Pharmacy and Therapeutics Committee Meeting Summary - November 10, 2006

Agenda and Introduction

The Medicaid Pharmacy & Therapeutics Committee met on Friday, November 10, 2006 from 8:45 a.m. to 3:00 p.m. in Meeting Room 6, Concourse, Empire State Plaza, Albany, New York.

Linda Jones, NYS Department of Health, Office of Medicaid Management (DOH/OMM), indicated that the prior authorization of Topical Immunomodulators agenda item had been removed from the agenda for this meeting. The Commissioner had not reviewed the recommendations from the September 19, 2006 Pharmacy and Therapeutics Committee meeting, which included a proposal to require prior authorization for drugs in the Topical Immunomodulator class under the Clinical Drug Review Program. Ms. Jones also indicated that DOH may monitor this drug category under its drug utilization review program.

Dr. Martin (Chairperson) noted appreciation on behalf of the Committee for the written materials that had been submitted in advance of the meeting. He indicated that the agenda items would be arranged to accommodate one executive session and that there were no Oregon Health & Science University presentations for this meeting. He also noted that the NYS Medicaid program does not have a formulary, that all drugs currently covered by Medicaid remain available under the preferred drug program, and that the determination of preferred and non-preferred drugs does not prohibit a prescriber from obtaining any of the medications covered under Medicaid.

A. Background Materials Provided:

The Committee was provided copies of written materials submitted by interested parties in advance of the meeting.

B. Public Comment Period:

The following speakers addressed the committee:

  1. Sanders, Alan, MD, Infectious Disease, Clinical Instructor in Medicine, Albany Medical Center Hospital and Albany Medical College, Albany, NY
  2. Robins, Perry, MD, Professor of Dermatology, NYU Medical Center, New York, NY
  3. Robles, Catherine, PharmD, Regional Scientific Associate Director, Novartis Pharmaceuticals Corporation, Hauppauge, NY
  4. Baker, David A., MD, Professor of Obstetrics, Gynecology and Reproductive Medicine; Director, Division of Infectious Diseases, Stony Brook University Medical Center, Stony Brook, NY
  5. Papariello, Anthony, PharmD, Regional Medical Scientist, GlaxoSmithKline, New York, NY
  6. Clare, Frederick, MD, Physician, New York, NY
  7. Price, Arlene, PharmD, Sr. Scientific Affairs Liaison, Ortho McNeil Janssen, Randolph, NJ
  8. Bertino Jr., Joseph S., PharmD, Scientific Director, Ordway Research Institute Drug Development Center, Albany, NY
  9. Lee-Wong, Mary, MD, Assistant Professor, Albert Einstein School of Medicine, Oscient Pharmaceutical, Hurricane, WV
  10. Notaristefano, Gina, MD, Family Practitioner, Oscient Pharmaceutical, Hurricane, WV
  11. Faria, Claudio, PharmD, MPH, Medical Science Liaison, Schering-Plough, Kenilworth, NJ
  12. Saperstone, James D., MD, Practicing Pediatrician/Medical Director, MVP Healthcare, Schenectady, NY
  13. deLeon, Dennis, President, Latino Commission on AIDS, New York, NY
  14. Freedland, Eric, MD, Director of Medical Affairs, Serono, Inc., Rockland, MA
  15. Carr, Teresa, RN, BSN, Managed Markets Account Manager, Serono, Inc., Mason, OH

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

Public comments:

On the topic of identification of preferred drugs in the therapeutic class of Anti-Fungals:

  • Information regarding Penlac (ciclopirox), including safety, efficacy, indications, adverse events, and cost effectiveness was presented.
  • The Committee was asked to consider the use of this topical medication in diabetics, the elderly, and in pediatric patients in the review of this category.

On the topic of identification of preferred drugs in the therapeutic class of Anti-Virals:

  • Information regarding clinical trial results (indications, dosing [initial, recurrent and suppression], safety, efficacy, adverse events, and pharmacokinetics) for drugs in this category was presented.
  • The Committee was asked to consider the use of these medications in special populations including HIV patients and discordant heterosexual couples, current national treatment guidelines, the importance of adherence, and dosing convenience in the review of this category.

On the topic of identification of preferred drugs in the therapeutic class of Fluoroquinolones:

  • Information regarding clinical trial results (safety, efficacy, indications, adverse reactions, drug and food interactions, dosing adjustments, contraindications, and duration of therapy) for drugs in this category was presented.
  • The Committee was asked to consider the place in therapy of fluoroquinolones with respect to antimicrobial resistance, and the importance of choosing the appropriate drug, dose, and duration of therapy for different indications, in the review of this category.

