September 2006

March 2007 ______

1st Quarter Update: Highmark Drug Formulary

Enclosed is the 1st Quarter 2007 update to the Highmark Drug Formulary and pharmaceutical management procedures. The formulary and pharmaceutical management procedures are updated on a quarterly basis, and the enclosed changes reflect the decisions made in December 2006 by our Pharmacy and Therapeutics Committee. These updates are effective on the dates noted throughout this document.

As an added convenience, you can also search the Highmark Drug Formulary online at http://highmark.formularies.com. This function allows you to search by the drug name or therapeutic class. You can also find other helpful information regarding the prescription drug program from our online Resource Center under the Pharmacy/Formulary Information link. (NaviNet® users: Simply click on the Resource Center button for quick access to the Pharmacy/Formulary Information link.)

Formulary changes will be reflective of both the Highmark Select/Choice Formulary (formerly the Highmark Closed/Incentive Formulary) and the Highmark Medicare-Approved Select/Choice Formulary. For each section, please refer to the header description to obtain information specific to that formulary.

Section I contains changes to the Highmark Select/Choice Formulary.

Section II contains changes to the Highmark Medicare-Approved Select/Choice Formulary. The Highmark Medicare-Approved Select/Choice Formulary can also be searched online at http://highmark.medicare-approvedformularies.com.

If you have any questions, contact your Provider Relations representative or call Pharmacy Affairs, toll-free, at 1-800-600-2227.

(over, please) Highmark Drug Formulary Update March 2007

Section I. Highmark Select/Choice Formulary (Formerly Closed/Incentive Formulary) A. Changes to the Highmark Select/Choice Formulary The Highmark Pharmacy and Therapeutics Committee has reviewed the medications listed in the tables below. Please note that since the Highmark Select/Choice Formulary is a complete subset of the Open Formulary, all medications added to the Select/Choice Formulary are automatically added to the Open Formulary. Products listed in the first table below were added to both the Select/Choice and the Open Formulary, effective Jan. 10, 2007, unless otherwise noted. For your convenience, you can search the Highmark Select/Choice Formulary online at http://highmark.formularies.com. An electronic copy of the Highmark Select/Choice Formulary for use with a portable handheld device can be downloaded free by visiting www.epocrates.com.

Table 1: Products Added Brand Name Generic Name Comments Advair® HFA fluticasone/salmeterol Advair® is also on the formulary. Acular LS® ketorolac tromethamine Acular® and Acular PF® are also on the formulary. Coreg® carvedilol Nonselective β-adrenergic blocking agent with α1- blocking activity Humira®* adalimumab Injectable monoclonal antibody for the treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis Ranexa®** ranolazine extended release New agent for the treatment of chronic angina in tablets combination with amlodipine, b-blockers or nitrates Travatan® Z travaprost Travatan® is also on the formulary.

Zolinza™*** vorinostat Oral therapy for cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) with progressive, persistent or recurrent disease on or following two systemic therapies *Added effective Nov. 29, 2006 **Added effective Feb. 1, 2007 ***Added effective March 1, 2007

Table 2: Products Not Added* Brand Name Generic Name Comments Abilify® Discmelt™ aripiprazole ODT Seroquel®, Risperdal® and Zyprexa® are on the formulary. Allegra® Oral fexofenadine oral suspension Allegra®, Zyrtec® and Zyrtec® syrup are on the Suspension formulary. Brovana™ arformoterol Albuterol nebulizer solution is on the formulary. Coreg™ CR carvedilol controlled release Multiple beta blockers are on the formulary. Desonate™ desonide gel 0.05% Desonide cream, lotion and ointment are on the formulary. Dutoprol™ Metoprolol Metoprolol tartrate and hydrochlorothiazide are on succinate/hydrochlorothiazide the formulary. Fentora™ fentanyl buccal tablet Hydromorphone, morphine sulfate and oxycodone are on the formulary. *Physicians may request coverage of these products using the Prescription Drug Medication Request Form, which can be found on page 8 of the 2007 Highmark Drug Formulary book. You may also access the form online in Highmark’s Provider Resource Center, under Provider Forms; select Miscellaneous Forms from the fly-out menu.

(continued)

2 A. Changes to the Highmark Select/Choice Formulary (continued) Table 2: Products Not Added* (continued) Brand Name Generic Name Comments Loestrin® 24 Fe ethinyl estradiol/norethindrone Yaz® is on the formulary. acetate ® ® MoviPrep PEG, NaSO4, NaCl, sodium Generic Colyte is on the formulary. ascorbate, ascorbic acid Noxafil® posaconazole Oral antifungal for prevention of invasive fungal infections or treatment of oropharyngeal candidiasis Verdeso™ desonide foam 0.05% Desonide cream, lotion and ointment are on the formulary. Xolegel™ ketoconazole gel Ketoconazole cream and ketoconazole shampoo are on the formulary. *Physicians may request coverage of these products using the Prescription Drug Medication Request Form, which can be found on page 8 of the 2007 Highmark Drug Formulary book. You may also access the form online in Highmark’s Provider Resource Center, under Provider Forms; select Miscellaneous Forms from the fly-out menu.

