Hyoscyamine Sulfate Extended-Release

County Line Pharmaceuticals, LLC

Hyoscyamine Sulfate Extended-Release Tablets, 0.375 mgPI-9328

FULL PRESCRIBING INFORMATION: CONTENTS*

• HYOSCYAMINE SULFATE EXTENDED-RELEASE DESCRIPTION
• CLINICAL PHARMACOLOGY
• HYOSCYAMINE SULFATE EXTENDED-RELEASE INDICATIONS AND USAGE
• HYOSCYAMINE SULFATE EXTENDED-RELEASE CONTRAINDICATIONS
• WARNINGS
• PRECAUTIONS
• HYOSCYAMINE SULFATE EXTENDED-RELEASE ADVERSE REACTIONS
• OVERDOSAGE
• HYOSCYAMINE SULFATE EXTENDED-RELEASE DOSAGE AND ADMINISTRATION
• HOW SUPPLIED
• PRINCIPAL DISPLAY PANEL

FULL PRESCRIBING INFORMATION

Rev 02/09     Rx Only

HYOSCYAMINE SULFATE EXTENDED-RELEASE DESCRIPTION

Hyoscyamine Sulfate Extended-Release Tablets contain 0.375 mg hyoscyamine sulfate in a formulation designed for oral b.i.d. dosage.

Hyoscyamine sulfate is one of the principal anticholinergic/antispasmodic components of belladonna alkaloids. The empirical formula is (C₁₇H₂₃NO₃)₂•H₂SO₄•2H₂O and the molecular weight is 712.85. Chemically, it is benzeneacetic acid, α-(hydroxymethyl)-, 8-methyl-8-azabicyclo [3.2.1] oct-3-yl ester, [3(S)-endo]-, sulfate (2:1), dihydrate with the following structure:

Each tablet also contains as inactive ingredients: Colloidal silicon dioxide, hydroxypropyl cellulose, magnesium stearate and microcrystalline cellulose.

CLINICAL PHARMACOLOGY

Hyoscyamine sulfate inhibits specifically the actions of acetylcholine on structures innervated by postganglionic cholinergic nerves and on smooth muscles that respond to acetylcholine but lack cholinergic innervation. These peripheral cholinergic receptors are present in the autonomic effector cells of the smooth muscle, cardiac muscle, the sinoatrial node, the atrioventricular node and the exocrine glands. At therapeutic doses, it is completely devoid of any action on the autonomic ganglia. Hyoscyamine sulfate inhibits gastrointestinal propulsive motility and decreases gastric acid secretion. Hyoscyamine sulfate also controls excessive pharyngeal, tracheal and bronchial secretions.

Hyoscyamine sulfate is absorbed totally and completely by oral administration. Once absorbed, hyoscyamine sulfate disappears rapidly from the blood and is distributed throughout the entire body. The half-life of hyoscyamine sulfate is 2 to 3 1/2 hours. Hyoscyamine sulfate is partly hydrolyzed to tropic acid and tropine but the majority of the drug is excreted in the urine unchanged within the first 12 hours. Only traces of this drug are found in breast milk. Hyoscyamine sulfate passes the blood brain barrier and the placental barrier.

Hyoscyamine Sulfate Extended-Release Tablets release 0.375 mg hyoscyamine sulfate at a controlled and predictable rate for 12 hours. Tablets may not completely disintegrate and may be excreted by some patients.

HYOSCYAMINE SULFATE EXTENDED-RELEASE INDICATIONS AND USAGE

Hyoscyamine Sulfate Extended-Release Tablets are effective as adjunctive therapy in the treatment of peptic ulcer. They can also be used to control gastric secretions, visceral spasm and hypermotility in spastic colitis, spastic bladder, cystitis, pylorospasm and associated abdominal cramps. May be used in functional intestinal disorders to reduce symptoms such as those seen in mild dysenteries, diverticulitis and acute enterocolitis. For use as adjunctive therapy in the treatment of irritable bowel syndrome (irritable colon, spastic colon, mucous colitis) and functional gastrointestinal disorders. Also used as adjunctive therapy in the treatment of neurogenic bladder and neurogenic bowel disturbances (including the splenic flexure syndrome and neurogenic colon). Hyoscyamine Sulfate Extended-Release Tablets are indicated along with morphine or other narcotics in symptomatic relief of biliary and renal colic; as a “drying agent” in the relief of symptoms of acute rhinitis; in the therapy of parkinsonism to reduce rigidity and tremors and to control associated sialorrhea and hyperhidrosis. May be used in the therapy of poisoning by anticholinesterase agents.

HYOSCYAMINE SULFATE EXTENDED-RELEASE CONTRAINDICATIONS

Glaucoma; obstructive uropathy (for example, bladder neck obstruction due to prostatic hypertrophy); obstructive disease of the gastrointestinal tract (as in achalasia, pyloroduodenal stenosis); paralytic ileus, intestinal atony of elderly or debilitated patients; unstable cardiovascular status in acute hemorrhage; severe ulcerative colitis; toxic megacolon complicating ulcerative colitis; myasthenia gravis.

WARNINGS

In the presence of high environmental temperature, heat prostration can occur with drug use (fever and heat stroke due to decreased sweating). Diarrhea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. In this instance, treatment with this drug would be inappropriate and possibly harmful. Like other anticholinergic agents, hyoscyamine sulfate may produce drowsiness, dizziness or blurred vision. In this event, the patient should be warned not to engage in activities requiring mental alertness such as operating a motor vehicle or other machinery or to perform hazardous work while taking this drug.

