WHAT IS NUCYNTA? 


Tapentadol (Nucynta) is a new centrally acting opioid analgesic. Like tramadol, tapentadol is a mu opioid receptor agonist that also inhibits norepinephrine reuptake. Nucynta is FDA-approved for the treatment of moderate to severe acute pain in patients older than 18 years and is available as 50-, 75-, or 100-mg tablets.


Nucynta is being marketed as having improved tolerability compared to other opioid analgesics. Clinical trials have revealed that tapentadol controls acute pain as well as oxycodone 10 mg but with less constipation, nausea, and vomiting.1 In a double-blind study assessing GI tolerability as the primary end point, tapentadol 50 and 75 mg were found to be superior to oxycodone 10 mg with regards to nausea, vomiting, and constipation.2 However, nausea, vomiting, constipation, dizziness, and somnolence remain the most commonly reported adverse effects of tapentadol.1 


Metabolism of tapentadol is primarily hepatic, and lower starting doses should be used in patients with moderate hepatic impairment. Furthermore, the drug has not been studied in patients with severe renal or hepatic impairment, and use cannot be recommended in these groups. Patients with a history of seizure disorder were excluded from clinical trials of tapentadol, and caution should be exercised if prescribing this medication in patients at risk for seizures. Tramadol, which is pharmacologically similar to tapentadol, has been associated with seizures in predisposed patients. Finally, because tapentadol inhibits the reuptake of norepinephrine, there is a theoretical risk of serotonin syndrome in patients taking monoamine oxidase inhibitors or serotonergic agents and tapentadol. 


The cost of Nucynta is similar to that of other brand-name opioids and is considerably more than the cost of generic oxycodone or tramadol. Consider reserving it for patients who require a strong opiate but who cannot tolerate GI side effects. Be aware that Nucynta is a schedule II controlled substance and that prescribing restrictions may exist in some states.


WHAT ARE GUIDELINES FOR BRIDGING WITH ENOXAPARIN 
AFTER PROSTHETIC VALVE REPLACEMENT? 


Thromboembolic risk is increased immediately after the insertion of a prosthetic valve. Warfarin therapy is indicated after surgery; however, many institutions bridge with either unfractionated heparin (UFH) or a low molecular weight heparin (LMWH) until the international normalized ratio (INR) is therapeutic. Many clinicians find enoxaparin appealing for its ease of outpatient administration and potential for reduced length of hospital stay. Its use is controversial, however, and requires weighing the risk of bleeding versus thrombotic complications.

Three guidelines address bridging anticoagulation after valve replacement surgery, but lack of clinical trials means that there is no consensus. The 2008 American College of Chest Physicians guidelines suggest using either SC LMWH or IV UFH until the INR is greater than 2.0 for 2 consecutive days.3 European guidelines recommend IV UFH over SC LMWH for safety reasons.4 If a LMWH such as enoxaparin is used, monitoring antifactor Xa levels to ensure optimal anticoagulation is recommended. The American College of Cardiology/American Heart Association guidelines do not make a recommendation but do acknowledge that many centers start UFH after prosthetic heart valve surgery to a goal activated partial thromboplastin time of 55 to 70 seconds.5


The primary benefit of UFH over LMWH is rapid reversal of anticoagulant effect if bleeding develops. If enoxaparin is used, the usual therapeutic dose is 1 mg/kg every 12 hours. The anticoagulant effect of enoxaparin is less predictable in patients with kidney disease and obesity. If enoxaparin is used, dose adjustments or antifactor Xa monitoring should be performed in these populations to ensure adequate anticoagulation. JAAPA


Larissa DeDea, PharmD, BCPS, PA-C, is a clinical pharmacist with Northern Arizona Healthcare, Flagstaff, Arizona. In addition to being board certified in pharmacotherapy, she is a graduate of the Yale University PA program.

REFERENCES


1. New drug: Nucynta (tapentadol). Pharmacist's Letter/Prescriber's Letter. 2009;25(7):250711.


2. Etropolski M, et al. Comparable efficacy and superior gastrointestinal tolerability (nausea, vomiting, constipation) of tapentadol compared with oxycodone hydrochloride. Adv Ther. 2011;28(5):401-417.


3. Salem DN, et al. Valvular and structural heart disease: American College of Chest Physicians Evidence-Based 
Clinical Practice Guidelines (8th edition). Chest. 2008;
133(6 suppl):593S-629S.


4. Butchart EG, et al. Recommendations for the management of patients after heart valve surgery. Eur Heart J. 2005;26(22):2463-2471.


5. Bonow RO, et al. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease. Circulation. 2008;118(15):
e523-661.