Pharmacy and Therapeutics Committee Meeting Summary - June 11, 2010

Agenda and Introduction

The Medicaid Pharmacy & Therapeutics Committee met on Friday, June 11, 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. Marble, Dwight A, PharmD, Senior Medical Science Liaison, Bristol-Myers Squibb, Rochester, NY
2. DeSantis, Jonathan, MD, Glens Falls Associates in Cardiology, Queensbury, NY
3. Szabo, Erika, MPH, Global Outcomes Liaison, Eli Lilly & Co, Carnegie, PA
4. Shapiro, Jeffrey, MD, Assistant Professor Of Medicine, New York Presbyterian / Columbia, Scarsdale, NY; representing Eli Lilly & Co/ Daiichi-Sankyo
5. Lewis, Charles (Tim), RPh, MBA, Managing Partner, Jasos Group, LLC, Lake Mary, FL; representing Allergan, Inc
6. Perrotta, Vincent G, MBA, RPh, Senior Area Manager, Allergan, Inc, West Plainview, NY
7. Zelefsky, Joseph, MD, Director of Glaucoma Service, Bronx Lebanon Hospital Center, Woodmere NY; representing Allergan, Inc
8. Brevetti, Teresa, MD, Regional Medical Research Specialist 1, Pfizer, Inc, NY, NY
9. Zangari, Lesley A, RN, Medical Science Liaison, Bayer Healthcare Pharmaceuticals, Inc, Wayne, NJ
10. DiFiore, Michael, PharmD, Medical Science Liaison, Biogen Idec, Cambridge, MA
11. Gordon, Mark Forrest, MD, Senior Associate Director, Medical Affairs, General Medicine, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT
12. Massad, Peter, PharmD, MPH, Medical Science Liaison, Bausch & Lomb, Madison, NJ
13. Parekh, Jai G, MD, FAAO, Partner, Brar-Parekh Eye Associates, West Paterson, NJ; Professor, The NY Eye & Ear Infirmary, NY, NY; representing Bausch & Lomb
14. Bundy, Kemp, MD, MBA, CapitalCare Medical Group, Clifton Park, NY; representing Alcon Laboratories
15. Osur, Scott L, MD, Certified Allergy & Asthma Consultants, Albany, NY
16. Baran, Daniel, MD, Region Medical Director, Merck & Co., Upper Gwynedd, PA

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:

Platelet Inhibitors:

• The Committee was asked to consider information regarding indications, safety, dosing and administration, contraindications, black box warnings, and efficacy versus adverse events, specifically bleeding, for the products in this class. Several clinical trials were noted, including COMMIT, CURE, and TRITON-TIMI 38. The Committee was also asked to consider the diminished effectiveness of clopidogrel in poor metabolizers and the use of prasugrel in this population.

Ophthalmic Beta Blockers:

• The Committee was asked to consider information regarding indications, efficacy, ocular side effects and patient comfort, and the advantages and place in therapy of a fixed dose combination drop for the treatment of glaucoma. The Committee was also asked to consider a clinical trial comparing the fixed dose beta blocker/alpha-2 agonist to a beta blocker alone when used as adjunctive therapy with a prostaglandin agonist.

Ophthalmic Prostaglandin Agonists:

• The Committee was asked to consider information regarding indications, safety, efficacy, side effects and tolerability, product potency, intraocular pressure (IOP) reductions and the effect of those reductions on disease progression, persistency on therapy, and discontinuation rates. The Committee was also asked to consider the results of clinical trials in which patients currently being treated with a prostaglandin agonist and in need of additional IOP lowering were changed to a different prostaglandin agonist.

Multiple Sclerosis Agents:

• The Committee was asked to consider information regarding indications, dose and frequency of dosing, efficacy, safety, tolerability, adherence to therapy and patient support programs. The Committee was also asked to consider clinical successes and long term data available for products in this class.

Non-Ergot Dopamine Receptor Agonists:

• The Committee was asked to consider information regarding indications, once a day dosing titrated to efficacy and tolerability, use as monotherapy and as adjunctive therapy with levodopa, the similarity in tolerability and safety of the extended release and the immediate release formulation of the drug, and side effects.

Ophthalmic Fluoroquinolones:

• The Committee was asked to consider information regarding clinical trials of a new ophthalmic fluoroquinolone with an active comparator as well as trials with a vehicle comparator, mechanism of action, indication, efficacy, microbiology, safety, tolerability, adverse events, dosing flexibility, vehicle properties, and resistance development.

