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, light-headedness, 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 Rising Pharma Holdings, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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

For Painful Musculoskeletal Conditions PRESCRIBING INFORMATION 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 CINO 2 Molecular Weight: 169.56 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. Inactive ingredients: anhydrous lactose, croscarmellose sodium, docusate sodium with sodium benzoate, magnesium stearate, microcrystalline cellulose and pregelatinized maize starch. FDA approved dissolution test specifications differ from USP . struct

DOSAGE AND ADMINISTRATION Usual Adult Dosage Chlorzoxazone tablets 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 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 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.

INDICATIONS AND USAGE 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 judgement 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 intercostals 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 CHLORZOXAZONE CHLORZOXAZONE ANHYDROUS LACTOSE CROSCARMELLOSE SODIUM DOCUSATE SODIUM SODIUM BENZOATE MAGNESIUM STEARATE MICROCRYSTALLINE CELLULOSE STARCH, CORN White to off white Capsule shaped tablet 126 CHLORZOXAZONE CHLORZOXAZONE CHLORZOXAZONE CHLORZOXAZONE ANHYDROUS LACTOSE CROSCARMELLOSE SODIUM DOCUSATE SODIUM SODIUM BENZOATE MAGNESIUM STEARATE MICROCRYSTALLINE CELLULOSE STARCH, CORN White to off white Capsule shaped tablet 1;2 CHLORZOXAZONE CHLORZOXAZONE CHLORZOXAZONE CHLORZOXAZONE ANHYDROUS LACTOSE CROSCARMELLOSE SODIUM DOCUSATE SODIUM SODIUM BENZOATE MAGNESIUM STEARATE MICROCRYSTALLINE CELLULOSE STARCH, CORN White to off white Capsule shaped tablet 124

ANDA213126

CHLORZOXAZONE

CHLORZOXAZONE

16571-725

HUMAN PRESCRIPTION DRUG

ORAL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL Rising® NDC 16571-725-01 Chlorzoxazone Tablets, USP 375 mg 100 Tablets Rx only Rising® NDC 16571-726-01 Chlorzoxazone Tablets, USP 500 mg 100 Tablets Rx only Rising® NDC 16571-727-01 Chlorzoxazone Tablets, USP 750 mg 100 Tablets Rx only chlorzoxazone-375 chlorzoxazone-500 chlorzoxazone-750

HOW SUPPLIED Chlorzoxazone tablets, USP are supplied as follows: 375 mg White to off white capsule shaped tablet, debossed ‘126’ on one side and plain on other side. Bottle of 100 tablets with child-resistant closure, NDC 16571-725-01 Bottle of 500 tablets with continuous thread (CT) closure, NDC 16571-725-50 500 mg White to off white capsule shaped tablet, debossed with a break line between “1 and 2” on one side and plain on other side. Bottle of 100 tablets with child-resistant closure, NDC 16571-726-01 Bottle of 500 tablets with continuous thread (CT) closure, NDC 16571-726-50 750 mg White to off white capsule shaped tablet, debossed ‘124’ on the trisected side and plain on the bisected side. Bottle of 100 tablets with child-resistant closure, NDC 16571-727-01 Bottle of 500 tablets with continuous thread (CT) closure, NDC 16571-727-50. Dispense in tight container as defined in the official compendium. Store at 20° to 25° C (68° to 77° F) [see USP Controlled Room Temperature]. Manufactured by: Graviti Pharmaceuticals Pvt. Ltd. Telangana-502307, INDIA. Mfg. Lic. No.: 12/SRD/TS/2017/F/G Manufactured for: Rising Pharma Holdings, Inc. East Brunswick, NJ 08816 Revised: 11/2022 PIR72750-03

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.