Pharmacy and Therapeutics Committee Meeting Summary - April 29, 2010

Agenda and Introduction

The Medicaid Pharmacy & Therapeutics Committee met on Thursday, April 29, 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. Bartucci, Marilyn, RN, Senior Manager, Scientific Affairs, Astellas Pharma Global Development US, Euclid, OH
  2. Hede, Shalini, PharmD, Executive Manager, Clinical Science and Outcomes, Takeda Pharmaceuticals, Deerfield, IL
  3. Pattugalan, Tomas Jr, MD, Takeda Pharmaceuticals, Deerfield, IL
  4. Thompson, Gina, Health Science Consultant, Merck, West Point, PA
  5. Kim, Andy, PharmD, Medical Science Liaison, Shire Pharmaceuticals, Wayne, PA
  6. Roglieri, Joseph M, DO, MS, Troy, NY
  7. Tallman, Anna M, PharmD, Director, Medical Affairs, Strativa Pharmaceuticals, Woodcliff Lake, NJ
  8. Lichiger, Simon, Physician, Shire Pharmaceuticals, Wayne, PA
  9. Van Zile, Peter, PharmD, Sr Regional Medical Scientist, GlaxoSmithKline, Research Triangle Park, NC
  10. Mechtler, Laszlo, MD, Vice President, Dent Headache Center, Amherst, NY
  11. Tolge, Bruno P, Neurologist, Schenectady Neurological Consultants, Schenectady, NY
  12. Price, Arlene, PharmD, Sr Scientific Affairs Liaison, Ortho McNeil Janssen, Randolph, NJ
  13. Setlak, Paul, Regional Clinical Executive, Abbott Laboratories, Marietta, GA
  14. Thomas, Jessy, Sr Medical Science Liaison, Amgen, Thousand Oaks, CA
  15. Tevlin, Brian, PharmD, Medical Science Liaison, Immunology, CB Inc., East Hampton, CT
  16. Bartles, Laura, PharmD, Medical Science Liaison, Shire Pharmaceuticals, Wayne, PA
  17. Reiss, Robert , PharmD, Sr Regional Medical Scientist, GlaxoSmithKline Pharmaceuticals, Research Triangle Park, NC
  18. Posta, Linda M, RPh, MBA, Scientific Liaison, Astellas Pharma Global Development, Inc., Deerfield, IL
  19. Kitchens, George, Consultant, Allergan, Tallahassee, FL
  20. Russell, David J, MD, FACS, Senior Medical Director, Pfizer, Albany, NY
  21. McBride, Thomas P, RPA-C, Adirondack Surgical Group/Urology, Saranac Lake, 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:

Prograf (tacrolimus):

  • The Committee was asked to consider information regarding indications, efficacy, safety, and factors that may influence drug concentrations in the blood. The presenter discussed the Citizen's Petition filed with the Food & Drug Administration (FDA) by the product manufacturer, and the FDA's response, and also provided the characteristics of drugs with a narrow therapeutic index.

Xanthine Oxidase Inhibitors:

  • The Committee was asked to consider information regarding mechanism of action, efficacy in lowering uric acid levels to goal, dosing in patients with renal or hepatic impairment, use in patients with cardiovascular risk factors, adverse events and the results of comparator studies with allopurinol.

Oral Fluoroquinolones:

  • The Committee was asked to consider updated product information including drug-drug interactions, warnings, post-marketing adverse effects and indications. The presenter also discussed the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) community acquired pneumonia (CAP) consensus guideline.

Phosphate Binder/Regulators:

  • The Committee was asked to consider information regarding indications, efficacy, safety, tolerability, dosing and administration, compliance, morbidity and mortality associated with cardiovascular disease in patients with end stage renal disease (ESRD), and the importance of controlling hyperphosphatemia. The presenter also discussed a 2009 head to head study between Fosrenol and Renagel.

Progestins (for Cachexia):

  • The Committee was asked to consider information regarding indications, the nanocrystal technology available with the ES formulation, and the absorption and bioavailability of Megace and Megace ES in fed and fasting states.

Sulfasalazine Derivatives:

  • The Committee was asked to consider information regarding the mechanism of action of 5-ASA, patient adherence, dosing, and the importance of good drug distribution to the mucosa with the goal of decreasing dysplasia.

Serotonin Receptor Agonists -Triptans:

  • The Committee was asked to consider information regarding efficacy, pharmacokinetics, safety, dosing formulations, patient variability, the use of a triptan in combination with a non-steroidal anti-inflammatory drug (NSAID), use in menstrual migraine, and the use of triptans to mitigate emergency room visits and opioid utilization.

Injectable Immunomodulators:

  • The Committee was asked to consider information regarding indications, dosing, onset and duration of response, compliance, safety, efficacy, including efficacy across indications, immunogenicity, use with or without methotrexate, clinical outcomes, adverse events, postmarketing experience, and the updated black box warning applicable to the TNF blocker products in this class.

Central Nervous System Stimulants:

  • The Committee was asked to consider information regarding indications, efficacy, safety, use in adults, pharmacokinetics, onset and duration of action, and the use of dosage delivery systems designed to discourage illicit use.

Injectable Anticoagulants:

  • The Committee was asked to consider information regarding fondaparinux product label changes including use in mild to moderate hepatic impairment, the removal of certain adverse events from the labeling, safety concerns in the pediatric population, and reinforcement of the pregnancy category rating. A black box warning update was also mentioned and pertains to all of the products in this class.

Urinary Tract Antispasmodics:

  • The Committee was asked to consider information regarding indications, dosing, efficacy, safety, tolerability, adverse events, the VIBRANT and VECTOR trials, comparative data with a change from a brand product to a generic product, and differences between tertiary and lipophilic amines versus quaternary amines. The Committee was also asked to consider the results of a placebo-controlled head-to-head superiority trial between two drugs in this class, and the importance of patient education and support in the treatment of overactive bladder.

Erythropoiesis Stimulating Agents (ESAs):

  • The Committee was asked to consider information regarding the updated Aranesp Product Information including the ESA APPRISE Oncology Program, and dosing to obtain hemoglobin levels adequate to avoid transfusion.

Pharmacy and Therapeutics Committee Comments:

  • A Committee member and the presenter discussed the head to head trials with allopurinol and febuxostat with regard to outcomes and adverse events.
  • A presenter clarified for a Committee member when he prefers febuxostat over allopurinol in his practice.
  • A presenter confirmed for a Committee member that there are no head-to-head trials between Treximet and another triptan.
  • A Committee member asked the presenter to comment on the use of non-triptan medications, including over-the-counter (OTC) medications, in the treatment of migraine headaches.
  • A committee member requested clarification regarding the different rates of constipation between the drugs in the VECTOR trial.

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)

Mandatory Generic Drug Program

Consideration of a request to exempt tacrolimus from the requirements of the Mandatory Generic Drug Program

Dr. Rogler provided background information on Prograf (tacrolimus) and noted tacrolimus oral capsules, an AB-rated generic, received approval in August 2009. She discussed the pharmacokinetics of the drug, noting interpatient and intrapatient variability of kinetics can be attributed to several factors including, but not limited to food, age, gender, race, and concomitant liver disease. She noted that the drug generally has low oral bioavailability, is highly protein bound, and is extensively metabolized by the cytochrome P-450 system. She also included dosage and administration information for the different transplant populations.

Dr. Correia quoted the New York State Social Services Law giving authority for the Mandatory Generic Drug Program (MGDP) and noted the Commissioner of Health is authorized to exempt, for good cause shown, any brand name drug from the Program. He provided background information on tacrolimus including indications and frequency of monitoring. He noted in 2006, the FDA published draft guidance on recommended studies to establish bioequivalence for generic versions of tacrolimus. In 2007, the manufacturer of the brand name product filed a Citizens Petition with the FDA, with a supplement to the Petition filed in September 2008, with specific concerns relevant to the approval process, labeling requirements, and bioequivalence for generic tacrolimus, including comments from the American Society of Transplant Surgeons. In August 2009, the FDA issued their official response to this Petition, addressing each of the issues presented in the Petition and the only part not denied by the FDA was the request that the different doses of tacrolimus products be clearly distinguishable.

Dr. Correia noted the exemption request submitted by the manufacturer of Prograf identifies that there is no published information pertaining to the U.S. generic formulation indicating either superiority of the brand name Prograf or variability of the generic product. He noted the last time the Committee reviewed a MGDP exemption request was for a drug with multiple reference listed brand name drugs and multiple A-rated generics. He also noted the immunosuppressant drug currently exempt from the MGDP has more than one reference listed brand name drug, and the available generics are rated to one or the other reference drugs, but not to both , a point that is emphasized in the products' black box warning. He indicated these circumstances are not relevant to the brand and generic formulations of Prograf.

Dr. Correia concluded that this review should not be considered an opinion on the bioequivalence of the brand and generic versions of drugs, and the NY Medicaid program defers to the FDA as the authority on such determinations. He indicated there has been no new evidence submitted, and current prescribing patterns within the NY Medicaid program do not support the proposition that the generic product needs to be exempt from the NY Medicaid MGDP. He noted lastly, brand name drugs remain available under the MGDP.

The Committee discussed the exemption request noting that currently, the generic would be dispensed unless the prescriber indicated on the prescription Dispense As Written. They discussed the current MGDP exclusions noting that some of the drugs have a narrow therapeutic index, may require routine monitoring, and may cause harm if correct drug levels are not maintained. It was suggested that the Committee review the entire list of drugs currently excluded and discuss the criteria to determine "good cause" for exemption from the Program. A motion was introduced to table the discussion to a future meeting. At that time the Committee will discuss the criteria to determine "good cause" for exemption from the MGDP and then discuss Prograf, as well as the other currently exempt drugs, within the context of those criteria and make a recommendation regarding MGDP exemption to the Commissioner of Health. The Committee also recommended that the current status of no MGDP prior authorization for Prograf be maintained until exemption criteria are discussed. The motion was seconded and the Committee voted unanimously in favor of the motion.

Preferred Drug Program: Initial Review

1. Proposal to identify preferred drugs in the therapeutic class of Biguanides

Drugs Affected: Fortamet (metformin HCl ER), Glucophage (metformin HCl), Glucophage XR (metformin HCl ER), Glumetza (metformin HCl ER), metformin HCl, metformin HCl ER, Riomet solution (metformin HCl)

Dr. Rogler presented an overview of the agents in this class noting indications, adverse reactions, warnings/precautions, dosage and administration and mechanism of action. She discussed the different extended release formulations noting the different delivery systems. Dr. Rogler also provided the committee the consensus algorithm for the initiation and adjustment of therapy from the American Diabetes Association and the European Association for the Study of Diabetes.

Dr. Correia restated that the products all contain the same active ingredient, metformin, in either an immediate or extended-release formulation. He provided a brief synopsis of the pharmacokinetics, dosing and safety of metformin. Dr. Correia noted that none of these products demonstrate overall superiority and it is preferable to include both immediate and extended-release agents as preferred products.

2. Proposal to identify preferred drugs in the therapeutic class of Xanthine Oxidase Inhibitors

Drugs Affected: allopurinol, Zyloprim (allopurinol), Uloric (febuxostat)

Dr. Rogler provided an overview of gout and discussed how it is divided into two phases: acute treatment and chronic prevention. She discussed the agents in the therapeutic class with regard to indications, pharmacokinetics, drug interactions, dose, contraindications, warnings and precautions. She discussed FACT, a comparative trial with febuxostat versus allopurinol. She noted that clinical outcomes (reduction in gout flares and in tophus area) were not different in either the febuxostat or allopurinol groups and that overall treatment related adverse events were similar for all treatment groups.

Dr. Correia reiterated that there are only two active drugs in this class, allopurinol and febuxostat. Dr. Correia stated allopurinol has over 40 years of clinical experience in its use and febuxostat was just approved in 2009. He noted febuxostat is only indicated for chronic management of gout, while allopurinol is labeled not only for use in gout but in other conditions as well. Dr. Correia discussed the dosage ranges and flexibility of dose titration for allopurinol. He also restated that febuxostat has a starting dose of 40 mg which can be increased to 80 mg after two weeks. Dr. Correia mentioned that the head to head clinical trials between febuxostat and allopurinol to date lack comparable drug dosing. He provided an example of this from the FACT trial. Dr. Correia reiterated contraindications and warnings for both products. He stated comparative evidence available does not demonstrate overall superiority in safety or efficacy for either of these drugs and each drug has its own adverse effect concerns.

A Committee member commented on the use of allopurinol and the concern with increasing doses in renal patients causing adverse reactions due to accumulation of an allopurinol metabolite.

Preferred Drug Program: Re-review

1. Re-review of the Third Generation Cephalosporin therapeutic class

Drugs Affected: Cedax (ceftibuten), cefdinir, cefditoren pivoxil, cefpodoxime proxetil, Omnicef (cefdinir), Suprax (cefixime), Spectracef (cefditoren), Vantin (cefpodoxime proxetil)

Dr. Rogler noted the availability of a new generic cefditoren and no other new clinical information was found for the class since the previous review.

Dr. Correia also stated that no new comparative evidence was found to differentiate effectiveness between the drugs in the class. The drugs in the class may be grouped according to gram-negative and gram-positive activity and it is suggested that drugs covering both spectrums of activity be represented as preferred agents.

2. Re-review of the Oral Fluoroquinolone therapeutic class

Drugs Affected: Avelox (moxifloxacin), ciprofloxacin, ciprofloxacin ER, Cipro (ciprofloxacin), Cipro XR (ciprofloxacin ER), Factive (gemifloxacin), Levaquin (levofloxacin), Noroxin (norfloxacin), ofloxacin, Proquin XR (ciprofloxacin)

Dr. Rogler noted that no new clinical information was found for the class since the previous review.

Dr. Correia reiterated that all of the fluoroquinolones are effective, although their utility continues to erode through resistance due to overuse. No new evidence was found to suggest any of the drugs demonstrate an overall advantage. As discussed during previous reviews of this class, it is suggested that both second and third generation drugs be represented on the Preferred Drug List (PDL).

3. Re-review of the Phosphate Binder/Regulator therapeutic class

Drugs Affected: calcium acetate, Eliphos (calcium acetate), Fosrenol (lanthanum), Phoslo (calcium acetate), Renagel (sevelamer HCL), Renvela (sevelamer carbonate)

Dr. Rogler noted a new formulation of sevelamer carbonate (Renvela) powder packets. She mentioned that the powder is available as 0.8 g and 2.4 g packets and should be mixed with water and consumed within 30 minutes of mixing.

Dr. Correia also noted the formulation of sevelamer carbonate (Renvela) powder packets. Dr. Correia reiterated that the powder does not dissolve, and the resulting suspension must be taken immediately after preparation. Dr. Correia discussed a recent review article in New England Journal of Medicine relevant to selection of oral phosphate binders in kidney failure. Dr. Correia stated the review identified areas needing research which include the lack of evidence to identify calcium-based therapy as a cause of vascular calcification. The review recommended calcium based therapy as the initial therapy and also noted that sevelamer and lanthanum were associated with more adverse events. Dr. Correia noted much of the discussion of the advantages and disadvantages is consistent with the Department's previous reviews of this drug class.

4. Re-review of the Progestins (for cachexia) therapeutic class

Drugs Affected: megestrol acetate, Megace (megestrol acetate), Megace ES (megestrol acetate)

Dr. Rogler presented an article about the effect of food on the bioavailability of two formulations of megestrol acetate oral suspension. She described results from three studies which evaluated the food effect on bioavailability of megestrol acetate oral suspension (MAOS) versus the nanocrystal dispersion megestrol acetate oral suspension (MA-ES).

Dr. Correia indicated the products in this class are the same drug in different dosage preparations and are all dosed once a day, as either a 5 ml dose or a 20 ml dose depending on product selection. Dr. Correia discussed the above mentioned article as well, noting it compared plasma drug concentrations based on studies conducted at different times, in different patient populations (with potential differences between these study populations) and possibly even different drug assays and sampling techniques. As Dr. Correia has previously stated, the products were both found to be equally effective in appetite scores in clinical trials. He reiterated that there is still no evidence of clinical superiority between the products.

5. Re-review of the Selective Alpha Adrenergic Blocker therapeutic class

Drugs Affected: Flomax (tamsulosin), Rapaflo (silodosin), tamsulosin, Uroxatral (alfuzosin)

Dr. Rogler noted the availability of generic tamsulosin. She also noted a labeling update to the entire class, cautioning concomitant use of drugs in this class with PDE5 inhibitors which potentially could cause symptomatic hypotension.

Dr. Correia reiterated the availability of generic tamulosin and the labeling update across the class. He stated there is no new comparative information for safety or effectiveness, and the drugs appear to be comparably clinically effective, with possibly differing adverse effect profiles.

6. Re-review of Sulfasalazine Derivatives therapeutic class

Drugs Affected: Asacol/Asacol HD (mesalamine), Apriso (mesalamine), Azulfidine (sulfasalazine), Azulfidine Entab (sulfasalazine DR/EC), balsalazide, Colazal (balsalazide), Dipentum (olsalazine), Lialda (mesalamine), Pentasa (mesalamine), sulfasalazine, sulfasalazine DR/EC

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

Dr. Correia provided background information for the treatment of ulcerative colitis, noting that regardless of the route of administration (oral or rectal), the beneficial effect of the active drug 5-ASA, also known as mesalamine, is believed to have its therapeutic effect via topical exposure to the affected gastrointestinal area (intestinal lumen, rectum, or left colon). He noted the products in this class are categorized either by indication for active disease versus maintenance, or by mechanism used to deliver the active drug. He noted the pro-drugs require chemical conversion to their active form within the intestine, whereas delayed-release forms achieve this via dosage formulations. He reiterated dosing regimens vary from once a day to four times a day depending on drug and indication, and each dose still requires use of multiple tablets or capsules. He concluded none of the agents demonstrates overall superiority in safety or efficacy and it would be preferable to include as broad a selection of these products as possible.

7. Re-review of the Serotonin Receptor Agonist (Triptan) therapeutic class

Drugs Affected: Amerge (naratriptan), Axert (almotriptan), Frova (frovatriptan), Imitrex (sumatriptan), Maxalt (rizatriptan), Relpax (eletriptan), sumatriptan, Treximet (sumatriptan/naproxen), Zomig (zolmitriptan)

Dr. Rogler discussed a Pharmacokinetic Study of fixed-dose sumatriptan and naproxen comparing the peak plasma concentration and time to peak concentration of the combination product to the single ingredients. She also discussed a Poor Responder Study comparing the fixed-dose product to placebo in patients labeled poor responders to triptans with a short half life.

Dr. Correia also discussed the clinical studies regarding the pharmacokinetic properties of sumatriptan and naproxen when combined in a single tablet formulation versus one or the other of its components, including the clinical relevance of the differences found. He pointed out advantages and disadvantages of dosing with a combination product. He concluded no new clinical information was found to change previous conclusions for the class.

8. Re-review of Anti-Emetic therapeutic class

Drugs Affected: Anzemet (dolasetron), granisetron, Granisol (granisetron), Kytril (granisetron), ondansetron, Sancuso (granisetron patch), Zofran (ondansetron)

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

Dr. Correia noted no new comparative evidence was found to differentiate effectiveness between the three drugs in the class, and all three are effective with none demonstrating an overall advantage.

9. Re-review of the Injectable Immunomodulator therapeutic class

Drugs Affected: Cimzia (certolizumab pegol), Enbrel (etanercept), Humira (adalimumab), Kineret (anakinra), Simponi (golimumab)

Dr. Rogler noted a boxed warning for the TNF blockers associated with an increased risk of lymphoma and other malignancies in children and adolescents. She also noted several other changes in the prescribing information regarding risks associated with these drugs, and an update to the Adverse Events section to include information on reported cases of new onset psoriasis. She also provided information for golimumab (Simponi) including indications, dosing and clinical trial results. She concluded by mentioning the Updated Consensus Statement on Biological Agents for the Treatment of Rheumatic diseases, 2009.

Dr. Correia presented a brief overview of the two main cytokine immune processes impacted by these drugs. A general review of the indications was provided including the commonalities across products. As described during the previous review of the class, evidence suggests anti-TNF products adalimumab and etanercept are more effective than anakinra but also have been associated with more serious side effects. A review of overlapping indications of the products was provided. Dr. Correia noted the availability of the new product golimumab (Simponi). No new comparative effectiveness evidence was found for this class.

10. Re-review of the Otic Fluoroquinolone therapeutic class

Drugs Affected: Cetraxal (ciprofloxacin), Cipro HC (ciprofloxacin/hydrocortisone), Ciprodex (ciprofloxacin/dexamethasone), Floxin (ofloxacin), ofloxacin

Dr. Rogler discussed a new product in the class, ciprofloxacin (Cetraxal Otic) including indications, dosing, administration and dosage form.

Dr. Correia also noted the new product, reiterating there are only two different fluoroquinolones in the class. He concluded all products are effective with none demonstrating an overall advantage.

A Committee member discussed the use of otic fluoroquinolones with a steroid component, noting that the addition of the steroid improved outcomes and questioned why the new product in the class did not contain a steroid.

11. Re-review of the Sedative Hypnotics/Sleep Agents therapeutic class

Drugs Affected: Ambien (zolpidem), Ambien CR (zolpidem CR), chloral hydrate, Dalmane (flurazepam), Doral (quazepam), Edluar (zolpidem sublingual tablet), estazolam, flurazepam, Halcion (triazolam), Lunesta (eszopiclone), Prosom (estazolam), Restoril (temazepam), Rozerem (ramelteon), Somnote (chloral hydrate), Sonata (zaleplon), temazepam, triazolam, zaleplon, zolpidem

Dr. Rogler noted the new zolpidem sublingual tablet formulation and the label update for quazepam regarding CYP2B6 enzyme inhibition.

Dr. Correia reiterated the information presented by Dr. Rogler and concluded there was no new clinical evidence submitted or found demonstrating overall superiority for any of the drugs in this class since the last re-review that would change the previous conclusions for this class.

12. Re-review of the Central Nervous System Stimulants therapeutic class

Drugs Affected: Adderall (amphetamine salt combo), Adderall XR (amphetamine salt combo XR), amphetamine salt combo, amphetamine salt combo ER, Concerta (methylphenidate), Daytrana (methylphenidate), Desoxyn (methamphetamine), Dexedrine (dextroamphetamine sulfate), Dexedrine Spansule (dextroamphetamine), dexmethylphenidate, 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, Nuvigil (armodafinil), Procentra (dextroamphetamine sulfate), Provigil (modafinil), Ritalin (methylphenidate), Ritalin SR (methylphenidate SR), Ritalin LA (methylphenidate LA), Vyvanse (lisdexamfetamine dimesylate)

Dr. Rogler provided an overview of Nuvigil (armodafinil) including indications, dosing and administration, warnings and precautions, pharmacokinetics and use in special populations including pregnant women and women who are nursing. She indicated safety and effectiveness have not been established in patients under 17 or over 65 years of age. She discussed the FDA sponsored study: Ongoing Safety Review of Stimulant Medications used in Children with ADHD. She noted that Dextrostat is no longer available, and label updates for Focalin XR and Vyvanse.

Dr. Correia noted the new product Nuvigil, an isomer of Provigil, which has the same indication. Therefore, the same additional clinical criteria as Provigil could be applied to Nuvigil for the indication related to shift work sleep disorder if needed. He discussed the FDA Safety Communication about an ongoing review of stimulant medications used in children, noting almost all products in the class have approved indications in children aged 6 years and older, except Provigil and Nuvigil. He mentioned the products that have a labeled indication for ADHD in adults. He concluded that overall, there is little good clinical evidence for comparative effectiveness for the drugs in this class, and conflicting evidence for comparative efficacy, and considering the potential for continued use over many years, still no real long-term evidence for safety. There is a lack of evidence to demonstrate an overall advantage for any drug for shared indications within the drug class, and it would be preferable to have drugs in the short, intermediate, and long acting ranges represented among the preferred drugs.

13. Re-review of the Injectable Anticoagulants therapeutic class

Drugs Affected: Arixtra (fondaparinux sodium), Fragmin (dalteparin sodium), Innohep (tinzaparin sodium), Lovenox (enoxaparin sodium)

Dr. Rogler discussed labeling changes for Arixtra (fondaparinux) including safety concerns with pediatric use and dosing recommendations in hepatic impairment. She also noted an update in the contraindications for Fragmin (dalteparin). She discussed the black box warning update for all the agents in the class regarding epidural or spinal hematomas in patients who are anticoagulated with low molecular weight heparins (LMWH).

Dr. Correia indicated there are additional warnings added to the FDA labeling for fondaparinux pertaining to use in children, small patients, and hepatic impairment. He noted all the agents had subtle changes to the language in the boxed warnings. He concluded there is a lack of new comparative information between the products within this drug class, and none of these products demonstrates an overall advantage in all situations.

14. Re-review of the Urinary Tract Antispasmodics therapeutic class

Drugs Affected: Detrol (tolterodine), Detrol LA (tolterodine LA), Ditropan (oxybutynin), Ditropan XL (oxybutynin XL), Enablex (darifenacin), Gelnique (oxybutynin gel), oxybutynin, oxybutynin ER, Oxytrol (oxybutynin), Sanctura (trospium), Sanctura XR (trospium), Toviaz (fesoterodine fumarate), Vesicare (solifenacin)

Dr. Rogler provided an overview of Gelnique (oxybutynin gel), including indications, dosing and administration, precautions and contraindications, and pharmacokinetics. She discussed a head-to-head placebo-controlled trial comparing fesoterodine and tolterodine extended release. In that trial, the mean reduction in the number of urgency urinary incontinence (UUI) episodes per 24 hours was greater from baseline to week 12 in the fesoterodine group than with tolterodine ER. There were no statistical differences established for several other variables, and fesoterodine resulted in a greater incidence of dry mouth. She also discussed the Agency for Healthcare Research and Quality (AHRQ) evidence-based review which states that no single drug in this class was superior to others including the newer versus the older agents.

Dr. Correia also discussed the above mentioned study indicating that although fesoterodine did statistically better at certain defined endpoint outcomes, when the overall clinical impact is evaluated, there is little difference in clinical effect between the drugs, and not a dramatic clinical difference for either product compared to placebo. He also noted fesoterodine demonstrated about twice the incidence of dry mouth along with an increased incidence of constipation compared to tolterodine LA, and the overall rate of discontinuation of fesoterodine due to lack of efficacy was double that of tolterodine ER, and the same as placebo.

He noted the Oregon Health and Sciences University (OHSU) Drug Effectiveness Review Report on drugs for overactive bladder indicates similarity between the drugs in this class. He also noted, as was discussed in the original review of these drugs, clinical trials demonstrated similarity in efficacy between immediate and sustained release dosage forms.

He discussed warning letters issued by the FDA to the manufacturers of Sanctura for claims in their promotional material and to the manufacturers of VesiCare for their webpage because of unsubstantiated claims of superiority and overstating the efficacy of their product. The FDA stated that citations to the STAR trial, which was submitted to the Committee last year, do not support their claims. The FDA further indicated that generally, claims of superiority must be supported by two adequate and well-controlled head-to-head clinical trials, comparing appropriate doses and dose regimens for the drug in question and the comparator drug. Dr. Correia noted that superior efficacy of one drug over another does not demonstrate overall clinical superiority of the drug over that comparator drug or the drug class as a whole.

Dr. Correia concluded that clinical evidence reviewed for this drug class again indicates similar adverse effect profiles, with slight variations between incidences or degree of individual effects in the various drugs, and any of these drugs provide comparable, albeit modest symptomatic relief, with none demonstrating an overall advantage.

15. Re-review of the Erythropoiesis Stimulating Agents (ESAs) therapeutic class

Drugs Affected: Aranesp (darbepoetin alfa), Epogen (epoetin alfa), Procrit (epoetin alfa)

Dr. Rogler discussed the TREAT study in which patients with diabetes and chronic kidney disease who received darbepoetin alfa were more likely to experience a stroke than those receiving a placebo. She also discussed the ESA APPRISE (Assisting Providers and Cancer Patients with Risk information for the Safe use of ESAs) Oncology program for healthcare professionals who prescribe ESAs to patients with cancer. The ESA APPRISE Oncology program is part of the Risk Evaluation and Mitigation Strategy (REMS), and is included in an updated black box warning for the class.

Dr. Correia noted the new information generally does not distinguish between the different products in the class, and the Aranesp study noted above was versus placebo, not erythropoietin, and therefore was not comparative. He reiterated the updated labeling and the REMS programs apply to all 3 products. He concluded the epoetin products are identical, and either epoetin or darbepoetin may have advantages or be preferable in specific situations or at different stages of disease progression, but neither demonstrates overall advantages at all stages or in all situations.

E. Executive Session:

The Committee recessed the public session at 11:35 AM to go into executive session for review of financial information relating to the recommendation of preferred drugs in the following classes: Biguanides, Xanthine Oxidase Inhibitors, Third Generation Cephalosporins, Oral Fluoroquinolones, Otic Fluoroquinolones, Phosphate Binder/Regulators, Progestins for Cachexia, Selective Alpha Adrenergic Blockers, Sulfasalazine Derivatives and Anti-Emetics. No official action was taken in the executive session. The executive session was recessed at 1:10 PM.

The Committee recessed the public session at 2:10 PM to go into executive session for review of financial information relating to the recommendation of preferred drugs in the following classes: Sedative Hypnotics/Sleep Agents, Central Nervous System Stimulants, Injectable Immunomodulators, Injectable Anticoagulants, ESAs, Triptans and Urinary Tract Antispasmodics. No official action was taken in the executive session. The executive session was recessed at 3:00 PM.

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 RecommendationsCommissioner's Final Determination
Proposal: The Committee will consider the request to exempt tacrolimus from the requirements of the Mandatory Generic Drug Program

The Committee unanimously recommended to table the discussion to another meeting and at that time review criteria to determine "good cause" for exemption from the Mandatory Generic Drug Program (MDGP). Prograf, as well as the other currently exempt drugs, will be considered for exemption or continued exemption within the context of those criteria, and a recommendation will be made to the Commissioner of Health. The Committee also recommended that Prograf not require prior authorization under the MGDP, until further review as described above.
Approved as Recommended
Proposal: Identification of preferred drugs in the category of Biguanides

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
metformin HCl, metformin HCl ER

Non-preferred Drugs
Fortamet (metformin HCl ER), Glucophage (metformin HCl), Glucophage XR (metformin HCl ER), Glumetza (metformin HCl ER), Riomet solution (metformin HCl)

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process:
  • 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
Proposal: Identification of preferred drugs in the category of Xanthine Oxidase Inhibitors

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 Drug
allopurinol

Non-preferred Drugs
Zyloprim (allopurinol), Uloric (febuxostat)

Approved as Recommended
Proposal: Identification of preferred drugs in the category of Third Generation Cephalosporins

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
cefdinir, cefpodoxime proxetil, Suprax (cefixime)

Non-preferred Drugs
Cedax (ceftibuten), cefditoren pivoxil, Omnicef (cefdinir), Spectracef (cefditoren), Vantin (cefpodoxime proxetil)

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.
Approved as Recommended
Proposal: Identification of preferred drugs in the category of Oral Fluoroquinolones

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
Avelox (moxifloxacin), Cipro Suspension (ciprofloxacin), ciprofloxacin, ofloxacin

Non-preferred Drugs
Cipro Tablets (ciprofloxacin), Cipro XR (ciprofloxacin ER), ciprofloxacin ER, Factive (gemifloxacin), Levaquin (levofloxacin), Noroxin (norfloxacin), Proquin XR (ciprofloxacin)

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.
Approved as Recommended
Proposal: Identification of preferred drugs in the category of Phosphate Binder/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
calcium acetate, Fosrenol (lanthanum), Phoslo (calcium acetate), Renagel (sevelamer HCL), Renvela tablet (sevelamer carbonate)

Non-preferred Drugs

Eliphos (calcium acetate), Renvela packets (sevelamer carbonate)

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.
Approved as Recommended
Proposal: Identification of preferred drugs in the category of Progestins (for Cachexia)

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
megestrol acetate

Non-preferred Drugs
Megace (megestrol acetate), Megace ES (megestrol acetate)

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.
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
Rapaflo (silodosin), tamsulosin

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.
Based on new financial information which became available subsequent to the P&T Committee meeting, the final determination for preferred and non-preferred drugs is as follows:

Preferred Drugs
tamsulosin, Uroxatral (alfuzosin)

Non-preferred Drugs
Flomax (tamsulosin), Rapaflo (silodosin)
Proposal: Identification of preferred drugs in the category of Sulfasalazine Derivatives

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
Apriso (mesalamine), Asacol (mesalamine), Dipentum (olsalazine), Pentasa (mesalamine), sulfasalazine, sulfasalazine DR/EC

Non-preferred Drugs
Asacol HD (mesalamine), Azulfidine (sulfasalazine), Azulfidine Entab (sulfasalazine), balsalazide, Colazal (balsalazide), Lialda (mesalamine)

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.
Approved as Recommended
Proposal: Identification of preferred drugs in the category of Serotonin Receptor Agonists -Triptans

A. Based on the submitted or presented clinical information and on the financial information provided during the executive session, the Committee recommended the following (by a vote of 8 to 1):

Preferred Drugs
Maxalt MLT (rizatriptan), Relpax (eletriptan), sumatriptan

Non-preferred Drugs
Amerge (naratriptan), Axert (almotriptan), Frova (frovatriptan), Imitrex (sumatriptan), Maxalt tablet (rizatriptan), Treximet (sumatriptan/naproxen), Zomig (zolmitriptan)

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.
Approved as Recommended
Proposal: Identification of preferred drugs in the category of Anti-Emetics

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 Drug
ondansetron

Non-preferred Drugs
Anzemet (dolasetron), granisetron, Granisol (granisetron), Kytril (granisetron), Sancuso (granisetron patch), Zofran (ondansetron)

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.
Approved as Recommended
Proposal: Identification of preferred drugs in the category of Injectable 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
Enbrel (etanercept), Humira (adalimumab)

Non-preferred Drugs
Cimzia (certolizumab pegol), Kineret (anakinra), Simponi (golimumab)

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.
Approved as Recommended
Proposal: Identification of preferred drugs in the category of Otic Fluoroquinolones

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
Ciprodex (ciprofloxacin/dexamethasone), ofloxacin

Non-preferred Drugs
Cetraxal (ciprofloxacin), Cipro HC (ciprofloxacin/hydrocortisone), Floxin (ofloxacin)

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.
Approved as Recommended
Proposal: Identification of preferred drugs in the category of Sedative Hypnotics/Sleep Agents

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
chloral hydrate, estazolam, flurazepam, temazepam, triazolam, zolpidem

Non-preferred Drugs
Ambien (zolpidem), Ambien CR (zolpidem CR), Doral (quazepam), Edluar (zolpidem sublingual tablet), Halcion (triazolam), Lunesta (eszopiclone), Restoril (temazepam), Rozerem (ramelteon), Somnote (chloral hydrate), Sonata (zaleplon), zaleplon

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.
Approved as Recommended
Proposal: Identification of preferred drugs in the category of Central Nervous System 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), dexmethylphenidate, dextroamphetamine sulfate, dextroamphetamine sulfate SA, Focalin (dexmethylphenidate), Focalin XR (dexmethylphenidate XR), Metadate ER (methylphenidate ER), Methylin (methylphenidate), Methylin ER (methylphenidate ER), methylphenidate, methylphenidate ER/SR, Vyvanse (lisdexamfetamine dimesylate)

Non-preferred Drugs
Adderall (amphetamine salt combo), amphetamine salt combo ER, Daytrana (methylphenidate), Desoxyn (methamphetamine), Dexedrine Spansule (dextroamphetamine), Metadate CD (methylphenidate CD), Nuvigil (armodafinil), Procentra (dextroamphetamine sulfate), Provigil (modafinil), Ritalin (methylphenidate), Ritalin SR (methylphenidate SR), Ritalin LA (methylphenidate LA)

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process and an additional clinical question for Nuvigil (armodafinil) and Provigil (modafinil) as follows:
  • Q: Is the patient being treated for excessive sleepiness associated with shift work sleep disorder or as an adjunct to standard treatment for obstructive sleep apnea?
Approved as Recommended
Proposal: Identification of preferred drugs in the category of Anticoagulants - Injectable

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
Arixtra (fondaparinux sodium), Fragmin (dalteparin sodium), Lovenox (enoxaparin sodium)

Non-preferred Drugs
Innohep (tinzaparin sodium)

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.
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, Oxytrol (oxybutynin), Sanctura (trospium), Sanctura XR (trospium), Vesicare (solifenacin)

Non-preferred Drugs
Detrol (tolterodine), Ditropan (oxybutynin), Ditropan XL (oxybutynin XL), Gelnique (oxybutynin gel), oxybutynin ER, Toviaz (fesoterodine fumarate)

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.
Approved as Recommended
Proposal: Identification of preferred drugs in the category of Erythropoiesis Stimulating Agents (ESAs)

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
Aranesp (darbepoetin alfa), Procrit (epoetin alfa)

Non-preferred Drug
Epogen (epoetin alfa)

B. The Committee unanimously recommended the standard clinical questions be used in the prior authorization review process.
Approved as Recommended

G. Election of Committee Chair and Co-Chair:

The Committee voted 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 3:10 PM

Meeting Summary Posted 06/04/2010

H. Final Determinations

1. Mandatory Generic Drug Program

The Commissioner deferred any final determination regarding Prograf (tacrolimus) pending analysis of "good cause" for exemption, to be discussed by the Committee at a future meeting.

The impact of this final determination is as follows:

a. State Public Health Population:

  • No impact.

b. Program Providers:

  • No impact.

c. State Health Program:

  • No impact.

2. 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 $45M. 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