Tramadol

Tramadol is a synthetic pharmaceutical that belongs to the opioid analgesic group of drugs. Tramadol is approved for the treatment of moderately severe to severe pain. In the WHO pain management schedule, tramadol is therefore classified as a weak-acting opioid, like tilidine, and is recommended for moderate to severe pain (level II of III). Tramadol is considered a safe opioid with a favorable side effect profile and low abuse and dependence potential.

Tramadol is more than 90% absorbed after oral administration and has an absolute bioavailability of about 70 percent independent of simultaneous food intake. The active substance is subject to only slight first-pass metabolism and is bound to serum proteins to about 20 percent. Tramadol crosses the blood-brain barrier and the placenta. The elimination half-life is approximately 6 hours regardless of application.

Tramadol is metabolized by N- and O-demethylation and by conjugation of the O-demethylation products with glucuronic acid. The O-demethyltramadol is a pharmacologically active metabolite that exceeds the potency of the parent compound by a factor of 2-4. Inhibition of CYP3A4 and/or CYP2D6 may affect the plasma concentration of tramadol and its active metabolite. Tramadol is predominantly eliminated renally. In renal dysfunction, a slight prolongation of half-lives must be expected.

The active substance can be administered perorally (capsule and drops), intravenously, intramuscularly, rectally as a suppository (100 mg) or subcutaneously.

Chronic use of tramadol should be avoided. Tramadol crosses the placenta. After birth, withdrawal symptoms in the newborn are possible. Tramadol should not be used during breastfeeding.

Tramadol must be dosed individually. The dose depends on the severity of the pain and the individual sensitivity of the patient. Dosage for moderately severe pain: adults and adolescents aged 12 years and over as a single dose: 20 drops (equivalent to 50 mg Tramadol HCl). If the pain is not relieved within 30 to 60 minutes, 20 drops are taken again. If a higher requirement is to be expected in the case of severe pain, 40 drops (equivalent to 100 mg tramadol HCl) are taken as a single dose. (equivalent to 100 mg Tramadol HCl) is taken as a single dose. The effect lasts 4-8 hours depending on the pain. Daily doses of 160 tr. (equivalent to 400 mg tramadol HCl) should not be exceeded (source: Red List).

The most commonly reported adverse reactions (≥10 percent of patients) are nausea and dizziness.

The following side effects may also occur frequently (≥ 1/100, <1/10): headache, drowsiness, constipation; dry mouth, vomiting, dry mouth, sweating, fatigue.

Rare: hypoglycemia (Juba KM et al 2020); serotonin syndrome and seizures.

Dermatologic UAWs are rare and limited to single-case reports; systemic contact dermatitis has been described following oral tramadol application. The initial contact sensitization was due to buprenorphine. (Kaae J et al. 2012)

Tramadol must not be used concomitantly with MAO inhibitors.

concomitant use of centrally depressant substances

concomitant administration of carbamazepine: reduction of serum concentration of tramadol

coumarin derivatives (e.g. warfarin) increased INR values; ecchymoses are possible

Serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, neuroleptics, and other seizure-lowering drugs (such as bupropion, mirtazapine, and tetrahydrocannabinol): possible precipitation of seizures

Serotoninergic drugs, MAO inhibitors, tricyclic antidepressants, mirtazapine: risk of serotonin syndrome

CYP3A4 inhibitors (e.g. ketoconazole, erythromycin, etc.): possible inhibition of tramadol metabolism.

5-HT3 antagonists(ondansetron): increased tramadol requirement in postoperative pain in clinical studies.

Sedatives: risk of sedation, respiratory depression, coma and death due to an additive CNS depressant effect is increased

Known hypersensitivity to tramadol

concomitant use or use up to 14 days ago of MAO inhibitors

epilepsy

drug substitution

The ability to drive is limited.

Psychological dependence may occur with prolonged use, rarely with short-term use. Prolonged use can lead to an accumulated release of dopamine and norepinephrine once the drug is stopped. This can lead to increased pain and discomfort in the first two to three weeks after discontinuation.

1. Beakley BD et al (2015) Tramadol, pharmacology, side effects, and serotonin syndrome: A review. Pain Physician 18:395-400.
2. Bravo L et al. (2017) Discovery and development of tramadol for the treatment of pain. Expert Opin Drug Discov 12:1281-1291.
3. Hassamal S et al (2018) Tramadol: understanding the risk of serotonin syndrome and seizures. Am J Med 131:1382.e1-1382.e6.
4. Juba KM et al (2020) A Review of the Food and Drug Administration Adverse Event Reporting System for Tramadol-Related Hypoglycemia. Ann Pharmacother 54:247-253
5. Kaae J et al. (2012) Systemic contact dermatitis following oral exposure to tramadol in a patient with allergic contact dermatitis caused by buprenorphine. Contact Dermatitis 66:106-107.