Opiate analogues.

Tramadol

One capsule contains 50 mg of tramadol hydrochloride

Prolonged release capsule, hard. The capsules are dark green and marked T50SR. The 100mg capsules are white and marked T100SR The 150mg capsules are dark green and marked T150SR The 200mg capsules are yellow and marked T200SR

Treatment of moderate to severe pain.

The capsules are intended for twice daily oral administration and can be taken independently of meal times, swallowed whole with water.

As with all analgesic drugs the dosing of Zamadol SR Capsules should be adjusted depending on the severity of the pain and the individual clinical response of the patient. The dose used should be the lowest dose that provides pain relief.

Adults:

The usual initial dose is 50-100 mg twice daily, morning and evening. This dose may be titrated up to 150-200 mg twice daily according to pain severity.

If long-term pain treatment with tramadol is necessary in view of the nature and severity of the illness, then careful and regular monitoring should be carried out (if necessary with breaks in treatment) to establish whether and to what extent further treatment is necessary.

A total oral daily dose of 400 mg should not be exceeded except in special clinical circumstances.

Elderly patients:

Dosing as for adults, however it should be noted that in patients over 75 years there tends to be an increase in absolute bioavailability of tramadol and a 17% increase in the terminal elimination half-life. An adjustment of the dosage or the dose interval may be required.

Patients with renal or hepatic insufficiency:

As the elimination of tramadol may be prolonged in patients with severe renal and/or hepatic impairment, the use of Zamadol SR Capsules is not recommended. In moderate cases an adjustment of the dosage interval may be required.

Patients who have difficulty in swallowing:

Zamadol SR Capsules can be opened, carefully, so that the pellets are deposited on a spoon. The spoon and pellets should be taken into the mouth, followed by a drink of water to rinse the mouth of all pellets. The pellets must not be chewed or crushed.

Children:

Over 12 years: Dosage as for adults.

Under 12 years: Zamadol SR Capsules have not been studied in children. Therefore, safety and efficacy have not been established and the product should not be used in children.

Not recommended.

Zamadol SR Capsules should not be given to patients who have previously shown hypersensitivity to the active substance tramadol or to any of the excipients.

The product should not be administered to patients suffering from acute intoxication with hypnotics, centrally acting analgesics, opioids, psychotropic drugs or alcohol.

Tramadol should not be administered to patients who are receiving monoamine oxidase inhibitors or within 2 weeks of their withdrawal.

Contra-indicated in patients suffering from uncontrolled epilepsy.

Tramadol must not be used for narcotic withdrawal treatment.

Warnings:

Tramadol has a low dependence potential. On long-term use tolerance, psychic and physical dependence may develop. In patients with a tendency to drug abuse or dependence, treatment should be for short periods under strict medical supervision. In rare cases at therapeutic doses, tramadol has the potential to cause withdrawal symptoms.

Zamadol SR Capsules are not a suitable substitute in opioid dependent patients. The product does not suppress morphine withdrawal symptoms although it is an opioid agonist.

Convulsions have been reported at therapeutic doses and the risk may be increased at doses exceeding the usual upper daily dose limit. Patients with a history of epilepsy or those susceptible to seizures should only be treated with tramadol if there are compelling reasons. The risk of convulsions may increase in patients taking tramadol and concomitant medication that can lower the seizure threshold.

Precautions:

Zamadol SR Capsules should be used with prudence in patients who have shown previous hypersensitivity to opiates, and in patients with severe renal or hepatic impairment, head injury, decreased level of consciousness, increased intracranial pressure, or patients in shock or at risk of convulsions.

At recommended therapeutic doses Zamadol SR Capsules are unlikely to produce clinically relevant respiratory depression. Care should however be taken when administering Zamadol SR Capsules to patients with existing respiratory depression or excessive bronchial secretion and in those patients taking concomitant CNS depressant drugs.

Patients treated with monoamine oxidase inhibitors within 14 days prior to the administration of the opioid pethidine have experienced life-threatening interactions affecting the central nervous system as well as the respiratory and circulatory centres. The possibility of similar interactions occurring between monoamine oxidase inhibitors and tramadol cannot be ruled out.

Tramadol may potentiate the CNS depressant effects of other centrally acting drugs (including alcohol) when administered concomitantly with such drugs.

