Pharmacy and Therapeutics Committee

New York State Office Of Medicaid Management
Pharmacy and Therapeutics Meeting Summary from Previous Meeting - March 9, 2006

Agenda

The Pharmacy & Therapeutics Committee met on Thursday, March 9, 2006, from 8:45 a.m. to 3:00 p.m., Meeting Room 6, Concourse, Empire State Plaza, Albany, New York.

A. Background Materials Provided:

The Committee was provided copies of written materials submitted by interested parties in advance of the meeting.

B. Public Comment Period:

The following speakers addressed the committee:

1. Gueye, Mouhamed, Pharm D., Medical Liaison, Primary Care, Roche , Nutley, NJ
2. Kaiser, Fran E., MD, Executive Medical Director, Merck & Co.., Dallas, TX
3. Zwick, Eric J., Pharm D, Scientific Manager, Procter & Gamble, Macungie, PA
4. Braverman-Panza, Jill, MD, Private Practice, Albany, NY
5. D'Ambrosio, Beth, Pharm D, Regional Account Scientific Associate Director, Novartis, Pittsford, NY
6. DoDoo, Benjamin, MD, Clinical Assistant Professor of Medicine, Greenburgh Health Center., White Plains, NY
7. Vichiendilokkul, Anna, Pharm D, MS, Glaxo Smith Kline, NY, NY
8. Singh, Binoy K.,MD, Assistant Professor of Medicine, Columbia University, Yorktown Heights, NY
9. Khan, Naeem, MD, Senior Regional Scientific Manager, Astra Zeneca, Wilmington, DE
10. El-Zaru, Mohamad, MD, Albany Associates in Cardiology, Albany, NY
11. Govaker, David, MD, Regional Medical Research Specialist, Medical Director, Pfizer, NY, NY

C. Key Issues Raised by Interested Parties and Pharmacy and Therapeutics Committee Response:

On the topic of identification of preferred drugs in the therapeutic class of Calcium Channel Blockers:

• Information regarding new studies that were not included in the Oregon Health & Sciences University (OHSU) was presented.
• The Committee was asked to consider that because Norvasc is prescribed more than any other calcium channel blocker, the impact of being non-preferred and the resulting prior authorizations would be resource intensive.

On the topic of identification of preferred drugs in the therapeutic class of Calcium Channel Blockers/ACEI Combinations:

• Information regarding trial results (indications, risk reduction and use in special populations) and general overviews of specific drugs in this class was presented.
• The Committee was asked to consider drugs that may be more effective in special populations especially those with complex drug regimens.

On the topic of identification of preferred drugs in the therapeutic class of Beta Blockers:

• Information regarding trial results (approved dosing, efficacy, select indications/mechanism of actions, safety profile and compliance) for drugs in this category was presented.
• The Committee was asked to consider drugs with a specific indication for heart failure for inclusion on the preferred drug list and drugs that are most prescribed in the Medicaid population.

On the topic of identification of preferred drugs in the therapeutic class of Bisphosphonates:

• Information regarding trial results (approved dosing, efficacy and compliance) for drugs in this category was presented.
• The Committee was asked to consider convenience, simplified therapy, patient preference as well as efficacy in the review of this category.

D. Clinical Presentation and Discussion: Proposal to identify preferred drugs in the therapeutic class of Dihydropyridine Calcium Channel Blockers

Calcium Channel Blockers
Drugs Affected: Adalat (nifedipine), Adalat CC (nifedipine CC), Afeditab CR (nifedipine CR), Cardene (nicardipine), Cardene SR (nicardipine SR), DynaCirc (isradipine), DynaCirc CR (isradipine CR), felodipine ER, isradipine, nicardipine HCl, Nifediac CC (nifedipine CC), Nifedical XL (nifedipine XL), nifedipine, nifedipine ER, nifedipine SA, Norvasc (amlodipine), Plendil (felodipine ER), Procardia (nifedipine), Procardia XL (nifedipine XL), Sular (nisoldipine)

