Pharmacy and Therapeutics Committee

New York State Office Of Medicaid Management
Pharmacy and Therapeutics Meeting Summary from Previous Meeting - September 19, 2006

Agenda and Introduction

The Medicaid Pharmacy & Therapeutics Committee met on Tuesday, September 19, 2006 from 8:45 a.m. to 3:00 p.m. in Meeting Room 6, Concourse, Empire State Plaza, Albany, New York.

Marilyn Desmond, NYS Department of Health, Office of Medicaid Management, introduced three new Committee members: Donna M. Chiefari, PharmD (pharmacist), John Westerman, RPh (pharmacist) and Kevin Huang-Cruz (consumer advocate). She then introduced Dr. David Lehmann, MD, PharmD, Professor of Medicine and Pharmacology, SUNY Upstate Medical University. Dr. Lehman has extensive experiences in the area of asthma and was the American College of Clinical Pharmacology representative to the Asthma Task Force for the National Institutes of Health. Dr. Lehmann will provide technical assistance and support to the Committee in their discussions of the asthma medications.

She then reminded the public that the purpose of the public comment is to allow representatives to provide comments regarding topics before the Committee. It was noted that written comments may be provided prior to the meeting, and that the public comment period be used as an opportunity to summarize those comments. Ms. Desmond reviewed the process to be used whereby the Committee reviews available clinical literature, especially clinical trials, regarding comparable efficacy, and evidence of clinical superiority in a therapeutic class, and then reviews confidential financial information relating to the determination of preferred drugs. The Committee then makes recommendations to the Commissioner of Health.

Dr. Martin (Chairperson) noted that testimony more recently has been of good quality and evidence based, and therefore has been more helpful to the Committee in the reviews of the therapeutic classes. He also noted that new clinical information is most helpful, and that Oregon Health and Sciences University assists in the review of some of the therapeutic classes.

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. Schroeder, Scott, MD, Director Pediatric Pulmonary, Albany Medical Center, Albany, NY
2. Cole, Michele, PharmD, Medical Science Specialist, Schering-Plough, Southampton, PA
3. Anton Konev for Honorable Peter M. Rivera, New York State Assembly, Albany, NY
4. Eggleston, Steven T., PharmD, Regional Medical Scientist, GlaxoSmithKline, Albany, NY
5. Iwanowicz, Peter M., Vice President, American Lung Association of New York State, Albany, NY
6. Beegle, Scott, MS, MD, Assistant Professor of Medicine, Albany Medical College, Albany, NY
7. Serfilippi, Geoffrey, MD, Director of Research, Pulmonary and Critical Care Services, Albany, NY
8. Lovick, Roberto G., PharmD, Regional Medical Scientist, Boehringer-Ingelheim
9. Tolat, Tejal, PharmD, Medical Science Liaison, Kos Pharmaceuticals, Inc., Cranbury, NJ
10. Saperstone, James, MD, Pediatrician/Medical Director, CapitalCare, MVP Healthcare, Schenectady, NY
11. Marcus, Philip, MD, MPH, Chief, Division of Pulmonary Medicine, St. Francis Hospital, Great Neck, NY
12. Dac-Korytko, Ia, PharmD, Senior Regional Scientific Manager, AstraZeneca, Buffalo, NY
13. Rathi, Dwarka P., MD, Medical Director, City Dialysis Unit, New York, NY
14. Horn, James F., MD, Capital District Renal Physicians, PC, Albany, NY
15. D'Ambrosio, Beth, PharmD, Regional Account Scientific Associate Director, Novartis Pharmaceuticals, Pittsford, NY

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

Public comments:

On the topic of identification of preferred drugs in the therapeutic class of Inhaled Beta ₂ Adrenergic Agents - Short Acting:

• Information regarding clinical trial results (safety, efficacy, indications, dosing, and adverse events) for drugs in this category was presented.
• The Committee was asked to consider the phase-out of inhalers containing chlorofluorocarbons (CFCs), the availability of alternative products, and the importance of having rescue asthma medications available.

On the topic of identification of preferred drugs in the therapeutic class of Inhaled beta ₂ Adrenergic Agents - Long Acting:

• Information regarding clinical trial results (indications, dosing, safety, adverse events) for drugs in this category was presented.
• The Committee was asked to consider the convenience of dosing devices, and the dosing in pediatrics and adults in the review of this category.

On the topic of identification of preferred drugs in the therapeutic class of Inhaled Anticholinergics:

• Information regarding clinical trial results (safety, efficacy, duration of action, tolerability, adverse reactions, lung function, health status, and effect on exacerbations and dyspnea) for drugs in this category was presented.
• The Committee was asked to consider the recommendations of national guidelines for the treatment of chronic obstructive pulmonary disease (COPD), the effects of the drugs in this class on health and functional status, and patient compliance in the review of this category.