On the topic of identification of preferred drugs in the therapeutic class of Third Generation Cephalosporins:

  • Information regarding the use of antibiotics, including third generation cephalosporins (appropriate use, dosing to achieve effective MICs in light of emerging resistance patterns) for drugs in this category was presented.
  • The Committee was asked to consider viral versus bacterial illness, national practice guidelines for antibiotics, effectiveness against resistant organisms, flexibility of dosing, and palatability of the different suspensions in the review of this category.

On the topic of the review of prior authorization criteria for Serostim:

  • Information regarding clinical trial results (indications, duration of treatment, contraindications) for Serostim was presented.
  • The Committee was asked to consider the current clinical criteria for Serostim, other treatments available for HIV-associated weight loss, relevant laboratory test results, and the importance of having a prior authorization process in place that is efficient and ensures appropriate utilization of Serostim in the review of this category.

Pharmacy and Therapeutics Committee Response:

  • A committee member asked for clarification that Factive does not have an indication for urinary tract infection (UTI) or acute sinusitis and the presenter indicated that that is correct.
  • A committee member asked the presenter to comment on Cipro XR and anthrax. The presenter indicated that Cipro has activity against anthrax, but could not comment on the use of the XR formulation for that indication.
  • A committee member asked for clarification regarding cefdinir as a first line versus second line agent in the practice guidelines mentioned in the testimony and the presenter indicated that it is generally recommended as a second line agent.
  • A committee member questioned the source of written comments provided to a presenter regarding the Medicaid prior authorization process for Serostim. The presenter indicated that she could provide him that information.

D. Clinical Presentation and Discussion: Proposal to identify preferred drugs in the therapeutic class of Anti-Fungals (used in the treatment of Onychomycosis)

Anti-Fungals (used in the treatment of Onychomycosis)

Drugs Affected: Fulvicin U/F (griseofulvin), Grifulvin V (griseofulvin), Gris-PEG (griseofulvin), griseofulvin, Lamisil (terbinafine), Penlac (ciclopirox), itraconazole, Sporanox (itraconazole)

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

Ms. Roberts provided a brief overview of onychomycosis and of the drugs included in the review, including indications, efficacy, pharmacokinetics, warnings, contraindications, drug interactions, adverse reactions, and dosing. She discussed the use of these agents in special populations including diabetics, pediatrics, immunocompromised patients, and use in pregnancy. She described clinical trials comparing different dosing regimens as well as a comparative trial of itraconazole versus terbinafine, and a trial of ciclopirox lacquer versus placebo. Based on a review of clinical studies, it was recommended that the oral agents be considered therapeutic alternatives.

Dr. Correia provided the Department's clinical review for this category. He spoke about the difference in efficacy between the oral agents and ciclopirox topical solution, based on information available in clinical studies. He indicated that although comparative evidence suggests that terbinafine may be somewhat more effective than itraconazole versus onychomycosis caused by dermatophytes, the dosage regimens used in the studies (continuous versus intermittent) may be considered inconsistent. Dr. Correia quoted the Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) Clinical Review and Evaluation for ciclopirox nail lacquer which states "...the pivotal studies fail to demonstrate statistically significant differences in complete cure or effective treatment when comparing Ciclopirox Nail Lacquer 8% to the vehicle lacquer." Considering the clinical information available, he concluded that any of the three oral products are effective and may have advantages for particular infections or patient populations, with none of these drugs demonstrating overall advantages for all cases, and that the topical preparation is of questionable effectiveness in resolving onychomycosis compared to the oral agents.

A committee member asked for clarification of microsized versus ultramicrosized griseofulvin, and also for clarification on intermittent dosing of Lamisil. Ms. Roberts noted that ultramicrosized preparations may be slightly more tolerable than microsized preparations, and that the approved Lamisil dosing is continuous, not intermittent.

A committee member asked if any of the clinical studies included diabetic patients. Ms. Roberts indicated that diabetics were not included in Penlac studies, and were included in very few studies of the oral agents.

A committee member commented that the oral agents have major drug interactions especially with medications taken by HIV infected patients and that Penlac is the drug of choice in that population. Dr. Correia indicated that Penlac should be considered an alternate medication in this population rather than a drug of choice since it may be the only option remaining, even though it has limited efficacy.

Ms. Roberts indicated, in response to a question from the Committee, that the Penlac studies did not indicate if the patients included had failed other agents, or were naïve to treatment.

