Paracetamol/ Orphenadrine Citrate

Registered South African indications:

• Muscle spasm
• Pain
• Fever

This product contains paracetamol which may be fatal in overdose. In the event of overdosage or suspected overdose and notwithstanding the fact that the person may be asymptomatic, the nearest doctor, hospital or poison centre must be contacted immediately.

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Severe liver function impairment
• Prostatic enlargement
• Achalasia
• Bladder neck obstruction
• Glaucoma
• Myasthenia gravis
• Peptic ulcer or stenosing and pyloric or duodenal obstruction
• Porphyria

Cautions

Caution in the following patient groups

• Pregnancy
• Breastfeeding
• Renal impairment
• Mild to moderate hepatic impairment
• Fertility
• Cardiac disease
• Arrhythmias
• Tachycardia

Excess dosages

• Dosages in excess of those recommended may cause severe liver damage

Liver or kidney disease

• Patients suffering from liver or kidney disease should take paracetamol/ orphenadrine citrate under medical supervision

Other central nervous system depression producing medication or anticholinergics

• Caution is recommended in patients on other central nervous system depression producing medication as well as patients on anticholinergics or medication with anticholinergic properties

Prolonged use

• Do not use continuously for more than 10 days without consulting your doctor

Severe cutaneous adverse reactions (SCARs)

• Severe cutaneous adverse reactions (SCARs) such as toxic epidermal necrolysis (TEN), Steven-Johnson syndrome (SJS), acute generalized exanthematous pustulosis (AGEP), eosinophilia and systemic (DRESS)/Drug-induced hypersensitivity syndrome (DIHS) and fixed drug eruptions (FDE) have been reported in patients treated with paracetamol containing medicines
• If a patient develops SCAR, treatment with paracetamol/ orphenadrine citrate must immediately be discontinued and appropriate treatment instituted

Effects on ability to drive and use machines

• This medicine may lead to drowsiness and impaired concentration that may be aggravated by the simultaneous intake of alcohol or other central nervous system depressants
• Patients should be advised, particularly at the initiation of therapy, against taking charge of vehicles or machinery or performing potentially hazardous tasks where loss of concentration could lead to accidents

Forms avail. in SA and covered in this monograph: tab

Muscle spasm - voluntary muscle
Fever
Pain - mild to moderate

Paracetamol/ Orphenadrine
450/35 (mg)

• Oral (tab): 2 tab, 6-8hrly

Not established for use in children

Recommendations for this combination product as per highest risk category when comparing individual active ingredients

Pregnancy

• Caution
• Safety in pregnancy has not been established

Breastfeeding

• Caution
• Safety in breastfeeding has not been established

Fertility

• Safety in fertility has not been established

Renal Impairment

• Caution; dose adjustment recommended (Paracetamol)
  No dose adjustment recommendations are available for this combination product
  Refer to the single agent monograph for Paracetamol

Hepatic Impairment

• Mild to moderate: Caution; no dose adjustment recommended
  Patients suffering from liver disease should take paracetamol/ orphenadrine citrate under medical supervision
• Severe: Contraindicated

Elderly

• Caution; no dose adjustment recommended (Orphenadrine)
  Refer to the single agent monograph for Orphenadrine

Porphyria Information

South African recommendations

• Contraindicated

Recommendations in other jurisdictions

• Porphyrinogenic (P)

Drugs in Sport

• Permitted - No warnings

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Paracetamol
Respiratory Disorders

• Bronchospasm

Hepatobiliary Disorders

• Hepatic dysfunction

Immune, Blood and Lymphatic System Disorders

• Anaphylaxis
• Cutaneous hypersensitivity reactions
• Angiodema
• Stevens Johnson syndrome
• Thrombocytopenia  
• Agranulocytosis
• Methaemoglobinaemia

Gastrointestinal Disorders

• Acute pancreatitis

Skin and Subcutaneous Tissue Disorders

• Toxic Epidermal Necrolysis
• Steven-Johnson syndrome
• Acute generalised exanthematous pustulosis
• Fixed drug eruption

Orphenadrine
Central Nervous System Disorders

• Dizziness
• Sedation
• Confusion
• Nervousness
• Hallucinations
• Convulsions
• Insomnia
• Euphoria
• Memory disturbances
• Co-ordination disturbances
• Restlessness

Cardiovascular Disorders

• Tachycardia

Gastrointestinal Disorders

• Dry mouth
• Gastrointestinal disturbances
• Nausea
• Constipation

Genitourinary Disorders

• Urinary retention

Immune System Disorder

• Hypersensitivity reaction

Sensory Disorders

• Accommodation disorders

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Paracetamol

• Metoclopramide
• Domperidone
• Colestyramine
• Oral anticoagulants
• Chloramphenicol
• Alcohol

Orphenadrine

• Antimuscarinic agents

None routine

Paracetamol
Paracetamol increases the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin synthesis. It does not inhibit cyclooxygenase in peripheral tissues and, thus, has no peripheral anti-inflammatory affects.

Orphenadrine
Orphenadrine citrate is a centrally acting anticholinergic. It relaxes skeletal muscle spasms without affecting normal muscle tone.

COMBINATIONS PREPARATIONS

Paracetamol/ Orphenadrine

Tablet 450mg/35mg

• Betaflex NC (Adcock)
• Besemax (Adcock)
• Besenol Nc (Adcock)
• Norflex Co (iNova) originator
• Uniflex (Adcock)