February 2012, Volume 5, Issue 1 The Prescriber e-Letter MassHealth Pharmacy Program Topical and Oral Antiviral Agents The topical antiviral agents acyclovir (Zovirax) and penciclovir (Denavir) creams are indicated for the treatment of recurrent, orolabial herpes (cold sores), while acyclovir (Zovirax) ointment is indicated in the management of initial (first occurrence) genital herpes and in limited non-life-threatening mucocutaneous herpes simplex virus infections in immuno-compromised patients. The oral antivirals acyclovir, famciclovir, and valacyclovir are indicated for the treatment of initial and recurrent orolabial and genital herpes episodes, as well as suppression of recurrent episodes of both conditions. In placebo-controlled randomized trials, treatment with the topical antivirals provided modest benefit in patients with sporadic recurrences of orolabial herpes, while treatment with the oral antivirals reduced the duration and severity of oral herpes symptoms compared to placebo. Despite being systemically absorbed, the oral antivirals are also well-tolerated as the agents are selectively converted to active compounds within virally infected cells. For the management of genital herpes, the Centers for Disease Control and Prevention does not recommend using topical antivirals due to minimal efficacy in comparison to the oral antivirals. Oral acyclovir, famciclovir, and valacyclovir are comparable in efficacy for the treatment of primary genital herpes and in the suppression of recurrent genital herpes. In addition to being well-tolerated and effective for the management of orolabial and genital herpes, the oral antiviral agents are available generically and are significantly less costly than topical antiviral agents. Therefore, all topical antivirals will now require prior authorization (PA). The PA process was implemented on January 23, 2012. Oral Antiplatelet Agents The oral P2Y12 platelet inhibitors, clopidogrel (Plavix), prasugrel (Effient), and ticagrelor (BRILINTA) are indicated for the reduction of thrombotic cardiovascular events in patients with acute coronary syndromes (ACS). Prasugrel is specifically indicated for ACS patients who are being managed with primary or delayed percutaneous coronary intervention (PCI). In the TRITON-TIMI 38 trial, treatment with prasugrel reduced the composite endpoint of death from cardiovascular causes, nonfatal myocardial infarction (MI), or nonfatal stroke to a greater extent than clopidogrel. However, treatment with prasugrel did not decrease overall mortality and increased the risk of bleeding compared to clopidogrel. Prasugrel is not recommended for patients at an increased risk of bleeding, including patients 75 years of age and older, patients weighing less than 60 kg, those with a past history of stroke or transient ischemic attack, and patients expected to undergo urgent coronary artery bypass graft surgery. In the PLATO trial, treatment with ticagrelor reduced the composite endpoint of death from vascular causes, MI, and stroke to a greater extent than clopidogrel. However, the efficacy of ticagrelor was reduced in North American patients receiving high doses of aspirin. Ticagrelor should not be used concomitantly with aspirin doses exceeding 100 mg and is also dosed twice daily compared to the once daily dosing of clopidogrel and prasugrel. Due to the observed mitigated efficacy of ticagrelor in North American patients receiving high doses of aspirin and the anticipated generic availability of clopidogrel, ticagrelor and prasugrel will require PA. The PA process for ticagrelor and prasugrel was implemented on January 9, 2012, and January 23, 2012, respectively. The Prescriber e-Letter is an update designed to enhance the transparency and efficiency of the MassHealth drug prior-authorization (PA) process and the MassHealth Drug List. Each issue will highlight key clinical information and updates to the MassHealth Drug List. The Prescriber E-Letter was prepared by the MassHealth Drug Utilization Review Program and the MassHealth Pharmacy Program. The Prescriber e-Letter February 2012, Volume 5, Issue 1 Recent MassHealth Drug List Updates Drug/Drug Class Antiparkinson agents Addition/Deletion/Change Change in PA status; requires PA amantadine tablet, selegiline capsule, and tolcapone (Tasmar) Rationale Amantadine tablets, selegiline capsules, and Tasmar tablets are used in the management of Parkinson’s Disease. There are more cost-effective alternatives for the management of the same clinical condition including amantadine capsules, selegiline tablets, and Comtan tablets. Amantadine capsules and selegiline tablets are