Prescription Drugs

CLINICAL PHARMACOLOGY Mechanism Of Action Atropine is a reversible antagonist of muscarine-like actions of acetyl-choline and is therefore classified as an antimuscarinic agent. Atropine is relatively selective for muscarinic receptors. Its potency at nicotinic receptors is much lower, and actions at non-muscarinic receptors are generally undetectable clinically. Atropine does not distinguish among the M1, M2, and M3 subgroups of muscarinic receptors. The pupillary constrictor muscle depends on muscarinic cholinoceptor activation. This activation is blocked by topical atropine resulting in unopposed sympathetic dilator activity and mydriasis. Atropine also weakens the contraction of the ciliary muscle, or cycloplegia. Cycloplegia results in loss of the ability to accommodate such that the eye cannot focus for near vision. Pharmacodynamics The onset of action after administration of atropine sulfate ophthalmic solution, USP 1%, is usually within 40 minutes with maximal effect being reached in about 2 hours. The effect can last for up to 2 weeks in a normal eye. Pharmacokinetics The bioavailability of atropine sulfate ophthalmic solution, USP 1% was assessed in six healthy subjects, 24 to 29 years of age. Subjects received either 0.3 mg atropine sulfate administered as bolus intravenous injection or 0.3 mg administered as 30 μl instilled unilaterally in the cul-de-sac of the eye. Plasma l-hyoscyamine concentrations were determined over selected intervals up to eight hours after dose administration. The mean bioavailability of topically applied atropine was 63.5 ± 29% (range 19 to 95%) with large inter-individual differences. Mean maximum observed plasma concentration for the ophthalmic solution was 288 ± 73 pg/mL. Maximum concentration was reached in 28 ± 27 min after administration. Terminal half-life of l-hyoscamine was not affected by route of administration and was calculated to be 3 ± 1.2 hours (intravenous) and 2.5 ± 0.8 hours (topical ophthalmic). In another placebo-controlled study, the systemic exposure to l-hyoscyamine, and the anti-cholinergic effects of atropine were investigated in eight ocular surgery patients 56 to 66 years of age, following single topical ocular 0.4 mg atropine dose (given as 40 microliters of atropine sulfate ophthalmic solution, USP 1%). The mean (± standard deviation (SD)) Cmax of l-hyoscyamine in these patients was 860 ± 402 pg/mL, achieved within 8 minutes of eyedrop instillation. Following intravenous administration, the mean (± SD) elimination half-life (t ) of atropine was reported to be longer in pediatric subjects under 2 years (6.9 ± 3.3 hours) and in geriatric patients 65 to 75 years (10.0 ± 7.3 hours), compared to in children over 2 years (2.5 ± 1.2 hours) and in adults 16 to 58 years (3.0 ± 0.9 hours). (see Pediatric Use). Atropine 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. The major metabolites of atropine are noratropine, atropin-n-oxide, tropine, and tropic acid. Atropine readily crosses the placental barrier and enters the fetal circulation, but is not found in amniotic fluid. Atropine binds poorly (about 44%) to plasma protein, mainly to alpha-1 acid glycoprotein; age has no effect on the serum protein binding of atropine. Atropine binding to α-1 acid glycoprotein was concentration dependent (2 to 20 mcg/mL) and nonlinear in vitro and in vivo. There is no gender effect on the pharmacokinetics of atropine administered by injection. Clinical Studies Topical administration of atropine sulfate ophthalmic solution, USP 1% results in cycloplegia and mydriasis which has been demonstrated in several controlled clinical studies in adults and pediatric patients. Maximal mydriasis usually occurs in about 40 minutes and maximal cycloplegia is usually achieved in about 60 to 90 minutes after single administration. Full recovery usually occurs in approximately one week, but may last a couple of weeks.

CLINICAL PHARMACOLOGY 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 also may be inhibited by atropine but this occurs less readily than with responses to injected (exogenous) choline esters. 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 Sulfate Injection, USP 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. Atropine disappears rapidly from the blood following injection and is distributed throughout the body. 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. The major metabolites of atropine are noratropin, atropine-n-oxide, tropine, and tropic acid. The metabolism of atropine is inhibited by oranophosphate pesticides (e.g., diazon). Atropine readily crosses the placental barrier and enters the fetal circulation, but is not found in amniotic fluid. Exercise, both prior to and immediately following intramuscular administration of atropine, significantly increases the absorption of atropine due to increased perfusion it eh muscle and significantly decreases the clearane of atropine. The pharmacokinetics of atropine is nonlinear after intravenous administration of 0.5 to 4 mg. Atropine binds poorly {about 44%} to plasma proteins, maily to alpha-1 acid glycoprotein; age has not effect on the serum protein binding of atropine. Atropine binding to α-1 acid glycoprotein was concentration-dependent (2-29 µg/ml) and nonlinerar in vitro and in vivo. 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 (2 - 64 years old). There is no gender effect on the phrmacokinetics and pharmacodynamics (heart rate changes) of atropine. The effects of intravenous atropine on heart rate (maximum heart rate) and saliva flow (minimum flow) after I.V. administrations (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 bu the time course of the changes in atropine levels and behavioral impairment indicates that pharmacokinetics is not the primary rate-limited mechanism for the central nervous system effect of atropine Sodium chloride added to render the solution isotonic for injection of the active ingredient is present in amounts insufficient to affect serum electrolyte balance of sodium (Na+) and chloride (Cl-) ions.