Marian McDonagh, PharmD, Oregon Health & Sciences University, Evidence-based Practice Center (OHSU EPC); Rob Coppola, PharmD, First Health Services Corporation (FHSC); Robert Correia, PharmD, NYS Department of Health, Office of Medicaid Management (DOH/OMM)

Dr. McDonagh (OHSU) provided a drug class review on calcium channel blockers. She described the search strategy, drugs, populations, study designs, outcomes and key questions included in the calcium channel blocker (CCB) study. Studies that address quality of life for hypertension and all-cause mortality in CCBs vs. Ace-Inhibitor and CCB vs. Diuretic or Beta Blocker, comparative efficacy of CCBs for hypertension, chronic stable angina, atrial fibrillation and systolic dysfunction, evidence on adverse events were discussed. Study findings regarding long-term safety for all-cause mortality, cancer, and breast cancer as well as comparative efficacy and safety in subgroups (e.g., patients with diabetes, renal insufficiency, coronary artery disease and older Japanese patients) were presented. Dr. McDonagh acknowledged that one of the trials mentioned during the public comment period was not included as it was not available at the time the OHSU review was performed. She also stated that the other trial mentioned was not included as the study population consisted of normo-tensive patients and could not, therefore, compare it to other studies in the review.

Dr. Mark Johnson questioned whether gingival hyperplasia associated with amlodipine was identified in any of the studies. Dr. McDonagh did not find any evidence of this in any of the studies. Dr. Johnson suggested dentists be alerted and asked to report this adverse event to the FDA.

Dr. Coppola of First Health Services Corporation (FHSC) presented further information on the category, and discussed the availability of brand and generic dihydropyridine CCBs (DHP CCBs) and their indications, dosing and common pharmacology. He advised that Nimotop (nimodipine) will not be considered in this therapeutic class review. The use of CCBs in the treatment of hypertension was reviewed. Dr. Coppola noted that there are a number of head to head trials for agents within this class comparing their relative ability to lower blood pressure. All agents have demonstrated the ability to lower blood pressure to goal and antihypertensive efficacy is similar among all agents. This is generally considered a class effect.

Dr. Coppola advised that calcium channel blockers are recommended for the treatment of angina when beta-blockers are not successful or are contraindicated. From the available evidence, there are few head to head studies available to determine the superiority of the CCBs in the treatment of angina and their efficacy in this use is considered a class effect.

Dr. Coppola advised calcium channel blockers have been shown to be generally well tolerated in clinical trials; however there are adverse events associated with this class of drug. Many reactions, particularly those relating to vasodilatation, are dose related and are generally considered a class effect. With regard to special populations, there is no evidence that any of the available dihydropyridine CCBs differ in their efficacy in any specific population.

Dr. Correia, Office of Medicaid Management, provided the Department's recommendations regarding the clinical reviews for this category of drugs. He noted that the DHP CCBs reviewed are all FDA approved for hypertension. Their benefit in vasospastic angina and chronic stable angina is considered to be a class effect.

Dr. Correia noted trial results and the lack of head-to-head trials to examine differences in all-cause mortality, cardiovascular mortality, or cardiovascular events among patients with hypertension. Use of active-control trials for indirect comparisons is severely limited by heterogenaeity and clinical differences of study designs. Neither head-to head trials nor indirect comparisons of active- or placebo-controlled trials provided evidence of difference between CCBs in efficacy for angina. Dr. Correia advised that there is no clear evidence of a difference in safety between CCBs in patients with hypertension or angina and that there was no evidence demonstrating differences between the CCBs in efficacy or safety in special patient populations (age,race, gender). Dr. Correia also addressed the issue of the clinical trial which wasn't available at the time of the OHSU review; that the study was of questionable relevance to this comparative review as it was a comparison of completely different combination therapies (DHP CCB plus an ACEI versus a BB plus a diuretic). Dr. Correia concluded that at this time there is not adequate evidence of overall clinical superiority to justify preferential availability of any specific DHP CCB.

