Tapentadol Immediate-release Tablets C-II (Nucynta™)
Pharmacology Update
Tapentadol Immediate-release Tablets C-II (Nucynta™)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationship to this field of study.
A new opioid analgesic with a dual mechanism of action has been released for market by PriCara, a division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. Tapentadol is a mu-opioid receptor agonist as well as an inhibitor of norepinephrine reuptake. The drug was originally approved by the FDA last year and will be marketed as a Schedule II narcotic under the brand name of Nucynta™.
Indications
Tapentadol is indicated for the relief or moderate-to-severe acute pain in adult patients (18 years of age and older).1
Dosage
The initial dose is 50 mg, 75 mg, or 100 mg every 4-6 hours depending on pain intensity. On the first day of dosing, a second dose may be taken 1 hour after the first dose if adequate pain relief has not been achieved. Subsequent doses should be given at an interval of 4-6 hours. Total doses greater than 700 mg the first day and 600 mg on subsequent days are not recommended. The drug may be given without regard to meals.1 No dosage adjustment is necessary in patients with mild-to-moderate renal impairment or mild hepatic impairment.
Tapentadol is supplied as 50 mg, 75 mg, and 100 mg immediate-release tablets.
Potential Advantages
Tapentadol does not inhibit or induce CYP P450 isoenzymes. It has a dual mechanism of action and appears to have better gastrointestinal tolerance than oxycodone IR tablets.2-5
Potential Disadvantages
Tapentadol carries similar warnings, contraindications, and precautions as other opioid analgesics (e.g., respiratory depression). Common adverse events (compared to placebo) include nausea (30% vs 13%), dizziness (24% vs 8%), vomiting (18% vs 4%), and somnolence (15% vs 3%).1
Comments
Tapentadol is a weak opioid receptor agonist. This action, along with inhibition of norepinephrine reuptake, results in potency about one-half to one-third of that of morphine.6 The safety and efficacy of tapentadol were shown in two phase III, randomized, double-blind, placebo-controlled, multiple-dose studies.1,2,4
In the first study, patients (n = 603) with moderate-to-severe postoperative (bunionectomy) pain were randomized to tapentadol 50 mg, 75 mg, 100 mg, placebo, or an active comparator (oxycodone IR 15 mg).2 Treatment was for 72 hours post bunionectomy. The primary efficacy endpoint was the sum of pain intensity difference (SPID) over the first 48 hours of treatment. Secondary endpoints included total pain relief (TOTAR), sum of pain relief and pain intensity difference (SPRID), time to onset of action, time to first rescue medication, and patient global impression of change. A minimum of 50% reduction in pain intensity at 48 hours was achieved in 58.0%, 56.7%, and 70.3% for the three doses of tapentadol, respectively, 30% for placebo, and 72.8% for oxycodone. All drug treatments were significantly different from placebo (P < 0.001). The median times to meaningful pain relief were 1:34-2:03 hours for tapentadol compared to 4:00 hours for placebo and 1:17 hours for oxycodone. Other endpoints showed a similar pattern. Gastrointestinal adverse events (nausea, vomiting) were lower for tapentadol compared to oxycodone.2
In the second study, tapentadol (50 mg, 75 mg) was compared to placebo and oxycodone in subjects (n = 666) with moderate-to-severe pain from end-stage joint disease.1,4 Subjects were randomized in a 1:1:1:1 ratio and dosed for 10 days followed by a 5-day follow-up period. The primary endpoint was sum of pain intensity difference over 5 days. The response rates (50% or greater reduction in pain intensity at day 5) were 27% and 26% for tapentadol 50 mg and 75 mg, respectively, 25% for oxycodone 10 mg, and 13% for placebo. Treatment continuation rates were 18% and 26% for tapentadol compared to 35% for oxycodone and 10% for placebo. The primary reasons for discontinuation were related to gastrointestinal and the central nervous system side effects.
In a 90-day study in patients with lower back pain or osteoarthritis pain of the hip or knee (n = 878), tapentadol (50 mg, 100 mg) showed better gastrointestinal tolerance (nausea and vomiting) but similar CNS adverse events (somnolence, dizziness) to oxycodone (10 mg or 15 mg), both dosed every 4-6 hours.5 In a single-dose study of postsurgical dental pain (n = 400), tapentadol was generally less effective than ibuprofen 400 mg.7
Clinical Implications
Tapentadol is a new opioid analgesic with a dual mechanism of action. While it appears to be better tolerated in terms of GI adverse events compared to oxycodone, it has not demonstrated a clear clinical advantage over currently available analgesics.
References
1. Nucynta Product Information. Raritan, NJ: PriCara; March 2009.
2. Daniels S, et al. A randomized, double-blind, phase III study comparing multiple doses of tapentadol IR, oxycodone IR, and placebo for postoperative (bunionectomy) pain. Curr Med Res Opin 2009; 25:765-776.
3. Daniels SE, et al. A randomized, double-blind, placebo-controlled phase 3 study of the relative efficacy and tolerability of tapentadol IR and oxycodone IR for acute pain. Curr Med Res Opin 2009;1551-1561.
4. Hertrick C, et al. Efficacy and tolerability of tapentadol immediate release and oxycodone HCl immediate release in patients awaiting primary joint replacement surgery for end-stage joint disease: A 10-day, phase III, randomized, double-blind, active- and placebo- controlled study. Clin Ther 2009;31:260-271.
5. Hale M, et al. Tolerability of tapentadol immediate release in patients with lower back pain or osteoarthritis of the hip or knee over 90 days: A randomized, double-blind study. Curr Med Res Opin 2009;25:1095-1104.
6. Tzschentke TM, et al. (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride (tapentadol HCl): A novel mu-opioid receptor agonist/norepinephrine reuptake inhibitor with broad-spectrum analgesic properties. J Pharmacol Exp Ther 2007;323:265-276.
7. Kleinert R, et al. Single dose analgesic efficacy of tapentadol in postsurgical dental pain: The results of a randomized, double-blind, placebo-controlled study. Anesth Analg 2008;107:2048-2055.
A new opioid analgesic with a dual mechanism of action has been released for market by PriCara, a division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.Subscribe Now for Access
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