COMPOSITION: Each 2 mL ampoule contains tramadol hydrochloride 100 mg.
PHARMACOLOGICAL CLASSIFICATION: A.2.9. Other analgesics
PHARMACOLOGICAL ACTION: Tramadol hydrochloride is a centrally-acting synthetic opioid analgesic binding to specific opioid receptors. It is a non-selective, pure agonist at mu, delta and kappa opioid receptors with a higher affinity for the mu receptor. Other mechanisms, which may contribute to its analgesic effect, are inhibition of neuronal re-uptake of noradrenaline and enhancement of serotonin release.
Tramadol hydrochloride does not promote histamine release.
Pharmacokinetics: Tramadol hydrochloride is readily absorbed following oral administration. Oral bioavailability is approximately 68% after a single dose and increases to 90% at steady state. Onset of action is dose dependent but generally occurs within one hour of dosing, peaking within 2 to 3 hours. Duration of analgesia is about 6 hours. The rate or extent of absorption is not significantly affected by co-administration with food.
The bioavailability of tramadol hydrochloride after intramuscular injection or intravenous administration is the same; the mean peak serum concentration is achieved after 45 minutes. Tramadol hydrochloride is primarily metabolised in the liver (90%) with one of its metabolites, mono-O-desmethyltramadol (M1), being 2 to 4 times as potent as the parent compound. Tramadol hydrochloride has a linear pharmacokinetic profile within the therapeutic dosage range.
Tramadol hydrochloride and its metabolites are excreted mainly in the urine. The elimination half-life is 5 to 7 hours, but is prolonged in impaired hepatic and renal function.
Tramadol hydrochloride crosses the blood-brain and placental barrier. Small amounts are excreted in breast milk unchanged or as the metabolite M1.
TRAMAZAC INJECTION is indicated for the management of moderate to moderately severe pain.
CONTRA-INDICATIONS: Hypersensitivity to tramadol hydrochloride or opioids.
Acute intoxication with alcohol, hypnotics, analgesic opioids or psychotropic medicines (due to the risk of respiratory depression).
Patients taking monoamine oxidase (MAO) inhibitors or within two weeks of their discontinuation (see INTERACTIONS).
Narcotic withdrawal treatment.
Respiratory depression especially in the presence of cyanosis and excessive bronchial secretions.
Increased intracranial pressure or central nervous depression due to head injury or cerebral disease.
Pregnancy and lactation.
WARNINGS: Avoid the use of TRAMAZAC INJECTION in patients with a history of addiction, as physical dependence of the morphine-type may develop. Reinstatement of physical dependence in patients that have previously been dependent, may occur with TRAMAZAC INJECTION.
Use with caution in patients with a history of epilepsy or those susceptible to seizures, (e.g. patients taking neuroleptics and other drugs that reduce the seizure threshold).
Use with caution in patients with renal or hepatic impairment and avoid if severe.
Monoamine oxidase inhibitors (MAOIs): Because of its inhibitory effect on serotonin uptake, TRAMAZAC INJECTION should not be used concomitantly with MAOIs or within 14 days after discontinuing such treatment (see CONTRA-INDICATIONS). Central nervous system (CNS) depression-producing medications, including alcohol and anaesthetics: Caution is recommended because concurrent use may potentiate the CNS depressant effects. The duration of anaesthesia may be prolonged when TRAMAZAC INJECTION is combined with barbiturates. Carbamazepine: Serum concentrations of TRAMAZAC INJECTION are reduced by carbamazepine, resulting in diminished analgesic activity of TRAMAZAC INJECTION. Inhibitors of CYP3A4 such as ketoconazole and erythromycin may inhibit the metabolism of TRAMAZAC INJECTION. Incompatibilities:
TRAMAZAC INJECTION solution is incompatible with the following injection solutions if mixed in the same syringe: Diclofenac, indomethacin, phenylbutazone, diazepam, flunitrazepam, midazolam, and glyceryl trinitrate.
PREGNANCY AND LACTATION: Safety in pregnancy and lactation has not been established (see CONTRA-INDICATIONS).
DOSAGE AND DIRECTIONS FOR USE: The dosage should be adjusted to the intensity of pain and the individuals response to the analgesic action of TRAMAZAC INJECTION. TRAMAZAC INJECTION should not be used for the treatment of minor pain.
Adults and children over the age of 14 years: Parenteral administration:
1 ampoule (100 mg injected slowly or diluted in solution for infusion and infused).
1 ampoule (100 mg).
1 ampoule (100 mg).
Intravenous injection must be given slowly over 2 to 3 minutes.