On the topic of identification of preferred drugs in the therapeutic class of Inhaled Corticosteroids:

• Information regarding clinical trial results (safety, efficacy, indications, duration of action, adverse events, oral bioavailability, and use in pregnancy) for drugs in this category was presented.
• The Committee was asked to consider dosing in pediatrics, the recommendations of national guidelines for the treatment of asthma and COPD, dosing flexibility, and the importance of prevention and education in treating asthma in the review of this category.

On the topic of identification of preferred drugs in the therapeutic class of Phosphate Binders/Regulators:

• Information regarding clinical trial results (safety, efficacy, indications, mechanisms of binding phosphorus, adverse events) for drugs in this category was presented.
• The Committee was asked to consider the importance of the calcium/phosphorus balance, the different mechanisms of action of the medications in this class, the number of tablets required per dose, and the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF K/DOQI) guidelines.

On the topic of identification of preferred drugs in the therapeutic class of Topical Immunomodulators:

• Information regarding clinical trial results (safety, efficacy, indications, adverse events, systemic absorption, and comparisons to topical corticosteroids) for drugs in this category was presented.
• The Committee was asked to consider the differences in the two medications in this category including the indications, and dosage strengths, and also their place in therapy in the review of this category.

Pharmacy and Therapeutics Committee Response:

• A Committee member asked if there is data to support the presenter's statement indicating increased hospitalizations in New York State as a result of inhaler shortages and patients changing inhaler therapy. The presenter indicated he did not have that data, but would forward it to the Committee if the data was available.
• A Committee member asked if the TORCH study had been presented recently. The presenter indicated that the results of the study had been presented, but not published.
• A Committee member asked what other treatment options the presenter had tried in addition to Fosrenol. The presenter indicated that he had tried all three medications in this class and finds dosing regimens with fewer tablets easier for his patients.

D. Clinical Presentation and Discussion: Proposal to identify preferred drugs in the therapeutic class of Inhaled beta ₂ Adrenergic Agents - Short Acting

Inhaled beta ₂ Adrenergic Agents - Short Acting

Drugs Affected:Accuneb (albuterol), albuterol, albuterol HFA, Alupent (metaproterenol), Maxair Autohaler (pirbuterol), metaproterenol, Proventil (albuterol), Proventil HFA (albuterol), Ventolin HFA (albuterol), Xopenex (levalbuterol), Xopenex HFA (levalbuterol)

Rob Coppola, PharmD, First Health Services Corporation (FHSC); Robert Correia, PharmD, NYS Department of Health, Office of Medicaid Management (DOH/OMM)

Dr. Coppola provided a brief overview of asthma and COPD, including the roles of bronchodilators and inhaled corticosteroids in therapy. He described the medications in this category, including indications, pharmacology, pharmacokinetics, dosing, B2 receptor specificity, and adverse effects. He discussed clinical trials, including head to head trials, as well as the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report, and the Global Initiative for Asthma (GINA) guidelines. Based on a review of clinical studies, it was recommended that there is no conclusive evidence of difference in efficacy between the drugs in this category.

Dr. Correia provided the Department's clinical review for this category. He reiterated that the Department evaluates comparative clinical information on drugs. He discussed the appropriate use of these medications in asthma, exercise-induced bronchospasm (EIB) and COPD. He indicated that the effectiveness of these drugs is measured by real-practice outcomes that may not necessarily correspond to changes in pulmonary function tests. He discussed the published comparative effectiveness data for these medications in both asthma and COPD, and reiterated that the focus of the review is evidence relevant to the Medicaid pharmacy program. Considering the clinical information available as well as manufacturer information and practice guidelines, he indicated that at this time there is no adequate evidence of overall clinical superiority to justify preferential availability of any one product.

E. Clinical Presentation and Discussion: Proposal to identify preferred drugs in the therapeutic class of Inhaled beta ₂ Adrenergic Agents - Long Acting

Inhaled beta ₂ Adrenergic Agents - Long Acting

Drugs Affected: Foradil (formoterol), Serevent Diskus (salmeterol)

Rob Coppola, PharmD, (FHSC); Robert Correia, PharmD, (DOH/OMM)

Dr. Coppola described the medications in this category, including indications, pharmacology, pharmacokinetics, dosing, B2 receptor specificity, and adverse effects. He discussed clinical trials in asthma, COPD and EIB, including SMART, and a meta-analysis of trials of safety of long acting beta ₂ agonists. He again referenced the NAEPP Expert Panel Report and the GINA guidelines, and mentioned the Food and Drug Administration Public Advisory with regard to the use of these medications in asthma. Based on a review of the available clinical information, it was recommended that there is no conclusive evidence of difference in efficacy between the two drugs in this category.

