Tramadol (Dosage)

Tramadol is an opioid analgesic used in the treatment of moderate to severe pain, acting on specific nerve cells in the spinal cord and brain. Identifying genetic polymorphisms of genes involved in tramadol metabolism, such as the CYP2D6 gene, may allow optimal adjustment of treatment dosing.

Tramadol is a centrally acting opioid analgesic, pure non-selective agonist of μ, delta and kappa opioid receptors, with higher affinity for μ receptor. It is widely used to treat moderate to intense pain.

CONTRAINDICATIONS

Tramadol is contraindicated in the following situations:

Hypersensitivity to tramadol; acute intoxication or overdose with CNS depressants (alcohol, hypnotics, other opioid analgesics); concomitance with MAOIs or patients who have been treated during the previous 2 weeks; concomitance with linezolid; severe hepatic or renal impairment; epilepsy not adequately controlled with treatment; severe respiratory failure; during lactation if a long-term treatment is necessary (more than 2 or 3 days); for the treatment of opioid withdrawal syndrome.

CAUTIONS

Precautions should be taken when prescribing tramadol in people older than 75 years old.

In patients with moderate renal and hepatic impairment tramadol should be given using prolonged dosing intervals.

Caution should be exercised in people dependent on opioids or with a tendency to abuse.

Caution should be exercised in patients who have suffered head trauma, shock, disturbance of knowledge of unknown origin.

Beware of prescribing codeine in patients with respiratory depression, intracranial hypertension, acute porphyria, alterations of the biliary tract, epileptics or patients tending to seizures.

Caution in patients treated with medications that lower the seizure threshold or metabolized by CYP3A4 or CYP2D6 or treated with CNS depressant medications.

Tramadol has a low dependency potential, but in the long term it can induce tolerance, dependence and withdrawal syndrome.

SIDE EFFECTS

Dizziness, headache, confusion, drowsiness, nausea, vomiting, constipation, dry mouth, sweating, fatigue.

PHARMACOLOGIC INTERACTIONS

The toxicity of tramadol can be enhanced by: central depressants, alcohol, ritonavir.

There is a risk of respiratory depression if it is taken in concomitance with: other morphine derivatives, benzodiazepines, barbiturates.

The effect of tramadol is diminished by: carbamazepine, buprenorphine, nalbuphine, pentazocine.

There is a risk of seizures in concomitance with: SSRIs, serotonin/norepinephrine reuptake inhibitors, tricyclic antidepressants, antipsychotics, and other medications that reduce the seizure threshold, such as bupropion, mirtazapine, tetrahydrocannabinol.

The requirements of tramadol are increased by ondasetron (postoperative pain).

BRAND NAMES

  • Adolonta ®
  • Dolpar ®
  • Gelotradol ®
  • Tioner ®
  • Tradonal ®
  • Zytram ®

Genes analyzed

CYP2D6

Bibliography

Arafa MH, Atteia HH. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6) are associated with long term tramadol treatment-induced oxidative damage and hepatotoxicity. Toxicol Appl Pharmacol. 2018 May 1;346:37-44.

Crews KR, Monte AA, Huddart R, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy. Clin Pharmacol Ther. 2021 Oct;110(4):888-896.

Matic M, Nijenhuis M, Soree B, et al. Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2D6 and opioids (codeine, tramadol and oxycodone). Eur J Hum Genet. 2022 Oct;30(10):1105-1113.

Muradian AA, Sychev DA, Blagovestnov DA, et al. The effect of CYP2D6 and CYP2C9 gene polymorphisms on the efficacy and safety of the combination of tramadol and ketorolac used for postoperative pain management in patients after video laparoscopic cholecystectomy. Drug Metab Pers Ther. 2021 Jul 12.

Reizine N, Danahey K, Schierer E, et al. Impact of CYP2D6 Pharmacogenomic Status on Pain Control Among Opioid-Treated Oncology Patients. Oncologist. 2021 Nov;26(11):e2042-e2052.

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