Each prefilled auto-injector provides a dose of the antidote atropine in a self-contained unit, specially designed for self or caregiver administration. Three strengths of AtroPen® are available; they are AtroPen® 0.5 mg, AtroPen® 1 mg, and AtroPen® 2 mg. When activated the AtroPen® 0.5 mg dispenses 0.42 mg atropine base (equivalent to 0.5 mg atropine sulfate), the AtroPen® 1 mg dispenses 0.84 mg atropine base (equivalent to 1 mg atropine sulfate), and the AtroPen® 2 mg dispenses 1.67 mg atropine base (equivalent to 2 mg atropine sulfate). Each AtroPen® delivers atropine in 0.7 mL of sterile pyrogen-free solution containing glycerin, phenol, citrate buffer and water for injection. The pH range is 4.0–5.0.

After the AtroPen® Auto-injector has been activated, the empty container should be disposed of properly (see DOSAGE AND ADMINISTRATION). It cannot be refilled, nor can the protruding needle be retracted.

Atropine, an anticholinergic agent (muscarinic antagonist), occurs as white crystals, usually needle-like, or as a white, crystalline powder. It is highly soluble in water with a molecular weight of 289.38. Atropine, a naturally occurring belladonna alkaloid, is a racemic mixture of equal parts of d- and l-hyoscyamine, whose activity is due almost entirely to the levo isomer of the drug. Chemically, atropine is designated as 1 H,5 H-Tropan-3 –ol (±) -tropate. Its empirical formula is C₁₇H₂₃NO₃ and its structural formula is:

Last updated on RxList: 11/20/2008

The AtroPen® Auto-injector is indicated for the treatment of poisoning by susceptible organophosphorous nerve agents having cholinesterase activity as well as organophosphorous or carbamate insecticides. The AtroPen auto-injector should be used by persons who have had adequate training in the recognition and treatment of nerve agent or insecticide intoxication. Pralidoxime chloride may serve as an important adjunct to atropine therapy.

The AtroPen® is intended as an initial treatment of the muscarinic symptoms of insecticide or nerve agent poisonings (generally breathing difficulties due to increased secretions); definitive medical care should be sought immediately. The AtroPen® Auto-injector should be administered as soon as symptoms of organophosphorous or carbamate poisoning appear (usually tearing, excessive oral secretions, wheezing, muscle fasciculations, etc.) In moderate to severe poisoning, the administration of more than one AtroPen® may be required until atropinization is achieved (flushing, mydriasis, tachycardia, dryness of the mouth and nose). (See DOSAGE AND ADMINISTRATION) In severe poisonings, it may also be desirable to concurrently administer an anticonvulsant if seizure is suspected in the unconscious individual since the classic tonic-clonic jerking may not be apparent due to the effects of the poison. In poisonings due to organophosphorous nerve agents and insecticides it may also be helpful to concurrently administer a cholinesterase reactivator such as pralidoxime chloride.

CAUTION! PRIMARY PROTECTION AGAINST EXPOSURE TO CHEMICAL NERVE AGENT AND INSECTICIDE POISONING IS THE WEARING OF PROTECTIVE GARMENTS INCLUDING MASKS, DESIGNED SPECIFICALLY FOR THIS USE.

INDIVIDUALS SHOULD NOT RELY SOLELY UPON THE AVAILABILITY OF ANTIDOTES SUCH AS ATROPINE AND PRALIDOXIME TO PROVIDE COMPLETE PROTECTION FROM CHEMICAL NERVE AGENT AND INSECTICIDE POISONING.

Immediate evacuation from the contaminated environment is essential. Decontamination of the poisoned individual should occur as soon as possible.

The AtroPen® Auto-injector is indicated for the treatment of poisoning by susceptible organophosphorous nerve agents having cholinesterase activity as well as organophosphorous or carbamate insecticides. The AtroPen® auto-injector should be used by persons who have had adequate training in the recognition and treatment of nerve agent or insecticide intoxication. Pralidoxime chloride may serve as an important adjunct to atropine therapy.

