COMPOSITION Each 2 mL contains (2 mL ampoule): Tramadol hydrochloride 100 mg
Water for injection q.s. to 2 mL
PHARMACOLOGICAL CLASSIFICATION A 2.9 Other analgesics
PHARMACOLOGICAL ACTION Tramadol is a centrally acting synthetic opioid analgesic from the aminocyclohexanol group with binding to specific opioid receptors. Tramadol is not derived from the natural sources of opiates nor is it chemically related to opiates.
Tramadol is an opioid agonist at the p(mu) receptors. It is an inhibitor of neuronal re-uptake of noradrenaline and enhances serotonin release.
Tramadol causes significantly less respiratory and cardiac depression than morphine, pethidine and buprenorphine and possesses a much lower dependence potential. In contrast to morphine, tramadol does not promote the release of histamine.
After intravenous administration, tramadol is distributed rapidly. It crosses the blood/brain and placental barrier and is excreted in very small amounts in breast milk, unchanged or as metabolite M1. Plasma protein binding is 20%. Plasma concentrations of tramadol are consistently well correlated with its analgesic activity.
After intramuscular administration, tramadol has mean absolute bioavailability of 100%.
Tramadol is mainly metabolised in the liver (90%). Following the hepatic metabolism, tramadol hydrochloride and its metabolites are almost completely excreted via the renal route (95%). The elimination half-life is 5 to 7 hours.
The terminal half-life is likely to be prolonged in patients with impaired hepatic or renal function.
INDICATIONS Management of moderate to severe pain.
CONTRA-INDICATIONS DOLOTRAM 100 is contra-indicated in known hypersensitivity to tramadol hydrochloride or opioids. DOLOTRAM 100 should not be administered during acute intoxication with alcohol, hypnotics, centrally acting analgesics, opioids and other psychotropic agents.
It should not be given to patients with respiratory depression, especially in the presence of cyanosis and excessive bronchial secretions and to patients with increased intracranial pressure or central nervous system depression due to head injury or cerebral disease.
DOLOTRAM 100 should not be administered to patients receiving monoamine oxidase inhibitors or within two weeks of their withdrawal.
WARNINGS Tramadol is likely to intensify and prolong the CNS effects of central nervous system depressant medicines. Patients should be warned not to operate dangerous machinery or drive a vehicle.
DOLOTRAM 100 is not suitable for children under the age of 14 years. Seizures Seizures have been reported in patients receiving tramadol at dosages within the recommended dosage range. The risk of seizures is enhanced in patients exceeding the recommended dose, or in patients taking tricyclic anti-depressants or other tricyclic compounds. The risk of seizures may also be increased in patients with epilepsy, with a history of seizures or in patients with a recognised risk for seizures e.g. drug and alcohol withdrawal and intracranial infections, head trauma, metabolic disorders and naloxone treatment with tramadol overdose. Patients known to suffer from cerebral convulsions should be carefully monitored during treatment with DOLOTRAM 100. Drug abuse and dependence Although tramadol has a low dependence potential, tolerance, psychic and physical dependence of the morphine-type (µ opioid) may develop with long-term use. The drug has been associated with craving, drug-seeking behaviour and tolerance development. Cases of abuse and dependence on tramadol have been reported. DOLOTRAM 100 should not be used in opioid-dependent patients. DOLOTRAM 100 can reinitiate physical dependence in patients that have been previously dependent or chronically using other opioids. Treatment with DOLOTRAM 100 is not recommended in patients with a tendency to drug abuse, a history of drug dependence or who are chronically using other opioids. INTERACTIONS Carbamazepine increases tramadol metabolism significantly leading to doubling of dosage of tramadol. Quinidine inhibits tramadol metabolism but the clinical nature of the consequences is not known. Cimetidine does not interact with tramadol. Alcohol, CNS depressants and MAO inhibitors all dangerously potentiate the effects of tramadol.
DOLOTRAM 100 must not be combined with a MAO-inhibitor, or within 14 days of discontinuation of it, as potentiation of serotonergic and noradrenergic effect may result.
PREGNANCY AND LACTATION Safety during pregnancy and lactation has not been established.
DOSAGE AND DIRECTIONS FOR USE DOLOTRAM 100 should not be used to treat minor pain.
Unless otherwise prescribed, DOLOTRAM 100 should be administered as follows: Single dose for adults and children older than 14 years of age:
100 mg injected slowly or diluted in solution for infusion and infused.
The total daily dose should not exceed 400 mg of tramadol.
An intravenous injection must be given slowly over 2 to 3 minutes.
For post-operative 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.
The dosage should be adjusted to the intensity of the pain and the individuals response to the analgesic action. Children DOLOTRAM 100 is not recommended for children younger than 14 years. Elderly A downward adjustment of the dose and/or prolongation of the interval between doses are recommended for patients older than 75 years. Renal Impairment/Dialysis/Hepatic Impairment In patients with renal and/or hepatic impairment, the elimination of tramadol may be prolonged. It is recommended that the usual initial dosage be used, but the dosage interval should be increased to 12 hours.
Haemodialysis or haemofiltration removes tramadol very slowly and therefore postdialysis administration to maintain analgesia is not usually necessary.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS The following side-effects have been reported: Gastrointestinal system: Nausea; vomiting; dry mouth; heartburn; diarrhoea; constipation. Central Nervous System and Psychiatric: Fatigue; sedation; drowsiness; dizziness; confusion; hallucinations; seizures (see WARNINGS); headache. Other: Sweating (especially when intravenous administration is too rapid); skin rashes; blurred vision; urinary retention; difficulty in passing urine; bradycardia; tachycardia; flushing; bronchospasm; angioedema; syncope; anaphylaxis; anaphylactic reactions have been reported. These reactions may occur after the first dose.
Postural hypotension or cardiovascular collapse has been observed and the potential for Toxic Epidermal Necrolysis and Steven-Johnson Syndrome. Abuse and dependence Tolerance develops very slowly and is significantly mild; withdrawal does not develop in all cases and is not as severe as with the opioids. Special precautions DOLOTRAM 100 should be used with caution in patients with severe renal- or hepatic function impairment or in patients prone to convulsion disorders or in shock.
Rapid intravenous administration should be avoided as it may be associated with higher incidence of adverse events.
DOLOTRAM 100 should not be used for the treatment of minor pain.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT Respiratory depression and convulsions may occur.
Respiratory depression can be antagonised with a pure opiate antagonist (naloxone). Naloxone may precipitate seizures and should be used cautiously.
Convulsions and/or restlessness can be treated with symptomatic and supportive therapy (benzodiazepines/barbiturates)
Tramadol is minimally eliminated from the serum by haemodialysis or haemofiltration and therefore it is not suitable for detoxification treatment.
IDENTIFICATION Clear colourless solution in 2 mL clear glass ampoule.
PRESENTATION 2 mL clear glass ampoules. 5 ampoules per carton
STORAGE INSTRUCTIONS Store in a cool (below 25°C), dry place.
KEEP OUT OF REACH OF CHILDREN.
REGISTRATION NUMBER 36/2.9/0338
NAME AND BUSINESS ADDRESS OF APPLICANT Pharmaplan (Pty) Ltd
DATE OF PUBLICATION OF THIS PACKAGE INSERT 8 October 2004
AMENDED 25 JANUARY 2005
New addition to this site: May 2014
Source: Pharmaceutical Industry