Tramadol may then be taken only as required for acute (breakthrough) pain. Other pain medications, such as acetaminophen and ibuprofen, may be given as well. Inquire with your doctor or pharmacist about the possibility of mixing tramadol with other medications. If you suddenly stop using this drug, particularly if you’ve been taking it for a long time or in large dosages, you may have withdrawal symptoms. Your doctor may gradually reduce your dosage to avoid withdrawal. If you have any withdrawal symptoms including restlessness, mental/mood problems (such as anxiety, insomnia, or suicidal thoughts), watery eyes, runny nose, nausea, diarrhoea, sweating, muscular pains, or abrupt changes in behaviour, contact your doctor or pharmacist immediately once. When used over an extended period of time, this drug may lose its effectiveness. If this medicine isn’t functioning properly, talk to your doctor. This drug may create addiction in some individuals, despite the fact that it benefits a lot of people. If you have a substance use problem (such as drug/alcohol abuse or addiction), your risk is likely to be greater. To reduce your risk of addiction, take this medicine precisely as directed. More information may be obtained from your physician or pharmacist. If your pain does not improve or worsens, contact your doctor right away.

Pharmacokinetics of Tramadol

Absorption

A 100 mg oral dosage has a mean absolute bioavailability of about 75%. In healthy individuals, the mean peak plasma concentration of racemic tramadol and M1 occurs two and three hours after delivery, respectively. Both enantiomers of tramadol and M1 have a similar time course in the body after single and repeated doses, but there are minor variations (less than 10%) in the absolute quantity of each enantiomer present.

Distribution

Following a 100 mg intravenous dosage, the volume of distribution of tramadol was 2.6 and 2.9 liters/kg in male and female participants, respectively. Tramadol binds to human plasma proteins around 20% of the time, and binding seems to be independent of concentration up to 10 g/mL.

Metabolism

After oral ingestion, tramadol is extensively metabolised by a variety of mechanisms, including CYP2D6 and CYP3A4, as well as conjugation of parent and metabolites.Approximately 30% of the dosage is eliminated in the urine as unmodified medication, whereas 60% is excreted as metabolites. The majority of the dosage is excreted in the form of metabolites. The activity of the CYP2D6 isoenzyme is decreased in around 7% of the population. Cytochrome P-450 is a kind of cytochrome. These people are “poor metabolizers” of the drug debrisoquine. Other medications include dextromethorphan and tricyclic antidepressants. On the basis of a population Tramadol concentrations were shown to be high in Phase I trials in healthy individuals, according to a PK study. “Poor metabolizers” have a 20 percent greater rate than “extensive metabolizers,” whereas the concentrations of M1 were 40% lower.

Elimination

Tramadol is mostly removed via the liver’s metabolism, while the metabolites are mostly eliminated through the kidneys. The half-lives of the average terminal plasma elimination half-lives of racemic tramadol and racemic M1 are 6.3 and 7.4 hours, respectively.