CLINICAL PHARMACOLOGY 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® (atropine) 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.

Find Lowest Prices on ATROPINE (atropine sulfate) Solution DESCRIPTION Atropine Sulfate Ophthalmic Solution, USP 1% is a sterile topical anticholinergic for ophthalmic use. The active ingredient is represented by the chemical structure: Chemical Name: Benzeneacetic acid, α-(hydroxymethyl)-, 8-methyl-8-azabicyclo[3.2.1.]oct-3-yl ester, endo –(±)-, sulfate (2:1) (salt), monohydrate. Molecular Formula: (C17H23NO3) •H2SO4•H2O Molecular Weight: 694.83 g/mol Each mL of Atropine Sulfate Ophthalmic Solution USP, 1% contains: Active: atropine sulfate 10 mg equivalent to 8.3 mg of atropine. Inactives: benzalkonium chloride 0.1 mg (0.01%), dibasic sodium phosphate, edetate disodium, hypromellose (2910), monobasic sodium phosphate, hydrochloric acid and/or sodium hydroxide may be added to adjust pH (3.5 to 6. 0), and water for injection USP.

DESCRIPTION ATROPINE SULFATE Injection, USP 0.1 mg/mI (Adult) 0.05 mg/mL (Pediatric) ABBOJECT® Unit of Use Syringe Atropine Sulfate Injection, USP is a sterile, nonpyrogenic isotonic solution of atropine sulfate monohydrate in water for injection with sodium chloride sufficient to render the solution isotonic. It is administered parenterally by subcutaneous, intramuscular or intravenous injection. Each milliliter (mL) contains atropine sulfate, monohydrate 0.1 mg (adult strength) or 0.05 mg (pediatric strength), and sodium chloride, 9 mg. May contain sodium hydroxide and/or sulfuric acid for pH adjustment 0.308 mOsmol/mL (calc.). pH 4.2 (3.0 to 6.5). The solution contains no bacteriostat, antimicrobial agent or added buffer (except for pH adjustment) and is intended for use only as a single-dose injection. When smaller doses are required the unused portion should be discarded. Atropine Sulfate Injection is a parenteral anticholinergic agent and muscarinic antagonist. Atropine Sulfate, USP is chemically designated 1a H, 5a H-Tropan-3-a ol (±)-tropate(ester), sulfate (2:1) (salt) monohydrate, (C17H23NO3)2 • H2SO4 • H2O, colorless crystals or white crystalline powder very soluble in water. It has the following structural formula: Atropine, a naturally occurring belladonna alkaloid, is a racemic mixture of equal parts of d- and 1-hyocyamine, whose activity is due almost entirely to the levo isomer of the drug. Sodium Chloride, USP is chemically designated NaCI, a white crystalline powder freely soluble in water. The syringe is molded from a specially formulated polypropylene. Water permeates from inside the container at an extremely slow rate which will have an insignificant effect on solution concentration over the expected shelf life. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the syringe material.

Find Lowest Prices on AtroPen® (auto-injector atropine) Injection FOR USE IN NERVE AGENT AND INSECTICIDE POISONING ONLY 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. SEEK IMMEDIATE MEDICAL ATTENTION AFTER INJECTION WITH ATROPEN® (atropine) . A STERILE SOLUTION FOR INTRAMUSCULAR USE ONLY DESCRIPTION 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® (atropine) are available; they are AtroPen® (atropine) 0.5 mg, AtroPen® (atropine) 1 mg, and AtroPen® (atropine) 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® (atropine) 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:

INDICATIONS Atropine Sulfate Ophthalmic Solution, USP 1% is indicated for: Cycloplegia Mydriasis Penalization Of The Healthy Eye In The Treatment Of Amblyopia DOSAGE AND ADMINISTRATION In individuals from three (3) months of age or greater, 1 drop topically to the cul-de-sac of the conjunctiva, forty minutes prior to the intended maximal dilation time. In individuals 3 years of age or greater, doses may be repeated up to twice daily as needed. HOW SUPPLIED Dosage Forms And Strengths Atropine Sulfate Ophthalmic Solution, USP 1%: each mL contains 10 mg of atropine sulfate equivalent to 8.3 mg of atropine. Storage And Handling Atropine Sulfate Ophthalmic Solution, USP 1% is supplied in a plastic dropper bottle with a red cap in the following sizes: NDC 17478-215-02 2 mL fill in 6cc bottle NDC 17478-215-05 5 mL fill in 6cc bottle NDC 17478-215-15 15 mL fill in 15cc bottle Storage Store at 20° to 25°C (68° to 77°F). Keep tightly closed. Manufactured by: Akorn, Inc. Lake forest, IL 60045. Revised July 2014

INDICATIONS Atropine Sulfate Injections, USP, is indicated when excessive (or sometime normal) muscarinic effects are judged to be life threatening or are producing symptoms sever enough to call of temporary, reversible muscarinic blockade. Examples, not an exhaustive list, of such possible uses are: 1. As an antisialogogue when reduction of secretions of the respiratory tract are thought to be needed; its routine use as a preanesthetic agent is discouraged 2. To blunt the increased vagal tone (decreased pulse and blood pressure) produced by intra-abdominal tract or ocular muscle traction, its routine use to prevent such events is discouraged 3. To temporarily increase heart rate or decrease AV-block until definitive intervention can take place, when bradycardia or AV-block are judged to be hemodynamically significant and thought to be due to excess vagal tone 4. As an antidote for inadvertent overdose of cholinergic drugs or for cholinesterase poisoning such as from organophosphorus insecticides 5. As an antidote for the "rapid type of mushroom poisoning due to the presence of the alkaloid muscarine, in certain species of fungus such as Amanita muscaria, and 6. To alleviate the muscarinic side effects of anticholinesterase drugs used for reversal of neuromuscular blockade DOSAGE AND ADMINISTRATION Atropine Sulfate Injection, USP in Ansyr Syringe is intended fo rintravenous use, but may be administered subcutaneously or intramuscularly. Its use usually requires titration, using heart rate, PR interval, blook pressure and/or patient's symptoms as a guide for having reached an appropriate dose. Adults Initial single doses in adults vary from around 0.5 mg to 1 mg (5 - 10 mL of the 0.1 mg/mL solution) for antisialagogue and other antivagal effects, to 2 to 3 mg (20 - 30 mL of the 0.1 mg/mL solution) as an antidote for organophosporous or muscarinic mushroom poisoning. When used as an antidote, the 2 to 3 mg dose should be repeated no less often that every 20 to 30 minutes until signs of poisoning are sufficiently lessened or signs of atropine poisoning (See ADVERSE REACTIONS and OVERDOSAGE) occur. When the recurrent use of atropine is essential in patients with coronary atery disease, the total dose should be restricted to 2 to 3 (maximum 0.03 to 0.04 mg/kg) to avoid the detrimental effects of atropine-induced tachycardia on myocardial oxygen demand. For patients with bradyasystolic cardiac arrest, a 1 mg dose of atropine is administered inbravenously and is repeated every 3-5 minutes if asystole persists. Three milligrams (0.04 mg/kg) given I.V. is a fully vagolytic dose in most patients. The administration of less than 0.5 mg can produce a paradoxical bradycardia because of the central or peripheral parasympathomimatic effects of low dose in adults. Endotracheal administration of atropine can be used in patients without I.V. access. The recommended adult dose of atropine for endotracheal administration is 1 to 2 mg diluted to a total not to exceed 10 ml of sterile water or normal saline. Titration intervals of one or two hours are recommended tin circumstances that are not life-threatening. Pediatrics Dosing information in pediatric populations ahs not been well studied. Usage history of initial dose has been in the range of 0.01to 0.03 mg/kg body weight. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS. HOW SUPPLIED Atropine Sulfate Injection, USP is supplied in single-dose containers as follows: List No. Container Size Conc. Total Content (Atropine) 9629 Ansyr® Plastic Syringe 5mL 0.1 mg/mL (Adult) 0.5 mg 1630 Ansyr® Plastic Syringe 10mL 0.1 mg/mL (Adult) 1 mg 9630 Ansyr® Plastic Syringe 5mL 0.05 mg/mL (Pediatric) 0.25 mg Store at controlled room temperature 15° to 30°C (59° to 86°F). Caution: Federal (USA) law prohibits dispensing without prescription.

