Oral Painful muscle spasm associated with musculoskeletal conditions
Adult: Available preparation:
Orphenadrine 35 mg and paracetamol 450 mg tab
2 tabs tid. Available preparations may vary among countries (refer to country-specific recommendations). Elderly: Dose reduction may be required.
Administration
May be taken with or without food. May be taken w/ meals if GI discomfort occurs.
Contraindications
Hypersensitivity to orphenadrine or paracetamol. Glaucoma, bladder neck obstruction or prostatic hypertrophy, oesophageal spasm, duodenal or pyloric obstruction, myasthenia gravis.
Special Precautions
Patient with cardiac decompensation, tachycardia, coronary insufficiency, cardiac arrhythmias; history of drug abuse or acute alcoholism, alcoholic liver disease, glucose-6-phosphate dehydrogenase (G6PD) deficiency. Renal and hepatic impairment. Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Hypersensitivity, anaphylactic reactions, CNS depression, hepatotoxicity. Blood and lymphatic system disorders: Haematological reactions. Cardiac disorders: Tachycardia, palpitation. Eye disorders: Blurred vision, pupil dilation, increased ocular tension. Gastrointestinal disorders: Dry mouth, nausea, constipation, dyspepsia. General disorders and administration site conditions: Weakness. Nervous system disorders: Dizziness, drowsiness, headache. Renal and urinary disorders: Urinary retention. Potentially Fatal: Rarely, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalised exanthematous pustulosis.
Patient Counseling Information
This drug may cause CNS depression, if affected, do not drive or operate machinery.
Monitoring Parameters
If for prolonged use, monitor urine, CBC, LFTs, and renal function.
Overdosage
Symptoms: Orphenadrine: Confusion, excitement, delirium leading to coma; tachycardia, convulsion, urinary retention, dilated pupils. Paracetamol: Abdominal pain, vomiting, sweating, drowsiness, hypotension, respiratory depression, cyanosis, coma; hepatic failure (e.g. metabolic acidosis, hypoglycaemia, jaundice). Management: Administer activated charcoal (50g in 150 mL of water and 150 mL sorbitol 50% solution) to reduce absorption; administer IV fluids (e.g. normal saline) concomitantly. Perform gastric lavage for patients unwilling or intolerable to take activated charcoal or sorbitol mixture. If ≤8 hours since ingestion, immediately administer IV acetylcysteine (even without positive urine test or serum level results). Administer diazepam for convulsion and delirium.
Drug Interactions
Orphenadrine: May increase the antimuscarinic effects of amantadine, certain antihistamines, phenothiazines, TCAs, butyrophenones.
Paracetamol: May enhance the effects of anticoagulants (prolonged use). Increased absorption with drugs that increase gastric emptying (e.g. metoclopramide). Decreased absorption with drugs that decrease gastric emptying (e.g. antidepressants with anticholinergic properties, propantheline, narcotic analgesics). May increase the plasma concentration of chloramphenicol. May increase the risk of toxicity with enzyme-inducing drugs (e.g. anticonvulsants).
Food Interaction
Orphenadrine: Alcohol may enhance the CNS depressant effect of orphenadrine; avoid concurrent use.
Paracetamol: May increase the risk of toxicity with alcohol.
Action
Description: Orphenadrine, a tertiary amine antimuscarinic, is an indirect skeletal muscle relaxant that is believed to work by central atropine-like effects. Additionally, it has weak antihistaminic and local anaesthetic properties.
Paracetamol, is a para-aminophenol derivative that has analgesic, antipyretic and weak anti-inflammatory effects. Although not fully explained it is thought to produce its analgesic effect by the activation of the descending serotonergic inhibitory pathways in the CNS. Additionally, it exerts its antipyretic effect by inhibiting the hypothalamic heat-regulating centre.
Synonym: Paracetamol: acetaminophen. Onset: Orphenadrine: 2-4 hours.
Paracetamol: <1 hour. Duration: Orphenadrine: 4-6 hours.
Paracetamol: Analgesia: 4-6 hours. Pharmacokinetics: Absorption: Orphenadrine: Readily absorbed from the gastrointestinal tract.
Paracetamol: Readily absorbed from the gastrointestinal tract. Time to peak plasma concentration: Approx 10-60 minutes. Distribution: Orphenadrine: Plasma protein binding: 20%.
Paracetamol: Distributed into most body tissues. Crosses the placenta and enters breast milk. Plasma protein binding: 10-25%. Metabolism: Orphenadrine: Almost completely metabolised in the liver into approx 8 metabolites.
Paracetamol: Undergoes first-pass metabolism. Mainly metabolised in the liver into sulfate and glucuronide conjugates; small amount is metabolised by CYP2E1 into N-acetyl-p-benzoquinone imine (NAPQI), a highly reactive intermediate, which is rapidly conjugated with glutathione and inactivated into nontoxic cysteine and mercapturic acid conjugates. Excretion: Orphenadrine: Mainly via urine (8% as unchanged drug). Elimination half-life: 14-16 hours.
Paracetamol: Via urine (<5% as unchanged drug; 60-80% as glucuronide metabolites; 20-30% as sulfate metabolites; approx 8% as cysteine and mercapturic acid metabolites). Elimination half-life: Approx 1-3 hours.
Chemical Structure
Orphenadrine Source: National Center for Biotechnology Information. PubChem Database. Orphenadrine, CID=4601, https://pubchem.ncbi.nlm.nih.gov/compound/Orphenadrine (accessed on Jan. 22, 2020)
Paracetamol Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 1983, Acetaminophen. https://pubchem.ncbi.nlm.nih.gov/compound/Acetaminophen. Accessed Apr. 27, 2022.
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