Muscol

/ Teva

Adults: 2 tablets, 3 times daily.

Relief of mild to moderate pain of acute musculoskeletal disorders.

• Hypersensitivity to the active substances (paracetamol or orphenadrine citrate) or to any of the excipients
• Glaucoma
• Prostatic hypertrophy or obstruction at the bladder neck
• Myasthenia gravis
• Oesophageal spasm and pyloric or duodenal obstruction

Orphenadrine citrate
Safety of continuous long-term therapy with orphenadrine has not been established. Therefore, if orphenadrine is prescribed for prolonged use, periodic monitoring of blood, urine and liver function is recommended.
Orphenadrine citrate should be used with caution in patients with tachycardia, cardiac decompensation, coronary insufficiency or cardiac arrhythmias, Gilbert’s syndrome and Glucose – 6 – phosphate – dehydrogenase deficiency.
Paracetamol
This medicinal product may be dangerous when used in large amounts or for long. Hepatotoxicity may occur with paracetamol even at therapeutic doses, after short treatment duration and in patients without pre-existing liver dysfunction. Hepatotoxicity may develop following as little as 10 to 15 g of paracetamol and hepatic failure is known to occur occasionally with long term use of paracetamol.
Paracetamol should be used with caution in patients with hepatic or renal dysfunction.
Caution is advised in patients with underlying sensitivity to aspirin and/or to non-steroidal anti- inflammatory drugs (NSAIDs).
Caution is advised in patients with known analgesic intolerance or known bronchial asthma as hypersensitivity reactions including bronchospasm are possible.
Severe cutaneous adverse reactions (SCARs): Paracetamol has been associated with a risk of rare but serious skin reactions. These skin reactions, known as Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), can be fatal.
Patients should be advised of the signs and symptoms and monitored closely for skin reactions. If symptoms or signs of SJS and TEN (e.g. progressive skin rash often with blisters or mucosal lesions) occur, patients should stop treatment immediately and seek medical advice.
Anyone who has experienced a serious skin reaction with paracetamol should not take the drug again and should contact their health care professional to discuss alternative pain relievers/fever reducers.
Paracetamol can cause accidental poisoning in toddlers and infants. Paracetamol-containing products should be kept well out of reach of children.
Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe illness such as severe renal impairment and sepsis, or in patients with malnutrition and other sources of glutathione deficiency (e.g. chronic alcoholism) who were treated with paracetamol at therapeutic dose for a prolonged period or a combination of paracetamol and flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, prompt discontinuation of paracetamol and close monitoring is recommended. The measurement of urinary 5-oxoproline may be useful to identify pyroglutamic acidosis as underlying cause of HAGMA in patients with multiple risk factors.
Effects on laboratory tests
Uric acid and blood glucose: Intake of paracetamol may affect the laboratory determination of uric acid by phosphotungstic acid and of blood glucose by glucose oxidase-peroxidase.
See prescribing information for full detail.

Adverse effects are mainly due to the anti-cholinergic action of orphenadrine and are usually associated with higher doses.
Orphenadrine citrate: More common reactions, The known adverse effects include; dryness of the mouth, tachycardia, palpitation, urinary hesitancy or retention, blurred vision, dilation of the pupils, increased ocular tension, weakness, nausea, headache, dizziness, restlessness, gastrointestinal disturbances, constipation and drowsiness. These effects can usually be eliminated by reducing the dose.
Paracetamol: Reports of adverse reactions are rare.
See prescribing information for full detail please .

