Download Express Scripts Drug Information & Wellness Center Drug Information Updates

July 2013
Volume 5 Issue 3
Express Scripts Drug Information & Wellness Center
Drug Information Updates
In the News:
FDA recommends zolpidem labeling change:
 As of May 2013 new zolpidem product labeling states:
Use lowest possible dose in all patients.
Women should be started on 5 mg, Men on 5 or 10 mg.
All patients should exercise caution the morning after using the controlled release formulation
due to the increased risk of next day psychomotor depression.
 Ambien, Ambien CR, and Edular are the only zolpidem products to receive the labeling update.
FDA backing away from new fecal transplant rules
 Fecal transplants have shown success in treating patients with resistant Clostridium difficile.

FDA had stated fecal microbiota meets the definition of a biologic product and wanted to require an IND before
use in humans. FDA is now stating there will be no negative consequences if the practitioners choose not to
obtain an IND provided they have informed consent and are using the fecal microbiota transplantation to treat
their patients with recurrent C. diff.
Statins may reduce benefits of exercise but result in decreased cardiovascular risk
A randomized controlled trial looked at effects of simvastatin on exercise.




37 subjects underwent a 12-week exercise program, 18 subjects took simvastatin 40 mg daily.
Cardiorespiratory fitness increased by 10% in exercise-alone group, only 1.5% in statin group.
Overall cardiovascular risk reduction and mortality risk between the groups were similar however and possibly
greater for the statin group when comparing the benefits of LDL reduction to increased cardiorespiratory fitness.
Special points of interest:
 In the News
 App of the Month
 New Formulations and Indications
 Newly Approved Drugs
 Recent Guideline Updates
 New Generic Approvals
 Drug Safety Recalls
 Resolved Drug Shortages
 New Drug Shortages
 Drug Information Question
FDA does not recommend stopping angiotensin receptor blockers without talking to a healthcare professional
 An article appearing in the Wall Street Journal presented the views of an FDA researcher who thinks that the
link between ARBs and cancer needs to be reexamined.
 The FDA responded with a statement that ARBs are still considered safe and that patients should not discontinue their medications without first speaking with a physician.
Apps of the Month The following application for smartphones has been reviewed and critiqued by students and pharmacists:
Name:
MediSafe Virtual Pillbox
Cost:
Free
Read: Personalized Medication
Journal
Free
Content:
The MediSafe Virtual Pillbox is a medication reminder app. It reminds patients when
to take their medications, even if their smartphone device is asleep. It also reminds
them to contact their local pharmacy when their month’s supply is running low. This
app can even sync-up with doctors by providing detailed progress reports of med
adherence.
Rating (1-5):
Create an account with Read and select s number of journals you would like to
receive updates from including Pain, JAMA, and NEJM. Staying current on multiple
journals has never been so easy!
Thank you to Laura Olsen, Scott Powers, and Chris Selby for
putting this newsletter together
Page 2
Express Scripts Drug Information & Wellness Center
Volume 5 Issue 3
New ly Approved Drugs
Breo Ellipta (fluticasone furoate and vilanterol inhalation powder)
Indication: Adult COPD
Dosing: fluticasone furoate 100 mcg/vilanterol 25 mcg per actuation
MOA: Fluticasone is a synthetic corticosteroid with potent antiinflammatory activity, while vilanterol is a long acting beta agonist. These
two medications both mediate a reduction in airway obstruction.
Invokana (canagliflozin)
Indication: Type II Diabetes Mellitus, adjunct therapy to diet and exercise
Dosing: 100 mg once daily before the 1st meal of the day, up to 300 mg
once daily.
MOA: Canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor. Inhibiting SGLT2 is believed to reduce blood glucose levels by increasing the amount of glucose excreted in the urine.
Liptruzet (ezetimibe and atorvastatin)
Indication: Hyperlipidemia
Dosing (ezetimibe/atorvastatin): 10/10 mg, 10/20 mg, 10/40 mg, and 10/80
mg
MOA: Ezetimibe reduces blood cholesterol by inhibiting the absorption of
cholesterol by the small intestine. Atorvastatin lowers plasma cholesterol
and lipoprotein levels by inhibiting cholesterol synthesis in the liver and by
increasing the number of hepatic LDL receptors on the cell-surface to
enhance uptake and catabolism of LDL.
