Pharmacy and Therapeutics Committee Meeting Summary - September 16, 2010

Agenda and Introduction

The Medicaid Pharmacy & Therapeutics Committee met on Thursday, September 16, 2010 from 8:30 a.m. to 4:30 p.m. in 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 provided comment to the committee:

1. Rosenthal, Harvey, Director, New York Association of Psychiatric Rehabilitation Services, Albany, NY
2. Liebman, Glenn, CEO, Mental Health Association in NYS, Albany, NY
3. Qualtere, Thomas A, MD, Psychiatric Group, Schenectady, NY
4. Morris, Adrian, MD, Glens Falls Hospital, Glens Falls, NY
5. Van Bellingham, Heidi, MD, Ellis Hospital Out-Patient Mental Health Services, Schenectady, NY
6. Breen-Lamb, Nancy, Director, National Alliance on Mental Illness NYS, Albany, NY
7. Roberts, Holly, MD, Pfizer, NY, NY
8. Self, Rachel, PhD, Bristol-Myers Squibb, Princeton, NJ
9. Price, Arlene, PharmD, Ortho-McNeil Janssen, Randolph, NJ
10. Szabo, Erika, MPH, Eli Lilly, Carnegie, PA
11. Street, Jamie, MD, AstraZeneca, Wilmington, DE
12. Hochfeld, Marla, MD, Novartis, Morris Township, NJ
13. Goldberg, Alan, RPh, Azur Pharma, Philadelphia, PA
14. Dietrich, Gary, MD, Merck, West Point, PA
15. Schroeder, Scott, MD, Albany Medical Center, Albany, NY
16. Mavumkal, Romy, Regional Medical Scientist, GSK, Research Triangle Park, NC
17. Zangrilli, James G, Director, AstraZeneca Pharmaceuticals, Wilmington, DE
18. Lepore, Mark, MD, TEVA Pharmaceuticals USA, Horsham, PA
19. Ham, Debby, MD, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT
20. Hede, Shalini, PharmD, Takeda Pharmaceuticals America, Deerfield, IL
21. Busch, Robert S, MD, The Endocrine Group, Albany, NY
22. Argoff, Charles E, MD, Albany Medical College, Albany NY
23. Dac-Korytko, Ia, PharmD, AstraZeneca, Wilmington, DE
24. Sanchez, Dorothea Y, PhD, Eisai Pharmaceuticals, Woodcliff Lake, NJ
25. Tolge, Bruno, MD, Schenectady Neurological Consultants, PC, Schenectady, NY

C. Key issues raised by interested parties and the Pharmacy and Therapeutics Committee pertaining to the clinical review of the following therapeutic classes/drugs:

Public comments:

Atypical Antipsychotics:

• The Committee was asked to consider the impact of placing the atypical antipsychotics into the Preferred Drug Program (PDP), even though based on the PDP prior authorization exemption, any drug in this therapeutic class determined to be non-preferred would not require prior authorization. The Committee was also asked to consider indications (adult and pediatric), mechanism of action, dosing, efficacy, safety, Boxed Warnings, adverse events, metabolic and tolerability profiles, the National Institute of Health & Clinical Excellence (NICE) Schizophrenia Meta-analysis, and the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE).

Inhaled Beta-2 Adrenergic Agents - Long Acting:

• The Committee was asked to consider the recent safety-related label updates for all long-acting beta agonists (LABA) indicated for the management of asthma.

Inhaled Corticosteroids:

• The Committee was asked to consider information regarding indications, dosing and dosage formulations, safety, efficacy, effectiveness in decreasing exacerbations and reducing the utilization of rescue inhalers. The LABA label update (in reference to the combination ICS/LABA products) and the National Institutes of Health (NIH) asthma guidelines were mentioned.

Inhaled Anticholinergics:

• The Committee was asked to consider a new indication, new warnings and precautions, and new adverse reaction information for tiotropium, and the latest FDA statement regarding the safety review for tiotropium.

Thiazolidinediones:

• The Committee was asked to consider clinical trial results for pioglitazone with regard to macrovascular events, cardiovascular events, bone fracture and bladder cancer, as well as the place in therapy for the TZDs considering obesity, insulin resistance and beta cell failure.