The AtroPen® is intended as an initial treatment of the muscarinic symptoms of insecticide or nerve agent poisonings (generally breathing difficulties due to increased secretions); definitive medical care should be sought immediately. The AtroPen® Auto-injector should be administered as soon as symptoms of organophosphorous or carbamate poisoning appear (usually tearing, excessive oral secretions, wheezing, muscle fasciculations, etc.) In moderate to severe poisoning, the administration of more than one AtroPen® may be required until atropinization is achieved (flushing, mydriasis, tachycardia, dryness of the mouth and nose). In severe poisonings, it may also be desirable to concurrently administer an anticonvulsant if seizure is suspected in the unconscious individual since the classic tonic-clonic jerking may not be apparent due to the effects of the poison. In poisonings due to organophosphorous nerve agents and insecticides it may also be helpful to concurrently administer a cholinesterase reactivator such as pralidoxime chloride.

It is recommended that three (3) AtroPen® auto-injectors be available for use in each person at risk for nerve agent or organophosphate insecticide poisoning; one (1) for mild symptoms plus two (2) more for severe symptoms as described below. No more than three (3) AtroPen® injections should be used unless the patient is under the supervision of a trained medical provider. Different dose strengths of the AtroPen® are available depending on the recipient's age and weight.

• Adults and children weighing over 90 lbs (generally over 10 years of age)..............AtroPen® 2 mg (green)
• Children weighing 40 lbs to 90 lbs (generally 4 to 10 years of age)..............AtroPen® 1 mg (dark red)
• Children weighing 15 lbs to 40 lbs (generally 6 months to 4 years of age)..............AtroPen® 0.5 mg (blue)

NOTE: Children weighing under 15 lbs (generally younger than 6 months old) should ordinarily not be treated with the AtroPen® auto-injector. Atropine doses for these children should be individualized at doses of 0.05 mg/kg.

Treatment of MILD SYMPTOMS

One (1) AtroPen® is recommended if two or more MILD symptoms of nerve agent (nerve gas) or insecticide exposure appear in situations where exposure is known or suspected.

Two (2) additional AtroPen® injections given in rapid succession are recommended 10 minutes after receiving the first AtroPen® injection if the victim develops any of the SEVERE symptoms listed below. If possible, a person other than the victim should administer the second and third AtroPen® injections.

Treatment of SEVERE SYMPTOMS:

If a victim is encountered who is either unconscious or has any of the SEVERE symptoms listed below, immediately administer three (3) AtroPen® injections into the victim's mid-lateral thigh in rapid succession using the appropriate weight-based AtroPen® dose.

MILD SYMPTOMS of nerve agent or insecticide exposure include the following:

-Blurred vision, miosis
-Excessive unexplained teary eyes
-Excessive unexplained runny nose
-Increased salivation such as sudden unexplained excessive drooling
-Chest tightness or difficulty breathing
-Tremors throughout the body or muscular twitching
-Nausea and/or vomiting
-Unexplained wheezing or coughing
-Acute onset of stomach cramps
-Tachycardia or bradycardia

SEVERE SYMPTOMS of exposure to nerve agent or insecticides include the following:

-Strange or confused behavior
-Severe difficulty breathing or severe secretions from your lungs/airway
-Severe muscular twitching and general weakness
-Involuntary urination and defecation (feces)
-Convulsions
-Unconsciousness

All victims should be evacuated immediately from the contaminated environment. Medical help should be sought immediately. Protective masks and clothing should be used when available. Decontamination procedures should be undertaken as soon as possible. If dermal exposure has occurred, clothing should be removed and the hair and skin washed thoroughly with sodium bicarbonate or alcohol as soon as possible.

Emergency care of the severely poisoned individual should include removal of oral and bronchial secretions, maintenance of a patent airway, supplemental oxygen and, if necessary, artificial ventilation. In general, atropine should not be used until cyanosis has been overcome since atropine may produce ventricular fibrillation and possible seizures in the presence of hypoxia.

Pralidoxime (if used) is most effective if administered immediately or soon after the poisoning. Generally, little is accomplished if pralidoxime is given more than 36 hours after termination of exposure unless the poison is known to age slowly or re-exposure is possible, such as in delayed continuing gastrointestinal absorption of ingested poisons. Fatal relapses, thought to be due to delayed absorption, have been reported after initial improvement. Continued administration for several days may be useful in such patients.

