Parafon Forte (Chlorzoxazone – Acetaminophen)

PARAFON FORTE®

Johnson & Johnson• Merck

Chlorzoxazone – Acetaminophen

Muscle Relaxant – Analgesic

Action And Clinical Pharmacology: Parafon Forte tablets combine the muscle-relaxant effect of chlorzoxazone with acetaminophen, a well-known analgesic.

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 humans during the first 30 minutes after oral administration of Parafon Forte tablets and peak levels may be reached in about 1 to 2 hours. Chlorzoxazone is rapidly metabolized and is excreted in the urine, primarily in a conjugated form as the glucuronide. Less than 1% of a dose of chlorzoxazone is excreted unchanged in the urine in 24 hours.

Acetaminophen provides analgesic action to supplement that which results secondarily from muscle relaxation. Acetaminophen is rapidly absorbed after oral administration, with peak plasma levels occurring in 1 to 2 hours. After 8 hours, only negligible amounts remain in the blood. Only 4% is excreted unchanged; 85% of the ingested dose is recovered in the urine in conjugated form as the glucuronide. Acetaminophen is distributed throughout most tissues of the body. Acetaminophen is metabolized primarily in the liver. Little unchanged drug is excreted in the urine, but most metabolic products appear in the urine within 24 hours.

The mode of action of chlorzoxazone has not been clearly identified, but may be related to its sedative properties. Chlorzoxazone does not directly relax tense skeletal muscles in man.

Following oral administration of chlorzoxazone in combination with acetaminophen, both drugs are rapidly absorbed. Mean drug plasma concentrations reach a peak level in the majority of subjects in 45 to 90 minutes.

The plasma elimination half-life is about 1 hour for chlorzoxazone and ranges from 1.5 to 3.5 hours for acetaminophen.

Metabolism is rapid; the principal metabolites are conjugates of glucuronic acid which are excreted primarily in the urine. Less than 1% of an administered dose of chlorzoxazone and less than 4% of an administered dose of acetaminophen is excreted unchanged in the urine in 24 hours. Only traces of unchanged drug are excreted through the bile into the feces.

Indications And Clinical Uses: As an adjunct to rest, physical therapy and other measures for the relief of discomfort associated with acute musculoskeletal conditions. Such conditions may include skeletal muscle spasm and pain associated with sprains, strains and other traumatic muscle injuries; myalgias; arthritides; low back pain; tension headache; torticollis; fibrositis; spondylitis; and cervical root and disc syndromes.

Contra-Indications: Hypersensitivity to the components, hepatic impairment and acute porphyria.

Precautions: Use 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.

There have been reports of liver damage associated with the use of chlorzoxazone-containing products. If any symptoms suggestive of liver dysfunction are observed, the drug should be discontinued.

Parafon Forte should be used with caution in patients with severe impairment of renal function.

Drowsiness and dizziness can occur with the use of Parafon Forte.

Occupational Hazards: Patients using this drug should be cautioned about driving a car or operating potentially hazardous machinery if they become drowsy, dizzy or show impaired mental or physical abilities while taking this medication.

Drug Interactions: Patients receiving antipsychotics, antianxiety agents or other CNS depressants (including alcohol) concomitantly with this drug may exhibit an additive CNS depression. When such combined therapy is contemplated, the dose of one or both agents should be reduced.

Avoid consumption of alcohol while using this product.

Pregnancy: Should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Chlorzoxazone and acetaminophen are not recommended during lactation because safety in nursing mothers has not been established. It is not known if chlorzoxazone is excreted in breast milk. Acetaminophen passes into breast milk but is not likely to have an adverse effect on the infant at therapeutic doses.

Children: Because safety and effectiveness of Parafon Forte have not been established in children such use is not recommended.

Adverse Reactions: Regular use of acetaminophen has been shown to produce a slight increase in prothrombin time in patients receiving oral anticoagulants, but the clinical significance of this effect is not clear. As with other nonprescription analgesic drugs, physicians should supervise the use of acetaminophen in patients with alcoholism, serious kidney or serious liver disease. Patients are advised to consult a physician if symptoms do not improve or if new problems such as high fever, rash, or headache occur. A physician should be consulted if the illness lasts more than 5 days despite treatment.

