0.7 ML atropine sulfate 2.86 MG/ML Auto-Injector

INDICATIONS AND USAGE Atropine sulfate is given parenterally as a preanesthetic medication to decrease salivation and bronchial secretions. It is useful in pylorospasm and other spastic conditions of the gastrointestinal tract. For ureteral and biliary colic, atropine sulfate given with morphine may be indicated. Atropine sulfate is indicated for relaxation of the upper gastrointestinal tract and colon during hypotonic radiography. Atropine is used as an antidote for pilocarpine, physostigmine, isoflurophate, choline esters, certain species of aminata and in poisoning by the organic phosphate cholinesterase inhibitors found in certain insecticides and by chemical warfare “nerve gases”. Large doses relieve the muscarine-like symptoms and some of the central nervous system manifestations.

DOSAGE AND ADMINISTRATION ATNAA is intended as an initial treatment as soon as symptoms appear; definitive medical care should be sought immediately. ( 2.1 ) Dosage for Mild Symptoms: If a service member experiences some or all of the mild symptoms, they should self-administer one injection intramuscularly into the lateral thigh muscle or buttocks. If, at any time after the first dose, the service member develops any of the severe symptoms or if the mild symptoms are not relieved, a buddy should administer two additional injections intramuscularly in rapid succession. ( 2.2 ) Dosage for Severe Symptoms: If a service member has any of the severe symptoms, immediately buddy-administer three injections intramuscularly into the service member's lateral thigh muscle or buttocks in rapid succession. ( 2.2 ) 2.1 Important Administration Information Three (3) ATNAA single-dose autoinjectors should be available for use by each service member at risk for organophosphorus nerve agent poisoning; one (1) for mild symptoms plus two (2) more for severe symptoms [see Dosage and Administration (2.2) ] . Note that individuals may not have all symptoms included under the mild or severe symptom category. For optimal reactivation of organophosphorus-inhibited cholinesterase, the ATNAA should be administered as soon as possible after appearance of symptoms of organophosphorus nerve agent poisoning. ATNAA should be self- or buddy–administered by service members after donning protective mask and hood at the first sign of a chemical attack, and only if some or all of the mild symptoms of organophosphorus nerve agent exposure are present. Only administer ATNAA to service members experiencing symptoms of organophosphorus nerve agent poisoning in a situation where exposure is known or suspected. The ATNAA autoinjector is intended as an initial treatment of the symptoms of organophosphorus nerve agent poisoning as soon as symptoms appear; definitive medical care should be sought immediately. Close supervision of all treated service members is indicated for at least 48 to 72 hours. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit [see Dosage Forms and Strengths (3) ] . 2.2 Dosage Information Dosage for Mild Symptoms First Dose : If you experience some or all of the mild symptoms of nerve agent exposure listed in Table 1, self-administer one (1) ATNAA injection intramuscularly into the lateral thigh muscle or buttocks. Wait 10 to 15 minutes for ATNAA to take effect. If, after 10 to 15 minutes, the symptoms of organophosphorus nerve agent poisoning are not relieved, seek someone else to check your symptoms. Another service member must administer the second and third injections. Additional Doses : If you encounter a service member suffering from severe symptoms of organophosphorus nerve agent poisoning listed in Table 1 and one ATNAA has been self-administered, administer two (2) additional ATNAA injections intramuscularly in rapid succession into the casualty's lateral thigh muscle or buttocks. Dosage for Severe Symptoms Casualties with severe symptoms may experience most or all of the mild symptoms of organophosphorus nerve agent poisoning, plus most or all of the severe symptoms listed in Table 1. If a service member is encountered suffering from severe signs of organophosphorus nerve agent poisoning and ATNAA self-aid has not been administered, immediately administer in rapid succession three (3) ATNAA injections into the casualty's lateral thigh muscle or buttocks. Table 1. Common Symptoms of Organophosphorus Nerve Agent Exposure Mild Symptoms Severe Symptoms Unexplained runny nose Unexplained sudden headache Sudden drooling Difficulty in seeing (dimness of vision and miosis) Tightness of chest or difficulty in breathing Wheezing and coughing Localized sweating and muscular twitching in the area of contaminated skin Stomach cramps Nausea, with or without vomiting Tachycardia followed by bradycardia Strange or confused behavior Increased wheezing and increased difficulty in breathing Severely pinpointed pupils Red eyes with tearing Vomiting Severe muscular twitching and general weakness Involuntary urination and defecation Convulsions Unconsciousness Respiratory failure Bradycardia 2.3 Administration Instructions The following instructions should be given to service members for the administration of ATNAA single-dose injections. Self-Aid Administer one (1) ATNAA into your lateral thigh muscle or buttocks as follows: Remove gray safety cap from back end. Place front end on outer thigh and push hard until injector functions. Hold firmly in place for ten seconds. Using a hard surface, bend needle into hook. Push ejected needle through a pocket flap (or other thick and conspicuous part of outer clothing). Wait 10 to 15 minutes for the antidote to take effect. If you are able to ambulate, know who you are, and where you are, you will NOT need a second injection. Giving yourself a second set of injections may cause an overdose of the ATNAA which could result in incapacitation. If symptoms of organophosphorus nerve agent poisoning are not relieved after administering one injection, seek someone else to check your symptoms. A buddy must administer the second and third injections, if needed. Buddy-Aid If you encounter a service member suffering from any of the severe symptoms of organophosphorus nerve agent poisoning, render the following aid: Mask the casualty, if necessary. Do not fasten the hood. If self-aid (one ATNAA injection) has been administered, administer in rapid succession two (2) additional ATNAA injections into the casualty's lateral thigh muscle or buttocks. Use the casualty's own ATNAAs when providing aid. Do not use your own autoinjectors on a casualty. If you do, you may not have any antidote available when needed for self-aid. If self-aid (one ATNAA injection) has not been administered, administer in rapid succession three (3) ATNAA injections into the casualty's lateral thigh muscle or buttocks.