INDICATIONS The AtroPen® (atropine) 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 (atropine) 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® (atropine) 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® (atropine) 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® (atropine) 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. DOSAGE AND ADMINISTRATION 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® (atropine) 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® (atropine) 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® (atropine) 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® (atropine) 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® (atropine) 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® (atropine) 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® (atropine) injections should be used unless the patient is under the supervision of a trained medical provider. Different dose strengths of the AtroPen® (atropine) are available depending on the recipient's age and weight. Adults and children weighing over 90 lbs (generally over 10 years of age)..............AtroPen® (atropine) 2 mg (green) Children weighing 40 lbs to 90 lbs (generally 4 to 10 years of age)..............AtroPen® (atropine) 1 mg (dark red) Children weighing 15 lbs to 40 lbs (generally 6 months to 4 years of age)..............AtroPen® (atropine) 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® (atropine) 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® (atropine) injections given in rapid succession are recommended 10 minutes after receiving the first AtroPen® (atropine) 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® (atropine) 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® (atropine) injections into the victim's mid-lateral thigh in rapid succession using the appropriate weight-based AtroPen® (atropine) 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® (atropine) (please refer to the illustrated Self Aid and Caregiver Directions for Use elsewhere): Warning: Giving additional AtroPen® (atropine) 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. HOW SUPPLIED The AtroPen® (atropine) 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® (atropine) 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

PATIENT INFORMATION Advise patients not to touch the dropper tip to any surface as this may contaminate the solution. Advise patients that drops will sting upon instillation and advise patients that they will experience sensitivity to light and blurred vision which may last for a couple of weeks.

PATIENT INFORMATION See WARNINGS, CONTRAINDICATIONS, and PRECAUTIONS.

PATIENT INFORMATION 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® (atropine) (GREEN LABEL) Children weighing 40 lbs to 90 lbs (generally 4 to 10 years of age) 1 mg AtroPen® (atropine) (DARK RED LABEL) Children weighing 15 lbs to 40 lbs (generally 6 months to 4 years of age) 0.5 mg AtroPen® (atropine) (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® (atropine) 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® (atropine) injections given in rapid succession are recommended 10 minutes after receiving the first AtroPen® (atropine) 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® (atropine) 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® (atropine) injections into the victim's mid-lateral thigh in rapid succession using the appropriate weight-based AtroPen® (atropine) dose. WARNING: Giving additional AtroPen (atropine) 0 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® (atropine) #00001 (A) Snap the grooved end of the plastic sleeve down and over the yellow safety cap. Remove the AtroPen® (atropine) 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® (atropine) 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® (atropine) , 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® (atropine) and either pin the used AtroPen® (atropine) to the victim's clothing or show the used AtroPen® (atropine) auto-injectors to the first medical person you see. This will allow medical personnel to see the number and dose of AtroPen® (atropine) autoinjectors administered. Move yourself and the exposed individual away from the contaminated area right away. Try to find medical help.

OVERDOSE In the event of accidental ingestion or toxic overdosage with atropine sulfate ophthalmic solution, supportive care may include a short acting barbiturate or diazepam 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 by slow intravenous injection of 1 to 4 mg (0.5 to 1 mg in pediatric populations), rapidly abolishes delirium and coma caused by large doses of atropine. Since physostigmine is rapidly destroyed, the patient may again lapse into coma after one to two hours, and repeated doses may be required. Artificial respiration with oxygen may be necessary. Cooling measures may be needed to help to reduce fever, especially in pediatric populations. The fatal adult dose of atropine is not known. In pediatric populations, 10 mg or less may be fatal. CONTRAINDICATIONS Hypersensitivity To Any Component Of This Medication Sections or subsections omitted from the full prescribing information are not listed. Atropine sulfate ophthalmic solution should not be used in anyone who has demonstrated a previous hypersensitivity or known allergic reaction to any ingredient of the formulation because it may recur.

OVERDOSE In the event of toxic overdosage (See ADVERSE REACTIONS), 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. Since physostigmine is rapidly destroyed, the patient may again lapse into coma after one to two hours, and repeated doses may be required. Artificial respiration with oxygen may be necessary. Ice bags and alcohol sponges help to reduce fever, especially in children. The fatal adult dose of atropine is not known; 200 mg doses have been used and doses as high as 1000 mg have been given. In children, 10 mg or less may be fatal. With a dose as low as 0.5 mg, undesirable minimal symptoms or responses of overdosage may occur. These increase in severity and extent with larger doses of the drug (excitement, hallucinations, delirium and coma with a dose of 10 mg or more). CONTRAINDICATIONS Atropine generally is contraindicated in patients with glaucoma, pyloric stenosis or prostatic hypertrophy, except in doses ordinarily used for preanesthetic medication.

