Approved November 20, 2008

TAPENTADOL HYDROCHLORIDE
(FDA Category 2S)

NUCYNTA(TM) (Ortho-McNeil-Janssen Pharmaceuticals, Inc) is a centrally-acting analgesic which works by acting as a mu-opioid agonist and inhibiting norepinephrine uptake.

DOSING INFORMATION: 50 mg, 75 mg, 100 mg orally (with or without food) every 4 to 6 hours, individualized depending on pain severity. If adequate pain control is not achieved after the first dose, a repeat dose may be administered one hour later. Maximum maintenance daily dose is 600 mg.

PHARMACOKINETICS: The mean absolute bioavailability of tapentadol is 32%. Maximum concentrations occurs at approximately 1.25 hours after dosing. After a high-fat, high-calorie meal, the tapentadol AUC and Cmax values increased by 25% and 16%, respectively. Tapentadol is approximately 20% bound to plasma protein and is metabolized extensively (about 97%) primarily in the liver by glucuronidation and to a lesser extent by CYP450 isoenzymes (CYP2C9, CYP2C19, CYP2D6). Tapentadol is excreted by the kidneys (99%) and the terminal half-life is 4 hours after dosing.

CAUTIONS: Contraindicated in patients with impaired pulmonary function or paralytic ileus and with the concomitant use of a MAOI or within 14 days of MAOI use. Use with caution in patients who are elderly or debilitated or patients with hypoxia, hypercapnia, or upper airway obstruction due to risk of respiratory depression. Tapentadol has additive CNS effects in patients who are taking alcohol, other opioids, or illicit drugs; additionally, addiction or abuse may occur. It is also associated with risk of increased cerebrospinal fluid pressure in patients with head injury or increased intracranial pressure, serotonin syndrome if used concomitantly with serotonergic agents, and seizures in patients with a history of seizures. The most common adverse reactions include nausea, dizziness, vomiting, and somnolence.

FDA APPROVED INDICATIONS: Tapentadol is indicated for the treatment of moderate to severe acute pain in patients ages 18 years or older.