Long Acting Narcotics:

• The Committee was asked to consider patient access to multiple formulations of long acting narcotics.

Prescription Non-Steroidal Anti-Inflammatory Drugs (NSAIDs):

• The Committee was asked to consider information regarding a combination naproxen/esomeprazole product including indications, dosing, pharmacokinetics and adverse events.

Alzheimer's Agents:

• The Committee was asked to consider information regarding indications, efficacy, safety, high dose (23mg) versus standard dose (10mg) donepezil, new safety information for the rivastigmine patch, and two clinical trials regarding combination therapy with a cholinesterase inhibitor and an N-methyl-D-aspartate (NMDA) receptor antagonist.

D. Clinical Presentation and Discussion

Barbara Rogler, PharmD, MS, Magellan Medicaid Administration; Marian McDonagh, PharmD, Oregon Health & Sciences University, Evidence-based Practice Center (OHSU EPC); Robert Correia, PharmD, NYS Department of Health, Office of Health Insurance Programs (DOH/OHIP)

Preferred Drug Program: Initial Review

1. Proposal to identify preferred drugs in the therapeutic class of Atypical Antipsychotics (AAP)

Dr. McDonagh from the OHSU EPC presented the Drug Effectiveness Review Project (DERP) Drug Class Review for the Atypical Antipsychotics.

Dr. Correia and Dr. Rogler discussed product indications and adverse event profiles, and noted that drug selection is often guided with consideration of the adverse event profile as well as efficacy of a drug for a particular indication. Dr. Rogler also discussed pharmacology, pharmacokinetics, boxed warnings, warnings and precautions, metabolic effects, drug interactions, use in special populations and dosage for the drugs in the class. Both discussed practice guidelines for the treatment of schizophrenia. Dr. Correia concluded it would be preferable to have as large a selection of different products as possible represented as preferred drugs within the program, noting that at this time no prior authorization would be required for any atypical antipsychotic determined to be non-preferred.

A Committee member and Dr. McDonagh discussed the impact of an open label lead in phase in trials. Another member pointed out the lack of head to head trials between clozapine and other AAPs. Dr. Correia noted that superior efficacy in one area in a trial is not necessarily indicative of overall superiority of a drug.

2. Proposal to identify preferred drugs in the therapeutic class of Rectal Benzodiazepines

Dr. Rogler provided a clinical review of diazepam rectal gel and Dr. Correia noted the products in the class are therapeutically equivalent and therefore no clinical comparison is warranted.

The presenters confirmed for a Committee member that the delivery systems for the brand and the generic products were comparable.

Preferred Drug Program: Re-review

1. Inhaled Beta-2 Adrenergic Agents - Short Acting

Drs. Correia and Rogler noted the new generic product (levalbuterol solution) in the class, and discussed the anticipated loss of the chlorofluorocarbon (CFC) propelled products.

2. Skeletal Muscle Relaxants

Drs. Correia and Rogler noted the new generic metaxalone product in the class.

3. Anti-Fungals

Drs. Correia and Rogler noted no new clinical evidence was found to change the previous assessment of the drugs in this class. Dr. Correia also noted again this year that the topical preparations in the class, when compared to the oral agents, are of questionable effectiveness in resolving onychomycosis.

4. Inhaled Beta-2 Adrenergic Agents - Long Acting

Drs. Correia and Rogler discussed the Food and Drug Administration (FDA) requirement that manufacturers revise their drug labels for all the drugs in the class due to safety concerns with their use in treating asthma. Dr. Rogler also noted the FDA is requiring a Risk Evaluation and Mitigation Strategy (REMS) for these products.

A Committee member confirmed that NY Medicaid Drug Utilization Review (DUR) is aware of and will continue to evaluate and address inappropriate LABA prescribing. It was also noted that there is currently no data to confirm that use of an inhaled corticosteroid in combination with an inhaled LABA mitigates the adverse effects that may occur with the use of a LABA alone for the treatment of asthma.

