Pharmacy and Therapeutics Committee Meeting Summary - June 14, 2007
Agenda and Introduction
The Medicaid Pharmacy & Therapeutics Committee met on Thursday, June 14th, 2007 from 8:45 a.m. to 3:30 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:
- McCabe, Dorothy, FACCP, PhD., Medical Director, Global Medical Team, Pfizer Inc., New York, NY
- Torosoff, Mikhail, MD, PhD, FACC, Assistant Professor of Medicine, Albany Medical College, Pfizer Inc., Albany, NY
- Do, Ira, PharmD, Regional Medical Scientist, GlaxoSmithKline, Research Triangle Park, NC
- Russell, David, MD, Senior Director, Regional Medical and Research Specialist, Pfizer Inc., Albany, NY
- Goris, Jose, MD, Private Practice, New York, NY
- Forman, Howard, PharmD, Regional Scientific Director, Novartis Pharmaceuticals, Getzville, NY
- Slatch, Harry, MD, Adirondack Urology Associates, Glens Falls, NY
- Kwiat, David, MD, Cataract Care Center, Johnstown, NY
- Lovelace, Cherie Ann, PharmD, Senior Regional Medical and Research Specialist, Ophthalmology, Pfizer Inc., Kennesaw, GA
- Fiscella, Richard, RPh, MPH, Clinical Professor, University of Illinois at Chicago, Allergan, Chicago, IL
- Pinto, Gregory, MD, Pfizer Inc., Saratoga Springs, NY
- Laroche, Daniel, MD, Director of Glaucoma, St. Lukes Hospital, President, Advanced Eyecare of New York, Queens, NY
- Adesman, Andrew, MD, Chief, Developmental & Behavioral Pediatrics Director, ADHD Center, Schneider Children's Hospital, Lake Success, NY
- Palumbo, Donna, PhD, Associate Professor of Neurology & Pediatrics, Director Strong Neurology ADHD Program, University of Rochester Medical Center, Rochester, NY
- Posta, Linda, RPh, MBA, Scientific Affairs Liaison, Ortho-McNeil Janssen, Milford, CT
- Kehner, George, PhD, Sr. Medical Science Liaison, Shire Pharmaceuticals, Wayne, PA
- Riolo, Jon, PhD, Regional Scientific Associate Director, Novartis Pharmaceuticals, Getzville, NY
- Lillquist, Patricia, MD, Board Certified Psychiatrist, Albany, NY
- Bailey, Nate, PharmD., Medical Science Liaison, UCB Inc., Smyrna, GA
C. Key issues raised by interested parties and the Pharmacy and Therapeutics Committee pertaining to the clinical review of the following therapeutic classes:
Public comments:
Ophthalmic Prostaglandin Agonists:
- The Committee was asked to consider information regarding clinical trial results including efficacy in lowering intraocular pressure (IOP), effectiveness, side effects, rates of ocular hyperemia and tolerability, persistency of therapy, mechanism of action, use in special populations, and adherence.
Selective Alpha Adrenergic Blockers:
- The Committee was asked to consider information regarding clinical trial results including selectivity for the alpha-1 receptor, the risk of syncope and orthostatic changes, pharmacokinetics, compliance and drug interactions.
Cyclooxygenase II (COX II) Inhibitors:
- The Committee was asked to consider information regarding clinical trial results including efficacy, safety with regard to the cardiovascular and gastrointestinal systems, and use in patients on anti-platelet aspirin therapy.
Central Nervous System (CNS) Stimulants:
- The Committee was asked to consider information regarding clinical trial results including efficacy and effectiveness, safety, tolerability, pharmacokinetics including onset, time of dosing, and duration of action, different dosage forms, length of therapy, indications in pediatrics, adolescents, and adults, and adverse events, including effects on growth in children. The Committee was also asked to consider the potential for abuse and diversion of the medications in this class.
Urinary Tract Antispasmodics:
- The Committee was asked to consider information regarding clinical trial results including indications, efficacy, safety, mechanism of action, tolerability, adverse events including cardiovascular and cognitive, and discontinuation rates.
