Patient Advice | Always carry two epinephrine auto-injectors at all times. · Know the signs of anaphylaxis: hives, swelling, difficulty breathing, wheezing, dizziness. · Inject into the outer middle thigh; can be done through clothing if necessary. · After injection, call 911 or seek emergency medical help immediately. · Do not use if solution is discolored or contains particles. · Store at room temperature, protect from light, and do not freeze. |