The Committee was provided sample prior authorization criteria questions based on Public Health Law and clinical considerations for discussion. These questions are applicable to both the DHP CCB category and the CCB/ACEI category of drugs.

E. Clinical Presentation and Discussion: Identification of preferred drugs in the therapeutic class of Calcium Channel Blockers/ACEI Combinations

Calcium Channel Blockers/ACEI Combinations
Drugs Affected: Lexxel (enalapril maleate/felodipine ER), Lotrel (benazepril HCL/amlodipine besylate), Tarka (trandolapril/verapamil HCL ER)

John Santa, MD, (OHSU EPC); Rob Coppola, PharmD, (FHSC); Robert Correia, PharmD, (DOH/OMM)

Dr. Coppola advised that both of these classes have already been reviewed by this committee with the exception of the non-dihydropyridine CCB verapamil. He also advised that these agents are all indicated for the treatment of hypertension and are used in those patients that do not respond to monotherapy. He noted highlights from JNC-VII relating to management of blood pressure with more than one agent and advised that several studies have been published demonstrating the benefits of combination therapy compared to monotherapy. Dr. Coppola reported that there are no pharmacokinetic profile changes with combination products versus each single agent except with verapamil SR 240 mg and trandolapril 4 mg (Tarka), in which an increase in AUC and Cmax are seen with verapamil.

Dr. Coppola advised that head-to-head trials of these combination agents have not been conducted. However, trials with the combination agent versus the individual components or a combination of the individual agents have shown that the combination agents are better at lowering blood pressure than the individual agents alone and an equal ability to lower blood pressure versus the individual agents taken together.

Dr. Correia noted that the CCB/ACEI combination products are only indicated for treatment of hypertension and can be considered convenience dosage forms. He noted that the ACEI therapeutic class was previously reviewed in the 2/2/06 P & T Meeting, with the determination of lack of overall clinical superiority among ACEIs. Additionally, no evidence has supported superiority of any ACEI or any CCB for treatment of hypertension and at this time there is not adequate evidence of clinical superiority to justify preferential availability of any CCB/ACEI combination product.

Dr. Santa advised this has been a difficult area to review and that the OHSU did not address these combination products.

The Committee was provided sample prior authorization criteria questions based on Public Health Law and clinical considerations for discussion. These questions are applicable to both the DHP CCB category and the CCB/ACEI category.

F. Clinical Presentation and Discussion: Identification of preferred drugs in the therapeutic class of Beta Blockers

Beta Blockers/Beta Blocker Diuretic Combinations
Drugs Affected: acebutolol, atenolol, atenolol/chlorthalidone, Betapace (sotalol), Betapace AF (sotalol AF), betaxolol, bisoprolol fumarate, bisoprolol fumarate/HCTZ, Blocadren (timolol), Cartrol (carteolol), Coreg (carvedilol), Corgard (nadolol), Corzide (nadolol/bendroflumethiazide), Inderal (propranolol), Inderal LA (propranolol LA), Inderide (propranolol/HCTZ), Inderide LA (propranolol LA/HCTZ), Innopran XL (propranolol XL), Kerlone (betaxolol), labetalol, Levatol (penbutolol), Lopressor (metoprolol tartrate), Lopressor HCT (metoprolol tartrate/HCTZ), metoprolol tartrate, metoprolol tartrate/HCTZ, nadolol, Normodyne (labetalol), pindolol, propranolol, propranolol/HCTZ), Sectral (acebutolol), Sorine (sotalol), sotalol, Tenoretic (atenolol/chlorthalidone), Tenormin (atenolol), Timolide (timolol maleate/HCTZ), timolol maleate, Toprol XL (metoprolol succinate XL), Trandate (labetalol), Zebeta (bisoprolol fumarate), Ziac (bisoprolol fumarate/HCTZ)