Nasal Antihistamines:

• The Committee was asked to consider information regarding a new pediatric indication and a new indication for perennial allergic rhinitis for one of the products in this class, efficacy, time to onset of relief, and side effects.

Nasal Corticosteroids:

• The Committee was asked to consider information regarding the incidence and impact of allergic rhinitis, compliance as related to product taste or scent, onset of action, indications, including a new indication for nasal congestion for one of the products in this class, and tolerability. The presenter described a study in which pre-pubertal growth retardation was addressed.

Pharmacy and Therapeutics Committee Comments:

• A Committee member and several presenters discussed clopidogrel, prasugrel, and the use of these medications in patients who are CYP2C19 poor metabolizers or who take medications that inhibit CYP2C19. The Committee member noted that genotyping patients may offer some benefit, although this type of testing is not currently reimbursed in his area. The presenter agreed treatment is a risk versus benefit decision made on an individualized patient basis.
• A Committee member and presenter discussed the difference between double masked versus double blinded studies, and the presenter also clarified that the study discussed (fixed dose beta blocker/alpha-2 agonist versus a beta blocker alone when used as adjunctive therapy with a prostaglandin agonist) had not yet been published.
• A Committee member and presenter discussed the Betaseron Zero-Copay Program.
• A Committee member asked for clarification regarding immediate versus delayed treatment and progression of multiple sclerosis.
• A Committee member asked for clarification regarding DNA gyrase and topoisomerase IV including their clinical relevance.
• A presenter mentioned pharmacogenomics with regard to the nasal antihistamines class, and a Committee member asked for clarification. Another member asked why the product the presenter was speaking on behalf of was better than other products in the class, and the presenter noted a non-inferiority trial, as well as differences in vehicles and side effect profiles.

D. Clinical Presentation and Discussion

Barbara Rogler, PharmD, MS, First Health Services Corporation; 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 Platelet Inhibitors

Dr. Rogler described arterial and venous thrombi and provided background information on aspirin, dipyridamole and the thienopyridines clopidogrel, ticlopidine and prasugrel. She compared clopidogrel and prasugrel in terms of indications, formulations, metabolism, excretion, use in special populations, and black box warnings. She discussed the PRoFESS, CURE, and TRITON-TIMI 38 trials. She concluded the platelet aggregation inhibitors are used to prevent and treat a variety of thrombotic events including myocardial infarction (MI), stroke and transient ischemic attack (TIA) and peripheral arterial disease (PAD).

Dr. Correia discussed aspects of the TRITON-TIMI study which raised the question of whether all of the conclusions are truly externally transferrable when compared to current clinical practice. He noted the investigators used a loading dose of only 300 mg of clopidogrel when current guidelines recommend a 600 mg loading dose for patients undergoing percutaneous coronary intervention (PCI). Along with a reported increased efficacy for prasugrel was an increased incidence of major bleeding, life-threatening bleeding, and fatal bleeding. Also, with regard to the effects seen in diabetic patients in this study, Dr. Correia noted it may be that this population needs and tolerates more aggressive platelet treatment, and the study was not designed to evaluate this population. He also noted baseline population differences in the diabetic group. He noted the incidence of major or minor bleeding not related to coronary artery bypass graft (CABG) in the diabetic group was actually numerically higher than in the full study population, and major bleeding related to CABG was omitted from the data reported for the diabetic subgroup analysis. He described the black box warning for prasugrel relative to these findings, as well as identifying patient subgroups that may be more susceptible to adverse effects.

Dr. Correia indicated the FDA has required a post-marketing Risk Evaluation and Mitigation Strategy (REMS) for prasugrel. He concluded with this class of drugs, it is a case of balancing efficacy and risk of adverse outcomes within each clinical situation, and each drug in the class may have advantages or disadvantages in particular clinical applications, with none demonstrating overall superiority.

The Committee and presenters discussed the placebo arm of the PROFESS trial. They also discussed relative versus absolute risk reduction and the number needed to treat to prevent thrombosis versus the risk of causing a bleed. A Committee member commented on the decreased efficacy of clopidogrel when taken with certain proton pump inhibitors (PPI), noting that other PPIs do not interact with and decrease the effectiveness of clopidogrel, and in fact provide protection against GI bleeds while on anti-platelet therapy.