WARNINGS AND PRECAUTIONS Cardiovascular (CV) Risks: Tachycardia, palpitations, premature ventricular contractions, flutter, fibrillation, etc. Use caution in individuals with known CV disease or conduction problems. ( 5.1 ) Heat Injury: May inhibit sweating and lead to hyperthermia; avoid excessive exercising and heat exposure. ( 5.2 ) Acute Glaucoma: May precipitate in susceptible individuals. ( 5.3 ) Urinary Retention : Administer with caution in individuals with bladder outflow obstruction. ( 5.4 ) Pyloric Stenosis: May convert into complete obstruction. ( 5.5 ) Exacerbation of Chronic Lung Disease: Atropine may cause inspiration of bronchial secretions and formation of dangerous viscid plugs in individuals with chronic lung disease; monitor respiratory status. ( 5.6 ) 5.1 Cardiovascular Risks Cardiovascular adverse reactions reported in the literature for atropine include, but are not limited to, sinus tachycardia, palpitations, premature ventricular contractions, atrial flutter, atrial fibrillation, ventricular flutter, ventricular fibrillation, cardiac syncope, asystole, and myocardial infarction. In individuals with a recent myocardial infarction and/or severe coronary artery disease, there is a possibility that atropine-induced tachycardia may cause ischemia, extend or initiate myocardial infarcts, and stimulate ventricular ectopy and fibrillation. ATNAA should be used with caution in individuals with known cardiovascular disease or cardiac conduction problems. 5.2 Heat Injury Atropine may inhibit sweating which, in a warm environment or with excessive exercise, can lead to hyperthermia and heat injury. To the extent feasible, avoid excessive exercise and heat exposure [see Overdosage (10.2) ]. 5.3 Acute Glaucoma Atropine should be administered with caution in individuals at risk for acute glaucoma. 5.4 Urinary Retention Atropine should be administered with caution in individuals with clinically significant bladder outflow obstruction because of the risk of urinary retention. 5.5 Pyloric Stenosis Atropine should be administered with caution in individuals with partial pyloric stenosis because of the risk of complete pyloric obstruction. 5.6 Exacerbation of Chronic Lung Disease Atropine may cause inspiration of bronchial secretions and formation of dangerous viscid plugs in individuals with chronic lung disease. Respiratory status should be monitored in individuals with chronic lung disease following administration of ATNAA.

CONTRAINDICATIONS Conditions at which inhibition of postganglionic cholinergic nerves are undesirable, such as glaucoma and tachycardia. Also contraindicated in asthma, because the parenteral dose which might relieve asthma would have an excessive drying effect upon mucous plugs in the bronchi. Prostatic hypertrophy, while not a contraindication, requires special attention to signs of urinary retention.

CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Atropine is 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 also may be inhibited by atropine but this occurs less readily than with responses to injected (exogenous) choline esters. 12.2 Pharmacodynamics 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. Atropine exerts a more potent and prolonged effect on heart, intestine and bronchial muscle than scopolamine, but its action on the iris, ciliary body and certain secretory glands is weaker than that of scopolamine. Unlike the latter, atropine in clinical doses does not depress the central nervous system but may stimulate the medulla and higher cerebral centers. Although mild vagal excitation occurs, the increased respiratory rate and (sometimes) 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 also may lessen the degree of partial heart block when vagal activity is an etiologic factor. In some patients 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 in infants and small children. The effects of intravenous atropine on heart rate (maximum heart rate) and saliva flow (minimum flow) after I.V. administration (rapid, constant infusion over 3 min.) are delayed by 7 to 8 minutes after drug administration and both effects are non-linearly related to the amount of drug in the peripheral compartment. Changes in plasma atropine levels following intramuscular administration (0.5 to 4 mg doses) and heart rate are closely overlapped but the time course of the changes in atropine levels and behavioral impairment indicates that pharmacokinetics is not the primary rate-limiting mechanism for the central nervous system effect of atropine. 12.3 Pharmacokinetics Absorption After intramuscular administration, atropine is absorbed with peak concentration occurring at 30 min following injection. Effects of exercise: Exercise following intramuscular administration of atropine significantly increases the absorption of atropine due to increased perfusion in the muscle, with an increase in AUC by approximately 20% and Cmax by approximately 80%. Distribution Atropine is distributed throughout the body. Atropine’s plasma protein binding is about 44% and saturable in the 2 to 20 mcg/mL concentration range. Elimination The pharmacokinetics of atropine is nonlinear after intravenous administration of 0.5 to 4 mg. Atropine disappears from the blood following injection with a plasma half-life of about 2-4 hours. Much of the drug is destroyed by enzymatic hydrolysis, particularly in the liver, with 13 to 50% is excreted unchanged in the urine. Metabolism The major metabolites of atropine are noratropine, atropin-n-oxide, tropine, and tropic acid. The metabolism of atropine is inhibited by organophosphate pesticides. Specific Populations Pregnant Women Atropine readily crosses the placental barrier and enters the fetal circulation, but is not found in amniotic fluid. Nursing Mother Traces are found in various secretions, including milk. Pediatric and Geriatric Patients The elimination half-life of atropine is more than doubled in children under two years, and the elderly (> 65 years old) compared to other age groups.