Paraxone 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.

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

Occupational hazards

Drowsiness can occur with the use of Paraxone. 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.

Paraxone contains sodium

Paraxone contains sodium. Each capsule of Paraxone 250 mg and 300 mg Capsules contains 0.349 mg sodium. This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-free’.

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 paracetamol 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. Paracetamol passes into breast milk but is not likely to have an adverse effect on the infant at therapeutic doses.

Paraxone 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 paracetamol.

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 paracetamol 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.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

·    Saudi Arabia

The National Pharmacovigilance Centre (NPC)

SFDA Call Center: 19999

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

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

·    Other GCC States

Please contact the relevant competent authority

Paracetamol

Typical Toxidrome: Significant overdoses of paracetamol 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 paracetamol, 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 paracetamol 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 paracetamol 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 paracetamol 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 paracetamol overdose exists, treatment should begin immediately and include appropriate decontamination of the gastrointestinal tract, proper supportive care, careful assessment of appropriately timed serum paracetamol 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 paracetamol overdose should consult with a Poison Control Centre immediately.

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

Paracetamol: 151.16

Pharmacotherapeutic group: peripherally, centrally and directly acting muscle relaxants, ATC code: M03BB03.

Mechanism of action

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.

Paracetamol

The mechanism of analgesic action has not been fully determined. Paracetamol 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 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.

Paracetamol

Paracetamol is readily absorbed from the gastro-intestinal tract with peak plasma concentrations occurring about 30 minutes to 2 hours after ingestion. It is metabolised in the liver and excreted in the urine mainly as glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half-life varies from about 1 to 4 hours. Plasma-protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations.

A minor hydroxylated metabolite which is usually produced in very small amounts by mixed-function oxidases in the liver and which is usually detoxified by conjugation with liver glutathione may accumulate following paracetamol overdosage and cause liver damage.

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

-    Sodium lauryl sulphate

-    Povidone

-    Sodium starch glycolate

-    Colloidal silicon dioxide

-    Magnesium stearate

Not applicable.

Store below 30°C.

Store in the original package.

PVC/PVDC-aluminum blisters.  

Pack sizes: 30 and/or 90 Capsules.

No special requirements for disposal.