OVERDOSE 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. CONTRAINDICATIONS 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).

SIDE EFFECTS The following serious adverse reactions are described below and elsewhere in the labeling: Photophobia and Blurred Vision [See WARNINGS AND PRECAUTIONS] Elevation in Blood Pressure [See WARNINGS AND PRECAUTIONS] The following adverse reactions have been identified following use of atropine sulfate ophthalmic solution. 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. Ocular Adverse Reactions Eye pain and stinging occurs upon instillation of atropine sulfate ophthalmic solution. Other commonly occurring adverse reactions include, blurred vision, photophobia, superficial keratitis and decreased lacrimation. Allergic reactions such as papillary conjunctivitis, contact dermatitis, and lid edema may also occur less commonly. Systemic Adverse Reactions Systemic effects of atropine are related to its anti-muscarinic activity. Systemic adverse events reported include dryness of skin, mouth, and throat from decreased secretions from mucus membranes; restlessness, irritability or delirium from stimulation of the central nervous system; tachycardia; flushed skin of the face and neck. DRUG INTERACTIONS Monoamine Oxidase Inhibitors (MAOI) The use of atropine and monoamine oxidase inhibitors (MAOI) is generally not recommended because of the potential to precipitate hypertensive crisis.

SIDE EFFECTS 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® (atropine) 0.5 mg, 1 mg and 2 mg in a case series of 240 children who received AtroPen® (atropine) 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. DRUG INTERACTIONS 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.

WARNINGS Included as part of the "PRECAUTIONS" Section PRECAUTIONS Photophobia And Blurred Vision Photophobia and blurred vision due to pupil unresponsiveness and cycloplegia may last up to 2 weeks. Elevation Of Blood Pressure Elevation in blood pressure from systemic absorption has been reported following conjunctival instillation of recommended doses of atropine sulfate ophthalmic solution, USP 1%. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Atropine sulfate was negative in the salmonella/microsome mutagenicity test. Studies to evaluate carcinogenicity and impairment of fertility have not been conducted. Use In Specific Populations Pregnancy Pregnancy Category C: There are no adequate and well-controlled studies of atropine sulfate in pregnant women. Animal development and reproduction studies have not been conducted with atropine sulfate. Since it is not known whether topically administered atropine sulfate can cause fetal harm, atropine sulfate ophthalmic solution, USP 1% should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Nursing Mothers Traces of atropine have been found in human milk following administration of atropine solution for injection. Because some systemic absorption occurs from topical administration, caution should be exercised when Atropine Sulfate Ophthalmic Solution, USP 1% is administered to a nursing woman. Pediatric Use Due to the potential for systemic absorption of atropine sulfate ophthalmic solution, the use of atropine sulfate ophthalmic solution, USP 1% in children under the age of 3 months is not recommended and the use in children under 3 years of age should be limited to no more than one drop per eye per day. Geriatric Use No overall differences in safety and effectiveness have been observed between elderly and younger adult patients.

WARNINGS Atropine is a highly potent drug and due care is essential to avoid overdosage, especially with intravenous administration. Children are more susceptible than adults to the toxic effects of anticholinergic agents. Atropine I.V. decreased the rate of mexiletine absorption without altering the relative oral bioavailability; this delay in mexiletine absorption was reversed by the combination of atropine and intravenous metoclopramide during pretreatment for anesthesia. Atropine is not removed by dialysis. PRECAUTIONS Do not administer unless solution is clear and seal is intact. Discard unused portion. Atropine Sulfate Injection, USP should be used with caution in all individuals over 40 years of age. Conventional systemic doses may precipitate acute glaucoma in susceptible patients, convert partial organic pyloric stenosis into complete obstruction, lead to complete urinary retention in patients with prostatic hypertrophy or cause inspissation of bronchial secretions and formation of dangerous viscid plugs in patients with chronic lung disease. Carcinogenesis, Mutagenesis, Impairment of Fertility: Studies have not been performed to evaluate the carcinogenic or mutagenic potential of atropine or its potential to adversely affect fertility. Pregnancy Category C. Animal reproduction studies have not been conducted with atropine. It also is not known whether atropine can cause fetal harm when given to a pregnant woman or can affect reproduction capacity. Atropine should be given to a pregnant woman only if clearly needed. Pediatric Use Safety and effectiveness in pediatric populations have not been estabilished. Geriatric Use An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient 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 of other drug therapy.

WARNINGS 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® (atropine) 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® (atropine) 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. PRECAUTIONS 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® (atropine) , 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.