E. Clinical Presentation and Discussion: Proposal to identify preferred drugs in the therapeutic class of Anti-Virals (used in the treatment of Herpes)

Anti-Virals (used in the treatment of Herpes)

Drug(s) Affected: acyclovir, Famvir (famciclovir), Valtrex (valacyclovir), Zovirax (acyclovir)

Mary Roberts, RPh, (FHSC); Robert Correia, PharmD, (DOH/OMM)

Ms. Roberts provided a brief overview of herpes infections including herpes zoster and genital herpes simplex virus (HSV), and explained the goals of treatment. She reviewed the drugs including the indications, efficacy, pharmacokinetics, adverse reactions, dosage forms, and dosing. She summarized clinical trials for both herpes zoster and genital HSV, reviewed the use of these medications in pediatrics and pregnancy, and reviewed the 2006 Federal Centers for Disease Control and Prevention (CDC) Treatment Guidelines for Sexually Transmitted Diseases (STDs) for the use of these drugs in genital herpes. Based on available clinical information, it was recommended that these agents be considered therapeutic alternatives.

Dr. Correia provided the Department's recommendations regarding the clinical review for this category of drugs. He clarified initial treatment versus recurrence versus suppression and also reviewed the CDC STD Guidelines for the use of these drugs in immunocompetent and HIV-infected patients. He discussed the data regarding the use of valacyclovir to prevent transmission of the virus in discordant couples. He addressed dosing regimens for the different indications and drugs with regard to "pill burden", indicating that according to the most recent federal guidelines, there are only minor differences in dosing frequency which may result in the same number of tablets, or one extra tablet taken per day. He noted that all three drugs are pregnancy category B and only acyclovir is approved for use in children. He concluded that based on the available clinical information, all three oral products are effective and any one may have advantages for a specific use or patient population.

A committee member asked for clarification regarding Famvir and heterosexual HSV-2 transmission and Ms. Roberts indicated that there was no data available.

F. Clinical Presentation and Discussion: Proposal to identify preferred drugs in the therapeutic class of Fluoroquinolones (Oral)

Fluoroquinolones (Oral)

Drug(s) Affected: Avelox (moxifloxacin), ciprofloxacin, ofloxacin, Cipro (ciprofloxacin), Cipro XR (ciprofloxacin ER), Factive (gemifloxacin), Floxin (ofloxacin), Levaquin (levofloxacin), Maxaquin (lomefloxacin), Noroxin (norfloxacin), Proquin XR (ciprofloxacin), Tequin (gatifloxacin)

Mary Roberts, RPh, (FHSC); Robert Correia, PharmD, (DOH/OMM)

Ms. Roberts provided an overview of fluoroquinolones including indications, spectrum of activity, pharmacokinetics, warnings, contraindications, drug interactions, adverse effects, dosing, and use in pregnancy, pediatrics, and renal disease. She reviewed clinical guidelines with respect to the fluoroquinolones for chronic bronchitis (AECB), bacterial sinusitis, community acquired pneumonia (CAP), prostatitis, skin infections, and sexually transmitted diseases. She discussed comparitive clinical trials, noting the importance of recognizing that there are regional variations in resistance patterns, and concluded by noting that there is little evidence that any one fluoroquinolone is better than another when used in equivalent doses for approved indications, and therefore the drugs in this category may be considered therapeutic alternatives for the diagnoses for which they are indicated.

Dr. Correia provided the Department's recommendations regarding the clinical review for this category of drugs. He explained the first, second and third generation quinolones and their differences in spectrum of activity. He noted that the effectiveness of the fluoroquinolones is concentration dependent, rather than time dependent. He described peak drug concentration, area under the curve (AUC) above minimum inhibitory concentration (MIC), and explained why this is relevant with regard to drug and food interactions, and length of therapy. He noted that while only ciprofloxacin has approval in pediatric patients; the American Academy of Pediatrics does not differentiate between fluoroquinolones in their guidelines. He concluded that based on available clinical information, none of these drugs demonstrate an overall advantage, but with the difference in spectrum of activity between the second and third generation fluoroquinolones, it was suggested to have both generations represented on the preferred drug list.

A committee member asked if any third generation fluoroquinolone achieved higher AUCs and Dr. Correia indicated that in his opinion, no one is better overall.

A question was raised regarding the effects of fluoroquinolones on the prolongation of the QTc interval, and it was noted that ciprofloxacin does not have QT guidance in the labeling and the third generation drugs all have similar QT guidance.

A committee member asked about the design of the clinical trials in this category and it was noted that there were few head to head trials, and most trials were either placebo controlled or compared fluoroquinolones to other antibiotic classes.

