Following is a P and T Committee update (from the March 24^th meeting). Starting date for specific programs is 30 March 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.

ceftolozane-tazobactam (Zerbaxa) – This intravenous drug is a combination of an advanced cephalosporin, ceftolozane with a beta-lactamase inhibitor, tazobactam, and approved to treat complicated urinary tract (cUTI) and complicated abdominal (cIAI) infections (the latter with metronidazole added). The dose for the above indications is 1.5 grams IV every 8 hours, infused over 1 hr., and there are renal dosage adjustments with CrCl < 50 mL/min.  The drug costs about $250 / day.  Due to high cost, questionable efficacy against various ESBLs, the need for metronidazole in cIAIs, decreased efficacy in elderly and renally impaired, and availability of similar lower cost drugs, Zerbaxa was classified as non-formulary, not stocked.  There is no automatic interchange for this agent, therefore, the physician should be contacted for alternative therapy.

avibactam-cefTAZidime (Avycaz) – This intravenous drug is a combination of ceftazidime with a beta-lactamase inhibitor, avibactam, and approved for the same indications as Zerbaxa above. The dose for both approved indications  is 2.5 g q 8 hrs with a renal dose adjustment if CrCl <50 mL/min.  The drug cost is expected to be about $250 / day.  Avycaz’s activity against resistant bacteria is believed to be higher than Zerbaxa.  This drug was approved for formulary status, restricted to ID physician use against documented CRE and ESBL producing bacteria when there is a history of documented allergy to or severe adverse reaction to carbepenams.  In case of the prescribing of Avycaz by a non- ID physician, the AMT will be available to assist with antibiotic regimen selection.    An automatic pharmacist renal dose adjustment per PI recommendations was also approved. 

minocycline (Minocin Intravenous) – This drug is a tetracycline derivative that covers a wide variety of bacteria and can be used for many different types of infections, including skin, respiratory tract, and urinary tract infections. It has been successfully used in multi-drug resistant (MDR) infections.  The normal dose is 100 mg per 1 hour IV infusion q 12 hrs., and costs about $170 / day.  The maximum dose is 400 mg / day.  There is a wide variety of ADRs that can occur in association with its use.  It was classified as a formulary drug, restricted to use by ID physicians for the treatment of MDR organisms.  Use will be monitored by the AMT.

tigecycline (Tygacil) – This broad spectrum intravenous antibiotic has been on the formulary without restrictions for many years. It is FDA approved for community acquired pneumonia, complicated skin/skin structure infections, and cIAIs, and is structurally similar to minocycline.  The dose is 100 mg initially, then 50 mg IV over 30 – 60 minutes q 12 hrs.  The cost is about $215 / day.  Recently, an increase in all-cause mortality was observed with its use in an analysis of Phase 3 and Phase 4 trials.  The FDA has issued guidelines for the drug to be used only when alternative agents are not an option.  It was approved to re-classify tigecycline as a non-formulary, not stocked drug, based on this newer information.  There are various other antibiotic options that provide similar coverage on the hospital formulary.  There is no automatic interchange for tigecycline.  If ordered, the physician should be contacted for selection of an alternative antibiotic regimen.   Date of implementation to be announced (after current supply reduced).

elvitegravir (Vitekta) – This new integrase strand transfer inhibitor is approved to treat HIV-1 infection in antiretroviral treatment (ART) experienced patients in combination with a protease inhibitor, ritonivir, and another antiretroviral drug. The dose is either 85 mg or 150 mg once daily, depending on the ART regimen.  The drug is involved with various drug interactions.  The normal dose costs about $36 / day. This drug is a component of Stribild, a 4-drug combination used to treat HIV-1.  However, the expiration date on Stribild is short once the original bottle is opened, causing significant wastage.  Therefore, it is approved to dispense the components of Stribild individually, including elvitegravir.  Elvitegravir was approved for formulary status, with only stocking the 85 mg tablet, and using 85 mg x 2 for the 150 mg tablet in order to decrease wastage, as low use is expected.  After the current supply of Stribild is used, it will be a non-formulary, not stocked product.

Viekira Pak - This new product is a combination of four different drugs and is approved to treat genotype 1 chronic hepatitis C virus (HCV) infection, including those with compensated cirrhosis. Depending on the case, the drug is given for 12 – 24 weeks, and may be combined with ribavirin.  The four drugs in Viekira Pak are ombitasvir 12.5 mg, paritapreivr 75 mg, ritonivir 50 mg (combined in one tablet) and dasabuvir 250 mg., with the combination tablet being taken as two tablets once daily, and dasabuvir being taken one tablet bid with meals.  If taken in the recommended regimens, it is quite effective and  produces sustained virologic response rates in the 95% - 100% range.   The cost is about $950 / day.  It was classified as non-formulary, not stocked, and initiation should be deferred to the outpatient setting.  If the drug is needed for an inpatient, they should use their own supply. 

