CHLORZOXAZONE

ADVERSE REACTIONS Chlorzoxazone containing products are usually well tolerated. It is possible in rare instances that chlorzoxazone may have been associated with gastrointestinal bleeding. Drowsiness, dizziness, lightheadedness, malaise, or over-stimulation may be noted by an occasional patient. Rarely, allergic type skin rashes, petechiae, or ecchymoses may develop during treatment. Angioneurotic edema or anaphylactic reactions are extremely rare. There is no evidence that the drug will cause renal damage. Rarely, a patient may note discoloration of the urine resulting from a phenolic metabolite of chlorzoxazone. This finding is of no known clinical significance. To report SUSPECTED ADVERSE EVENTS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800- FDA-1088 or http://www.fda.gov/ for voluntary reporting of adverse reactions.

CONTRAINDICATIONS Chlorzoxazone is contraindicated in patients with known intolerance to the drug.

DESCRIPTION Chlorzoxazone USP is a centrally acting skeletal muscle relaxant, available as tablets of 500 mg for oral administration. Its chemical name is 5-Chloro-2-benzoxazolinone, and its structural formula is: Chlorzoxazone,USP is a white or practically white, practically odorless, crystalline powder. Chlorzoxazone is slightly soluble in water; sparingly soluble in alcohol, in isopropyl alcohol, and in methanol; soluble in solutions of alkali hydroxides and ammonia. Chlorzoxazone tablets contain the inactive ingredients -Lactose monohydrate USNF, Microcrystalline cellulose USNF, FD&C Yellow 6/Sunset Yellow FCF Aluminium lake, D&C Red 27/Phloxine Aluminium lake, Hypromellose USP (a) structure Binder solution Hypromellose USP (b), Polysarbate 80 USNF, Ethanol (96%v/v). Extragranrular Pregelatinized Starch USNF, Sodium starch glycolate USNF, Magnesium stearate USNF. FDA approved dissolution method differs from that of the USP.

DOSAGE AND ADMINISTRATION Usual Adult Dosage One tablet three or four times daily. If adequate response is not obtained with this dose, it may be increased to one and one-half tablets (750 mg) three or four times daily. As improvement occurs dosage can usually be reduced.

INDICATIONS Chlorzoxazone is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions. The mode of action of this drug has not been clearly identified, but may be related to its sedative properties. Chlorzoxazone does not directly relax tense skeletal muscles in man.

WARNINGS Serious (including fatal) hepatocellular toxicity has been reported rarely in patients receiving chlorzoxazone. The mechanism is unknown but appears to be idiosyncratic and unpredictable. Factors predisposing patients to this rare event are not known. Patients should be instructed to report early signs and/or symptoms of hepatotoxicity such as fever, rash, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, or jaundice. Chlorzoxazone should be discontinued immediately and a physician consulted if any of these signs or symptoms develop. Chlorzoxazone use should also be discontinued if a patient develops abnormal liver enzymes (e.g., AST, ALT, alkaline phosphatase and bilirubin.) The concomitant use of alcohol or other central nervous system depressants may have an additive effect. Usage in Pregnancy The safe use of chlorzoxazone has not been established with respect to the possible adverse effects upon fetal development. Therefore, it should be used in women of childbearing potential only when, in the judgment of the physician, the potential benefits outweigh the possible risks.

OVERDOSAGE Symptoms Initially, gastrointestinal disturbances such as nausea, vomiting, or diarrhea together with drowsiness, dizziness, lightheadedness or headache may occur. Early in the course there may be malaise or sluggishness followed by marked loss of muscle tone, making voluntary movement impossible. The deep tendon reflexes may be decreased or absent. The sensorium remains intact, and there is no peripheral loss of sensation. Respiratory depression may occur with rapid, irregular respiration and intercostal and substernal retraction. The blood pressure is lowered, but shock has not been observed. Treatment Gastric lavage or induction of emesis should be carried out, followed by administration of activated charcoal. Thereafter, treatment is entirely supportive. If respirations are depressed, oxygen and artificial respiration should be employed and a patent airway assured by use of an oropharyngeal airway or endotracheal tube. Hypotension may be counteracted by use of dextran, plasma, concentrated albumin or a vasopressor agent such as norepinephrine. Cholinergic drugs or analeptic drugs are of no value and should not be used.

CLINICAL PHARMACOLOGY Chlorzoxazone is a centrally-acting agent for painful musculoskeletal conditions. Data available from animal experiments as well as human study indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex arcs involved in producing and maintaining skeletal muscle spasm of varied etiology. The clinical result is a reduction of the skeletal muscle spasm with relief of pain and increased mobility of the involved muscles. Blood levels of chlorzoxazone can be detected in people during the first 30 minutes and peak levels may be reached, in the majority of the subjects, in about 1 to 2 hours after oral administration of chlorzoxazone. Chlorzoxazone is rapidly metabolized and is excreted in the urine, primarily in a conjugated form as the glucuronide. Less than one percent of a dose of chlorzoxazone is excreted unchanged in the urine in 24 hours.

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CHLORZOXAZONE CHLORZOXAZONE LACTOSE MONOHYDRATE MICROCRYSTALLINE CELLULOSE FD&C YELLOW NO. 6 D&C RED NO. 27 HYPROMELLOSE 2910 (3 MPA.S) POLYSORBATE 80 ALCOHOL STARCH, CORN SODIUM STARCH GLYCOLATE TYPE A POTATO MAGNESIUM STEARATE CHLORZOXAZONE CHLORZOXAZONE Light orange to orange flat, hexagonal N;500

ANDA089853

CHLORZOXAZONE

CHLORZOXAZONE

71335-2009

HUMAN PRESCRIPTION DRUG

ORAL

Chlorzoxazone 500mg Tablet Label

HOW SUPPLIED NDC: 71335-2009-1: 20 TABLETs in a BOTTLE NDC: 71335-2009-2: 30 TABLETs in a BOTTLE NDC: 71335-2009-3: 40 TABLETs in a BOTTLE NDC: 71335-2009-4: 90 TABLETs in a BOTTLE NDC: 71335-2009-5: 60 TABLETs in a BOTTLE NDC: 71335-2009-6: 100 TABLETs in a BOTTLE NDC: 71335-2009-7: 14 TABLETs in a BOTTLE NDC: 71335-2009-8: 7 TABLETs in a BOTTLE NDC: 71335-2009-9: 120 TABLETs in a BOTTLE

PRECAUTIONS Chlorzoxazone should be used with caution in patients with known allergies or with a history of allergic reactions to drugs. If a sensitivity reaction occurs such as urticaria, redness, or itching of the skin, the drug should be stopped. If any symptoms suggestive of liver dysfunction are observed, the drug should be discontinued.