G. Clinical Presentation and Discussion: Proposal to identify preferred drugs in the therapeutic class of Third Generation Cephalosporins

Third Generation Cephalosporins

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

Steve Liles, PharmD, Provider Synergies; Robert Correia, PharmD, (DOH/OMM)

Dr. Liles began with a brief explanation of the three generations of oral cephalosporins. He then described the medications in the third generation category, including spectrum of activity, indications, pharmacokinetics, warnings and contraindications, drug interactions, adverse reactions, dosing and dosage forms, and use in pediatrics and pregnancy. He noted that there are not a lot of controlled randomized studies for this category, and the studies tend to have high drop out rates. The general findings in the available studies are that the drugs in this class have similar rates of clinical cure and bacterial eradication and because susceptibility patterns vary, it is hard to find superiority. He reviewed practice guidelines with regard to drugs in this category for CAP, AECB, acute otitis media, pharyngitis, gonorrhea, skin, and urinary tract infection. He noted that in all of the guidelines, these drugs have a limited role and are rarely recommended as first line therapy.

Dr. Correia provided the Department's recommendations regarding the clinical review for this category of drugs. He reiterated the spectrum of activity of the drugs and noted differences within the class with regard to relative gram negative and gram positive coverage, noting that none demonstrated an overall advantage. He concluded that based on available clinical information, all of the drugs in this class are effective and suggested that drugs in the gram negative and gram positive group be represented on preferred drug list.

A committee member asked Dr. Liles if he knew why there was a high drop out rate in these studies and Dr. Liles indicated that as often occurs in outpatient antibiotic trials, patients take the drug, feel better and don't return. It was also noted that taste of the antibiotic did not seem to be a factor in the drop out rates in the pediatric population.

H. Review and Discussion of Prior Authorization Criteria for Serostim

Robert Correia, PharmD, (DOH/OMM)

Dr. Correia stated that the purpose of this discussion was to review the established criteria for the prior authorization of Serostim and decide if these criteria continue to be clinically appropriate when determining medical necessity for Serostim. The criteria are publicly available on the DOH website and the Committee was provided a copy of the criteria prior to the meeting as follows:

  1. Dose (based on weight, chart included)
  2. Day supply (maximum 28 days)
  3. Does patient have clearly documented HIV infection or AIDS?
  4. Is patient 18 years of age or older?
  5. Is patient receiving at least 100% of estimated caloric requirement on current nutritional regimen?
  6. Are you or have you consulted with an HIV specialist?
  7. Does patient have unintentional weight loss of at least 5% or greater from baseline pre-morbid weight or weigh an amount that indicates a recent significant weight loss has occurred (BMI<20kg/m2) in the absence of opportunistic infection?
  8. Is patient on current anti-viral therapy with good viral suppression?
  9. Does the patient have recent blood work to confirm an amylase level ≤ 3 times the upper normal limit, a creatinine level ≤ 2mg/dl or a fasting triglyceride level ≤ 500mg/dl?
  10. Does the patient have an active malignancy (other than Kaposi's Sarcoma) or are they undergoing systemic chemotherapy or being treated with interferon, anabolic steroids or investigational drugs?
  11. Does the patient have evidence of GI bleeding, intestinal obstruction, malabsorption syndrome, or severe liver dysfunction?
  12. Does the patient have angina pectoris, coronary artery disease, congestive heart failure, renal failure, or serious chronic edema?
  13. Does the patient have a history of glucose intolerance or uncontrolled hypertension?
  14. Have other treatment modalities been tried and failed?
  15. Patient's current weight in pounds
  16. Patient's height in inches
  17. Patient's current Body Mass Index (BMI)
Serostim Dosing Chart:
Weight RangeAppropriate Dose
>121 pounds (>55 kilograms)6 mg SC daily
99 to 121 pounds (45-55 kilograms)5 mg SC daily
77 to 98 pounds (35-44 kilograms)4 mg SC daily

Dr. Correia reiterated that these criteria are not new and have been in use since 2002. On October 18, 2006, prior authorization for Serostim was transitioned from the voice interactive phone system (VIPS) to the Clinical Drug Review Program (CDRP). Under this program, the prescriber must call to personally request the prior authorization with verification of prescriber identity prior to issuance of the authorization.

A Committee member commented that he feels that the process should be stringent, perhaps even more stringent, and agreed that there is abuse and diversion of this drug. He voiced concern with the letters from prescribers regarding the new prior authorization process referenced in the public comment period. Serostim is indicated for treatment of wasting in HIV infected patients, and he agreed that these patients should be able to obtain the drug if needed. He indicated that he is in favor of prescribers being required to speak to a person at the clinical call center.

