NuLev

Alaven Pharmaceutical LLC

(hyoscyaminesulfate USP)0.125 mg/tablet

FULL PRESCRIBING INFORMATION: CONTENTS*

• NULEV DESCRIPTION
• CLINICAL PHARMACOLOGY
• NULEV INDICATIONS AND USAGE
• NULEV CONTRAINDICATIONS
• WARNINGS
• PRECAUTIONS
  • General
  • Information for Patients
  • Drug Interactions
  • Carcinogenesis, Mutagenesis, Impairment of Fertility
  • Pregnancy-Pregnancy Category C
  • Nursing Mothers
  • Geriatric Use
• NULEV ADVERSE REACTIONS
• OVERDOSAGE
• NULEV DOSAGE AND ADMINISTRATION
  • Adults and pediatric patients 12 years of age and older
  • Pediatric patients 2 to under 12 years of age:
• HOW SUPPLIED
• Package Label – Principal Display Panel - 100-count Bottle, 0.125 mg Tablets

FULL PRESCRIBING INFORMATION

Rx Only

NULEV DESCRIPTION

Each round, white, peppermint flavored tablet can be chewed or placed on tongue for disintegration and contains 0.125 mg of hyoscyamine sulfate USP.

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), dehydrate with the following structure:

Inactive ingredients include: lactose monohydrate, magnesium stearate, mannitol USP, peppermint flavor, starch, stearic acid.

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 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 3½ 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.

NULEV INDICATIONS AND USAGE

NuLev^® is effective as adjunctive therapy in the treatment of peptic ulcer. It can also be used to control gastric secretion, 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). NuLev^® is 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.

NULEV 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, NuLev^® 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, shortterm memory loss, hallucinations, dysarthria, ataxia, euphoria, 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

General

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 drug since they may increase the heart rate. Use with caution in patients with hiatal hernia associated with reflux esophagitis.

Information for Patients

Like other anticholinergic agents, NuLev^® 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 NuLev^® 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.

Drug Interactions

Additive adverse effects resulting from cholinergic blockade may occur when NuLev^® 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. Administer NuLev^® before meals; antacids after meals.

Carcinogenesis, Mutagenesis, Impairment of Fertility

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.

Pregnancy-Pregnancy Category C

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. NuLev^® should be given to a pregnant woman only if clearly needed.

Nursing Mothers

Hyoscyamine sulfate is excreted in human milk. Caution should be exercised when NuLev^® is administered to a nursing woman.

Geriatric Use

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.

NULEV ADVERSE REACTIONS

All of the following adverse reactions have been reported with hyoscyamine sulfate. Adverse reactions may include dryness of the mouth; urinary hesitancy and retention; blurred vision; tachycardia; palpitations; mydriasis; increased ocular tension; loss of taste; headache; nervousness; drowsiness; weakness; fatigue; dizziness; insomnia; nausea; vomiting; impotence; 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 that 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.

NULEV DOSAGE AND ADMINISTRATION

Dosage may be adjusted according to the conditions and severity of symptoms. NuLev^® Chewable Melt (Hyoscyamine Sulfate tablets, 0.125 mg) may be chewed or placed on tongue and allowed to disintegrate. Tablets may be taken with or without water.

Adults and pediatric patients 12 years of age and older

1 to 2 tablets every four hours or as needed. Do not exceed 12 tablets in 24 hours.

Pediatric patients 2 to under 12 years of age:

½ to 1 tablet every four hours or as needed. Do not exceed 6 tablets in 24 hours.

HOW SUPPLIED

NuLev^® Chewable Melt (Hyoscyamine Sulfate tablets, 0.125 mg) are round, white, peppermint flavored tablets with "AP" debossed on one side and “nu” debossed on the opposite side.

Bottles of 100 tablets                    NDC 68220-118-10

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

Store at controlled room temperature between 20°-25°C (68°-77°F), see USP Controlled Room Temperature. Avoid exposure to heat.

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN. IN CASE OF ACCIDENTAL OVERDOSE, SEEK PROFESSIONAL ASSISTANCE OR CALL A POISON CONTROL CENTER IMMEDIATELY.

Manufactured for:

ALAVEN^® PHARMACEUTICAL LLC

Marietta, GA 30062

www.alavenpharm.com

For Medical Inquiries

Call toll free 1-888-317-0001

04/2009

500384

Printed in USA

Package Label – Principal Display Panel - 100-count Bottle, 0.125 mg Tablets

NDC 68220-118-10

NuLev^®

Chewable Melt Tablets

(hyoscyamine sulfate USP)

0.125 mg/tablet

Rx only 100 tablets

Manufactured for:

ALAVEN^® PHARMACEUTICAL LLC

Marietta, GA 30062

www.alavenpharm.com

For medical inquiries call 1-888-317-0001