Gastrointestinal: Occasional patients may develop gastrointestinal disturbances and abdominal pain. It is possible in rare instances that chlorzoxazone may have been associated with gastrointestinal bleeding.

CNS: Drowsiness, dizziness, lightheadedness, malaise, or overstimulation may be noted by an occasional patient.

Allergic: Rarely, allergic-type skin rashes, petechiae, or ecchymoses may develop during treatment. Angioneurotic edema or anaphylactic reactions are extremely rare.

Renal Toxicity: There is no evidence that Parafon Forte 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.

Hepatotoxicity: 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 or bilirubin).

In a controlled multidose clinical trial with chlorzoxazone 500 mg, the following adverse events occurred in ³1% of patients receiving chlorzoxazone or occurred in
Body as a Whole: asthenia (2%), body pain, edema.

CNS: anxiety, dizziness (6%), drowsiness (9%), headache (5%), nervousness, paresthesia, vertigo.

Gastrointestinal: abnormal pain, anorexia, diarrhea (2%), dyspepsia (1%), flatulence, melena, nausea (3%).

Skin: pruritus, rash, skin discoloration.

Urogenital: polyuria.

Symptoms And Treatment Of Overdose: Symptoms: Chlorzoxazone: 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.

Acetaminophen: In acute acetaminophen overdosage, dose-dependent, potentially fatal hepatic necrosis is the most serious effect. Renal tubular necrosis, hypoglycemia, coma, and thrombocytopenia may also occur. In adults, hepatotoxicity from acetaminophen is unlikely to occur with overdoses of less than 10 g ingested at one time and fatalities are unlikely to occur with overdoses of less than 15 g ingested at one time. Importantly, young children seem to be more resistant than adults to the hepatotoxic effect of an acetaminophen overdose. Despite this, the measures outlined below should be initiated in any adult or child suspected of having ingested an acetaminophen overdose.

Early symptoms following a potentially hepatotoxic overdose may include gastrointestinal irritability, nausea, vomiting, anorexia, diaphoresis and general malaise. However, the early clinical presentation of acetaminophen overdose is nonspecific and symptoms may even be lacking. A high index of suspicion for acetaminophen ingestion is required. Clinical and laboratory evidence of hepatic toxicity may not become evident until 48 to 72 hours post-ingestion.

Treatment: Chlorzoxazone: Appropriate gastrointestinal tract decontamination procedures should be undertaken. Thereafter treatment is entirely supportive. If consciousness is impaired, institute measures to protect the airway. If respiration is impaired, ventilation of the patient may be required. Blood pressure and tissue perfusion should be monitored and maintained by the usual techniques. Cholinergic drugs or analeptic drugs are of no value and should not be used.

Acetaminophen: Appropriate gastrointestinal tract decontamination procedures should be implemented. Patients’ estimates of the quantity of drug ingested are notoriously unreliable. Therefore, if an acetaminophen overdose is suspected, a serum acetaminophen assay should be obtained as early as possible, but no sooner than 4 hours following ingestion. Liver function studies should be obtained initially and repeated at 24-hour intervals.

The antidote, N-acetylcysteine, should be administered as early as possible, preferably within 16 hours of ingestion of the overdosage, but in any case, within 24 hours. Following recovery, there are no residual, structural or functional hepatic abnormalities.

Further information on the clinical course of acetaminophen overdose and its treatment with N-acetylcysteine is available from a Regional Poison Control Centre.

Dosage: Adults: 2 tablets 4 times a day. It is hazardous to exceed 8 tablets/day.

Availability And Storage: Each round, hard, flat-faced, beveled, light green tablet, scored on one side and hexabeveled and imprinted “McNEIL” on the other, contains: chlorzoxazone 250 mg and acetaminophen 300 mg. Nonmedicinal ingredients: cellulose, cornstarch, D&C Yellow No. 10, dioctyl sodium succinate, FD&C Blue No. 1 and magnesium stearate. Energy: 1.205 kJ (0.286 kcal). Sodium:
Protect from light in a tightly closed container. Under normal storage conditions at room temperature, Parafon Forte tablets are stable for 2 years from date of manufacture.

PARAFON FORTE® Johnson & Johnson• Merck Chlorzoxazone – Acetaminophen Muscle Relaxant – Analgesic

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