2. Proposal to identify preferred drugs in the therapeutic class of Ophthalmic Beta Blockers

Dr. Rogler described glaucoma including risk factors for the disease, and the eye drops commonly used in treatment, focusing on the ophthalmic beta-blockers. She discussed mechanism of action, adverse events, contraindications, drug interactions, use in special populations and dosage.

Dr. Correia noted a lack of direct comparative evidence between the products in this class. He explained the products have the same indications and are comparably effective for reduction of elevated intraocular pressure, with the exception of Combigan, which is indicated as adjunct or replacement therapy. He noted dosing is either once daily or twice daily depending on the product, and there is some variation in the vehicles used (solution, suspension, gel). All products have comparable precautions and tolerability with the possible exception of timolol LA which seems to have a higher incidence of burning and stinging. He concluded no product in the class demonstrates overall superiority.

Preferred Drug Program: Re-review

1. Ophthalmic Alpha-2 Adrenergic Agonists

Dr. Rogler made note of the new generic apraclonidine 0.5% ophthalmic solution (generic for Iopidine). Dr. Rogler and Dr. Correia noted that no new clinical information was found for this class.

2. Ophthalmic Prostaglandin Agonists

Dr. Rogler noted Travatan ophthalmic solution 0.004% will be discontinued by the manufacturer, and Travatan Z ophthalmic solution 0.004% will remain available. She found no other new clinical information for the class since the last review.

Dr. Correia discussed a head to head study of bimatoprost versus travoprost in patients previously treated with latanoprost. He discussed the limitations of the trial and concluded that either drug provided additional lowering of intraocular pressure. As discussed previously, small differences between study results of absolute change in intraocular pressures may only be statistically, but not clinically significant, once patient physical variability is accounted for.

The Committee discussed "masking" versus "blinding" in clinical trials.

3. Topical Anti-Virals

Dr. Rogler found no new clinical information for the class since the last review.

Dr. Correia stated these products are primarily used for cold sores to marginally shorten the course of a spontaneously resolving condition, with the exception of acyclovir ointment, which is indicated for genital herpes.

4. Multiple Sclerosis Agents

Dr. Rogler and Dr. Correia discussed Extavia, a new interferon beta-1b subcutaneous injection. Dr. Rogler explained that the two current interferon beta-1b subcutaneous injection products are manufactured by one company, and distributed by two different companies. She discussed the BEYOND trial, and provided a comparison of dosing and administration for the products in the class. Dr. Correia concluded that there is no evidence that any of these agents is better overall for all patients, and each may demonstrate favorable efficacy or tolerability for different patients.

5. Non-Ergot Dopamine Receptor Agonists

Dr. Rogler noted a new strength of Requip, the approval of Mirapex ER and a new generic pramipexole (generic Mirapex).

Dr. Correia noted that there are two drugs in this class and both are now available in immediate or extended release dosage forms, and all are indicated for Parkinson's disease. In addition, the immediate release forms of pramipexole and ropinirole are indicated for Restless Legs Syndrome. He concluded there is no evidence that any of these products is better overall for all patients for either diagnosis or point of disease progression, and each may demonstrate favorable efficacy or tolerability for different patients.

6. Ophthalmic Antihistamines

Dr. Rogler and Dr. Correia provided information on Bepreve (bepotastine), a new drug in the class since the previous review. Dr. Correia noted that the pediatric indication for Bepreve (bepotastine) allows for use in children as young as 2 years of age, while the other products in the class are indicated for children 3 years of age and over. They also noted a new generic azelastine 0.05% ophthalmic solution (generic for Optivar). Dr. Rogler provided a comparison of dosing for the products in the class. Dr. Correia concluded any of the available products are effective for the treatment of allergic conjunctivitis, with none of these drugs demonstrating overall advantages for all cases.

7. Ophthalmic NSAIDs

Dr. Rogler and Dr. Correia provided information on Acuvail (ketorolac tromethamine 0.45% ophthalmic solution), a new drug in the class since the previous review. They also noted the new generics ketorolac 0.4% and 0.5% ophthalmic solution (generic for Acular LS and Acular, respectively). Dr. Correia concluded a review of the clinical evidence available, including limited comparative evidence, did not reveal any overall clinical superiority for any drug in this class.

8. Ophthalmic Fluoroquinolones

Dr. Rogler and Dr. Correia discussed Besivance (besifloxacin 0.6% ophthalmic solution), a new drug in the class since the previous review. Dr. Rogler noted a comparative trial between besifloxacin 0.6% and moxifloxacin 0.5%. She provided a comparison of indications and dosing for the products in the class. Dr. Correia noted that besifloxacin has already demonstrated cross-resistance with some of the existing fluoroquinolones and per FDA safety review materials had a higher incidence of patients with at least one adverse event in clinical trials. He reiterated the spectrum of activity for the different generations of drugs in the class, and recommended the full spectrum be represented on the preferred drug list. Dr. Rogler closed by noting the goals of treatment for bacterial conjunctivitis and factors to consider when choosing treatment.

9. Topical Antibiotics

Dr. Rogler and Dr. Correia noted the availability of Centany (mupirocin 2% ointment). They noted no other new clinical information had been found for the class since the last review. Dr Correia reiterated there are two antibiotics in the class, available in a variety of vehicles and package sizes. He concluded that in general, each antibiotic has a place in therapy for specific applications or resistant organisms, with none of the products being preferential for overall clinical use.

10. Topical Agents for Psoriasis

Dr. Rogler and Dr. Correia discussed Vectical (calcitriol 3mcg/g ointment), a new drug in the class since the previous review. Dr. Rogler noted the product has the potential to increase serum calcium levels. They both provided information on a comparative trial between calcitriol ointment and calcipotriene ointment in patients with mild to moderate chronic plaque-type psoriasis. Dr. Rogler also noted The Journal of the American Academy of Dermatology updated guidelines regarding the management and treatment of psoriasis with topical therapies. Dr. Correia concluded that these products represent alternatives in mechanisms of action, as well as different adverse effects or types of application, which may be required at different times by different patients.

11. Oral Antihistamines

Dr. Rogler and Dr Correia noted a new generic fexofenadine with pseudoephedrine (generic Allegra-D), and the expanded pediatric indication for Xyzal (levocetirizine). Dr Correia also elaborated on pediatric dosing for other products in this therapeutic class. He explained that the over-the-counter (OTC) antihistamines in this class are covered under the NY Medicaid pharmacy program by way of a fiscal order from a physician.

A Committee member commented that the OTC antihistamines are not labeled for use down to six months of age due to a potential lack of medical supervision with OTC use, and Dr. Correia concurred.

12. Nasal Antihistamines

Dr. Rogler and Dr. Correia noted the new dosage strength for Astepro (azelastine 0.15% nasal spray) as well as an expanded indication for perennial allergic rhinitis. They also noted Patanase (olopatadine) received approval for use in pediatric patients six years of age and older. Dr. Correia concluded based on available evidence, there does not appear to be any clinically significant difference between these products, and they appear comparable in terms of overall efficacy and incidence of adverse effects.

13. Nasal Corticosteroids

Dr. Rogler and Dr. Correia noted an update to the Warnings and Precautions for Veramyst regarding hypersensitivity reactions. Dr Correia also elaborated on pediatric dosing for the products in this therapeutic class. He concluded that he found no new comparative clinical information which would change the previous evaluation of the drugs in this class.

E. Executive Session:

The Committee recessed the public session at 11:00 AM 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 12:50 PM.