Interactions have been reported between orphenadrine and phenothiazines and other drugs with anti-muscarinic properties.
Concomitant use with alcohol or other CNS depressants should be avoided.
Anticoagulants: Paracetamol may increase the risk of bleeding in patients taking warfarin and other antivitamin K medicines. Anticoagulant dosage may require reduction, and patients should be monitored for appropriate coagulation and bleeding complications.
Chloramphenicol: Paracetamol may increase chloramphenicol concentrations by slowing down excretion, entailing the risk of increased toxicity.
Cholestyramine: reduces the absorption of paracetamol if given within 1 hour of paracetamol. Chelating resins can decrease the intestinal absorption of paracetamol and potentially decrease its efficacy if taken simultaneously. In general, there must be an interval of more than 2 hours between taking the resin and taking paracetamol, if possible.
Drugs which affect motility: Paracetamol absorption is increased by medicines that increase gastric emptying, e.g. metoclopramide and domperidone
Paracetamol absorption is decreased by medicines that decrease gastric emptying, e.g. propantheline, antidepressants with anticholinergic properties and narcotic analgesics.
Flucloxacillin: Co-administration of flucloxacillin with paracetamol may lead to high anion gap metabolic acidosis due to pyroglutamic acidosis, particularly in patients presenting risks factors of glutathione depletion, such as sepsis, malnutrition or chronic alcoholism.
Probenecid: Paracetamol excretion may be affected and plasma concentrations altered when given probenecid.
Zidovudine: Paracetamol may competitively inhibit the hepatic glucuronidation and decrease the clearance of zidovudine. Zidovudine may also inhibit the hepatic glucuronidation of paracetamol. When used concurrently with zidovudine, an increased tendency for neutropenia may develop. Combination of Paracetamol and zidovudine should be avoided, because the toxicity of either or both medications may be potentiated.
Hepatotoxic Drugs and Liver Microsomal Enzyme Inducers: The risk of paracetamol toxicity may be increased in patients receiving other potentially hepatotoxic drugs or drugs that induce liver microsomal enzymes, such as antiepileptics (such as phenobarbital, phenytoin, carbamazepine, topiramate), alcohol, barbiturates and rifampicin. The induced metabolism results in an elevated production of the hepatotoxic oxidative metabolite of paracetamol. Hepatotoxicity will occur if this metabolite exceeds the normal glutathione binding capacity.
See prescribing information for full detail.

Pregnancy: This medicinal product is not recommended for use during pregnancy.
Breastfeeding: This medicinal product should not be taken during lactation as orphenadrine and paracetamol are excreted into breast milk.

No specific information is available on overdose with Muscol. Overdose of paracetamol can result in severe liver damage and sometimes acute renal tubular necrosis.
Symptoms and Signs: Orphenadrine overdose: Known symptoms of overdose with orphenadrine include tachycardia, excitement, confusion and delirium leading to coma. Convulsions, dilated pupils and urinary retention may occur. Paracetamol overdose: Toxic symptoms following an overdose with paracetamol include vomiting, abdominal pain, hypotension, sweating, central stimulation with exhilaration and convulsions in children, drowsiness, respiratory depression, cyanosis and coma. In adults, hepatotoxicity may occur after ingestion of a single dose of paracetamol 10 to 15g; a dose of 25g or more is potentially fatal. Symptoms during the first two days of acute poisoning by paracetamol do not reflect the potential seriousness of the intoxication. Major manifestations of liver failure such as jaundice, hypoglycaemia and metabolic acidosis may take at least three days to develop.
Treatment: Prompt treatment is essential even when there are no obvious symptoms. In cases of overdose, methods of reducing absorption of ingested medicine are important. Prompt administration of activated charcoal 50 g in 150 mL of water and 150 ml sorbitol 50% solution by mouth may reduce absorption. It is recommended that intravenous fluids such as normal saline be given concurrently. Gastric lavage is indicated if the patient is unwilling or unable to drink an activated charcoal/sorbitol mixture. If the history suggests that paracetamol 150 mg/kg body weight or 15 g total or more has been ingested, administer the following antidote: Intravenous acetylcysteine 20%: Administer acetylcysteine immediately without waiting for positive urine test or plasma level results if 8 hours or less since overdose ingestion. Initial dose 150 mg/kg over 15 minutes, followed by continuous infusion of 50 mg/kg in glucose 5% 500 ml over four hours and 100 mg/kg in glucose 5% 1 L over 16 hours. If more than eight hours have elapsed since the overdose was taken, the antidote may be less effective. Convulsions and delirium respond to relatively large doses of diazepam, preferably by mouth. Adequate hydration of the patient is important.