Dr. Correia provided the Department's recommendations regarding the clinical review for this category of drugs. He reiterated the product indications, and that they are not meant for first line therapy for asthma. Dr. Correia indicated that in an overall review of comparative studies for asthma, seven studies found no significant difference between these drugs for symptoms, use of rescue medications, healthcare utilization, and quality of life. In COPD, one study showed no significant difference in respiratory symptoms between these drugs. He indicated that marginal potential differences in benefits seem to balance with differences in risks between these two drugs, with no evidence of overall clinical superiority to justify preferential availability of either one of these products.

A Committee member asked for clarification that with regard to efficacy and adverse events, for the short acting beta ₂ agonists, there were no significant differences, and for the long acting beta ₂ agonists, the differences were minimal. Drs. Coppola and Correia concurred that there was no evidence of superiority.

Dr. Martin asked Dr. Lehmann to share with the Committee his comments on the clinical information presented on the short and long acting beta ₂ agonists.

Dr. Lehmann stated that in clinical trials of the medications in this category, different subpopulations respond differently to study medications at the receptor level, resulting in either a decreased response, or a need for higher doses of medication which may result in increased adverse effects. This could account for variability in the trials. He noted that it is important to take this into account.

A Committee member asked Dr. Lehmann if anything presented with regard to the two classes indicated superiority, Dr. Lehmann indicated no, in his opinion.

F. Clinical Presentation and Discussion: Proposal to identify preferred drugs in the therapeutic class of Inhaled Anticholinergics

Inhaled Anticholinergics

Drugs Affected: Atrovent (ipratropium), Atrovent HFA (ipratropium), Combivent (ipratropium/albuterol), Duoneb (ipratropium/albuterol), ipratropium, Spiriva (tiotropium)

Rob Coppola, PharmD, (FHSC); Robert Correia, PharmD, (DOH/OMM)

Dr. Coppola described the medications in this category, including pharmacology, indications, dosing, pharmacokinetic properties, mechanism of action, efficacy, adverse events, and use in special populations. He discussed three clinical trials comparing ipratropium and tiotropium. He discussed the Global initiative for chronic Obstructive Lung Disease (GOLD) treatment guidelines noting the stepwise approach to treating COPD based on disease severity. Based on a review of the available clinical information, it was recommended that these medications may be considered therapeutic alternatives.

Dr. Correia provided the Department's recommendations regarding the clinical review for this category of drugs. He noted that the evaluation of effectiveness of drugs used to treat COPD is complicated by the fact that measurements of lung function do not consistently predict symptom improvements. All categories of bronchodilators have been shown to increase exercise capacity in COPD, without necessarily producing significant changes in FEV-1. Dr. Correia discussed clinical trials, including head to head trials, and noted that there is limited evidence directly comparing tiotropium to ipratropium in terms of symptoms, exacerbations, and outcomes. He also noted the importance of the size and baseline lung function of a study population and also the times and intervals at which lung function measurements are taken when evaluating clinical trials for these drugs. Finally, he explained that in health and quality of life surveys used to measure health outcomes, the majority of the results showed no difference between ipratropium and tiotropium. He concluded that at this time, there is not good evidence of differences in significant clinical outcomes between these anticholinergics. Some of the current clinical trials raise additional questions as to how this effectiveness may be clarified in the future.

Dr. Martin asked Dr. Lehmann to share with the Committee his comments on the clinical information presented on the inhaled anticholinergics.

Dr. Lehmann noted that it is important, when evaluating studies for these drugs, to note the difference between efficacy and effectiveness, and to look at health outcomes. In response to a question from the Committee, Dr. Lehmann noted that because COPD tends to be resistant to treatment, anticholinergics are often used as maintenance treatment, and may be combined with beta ₂ agonists.

G. Clinical Presentation and Discussion: Proposal to identify preferred drugs in the therapeutic class of Inhaled Corticosteroids

Inhaled Corticosteroids

Drugs Affected: Advair Diskus (fluticasone/salmeterol), Aerobid/Aerobid-M (flunisolide), Asmanex (mometasone), Azmacort (triamcinolone), Flovent HFA (fluticasone), Pulmicort (budesonide),Qvar (beclomethasone)

Richard Hansen, PhD, RPh, Oregon Health & Science University, Evidence-based Practice Center (OHSU EPC); Rob Coppola, PharmD, (FHSC); Robert Correia, PharmD, (DOH/OMM)

Dr. Hansen presented the summary of the OHSU review of inhaled corticosteroids and discussed the outcomes of key areas of inquiries based on findings from clinical trials, including head to head trials. He provided the outcomes of studies comparing efficacy and effectiveness, tolerability, and safety. He discussed general efficacy in asthma and COPD. He also discussed studies addressing specific adverse events and use within certain subgroups.