Nesina (alogliptin)
Indication: Type II Diabetes Mellitus, adjunct therapy to diet and exercise
Dosing: 25 mg once daily, with or without food.
MOA: Alogliptin is a DDP-IV inhibitor. DPP-4 inhibitors slow the inactivation of incretin hormones GLP-1 (glucagon-like peptide-1) and GIP
(glucose-dependent insulinotropic peptide), both of which play a role in
regulating blood glucose levels.
Quartette (levonorgestrel/ethinyl estradiol and ethinyl estradiol)
Indication: Pregnancy prevention
Dosing: Phase 1: 0.15 mg levonorgestrel0.02 mg ethinyl estradiol. Phase
2: 0.15 mg levonorgestrel0.025 mg ethinyl estradiol. Phase 3: 0.15 mg
levonorgestrel0.03 mg ethinyl estradiol. Phase 4: 0.01 mg ethinyl estradiol.
MOA: Quarette prevents conception primarily by suppressing ovulation. It
may also induce cervical mucus changes that inhibit sperm penetration
and endometrial changes that reduce the likelihood of implantation.
Tecfidera (dimethyl fumarate)
Indication: Adult patients with relapsing multiple sclerosis
Dosing: Initial dosing is 120 mg twice a day orally. After 7 days, the dose
increases to the maintenance dose of 240 mg twice a day orally.
MOA: At this time, the exact mechanism is unknown, but it has been postulated that dimethyl fumarate has the potential to reduce the activity and
impact of inflammatory cells on the central nervous system (CNS) and
induce direct cytoprotective responses in CNS cells.
Recent Guideline Updates
Comprehensive Diabetes Algorithm (2013)
American Association of Clinical Endocrinologists
 Includes treatment algorithms for prediabetes, glycemic control, adding /
intensifying insulin, and cardiovascular disease risk factor modifications.
 Also provided are goals of glycemic control, profiles of hypoglycemic medications, and principles for treatment of type 2 diabetes.
Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery (2013)
American Society of Health-System Pharmacists, Infectious Diseases Society of America, Surgical Infection Society, and Society for Healthcare Epidemiology of America
 The optimal time for administration of preoperative doses is within 60
minutes before surgical incision. This is a more specific time frame than the
previously recommended time, which was “at induction of anesthesia.”
 Includes information regarding the approach to weight-based dosing in
obese patients and the need for repeat doses during prolonged procedures.
 New recommendations for a shortened postoperative course of antimicrobials involving a single dose or continuation for less than 24 hours are provided.
 A section addressing concepts that apply to all types of surgical procedures
has been added.
Clinical Practice Guidelines for the Perioperative Nutritional, Metabolic, and
Nonsurgical Support of the Bariatric Surgery Patient (2013)
American Association of Clinical Endocrinologists, The Obesity Society,
and American Society for Metabolic & Bariatric Surgery
 There are 74 recommendations (of which 56 are revised and 2 are new) in
the 2013 update, compared with 164 original recommendations in the 2008
guidelines.
 Patients with diabetes or metabolic syndrome and a BMI of 30 to 34.9 kg/m2
may be offered a bariatric procedure.
 Other updates address perioperative management, medical clearance, early
postoperative care, optimal follow-up care, and criteria for postoperative
hospital admission.
New Generic Approvals
Candesartan cilexetil tablets by Sandoz (5/3/2013)
Strength: 4 mg, 8 mg, 16 mg, and 32 mg
Generic for: Atacand
Zolmitriptan tablets (5/15/2013)
Strength: 2.5 mg and 5 mg
Generic for: Zomig tablets
Zolmitriptan orally disintegrating tablets by Apotex Corp, Glenmark Generics, and Mylan Pharmaceuticals Inc. (5/15/2013)
Strength: 2.5 mg and 5 mg
Generic for: Zomig-ZMT tablets
Voriconazole for suspension by Mylan Pharmaceuticals Inc. (5/28/2013)
Strength: 200 mg / 5 mL
Generic for: Vfend for oral suspension
Page 3
Express Scripts Drug Information & Wellness Center
Volume 5 Issue 3
Resolved Drug Shortages
New Formulas & Indications
Amitiza (lubiprostone)
Indication: Opioid induced constipation in adult with noncancer related
chronic pain.
