CHLORZOXAZONE: 426 Adverse Event Reports & Safety Profile

DESCRIPTION Each 375 mg chlorzoxazone tablet contains: Chlorzoxazone USP 375 mg.

Each

500 mg chlorzoxazone tablet contains: Chlorzoxazone USP 500 mg.

Each

750 mg chlorzoxazone tablet contains: Chlorzoxazone USP 750 mg.

Chemical

Name: 5-Chloro-2-benzoxazolinone.

Structural

Formula: Molecular Formula: C 7 H 4 ClNO 2 Molecular Weight:

169.56 Chlorzoxazone, USP is a white or practically white, practically odorless, crystalline powder. Chlorzoxazone USP is slightly soluble in water; sparingly soluble in alcohol, in isopropyl alcohol, and in methanol; soluble in solutions of alkali hydroxides and ammonia. Inactive ingredients: 375 mg contains colloidal silicon dioxide, corn starch, croscarmellose sodium, docusate sodium with sodium benzoate, lactose monohydrate, magnesium stearate and microcrystalline cellulose. 500 mg contains D&C Red 27/Phloxine Aluminium lake, FD&C Yellow 6/Sunset Yellow FCF Aluminium lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polysorbate 80, pregelatinized starch, sodium starch glycolate. 750 mg contains colloidal silicon dioxide, corn starch, croscarmellose sodium, docusate sodium with sodium benzoate, lactose monohydrate, magnesium stearate and microcrystalline cellulose. Meets USP dissolution test 5 for 500 mg. FDA approved dissolution method differs from that of the USP for 375 mg and 750 mg. str

INDICATIONS AND USAGE Chlorzoxazone tablets are 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.

DOSAGE AND ADMINISTRATION Usual Adult Dosage Chlorzoxazone tablets USP, 375 mg: One tablet three or four times daily. If adequate response is not obtained with this dose, the 375 mg tablets may be increased to two tablets (750 mg) three or four times daily. As improvement occurs dosage can usually be reduced. Chlorzoxazone tablets USP, 500 mg: 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. Chlorzoxazone tablets USP, 750 mg: 1/3 tablet (250 mg) three or four times daily. Initial dosage for painful musculoskeletal conditions should be 2/3 tablet (500 mg) three or four times daily. If adequate response is not obtained with this dose, it may be increased to one tablet (750 mg) three or four times daily. As improvement occurs dosage can usually be reduced.

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

ADVERSE REACTIONS After extensive clinical use of chlorzoxazone-containing products, it is apparent that the product is well tolerated and seldom produces undesirable side effects. Occasional patients may develop gastrointestinal disturbances. It is possible in rare instances that chlorzoxazone may have been associated with gastrointestinal bleeding. Drowsiness, dizziness, lightheadedness, malaise, or overstimulation 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 REACTIONS, contact Camber Pharmaceuticals, Inc. at 1-866-495-1995 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch for voluntary reporting of adverse reactions.

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.

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.

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.