Mark Helfand, MD, (OHSU EPC); Rob Coppola, PharmD, (FHSC); Robert Correia, PharmD, (DOH/OMM)

Dr. Helfand presented the OHSU review of beta blockers and discussed head to head trials, efficacy and side effects and drugs in this class used in heart failure. Differences in efficacy of drugs in race were also discussed. Dr. Martin inquired about the tolerability of beta blockers in heart failure. Dr. Helfand explained that as the tolerability is not related to any one agent, there is not particular benefit to start with any particular agent.

Dr. Coppola presented clinical information on beta blockers noting all of the beta blockers are indicated for hypertension but other approved indications include the treatment of arrhythmias, angina, heart failure, MI, and migraines. He advised that sotalol, will not be discussed in the context of this review due to its unique classification as an antiarrhythmic and its black box warnings.

Dr. Coppola discussed the various beta blockers and their use in hypertension, MI, arrythmias and heart failure. Dr. Coppola advised in conclusion, according to the evidence, all beta-blockers appear to be equally effective for treatment of hypertension, preventing and treating ventricular arrhythmias, and slowing the rapid ventricular rate associated with atrial tachyarrhythmias and it is recommended that the agents in this class be considered therapeutic alternates. For the treatment of heart failure, according to the ACC/AHA guidelines, either bisoprolol, carvedilol or metoprolol succinate is recommended for the treatment of heart failure. There is no evidence to support one agent over another in the treatment of heart failure.

Dr. Correia presented an overview of the beta blockers class discussing their varying effects on specific adrenergic receptors, intrinsic sympathomimetic activity, and duration of effect and elimination. He advised there is overlap between these categorizations, as well as dose-dependent decreases in specificity of some effects. The beta blockers included in the PDL review are all approved for multiple indications, and many are efficacious for multiple uses beyond those specifically listed noting the indication common to all of the beta blockers is hypertension.

Dr. Correia advised there is a lack of evidence to demonstrate overall comparative advantage for any one beta blocker for indications shared by the entire class. Any additional specific indication for a non- preferred drug for a special population (such as impaired liver function, heart failure, or migraine) may be addressed in prior authorization criteria if needed.

G. Clinical Presentation and Discussion: Identification of preferred drugs in the therapeutic class of Bisphosphonates

Bisphosphonates
Drugs Affected: Actonel, Actonel with Calcium, Boniva, Fosamax tablet, Fosamax solution, Fosamax Plus D

Jeanne Kennicutt, RPh, MBA, (FHSC); Robert Correia, PharmD, (DOH/OMM)

Ms. Kennicutt presented an overview of the bisphosphonate class of drugs stating there are currently three oral bisphosphonates available in the US, alendronate (Fosamax), risedronate (Actonel) and ibandronate (Boniva). These oral bisphosphonates share common (class effect) indications for prevention and treatment of osteoporosis in women and men, glucocorticoid-induced osteoporosis and Paget's disease. She noted that all of the bisphosphonates carry the same warnings regarding esophageal irritation and carry special administration instructions; but overall, oral bisphosphonates are generally well tolerated. Contraindications, common adverse effects and drug interactions are considered class effect. Ms. Kennicutt advised available clinical trials assess efficacy and consist mainly of placebo controlled trials. All trials show either or both increased bone mineral density (BMD) and consistent reduction of fracture as well as similar side effect profiles and varying opinions exist in the published medical literature about the extent to which increases in BMD and changes in bone turnover markers for patients receiving bisphosphonates correlate to fracture risk reduction. Ms. Kennicutt concluded the primary goal in the prevention and treatment of osteoporosis is the prevention of hip and vertebral fractures. There is no conclusive evidence establishing differences in efficacy between any of the bisphosphonates. Direct comparative evidence with equivalent dosing is lacking related to incidence of fracture. There is no durable evidence demonstrating increased compliance between daily, weekly or monthly dosing regimens.