B. Updates to the Prior Authorization Program 1. Testosterone (Androgens) Effective Dec. 6, 2006, the prior authorization criteria for androgens was revised to allow for consideration of both total and free testosterone levels when determining eligibility for coverage. When a benefit, androgens will be approved for the following treatment conditions: • primary or secondary hypogonadism in males who have documented testosterone deficiency as defined by a total testosterone level of <270 ng/ml OR a total testosterone level <350 ng/ml AND a free testosterone level of <50 pg/ml or <9 nmol/L • delayed puberty in males > 15 years of age with either physical or laboratory evidence of hypogonadism (total testosterone level of <270 ng/ml OR a total testosterone level <350 ng/ml AND a free testosterone level of <50 pg/ml or <9 nmol/L) • vulvar dystrophies in women (topical ointment only) • palliative treatment in female patients with metastatic breast cancer

Androgens are not indicated for male contraception and will not be approved for this diagnosis. For patients with acquired hypogonadotropic hypogonadism with reduced libido and impotence, prolactin levels should be evaluated. Testosterone-containing products will not be approved for untreated hyperprolactinemia.

If approved, authorization may be granted for a period of up to one year.

2. EGFR/Tyrosine Kinase Inhibitors Effective Dec. 6, 2006, the prior authorization criteria for human epidermal growth factor receptor (EGFR)/tyrosine kinase inhibitors, including gefitinib (Iressa™) and erlotinib (Tarceva®), was revised to include consideration of ECOG performance status. When a benefit and prescribed under the supervision of an oncologist/hematologist, a tyrosine kinase inhibitor may be approved when one of the following criteria is met: • After documented failure of both platinum-based [i.e., cisplatin, Platinol®-AQ, carboplatin (Paraplatin®) and oxaliplatin (EloxatinTM)] and docetaxel (Taxotere®) or paclitaxel (Taxol®) or gemcitabine (Gemzar®) chemotherapies, or • The member has an ECOG performance status of 2 and has documented failure of at least one single agent chemotherapy regimen, or • The member has an ECOG performance status of 3 or 4, or • Erlotinib will be covered for the treatment of pancreatic cancer as first-line treatment when used in combination with gemcitabine. (continued)

3 B. Updates to the Prior Authorization Program (continued) 2. EGFR/Tyrosine Kinase Inhibitors (continued) Coverage of tyrosine kinase inhibitors as salvage therapy for disease states outside of their FDA- approved indications should be evaluated based on the member’s diagnosis, based on documented failure of all FDA-approved therapies for their diagnosis and in accordance to Highmark Medical Policy G-16.

Coverage of tyrosine kinase inhibitors for disease states outside of their FDA-approved indications will be denied based on the lack of clinical data to support their effectiveness and safety in other conditions.

If approved, authorization may be granted for up to one year.

3. GleevecTM (imatinib) Effective Dec. 6, 2006, the prior authorization criteria for imatinib will be revised to include new FDA-approved indications. When a benefit, imatinib may be approved when prescribed under the supervision of an oncologist/hematologist and used for the treatment of one of the following diagnoses: • chronic myeloid leukemia (CML) of any phase • documented c-KIT expressing gastrointestinal stromal tumors (GIST) • adult dermatofibrosarcoma protuberans (DFSP) • adult relapsed/refractory PH+ ALL • adult hypereosinophilic syndrome/chronic eosinophilic leukemia (HES/CEL) • adult aggressive systemic mastocytosis (ASM) in patients without documented D816V c-KIT mutation • adult myeloproliferative diseases (MPD) after treatment with at least one therapeutic regimen (i.e., hydroxyurea, anagrelide, etc.) • adult myelodysplastic syndrome (MDS)

Use of imatinib for disease states outside of its FDA-approved indications will be denied based on the lack of clinical data to support its effectiveness and safety in other conditions.

If approved, authorization may be granted for a period of up to one year.

4. Forteo® (teriparatide) Effective Dec. 6, 2006, the prior authorization criteria and duration of authorization for teriparatide will be revised. When a benefit, teriparatide may be approved when the following criteria are met: • The member is currently taking appropriate calcium and vitamin D supplements, AND • The member does not have an underlying hypercalcemic disorder, such as hypercalcemia, hyperparathyroidism or hypoparathyroidism, or is at risk for osteosarcoma (e.g., Paget’s disease, prior radiation therapy, bone metastases, open epiphyses, etc.), AND • The member has postmenopausal osteoporosis (women) or primary or hypogonadal osteoporosis (men) [T Score ≤-2.5] and is intolerant to or has a contraindication to at least two osteoporotic therapies, one of which must be a bisphosphonate (i.e., Actonel®, Fosamax®). Other therapies include a selective estrogen receptor modulator (i.e., Evista®), calcitonin or hormone replacement therapy with estrogens, OR • The member has a documented failure with at least one bisphosphonate (i.e., Actonel®, Fosamax®, Boniva®). At least a six to 12-month trial of oral bisphosphonates will be considered adequate to determine a treatment failure. Failure will be defined as: 1. new osteoporotic fracture despite bisphosphonate therapy, or 2. a T-Score ≤-3.0 despite bisphosphonate therapy (continued)

4 B. Updates to the Prior Authorization Program (continued) 4. Forteo® (teriparatide) (continued) If approved, authorization will be granted for a two-year period. Additional requests for the use of Forteo beyond two years of therapy will not be considered, as insufficient evidence exists to support its use for longer durations.

5. ZolinzaTM (vorinostat) Effective March 1, 2007, Zolinza™ (vorinostat) will be added to Highmark’s Prior Authorization program. Vorinostat inhibits the enzymatic activity of histone deacetylases HDAC1, HDAC2, HDAC3 (Class I) and HDAC6 (Class II). In some cancer cells, there is an over-expression of HDACs or an aberrant recruitment of HDACs to oncogenic transcription factors. HDACs are involved in the remodeling of chromatin, regulating gene expression without altering DNA sequence. Histone deacetylation is believed to be a key mechanism by which cancer cells inactivate tumor-suppressor genes, resulting in uncontrolled proliferation of tumor cells.

Vorinostat is approved for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. Systemic therapies include bexarotene (Targretin®), interferon-α, extracorporeal photochemotherapy, PUVA and single-agent or combination chemotherapies.

When a benefit, vorinostat may be approved when all of the following criteria are met: • Vorinostat is to be prescribed under the supervision of an oncologist/hematologist. • Vorinostat is to be used for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. • Use of vorinostat for disease states outside of its FDA-approved indications will be denied based on the lack of clinical data to support its effectiveness and safety in other conditions.

If approved, authorization may be granted for a period of up to one year.

6. Oral transmucosal fentanyl citrate (Actiq®; Fentora™) Actiq® and Fentora™ will be added to Highmark’s Prior Authorization program effective May 1, 2007. Actiq® and Fentora™ (oral transmucosal fentanyl citrate) are potent, immediate release, short-acting opioid analgesics that are indicated for the management of breakthrough cancer pain in patients who are already receiving and tolerant to opioid therapy for their underlying persistent cancer pain. Actiq and Fentora are administered as one unit over 15 minutes as needed for breakthrough pain. Once a successful dose has been found, patients should consume no more than four units per day. If more units are required on a daily basis for the management of breakthrough cancer pain, an increase in the around-the-clock opioid dose for persistent pain should be considered. Oral transmucosal fentanyl citrate should not be used for acute pain conditions or in situations involving chronic pain in which the patient is not receiving maintenance doses of long-acting opioid analgesics. When a benefit, oral transmucosal fentanyl citrate may be approved when the following criteria are met: • For the management of breakthrough cancer pain in patients who are currently receiving and tolerant to long-acting opioid therapy. • Upon approval, coverage will be limited to 120 units total (Fentora or Actiq) per 25 days. If more units are required on a daily basis for the management of breakthrough cancer pain, an increase in the around-the-clock opioid dose for persistent pain should be considered.

Oral transmucosal fentanyl citrate should not be used for acute pain conditions, chronic pain conditions which are not related to cancer or in situations involving chronic pain in which the patient is not receiving maintenance doses of long-acting opioid analgesics.

If approved, authorization may be granted for a period of up to one year.

5 C. Updates to the Managed Prescription Drug Coverage (MRxC) Program 1. Ranexa® (ranolazine) Effective Feb. 1, 2007, Ranexa® (ranolazine) was added to Highmark’s MRxC program. Ranolazine is the first in a new class of anti-anginal agents. The mechanism of anti-anginal activity is thought to be through a shift from fatty acid oxidation to carbohydrate oxidation for the production of adenosine triphosphate (ATP). Because carbohydrate oxidation requires less oxygen, ranolazine provides a more oxygen-efficient means of ATP production. This is preferred during ischemia when oxygen is limited. Although this is a possible mechanism of action for ranolazine, it is not a proven mechanism of action.

Ranolazine is FDA-approved for the treatment of chronic angina in patients who have not achieved an adequate response with other anti-anginal drugs. It is indicated for use in combination with amlodipine, b-blockers or nitrates. Ranolazine is currently being studied for the treatment of acute coronary syndromes (ACS) and for long-term prevention of ACS. There is inadequate data to support this diagnosis at this time.

When a benefit, coverage for ranolazine will be approved if members meet the following criteria: • There are claims for a nitrate plus one other anti-anginal agent in the member’s pharmacy profile in the previous six months. Other anti-anginal agents include beta-adrenergic receptor blockers (i.e., metoprolol, atenolol, bisoprolol, labetelol, etc.) or calcium channel antagonists (i.e., nifedipine, amlodipine, felodipine, etc). • Members who meet the criteria outlined above will receive automatic authorization at the pharmacy without documentation of additional information. Claims will adjudicate automatically, with no prior authorization required.

If the member does not meet the criteria above, a medication request form will need to be submitted by the physician to request coverage.

If approved, authorization may be granted for a period of up to one year.

2. Leukotriene Receptor Antagonists (Singulair®, Accolate®, Zyflo®) Effective Dec. 6, 2006, the Leukotriene receptor antagonist MRxC policy was revised to reflect the FDA approval of Singulair® for use in children 6 months of age and older. The approval criteria remain the same for this policy.

3. Fentora (fentanyl buccal tablet) Effective May 1, 2007, Fentora will be added to Highmark’s MRxC program. Fentora will be limited to 120 tablets per 25 days at retail. Physicians may request additional quantities by contacting the Pharmacy Service Center at 1-800-600-2227, Option 1. For clinical consideration, requests must contain the members’ around-the-clock opioid analgesic dosing regimen.

D. Quantity Level Limit (QLL) Program Additions Effective Jan. 1, 2007, the following products were added to Highmark’s Quantity Level Limit (QLL) program.

Table 3: Additions to the QLL program Generic Up to 34 Days’ Supply Limit 35-90 Days’ Supply Limit (Retail Brand Name Name (Retail) or Mail) Emend® aprepitant 1 capsule 1 capsule (40mg)

Exubera®* insulin human 1 inhaler kit/year 1 inhaler kit/year *Exubera was added Feb. 1, 2007. (continued)

6 D. Quantity Level Limit (QLL) Program Additions (continued) Table 3: Additions to the QLL program (continued) Generic Up to 34 Days’ Supply 35-90 Days’ Supply Limit Brand Name Name Limit (Retail) (Retail or Mail) Glucagon Emergency glucagon 1 kit 1 kit Kit™ Plan B®** levonorgestrel 1 kit 1 kit Twinject® epinephrine 2 devices 2 devices ** Plan B® is not covered for patients ≥18 years of age; it is covered for patients <18 years of age.

E. Updates to Highmark’s Formulary Policies 1. General non-formulary request criteria Effective Dec. 6, 2006, Highmark’s general non-formulary request criteria policy was updated to include the statement that no exception for coverage will be made for requests for prescription products that are not approved as federal legend drugs by the FDA, including medical foods (such as Foltx® and Metanx®) and medical devices (excluding diabetic testing supplies).

2. Noxafil® (posaconazole) Noxafil® (posaconazole) is a novel oral, broad-spectrum antifungal agent that is indicated for the prophylaxis of life-threatening fungal infections caused by Aspergillus or Candida in patients, 13 years of age or older, who are at high risk of developing these infections due to being severely immunocompromised. This indication includes hematopoietic stem cell transplant (HSCT) recipients with graft versus host disease (GVHD) or patients with hematologic malignancies with prolonged neutropenia due to chemotherapy. Noxafil® (posaconazole) is also indicated for the treatment of oropharyngeal candidiasis, including oropharyngeal candidiasis that is refractory to itraconazole and/or fluconazole. Effective Dec. 6, 2006, posaconazole may be approved for members with a Select (closed) formulary design when any of the following criteria are met: • First line for the prophylaxis of life-threatening invasive fungal infections in immunocompromised patients over the age of 13 years. • For the treatment of oropharyngeal candidiasis after documented failure of, or intolerance to, at least two other systemic antifungal therapies. • For the treatment of invasive fungal infections after documented failure of, or intolerance to, at least two other systemic antifungal therapies. • A request for treatment of invasive fungal infections or oropharyngeal candidiasis based on the reasoning that “the patient is currently stable and cannot be switched to another agent” will not be considered legitimate unless the patient has tried and failed two formulary products (as listed above).

F. Additions to Highmark’s Pharmaceutical Management Procedures 1. Additions to the Specialty Tier Copay Option Effective March 1, 2007, Tyzeka® and Zolinza will be added to the Specialty Tier Copay Option program.

Section II. Highmark Medicare-Approved Select/Choice Formulary A. Changes to the Highmark Medicare-Approved Select/Choice Formulary The Highmark Pharmacy and Therapeutics Committee has reviewed the medications listed in the following tables. As a reminder, the Highmark Medicare-Approved Select/Choice Formulary applies only to Highmark Medicare Advantage and BlueRxSM members. For your convenience, you can search the Highmark Medicare-Approved Select/Choice Formulary online at: http://highmark.medicare-approvedformularies.com. (continued)

7 A. Changes to the Highmark Medicare-Approved Select/Choice Formulary (continued) Table 1: Products Added (effective Jan. 1, 2007, unless otherwise noted) Brand Name Generic Name Comments Abilify® Discmelt™ aripiprazole ODT Risperdal® M-Tab™ and Zyprexa® Zydis® are also on the formulary. Acular LS®* ketorolac tromethamine Acular® and Acular PF® are also on the formulary. Advair® HFA* fluticasone/salmeterol Advair® is also on the formulary. Atrixtra® fondaparinux sodium Inhibitor of activated Factor X (Xa)

Baraclude® enticavir Epivir® HBV and Hepsera® are also on the formulary. Bidil® isosorbide dinitrate and A combination product for the treatment of heart hydralazine hydrochloride failure Boniva® IV ibandronate sodium An injectable bisphosphonate for the treatment of osteoporosis Cefepime cefepime A fourth-generation cephalosporin cilostazol cilostazol For the treatment of intermittent claudication

Colistimethate sodium colistimethate sodium An antibiotic for the treatment of acute or chronic infections due to sensitive strains of certain gram- negative bacilli Cubicin® daptomycin An IV antibiotic for the treatment of complicated skin and skin structure infections and S. Aureus bacteremia Elaprase™ iduronate-2-sulfatase An enzyme replacement therapy for the treatment of Hunter syndrome GlucaGen® HypoKit™ glucagon Approved for severe hypoglycemic reactions in diabetic patients Glucagon emergency kit glucagon Approved for severe hypoglycemic reactions in diabetic patients glycopyrrolate glycopyrrolate An anticholinergic agent halobetasol halobetasol A topical corticosteroid

Humira®*+ adalimumab An injectable monoclonal antibody for the treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis Levaquin®** levofloxacin Ciprofloxacin and Avelox® are also on the formulary Oxsoralen® methoxsalen An adjunct to UV light for the symptomatic control of psoriasis ® Prolastin alpha1-proteinase inhibitor Replacement therapy for alpha1-antitrypsin [human] deficiency Proquad® Measles, Mumps, Rubella and A combination vaccine for MMR and chickenpox Varicella (Oka/Merck) Virus Vaccine Live *Added January 2007; **Will be added effective May 1, 2007; ***Added effective March 1, 2007; +Requires Prior Authorization

(continued)

8 A. Changes to the Highmark Medicare-Approved Select/Choice Formulary (continued) Table 1: Products Added (effective Jan. 1, 2007, unless otherwise noted) (continued) Brand Name Generic Name Comments

Ranexa®+ ranolazine A new agent for the treatment of chronic angina in combination with amlodipine, beta-blockers or nitrates Revatio™+ sildenafil citrate A phosphodiesterase Type 5 inhibitor for pulmonary arterial hypertension (PAH) Solaraze® diclofenac sodium A topical NSAID for treatment of actinic keratosis

Travatan® Z* travaprost Travatan is also on the formulary

Tygecil® tigecycline A glycylcycline antibacterial for intravenous infusion

Zolinza™***+ vorinostat Oral therapy for cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) with progressive, persistent or recurrent disease on or following 2 systemic therapies Zymar®* gatifloxacin A fourth-generation fluoroquinolone for ophthalmic use *Added January 2007; **Will be added effective May 1, 2007; ***Added effective March 1, 2007; +Requires Prior Authorization

Table 2: Products Not Added* Brand Name Generic Name Comments Allegra® Oral fexofenadine oral suspension Allegra® is on the formulary. Suspension Brovana™ arformoterol Albuterol nebulizer solution is on the formulary. Nebulizer solutions are eligible for Medicare Part D coverage for members residing in a long- term care facility. Coreg™ CR carvedilol controlled release Multiple beta blockers are on the formulary. Desonate™ desonide gel 0.05% Desonide cream, lotion and ointment are on the formulary. Dutoprol™ metoprolol Metoprolol tartrate and hydrochlorothiazide are on succinate/hydrochlorothiazide the formulary. Fentora™ fentanyl buccal tablet Hydromorphone, morphine sulfate and oxycodone are on the formulary. ® ® MoviPrep PEG, NaSO4, NaCl, sodium Generic Colyte is on the formulary. ascorbate, ascorbic acid Noxafil® posaconazole Oral antifungal for prevention of invasive fungal infections or treatment of oropharyngeal candidiasis Verdeso™ desonide foam 0.05% Desonide cream, lotion and ointment are on the formulary. Xolegel™ ketoconazole gel Ketoconazole cream and ketoconazole shampoo are on the formulary. *Physicians may request coverage of these products using the Prescription Drug Medication Request Form, which can be found on page 8 of the 2007 Highmark Drug Formulary book. You may also access the form online in Highmark’s Provider Resource Center, under Provider Forms; select Miscellaneous Forms from the fly-out menu. (continued)

9 A. Changes to the Highmark Medicare-Approved Select/Choice Formulary (continued) Table 3: Products to be Removed* From the Formulary (effective Jan. 1, 2007, unless otherwise noted) Brand Name Generic Name Comments ProAir® HFA (formerly known as albuterol Xopenex HFA and Proventil HFA are on albuterol HFA) the formulary. Android® methyltestosterone Multiple androgens are on the formulary. belladonna alkaloids** Products include Antispas®, Classified as a Less Than Effective (LTE) Donnatal®, Bellergal-S®, DESI drug bellamine, belladonna w/phenobarbital, etc. Caverject® alprostadil Products for erectile dysfunction are no longer covered under Medicare Part D. chlorpheneramine/phenylephrine/ Products include Drize®-R, Classified as a Less Than Effective (LTE) methscopolamine** Vanex® Forte-D, etc. DESI drug Cialis® tadalafil Products for erectile dysfunction are no longer covered under Medicare Part D. codeine sulfate** codeine sulfate Classified as a Less Than Effective (LTE) DESI drug cyanocobalamin cyanocobalamin Vitamins are not covered under Medicare Part D. cyclobenzaprine cyclobenzaprine This medication has been identified as a drug to avoid in the elderly. dipyridamole dipyridamole This medication has been identified as a drug to avoid in the elderly. Engerix B® Hepatitis B vaccine This product may be covered under Medicare Part B. esterified estrogens and Products include Estratest®, Classified as a Less Than Effective (LTE) methyltestosterone** Estratest® HS, Syntest® HS, DESI drug Syntest® DS, etc. flavoxate flavoxate Multiple other drugs are on the formulary for overactive bladder. folic acid folic acid Vitamins are not covered under Medicare Part D. hydrocortisone acetate** Products include Anusol- Classified as a Less Than Effective (LTE) HC®, Anucort-HC®, DESI drug Proctocort®, Proctosol-HC®, etc. hydrocortisone Products include Pramosone®, Classified as a Less Than Effective (LTE) acetate/pramoxine** Analpram® HC, Novacort®, DESI drug etc. iodochlorohydroxyquin** clioquinol with Classified as a Less Than Effective (LTE) hydrocortisone DESI drug iodoquinol/hydrocortisone** Products include Alcortin®, Classified as a Less Than Effective (LTE) Vtyone®, etc. DESI drug iron dextran iron dextran Vitamins are not covered under Medicare Part D. *Physicians may request coverage of these products using the Prescription Drug Medication Request Form, which can be found on page 8 of the 2007 Highmark Drug Formulary book. You may also access the form online in Highmark’s Provider Resource Center, under Provider Forms; select Miscellaneous Forms from the fly-out menu. **Effective Feb. 1, 2007; ***Effective May 1, 2007 (continued)

10 A. Changes to the Highmark Medicare-Approved Select/Choice Formulary (continued) Table 3: Products to be Removed* From the Formulary (effective Jan. 1, 2007, unless otherwise noted) (continued) Brand Name Generic Name Comments isometheptene, dichloralphenazone, Products include Midrin®, Classified as a Less Than Effective (LTE) acetaminophen** Duradrin™, Migquin™, DESI drug Migratine™, etc. Levitra® vardenafil Products for erectile dysfunction are no longer covered under Medicare Part D. Mepergan Fortis®** meperidine/promethazine Classified as a Less Than Effective (LTE) DESI drug mesoridazine mesoridazine Multiple other antipsychotics are on the formulary. Methitest™ methyltestosterone Other androgens are on the formulary. Muse® alprostadil Products for erectile dysfunction are no longer covered under Medicare Part D. Noroxin®*** norfloxacin Avelox® and ciprofloxacin are on the formulary. paregoric paregoric Diphenoxylate/atropine is on the formulary. phenylephrine/guaifenesin phenylephrine/guaifenesin Cough and cold products are not covered under Medicare Part D. piroxicam piroxicam Multiple NSAID products are on the formulary. Pravachol® pravastatin The generic is on the formulary. propoxyphene/caffeine/aspirin propoxyphene/caffeine/aspirin This medication has been identified as a drug to avoid in the elderly. Proscar® finasteride The generic is on the formulary. pseudoephedrine/chlorpheniramine/ Products include Stahist™, Classified as a Less Than Effective (LTE) belladonna alkaloids** Sta-D™ DESI drug pseudoephedrine/guaifenesin pseudoephedrine/guaifenesin Cough and cold products are not covered under Medicare Part D. Testred® methyltestosterone Other androgens are on the formulary. theophylline/ephedrine** theophylline/ephedrine Classified as a Less Than Effective (LTE) DESI drug ticlopidine ticlopidine This medication has been identified as a drug to avoid in the elderly. trimethobenzamide** Products include Tigan®, Classified as a Less Than Effective (LTE) Tebamide®, etc. DESI drug trypsin/balsam peru/castor oil** Products include Granulex®, Classified as a Less Than Effective (LTE) Xenaderm™, Granul- DESI drug; alternative agents on the Derm™, etc. formulary include Accuzyme®, Panafil®, and Santyl®. Ultracet® tramadol The generic is on the formulary. hydrochloride/acetaminophen Unguentum Bossi** Ammoniated Classified as a Less Than Effective (LTE) mercury/methenamine DESI drug sulfosalicylate/coal tar Vasodilan®** isoxuprine Classified as a Less Than Effective (LTE) DESI drug *Physicians may request coverage of these products using the Prescription Drug Medication Request Form, which can be found on page 8 of the 2007 Highmark Drug Formulary book. You may also access the form online in Highmark’s Provider Resource Center, under Provider Forms; select Miscellaneous Forms from the fly-out menu. **Effective Feb. 1, 2007; ***Effective May 1, 2007 (continued)

11 A. Changes to the Highmark Medicare-Approved Select/Choice Formulary (continued) Table 3: Products to be Removed* From the Formulary (effective Jan. 1, 2007, unless otherwise noted) (continued) Brand Name Generic Name Comments Viagra® sildenafil citrate Products for erectile dysfunction are no longer covered under Medicare Part D. zinc sulfate zinc sulfate Vitamins are not covered under Medicare Part D. Zocor® simvastatin The generic is on the formulary. *Physicians may request coverage of these products using the Prescription Drug Medication Request Form, which can be found on page 8 of the 2007 Highmark Drug Formulary book. You may also access the form online in Highmark’s Provider Resource Center, under Provider Forms; select Miscellaneous Forms from the fly-out menu. **Effective Feb. 1, 2007; ***Effective May 1, 2007

B. Prior Authorization Program 1. Testosterone (Androgens) Effective Dec. 6, 2006, the prior authorization criteria for androgens for Medicare Advantage and BlueRxSM members was revised to allow for consideration of both total and free testosterone levels when determining eligibility for coverage. When a benefit, androgens will be approved for the following treatment conditions: • primary or secondary hypogonadism in males who have documented testosterone deficiency as defined by a total testosterone level of <270 ng/ml OR a total testosterone level <350 ng/ml AND a free testosterone level of <50 pg/ml or <9 nmol/L. • delayed puberty in males >15 years of age with either physical or laboratory evidence of hypogonadism (total testosterone level of <270 ng/ml OR a total testosterone level <350 ng/ml AND a free testosterone level of <50 pg/ml or <9 nmol/L). • vulvar dystrophies in women (topical ointment only) • palliative treatment in female patients with metastatic breast cancer

If approved, authorization may be granted for a period of up to one year.

2. EGFR/Tyrosine Kinase Inhibitors Effective Dec. 6, 2006, the prior authorization criteria for human epidermal growth factor receptor (EGFR)/tyrosine kinase inhibitors, including gefitinib (Iressa™) and erlotinib (Tarceva®), for Medicare Advantage and BlueRx members will be revised to include consideration of ECOG performance status. When a benefit and prescribed under the supervision of an oncologist/hematologist, a tyrosine kinase inhibitor may be approved when one of the following criteria is met: • After documented failure of both platinum-based [i.e., cisplatin, Platinol®-AQ, carboplatin (Paraplatin®) and oxaliplatin (EloxatinTM)] and docetaxel (Taxotere®) or paclitaxel (Taxol®) or gemcitabine (Gemzar®) chemotherapies, or • The member has an ECOG performance status of 2 and has documented failure of at least one single agent chemotherapy regimen, or • The member has an ECOG performance status of 3 or 4, or • Erlotinib will be covered for the treatment of pancreatic cancer as first-line treatment when used in combination with gemcitabine.

(continued)

12 B. Prior Authorization Program (continued) 2. EGFR/Tyrosine Kinase Inhibitors (continued) Coverage of tyrosine kinase inhibitors as salvage therapy for disease states outside of their FDA- approved indications will be evaluated based on the member’s diagnosis, based on documented failure of all FDA-approved therapies for their diagnosis and in accordance to Highmark Medical Policy G-16.

Coverage of tyrosine kinase inhibitors for disease states outside of their FDA-approved indications should be denied based on the lack of clinical data to support their effectiveness and safety in other conditions.

If approved, authorization may be granted for up to one year.

3. GleevecTM (imatinib) Effective Dec. 6, 2006, the prior authorization criteria for imatinib for Medicare Advantage and BlueRxSM members was revised to include new FDA-approved indications. When a benefit, imatinib may be approved when prescribed under the supervision of an oncologist/hematologist and used for the treatment of one of the following diagnoses: • chronic myeloid leukemia (CML) of any phase • documented c-KIT expressing gastrointestinal stromal tumors (GIST) • adult dermatofibrosarcoma protuberans (DFSP) • adult relapsed/refractory PH+ ALL • adult hypereosinophilic syndrome/chronic eosinophilic leukemia (HES/CEL) • adult aggressive systemic mastocytosis (ASM) in patients without documented D816V c-KIT mutation • adult myeloproliferative diseases (MPD) after treatment with at least one therapeutic regimen (i.e., hydroxyurea, anagrelide, etc.) • adult myelodysplastic syndrome (MDS)

Use of imatinib for disease states outside of its FDA-approved indications should be denied based on the lack of clinical data to support its effectiveness and safety in other conditions.

If approved, authorization may be granted for a period of up to one year.

4. Forteo® (teriparatide) Effective Dec. 6, 2006, the prior authorization criteria and duration of authorization for teriparatide for Medicare Advantage and BlueRx members was revised. When a benefit, teriparatide may be approved when the following criteria are met: • The member is currently taking appropriate calcium and vitamin D supplements, AND • The member does not have an underlying hypercalcemic disorder such as hypercalcemia, hyperparathyroidism or hypoparathyroidism, or is at risk for osteosarcoma (e.g., Paget’s disease, prior radiation therapy, bone metastases, open epiphyses, etc.), AND • The member has postmenopausal osteoporosis (women) or primary or hypogonadal osteoporosis (men) [T Score ≤-2.5] and is intolerant to or has a contraindication to at least two osteoporotic therapies, one of which must be a bisphosphonate (i.e., Actonel®, Fosamax®). Other therapies include a selective estrogen receptor modulator (i.e., Evista®), calcitonin or hormone replacement therapy with estrogens, OR • The member has a documented failure with at least one bisphosphonate (i.e., Actonel®, Fosamax®, Boniva®). At least a six to 12-month trial of oral bisphosphonates will be considered adequate to determine a treatment failure. Failure will be defined as: 1. new osteoporotic fracture despite bisphosphonate therapy, or 2. a T-Score ≤-3.0 despite bisphosphonate therapy (continued)

13 B. Prior Authorization Program (continued) 4. Forteo® (teriparatide) (continued) If approved, authorization will be granted for a two-year period. Additional requests for the use of Forteo beyond two years of therapy will not be considered, as insufficient evidence exists to support its use for longer durations.

5. ZolinzaTM (vorinostat) Effective March 1, 2007, Zolinza (vorinostat) will be added to Highmark’s Prior Authorization program for Medicare Advantage and BlueRxSM members. Vorinostat inhibits the enzymatic activity of histone deacetylases HDAC1, HDAC2, HDAC3 (Class I) and HDAC6 (Class II). In some cancer cells, there is an overexpression of HDACs or an aberrant recruitment of HDACs to oncogenic transcription factors. HDACs are involved in the remodeling of chromatin, regulating gene expression without altering DNA sequence. Histone deacetylation is believed to be a key mechanism by which cancer cells inactivate tumor-suppressor genes, resulting in uncontrolled proliferation of tumor cells.

When a benefit, vorinostat may be approved when all of the following criteria are met: • Vorinostat is to be prescribed under the supervision of an oncologist/hematologist. • Vorinostat is to be used for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. • Use of vorinostat for disease states outside of its FDA-approved indications should be denied based on the lack of clinical data to support its effectiveness and safety in other conditions.

If approved, authorization may be granted for a period of up to one year.

6. Oral transmucosal fentanyl citrate (Actiq®; Fentora™) Actiq® and Fentora™ will be added to Highmark’s Prior Authorization program effective July 1, 2007. Actiq® and Fentora™ (oral transmucosal fentanyl citrate) are potent, immediate release, short-acting opioid analgesics that are indicated for the management of breakthrough cancer pain in patients who are already receiving and tolerant to opioid therapy for their underlying persistent cancer pain. Actiq and Fentora are administered as one unit over 15 minutes as needed for breakthrough pain. Once a successful dose has been found, patients should consume no more than four units per day. If more units are required on a daily basis for the management of breakthrough cancer pain, an increase in the around-the-clock opioid dose for persistent pain should be considered. Oral transmucosal fentanyl citrate should not be used for acute pain conditions or in situations involving chronic pain in which the patient is not receiving maintenance doses of long-acting opioid analgesics. When a benefit, oral transmucosal fentanyl citrate may be approved when the following criteria are met: • For the management of breakthrough cancer pain in patients who are currently receiving and tolerant to long-acting opioid therapy. • Upon approval, coverage will be limited to 120 units total (Fentora or Actiq) per 25 days. If more units are required on a daily basis for the management of breakthrough cancer pain, an increase in the around-the-clock opioid dose for persistent pain should be considered.

If approved, authorization may be granted for a period of up to one year.

