ACUPAN tablets
White, round, biconvex, film-coated tablets (7 mm diameter) engraved APN on one face. Each tablet contains nefopam hydrochloride 30 mg. The tablet formulation is colour-free, preservative-free, sugar-free, and does not contain gluten or lactose.
ACUPAN injection
Each clear glass ampoule contains nefopam hydrochloride 20 mg in phosphate- buffered Water for Injections BP 1 ml. The injection formulation is colour-free, preservative-free, sugar-free, and does not contain gluten or lactose.
ACUPAN is a centrally acting analgesic with a rapid onset of action. The main site of action appears to be in the central nervous system both at the brain and spinal levels.
In vitro
experiments have shown nefopam to inhibit the re-uptake of various catecholamines (including noradrenaline, serotonin and dopamine). It is possible that the mechanism of action of nefopam is at least in part by altering the levels of these neuromodulators in the brain and at the spinal level. Nefopam has been shown to have sympathomimetic and anticholinergic actions.
ACUPAN is totally distinct from the other centrally acting analgesics such as morphine, codeine, pentazocine and propoxyphene. Unlike the narcotic agents, ACUPAN has been shown not to cause respiratory depression. There is no evidence from pre-clinical research of habituation occurring with ACUPAN.
The absorption of ACUPAN after oral administration or intramuscular injection is rapid with peak concentrations being reached in 11/2 to 2 hours. The elimination from plasma occurs with a mean half life of 6 hours and 4 hours respectively. The medicine undergoes extensive metabolism by the liver and both unchanged medicine and metabolites are excreted principally in the urine, with approximately 6% in the faeces. Most of the dose is eliminated within 24 hours. A moderate to severe impairment of renal or hepatic function may reduce the elimination rate constant and cause some accumulation of ACUPAN or its metabolites.
ACUPAN is indicated for the relief of acute pain, including post-operative, dental, musculo-skeletal and acute traumatic pain.
ACUPAN tablets
Dosage may range from 1 to 3 tablets three times daily depending on response. The recommended starting dosage is 2 tablets three times daily.
ACUPAN injection
20 mg (1 ml) intramuscularly repeated if necessary every six hours (see instructions for administration). Onset of effect after intramuscular injection is within 15 to 20 minutes and peak effect is reached one to one-and-a-half hours after administration.
ACUPAN is not recommended for children under the age of 12 years.
Elderly patients may require reduced dosage due to slower metabolism. It is strongly recommended that the starting dose does not exceed one tablet three times daily as the elderly appear more susceptible to, in particular, the CNS side effects of nefopam and some cases of hallucination and confusion have been reported in this age group.
ACUPAN Injection should always be given with the patient lying down and after injection the patient should remain lying down for 15 to 20 minutes. The patient should then get up slowly. Treatment started with ACUPAN injection may be continued with ACUPAN tablets. 60 mg ACUPAN (two tablets) is approximately bioequivalent to 20 mg (one ampoule) given by injection.
ACUPAN is contraindicated in patients with a history of convulsive disorders and should not be given to patients taking monoamine oxidase (MAO) inhibitors. ACUPAN should not be used in the treatment of myocardial infarction. This advice is based on the lack of clinical experience for this indication.
Hepatic and renal insufficiency may interfere with the metabolism and excretion of nefopam. ACUPAN should be used with caution in patients with glaucoma and with or at risk of urinary retention. Caution should be exercised when nefopam is administered concurrently with tricyclic antidepressants. The side effects of ACUPAN may be additive to those of other agents with anticholinergic or sympathomimetic activity. Nefopam may cause adverse sympathomimetic effects including tachycardia and aggravation or precipitation of angina. Caution should be exercised in patients with a history of ischaemic heart disease.
Use in Pregnancy
ACUPAN is not recommended for pregnant women or those likely to become pregnant unless the expected benefit to the mother outweighs any potential risk to the foetus. There has been little human usage and no evidence of safety during pregnancy can be assumed from preclinical animal studies.
Use in Lactation
Evidence suggests that nefopam is excreted in human milk. A decision should be made whether to discontinue nursing or discontinue the medication, taking into account the potential for adverse effects for the foetus and the importance of treatment to the mother.
More common reactions Nausea, nervousness, dry mouth, lightheadedness and urinary retention may occur. Less common reactions Vomiting, blurred vision, drowsiness, sweating, insomnia, headache, confusion, hallucinations, tachycardia and aggravation of angina have been reported. Rarely a temporary harmless pink discolouration of the urine has occurred. Hypersensitivity Hypersensitivity reactions including erythema multiforme have been reported.
The side effects of ACUPAN may be additive to those of other agents with anticholinergic or sympathomimetic activity. ACUPAN should be used with caution in patients on tricyclic anti-depressants and is contraindicated in patients on MAO inhibitors.
Nefopam toxicity is manifested by neurological symptoms (convulsions, hallucinations, agitation) and cardiovascular response (tachycardia with hyperdynamic circulation).
Supportive treatment is suggested including gastric lavage, forced emesis and diuresis. Oral administration of activated charcoal may help prevent absorption. Convulsions and hallucinations may be controlled (eg with diazepam iv or pr). Beta-adrenergic blockers may be of use in controlling the cardiovascular complications.
Storage conditions Dilution of the injection
Store below 25degC.
ACUPAN injection should not be mixed with alkaline solutions.
Prescription Medicine
ACUPAN tablets blister foil packs of 90 tablets ACUPAN injection packs of 5 clear glass 1ml ampoules
Nil.
iNova Pharmaceuticals (New Zealand) Limited C/o Simpson Grierson 88 Shortland Street Auckland Distributed by: Douglas Pharmaceuticals Limited, Auckland Telephone: (09) 835 0660 Facsimile: (09) 835 0685
3 September 2007