Dr. Correia presented an overview of this class of drugs stating all oral bisphosphonates are FDA approved for treatment of osteoporosis in post-menopausal women. Efficacy for other indications appear to be class effects. He advised the critical relevant efficacy measure for use of these drugs is prevention of fractures. Bone mineral density (BMD) or biochemical markers of bone turnover are often measured in clinical studies, but these are only surrogate markers and do not consistently translate to equivalent changes in fracture rates.

Dr. Correia discussed drug trials with these agents, dosing and adherence noting as yet there is no evidence demonstrating increased compliance with monthly dosing over daily or weekly. In fact large studies (over 10,000 women) presented within the past year indicated no increase in adherence with decreased dosing frequency of these drugs. Dr. Correia concluded there is a lack of comparative evidence to demonstrate advantage between bisphosphonates in terms of efficacy or safety. Any additional specific indications for special populations (such as Paget's disease), may be addressed in prior authorization criteria if needed. At this time there is not adequate evidence of overall clinical superiority to justify preferential availability of any specific drug.

H. Executive Session:

The Committee recessed the public session at 10:30 A.M. to go into executive session for review of financial information relating to the determination of preferred drugs in the following classes: Dihydropyridine Calcium Channel Blockers and the Calcium Channel Blockers/ACEI Combinations. No official action was taken in the executive session. The executive session was recessed at 12:15 P.M.

The Committee recessed the public session at 1:15 P.M. to go into executive session for review of financial information relating to the determination of preferred drugs in the following classes: Beta Blockers and Bisphosphonates. No official action was taken in the executive session. The executive session was recessed at 2:20 P.M.

I. Recommendations of the Pharmacy and Therapeutics Committee:

The following recommendations developed by the P&T Committee are to be submitted to the Commissioner of Health for final determination.

Description of Recommendations	Commissioner's Final Decision
Proposal: Identification of preferred drugs in the category of dihydropyridine calcium channel blockers A. The Committee unanimously recommended the following: Preferred Drugs: Afeditab CR, Dynacirc, Dynacirc CR, felodipine ER, isradipine, nicardipine HCl, Nifediac CC, Nifedical XL, nifedipine, nifedipine ER, nifedipine SA, Norvasc, Sular Non-preferred Drugs: Adalat, Adalat CC, Cardene, Cardene SR, Plendil, Procardia, Procardia XL B. The Committee unanimously recommended the following clinical questions be used as the basis for approving use of the non-preferred drug: Q: Has your patient experienced treatment failure with a preferred calcium channel blocker? Q: Has your patient experienced an adverse drug reaction with a preferred calcium channel blocker? Q: Is there a documented history of successful therapeutic control with a non-preferred calcium channel blocker and transition to a preferred calcium channel blocker is medically contraindicated? C. Other: The Committee recommends revisiting this drug category in one year.	Approved as Recommended
Proposal: Identification of preferred drugs in the category of Calcium Channel Blockers/ACEI Combinations A. The Committee unanimously recommended the following: Preferred Drugs: Lotrel, Tarka Non-preferred Drugs: Lexxel B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process (reflected in the calcium channel blocker proposal above).	Approved as Recommended
Proposal: Identification of preferred drugs in the category of Beta Blockers A. The Committee recommended the following (with a vote of 5 to 3): Preferred Drugs:Acebutolol, atenolol, betaxolol, bisoprolol, labetalol HCl, metoprolol tartrate, nadolol, pindolol, propranolol HCl solution, propranolol HCl tablet, timolol maleate Non-preferred Drugs:Cartrol, Corgard, Inderal, Inderal LA, Innopran XL, Kerlone, Levatol, Lopressor, Sectral, Tenormin, Toprol XL, Trandate, Zebeta, Coreg B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process and that the following additional clinical question be added for this drug class: Q: Does this patient have heart failure? No action was taken on Beta Blocker Combination products.	Preferred and non-preferred drugs approved as recommended. Utilization patterns of drugs in this category will be monitored. After the category has been subject to the PDP for six months, it will be reviewed to evaluate how drugs are being used relevant to treatment of heart failure. Review criteria for prior authorization are amended, with the initial questions presented to the prescriber for approval of a PA relevant to heart failure. Questions are amended as follows: Is this patient being treated for heart failure? Were the heart failure symptoms previously controlled with another medication? Has your patient experienced treatment failure with a preferred beta blocker? Has your patient experienced an adverse drug reaction with a preferred beta blocker? Is there documented history of successful therapeutic control with a non-preferred beta blocker and transition to a preferred beta blocker is medically contraindicated?
Proposal: Identification of preferred drugs in the category of Bisphosphonates A. The Committee unanimously recommended the following: Preferred Drugs: Fosamax tablet, Fosamax solution, Fosamax Plus D Non-preferred Drugs: Actonel, Actonel with Calcium, Boniva B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.	Approved as Recommended

