Atropen Drug Information

is indicated for the treatment of poisoning by susceptible organophosphorus nerve agents having cholinesterase activity as well as organophosphorus or carbamate insecticides in adult and pediatric patients. ATROPEN is a cholinergic muscarinic antagonist indicated for the treatment of poisoning by susceptible organophosphorus nerve agents having cholinesterase activity as well as organophosphorus or carbamate insecticides in adult and pediatric patients.

• The following serious adverse reactions are described elsewhere in the labeling: Cardiovascular Risks Heat Injury Acute Glaucoma Urinary Retention Pyloric Stenosis Exacerbation of Chronic Lung Disease Hypersensitivity The following adverse reactions associated with the use of atropine were identified in the literature. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Mild to moderate pain may be experienced at the site of injection. Common adverse reactions of atropine include dryness of mouth, blurred vision, dry eyes, photophobia, confusion, headache, dizziness, tachycardia, palpitations, flushing, urinary hesitance or retention, constipation, abdominal pain, abdominal distention, nausea, vomiting, loss of libido, and impotency. To report SUSPECTED ADVERSE REACTIONS, contact Meridian Medical Technologies ®, LLC at 1-833-739-0945 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Adverse Reactions at Recommended Doses Common adverse reactions of atropine can be attributed to its antimuscarinic action. These include dryness of the mouth, blurred vision, dry eyes, photophobia, confusion, headache, dizziness, tachycardia, palpitations, flushing, urinary hesitancy or retention, constipation, abdominal pain, abdominal distention, nausea and vomiting, loss of libido, and impotence. Anhidrosis may produce heat intolerance and impairment of temperature regulation in a hot environment. Dysphagia, paralytic ileus, acute angle closure glaucoma, maculopapular rash, petechial rash, and scarlatiniform rash have also been reported. Adverse cardiac reactions, including arrhythmias and myocardial infarction, have been reported with atropine. Larger doses of atropine may produce central nervous system effects such as restlessness, tremor, fatigue, locomotor difficulties, delirium, hallucinations, depression and ultimately, medullary paralysis and death . Large doses can also lead to circulatory collapse. In such cases, blood pressure declines and death due to respiratory failure may ensue following paralysis and coma. Hypersensitivity Hypersensitivity reactions will occasionally occur with atropine; these are usually seen as skin rashes and may progress to exfoliation. Anaphylactic reaction and laryngospasm have also occurred. Pediatric Patients Adverse events seen in pediatrics are similar to those that occur in adult patients although central nervous system complaints are often seen earlier and at lower doses. Additional Adverse Reactions to Atropine by Organ System The following adverse reactions were reported in published literature for atropine in both adults and children: Cardiovascular : Sinus tachycardia, supraventricular tachycardia, junctional tachycardia, ventricular tachycardia, bradycardia, palpitations, ventricular arrhythmia, ventricular flutter, ventricular fibrillation, atrial arrhythmia, atrial fibrillation, atrial ectopic beats, ventricular premature contractions, bigeminal beats, trigeminal beats, nodal extrasystole, ventricular extrasystole, supraventricular extrasystole, asystole, cardiac syncope, prolongation of sinus node recovery time, cardiac dilation, left ventricular failure, myocardial infarction, intermittent nodal rhythm (no P wave), prolonged P wave, shortened PR segment, R on T phenomenon, shortened RT duration, widening and flattening of QRS complex, prolonged QT interval, flattening of T wave, repolarization abnormalities, altered ST-T waves, retrograde conduction, transient atrioventricular (AV) dissociation, increased blood pressure, decreased blood pressure, labile blood pressure, weak or impalpable peripheral pulses. Eye : Mydriasis, blurred vision, pupils poorly reactive to light, photophobia, decreased contrast sensitivity, decreased visual acuity, decreased accommodation, cycloplegia, strabismus, heterophoria, cyclophoria, acute angle closure glaucoma, conjunctivitis, keratoconjunctivitis sicca, blindness, tearing, dry eyes/dry conjunctiva, irritated eyes, crusting of eyelid, blepharitis.
• Gastrointestinal: Nausea, abdominal pain, paralytic ileus, decreased bowel sounds, distended abdomen, vomiting, delayed gastric emptying, decreased food absorption, dysphagia.
• General: Hyperpyrexia, lethargy, somnolence, chest pain, excessive thirst, weakness, syncope, insomnia, tongue chewing, dehydration, feeling hot, injection site reaction.
• Immunologic: Anaphylactic reaction.