5. Inhaled Anticholinergics

Dr. Correia reiterated the systematic review and meta-analysis of ipratropium and tiotropium which found increased risk in the data for both products for cardiovascular adverse events. He and Dr. Rogler both reiterated that the FDA issued an Early Communication in 2008 based on analysis of clinical trials of patients with COPD. The FDA found that patients in the inhaled tiotropium group experienced a possible increased risk of cardiovascular morbidity and mortality. He and Dr. Rogler also both noted the results of the January 2010 Follow-up to the Early Communication which states the FDA final review of tiotropium indicates the data do not support an association between tiotropium and these serious adverse events. Dr. Rogler noted a new indication for tiotropium. Dr. Correia concluded there has been no new evidence since the last review to support overall clinical superiority or increased risk differentially between these products.

6. Inhaled Corticosteroids (ICS)

Dr. Correia and Dr. Rogler discussed the new combination product in the class mometasone furoate and formoterol. They also discussed product indications and the FDA safety information that pertains to the long-acting beta agonist component of several of the products in this class. They again noted this warning pertains to use of the products for the treatment of asthma. They also discussed an unpublished non-inferiority trial between mometasone furoate/formoterol and fluticasone propionate/salmeterol. Dr. Correia concluded there is no adequate new evidence of clinical superiority for any of these products to justify preferential availability.

7. Thiazolidinediones

Dr. Rogler presented information on the new pioglitazone/metformin XR product. She and Dr. Correia both discussed the FDA advisory panel's recommendation to the FDA to keep rosiglitazone on the market, with some members voting for enhanced warnings or restricted use. Dr. Rogler noted two new studies published prior to the panel's meeting that pertain to the cardiovascular safety of rosiglitazone. It was noted the FDA final determination regarding the market status of rosiglitazone is expected in the coming months. Dr. Correia concluded at this time, there is still no comparative evidence which clearly demonstrates overall advantage of either of these products.

8. Long Acting Narcotics

Drs. Correia and Rogler discussed the new hydromorphone extended release and morphine sulfate/naltrexone products, and the new oxycodone CR formulation noting that manufacturers are attempting to reduce the abuse potential of long acting narcotics by pharmaceutically modifying their dosage forms in different ways. There is currently no evidence that this is effective, and the FDA is requiring of one manufacturer a post market study to collect data on the new formulation. Dr. Correia concluded there is no new comparative clinical evidence since the last re-review to indicate any of these drugs offers an overall advantage within the class.

A Committee member commented on the advisability of another hydromorphone product without product modification to prevent diversion as this narcotic is known to be subject to diversion and abuse.

9. Prescription Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Dr. Correia and Dr. Rogler discussed the new products in this class including two new diclofenac products and a combination naproxen and esomeprazole product. They focused on new clinical information relating to diclofenac including a new study indicating an increased risk of cardiovascular morbidity and mortality and new labeling for increased risk of elevated liver enzymes. Dr. Correia discussed the use of dimethylsufoxide (DMSO) as a vehicle, and also discussed a systematic review assessing the adverse effects of oral and topical NSAIDs reported in older adults. He noted both the oral and topical products share a common boxed warning as well as additional warnings and precautions. He concluded no new evidence was found for clear differences between NSAIDs with regard to efficacy, and no NSAID is consistently safer or associated with fewer adverse events.

A Committee member commented on the history of the "fenacs" class in general and on the topical use of diclofenac in particular, taking into consideration the drug's potential to cause liver toxicity.

10. Alzheimer's Agents

Dr. Correia and Dr. Rogler discussed the Effectiveness and Tolerability of High-Dose Versus Standard-Dose Donepezil in Moderate to Severe AD trial. Dr. Correia discussed new evidence presented for the addition of an NMDA inhibitor to cholinesterase inhibitor therapy. Dr. Rogler noted the availability a new generic rivastigmine capsule. In conclusion, Dr. Correia noted while the drugs in this class have been proven effective, the clinical treatment effect is very modest, and current evidence does not predict which patient will respond better to which drug, and no one drug has demonstrated overall superiority.

11. Anti-Virals

Drs. Correia and Rogler both noted the label update for Valtrex for increased risk of central nervous system adverse effects in adults and children. Dr. Rogler noted the new generic valacyclovir tablet.

E. Executive Session:

The Committee recessed the public session at 12:00 PM to go into executive session for review of financial information relating to the Committee's recommendations of preferred drugs. No official action was taken in the executive session. The executive session was recessed at 1:40 PM.

