Tramadol hydrochloride is a centrally acting synthetic opioid analgesic used for the management of moderate to moderately severe pain. It is a racemic mixture of two enantiomers, each contributing to its analgesic activity via complementary mechanisms: (+)-tramadol and its metabolite (+)-O-desmethyltramadol (M1) are μ-opioid receptor agonists, while (-)-tramadol inhibits serotonin and norepinephrine reuptake. This dual mechanism provides effective analgesia with a lower risk of respiratory depression and dependence compared to classical opioids, though these risks are still present. In India, it is a widely prescribed analgesic but is strictly regulated under the Narcotic Drugs and Psychotropic Substances (NDPS) Act.
Adult: For moderate to moderately severe pain: 50-100 mg every 4-6 hours as needed for pain relief. Maximum initial dose: 100 mg. Total daily dose should not exceed 400 mg in patients under 75 years without risk factors.
Note: Tablet can be taken with or without food. Swallow whole with a glass of water. Do not crush, break, or chew. For acute pain, take at the first sign of pain. For chronic pain, take at regular intervals as prescribed. Do not abruptly discontinue after long-term use; taper dose.
Tramadol exerts its analgesic effect through a dual mechanism: 1) Weak agonism at μ-opioid receptors, primarily mediated by its O-desmethyl (M1) metabolite which has a 200-fold higher affinity for the μ-receptor than the parent compound. 2) Inhibition of neuronal reuptake of serotonin and norepinephrine in the central nervous system, enhancing inhibitory effects on pain transmission in the spinal cord.
Pregnancy: Category C: Use only if potential benefit justifies potential risk to the fetus. Prolonged use during pregnancy can result in Neonatal Opioid Withdrawal Syndrome (NOWS), which may be life-threatening. Avoid use during labor/delivery of premature infants.
Driving: May impair mental and/or physical abilities required for driving or operating machinery. Dizziness and somnolence are common. Patients should be cautioned not to drive until they know how the medication affects them.
| Selective Serotonin Reuptake Inhibitors (SSRIs: Sertraline, Fluoxetine) | Increased risk of serotonin syndrome and seizures. | Major |
| Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs: Venlafaxine, Duloxetine) | Increased risk of serotonin syndrome and seizures. | Major |
| Tricyclic Antidepressants (TCAs: Amitriptyline) | Increased risk of serotonin syndrome, seizures, and CNS depression. | Major |
| Monoamine Oxidase Inhibitors (MAOIs: Phenelzine) | Risk of life-threatening serotonin syndrome. Contraindicated. | Contraindicated |
| Other Opioid Analgesics (Morphine, Codeine) | Additive CNS and respiratory depression. | Major |
| Benzodiazepines (Alprazolam, Clonazepam) | Profound sedation, respiratory depression, coma, death. | Major |
| CYP2D6 Inhibitors (Quinidine, Paroxetine) | Reduced formation of active M1 metabolite, potentially decreasing analgesia. | Moderate |
| CYP3A4 Inducers (Carbamazepine, Rifampicin) | Increased metabolism of tramadol, reducing its efficacy. | Moderate |
| CYP3A4 Inhibitors (Ketoconazole, Erythromycin) | Decreased metabolism, increasing tramadol levels and risk of toxicity. | Moderate |
| Alcohol | Additive CNS depression and risk of respiratory depression. | Major |
Same composition (Tramadol (50mg)), different brands: