Following is a P and T Committee update (from the January 27^th meeting). Starting date for specific programs is 2 February 2015, unless otherwise noted. Please let me know if you have any questions or comments. Don’t forget to check the “New Drug Monitoring Spotlight” section of the website, which provides important monitoring information about newly approved drugs. Also, attached is the updated version of the “Not Stocked, Not Ordered” drug list with the new additions highlighted in red. 

Below is the memo with links to the drug monographs, protocols, and formulary documents. Click to access the full P&T packet for this month, or here to access the P&T packet archive.

• oritavancin (Orbactiv) – This is a semisynthetic lipoglycopeptide antibacterial chemically related to vancomycin and is indicated for the treatment of acute bacterial skin and skin structure infections caused by designated susceptible strains of gram-positive bacteria. It has a half-life of about 10 days and is dosed 1200 mg x 1 dose only, infused over 3 hours.  The cost is approximately $2,750 per dose.  This drug was classified as a formulary agent but restricted to the hospital outpatient and clinic settings by infectious disease physicians (i.e. outpatient medical dep’t, hospital clinic area).  If ordered in the inpatient setting, the physician will be contacted and other drugs that cover gram-positive organisms will be discussed as options.  A protocol is available to facilitate prescribing, administering, and monitoring in the outpatient setting. 

• cobicistat (Tybost) – This drug is indicated to increase systemic exposure of atazanavir or darunavir (once daily regimen) in combination with other antiretrovital agents in the treatment of HIV-1 infection. The dose is 150 mg orally once daily.  It is involved in various CYP3A4 drug interactions, but is more selective for the CYP3A subfamily enzymes than ritonavir and thus has lower potential for CYP induction.  The cost per day is $5.71, which is less than ritonavir 100 mg daily.  Cobicistat was approved as a formulary agent, unusual use is expected.  The patient may use their own drug supply if needed.

• Stribild– This anti-HIV-1 combination drug includes cobicistat 150 mg, elvitegravir 150 mg, emtricitabine 200 mg, and tenofovir 300 mg. and is given once daily. This drug was previously classified as a formulary agent, because cobicistat and elvitegravir were not available as separate agents.  However, both are now available as individual drugs, and all 4 of these drugs are on the formulary in the strengths available in Stribild.  Thus, Stribild was reclassified as a non-formulary agent, and in the unusual cases where it may be needed for an inpatient, the 4 drugs should be dispensed and administered separately.   The current Stribild supply will be used up prior to starting this interchange.

• Harvoni - This is a new combination drug for treatment of chronic hepatitis C type 1, and is composed of sofosbuvir (Solvadi) and ledipasvir; ledipasvir is not available as a separate agent.  This drug does not require co-administration with ribavirin or interferon, and is dosed orally once daily, generally for 12 weeks.  The cure rates have been very good with this drug, but the cost is $1,200 per tablet or about $114,000 for 12 weeks of treatment.  There are drug interactions with drugs that alter GI pH, and with drugs acting via the P-gp system.  Harvoni was classified as a non-formulary, not stocked agent, and initiation should be deferred to the outpatient setting where financial management can be planned for the patient.  The patient should use their own supply if needed in the hospital.  Rare use is expected.

• Lipiodol - This is an iodinated radiocontrast agent composed of ethyl esters of iodized fatty acids of poppy seed oil containing 480 mg of iodine per mL., and restricted for use to Dr. Alex Johnson and Dr. Robert Tomalty for use in selected interventional radiology cases only. A new interventional radiologist partner, Dr. Charles Ritchie, was approved to use the drug in those situations also.

• Potassium Chloride Oral – Liquid versus Packets – KCL oral powder packets are now on national shortage, and the costs have greatly increased. The KCL liquid is in good supply and the price remains low.  The KCL 20 meq and 40 meq unit dose liquid was approved for use in place of the packets.   This interchange should save approximately $50,000 annually.

• oseltamivir (Tamiflu) Renal Dose – New renal dose guidelines have been announced by the FDA for this drug, based only on Monte Carlo simulation studies.  Dosage reduction to 30 mg doses starts at CrCl levels of < 60 mL/min/1.73 sq meters.  However, established recommendations were dosage reduction only at CrCl levels of < 30 ml/min/1.73 sq meters.  It was approved for an automatic pharmacist renal dosing adjustment with this drug according to the previously established recommendations, only if CrCl < 30 mL/min. 

• Vitamin K Parenteral – Intramuscular administration of vitamin K results in irregular and unpredictable absorption, may cause hematoma formation, and is not generally recommended. Severe reactions, including fatalities, have been reported following intramuscular administration.  It was approved for pharmacists  to automatically interchange the intramuscular route to the subcutaneous route in the same dosage, due to improved safety and efficacy. 

• vancomycin – Consideration will be given to classifying high vancomycin serum trough levels as “critical values”  where the physician would be notified about the abnormal value in a timely manner.

• ondansetron (Zofran) – There has been a FDA labeling change involving drug dosing, in that parenteral doses of over 16 mg are not recommended. This is based on a greater potential for prolonging the QTc interval with higher doses.  It was approved to limit both parenteral and oral ondansetron single doses to a maximum of 16 mg.  This sets a consistent pattern for dose limitation, and addresses the issue of larger doses of oral ondansetron being given concomitantly with other drugs that can prolong the QTc interval. 

• tigecycline Medication Use Evaluation – This broad spectrum antibiotic is FDA approved for complicated intra-abdominal infections, community acquired pneumonia, and skin/skin structure (SSI) infections, all caused by specific pathogens for the given indications. This drug is not widely used nationally due to a black box warning for increased all cause mortality, and use is justified only in patients with multiple drug allergies where other drug options could not be used, or in patients with multi-drug resistant organisms susceptible to tigecycline when drug allergies are present (last line drug).  Through retrospective chart review, 94 patients receiving the drug were evaluated, and 97% of cases did not meet the above indication criteria.  About 60% of the cases were for pneumonia or SSI treatment, and most of the cases involved Coli, Staphlococcus aureus, or Pseudomonas aeruginosa.  The Committee will conduct an evaluation of parenteral minocycline for use in hospital infections as an alternative to tigecycline. 

• Antibiotic Decision Tree – Several nomograms for cost-effective antibiotic use with principles of antibiotic stewardship were reviewed and approved. These nomograms involve different forms of pneumonia, COPD exacerbation, UTI, and cellulitis, and include information on organisms of concern, risk factors, illness severity, and drug selection and dosage.  These nomograms will be used for educational tools and general recommendations.

• Neupogen versus Granix in Engraftment with Stem Cell Patients – The objective of this MUE project was to compare efficacy and safety of these 2 versions of filgrastim for neutropenia prophylaxis in autologous stem cell transplant patients. Chart reviews were completed to determine time to white blood cell and platelet engraftment, occurrence of febrile neutropenia, duration of febrile neutropenia, and duration of antimicrobial therapy.  No significant differences in measured outcomes were demonstrated between these 2 agents.  This project supports the formulary interchange of filgrastim to tbo-filgrastim in this population.