Psychosis has been reported in sensitive individuals given anticholinergic drugs including hyoscyamine sulfate. CNS signs and symptoms include confusion, disorientation, short-term memory loss, hallucinations, dysarthria, ataxia, coma, euphoria, anxiety, decreased anxiety, fatigue, insomnia, agitation and mannerisms and inappropriate affect. These CNS signs and symptoms usually resolve within 12 to 48 hours after discontinuation of the drug.

PRECAUTIONS

Use with caution in patients with: autonomic neuropathy, hyperthyroidism, coronary heart disease, congestive heart failure, cardiac arrhythmias, hypertension and renal disease. Investigate any tachycardia before giving any anticholinergic drugs since they may increase the heart rate. Use with caution in patients with hiatal hernia associated with reflux esophagitis.

Like other anticholinergic agents, hyoscyamine sulfate may produce drowsiness, dizziness or blurred vision. In this event, the patient should be warned not to engage in activities requiring mental alertness such as operating a motor vehicle or other machinery or to perform hazardous work while taking this drug.

Use of hyoscyamine sulfate may decrease sweating resulting in heat prostration, fever or heat stroke; febrile patients or those who may be exposed to elevated environmental temperatures should use caution. Tablets may not completely disintegrate and may be excreted by some patients.

Additive adverse effects resulting from cholinergic blockade may occur when hyoscyamine sulfate is administered concomitantly with other antimuscarinics, amantadine, haloperidol, phenothiazines, monoamine oxidase (MAO) inhibitors, tricyclic antidepressants or some antihistamines.

Antacids may interfere with the absorption of hyoscyamine sulfate.

No long-term studies in animals have been performed to determine the carcinogenic, mutagenic or impairment of fertility potential of hyoscyamine sulfate; however, 40 years of marketing experience with hyoscyamine sulfate shows no demonstrable evidence of a problem.

Animal reproduction studies have not been conducted with hyoscyamine sulfate. It is also not known whether hyoscyamine sulfate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Hyoscyamine Sulfate Extended-Release Tablets should be given to a pregnant woman only if clearly needed.

Hyoscyamine sulfate is excreted in human milk. Caution should be exercised when Hyoscyamine Sulfate Extended-Release Tablets are administered to a nursing woman.

Reported clinical experience has not identified differences in safety between patients aged 65 and over 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 or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

HYOSCYAMINE SULFATE EXTENDED-RELEASE ADVERSE REACTIONS

The following adverse reactions have been reported for hyoscyamine sulfate and for pharmacologically similar drugs with anticholinergic/antispasmodic action. Adverse reactions may include dryness of the mouth; urinary hesitancy and retention; blurred vision; tachycardia; palpitations; mydriasis; cycloplegia; increased ocular tension; loss of taste; headache; nervousness; drowsiness; weakness; fatigue; dizziness; insomnia; nausea; vomiting; impotence; suppression of lactation; constipation; bloated feeling; abdominal pain; diarrhea; allergic reactions or drug idiosyncrasies; urticaria and other dermal manifestations; ataxia; speech disturbance; some degree of mental confusion and/or excitement (especially in elderly persons); short-term memory loss; hallucinations; and decreased sweating.

OVERDOSAGE

The signs and symptoms of overdose are headache, nausea, vomiting, blurred vision, dilated pupils, hot dry skin, dizziness, dryness of the mouth, difficulty in swallowing and CNS stimulation.

Measures to be taken are immediate lavage of the stomach and injection of physostigmine 0.5 to 2 mg intravenously and repeated as necessary up to a total of 5 mg. Fever may be treated symptomatically (tepid water sponge baths, hypothermic blanket). Excitement to a degree which demands attention may be managed with sodium thiopental 2% solution given slowly intravenously or chloral hydrate (100-200 mL of a 2% solution) by rectal infusion. In the event of progression of the curare-like effect to paralysis of the respiratory muscles, artificial respiration should be instituted and maintained until effective respiratory action returns.

In rats, the LD₅₀ for hyoscyamine is 375 mg/kg. Hyoscyamine sulfate is dialyzable.

HYOSCYAMINE SULFATE EXTENDED-RELEASE DOSAGE AND ADMINISTRATION

Dosage may be adjusted according to the conditions and severity of symptoms.

Adults and pediatric patients 12 years of age and older: 1 to 2 tablets every 12 hours. Do not crush or chew tablets. Do not exceed 4 tablets in 24 hours.

HOW SUPPLIED

Hyoscyamine Sulfate Extended-Release Tablets, 0.375 mg are white, capsule shaped, biconvex tablets debossed with “CL” on one side and “14” on the other.

Bottles of 100
NDC 43199-014-01

Store at controlled room temperature 20°-25°C (68°-77°F); excursion permitted to 15°-30°C (59°-86°F). Please refer to current USP.

Dispense in tight, light-resistant containers as defined in USP/NF with a child-resistant closure.

KEEP OUT OF REACH OF CHILDREN

Manufactured for:

County Line Pharmaceuticals, LLC
Brookfield, WI 53005

For inquiries call toll free 1-866-207-5636.

PI-9328
Rev 02/09

PRINCIPAL DISPLAY PANEL

NDC 43199-014-01

100 Tablets

Hyoscyamine Sulfate Extended-Release Tablets

0.375 mg

Rx Only

Each tablet contains 0.375 mg hyoscyamine sulfate, USP.

USUAL DOSAGE: See package insert for full prescribing information.

Dispense in tight, light-resistant containers as defined in USP/NF with a child-resistant closure.

Store at controlled room temperature 20°-25°C (68°-77°F) excursions permitted to 15°-30°C (59°-86°F). Please refer to the current USP.