NUCYNTA Tapentadol , is a centrally acting opioid analgesic approved for the relief of moderate to severe pain in adults.

It has two mechanisms of action: in addition to acting at the mu opioid receptor, tapentadol blocks norepinephrine uptake, although the clinical relevance of this additional action is not known. [ corrected]

It is currently available in an immediate-release form, which is approved for adults with severe acute pain, and an extended-release form, which is used for moderate to severe chronic pain.

Extended release tapentadol is not intended for the management of acute or postoperative pain. Tapentadol is classified as a U.S. Drug Enforcement Administration (DEA) schedule II-controlled substance.

NUCYNTA Tapentadol is rapidly absorbed, with a maximum serum concentration (Cmax) typically observed between 1.25 and 1.5 hours.

Dose-proportional increases in the Cmax and area-under-the-curve (AUC) values of tapentadol have been observed above the 50- to 150-mg dose range, suggesting linear pharmacokinetics.

Tapentadol’s AUC and Cmax are increased by 25% and 16%, respectively, following a high-fat, high-calorie meal. The mean absolute bioavailability after a single dose is 32% as a result of the medication’s extensive first-pass metabolism.

Tapentadol is widely distributed throughout the body, with a volume of distribution of approximately 540 liters. Plasma binding is low and has been reported at approximately 20%.

Tapentadol is primarily and extensively (70%) metabolized via glucuron-idation by the UGT1A9 and UGT2B7 enzymes to inactive metabolites.

Phase 1 metabolites include N-desmethyl tapentadol (13%) as a result of metabolism by CYP 2C9 and 2C19, and hydroxytapentadol (2%), as a result of metabolism by CYP 2D6, which are further metabolized by conjugation.

The metabolites of tapentadol do not contribute to the drug’s analgesic activity. Tapentadol is excreted primarily by the renal system (99%); 69% is excreted in the form of conjugates, 27% as other metabolites, and 3% as unchanged drug.

Fecal clearance accounts for 1% of tapentadol’s elimination.

The apparent half-life of tapentadol following oral administration is 3.93 hours, and more than 95% of the drug is excreted within 24 hours of dosing. The total tapentadol clearance is 1,530 ± 177 mL/minute.

The pharmacokinetic properties of tapentadol do not appear to be affected by renal impairment. Moderate hepatic impairment results in decreased metabolism of tapentadol, resulting in higher exposures and serum tapentadol levels.

The pharmacokinetic parameters of tapentadol have not been evaluated in patients with severe hepatic impairment.