available without PA. However, Comtan tablets also require PA to ensure appropriate utilization. Drug/Drug Class brentuximab (ADCETRIS) Addition/Deletion/Change Addition; requires PA Rationale ADCETRIS is a CD30-directed antibody-drug conjugate that is FDA-approved for the treatment of patients with Hodgkin’s lymphoma after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates. This agent is also approved for the treatment of systemic anaplastic large cell lymphoma in patients who have failed at least one prior multi-agent chemotherapy regimen. Given the high cost and limited indication of this medication, ADCETRIS requires PA. Drug/Drug Class calcium acetate (Phoslyra) Addition/Deletion/Change Addition; does not require PA Rationale Phoslyra is a phosphate binder that is FDA-approved for the reduction of serum phosphorus in patients with end stage renal disease. Drug/Drug Class chlorzoxazone Addition/Deletion/Change Addition; 375 mg and 750 mg tablets require PA Rationale Chlorzoxazone is a skeletal muscle relaxant that is FDA-approved for the treatment of musculoskeletal pain. Chlorzoxazone 500 mg tablets are less costly and are available without PA. Drug/Drug Class crizotinib (Xalkori) Addition/Deletion/Change Addition; requires PA Rationale Xalkori is a kinase inhibitor that is FDA-approved for the treatment of patients with locally advanced or metastatic non-small cell lung cancer that is anaplastic lymphoma kinase -positive as detected by an FDA- approved fluorescence in situ hybridization test. Given the high cost and limited indication of this medication, Xalkori requires PA. Drug/Drug Class emtricitabine/rilpivirine/tenofovir (Complera) Addition/Deletion/Change Addition; does not require PA Rationale Complera, a combination of two NRTIs and one NNRTI, is FDA-approved for use as a complete regimen for the treatment of HIV-1 infection in treatment-naïve adults. Drug/Drug Class lidocaine/hydrocortisone (LidaMantle HC) Addition/Deletion/Change Deletion; no longer on MassHealth Drug List Rationale This product has been removed from the MassHealth Drug List because it is not approved by the FDA. Drug/Drug Class gabapentin ER (GRALISE) Addition/Deletion/Change Addition; requires PA Rationale GRALISE is FDA-approved for the management of postherpetic neuralgia in adults ages 18 and older. There are more cost-effective alternatives available without PA for the management of the same clinical condition, including generic immediate-release gabapentin. Drug/Drug Class ibuprofen/famotidine (DUEXIS) Addition/Deletion/Change Addition; requires PA < 60 years Rationale DUEXIS is a combination product containing the nonsteroidal anti-inflammatory drug (NSAID), ibuprofen, and the histamine H2-receptor antagonist, famotidine. This agent is FDA-approved to relieve the signs and symptoms of rheumatoid arthritis and osteoarthritis, in addition to decreasing a patient’s risk of developing an upper gastrointestinal ulcer while taking ibuprofen. The risk of NSAID-associated GI complications increases with age. Therefore, MassHealth has determined that PA is required for DUEXIS in members < 60 years of age to ensure that this medication is reserved for members at an increased risk for GI toxicity. PA is not required for the generic single-entity components of DUEXIS. Drug/Drug Class icatibant (FIRAZYR) Addition/Deletion/Change Addition; requires PA Rationale FIRAZYR is a bradykinin B2 receptor antagonist that is FDA-approved for the treatment of acute attacks of hereditary angioedema in adults ages 18 and older. Given the high cost and limited indication of this medication, FIRAZYR requires PA. Drug/Drug Class indacaterol (Arcapta) Addition/Deletion/Change Addition; requires PA Rationale Arcapta is a long-acting beta agonist (LABA) that is FDA-approved for the long term, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease, including chronic bronchitis and emphysema. A LABA can be used as monotherapy in patients with chronic obstructive pulmonary disease and as add-on therapy to inhaled corticosteroids in patients with asthma, though Arcapta is not indicated for asthma. MassHealth requires PA for all LABAs, including Arcapta. Drug/Drug Class tramadol ER (Conzip ER) Addition/Deletion/Change Addition; requires PA Rationale Conzip ER is an opioid agonist that is FDA-approved for the management of moderate to moderately severe chronic pain in adults who require around-the-clock treatment of their pain for an extended period of time. There are more cost-effective alternatives available without PA for the management of this condition, including generic immediate-release tramadol. Drug/Drug Class rivaroxaban (Xarelto) Addition/Deletion/Change Addition; 15 mg and 20 mg tablets require PA Rationale Xarelto 15 mg and 20 mg daily is FDA-approved to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF). There are more cost-effective alternatives available without PA for the management of nonvalvular AF including warfarin and aspirin. Drug/Drug Class prednisolone suspension (Flo-pred) Addition/Deletion/Change Addition; requires PA Rationale Flo-Pred is an anti-inflammatory or immunosuppressive agent that is FDA-approved for certain types of allergic, dermatologic, endocrine, gastrointestinal, hematologic, neoplastic, nervous system, ophthalmologic, renal, respiratory, and rheumatologic conditions. The agent is also indicated for specific spinal infectious diseases and organ transplantation. There are more cost-effective alternatives available without PA for the management of the same clinical conditions, including prednisolone tablet and solution. Drug/Drug Class praziquantel (Biltricide) Addition/Deletion/Change Addition; does not require PA Rationale Biltricide is an antihelmintic agent that is FDA-approved for the treatment of infections due to liver flukes (Clonorchis sinensis and Opisthorchis viverrini) and all species of schistosoma. Drug/Drug Class rivaroxaban (Xarelto) Addition/Deletion/Change Addition; 10 mg tablets require PA > 10 mg/day and > 35 tablets/ 365 days Rationale Xarelto 10 mg daily is FDA-approved for the prophylaxis of deep vein thrombosis (DVT) in patients undergoing knee or hip replacement surgery. Xarelto 10 mg is available without PA in doses ? 10 mg daily and in quantities ? 35 tablets per 365 days. Drug/Drug Class prasugrel (Effient) Addition/Deletion/Change Change in PA status; requires PA Rationale Effient is FDA-approved for the reduction of thrombotic cardiovascular events, including stent thrombosis, in patients with ACS such as unstable angina (USA), non-ST elevation MI (NSTEMI), and ST elevation MI (STEMI), who are being managed with primary or delayed percutaneous coronary intervention (PCI). Due to the anticipated generic availability of clopidogrel in 2012, Effient requires PA. Drug/Drug Class sitagliptin/simvastatin (Juvisync) Addition/Deletion/Change Addition; requires PA Rationale Juvisync is indicated in patients for whom treatment with both sitagliptin and simvastatin is appropriate. Sitagliptin is FDA-approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Simvastatin is indicated for the reduction of LDL cholesterol. There are more cost- effective alternatives available for the management of the same clinical condition, including Januvia and generic simvastatin. Simvastatin is available without PA. Drug/Drug Class tadalafil (Cialis) Addition/Deletion/Change Addition; requires PA Rationale In addition to previously approved indications, Cialis is now FDA-approved for the treatment of the signs and symptoms of benign prostatic hyperplasia. There are more cost-effective alternatives available without a PA for the management of this condition, including generics doxazosin, tamsulosin, and terazosin. Please note: The MassHealth agency does not pay for any drug when used for the treatment of male or female sexual dysfunction as described in 130 CMR 406.413(B). Drug/Drug Class tapentadol ER (Nucynta ER) Addition/Deletion/Change Addition; requires PA Rationale Nucynta ER is an opioid analgesic that is FDA-approved for the management of moderate to severe chronic pain in adults who require a continuous, around-the-clock opioid analgesic for an extended period of time. There are more cost-effective alternatives available for the management of this condition, including generic fentanyl, methadone, and morphine ER. Drug/Drug Class ticagrelor (BRILINTA) Addition/Deletion/Change Addition; requires PA Rationale BRILINTA is FDA-approved to reduce the rate of thrombotic cardiovascular events in patients with ACS, which includes UA, NSTEMI, and STEMI. Due to the observed mitigated efficacy of BRILINTA in North American patients receiving high doses of aspirin in the PLATO trial and the anticipated generic availability of clopidogrel in 2012, BRILINTA requires PA. Drug/Drug Class vemurafenib (Zelboraf) Addition/Deletion/Change Addition; requires PA Rationale Zelboraf is a BRAF serine-threonine kinase protein inhibitor that is FDA-approved for the treatment of patients with unresectable or metastatic melanoma with BRAF-V600E mutation, as detected by the FDA- approved cobas 4800 BRAF V600 Mutation Test. Given the high cost and limited indication of this medication, Zelboraf requires PA. Please send any suggestions or comments to: PrescriberELetter@state.ma.us