edoxaban (Savaysa) – This is a new oral direct acting, selective factor Xa inhibitor anticoagulant agent similar to apixaban. It is indicated for non-valvular atrial fibrillation (dose 60 mg once daily and reduced if CrCl < 50 ml/min) and treatment of DVT or PE (dose 60 mg once daily and reduced if patient weighs < 60 kg, if CrCl < 50 ml/min., or if concurrently receiving strong P-gp inhibitors i.e. verapamil, quinidine).  For atrial fibrillation, the drug should not be started if the CrCl > 95 ml/min due to decreased efficacy.  The cost is $8.70 per dose.  This drug was classified as a formulary agent, with automatic dosage adjustment per PI recommendations by pharmacists.  There will be a computer prompt for pharmacists to evaluate this drug for proper use when prescribed.

Remifentanil (Ultiva) in Pediatrics – This intravenous drug is a mu-opioid agonist exhibiting analgesic effects with a rapid onset and short duration, and is a schedule II agent. It is FDA approved for use during anesthesia induction and maintenance, for continuation of analgesia immediately post-operative, and in monitored anesthesia care.  Analgesia for mechanically ventilated ICU patients is an off-label use.  Currently, this drug is approved for formulary use in craniotomy procedures and pilot use in TEE.  It was approved to expand the formulary indications for use to the following:  use by pediatric anesthesia during spinal fusion surgeries, use in pediatric critical care neurological patients requiring frequent neurological evaluations, and use by pediatric critical care physicians in patients with difficult airways who need to be extubated.  With these situations, remifentanil use is still expected to be infrequent.  This drug is more expensive than some other similar drugs.

Happy Hiney Diaper Rash Cream – This product is prepared in the pharmacy and consists of nystatin ointment, zinc oxide cream, and Maalox susp. The components are already all formulary agents.  This product will be used mainly in pediatrics.

Oncowash Without Lidocaine – The standard Oncowash prepared by Pharmacy contains 60 mL each of nystatin susp., Maalox, viscous lidocaine 2%, and diphenhydramine liquid. There is also a formulary  preparation without nystatin.  A third formula, without lidocaine, has been added to formulary information; this preparation contains 60 mL each of Maalox, diphenhydramine liquid, and nystatin susp.  These components are all already formulary agents.

Pediatric Intravenous Medication Dose Rounding – It was approved that pediatric orders written for various intravenous drugs (on official list) may be rounded up or down by up to 10% if this results in allowing the pharmacy to dispense a commercially available preparation rather than compound a patient specific dose. The rounded dose should be within the acceptable dosing range for the medication.  Examples of intravenous drugs included in this dose rounding policy are several cephalosporins, ampicillin, meropenem, fluconazole, metronidazole, vancomycin, and Zosyn.   Date of implementation to be announced.

Prednisolone Dose Standardization in Pediatrics – Two new standard doses of prednisolone, 4.5 mg and 12 mg, were approved for dose rounding purposes with this drug. Date of implementation to be announced.

Extravasation Protocol – Pediatrics – Due to the ongoing national drug shortage with phentolamine injection, other protocol options to use in vasopressor extravasation cases were evaluated. Due to little pediatric information on other drug options, it was approved to include only non-pharmacologic options on the pediatric protocol.  In more severe cases, the use of terbutaline or topical nitroglycerine will be evaluated on a case by case basis.

Metoclopramide Renal Adjustment – Currently, this drug is automatically dose adjusted by the pharmacist in patients with renal insufficiency as follows: If CrCl < 50 mL/min, use 50% of normal dose (i.e. 5 mg q 6 hrs), if CrCl < 10 mL/min., use 25% of normal dose.  However, new recommendations appear in the major drug information resources, as follows:  If CrCl < 40 mL/min, use 50% of normal dose.  It was approved to change the pharmacist renal dose adjustment to the latter newer recommendation. 

Prosthetic Joint Infection Adult Order Set – This new order set was reviewed and approved. It focuses on antibiotic selection in different clinical situations, and includes cefazolin, vancomycin per PKS, daptomycin, meropenem, Zosyn, and cefepime as options for specific situations.  Date of implementation to be announced.

Tranexamic Acid in Orthopedic Surgery MUE – This was a retrospective review of 101 patients who had undergone elective TKA or THA, with 51 patients receiving tranexamic acid during surgery and 50 not receiving the drug. For both TKA and THA patients, data collected were amount of blood loss in the OR and in the post-op period, hemoglobin and hematocrit at 24 h and 48 h post-op, and number of blood transfusions.  There were no significant differences between the 2 groups in the hemoglobin and hematocrit labs at 24 h and 48 h, or in OR blood loss.  Post-op blood loss was significantly decreased for THA but not TKA patients.  Fewer blood transfusions were required for the treatment group versus control group, with a greater difference in the THA group.