Tramadol
Class: analgesic – opioid (with extra effect on inhibitory pain pathways)
Indications: step 2 on the WHO analgesic ladder – moderate to severe pain
Contraindications/cautions: epilepsy, drug abuse, respiratory depression; genetic polymorphism in CYP2D6 affects metabolism of tramadol; renal or hepatic impairment
Adverse reactions: common: nausea, vomiting, diarrhoea, sweating (dose related); less common: dry mouth, sedation, headache, hypertension, confusion
Metabolism/clearance: metabolised by metabolising enzyme CYP2D6 mainly in the liver to an active metabolite – individual variability due to being poor or ultra-rapid metabolisers
Interactions:
- increased clinical effect/toxicity of tramadol (due to increased blood concentrations) may occur with some CYP metabolising enzyme inhibitors (see above) e.g. bupropion, fluoxetine, paroxetine, quinine
- additive CNS effects with other CNS depressants e.g. benzodiazepines (e.g. lorazepam), phenothiazines (e.g. chlorpromazine), other opioids, alcohol
- additive risk of serotonin syndrome (potentially fatal syndrome – symptoms include sweating, diarrhoea, confusion) with other serotonergic drugs e.g. amitriptyline, carbamazepine, citalopram, fluoxetine, lithium, paroxetine
- decreases seizure threshold so may interact with anticonvulsants e.g. carbamazepine
- May prolong the INR in patients taking warfarin – monitor
| Dosing: | ||
|---|---|---|
| oral: | normal release | 50 to 100 mg 4 hourly (max. 400 mg/24 hours) |
| slow release | 100 to 200 mg twice a day | |
| subcut: | not available | |
| rectal: | not available | |
Syringe driver: give separately as compatibility as yet unknown
Mechanism of action: Tramadol is an agonist at opioid receptors resulting in inhibition of ascending pathways in the brain and spinal cord, altering the perception and response to pain. Tramadol also inhibits reuptake of noradrenaline and serotonin which may contribute to its analgesic activity. Enhances effect on descending inhibitory pathways
Peak effect: oral: normal release 0.5 to 1 hour
Duration: oral: normal release 3 to 7 hours
Notes:
- place in palliative therapy still to be established
- may be useful in patients who are constipated on codeine as it is less constipating generally
- start with low dose to minimise adverse effects
- it is not a controlled drug
- halve the starting dose in severe renal impairment