Dr. Coppola described the medications in this category, including indications, dosing and dosage forms, onset of action, adverse events, and use in pediatrics and pregnancy. Based on a review of the available clinical information, it was recommended that there is no conclusive evidence of difference in efficacy between the drugs in this category when given in equipotent doses.

Dr. Correia provided the Department's recommendations regarding the clinical review for this category of drugs. He noted the use of these drugs in pregnancy and pediatrics. He discussed the dosing of the different inhalers and noted, based on available evidence, that these drugs do not differ in their effectiveness when administered at equipotent doses. Evidence also does not clearly support any particular inhalation device for improving efficacy or safety. He noted that Advair is a combination product that accommodates the addition of a long acting beta ₂ agonist to inhaled corticosteroid therapy when indicated for patients with higher levels of disease severity. He concluded that at this time, there is not adequate evidence of overall clinical superiority of any one of these products to justify preferential availability.

Dr. Martin asked Dr. Lehmann to share with the Committee his comments on the clinical information presented on the inhaled corticosteroids.

Dr. Lehmann agreed that the medications in this category are equivalent and recommended that the Committee consider the number of doses per day and the number of inhalations per dose when discussing this category. Responding to a question regarding pregnancy category, he indicated that the number one issue in pregnancy is delivering adequate oxygen to the baby.

H. Clinical Presentation and Discussion: Proposal to identify preferred drugs in the therapeutic class of Phosphate Binders/Regulators

Phosphate Binders/Regulators

Drugs Affected: Fosrenol (lanthanum), Phoslo (calcium acetate), Renagel (sevelamer)

Rob Coppola, PharmD, (FHSC); Robert Correia, PharmD, (DOH/OMM)

Dr. Coppola presented a brief description of hyperphosphatemia as related to chronic kidney disease. He described the medications in this category, including indications, pharmacology, dosing, and adverse effects, and emphasized the importance of the calcium phosphorus balance. He explained the differences in the three drugs in the category. He discussed clinical trials including head to head trials and pediatric studies. He spoke about the K/DOQI guidelines on management of hyperphosphatemia. Based on a review of the available clinical information, it was recommended that the drugs in this category be considered therapeutic alternatives.

Dr. Correia provided the Department's recommendations regarding the clinical review for this category of drugs. He briefly explained the differences between the drugs including the mechanism of action, bioavailability and effect on calcium. He noted the change in the NKF-K/DOQI guidelines in 2003 and how that may affect the dosing of the drugs. He indicated that the three drugs under consideration represent two major treatment approaches, and either approach may have advantages at different stages of disease progression, with none of these drugs demonstrating overall advantages at all stages.

I. Clinical Presentation and Discussion: Proposal to identify preferred drugs in the therapeutic class of Topical Immunomodulators

Topical Immunomodulators

Drug(s) Affected: Elidel (pimecrolimus), Protopic (tacrolimus)

Rob Coppola, PharmD, (FHSC); Robert Correia, PharmD, (DOH/OMM)

Dr. Coppola presented a brief background on atopic dermatitis and a description of the medications in this category, including indications, pharmacology, efficacy, adverse reactions, and drug interactions. He explained recent labeling changes and the black box warning associated with these drugs. He noted that there are no head to head trials for these drugs and that indirect evidence showed comparable efficacy and adverse effects. Based on a review of the available clinical information, it was recommended that there is no conclusive evidence of difference in efficacy between the drugs in this category.

Dr. Correia provided the Department's recommendations regarding the clinical review for this category of drugs. He clarified that these medications are not indicated for use in children less than two years of age, and that Protopic is available in two strengths, one for patients sixteen years of age and over. He noted that the two medications are indicated for a different range of symptoms (mild-moderate and moderate-severe) and are second line therapy. He mentioned the black box warning and the concerns related to reported cases of malignancies. He indicated that at this time there is no evidence to indicate that either product is more safe or effective overall.

A Committee member commented that these medications are often prescribed in place of steroids and Dr. Coppola replied that they are indicated for use after other topical therapies have been tried or are deemed inappropriate. Dr. Correia commented that the long-term impact of topical immunosuppressants, especially in children, is currently in question.

