Drug Class Description

Generic Name

Drug Description

Presentation

Indications

Adult Dosage

Route of Administration Oral.

The dose should be adjusted to the severity of the pain and the individual clinical response of the patient. For doses not realisable / practicable with this medicinal product, other strengths of this medicinal product are available.

Unless otherwise prescribed, Zeridame SR Prolonged Release Tablets should be given as follows: Adults and adolescents older than 12 years: The usual initial dose is 100mg, twice daily, in the morning and evening. Dependent upon the needs of the patient, subsequent doses may be administered earlier than 12 hours, but must not be administered earlier than 8 hours after the previous dose.

Under no circumstances should more than two doses be taken in any one 24 hour period. If the painkilling is insufficient, the dose may be increased to: 150mg, twice daily or 200mg, twice daily. Zeridame SR Prolonged Release Tablets should be swallowed completely, without breaking or chewing, independent of meals, with sufficient liquid.

The smallest effective analgesic dose should always be used. Daily doses of 400 mg of active substance must not be exceeded, unless exceptional medical reasons require so. Under no circumstances should Zeridame SR be used for longer than absolutely necessary. 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.

Renal impairment, dialysis and hepatic impairment In patients with serious renal or hepatic impairment the use of Zeridame SR is not recommended. In moderate cases, an adjustment of the dosage interval may be considered.

Child Dosage

Elderly Dosage

Contra Indications

Zeridame SR Prolonged Release Tablets must not be used in: - hypersensitivity to tramadol hydrochloride, or to any of the excipients in the medicinal product, - in acute intoxication with alcohol, hypnotics, analgesics, opioids or psychotropic drugs. in patients receiving MAO – inhibitors, or within 2 weeks of their withdrawal. - in patients with epilepsy not adequately controlled by treatment Zeridame SR Prolonged Release Tablets should not be used for opioid withdrawal treatment.

Special Precautions

Zeridame SR should only be used following a strict benefit – risk evaluation and appropriate precautionary measures in the following cases: in patients dependent on opioids, patients suffering head injuries, shock, decreased level of consciousness of unknown origin, disturbances of the respiratory centre or function, or increased intracranial pressure, patients with moderate to severe impaired liver or kidney function.

Zeridame SR should not be used in combination with alcohol. In patients sensitive for opioids the medicine should be used cautiously. Convulsions have been reported at therapeutic doses and the risk may be increased at doses exceeding the usual upper daily dose limit (400 mg). The risk on convulsions may increase in patients taking tramadol and concomitant medication that can lower the seizure threshold. (See Interaction). Patients with a history of epilepsy or those susceptible to seizures should only be treated with tramadol if there are compelling reasons.

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

Interactions

Tramadol / MAO – inhibitors

Zeridame SR should not be combined with MAOinhibitors. Life threatening interactions affecting the central nervous system as well as respiratory and cardiovascular function have been observed in patients who have been treated with MAO inhibitors within 14 days prior to the administration of the opioid pethidine. The same interactions with Zeridame SR as with MAO inhibitors cannot be ruled out.

Tramadol / Other centrally acting active substances

In concomitant use of Zeridame SR and other centrally acting drugs, including alcohol, a potentiation of CNS effects should be taken into consideration.

Tramadol / Enzyme inhibitor / inducer

The results of pharmacokinetic research, so far, showed that no interactions need to be expected in concomitant or prior use of cimetidine (enzyme inhibitor).

The concomitant or prior use of carbamazepine (enzyme inducer) may reduce the analgesic effectiveness and shorten the duration of the action.

Tramadol / Mixed opioid agonists / antagonists

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.

Tramadol / Seizure threshold lowering drugs

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

Tramadol / Serotonergic agents

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, sweating, ataxia, hyperreflexia, myoclonia and diarrhoea. Withdrawal of the serotonergic agent produces a rapid improvement. It depends on the nature and severity of symptoms whether medicinal treatment is to be considered.

Tramadol / Coumarin derivatives

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.

Tramadol / CYP3A4 Inhibitors

Other medicinal products with a known inhibiting effect on CYP3A4, such as ketoconazole and erythromycin, could inhibit the metabolism of tramadol (N-demethylation) and probably also the metabolism of the active O-demethyl-metabolite. The clinical relevancy of this interaction has not been investigated.

Tramadol / Ondansetron

In a limited number of studies the pre – or postoperative application of the antiemetic 5 – HT₃ antagonist ondansetron increased the requirement of tramadol in patients with postoperative pain.

Adverse Reactions

The most commonly reported adverse drug reactions are nausea and dizziness, both occurring in > 1 / 10 of patients, very common.

Cardiovascular disorders:

Uncommon (> 1 / 1000 to 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 / 10000 to < 1 / 1000): bradycardia, increase in blood pressure.

Nervous system disorders:

Very common (> 1 / 10): dizziness

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

Rare (>1 / 10000 to < 1 / 1000): changes in appetite, paraesthesia, tremor, respiratory depression, epileptiform convulsions, involuntary muscle contractions, and syncope.

If the recommended doses are considerably exceeded and other centrally depressant substances are administered concomitantly (see section 4.5) respiratory depression may occur.

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.

Psychiatric disorders:

Rare (> 1 / 10000 to < 1 / 1000): hallucinations, confusion, anxiety, sleep distubances and nightmares. Psychic side-effects may 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).

Dependence, abuse and addiction may occur.

Eye disorders:

Rare (> 1 / 10000 to < 1 / 1000): blurred vision

Respiratory disorders:

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

Gastrointestinal disorders:

Very common (> 1 / 10): nausea

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

Uncommon (> 1 / 1000 to < 1 / 100): Retching, gastrointestinal irritation (a feeling of pressure in the stomach, bloating).

Skin and subcutaneous tissue disorders:

Common (> 1 / 100 to < 1 / 10): sweating

Uncommon (> 1 / 1000 to < 1 / 100): dermal reactions (e.g. pruritus, rash, urticaria)

Musculoskeletal disorders:

Rare (> 1 / 10000 to < 1 / 1000): motorial weakness

Hepato-biliary disorders:

Very rare (< 1 / 10000) an increase in liver enzyme values has been reported after use of tramadol.

Renal and urinary system disorders:

Rare (> 1 / 10000 to < 1 / 1000): micturition disorders (difficulty in passing urine and urinary retention).

Immune system disorders:

Rare (> 1 / 10000 to < 1 / 1000): Allergic reactions (e.g. dyspnoea, bronchospasm, wheezing, angioneurotic oedema) and anaphylaxis;

General disorders:

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

Physical Dependence

Dependence, abuse, addiction, and withdrawal reactions may occur. Symptoms which occur on withdrawal, identical to withdrawal symptoms in opioids, may be: agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and gastro intestinal symptoms. Very rare (< 1 / 10000) atypical withdrawal symptoms have been reported: panic attack, severe anxiety, hallucinations, paraesthesia, tinnitus, and other unusual central nervous system symptoms.

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