J. Additional Discussion:

During the discussion of the Beta Blocker category, a member stated the position that Coreg and Toprol XL should also be included as preferred drugs based on their indication for heart failure.

K. Reports:

Mr. Anthony Merola, RPh, MBA (DOH/OMM) presented a report on the outcomes of the Proton Pump Prior Inhibitor Authorization Program. Mr. Merola provided the Committee with background on the administration of the program. He noted that a full evaluation cannot be completed until six months after implementation when the transition period is complete. In the interim, however, there were the following findings:

• Initial data demonstrates significant reductions in prescribing practices and payments for all proton pump inhibitors (PPIs)
• Utilization of prescription PPIs has decreased from 99% of PPI claims in the three months prior to implementation, to approximately 70% of all PPI claims in December 2005
• Conversely the use of OTC PPIs has increased from less than 1% of all PPI claims to almost 30%
• Average gross cost per claim has declined from $139 in the quarter prior to implementation, to $108 in December 2005
• Total Medicaid expenditures for PPIs has declined from an average monthly cost of $26M in the quarter prior to implementation to $15.5M in December 2005, a reduction of almost 40% in the initial three months
• It is anticipated that additional savings will be realized after the 180 day prescription expiration period ends on April 2, 2006. Additional findings will be presented to the Committee when the implementation phase is completed.

The meeting adjourned at 3:00 PM.

L. Final Determinations:

The Commissioner has determined that Medicaid will require prior authorization under the Preferred Drug Program (PDP) for non-preferred drugs, as listed above, in the following classes: Dihydropyridine Calcium Channel Blockers; Calcium Channel Blockers/ACEI Combinations; Beta Blockers and Bisphosphonates. Preferred drugs will not require prior authorization. The criteria for approval of Beta Blockers are revised as noted above, and utilization patterns of non-preferred drugs will be analyzed after this category of drugs has been subject to the PDP for a period of six months.

The impacts of this final determination are as follows:

1. State Public Health Population:

• Minimal effects as a large majority of Medicaid patients currently utilize those drugs which have been determined to be preferred.
• Use of prior authorization for non-preferred products encourages use of more cost effective drugs within the same therapeutic class when appropriate.

2. Program Providers:

• Limited additional time and effort will be required by prescribers to complete the prior authorization process for non-preferred drugs.
• Utilization of non-preferred Beta Blockers will be reviewed after six months to assure appropriate medications are available for the subset of recipients who require treatment for heart failure.

3. Fiscal Impact to State Health Program:

• Through the changes in utilization to more cost effective drugs, and the receipt of supplemental rebates from pharmaceutical manufacturers, annual savings for the Preferred Drug Program are estimated at $16M, adjusting for the implementation of Medicare Part D.

Posted April 27, 2006