Close supervision of all moderately to severely poisoned patients is indicated for at least 48 to 72 hours.

An anticonvulsant such as diazepam may be administered to treat convulsions if suspected in the unconscious individual. The effects of nerve agents and some insecticides can mask the motor signs of a seizure.

IMPORTANT: PHYSICIANS AND/OR OTHER MEDICAL PERSONNEL ASSISTING EVACUATED VICTIMS OF NERVE AGENTS AND INSECTICIDE POISONING SHOULD AVOID EXPOSING THEMSELVES TO CONTAMINATION BY THE VICTIM'S CLOTHING. AGGRESSIVE AND SAFE DECONTAMINATION IS STRONGLY SUGGESTED.

Instructions for administering AtroPen® (please refer to the illustrated Self Aid and Caregiver Directions for Use elsewhere):

Warning: Giving additional AtroPen® injections by mistake in the absence of actual nerve agent or insecticide poisoning may cause an overdose of atropine which could result in temporary incapacitation (inability to walk properly, see clearly or think clearly for several or more hours). Patients with cardiac disease may be at risk for serious adverse events, including death.

The AtroPen® is supplied in three strengths. The AtroPen® 0.5 mg provides Atropine Injection (atropine, 0.42 mg/0.7 ml), AtroPen® 1 mg provides Atropine Injection (atropine, 0.84 mg/0.7 ml), and AtroPen® 2 mg provides Atropine Injection (atropine, 1.67 mg/0.7 ml) in sterile solution for intramuscular injection. The AtroPen® is a self-contained unit designed for self or caregiver administration.

Store at 25° C (77° F); excursions permitted to 15–30° C (59–86° F)

[see USP Controlled Room Temperature]

Keep from freezing. Protect from light.

Manufactured by: MERIDIAN MEDICAL TECHNOLOGIES, INC., 10240 Old Columbia Road, COLUMBIA, MD 21046. FDA Rev date: 9/17/2004

Last updated on RxList: 11/20/2008

Mild to moderate pain may be experienced at the site of injection.

The major and most common side effects of atropine can be attributed to its antimuscarinic action. These include dryness of the mouth, blurred vision, photophobia, confusion, headache, dizziness, tachycardia, palpitations, flushing, urinary hesitance or retention, constipation, abdominal distention, nausea, vomiting, loss of libido and impotency. Anhidrosis may produce heat intolerance and impairment of temperature regulation especially in a hot environment. Larger or toxic doses may produce such central effects as restlessness, tremor, fatigue, locomotor difficulties, delirium, followed by 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 reactions will occasionally occur with atropine: these are usually seen as skin rashes, on occasion progressing to exfoliation. 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.

When atropine and pralidoxime are used together, the signs of atropinization may occur earlier than might be expected than when atropine is used alone. This is especially true if the total dose of atropine has been large and the administration of pralidoxime has been delayed. 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.

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 ECGs, no abnormalities were noted other than sinus tachycardia; 22 children had severe tachycardia of 160-190 bpm. Neurologic abnormalities consisted of irritability, agitation, confusion, lethargy, and ataxia.

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 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 BUN, elevated hemoglobin, elevated erythrocytes, low hemoglobin, hypoglycemia, hyperglycemia, hypokalemia, increase in photic stimulation on 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, opisthotnos, 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 micturation, 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.

Drug Abuse And Dependence

Atropine possesses no known potential for dependence.

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 than when atropine is used alone because pralidoxime may potentiate the effect of atropine.

The following precautions should be kept in mind in the treatment of anticholinesterase poisoning although they do not bear directly on the use of atropine and pralidoxime. Since barbiturates are potentiated by the anticholinesterases, they should be used cautiously in the treatment of convulsions.

Last updated on RxList: 11/20/2008

CAUTION! PRIMARY PROTECTION AGAINST EXPOSURE TO CHEMICAL NERVE AGENTS AND INSECTICIDE POISONING IS THE WEARING OF PROTECTIVE GARMENTS INCLUDING MASKS DESIGNED SPECIFICALLY FOR THIS USE.