J. Executive Session

The Committee recessed the public session at noon to go into executive session for review of financial information relating to the determination of preferred drugs in the following classes: Short Acting beta ₂ Adrenergic Agents, Long Acting beta ₂ Adrenergic Agents, Inhaled Anticholinergics, and Inhaled Corticosteroids. No official action was taken in the executive session. The executive session was recessed at 1:00 P.M.

The Committee recessed the public session again at 1:45 P.M. to go into executive session for review of financial information relating to the determination of preferred drugs in the following classes: Phosphate Binders/Regulators, and Topical Immunomodulators. No official action was taken in the executive session. The executive session was recessed at 2:40 P.M.

K. 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 Inhaled beta 2 Adrenergic Agents - Short Acting A. Based on the submitted or presented clinical information and on the financial information provided during the executive session, the Committee unanimously recommended the following: Preferred Drugs albuterol, Maxair Autohaler, Proventil HFA, Ventolin HFA, Xopenex, Xopenex HFA Non-preferred Drug Accuneb, Alupent, metaproterenol, ProAir HFA, Proventil B. The Committee unanimously recommended the following clinical questions be used as the basis for approving use of a non-preferred drug, should the Commissioner's final decision include a non-preferred drug: Q: Has your patient experienced treatment failure with a preferred short acting inhaled beta 2 adrenergic agent? Q: Has your patient experienced an adverse drug reaction with a preferred short acting inhaled beta 2 adrenergic agent? Q: Is there a documented history of successful therapeutic control with a non-preferred short acting inhaled beta 2 adrenergic agent and transition to a preferred short acting inhaled beta 2 adrenergic agent is medically contraindicated?	Approved as Recommended
Proposal: Identification of preferred drugs in the category of Inhaled beta 2 Adrenergic Agents - Long Acting A. Based on the submitted or presented clinical information and on the financial information provided during the executive session, the Committee unanimously recommended the following: Preferred Drugs Foradil, Serevent Diskus Non-preferred Drug None B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process, should the Commissioner's final decision include a non-preferred drug.	Approved as Recommended
Proposal: Identification of preferred drugs in the category of Inhaled Anticholinergics A. Based on the submitted or presented clinical information and on the financial information provided during the executive session, the Committee unanimously recommended the following: Preferred Drugs Atrovent, Atrovent HFA, Combivent, ipratropium, Spiriva Non-preferred Drug Duoneb B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.	Approved as recomended
Proposal: Identification of preferred drugs in the category of Inhaled Corticosteroids A. Based on the submitted or presented clinical information and on the financial information provided during the executive session, the Committee unanimously recommended the following: Preferred Drugs Advair Diskus, Advair HFA, Asmanex, Azmacort, Flovent HFA, Qvar Non-preferred Drugs Aerobid, Aerobid-M, Pulmicort Turbuhaler 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 Pulmicort Turbuhaler only: Q: Is this prior authorization request due to concerns related to pregnancy?	Approved as recommended
Proposal: Identification of preferred drugs in the category of Phosphate Binders/Regulators A. Based on the submitted or presented clinical information and on the financial information provided during the executive session, the Committee unanimously recommended the following: Preferred Drugs Fosrenol, Phoslo, Renagel Non-preferred Drugs None B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process, should the Commissioner's final decision include a non-preferred drug.	Approved as recommended
Proposal: Identification of preferred drugs in the category of Topical Immunomodulators A. Based on the submitted or presented clinical information and on the financial information provided during the executive session, the Committee unanimously recommended the following: Preferred Drugs Elidel, Protopic Non-preferred Drugs None B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process, should the Commissioner's final decision include a non-preferred drug. In addition, the Committee recommends reviewing this drug class under the Clinical Drug Review Program at the next meeting of the Pharmacy and Therapeutics Committee.	Approved as recommended Determined clinical intervention to be performed through the Drug Utilization Review (DUR) program rather than the Clinical Drug Review Program (CDRP).

L. Additional Discussion

Dr. Martin announced that Marilyn Desmond would be retiring shortly and that Linda Jones, RN, Assistant Director of the Bureau of Program Guidance, will replace her at the Pharmacy and Therapeutics Committee meetings. He thanked Ms. Desmond for her service to the Committee and the State

The meeting adjourned at 3:00 PM.

M. 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: Inhaled Beta₂ Adrenergic Agents - Short Acting, Inhaled Beta ₂ Adrenergic Agents - Long Acting, Inhaled Anticholinergics, Inhaled Corticosteroids, Phosphate Binders/Regulators and Topical Immunomodulators.
Preferred drugs will not require prior authorization.

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.

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 these categories of drugs under the Preferred Drug Program are estimated at $13.9M.

Meeting Summary Posted November 17, 2006