Pharmacy and Therapeutics Committee Comments:
- A committee member asked the presenter to comment on Travatan Z versus Travatan with regard to compliance, and degree of hyperemia. The presenter indicated that the Travatan Z was a new formulation that may provide a benefit to some patients, and may account for less hyperemia by a few percentage points.
- A committee member asked for clarification of the importance of the eight and twelve hour durations of action of CNS stimulants. The presenter indicated that individual patient circumstance dictates the need for coverage, for example a younger child may need coverage throughout the school day and early evening, while an adolescent may need coverage later into the evening for homework and driving.
D. Clinical Presentation and Discussion
Marian McDonagh, PharmD, Oregon Health & Sciences University, Evidence-based Practice Center (OHSU EPC); Barbara Rogler, PharmD, MS, First Health Services Corporation; Robert Correia, PharmD, NYS Department of Health, Office of Health Insurance Programs (DOH/OHIP); Anthony Merola, RPh, MBA, (DOH/OHIP)
1. Proposal to identify preferred drugs in the therapeutic class of Ophthalmic Prostaglandin Agonists
Drugs Affected: Lumigan (bimatoprost), Travatan (travoprost), Travatan Z (travoprost), Xalatan (latanoprost)
Dr. Rogler reviewed the risk factors for glaucoma, eye drops commonly used in the treatment of glaucoma, and the drugs included in this review. She noted indications, mechanism of action, dosing, warnings and precautions, use in special populations, and adverse reactions. She discussed results from several head to head clinical studies and a safety and efficacy study. She concluded that the ophthalmic prostaglandins all effectively reduce intraocular pressure.
Dr. Correia provided the Department's clinical review for this category. He discussed the different mechanisms of action with regard to the outflow of aqueous humor, noting the relevant point is clinical effect of the drugs. He discussed the Food and Drug Administration (FDA) trial comparing Travatan and Travatan Z noting the difference in conjunctival hyperemia was not statistically significant. He explained there is no absolute threshold IOP for progression of disease, and while all the drugs in the class lower IOP comparably, decreases in IOP vary with baseline patient characteristics. He noted that small differences in clinical study results may be statistically, but not clinically significant, and are resolved when patient physical variability is accounted for. He also noted findings of a recent clinical study, published in April 2007, which specifically investigated potential impact of race in response to these drugs. The investigators found no statistically significant difference in response between African-American and white individuals, and concluded that clinicians should not base choice of drug on ethnicity of the patient. Dr. Correia concluded that marginal differences claimed by each manufacturer tend to balance between slight study variations in change in IOP and tolerability due to adverse events, with none demonstrating an overall advantage.
Committee members inquired if there were head to head trials comparing the effects of these drugs on iris pigmentation, and if one drug was more likely than another to cause iris pigmentation changes or hyperemia. Drs. Correia and Rogler knew of no studies directly comparing the incidence of iris pigmentation, and indicated that the Xalatan literature notes a slightly lower incidence of hyperemia.
2. Proposal to identify preferred drugs in the therapeutic class of Selective Alpha Adrenergic Blockers (used in the treatment of Benign Prostatic Hyperplasia)
Drugs Affected: Flomax (tamsulosin), Uroxatral (alfuzosin)
Dr. Rogler reviewed the etiology of benign prostatic hyperplasia (BPH). She discussed the pharmacology, dosing, contraindications, warnings, and precautions for the selective alpha adrenergic blockers. She discussed a head to head clinical trial of the two drugs in this therapeutic class. She concluded with a statement from the American Urological Association (AUA) treatment guidelines for BPH which indicates that alfuzosin and tamsulosin (as well as two non-selective alpha adrenergic blockers) have equal clinical effectiveness, with slight differences in adverse event profiles.
Dr. Correia concurred with the AUA statement and concluded that both drugs are comparably clinically effective, with slightly different adverse event profiles.
3. Review of the Cyclooxygenase II (COX II) Inhibitors therapeutic class for inclusion to the Preferred Drug Program (PDP)
Drug Affected: Celebrex (celecoxib)
Mr. Merola indicated the purpose of the review of the COX II Inhibitors therapeutic class is to determine if the class should be included in the Preferred Drug Program (PDP). He noted that there is only one drug in the class; therefore there would be no comparative analysis. He indicated that with the ongoing research in this area, adding this class to the PDP would allow the Pharmacy and Therapeutics Committee to address any newly approved drugs that fall into this therapeutic class using the procedure developed for newly approved drugs subject to the PDP.
Dr. Rogler described the pharmacology of the COX II Inhibitors, and noted the indications for Celebrex.
Several members of the Committee discussed the use of a Cox II Inhibitor versus traditional non-steroidal anti-inflammatory drugs (NSAID) in patients taking low-dose aspirin, and also noted the need for prescribers to clarify the cardiovascular effects associated with this drug class to patients.
4. Proposal to identify preferred drugs in the therapeutic class of Central Nervous System (CNS) Stimulants
Drugs Affected: Adderall (amphetamine salt combo), Adderall XR (amphetamine salt combo XR), amphetamine salt combo, Concerta (methylphenidate), Cylert (pemoline), Daytrana (methylphenidate), Desoxyn (methamphetamine), Dexedrine (dextroamphetamine sulfate), Dexedrine Spansule (dextroamphetamine), dextroamphetamine sulfate, dextroamphetamine sulfate SA, Dextrostat (dextroamphetamine sulfate), Focalin (dexmethylphenidate), Focalin XR (dexmethylphenidate XR), Metadate CD (methylphenidate CD), Metadate ER (methylphenidate ER), Methylin ER (methylphenidate ER), Methylin (methylphenidate), methylphenidate, methylphenidate ER, pemoline, Provigil (modafinil), Ritalin (methylphenidate), Ritalin SR (methylphenidate SR), Ritalin LA (methylphenidate LA)
Dr. McDonagh presented the summary of the OHSU review of Pharmacologic Treatments in ADHD and discussed the outcomes of key areas of inquiries based on findings from clinical trials, including head-to- head trials. She provided the outcomes of studies in children comparing efficacy (no effectiveness trials were found), long term effects, adverse effects, weight and height change, use in subpopulations, and in subpopulations with comorbidities. She also discussed direct, indirect, and long term evidence for the use of these drugs in adults.
Dr. Rogler provided an overview of Attention-Deficit/Hyperactivity Disorder (ADHD), and of the drugs in the CNS Stimulant therapeutic class. She described the pharmacology, black box warning, contraindications, and warnings and precautions for the CNS stimulants. She explained the adverse cardiovascular events associated with this class of drugs. She described different delivery systems and corresponding durations of action for drugs in this class. She reviewed several clinical trials, and explained that different rating scales used in different clinical trials makes it difficult to compare the studies. She concluded by noting that based on a 2006 meta-analysis (Pliszka, et al.), none of the drugs in this class are inherently more effective than another.
Dr. Correia provided the Department's clinical review for this category. He noted that comparative efficacy evidence for various indications is often contradictory, and can vary based on subtype of ADHD diagnosis, baseline disease severity, or comorbidities. He also noted that different measurement tools, timing of measurements, assessment scales and persons making assessments may all contribute to conflicting data. He emphasized there is no comparative evidence from clinical trials for effectiveness. He discussed safety and adverse events including weight loss, lack of weight gain, the risk for sudden death, and the black box warning for abuse and dependence. He noted a significant overlap in indications for the drugs in this class, and as evidence for overall comparative advantage is lacking for any drug with shared indications; subtle differences could be addressed in prior authorization criteria if needed. He concluded that it would be preferable to include drugs with relatively short, intermediate and long durations of action as preferred drugs; however, there is not adequate evidence of overall clinical superiority for any drug in this class.
Several Committee members commented on off-label uses for modafinil.
5. Proposal to identify preferred drugs in the therapeutic class of Urinary Tract Antispasmodics
Drugs Affected: Detrol (tolterodine), Detrol LA (tolterodine LA), Ditropan (oxybutynin), Ditropan XL (oxybutynin XL), Enablex (darifenacin), oxybutynin, oxybutynin ER, Oxytrol (oxybutynin), Sanctura (trospium), Vesicare (solifenacin)
Dr. McDonagh presented the summary of the OHSU review of Drugs for Overactive Bladder and discussed the outcomes of key areas of inquiries based on findings from clinical trials, including head-to-head trials. She presented several comparative efficacy trials for the drugs in this therapeutic class including trials of immediate versus immediate release, immediate versus extended release, extended versus extended release, transdermal versus immediate release, transdermal versus extended release. She noted comparative evidence of adverse events overall, dry mouth, and withdrawals due to adverse events. She discussed subpopulations noting there is insufficient evidence to indicate a difference between these drugs based on subpopulation characteristics.
Dr. Rogler provided an overview of overactive bladder (OAB), types of urinary incontinence, and of the drugs in the Urinary Tract Antispasmodics therapeutic class. She described the pharmacology, dosage forms, and indications for the drugs in this class. She described the use of these drugs in special populations, including pregnancy and pediatrics. She presented the results of several head to head clinical trials and concluded that all the agents in the therapeutic class are equally effective in reducing episodes of urinary incontinence.
Dr. Correia provided the Department's clinical review for this category. He noted again the importance of differentiating between statistical significance and clinical significance and effectiveness. He noted that the clinical trials reviewed varied in study length, methods of obtaining data, and measures of efficacy, some of which could be considered subjective. He indicated that the trials reviewed demonstrated similarity in efficacy between immediate and extended release dosage forms, and while the extended release forms may have shown a slight advantage of less adverse effects, this was not generally reflected in the discontinuation rates. In conclusion, he stated that the clinical evidence reviewed indicates that any of the drugs in the class provide comparable symptom relief, with none demonstrating an overall advantage.
The Committee discussed the side effect profiles of the newer, more selective drugs in the class, noting that compared to the older drugs, there may be a slight, dose related advantage. The importance of exercise and behavioral modification was also noted. A question was raised regarding evidence of less negative cognitive effects with newer, more selective drugs, and while a slight advantage may be measurable, the importance of taking dosing into consideration when measuring cognitive effects was discussed.
E. Executive Session:
The Committee recessed the public session at 11:25 A.M. to go into executive session for review of financial information relating to the determination of preferred drugs in the following classes: Ophthalmic Prostaglandin Agonists, Selective Alpha Adrenergic Blockers, COX II Inhibitors. No official action was taken in the executive session. The executive session was recessed at 12:30 P.M.
The Committee recessed the public session at 1:55 P.M. to go into executive session for review of financial information relating to the determination of preferred drugs in the following classes: CNS Stimulants, Urinary Tract Antispasmodics. No official action was taken in the executive session. The executive session was recessed at 2:45 P.M.
F. 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 Ophthalmic Prostaglandin Agonists 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 Travatan (travoprost), Travatan Z (travoprost), Xalatan (latanoprost) Non-preferred Drug Lumigan (bimatoprost) B. The Committee unanimously recommended the following standard clinical questions be used as the basis for approving use of the non-preferred drug:
|
Approved as Recommended |
| Proposal: Identification of preferred drugs in the category of Selective Alpha Adrenergic Blockers 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 Flomax (tamsulosin), Uroxatral (alfuzosin) 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: Review of the Cyclooxygenase II (COX II) Inhibitors therapeutic class A. The Committee unanimously recommended that the Cyclooxygenase II (COX II) therapeutic class be included in the Preferred Drug Program. 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 Drug Celebrex (celecoxib) Non-preferred Drugs None |
Approved as Recommended |
| Proposal: Identification of preferred drugs in the category of Central Nervous System (CNS) Stimulants 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 Adderall XR (amphetamine salt combo XR), amphetamine salt combo, Concerta (methylphenidate ER), dextroamphetamine sulfate, dextroamphetamine sulfate SA, Focalin (dexmethylphenidate), Focalin XR (dexmethylphenidate XR), Metadate CD (methylphenidate CD), Metadate ER (methylphenidate ER), Methylin (methylphenidate) tablet/chew/solution, Methylin ER (methylphenidate ER), methylphenidate, methylphenidate ER, Ritalin LA (methylphenidate LA) Non-preferred Drugs Adderall (amphetamine salt combo), Cylert (pemoline), Daytrana (methylphenidate), Desoxyn (methamphetamine), Dexedrine (dextroamphetamine sulfate), Dexedrine Spansule (dextroamphetamine sulfate SR), Dextrostat (dextroamphetamine sulfate), pemoline, Provigil (modafinil), Ritalin (methylphenidate), Ritalin SR (methylphenidate SR) B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process and an additional clinical question for Provigil (modafinil) as follows:
|
Approved as Recommended |
| Proposal: Identification of preferred drugs in the category of Urinary Tract Antispasmodics 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 Detrol LA (tolterodine LA), Enablex (darifenacin), oxybutynin tablet/solution, Vesicare (solifenacin) Non-preferred Drugs Detrol (tolterodine), Ditropan (oxybutynin) tablet/solution, Ditropan XL (oxybutynin XL), oxybutynin ER, Oxytrol (oxybutynin), Sanctura (trospium) B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process. |
Approved as Recommended |
G. Topical Immunomodulator Drug Utilization Review (DUR) Status Report:
Steven Espy, RPh, Director of Drug Utilization Review (DUR), Health Information Designs, presented the Topical Immunomodulator DUR Status Report.
The Topical Immunomodulator therapeutic class was reviewed for inclusion in the PDP at the September 2006 meeting of the Pharmacy and Therapeutics Committee. Both Elidel (pimecrolimus) and Protopic (tacrolimus) were recommended to be preferred. Due to long term safety concerns and the availability of alternative first line therapy, the Committee recommended that a clinical intervention be performed through the DUR program. The DUR board accepted the recommendation.
Intervention letters were generated based on criteria determined by the DUR board. An evaluation of pre and post intervention data showed a significant decrease in the number of prescriptions filled for Elidel (pimecrolimus) and Protopic (tacrolimus). A Committee member commented on the potential cyclical nature of the use of these drugs. The Committee made the following recommendations to the DUR Board:
- Quarterly review of the Topical Immunomodulator therapeutic class for one year
- Identification of recalcitrant prescribers
- The Committee would like to hear feedback from prescribers
H. Election of Committee Chair and Co-Chair:
The Committee voted via paper ballot and elected a Committee Chair and Vice-Chair. The following members were re-elected:
- Chairperson: Glenn Martin, MD
- Vice Chairperson: William Scheer, RPh
The meeting adjourned at 2:50 PM.
Meeting Summary Posted 7/6/07
I. Final Determinations:
The Commissioner has determined that the Medicaid program will require prior authorization under the Preferred Drug Program (PDP) for non-preferred drugs, as listed above, in the following classes: Ophthalmic Prostaglandin Agonists, Selective Alpha Adrenergic Blockers, Cyclooxygenase II (COX II) Inhibitors, Central Nervous System (CNS) Stimulants and Urinary Tract Antispasmodics.
Preferred drugs will not require prior authorization.
The impact of this final determination is as follows:
- State Public Health Population:
- Minimal effect on Medicaid enrollees as a large majority currently utilize the preferred products.
- Non-preferred products remain available when prior authorized.
- Program Providers:
- No impact on prescribers or pharmacies when ordering the preferred product. Prescribers, or their agents, will need to initiate the prior authorization process when ordering a non-preferred product. Pharmacies will need to complete the prior authorization process for non-preferred products.
- Fiscal Impact to State Health Program:
- Annual gross savings associated with these therapeutic classes under the Preferred Drug Program are estimated at $18.8 M. The savings are achieved through changes in utilization to more cost effective drugs, and the receipt of supplemental rebates from pharmaceutical manufacturers based on product utilization.
Final Determinations Posted 8/27/2007