INDIVIDUALS SHOULD NOT RELY SOLELY UPON ANTIDOTES SUCH AS ATROPINE AND PRALIDOXIME TO PROVIDE COMPLETE PROTECTION FROM CHEMICAL NERVE AGENTS AND INSECTICIDE POISONING.

Patients who have had previous anaphylactic reactions to atropine who have mild symptoms of organophosphorous or nerve agent poisoning should not be treated without adequate medical supervision.

While AtroPen® can be administered to all individuals with a life-threatening exposure to organophosphorous nerve agents and insecticides, it should be administered with extreme caution to individuals with the following disorders when the symptoms of nerve agent poisoning are less severe: individuals who are hypersensitive to any component of the product, disorders of heart rhythm such as atrial flutter, severe narrow angle glaucoma, pyloric stenosis, prostatic hypertrophy, significant renal insufficiency, or a recent myocardial infarction.

More than one dose of atropine (AtroPen® Auto-injector) may be necessary initially, especially when exposure is massive or symptoms are severe. However, no more than three doses should be administered unless under the supervision of trained medical personnel. High doses of atropine may be required for many hours following high-dose exposure to maintain atropinization. (See DOSAGE AND ADMINISTRATION.)

Children and the elderly may be more susceptible to the pharmacologic effects of atropine.

Severe difficulty in breathing requires artificial respiration in addition to the use of atropine since atropine is not dependable in reversing the weakness or paralysis of the respiratory muscles.

General

The desperate condition of the organophosphorous-poisoned individual will generally mask such minor signs and symptoms of atropine treatment as have been noted in normal subjects.

Atropine should be used with caution in individuals with cardiac disease. Conventional systemic doses may precipitate acute glaucoma in susceptible individuals, convert partial pyloric stenosis into complete pyloric obstruction, precipitate urinary retention in individuals with prostatic hypertrophy, or cause inspissation of bronchial secretions and formation of dangerous viscid plugs in individuals with chronic lung disease.

Laboratory Tests

Treatment of organophosphorous nerve agent and insecticide poisoning should be instituted without waiting for the results of laboratory tests. Red blood cell and plasma cholinesterase, and urinary paranitrophenol measurements (in the case of parathion exposure) may be helpful in confirming the diagnosis and following the course of the illness. A reduction in red blood cell cholinesterase concentration to below 50% of normal has been seen only with organophosphorous ester poisoning.

Information for Patients

Appropriate steps must be taken to insure that users understand the indications for and use of the AtroPen®, including review of symptoms of poisoning and operation of the AtroPen® (see DOSAGE AND ADMINISTRATION).

Carcinogenesis, Mutagenesis, Impairment of Fertility

No reports regarding the potential of atropine for carcinogenesis, mutagenesis, or impairment of fertility have been published in the literature. Since atropine is indicated for short-term emergency use only, no investigations of these aspects have been conducted.

Pregnancy

Teratogenic Effects – Pregnancy Category C: Adequate animal reproduction studies have not been conducted with atropine. It is not known whether atropine can cause fetal harm when administered to a pregnant woman or if these agents can affect reproductive capacity. Atropine should be administered to a pregnant woman only if clearly needed.

Nursing Mothers

Atropine is found in human milk in trace amounts. Caution should be exercised when atropine is administered to a nursing woman.

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. The starting dose is 0.05 mg/kg IM every 5 to 20 minutes as needed to provide complete atropinization. (see ADVERSE REACTIONS and DOSAGE AND ADMINISTRATION sections)

Geriatric Use

In general, dose selection for an elderly individual should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Last updated on RxList: 11/20/2008

Symptoms

Serious overdosage with atropine is characterized by widespread paralysis of parasympathetically innervated organs. Dry mucous membranes, widely dilated and nonresponsive pupils, tachycardia, fever and cutaneous flush are especially prominent, as are mental and neurological symptoms. Disorientation, mania, hallucinations, gait disturbances and symptoms may last 48 hours or longer. In instances of severe intoxication, respiratory depression, coma, circulatory collapse and death may occur.