• Special Investigations: Leukocytosis, hyponatremia, elevated blood urea nitrogen (BUN), elevated hemoglobin, elevated erythrocytes, low hemoglobin, hypoglycemia, hyperglycemia, hypokalemia, increase in photic stimulation on electroencephalogram (EEG), signs of drowsiness on EEG, runs of alpha waves on EEG, alpha waves (EEG) blocked upon opening eyes.
• Metabolic: Failure to feed.
• Central Nervous System: Ataxia, hallucinations (visual or aural), seizures (generally tonic-clonic), abnormal movements, coma, confusion, stupor, dizziness, amnesia, headache, diminished tendon reflexes, hyperreflexia, muscle twitching, opisthotonos, Babinski's reflex/Chaddock's reflex, hypertonia, dysmetria, muscle clonus, sensation of intoxication, difficulty concentrating, vertigo, dysarthria.
• Psychiatric: Agitation, restlessness, delirium, paranoia, anxiety, mental disorders, mania, withdrawn behavior, behavior changes.
• Genitourinary: Difficulty in micturition, urine urgency, distended urinary bladder, urine retention, bed-wetting.
• Pulmonary: Tachypnea, slow respirations, shallow respirations, breathing difficulty, labored respirations, inspiratory stridor, laryngitis, laryngospasm, pulmonary edema, respiratory failure, subcostal recession.
• Dermatologic: Dry mucous membranes, dry warm skin, flushed skin, oral lesions, dermatitis, petechiae, rash, macular rash, papular rash, maculopapular rash, scarlatiniform rash, erythematous rash, sweating/moist skin, cold skin, cyanosed skin, salivation. Injection Site Muscle tightness and pain may occur at the injection site. Inadvertent Injection In cases where ATROPEN is inadvertently administered to people who are not poisoned with nerve agent or organophosphorus insecticide, the following effects on their ability to function normally may occur. Patients with cardiac disease may be at risk for serious adverse events, including death. Atropine 2 mg IM, when given to healthy male volunteers, is associated with minimal effects on visual, motor, and mental functions, though unsteadiness walking and difficulty concentrating may occur. Atropine reduces body sweating and increases body temperature, particularly with exercise and under hot conditions. Atropine 4 mg IM, when given to healthy male volunteers, is associated with impaired visual acuity, visual near point accommodation, logical reasoning, digital recall, learning, and cognitive reaction time. Ability to read is reduced or lost. Subjects are unsteady and need to concentrate on walking. These effects begin about 15 minutes to one hour or more post-dose. Atropine 6 mg IM, when given to healthy male volunteers, is associated with the effects described above plus additional central nervous system effects including poor coordination, poor attention span, and visual hallucinations (colored flashes) in many subjects. Frank visual hallucinations, auditory hallucinations, disorientation, and ataxia occur in some subjects. Skilled and labor-intense tasks are performed more slowly and less efficiently. Decision making takes longer and is sometimes impaired. It is unclear if the above data, obtained from studies of healthy adult subjects, can be extrapolated to other populations. In the elderly and patients with co-morbid conditions, the effects of ≥2 mg atropine on the ability to see, walk, and think properly are unstudied; effects may be greater in susceptible populations. Patients who are mistakenly injected with ATROPEN should avoid potentially dangerous overheating, avoid vigorous physical activity, and seek medical attention as soon as feasible. Adverse Reactions Observed in Pediatric Patients after Inappropriate Administration of ATROPEN Amitai et el (JAMA 1990) evaluated the safety of ATROPEN 0.5 mg, 1 mg, and 2 mg in a case series of 240 children who received ATROPEN inappropriately (i.e., no nerve agent exposure) during the 1990 Gulf War Period. Overall, severity of atropinization followed a nonlinear correlation with dose. Estimated doses up to 0.045 mg/kg produced no signs of atropinization. Estimated doses between 0.045 mg/kg to 0.175 mg/kg and even greater than 0.175 mg/kg were associated with mild and severe effects, respectively. Actual dosage received by children may have been considerably lower than estimated since incomplete injection in many cases was suspected. Regardless, adverse events reported were generally mild and self-limited. Few children required hospitalization. Adverse reactions reported were dilated pupils (43%), tachycardia (39%), dry membranes (35%), flushed skin (20%), temperature 37.8°C or 100°F (4%), and neurologic abnormalities (5%). There was also local pain and swelling. In 91 children with electrocardiograms (ECGs), no abnormalities were noted other than sinus tachycardia; 22 children had severe tachycardia of 160 bpm to 190 bpm. Neurologic abnormalities consisted of irritability, agitation, confusion, lethargy, and ataxia