A total daily dose of more than 400 mg per day must not be exceeded.
For postoperative pain, administer an initial bolus of 100 mg. During the 90 minutes following the initial bolus further doses of 50 mg may be given every 30 minutes, up to a total dose of 250 mg including the initial bolus. Subsequent doses should be 50 mg or 100 mg 4 to 6 hourly up to a total daily dose of 600 mg. For less severe pain administer 50 mg or 100 mg 4 to 6 hourly. Elderly: The usual doses may be used except in patients 75 years of age and over. A downward adjustment of the dose and/or prolongation of the interval between doses are recommended. Renal impairment: The elimination of TRAMAZAC INJECTION may be prolonged. The usual initial dose should be used, but for patients with creatinine clearance < 30 mL/min, the dosage interval should be increased to 12 hours. Hepatic impairment: The elimination of TRAMAZAC INJECTION may be prolonged. The usual initial dose should be used but in severe hepatic impairment, the dosage interval should be increased to 12 hours. Duration of treatment: Under no circumstances should TRAMAZAC INJECTION be given for longer than absolutely necessary. If the nature and severity of the disease require long-term pain treatment with TRAMAZAC INJECTION, evaluation should be carried out initially and at regular intervals to assess efficacy, adverse events, and the need for further treatment.
SIDE EFFECTS AND SPECIAL PRECAUTIONS: Side effects:
Cardiovascular disorders: Less frequent: Flushing, syncope, bradycardia, tachycardia, postural hypotension, cardiovascular collapse. Neurological disorders: Frequent: Fatigue, sedation, drowsiness, dizziness, headache. Less frequent: Parasthesia, amnesia, confusion, hallucinations, seizures (see WARNINGS), syncope. Gastrointestinal disorders: Frequent: Nausea, vomiting, dry mouth, dyspepsia, constipation, diarrhoea, anorexia, abdominal pain. Renal and urinary disorders: Less frequent: Urinary retention, urinary frequency. Hepato-biliary disorders: Less frequent: Increase in liver enzymes. Eye disorders: Less frequent: Blurred vision. Skin and subcutaneous tissue disorders: Frequent: Sweating (especially when IV administration is too rapid), skin rashes, pruritus. Less frequent: Vesicles, urticaria Other: Less frequent: Angioedema, bronchospasm, anaphylaxis, and anaphylactoid reactions. These reactions may occur after the first dose. Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome have been reported.
Special precautions: The administration of TRAMAZAC INJECTION concurrently with other central nervous system medicines is likely to intensify and prolong CNS effects (see INTERACTIONS). Patients should be warned not to operate machinery or drive a car while using TRAMAZAC INJECTION.
The possibility of respiratory depression cannot be excluded if the recommended dose is exceeded or other centrally depressant medicines are given concomitantly. TRAMAZAC INJECTION should not be used for the treatment of minor pain.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT: Symptoms of overdose: (See SIDE EFFECTS AND SPECIAL PRECAUTIONS)
Symptoms of overdosage are typical of opioids, and include pinpoint pupils, slow heartbeat, slow or troubled breathing, weakness, seizures, and cold, clammy skin. Treatment of overdose: Supportive measures such as maintaining the patency of the airway and maintaining cardiovascular function should be instituted. Treatment of restlessness is symptomatic and supportive.
Naloxone should be used to reverse some, but not all, symptoms caused by overdosage with TRAMAZAC INJECTION. Administration of naloxone should be done with caution because it may precipitate seizures.
Diazepam has been found to be effective in treating convulsions caused by TRAMAZAC INJECTION toxicity.
Haemodialysis is not recommended in overdose, since it removes less than 7% of the administered dose of TRAMAZAC INJECTION in a 4-hour dialysis period.
IDENTIFICATION: Clear colourless solution, free from particulate matter and fibres, filled in 2 mL clear, type I glass ampoules.
PRESENTATION: Blister packs of seven, 2 mL glass ampoules packed in outer carton either containing 2 blister packs (14 ampoules) or 40 blister packs (560 ampoules).
Paper rondo tray containing ten, 2 mL glass ampoules.
STORAGE INSTRUCTIONS: Store in a cool (below 25ºC), dry place.
KEEP OUT OF REACH OF CHILDREN.
REGISTRATION NUMBER: 39/2.9/0418
NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION: Zydus Healthcare S.A. (Pty) Ltd.
Adrina Building, 1st Floor
32-34 Klinkenberg Street
DATE OF PUBLICATION OF THE PACKAGE INSERT: 23 February 2005
New addition to this site: December 2006
Source: Pharmaceutical Industry