The fatal dose of atropine is not known. In the treatment of organophosphorous poisoning, cumulative doses of approximately 2300-3300 mg or more have been administered over several days to 4-5 weeks. In children, medical literature published prior to 1951 reports four deaths, all in patients 10 months to 3 years of age, and all associated with atropine eye drops or ointment. Total estimated ophthalmic doses were 1.6, 2, 4, and 18 mg given as a single dose (2 mg) or over 1-2 days. Review of current published literature since 1950 identified no pediatric deaths associated with atropine. The few deaths in adults were generally seen using typical clinical doses of atropine often in the setting of bradycardia associated with an acute myocardial infarction.

With a dose as low as 0.5 mg, undesirable symptoms or responses of overdosage may occur. These increase in severity and extent with larger doses of the drug (excitement, hallucinations, delirium and coma). Extreme hyperthermia in a newborn has been reported with as little as 0.065 mg orally. However, in the presence of organophosphorous poisoning, much higher doses of atropine appear to be tolerated and required for optimal therapy.

Treatment

Supportive treatment should be administered as indicated. If respiration is depressed, artificial respiration with oxygen is necessary. Ice bags, alcohol sponges or a hypothermia blanket may be required to reduce fever, especially in children. Catheterization may be necessary if urinary retention occurs. Since atropine elimination takes place through the kidney, output must be maintained and increased if possible, however, dialysis has not been shown to be helpful in overdose situations. Intravenous fluids may be indicated. Because of the affected person's photophobia, the room should be darkened.

In the event of toxic overdosage, a short-acting barbiturate or diazepam may be given as needed to control marked excitement and convulsions. Large doses for sedation should be avoided because central depressant action may coincide with the depression occurring late in atropine poisoning. Central stimulants are not recommended. Physostigmine, given as an atropine antidote by slow intravenous injection of 1 to 4 mg (0.5 to 1.0 mg in children), rapidly abolishes delirium and coma caused by large doses of atropine in most situations. Since physostigmine has a short duration of action, the patient may again lapse into coma after one or two hours and repeated doses are likely to be required. Neostigmine, pilocarpine and methacholine are of little real benefit, since they do not penetrate the blood-brain barrier.

In the face of life-threatening poisoning by organophosphorous nerve agents and insecticides, there are no absolute contraindications for the use of atropine (see WARNINGS).

Last updated on RxList: 11/20/2008

Mechanism of Action

Atropine is commonly classified as an anticholinergic or antiparasympathetic (parasympatholytic) drug. More precisely, however, it is termed an antimuscarinic agent since it antagonizes the muscarine-like actions of acetylcholine and other choline esters.

Atropine inhibits the muscarinic actions of acetylcholine on structures innervated by postganglionic cholinergic nerves, and on smooth muscles, which respond to endogenous acetylcholine but are not so innervated. As with other antimuscarinic agents, the major action of atropine is a competitive or surmountable antagonism, which can be overcome by increasing the concentration of acetylcholine at receptor sites of the effector organ (e.g., by using anticholinesterase agents, which inhibit the enzymatic destruction of acetylcholine). The receptors antagonized by atropine are the peripheral structures that are stimulated or inhibited by muscarine, (i.e., exocrine glands and smooth and cardiac muscle). Responses to postganglionic cholinergic nerve stimulation may also be inhibited by atropine, but this occurs less readily than with responses to injected (exogenous) choline esters.

Pharmacodynamics

Atropine reduces secretions in the mouth and respiratory passages, relieves the constriction and spasm of the respiratory passages, and may reduce the paralysis of respiration, which results from actions of the toxic agent on the central nervous system. Atropine-induced parasympathetic inhibition may be preceded by a transient phase of stimulation, especially on the heart where small doses first slow the rate before characteristic tachycardia develops due to paralysis of vagal control. Although mild vagal excitation occurs, the increased respiratory rate and occasionally increased depth of respiration produced by atropine are more probably the result of bronchiolar dilatation. Accordingly, atropine is an unreliable respiratory stimulant and large or repeated doses may depress respiration.