Pralidoxime

When atropine and pralidoxime are used together, the signs of atropinization (flushing, mydriasis, tachycardia, dryness of the mouth and nose) may occur earlier than might be expected when atropine is used alone because pralidoxime may potentiate the effect of atropine. Excitement and manic behavior immediately following recovery of consciousness have been reported in several cases. However, similar behavior has occurred in cases of organophosphate poisoning that were not treated with pralidoxime.

Barbiturates Barbiturates are potentiated by the anticholinesterases; therefore, barbiturates should be used

cautiously in the treatment of convulsions resulting from exposure to atropine.

Pregnancy Risk Summary Atropine readily crosses the placental barrier and enters fetal circulation. There are no adequate data on the developmental risk associated with the use of atropine in pregnant women. Adequate animal reproduction studies have not been conducted with atropine.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Pediatric Use A review of published literature supports the safety and effectiveness of atropine in the setting of organophosphate insecticide poisoning in all pediatric age groups. Adverse events seen in pediatric patients treated with atropine are similar to those that occur in adult patients, although central nervous system effects are often seen earlier and at lower doses. Overheating (atropine fever) caused by suppression of sweat gland activity may be more pronounced in infants and small children.

Extreme hyperthermia in a newborn has been reported with as little as 0.065 mg orally.

Symptoms Manifestations of atropine overdose are dose-related and include flushing, dry skin and mucous membranes, tachycardia, widely dilated pupils that are poorly responsive to light, blurred vision, and fever (which can sometimes be dangerously elevated). Locomotor difficulties, disorientation, hallucinations, delirium, confusion, agitation, coma, and central depression can occur and may last 48 hours or longer. In instances of severe atropine intoxication, respiratory depression, coma, circulatory collapse, and death may occur. Treatment For atropine overdose, supportive treatment should be administered.

If respiration is depressed, artificial respiration with oxygen is necessary. Ice bags, a hypothermia blanket, or other methods of cooling may be required to reduce atropine-induced fever, especially in pediatric patients . Catheterization may be necessary if urinary retention occurs. Since atropine elimination takes place through the kidney, urinary output must be maintained and increased if possible: intravenous fluids may be indicated.

Because of atropine-induced photophobia, the room should be darkened. A benzodiazepine may be needed to control marked excitement and convulsions. However, large doses for sedation should be avoided because the central nervous system depressant effect may coincide with the depressant effect occurring late in severe atropine poisoning.

Barbiturates are potentiated by the anticholinesterases; therefore, barbiturates should be used cautiously in the treatment of convulsions. Central nervous system stimulants are not recommended.