DOLL Tablet

For the short-term treatment (i.e. 3 days or less) of mild to moderate acute pain.

Dosage and Directions for use

Adults (17 years of age and over)

The total daily dose may be increased by 50mg as tolerated every 3 days to reach 200mg/day (50mg 1.i.d).

Tramadol hydrochloride tablets 50-100mg can be administered as needed for pain relief every 4-6 hours, not to exceed 40mg/day.

* In all patients with creatinine clearance less than 30mL/min, it is recommended that the dosing interval of tramadol hydrochloride tablets be increased to 12 hours, with a maximum daily dose of 200mg. Since only 7% of an administered dose is removed by hemodialysis, dialysis patients can receive their regular dose on the day of dialysis.

* The recommended dose for adults patients with cirrhosis is 50mg every 12 hours.

* In general, dose selection for an elderly patient over 65 years old should be cautions, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy. For elderly patients over 75 years old, total dose should not exceed 300mg/day.

Tramadol hydrochloride tablets should not be administered to patients who have previously demonstrated hypersensitivity to tramadol, any other component of this product or opioids. Tramadol hydrochloride is contraindicated in any situation where opioids are contraindicated, including acute intoxication with any of the following: alcohol, hypnotics, narcotics, centrally acting analgesics, opioids or psychotropic drugs. Tramadol may worsen central nervous system and respiratory depression in these patients.

The most frequently reported side effects were of the gastrointestinal and central nervous systems. These include:

Gastrointestinal system: Nausea, abdominal pain, constipation, flatulence, vomiting, dry mouth, dyspepsia and diarrhea.

Central Nervous System and Psychiatric: Dizziness, headache, nervousness, anxiety, agitation, euphoria, emotional lability, hallucinations, hypertonia and tremor. Somnolence, insomnia, anorexia, anxiety, confusion, euphoria and nervousness.

Other reported side-effects include pruritus, fatigue, upper respiratory tract infection, increased sweating, hot flushes, rashes and asthenia.

Other side-effects reported with the use of tramadol include: anaphylaxis, increased liver enzyme values, postural hypotension or cardiovascular collapse and the potential for Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome.

In vitro studies indicate that tramadol is unlikely to inhibit the CYP3A4-mediated metabolism of other drugs when tramadol is administered concomitantly at therapeutic doses. Use with Carbamazepine patients taking carbamazepine increases tramadol metabolism and because of the seizure risk associated with tramadol, concomitant administration of tramadol hydrochloride tablets and carbamazepine is not recommended.

See the package insert about the details below:

- Quinidine

- Cimetidine

- MAO inhibitors

Tramadol hydrochloride is a centrally acting synthetic opioid analgesic. Although its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to µ-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin.

Opioid activity is due to both low affinity binding of the parent compound and higher affinity binding of the O-demerhylated metabolite M1 to µ-opioid receptors. In animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in µ-opioid binding. Tramadol-induced analgesia is only partially antagonized by the opiate antagonist naloxone in several animal tests. The relative contribution of both tramadol and M1 to human analgesia is dependent upon the plasma concentrations of each compound.

Tramadol has been shown to inhibit reuptake of norepinephrine and serotonin in vitro, as have some other opioid analgesics. These mechanisms may contribute independently to the overall analgesic profile of tramadol hydrochloride tablets. Analgesia in humans begins approximately within 1 hour after administration and reaches a peak in approximately 2-3 hours.