Adequate doses of atropine abolish various types of reflex vagal cardiac slowing or asystole. The drug also prevents or abolishes bradycardia or asystole produced by injection of choline esters, anticholinesterase agents or other parasympathomimetic drugs, and cardiac arrest produced by stimulation of the vagus. Atropine may also lessen the degree of partial heart block when vagal activity is an etiologic factor. In some individuals with complete heart block, the idioventricular rate may be accelerated by atropine; in others, the rate is stabilized. Occasionally, a large dose may cause atrioventricular (A-V) block and nodal rhythm.

Atropine in clinical doses counteracts the peripheral dilatation and abrupt decrease in blood pressure produced by choline esters. However, when given by itself, atropine does not exert a striking or uniform effect on blood vessels or blood pressure. Systemic doses slightly raise systolic and lower diastolic pressures and can produce significant postural hypotension. Such doses also slightly increase cardiac output and decrease central venous pressure. Occasionally, therapeutic doses dilate cutaneous blood vessels, particularly in the "blush" area (atropine flush), and may cause atropine "fever" due to suppression of sweat gland activity especially in infants and small children.

Pharmacokinetics

Atropine is rapidly and well absorbed after intramuscular administration. Atropine disappears rapidly from the blood and is distributed throughout the various body tissues and fluids. Much of the drug is destroyed by enzymatic hydrolysis, particularly in the liver; from 13 to 50% is excreted unchanged in the urine. Traces are found in various secretions, including milk. Atropine readily crosses the placental barrier and enters the fetal circulation.

The approximate Cmax of atropine following 1.67 mg atropine given intramuscularly to adults by the 2 mg AtroPen® delivery system was 9.6 ± 1.5 (mean ± SEM) ng/ml. The mean T max was 3 minutes. The T½ of intravenous atropine in pediatric subjects under 2 years is 6.9 ± 3.3 (mean ± SD) hours; in children over 2 years, the T½ is 2.5 ± 1.2 (mean ± SD) hours; in adults 16–58 years the T½ is 3.0 ± 0.9 (mean ± SD) hours; in geriatric patients 65–75 years it is 10.0 ± 7.3 (mean ± SD) hours. The protein binding of atropine is 14 to 22% in plasma. There are gender differences in the pharmacokinetics of atropine. The AUC(0-inf) and Cmax were 15% higher in females than males. The half-life of atropine is slightly shorter (approximately 20 minutes) in females than males.

Last updated on RxList: 11/20/2008

Self-Aid and Caregiver Aid Directions for Use.

FOLLOW THESE INSTRUCTIONS ONLY WHEN READY TO ADMINISTER ATROPINE

Step 1	USE THE CORRECT DOSE	Adults and children weighing over 90 lbs (generally over 10 years of age) 2 mg AtroPen® (GREEN LABEL)
		Children weighing 40 lbs to 90 lbs (generally 4 to 10 years of age) 1 mg AtroPen® (DARK RED LABEL)
		Children weighing 15 lbs to 40 lbs (generally 6 months to 4 years of age) 0.5 mg AtroPen® (BLUE LABEL)
		NOTE: Children weighing under 15 lbs (generally younger than 6 months old) should ordinarily not be treated with the AtroPen® auto-injector. Atropine doses in this age group should be individualized at doses of 0.05 mg/kg.
Step 2	KNOW NERVE AGENT AND INSECTICIDE POISONING SYMPTOMS	In an environment where nerve agent (or nerve gas) or insecticide exposure is known or suspected, the following are mild and severe symptoms of nerve agent intoxication. You may not have all of these symptoms:
		MILD symptoms  Blurred vision and sore eyes  Teary eyes  Runny nose  Increased salivation such as sudden drooling  Chest tightness or difficulty breathing  Tremors throughout the body or muscular twitching  Nausea and vomiting  Involuntary secretions (phlegm from your lungs/airway)	SEVERE symptoms  Strange or confused behavior  Severe difficulty breathing or severe secretions from your lungs/airway  Severe muscular twitching and general weakness  Involuntary urination and defecation (feces)  Convulsions  Unconsciousness
Step 3	TREATMENT OF MILD SYMPTOMS	FIRST DOSE: Give one (1) AtroPen® if you experience two or more MILD symptoms of nerve gas or insecticide exposure. Look for a helper and have them check you for continued or worsening symptoms. Get medical attention immediately. ADDITIONAL DOSES: Two (2) additional AtroPen® injections given in rapid succession are recommended 10 minutes after receiving the first AtroPen® injection if the victim develops any of the SEVERE symptoms listed above. If possible, a person other than the victim should administer the second and third AtroPen® injections.
	TREATMENT OF SEVERE SYMPTOMS	If a victim is encountered who is either unconscious or has any of the SEVERE symptoms listed above, immediately administer three (3) AtroPen® injections into the victim's mid-lateral thigh in rapid succession using the appropriate weight-based AtroPen® dose. WARNING: Giving additional AtroPen0 injections by mistake in the absence of nerve agent or insecticide poisoning may cause an overdose of atropine which might result in temporary incapacitation (inability to see clearly or walk properly for several or more hours). Patients with cardiac disease may be at risk for serious adverse events, including death.