Tramadol may increase the potential for selective serotonin re-uptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), anti-psychotics and other seizure threshold lowering drugs to cause convulsions.

Isolated cases of serotonergic syndrome have been reported with the therapeutic use of tramadol in combination with other serotonergic agents such as selective serotonin re-uptake inhibitors (SSRIs). Serotonergic syndrome can be manifested by symptoms such as confusion, restlessness, fever, sweat, ataxia, hyperreflexia, myoclonia and diarrhoea. Withdrawal of the serotonergic agent produces a rapid improvement.

Administration of Zamadol SR Capsules together with carbamazepine results in markedly decreased serum concentrations of tramadol which may reduce analgesic effectiveness and shorten the duration of action.

Caution should be exercised during concomitant treatment with tramadol and coumarin derivatives (e.g. warfarin) due to reports of increased INR and ecchymoses in some patients.

The combination of mixed agonists/antagonists (e.g. buprenorphine, nalbuphine, pentazocine) and tramadol is not recommended because it is theoretically possible that the analgesic effect of a pure agonist is attenuated under these circumstances.

There is no interaction with food.

The most commonly reported adverse drug reactions are nausea and dizziness, both occurring in more than 10% of patients.

Immune system disorders:

Rare (>1/10,000, <1/1,000): Allergic reactions (e.g. dyspnoea, bronchospasm, wheezing, angioneurotic oedema) and anaphylaxis.

Metabolism and nutrition disorders:

Rare (>1/10,000, <1/1,000): Changes in appetite.

Psychiatric disorders:

Rare (>1/10,000, <1/1,000): psychic side-effects may occur following administration of tramadol which vary individually in intensity and nature (depending on personality and duration of medication). These include changes in mood (usually elation, occasionally dysphoria), changes in activity (usually suppression, occasionally increase) and changes in cognitive and sensorial capacity (e.g. decision behaviour, perception disorders), hallucinations, confusion, sleep disturbances and nightmares.

Prolonged administration of Zamadol SR Capsule may lead to dependence. Symptoms of withdrawal reactions, similar to those occurring during opiate withdrawal, may occur as follows: agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and gastrointestinal symptoms.

Nervous system disorders:

Very common (>1/10) dizziness.

Common (>1/100, <1/10): headache, drowsiness.

Rare (>1/10,000, <1/1,000): epileptiform convulsions occurred mainly after administration of high doses of tramadol or after concomitant treatment with drugs which can lower the seizure threshold or themselves induce cerebral convulsions.

Paraesthesia and tremor.

Very rare (<1/10,000): vertigo

Eye disorders:

Rare (>1/10,000, <1/1,000): blurred vision.

Cardiac disorders:

Uncommon (>1/1,000, <1/100): effects on cardiovascular regulation (palpitation, tachycardia, postural hypotension or cardiovascular collapse). These adverse effects may occur especially on intravenous administration and in patients who are physically stressed.

Rare (>1/10,000, <1/1,000): bradycardia, increase in blood pressure.

Vascular disorders:

Very rare (<1/10,000): flushing.

Respiratory disorders:

Worsening of asthma has also been reported, though a causal relationship has not been established.

Respiratory depression has been reported. If the recommended doses are considerably exceeded and other centrally depressant substances are administered concomitantly respiratory depression may occur.

Gastrointestinal disorders:

Very common (>1/10): vomiting, nausea.

Common (>1/100, <1/10): constipation, dry mouth.

Uncommon (>1/1,000, <1/100): retching, gastrointestinal irritation (a feeling of pressure in the stomach, bloating).

Hepato-biliary disorders:

In a few isolated cases an increase in liver enzyme values has been reported in a temporal connection with the therapeutic use of tramadol.

Skin and subcutaneous tissue disorders:

Common (>1/100, <1/10): sweating.

Uncommon (>1/1,000, <1/100): dermal reactions (e.g. pruritus, rash, urticaria).

Musculoskeletal, connective tissue and bone disorders:

Rare (>1/10,000, <1/1,000): motorial weakness.

Renal and urinary system disorders:

Rare (>1/10,000, <1/1,000): micturition disorders (difficulty in passing urine and urinary retention).

General disorders:

Common (>1/100, <1/10): fatigue.

Meda Pharmaceuticals

(POM)

18 May 2009