The Committee recessed the public session at 2:35 PM to go into executive session for review of financial information relating to the Committee's recommendation of preferred drugs. No official action was taken in the executive session. The executive session was recessed at 3:45 PM.

F. Recommendations of the Pharmacy and Therapeutics Committee submitted to the Commissioner of Health for final determination.

Based on the submitted or presented clinical information and on the financial information provided during the executive session, the Committee unanimously (unless otherwise noted) recommended the following:

Recommendations of Pharmacy and Therapeutics Committee	Commissioner's Final Determination
The standard clinical questions be used in the prior authorization review process for non-preferred drugs: Q: Has your patient experienced treatment failure with preferred drugs in the class? Q: Has your patient experienced an adverse drug reaction with preferred drugs in the class? Q: Is there a documented history of successful therapeutic control with a non-preferred drug and transition to a preferred drug is medically contraindicated? Atypical Antipsychotics: The Committee recommended the following (by a vote of 5 to 3): Preferred Drugs Abilify (aripiprazole), clozapine, Clozaril (clozapine), Fanapt (iloperidone), FazaClo (clozapine), Geodon (ziprasidone), Invega (paliperidone), risperidone, Risperdal (risperidone), Saphris (asenapine), Seroquel (quetiapine), Seroquel XR (quetiapine), Zyprexa (olanzapine) Non-preferred Drugs None	Approved as Recommended
Benzodiazepines - Rectal: Preferred Drugs Diastat 2.5mg Kit (diazepam), Diastat AcuDial System (diazepam) Non-preferred Drugs diazepam kits (2.5, 10 and 20mg)	Approved as Recommended
Inhaled Beta-2 Adrenergic Agents - Short Acting: Preferred Drugs albuterol solution, Maxair Autohaler (pirbuterol), Proventil HFA (albuterol), Ventolin HFA (albuterol) Non-preferred Drugs Accuneb (albuterol), levalbuterol solution, ProAir HFA (albuterol), Xopenex HFA (levalbuterol), Xopenex solution (levalbuterol)	Approved as Recommended
Skeletal Muscle Relaxants: Preferred Drugs baclofen, chlorzoxazone, cyclobenzaprine, dantrolene, methocarbamol, orphenadrine, orphenadrine compound, orphenadrine compound forte, tizanidine Non-preferred Drugs Amrix (cyclobenzaprine ER), carisoprodol, carisoprodol compound, carisoprodol compound-codeine, Dantrium (dantrolene), Fexmid (cyclobenzaprine), metaxalone, Parafon Forte DSC (chlorzoxazone), Robaxin (methocarbamol), Skelaxin (metaxalone), Soma (carisoprodol), Zanaflex (tizanidine)	Approved as Recommended
Anti-Fungals: Preferred Drugs ciclopirox laquer, Gris-PEG (griseofulvin), griseofulvin suspension, terbinafine Non-preferred Drugs Grifulvin V tablet (griseofulvin), itraconazole, Lamisil (terbinafine), Penlac (ciclopirox), Sporanox (itraconazole)	Approved as Recommended
Inhaled Beta-2 Adrenergic Agents - Long Acting: Preferred Drugs Foradil (formoterol), Serevent Diskus (salmeterol) Non-preferred Drugs Brovana (arformoterol), Perforomist (formoterol)	Approved as Recommended
Inhaled Anticholinergics: Preferred Drugs Atrovent HFA (ipratropium), Combivent (ipratropium/albuterol), ipratropium, ipratropium/albuterol, Spiriva (tiotropium) Non-preferred Drugs Duoneb (ipratropium/albuterol)	Approved as Recommended
Corticosteroids - Inhaled: Preferred Drugs Advair Diskus (fluticasone/salmeterol), Advair HFA (fluticasone/salmeterol), Asmanex (mometasone), Azmacort (triamcinolone), Flovent Diskus (fluticasone), Flovent HFA (fluticasone), Qvar (beclomethasone), Symbicort (budesonide/formoterol) Non-preferred Drugs Aerobid/Aerobid-M (flunisolide), Alvesco (ciclesonide), Dulera (mometasone furoate/formoterol fumarate dihydrate), Pulmicort Flexhaler (budesonide) Continue to use the one additional clinical prior authorization question for specific product indications: Q: Is the prior authorization request due to concerns related to pregnancy?	Approved as Recommended