Step 4	DIRECTIONS FOR THE USE OF THE ATROPEN® #00001
		(A) Snap the grooved end of the plastic sleeve down and over the yellow safety cap. Remove the AtroPen® from the plastic sleeve. Caution: Do not place fingers on green tip.
		(B) Firmly grasp the AtroPen® with the green tip pointed down.
		(C) Pull off the yellow safety cap with your other hand.
		(D) Aim and firmly jab the green tip straight down (a 90° angle) against the outer thigh. The AtroPen® device will activate and deliver the medicine when you do this. It is okay to inject through clothing but make sure pockets at the injection site are empty. Very thin people and small children should also be injected in the thigh, but before giving the AtroPen®, bunch up the thigh to provide a thicker area for injection.
		(E) Hold the auto-injector firmly in place for at least 10 seconds to allow the injection to finish.
		(F) Remove the AtroPen® and massage the injection site for several seconds. If the needle is not visible, check to be sure the yellow safety cap has been removed, and repeat steps C and E, but press harder.
		(G) After use, using a hard surface, bend the needle back against the AtroPen® and either pin the used AtroPen® to the victim's clothing or show the used AtroPen® auto-injectors to the first medical person you see. This will allow medical personnel to see the number and dose of AtroPen® autoinjectors administered. Move yourself and the exposed individual away from the contaminated area right away. Try to find medical help.

Last updated on RxList: 11/20/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

ATROPINE AUTO-INJECTOR - INJECTION

(AT-trow-peen)

COMMON BRAND NAME(S): Atropen

USES: This medication is used to treat nerve agent poisoning by certain chemicals known as anticholinesterase agents (e.g., carbamate/organophosphate insecticides such as parathion, "nerve gas" such as sarin, other nerve agents such as VX). Pralidoxime is used with atropine for certain organophosphate poisonings but not carbamate poisonings. Atropine works by blocking the activity of a certain natural substance (acetylcholine) that is increased in poisoning. Symptoms of nerve agent/insecticide poisoning may include trouble breathing, headache, runny nose, drooling, vision changes, sweating, abdominal cramps, nausea, vomiting, diarrhea, muscle twitching/jerking, drowsiness, confusion, and seizures.

Atropine treats symptoms of poisoning such as wheezing, increased sweating/saliva, abdominal cramps, vomiting, and diarrhea. Another drug (pralidoxime) works mostly on the muscles (including breathing muscles) to decrease twitching, cramping, weakness, and paralysis in organophosphate poisoning.

HOW TO USE: Talk with your doctor about when you should use this product. Know the symptoms of nerve agent poisoning. (See also Uses section.)

Learn how to properly inject this medication in advance so you will be prepared when you actually need to use it. Also teach another person what to do in case you cannot inject the medication yourself. When treating another person, use their auto-injector if possible. Try to avoid using your own injectors on someone else so that you have an antidote available if needed for self-aid.

This medication is given by injection into the muscle of the outer thigh, through clothing if necessary, as soon as possible after exposure. Hold the injector firmly in place for 10 seconds. Massage the area of injection.