14 C. Updates to the Managed Prescription Drug Coverage (MRxC) Program 1. Ranexa® (ranolazine) Effective Feb. 1, 2007, the approval criteria for Highmark’s MRxC policy for Ranexa® was revised for Medicare Advantage and BlueRxSM members. When a benefit, coverage for ranolazine will be approved if members meet the following criteria: • There are claims for a nitrate plus one other anti-anginal agent in the member’s pharmacy profile in the previous six months. Other anti-anginal agents include beta-adrenergic receptor blockers (i.e., metoprolol, atenolol, bisoprolol, labetelol, etc.) or calcium channel antagonists (i.e., nifedipine, amlodipine, felodipine, etc). • Members who meet the criteria outlined above will receive automatic authorization at the pharmacy without documentation of additional information. Claims will automatically adjudicate online, with no prior authorization required.

If the member does not meet the criteria above, a medication request form will need to be submitted by the physician to request coverage.

If approved, authorization may be granted for a period of up to one year.

2. Leukotriene Receptor Antagonists (Singulair®, Accolate®, Zyflo®) Effective Dec. 6, 2006, the Leukotriene receptor antagonist MRxC policy for Medicare Advantage and BlueRx members was revised to reflect the FDA approval of Singulair® for use in children 6 months of age and older. The approval criteria remain the same for this policy.

3. Fentora (fentanyl buccal tablet) Effective July 1, 2007, Fentora will be added to Highmark’s MRxC program. Fentora will be limited to 120 tablets per 25 days at retail. Physicians may request additional quantities by contacting the Pharmacy Service Center at 1-800-600-2227, Option 1. For clinical consideration, requests must contain the members’ around-the-clock opioid analgesic dosing regimen.

D. Benefit Changes Effective Jan. 1, 2007, medications used for the treatment of erectile dysfunction (ED), as well as medications classified as DESI (Less Than Effective) drugs, will no longer be covered for Medicare Advantage and BlueRx members, as outlined in the final CMS 2007 Formulary guidelines. For additional information regarding DESI products or for a complete list of products, please visit the CMS Web site at http://www.cms.hhs.gov/MedicaidDrugRebateProgram/12_LTEIRSDrugs.asp.

In addition, Highmark’s Quantity Level Limit (QLL) program criteria will no longer be applied to Medicare Advantage and BlueRx members. However, the use of medications covered under the Quantity Level Limit (QLL) program will continue to be monitored for appropriateness.

E. Updates to Highmark’s Formulary policies 1. General non-formulary request criteria Effective Dec. 6, 2006, Highmark’s general non-formulary request criteria policy for Medicare Advantage and BlueRx members was updated to include the statement that no exception for coverage will be made for requests for prescription products that are not approved as federal legend drugs by the FDA, including medical foods (such as Foltx® and Metanx®) and medical devices (excluding diabetic testing supplies).

2. Noxafil® (posaconazole) Noxafil® (posaconazole) is a novel oral, broad spectrum antifungal agent that is indicated for the prophylaxis of life-threatening fungal infections caused by Aspergillus or Candida in patients, 13 years of age or older, who are at high risk of developing these infections due to being severely (continued)

15 E. Updates to Highmark’s Formulary policies (continued) 2. Noxafil® (posaconazole) (continued) immunocompromised. This indication includes hematopoietic stem cell transplant (HSCT) recipients with graft versus host disease (GVHD) or patients with hematologic malignancies with prolonged neutropenia due to chemotherapy. Noxafil® (posaconazole) is also indicated for the treatment of oropharyngeal candidiasis, including oropharyngeal candidiasis that is refractory to itraconazole and/or fluconazole. Effective Dec. 6, 2006, posaconazole may be approved for Medicare Advantage and BlueRxSM members when any of the following criteria are met: • First line for the prophylaxis of life-threatening invasive fungal infections in immunocompromised patients over the age of 13 years. • For the treatment of oropharyngeal candidiasis after documented failure of, or intolerance to, at least two other systemic antifungal therapies. • For the treatment of invasive fungal infections after documented failure of, or intolerance to, at least two other systemic antifungal therapies. • A request for treatment of invasive fungal infections or oropharyngeal candidiasis based on the reasoning that “the patient is currently stable and cannot be switched to another agent” will not be considered legitimate unless the patient has tried and failed two formulary products (as listed above).

F. Additions to Highmark’s Pharmaceutical Management Procedures 1. Additions to the Specialty Tier Copay Option Effective March 1, 2007, Elaprase, Fentora, Tyzeka, Zolinza and fentanyl citrate lollipops will be added to the Specialty Tier Copay Option program for BlueRx members.

Section III. Miscellaneous Updates A. Status of CFC-containing Albuterol Metered-dose Inhalers (MDIs) The production of ozone-depleting substances is being phased out worldwide under the terms of an international agreement called the Montreal Protocol on Substances that Deplete the Ozone. Since most of the metered-dose inhalers (MDIs) available in the United States contained ozone-depleting chlorofluorocarbons (CFCs), many MDIs are being reformulated. Several non-CFC MDIs are currently approved and/or marketed (including non-CFC MDI versions for albuterol, beclomethasone, fluticasone and ipratropium, as well as dry powder versions of fluticasone, formoterol and salmeterol). Several more non-CFC products are in development. Production and sale of CFC-containing MDIs will be phased out, as the FDA determines their use to be no longer medically essential.

The FDA has announced a rule which establishes Dec. 31, 2008, as the date by which production and sale of single-ingredient albuterol CFC MDIs must stop. This rule only affects albuterol CFC MDIs. All other CFC-containing MDIs — including Combivent MDI, which contains albuterol, as well as ipratropium — will be considered separately to determine when they are no longer essential, based on the availability of non-CFC-containing alternatives in adequate supplies, with sufficient post- marketing data.

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