Tramadol hydrochloride tablet

Tramadol hydrochloride tablet is a centrally acting analgesic. The chemical name for tramadol hydrochloride is (±)cis-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl) cyclohexanol hydrochloride. Its structural formula is shown in the right side of this page

Molecular formula is C₁₆H₁₃NO₂•HCl

The molecular weight of tramadol hydrochloride is 299.8. Tramadol hydrochloride is a white, bitter, crystalline and odorless powder. It is readily soluble in water and ethanol and has a pKa of 9.41. The noctanol/water log partition coefficient (logP) is 1.35 at pH7. Tramadol hydrochloride tablets, for oral administration contain 50 mg of tramadol hydrochloride. In addition, each tablet contains the following inactive ingredients: pregelatinized starch, lactose anhydrous, magnesium stearate, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, titanium dioxide.

DOSAGE AND ADMINISTRATION

Adults (17 years of age and over)

For patients with moderate to moderately severe chronic pain not requiring rapid onset of analgesic effect the tolerability of tramadol hydrochloride can be improved by initiating therapy with a titration regimen: The total daily dose may be increased by 50 mg as tolerated every 3 days to reach 200 mg/day (50 mg q.i.d.) After titration, tramadol hydrochloride tablets 50 mg to 100 mg can be administered as needed for pain relief every four to six hours, not to exceed 400 mg per day.

For the subset of patients for whom rapid onset of analgesic effect is required and for whom the benefits outweigh the risk of discontinuation due to adverse events associated with higher initial doses, tramadol hydrochloride tablets 50 mg to 100 mg can be administered as needed for pain relief every four to six hours not to exceed 400 mg per day.

Individualization of Dose

Good pain management practice dictates that the dose be individualized according to patient need using the lowest beneficial dose. Studies with tramadol in adults have shown that starting at the lowest possible dose and titrating upward will result in fewer discontinuations and increased tolerability

• In all patients with creatinine clearance less than 30 mL/min, it is recommended that the dosing interval of tramadol hydrochloride tablets be increased to 12 hours, with a maximum daily dose of 200 mg. 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 50 mg every 12 hours

  
  

• In general, dose selection for an elderly patient over 65 years old should be cautious, 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 300 mg/day.

  
  

DRUG INTERACTIONS

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. Tramadol does not appear to induce its own metabolism in humans, since observed maximal plasma concentrations after multiple oral doses are higher than expected based on single-dose data. Tramadol is a mild inducer of selected drug metabolism pathways measured in animals.

Use with Carbamazepine

Patients taking carbamazepine may have a significantly reduced analgesic effect of tramadol hydrochloride tablets Because carbamazepine increases tramadol metabolism and because of the seizure risk associated with tramadol concomitant administration of tramadol hydrochloride tablets and carbamazepine is not recommended.

Use with Quinidine

Tramadol is metabolized to M1 by CYP2D6. Quinidine is a selective inhibitor of that isoenzyme, so that concomitant administration of quinidine and tramadol hydrochloride tablets results in increased concentrations of tramadol and reduced concentrations of M1. The clinical consequences of these findings are unknown. In vitro drug interaction studies in human liver microsomes indicate that tramadol has no affect on quinidine metabolism.

Use with Inhibitors of CYP2D6

In vitro drug interaction studies in human liver microsomes indicate that concomitant administration with inhibitors of CYP2D6 such as fluoxetine, paroxetine, and amitriptyline could result in some inhibition of the metabolism of tramadol.

Use with Cimetidine

Concomitant administration of tramadol hydrochloride tablets with cimetidine does not result in clinically significant changes in tramadol pharmacokinetics. Therefore, no alteration of the tramadol hydrochloride tablets dosage regimen is recommended.

Use with MAO Inhibitors

Interactions with MAO Inhibitors, due to interference with detoxification mechanisms, have been reported for some centrally acting drugs.

Use with Digoxin and Warfarin

Post-marketing surveillance has revealed rare reports of digoxin toxicity and alteration of warfarin effect including elevation of prothrombin times.