To prevent further exposure to poison, leave the contaminated area. The victim (and any others who treat or have contact with the victim) must immediately put on protective equipment (e.g., breathing mask, protective clothing) and perform rapid decontamination procedures (e.g., removing contaminated clothing, washing skin and hair with sodium bicarbonate or alcohol).

Give atropine as soon as you notice symptoms of poisoning (e.g., severely watering eyes, drooling, difficulty breathing, muscle spasms). If needed, another drug (pralidoxime) may be injected after the atropine. For mild symptoms (watering eyes, increased saliva, wheezing, mild muscle twitching), use 1 injection. If severe symptoms of poisoning are still present 10 minutes after the first injection, give 2 more doses of atropine in a row into the muscle of the outer thigh or buttock. You should give only the first dose to yourself. Try to find someone else to give you any further injections. If the victim is unconscious or symptoms are severe (e.g., strange/confused behavior, severe difficulty breathing, seizures, loss of bladder or bowel control), and no atropine has been given, give 3 injections in a row into the muscle of the outer thigh or buttock.

After using this medication, seek immediate medical attention for follow-up treatment. Do not give more than 3 injections unless directed by a doctor.

Dosage of atropine is based on your age, weight, medical condition, and poisoning symptoms. Check the dose of your auto-injector to make sure it is the right dose for you. Auto-injectors are color-coded for dose.

From time to time, check this product visually for particles or discoloration. If either is present, do not use the liquid. Obtain a new injector.

SIDE EFFECTS: Dizziness, drowsiness, or pain at the injection site may occur. Normal effects from atropine include flushing, fever, large pupils, fast heartbeat, and dryness of the mouth and nose. If any of these effects persist or worsen, tell your doctor, pharmacist, or other medical professional promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the life-saving benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

If atropine is given without exposure to poison, serious side effects may occur. These effects are very similar to the effects of poisoning. Seek immediate medical attention if any of the following symptoms occur: chest pain, confusion/hallucinations, inability to walk, severe vision problems.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, worsening dizziness, worsening trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Severe nerve agent poisoning is life-threatening and requires quick treatment. Treatment of severe poisoning should not be delayed. Discuss your medical history with your doctor before treatment is needed. Be sure you understand when to self-treat, what dose to use, and how many doses to give.

Before using atropine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

Before you need to use this medication, tell your doctor or pharmacist your medical history, especially of: a certain eye condition (narrow-angle glaucoma), blockage in the stomach/intestines (pyloric stenosis), heart problems (e.g., recent heart attack, irregular heartbeat), kidney disease, prostate problems (prostatic hypertrophy).

This drug may make you dizzy or drowsy. Use caution while driving, using machinery, or doing any activity that requires alertness. Avoid alcoholic beverages.

This medication can decrease sweating. To prevent heatstroke, avoid becoming overheated in hot weather, saunas, or during exercise/other strenuous activities.

Caution is advised when using this drug in children because they may be more sensitive to the effects of the drug. Dosage is based on weight in children.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This drug may pass into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Tell your doctor that you have been given this medication. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Do not use the following drugs in patients who have been poisoned with an organophosphate/carbamate nerve agent/insecticide: morphine, aminophylline/theophylline, succinylcholine, reserpine, phenothiazines (e.g., chlorpromazine, prochlorperazine).

Nerve agents may increase the effect of the following medications: barbiturates (e.g., phenobarbital).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, or if this drug is injected accidentally without exposure to a nerve agent, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. In people with overdose and people not exposed to poison, symptoms of overdose may include: restlessness, shakiness (tremor), difficulty walking, confusion, hallucinations.

NOTES: After first-aid treatment and decontamination, additional treatment in a hospital is usually needed. Consult your doctor for more details.

MISSED DOSE: Not applicable.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not freeze. Do not store in the bathroom. Keep all medicines away from children and pets.

From time to time, check the expiration date, and also check this product visually for particles or discoloration. Replace the unit before it expires or if particles/discoloration are present.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this medication when it is expired, used, or no longer needed. Consult your pharmacist or local waste disposal provider for more details about how to safely discard your medication.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.