Adult Dosing

Organophosphorous poisoning

• Mild symptoms
• Administer 1 dose [2.1 mg/600 mg] (atropine/pralidoxime) IM into the mid-lateral thigh if the patient experiences two or more mild symptoms
• If severe symptoms develop after the first dose, administer 2 additional doses [4.2 mg/1200 mg] (atropine/pralidoxime) in rapid succession and promptly seek definitive medical care

• Severe symptoms
• Administer 3 doses [6.3 mg/1800 mg] (atropine/pralidoxime) IM in rapid succession and seek definitive medical care
• Max: 3 doses [6.3 mg/1800 mg] (atropine/pralidoxime)

Note:

• Only for initial symptomatic treatment of organophosphorous poisoning; initiate definitive medical care promptly
• Monitor severely poisoned patients for at least 48-72 hrs
• To be injected into the mid-lateral thigh; can be injected through clothing
• Do not remove gray safety release until ready to use; never touch the green tip (needle end)

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Treatment of poisoning by organophosphorous nerve agents and organophosphorous insecticides

• No absolute contraindications exist in the presence of life-threatening poisoning by organophosphorous insecticides or nerve agents

• N/A

Renal Dose Adjustment

• Renal impairment: Use with caution; dose adjustments not defined. Dose reduction should be considered for patients with renal impairment

Hepatic Dose Adjustment

• Hepatic impairment: Dose adjustments not defined

• Atropine/pralidoxime should only be administered by emergency medical services personnel well experienced in the recognition and treatment of nerve agent or insecticide poisoning
• Advise patients not to rely solely upon atropine/pralidoxime for complete protection against nerve agent and insecticide poisoning. Use of specially designed protective garments and masks is recommended as primary protective measures against organophosphorous poisoning
• Promptly undertake evacuation and decontamination procedures. Medical personnel assisting victims of poisoning should avoid exposure to the victim's clothing in order to prevent self contamination
• Atropine-induced tachycardia may lead to ischemia, onset or extension of myocardial infarcts, and stimulate ventricular ectopy and fibrillation, especially in patients with a recent MI or severe CAD. Use with caution in such patients
• In rare cases, atropine may also cause ventricular ectopy and ventricular tachycardia in patients without cardiac disease
• Atropine has been known to cause precipitation of acute glaucoma in susceptible individuals, progression of partial pyloric stenosis into complete pyloric obstruction, urinary retention in individuals with prostatic hypertrophy, and inspiration of bronchial secretions leading to dangerous viscid plug formation in patients with chronic lung disease. Use with caution in such patients
• Maximum dosage of atropine/pralidoxime should not exceed >3 doses in the absence of definitive medical care (e.g., hospitalization, respiratory support)
• Use of artificial respiration is recommended along with atropine/pralidoxime therapy
• Atropine may inhibit sweating, which may lead to hyperthermia and heat injury in warm environment or during exercise
• Elderly and children may be more prone to the effects of atropine
• Pralidoxime may cause decrease in renal function, leading to increased drug levels in blood
• Elevations in systolic and diastolic blood pressures have been reported following administration of atropine/pralidoxime
• In cases of known or suspected organophosphorous poisoning, initiate treatment without diagnostic confirmation. Measurement of red blood cell and plasma cholinesterase, and urinary paranitrophenol levels may be useful in diagnosis of poisoning. Red blood cell cholinesterase concentration <50% of normal usually indicates organophosphorous poisoning

Cautions: Use cautiously in

• Hypersensitivity to any of the ingredients of the product
• Heart disease
• Arrhythmias
• Severe narrow angle glaucoma
• Pyloric stenosis
• Prostatic hypertrophy
• Severe renal insufficiency
• Chronic pulmonary disease

Pregnancy Category:C

Breastfeeding: Literature is not available on use of atropine during breastfeeding. Prolonged use of atropine may reduce milk production/milk letdown, but a single systemic or ophthalmic dose is unlikely to interfere with breastfeeding. During prolonged use, monitor for signs of decreased lactation such as insatiety, poor weight gain. This information is available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 06 July 2011). It is unknown if pralidoxime is excreted in breast milk. Manufacturer advises caution.

• CV: Tachycardia, palpitations, flushing, circulatory collapse, decrease in blood pressure, increased systolic and diastolic blood pressure, sinus tachycardia, premature ventricular contractions, atrial flutter, atrial fibrillation, ventricular flutter, ventricular fibrillation, cardiac syncope, asystole, MI
• CNS: Confusion, headache, dizziness, drowsiness, restlessness, fatigue, delirium, medullary paralysis, coma
• NEURO: Tremor, locomotor difficulties, medullary paralysis, ataxia
• PSYCHIATRIC: Hallucinations, depression, excitement, manic behavior
• GI: Dry mouth, constipation, abdominal pain, abdominal distention, nausea, vomiting, dysphagia, paralytic ileus
• GU: Urinary hesitancy/retention, decreased renal function
• DERM: Anhidrosis, maculopapular rash, petechial rash, scarletiniform rash, dry skin
• EENT: Blurred vision, dry eyes, photophobia, acute angle-closure glaucoma, diplopia, impaired visual accommodation
• RESP: Respiratory failure, hyperventilation
• REPRODUCTIVE: Loss of libido, impotence
• LABTEST: Elevated SGOT and SGPT, elevated creatine kinase
• MUSC: Muscular weakness
• LOCAL: Pain at injection site, muscle tightness at injection site
• HYPERSENSITIVITY: Hypersensitivity reactions (skin rashes, exfoliation), anaphylactic reaction, laryngospasm
• MISC: Heat intolerance, impaired body temperature regulation, death

Atropine

• Anticholinergic agent; selectively blocks the action of acetylcholine, including excess acetylcholine due to organophosphorous poisoning at muscarinic cholinergic receptors
• Rapidly and well absorbed after IM injection
• Metabolized in the liver via enzymatic hydrolysis
• Excreted in urine (30-50% unchanged)
• Half-life: 2.4 +/- 0.3 hrs (20 minutes shorter in females than males)

Pralidoxime

• Cholinesterase reactivator; reactivates acetylcholinesterase that has been inactivated by phosphorylation due to an organophosphate compound. Also, slows the process of aging of phosphorylated cholinesterase to a non-reactivatable form and detoxifies some organophosphates by direct chemical reaction
• Rapidly absorbed after IM injection
• Metabolized by liver
• Excreted in urine as unchanged drug and metabolite
• Half-life: 2 +/- 1 hr

US Trade Name(s)

• DuoDote

US Availability

DuoDote (atropine/pralidoxime)

• INJ (prefilled auto-injector): [2.1 mg/0.7 mL]/[600 mg/2 mL]

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Emergency/Critical Care

Antidotes; Combination