PARAFON Capsules are indicated

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

Adults: (12 years of age and older) 2 tablets 4 times a day. It is hazardous to exceed 8 tablets per day

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

Occupational hazards

Drowsiness can occur with the use of Parafon Forte. Patients using this drug should be cautioned about driving a car or operating potentially hazardous machinery if they become drowsy or show impaired mental or physical abilities while taking this medication

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 is 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

PARAFON may cause dizziness or drowsiness, therefore, patients should be cautious when driving or using a machine

The classic gastrointestinal irritation with NSAIDs, including ASA, does not occur with acetaminophen

Sensitivity reactions are rare and may manifest as rash or urticarial

Cross-reactivity in ASA-sensitive persons has been rarely reported. If sensitivity is suspected, discontinue use of the drug

Patients who concomitantly medicate with warfarin-type anticoagulants and regular doses of acetaminophen have occasionally been reported to have unforeseen elevations in their INR. Physicians should be cognizant of this potential interaction and monitor the INR in such patients closely while therapy is established

Gastrointestinal

Occasionally 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 this medicine 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 >1% of patients receiving chlorzoxazone or occurred in < 1% of patients but resulted in patient withdrawal from the study and were considered possibly, probably or definitely related to chlorzoxazone

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

The following adverse reports occurred with a frequency of <1% and the relationship to chlorzoxazone remains undetermined; chills, tachycardia, vasodilation, abnormal thinking, confusion, depression, emotional liability, hypotonia, insomnia, constipation, dry mouth, thirst, vomiting, cough increase, dyspnea, flu symptoms, rhinitis, sweating, increased urinary frequency, menorrhagia

To report any side effects

- The National Pharmacovigilance Center (NPC):

o Fax: +966-11-205-7662

o SFDA Call Center: 19999

o E-mail: npc.drug@sfda.gov.sa

o Website: https://ade.sfda.gov.sa

Acetaminophen: Typical Toxidrome: Significant overdoses of acetaminophen may result in potentially fatal hepatotoxicity. The physician should be mindful that there is no early presentation that is pathoneumonic for the overdose. A high degree of clinical suspicion must always be maintained

Due to the wide availability of acetaminophen, it is commonly involved in single and mixed drug overdose situations and the practitioner should have a low threshold for screening for its presence in a patient’s serum

Acute toxicity after single dose overdoses of acetaminophen can be anticipated when the overdose exceeds 150 mg/kg. Chronic alcohol abusers, cachectic individuals, and persons taking pharmacologic inducers of the hepatic P450 microsomal enzyme system may be at risk with lower exposures

There have been rare reports of chronic intoxication in persons consuming in excess of 150 mg/kg of acetaminophen daily for several days

Specific Antidote: NAC (N-acetylcysteine) administered by either the i.v. or the oral route is known to be a highly effective antidote for acetaminophen poisoning. It is not effective when administered within 8 hours of a significant overdose buy reports have indicated benefits to treatment initiated well beyond this time period. It is imperative to administer the antidote as early as possible in the time course of acute intoxication to reap the full benefits of the antidote’s protective effects

General Management

When the possibility of acetaminophen overdose exists, treatment should begin immediately and include appropriate decontamination of the gastrointestinal tract, proper supportive care, careful assessment of appropriately timed serum acetaminophen estimations evaluated against the Mattew-Rumack nomogram, timely administration of NAC as required and appropriate follow-up care. Physicians unfamiliar with the current management of acetaminophen overdose should consult with a Poison Control Centre immediately. Telephone numbers for local Poison Control Centres are available in the local phone directory.

Delays in initiation of appropriate therapy may jeopardize the patient’s chances for a full recovery

Chlorzoxazone: Typical Toxidrome: extreme weakness (voluntary muscles), CNS depression, labored breathing

Specific antidote: none

General Management: stabilize the patient (A, B, C’s), undertake appropriate gastrointestinal tract decontamination procedures, initiate supportive care, consult with a Regional Poison Control Centre regarding ongoing management, and arrange for appropriate follow-up care

Physicochemical characteristics

Molecular weight-

Chlorzoxazone: 169.57

Acetaminophen: 151.16

Mechanism of action/Effect

Chlorzoxazone

The precise mechanism of action has not been determined. Chlorzoxazone acts in the central nervous system (CNS) rather than directly on skeletal muscle. It acts primarily at the spinal cord level and at subcortical areas of the brain and preferentially depresses polysynaptic reflexes. The muscle relaxing effects may also be related to chlorzoxazone's CNS depressant

Acetaminophen

The mechanism of analgesic action has not been fully determined. Acetaminophen may act by inhibiting prostaglandin synthesis in the CNS and through a peripheral action by blocking pain-impulse generation. The peripheral action may also be due to inhibition of the synthesis of prostaglandins, or to inhibition of the synthesis or actions of other substances, which sensitize pain receptors to mechanical or chemical stimulation

Chlorzoxazone

Blood levels of chlorzoxazone can be detected in humans during the first 30 minutes after oral administration 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

Acetamiophen

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

Following oral administration 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 principle 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

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC

Gelatin
Glycerol
Talc
Colloidal anhydrous silica
Magnesium stearate
Capsule shell (size 0) (RP 87

None known

Store below 30 °C
Store in the original pack to protect from light and moisture

Pack contains 3 blisters, each Transparent PVC film / Aluminum foil blister of 10 Capsules

Not applicable