Thiazolidinediones: The Committee recommended the following (by a vote of 7 to 1): Preferred Drugs Actos (pioglitazone), Actoplus Met (pioglitazone/metformin), Duetact (pioglitazone/glimepiride) Non-preferred Drugs Actoplus Met XR (pioglitazone/metformin), Avandia (rosiglitazone), Avandamet (rosiglitazone/metformin), Avandaryl (rosiglitazone/glimepiride)	Approved as Recommended
Long Acting Narcotics: Preferred Drugs Duragesic (fentanyl), Kadian (morphine sulfate SR), morphine sulfate SR, Opana ER (oxymorphone ER), Oramorph SR (morphine sulfate SR) Non-preferred Drugs Avinza (morphine sulfate ER), Embeda (morphine sulfate and naltrexone hydrochloride ER), Exalgo (hydromorphone HCL ER), fentanyl patch, MS Contin (morphine sulfate CR), oxycodone HCl CR, Oxycontin (oxycodone HCl CR)	Approved as Recommended
Prescription Non-Steroidal Anti-Inflammatory Agents: Preferred Drug diclofenac potassium, diclofenac sodium, diclofenac sodium XR, diflunisal, etodolac, etodolac SA, fenoprofen, flurbiprofen, ibuprofen, indomethacin, indomethacin SR, ketoprofen, ketoprofen SA, ketorolac, meclofenamate, mefenamic acid, meloxicam, nabumetone, naproxen, naproxen sodium, naproxen EC, oxaprozin, piroxicam, sulindac, tolmetin, Voltaren Gel (diclofenac sodium) Non-preferred Drugs Anaprox (naproxen sodium), Anaprox DS (naproxen sodium DS), Arthrotec (diclofenac sodium/misoprostol), Cataflam (diclofenac potassium), Clinoril (sulindac), Daypro (oxaprozin), Feldene (piroxicam), Flector (diclofenac epolamine), Indocin (indomethacin), Mobic (meloxicam), Nalfon (fenoprofen), Naprelan (naproxen sodium CR), Naprosyn (naproxen), Naprosyn EC (naproxen EC), Pennsaid (diclofenac sodium topical solution), Ponstel (mefenamic acid), Vimovo (naproxen and esomeprazole magnesium), Voltaren (diclofenac sodium), Voltaren XR (diclofenac sodium DR), Zipsor (diclofenac potassium)	Approved as Recommended
Alzheimer's Agents: Preferred Drugs Aricept 5mg and 10mg (donepezil), Aricept ODT (donepezil), Exelon Solution (rivastigmine), Exelon Patch (rivastigmine), galantamine, galantamine ER, Namenda (memantine), rivastigmine Non-preferred Drugs Aricept 23mg (donepezil), Exelon capsule (rivastigmine), Razadyne (galantamine), Razadyne ER (galantamine ER)	Approved as Recommended
Anti-Virals: Preferred Drugs acyclovir, Valtrex (valacyclovir) Non-preferred Drugs famciclovir, Famvir (famciclovir), valacyclovir, Zovirax (acyclovir)	Approved as Recommended

The meeting adjourned at 3:50 PM

Meeting Summary Posted 10/5/2010

G. Final Determinations

Preferred Drug Program

The Commissioner has determined that the Medicaid program will require prior authorization under the Preferred Drug Program (PDP) for non-preferred drugs in each of the drug classes as listed in Section F (except where prior authorization is prohibited by law).

Preferred Drugs will not require prior authorization

The impact of this final determination is as follows:

a. State Public Health Population:

• Minimal effect on Medicaid enrollees, as a large majority of enrollees currently utilize preferred products.
• Non-preferred products remain available with prior authorization when required.

b. Program Providers:

• No impact on prescribers or pharmacies when utilizing preferred products. Prescribers, or their agents, will need to initiate the prior authorization process when ordering non-preferred products except where prior authorization is prohibited by law. Pharmacies will need to complete the prior authorization process as required.

c. State Health Program:

• Annual gross savings associated with these therapeutic classes under the PDP are estimated at $22M. The savings are achieved through changes in utilization to equally effective and less expensive drugs including the receipt of supplemental rebates from pharmaceutical manufacturers.

Final Determinations Posted 11/01/2010