The Committee recessed the public session at 1:25 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 1:50 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?	Approved as Recommended
Platelet Inhibitors: Preferred Drugs Aggrenox (dipyridamole ER/aspirin), dipyridamole, Effient (prasugrel), Plavix (clopidogrel) Non-preferred Drugs Persantine (dipyridamole), ticlopidine	Approved as Recommended
Ophthalmic Beta Blockers: Preferred Drugs betaxolol HCl, Betimol (timolol), Betoptic S (betaxolol HCl), carteolol HCl, Combigan (brimonidine tartrate/timolol maleate), Istalol (timolol maleate), levobunolol HCl, metipranolol, timolol maleate solution/gel Non-preferred Drugs Betagan (levobunolol HCl), Optipranolol (metipranolol), Timoptic (timolol maleate), Timoptic-XE (timolol maleate gel)	Approved as Recommended
Ophthalmic Alpha-2 Adrenergic Agonists: Preferred Drugs Alphagan P (brimonidine), brimonidine Non-preferred Drugs apraclonidine, Iopidine (apraclonidine)	Approved as Recommended
Ophthalmic Prostaglandin Agonists: Preferred Drugs Travatan (travoprost), Travatan Z (travoprost), Xalatan (latanoprost) Non-preferred Drugs Lumigan (bimatoprost)	Approved as Recommended
Topical Anti-Virals: Preferred Drugs Abreva (docosanol), Zovirax (acyclovir)ointment Non-preferred Drugs Denavir (penciclovir), Zovirax (acyclovir) cream	Approved as Recommended
Multiple Sclerosis Agents: Preferred Drugs Avonex (interferon beta-1a), Betaseron (interferon beta-1b), Copaxone (glatiramer acetate), Rebif (interferon beta-1a) Non-preferred Drugs Extavia (interferon beta-1b)	Approved as Recommended
Non-Ergot Dopamine Receptor Agonists: Preferred Drugs Mirapex (pramipexole), ropinirole Non-preferred Drugs Mirapex ER (pramipexole ER), pramipexole, Requip (ropinirole), Requip XL (ropinirole ER)	Approved as Recommended
Ophthalmic Antihistamines: Preferred Drugs Patanol (olopatadine), Pataday (olopatadine) Non-preferred Drugs azelastine, Bepreve (bepotastine), Elestat (epinastine), Emadine (emedastine), Optivar (azelastine)	Approved as Recommended
Ophthalmic NSAIDs: Preferred Drugs diclofenac, flurbiprofen, ketorolac Non-preferred Drugs Acular (ketorolac), Acular LS (ketorolac), Acular PF (ketorolac), Acuvail (ketorolac tromethamine), Nevanac (nepafenac), Ocufen (flurbiprofen), Voltaren (diclofenac), Xibrom (bromfenac)	Approved as Recommended
Ophthalmic Fluoroquinolones: Preferred Drug ciprofloxacin, ofloxacin, Vigamox (moxifloxacin) Non-preferred Drugs Besivance (besifloxacin), Ciloxan (ciprofloxacin), IQUIX (levofloxacin), Ocuflox (ofloxacin), Quixin (levofloxacin), Zymar (gatifloxacin)	Approved as Recommended
Topical Antibiotics: Preferred Drugs Altabax (retapamulin), Bactroban cream (mupirocin), mupirocin ointment Non-preferred Drugs Bactroban ointment (mupirocin), Bactroban nasal ointment (mupirocin), Centany (mupirocin) Continue to use the one additional clinical prior authorization question for specific product indications: Q: Is this medication being used for the eradication of nasal colonization with methicillin resistant Staphylococcus aureus (MRSA) in a patient greater than 12 years of age?	Approved as Recommended
Topical Agents for Psoriasis: Preferred Drugs calcipotriene scalp solution, Dovonex cream (calcipotriene) Non-preferred Drugs Dovonex scalp solution (calcipotriene), Taclonex (calcipotriene/betamethasone dipropionate), Vectical (calcitriol)	Approved as Recommended
Oral Antihistamines: Preferred Drugs cetirizine/cetirizine-D OTC, loratadine/loratadine-D OTC Non-preferred Drugs Allegra/Allegra-D (fexofenadine/fexofenadine PSE), Clarinex/Clarinex-D (desloratadine/desloratadine PSE), fexofenadine/fexofenadine-D, Semprex-D (acrivastine/PSE), Xyzal (levocetirizine) Continue to use the one additional clinical prior authorization question for specific product indications: Q: Is the patient under twenty-four (24) months of age?	Approved as Recommended
Nasal Antihistamines: Preferred Drugs Astelin (azelastine), Astepro (azelastine), Patanase (olopatadine) Non-preferred Drugs None	Approved as Recommended
Nasal Corticosteroids: Preferred Drugs fluticasone propionate, Nasacort AQ (triamcinolone acetonide) Non-preferred Drugs Beconase AQ (beclomethasone dipropionate), Flonase (fluticasone propionate), flunisolide, Nasonex (mometasone furoate), Omnaris (ciclesonide), Rhinocort Aqua (budesonide), Veramyst (fluticasone furoate)	Approved as Recommended

G. Additional discussion:

Anthony Merola, RPh, MBA, (DOH/OHIP) reminded the public to monitor the DOH website for future meeting notices. He indicated that the Atypical Antipsychotic therapeutic class, which is currently exempt from prior authorization under the Preferred Drug Program (PDP), may be reviewed by the P&T Committee at a future meeting. Based on the PDP prior authorization exemption, any atypical antipsychotics determined to be non-preferred would not require prior authorization.

The meeting adjourned at 2:00 PM

Meeting Summary Posted 06/25/2010

H. Final Determinations

1. 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.

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 when prior authorized.

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. Pharmacies will need to complete the prior authorization process for non-preferred products.

c. State Health Program:

• Annual gross savings associated with these therapeutic classes under the PDP are estimated at $27M. 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 07/21/2010