Atropine Sulfate

Name: Atropine Sulfate

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

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.

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.

Advice to Patients

  • Seek immediate medical attention after injection with an atropine injection auto-injector.105

  • Advise that dry mouth may occur.105 b

  • Advise of risk of hyperthermia and heat prostration; avoid exposure to high environmental temperatures and avoid use when febrile.c

  • Advise patients receiving chronic therapy of possible blurred vision with the drug; activities that require good, clear vision should be avoided.105 b

  • Risk of dizziness or drowsiness; avoid driving or operating machinery until effects on individual are known.c

  • For IM self-administration in nerve gas and pesticide poisoning, proper techniques for storage, attention to expiration dating (replacing before expiration), use, and disposal of the prefilled auto-injector (e.g., AtroPen) and for administration of the drug.105

  • For IM self-administration in nerve gas and pesticide poisoning, importance of understanding the indications for use and the symptoms of poisoning.105

  • For IM self-administration in nerve gas and pesticide poisoning, importance of ensuring adequate understanding of the recognition and treatment of such poisoning and when concomitant cholinesterase reactivator (pralidoxime chloride) therapy may be necessary.105

  • For IM self-administration in nerve gas and pesticide poisoning, importance of not exceeding 3 doses unless under medical supervision.105

  • For IM self-administration in nerve gas and pesticide poisoning, importance of seeking immediate medical attention once the initial dose(s) is administered because respiratory and other supportive care and prolonged atropinization may be needed.105

  • For IM self-administration in nerve gas and pesticide poisoning, importance of recognizing that inadvertent administration when such poisoning is not present could result in atropine toxicity and temporary incapacitation (inability to walk properly, see clearly, or think clearly for several hours or longer).105

  • For self-administration in nerve gas and pesticide poisoning, importance of not contaminating other individuals (e.g., medical and emergency personnel) by clothing exposure; aggressive and safe decontamination by trained personnel is strongly suggested.105

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.105 b

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.105

  • Importance of informing patients of other important precautionary information.105 b (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Atropine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder

Parenteral

Injection

equivalent to Atropine Sulfate 0.25 mg/0.3 mL

AtroPen Auto-Injector (“yellow label”)

Meridian

equivalent to Atropine Sulfate 0.5 mg/0.7 mL

AtroPenAuto-Injector (“blue label”)

Meridian

equivalent to Atropine Sulfate 1 mg/0.7 mL

AtroPenAuto-Injector (“dark red label”)

Meridian

equivalent to Atropine Sulfate 2 mg/0.7 mL

AtroPenAuto-Injector (“green label”)

Meridian

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Atropine Sulfate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder*

Parenteral

Injection

0.05 mg/mL*

Atropine Sulfate Injection

0.1 mg/mL*

Atropine Sulfate Injection

0.4 mg/mL*

Atropine Sulfate Injection

1 mg/mL*

Atropine Sulfate Injection

(web3)