Oral
Moderate to severe pain
Adult: As conventional tab/cap/orodispersible or dispersible tab: 50-100 mg 4-6 hourly. Max: 400 mg daily. As modified release (12-hourly) cap: Initially, 50-100 mg bid, may be titrated to 150 mg or 200 mg bid if necessary. Max: 400 mg daily. As modified release (24-hourly) tab/cap: Initially, 100 mg or 150 mg once daily. Max: 300 mg or 400 mg daily. Use the lowest effective dose for the shortest possible treatment duration. Adjust dose based on the severity of pain and individual sensitivity. Dosage recommendations may vary among countries and individual product (refer to detailed product guideline).
Child: ≥12 years Same as adult dose.
Elderly: >75 years Dosage interval may be prolonged according to individual requirements. Treatment recommendations may vary among countries and individual products (refer to detailed product guideline).
Renal impairment:
CrCl (ml/min) | Dosage Recommendation |
<10 | As conventional tab/cap: Not recommended. |
<30 | As conventional tab/cap: Increase dosage intervals to 12 hourly. Max: 200 mg daily. |
Parenteral
Moderate to severe pain
Adult: 50-100 mg 4-6 hourly via slow IV over 2-3 minutes, IM, or SC inj. Max: 600 mg daily.
Child: ≥12 years Same as adult dose.
Elderly: >75 years Dosage interval may be prolonged according to individual requirements.
Renal impairment:
CrCl (ml/min) | Dosage Recommendation |
<10 | Not recommended. |
<30 | Increase dosage intervals to 12 hourly. |
Incompatibility: IV/IM/SC: May form precipitates when mixed in the same syringe with diazepam, diclofenac Na, flunitrazepam, glyceryl trinitrate, indometacin, midazolam, piroxicam, and phenylbutazone.
Parenteral
Postoperative pain
Adult: Initially, 100 mg via slow IV, IM, or SC inj, followed by 50 mg every 10-20 minutes up to a total of 250 mg (including the initial dose) in the 1st hour. Subsequent doses of 50 mg or 100 mg 4-6 hourly may be given. Max: 600 mg daily.
Child: ≥12 years Same as adult dose.
Elderly: >75 years Dosage interval may be prolonged according to individual requirements.
Renal impairment:
CrCl (ml/min) | Dosage Recommendation |
<10 | Not recommended. |
<30 | Increase dosage intervals to 12 hourly. |
Incompatibility: IV/IM/SC: May form precipitates when mixed in the same syringe with diazepam, diclofenac Na, flunitrazepam, glyceryl trinitrate, indometacin, midazolam, piroxicam, and phenylbutazone.
Special Populations: Patient taking benzodiazepine: Use the lowest effective dose for the shortest possible duration. Pharmacogenomics: Tramadol is metabolised in the liver by the CY2D6 isoenzyme to form the active metabolite, O-desmethyltramadol (M1), which has a significantly higher affinity for opioid receptors. CYP2D6 is a highly polymorphic gene which may be associated with the clinical effect and safety of tramadol. Genetic testing may be considered prior to therapy. According to studies, CYP2D6 ultrarapid metabolisers have 1.1 to 5.9-fold higher M1 concentrations than normal metabolisers. An approximate of 2-4-fold higher nonresponse rate to tramadol were reported among CYP2D6 poor metabolisers than normal metabolisers or intermediate metabolisers. Variations in CYP2D6 polymorphism occur at different frequencies among subpopulations of different ethnic or racial origin. Some individuals may be ultrarapid metabolisers of CYP2D6. The prevalence of CYP2D6 ultrarapid metabolisers varies widely and has been estimated to be 29% in African/Ethiopian, 3.4-6.5% in African American, 1.2-2% in Asian, 3.6-6.5% in Caucasian, 6% in Greek, 1.9% in Hungarian, and 1-2% in Northern European populations. Meanwhile, up to 7% of the Caucasian population has a deficiency or is completely lacking functional CYP2D6 activity. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline as of December 2020: CYP2D6 ultrarapid metabolisers Patients who have increased formation of the active metabolite, O-desmethyltramadol, resulting in increased risk of toxicity. CPIC recommends avoiding the use of tramadol due to the potential for toxicity. If opioid use is needed, may consider a non-codeine opioid as an alternative. CYP2D6 intermediate metabolisers Patients who have decreased O-desmethyltramadol formation. No dose adjustments needed, however, if there is no response and opioid use is warranted, it is recommended to consider the use of a non-codeine opioid. CYP2D6 poor metabolisers Patients who have greatly reduced O-desmethyltramadol formation resulting in diminished therapeutic effect. CPIC recommends avoiding tramadol use due to the possibility of diminished analgesic effect. If opioid use is needed, may consider a non-codeine opioid. The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group (DPWG) Guideline as of November 2018: CYP2D6 ultrarapid metabolisers Patients with increased conversion of tramadol into the active metabolite which may result in a greater risk of potentially life-threatening adverse effects. DPWG recommends choosing an alternative agent that is not metabolised by CYP2D6 (e.g. morphine). If an alternative is not possible, may use 40% of the usual dose and advise the patient to report adverse effects (e.g. drowsiness, confusion, respiratory depression). CYP2D6 intermediate metabolisers Patients with reduced conversion of tramadol into the active metabolite which may result in reduced analgesic effect. DPWG recommends being vigilant for the reduced effect. In case of inadequate response, a dose increase may be considered and if there is no response, an alternative agent that is not metabolised by CYP2D6 (e.g. morphine) may be given. If no alternative agent is selected, advise patient to report for inadequate analgesic effect. CYP2D6 poor metabolisers Patients with reduced conversion of tramadol into the active metabolite which may result in reduced analgesic effect. DPWG recommends being vigilant for the reduced effect. In case of inadequate response, a dose increase may be considered and if there is no response, an alternative agent that is not metabolised by CYP2D6 (e.g. morphine) may be given. If no alternative agent is selected, advise patient to report for inadequate analgesic effect. Additionally, the annotation of FDA label for tramadol recommends that CYP2D6 ultrarapid metabolisers must not use tramadol due to the risk of life-threatening respiratory depression even at labelled dosage regimens. Treatment recommendations may vary among local treatment guidelines. Refer to country-specific guidelines.