After further discussion and considering the information and concerns raised by the interested parties and the membership, the committee voted unanimously to accept the current prior authorization criteria.

I. Executive Session:

The Committee recessed the public session at noon to go into executive session for review of financial information relating to the determination of preferred drugs in the following classes: Anti-Fungals, Anti-Virals, Fluoroquinolones, and Third Generation Cephalosporins. No official action was taken in the executive session. The executive session was recessed at 1:45 P.M.

J. 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 Decision
Proposal: Identification of preferred drugs in the category of Anti-Fungals (used in the treatment of Onychomycosis)

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
Fulvicin U/F, Grifulvin V tablet, Gris-PEG, griseofulvin suspension, Lamisil

Non-preferred Drugs
Grifulvin V suspension, Penlac, itraconazole capsule, Sporanox capsule, Sporanox solution

B.The Committee unanimously recommended the following clinical questions be used as the basis for approving use of the non-preferred drug:

  • Q: Has your patient experienced treatment failure with a preferred anti-fungal agent?

  • Q: Has your patient experienced an adverse drug reaction with a preferred anti-fungal agent?

  • Q: Is there a documented history of successful therapeutic control with a non-preferred anti-fungal agent and transition to a preferred anti-fungal agent is medically contraindicated?

Approved as Recommended
Proposal: Identification of preferred drugs in the category of Anti-Virals (used in the treatment of Herpes)

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
acyclovir tablet, acyclovir suspension, Famvir, Valtrex

Non-preferred Drugs
Zovirax tablet, Zovirax suspension

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 Fluoroquinolones (Oral)

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, Avelox ABC Pack, ciprofloxacin tablet, ciprofloxacin suspension, ofloxacin

Non-preferred Drugs
Cipro tablet, Cipro suspension, Cipro XR, Factive, Floxin, Levaquin tablet, Levaquin solution, Maxaquin*, Noroxin, Proquin XR, Tequin*

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

*These medications have been discontinued by their manufacturers.

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
Cedax capsule, Cedax suspension, cefpodoxime proxetil tablet, Omnicef capsule, Omnicef suspension, Suprax

Non-preferred Drugs
Spectracef, Vantin tablet, Vantin suspension

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

C. The Committee recommended targeted outreach/intervention regarding the appropriate utilization of the third generation cephalosporins.

Approved as Recommended
Proposal: Review of Prior Authorization Criteria for Serostim

The Committee unanimously recommended that Medicaid continue to use the existing Serostim prior authorization clinical criteria.

Approved as Recommended

K. Additional Discussion:

Ms. Jones announced that the next Medicaid Pharmacy and Therapeutics Committee meeting will take place on December 8, 2006, and the agenda is posted on the DOH website.

Dr. Martin requested that DOH provide feedback to the committee on the prior authorization process at the December meeting.

L. Final Determinations:

The Commissioner has determined that Medicaid will require prior authorization under the Preferred Drug Program (PDP) for non-preferred drugs, as listed above, in the following classes: Anti-Fungals, Anti-Virals, Fluoroquinolones and Third Generation Cephalosporins. Preferred drugs will not require prior authorization.

The impacts of this final determination are as follows:

  • 1. State Public Health Population:
    • Minimal effects as a large majority of Medicaid patients currently utilize those drugs which have been determined to be preferred.
    • Use of prior authorization for non-preferred products encourages use of more cost effective drugs within the same therapeutic class when appropriate.
  • 2. Program Providers:
    • Limited additional time and effort will be required by prescribers to complete the prior authorization process for non-preferred drugs.
  • 3. Fiscal Impact to State Health Program:
    • Through the changes in utilization to more cost effective drugs, and the receipt of supplemental rebates from pharmaceutical manufacturers, annual savings for these categories of drugs under the Preferred Drug Program are estimated at $10.8M.

The Commissioner has determined that Medicaid will continue to use the existing clinical criteria for the prior authorization of Serostim under the Clinical Drug Review Program.

The impacts of this final determination are as follows:

  • 1. State Public Health Population:
    • No effect on Medicaid recipients, as Serostim has required prior authorization since 2002.
  • 2. Program Providers:
    • No effect on Medicaid providers, as the existing clinical criteria will continue to be used in the prior authorization process.
  • 3. Fiscal impact to State Health Program:
    • No fiscal impact.

Final Determinations Posted 1/11/07