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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DUODOTE (DUODOTE).
| Breastfeeding | Atropine is excreted into breast milk in small amounts; the M/P ratio is approximately 0.5–1.0. Pralidoxime is likely excreted into breast milk, but data are unavailable. Due to potential anticholinergic effects in the infant (e.g., tachycardia, decreased gastric motility, urinary retention), caution is advised. The American Academy of Pediatrics considers atropine compatible with breastfeeding; however, pralidoxime's compatibility is unknown. The decision to breastfeed during Duodote therapy should consider the mother's clinical need and the infant's risk. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to atropine or pralidoxime","Hypersensitivity to sulfites (pralidoxime contains sulfites)"]
| 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"] |
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| 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. |