Description

Tramadol, sold under the brand name Ultram among others, is an opioid pain medication used to treat moderate to moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an hour. It is also available by injection. It may be sold in combination with paracetamol (acetaminophen) or as longer-acting formulations.

As is typical of opioids, common side effects include constipation, itchiness, and nausea. Serious side effects may include seizures, increased risk of serotonin syndrome, decreased alertness, and drug addiction. A change in dosage may be recommended in those with kidney or liver problems. It is not recommended in those who are at risk of suicide or in those who are pregnant. While not recommended in women who are breastfeeding, those who take a single dose should not generally stop breastfeeding. Tramadol is converted in the liver to O-desmethyl tramadol, an opioid with stronger binding to the μ-opioid receptor. Tramadol is also a serotonin-norepinephrine reuptake inhibitor (SNRI).

Tramadol was patented in 1963 and launched under the name “Tramal” in 1977 by the West German pharmaceutical company Grünenthal GmbH. In the mid-1990s, it was approved in the United Kingdom and the United States. It is available as a generic medication and marketed under many brand names worldwide. In the United States, the wholesale cost is less than US$0.05 per dose as of 2018. In 2016, it was the 39th most prescribed medication in the United States, with more than 19 million prescriptions

Medical uses

Tramadol is used primarily to treat mild to severe pain, both acute and chronic. There is fair evidence for use as a second-line treatment for fibromyalgia but is not FDA approved for this use.

Its analgesic effects take about one hour to come into effect and 2 to 4 h to peak after oral administration with an immediate-release formulation. On a dose-by-dose basis, tramadol has about one-tenth the potency of morphine and is practically equally potent when compared with pethidine and codeine. For pain moderate in severity, its effectiveness is equivalent to that of morphine; for severe pain it is less effective than morphine. These painkilling effects last about 6 h. The potency of analgesia varies considerably as it depends on an individual’s genetics. People with specific variants of CYP2D6 enzymes may not produce adequate amounts of the active metabolite (desmetramadol) for effective pain control.

Contraindications

Tramadol may not provide adequate pain control for individuals with certain genetic variants of CYP2D6 enzymes as they metabolize tramadol to the active molecule. These genetic polymorphisms are not currently routinely tested for in clinical practice.

Pregnancy and lactation

Tramadol’s use in pregnancy is generally avoided, as it may cause some reversible withdrawal effects in the newborn. A small prospective study in France found, while an increased risk of miscarriages existed, no major malformations were reported in the newborn. Its use during lactation is also generally advised against, but a small trial found that infants breastfed by mothers taking tramadol were exposed to about 2.88% of the dose the mothers were taking. No evidence of this dose having a harmful effect on the newborn was seen.

Labor and delivery

Its use as an analgesic during labor is not advised due to its long onset of action (1 hour). The ratio of the mean concentration of the drug in the fetus compared to that of the mother when it is given intramuscularly for labor pains has been estimated to be 1:94.

Children

Its use in children is generally advised against, although it may be done under the supervision of a specialist. On September 21, 2015, the FDA started investigating the safety of tramadol in use in persons under the age of 17. The investigation was initiated because some of these people have experienced slowed or difficult breathing. The FDA lists age under 12 years old as a contraindication.

Elderly

The risk of opioid-related adverse effects such as respiratory depression falls, cognitive impairment and sedation are increased. Tramadol may interact with other medications and increase the risk of adverse events.

Liver and kidney failure

The drug should be used with caution in those with liver or kidney failure, due to metabolism in the liver (to the active molecule desmetramadol) and elimination by the kidneys.

Side effects

The most common adverse effects of tramadol include nausea, dizziness, dry mouth, indigestion, abdominal pain, vertigo, vomiting, constipation, drowsiness, and headache. Other side effects may result from interactions with other medications. Tramadol has the same dose-dependent adverse effects as morphine including respiratory depression.