MOA: Lubiprostone enhances chloride secretion in the intestines which
leads to increase GI motility.
New: Indication
Cetrorelix acetate for injection (Certrotide) 25 mg by EMD Serono, Inc.
Related Information: No further supply issues anticipated.
Sustiva
Indication: Treatment of HIV-1 infection in patients as young as 3
months and weighing at least 3.5 kg.
MOA: A non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1,
activity is mediated predominantly by noncompetitive inhibition of HIV-1
reverse transcriptase.
New: Expanded indication covers younger patients.
Isoniazid tablets by Teva Pharmaceuticals, Sandoz, and VersaPharm.
Related Information: No further supply issues anticipated.
Xgeva (denosumab)
Indication: Giant Cell Bone Tumors
MOA: Binds to receptor activator of nuclear factor-kappa B ligand, a
protein essential for the formation, function, and survival of osteoclasts.
New: Indication
Doxorubicin liposomal injection by Sun Pharma Global FZE and Janssen Products, LP.
Related Information: Product is currently available.
Phentolamine mesylate for injection, 5 mg lyophilized vial by Bedford.
Related Information: No further supply issues anticipated.
Propofol (Diprivan) injection by Fresenius Kabi USA, Hospira Inc., and Teva
Pharmaceuticals.
Related Information: Product is currently available.
Pyridostigmine bromide (Regonolol) injection by Sandoz, Inc.
Related Information: No further supply issues anticipated.
2013 New Drug Shortages
Drug Recalls
Warfarin: Zydus Pharmaceuticals. Lot #MM5767
Reason/Problem: Oversized tablets which may contain excess amount of
drug.
Main Street Family Pharmacy (TN). All sterile products
Reason/Problem: Potential for non-sterility.
Olympia Pharmacy/Lowlite Investments All sterile products
Reason/Problem: Potential for non-sterility.
Freestyle InsuLinx Blood Glucose Meters
Reason/Problem: Risk of incorrect test result at extremely high blood glucose
readings.
Piperacillin/Tazobactam: Apotex Corp. 21 lots recalled
Reason/Problem: Possibility of precipitation/crystallization in IV bag or IV line
upon reconstitution
Copper injection (cupric chloride) by American Regent/Luitpold and Hospira Inc. (4/25/2013)
Products:
 0.4 mg/mL (10 mL vials)
Reason: American Regent is not releasing the injection, and Hospira reports
manufacturing delay.
Related Information: American Regent cannot estimate date of availability, and
Hospira anticipates a recovery to occur in the third quarter of 2013.
Desmopressin acetate (DDAVP) injection by Hospira Inc. and Teva Pharmaceuticals (5/7/2013)
Products:
 4 mcg/mL (1 mL ampule and 10 mL vial)
Reason: Hospira shortage due to manufacturing delay and Teva shortage due
to method remediation and transfer.
Related Information: Hospira anticipates a release date and full recovery to
occur in 2014. Teva anticipates next delivery to occur in 2016.
July is National UV Safety Month
A black ribbon is used to symbolize melanoma awareness. Do your part to help protect family, patients and friends from
this and other types of skin cancers by following these sun safety tips!
 Use a broad spectrum (UVA/UVB) sunscreen with SPF 15 or higher. Apply enough sunscreen (about an ounce) to
generously coat exposed skin 30 minutes before going outside, every two hours, and after you swim or sweat.
 Limit sun exposure between 10 a.m. and 4 p.m.
 Cover up with long sleeves, a wide brim hat, and UV blocking sunglasses.
 Avoid indoor tanning devices. Try a sunless tanning product if you want that summer glow!
Express Scripts
Drug Information & Wellness Center
Southern Illinois University Edwardsville
Monday — Friday
8 a.m. — 4 p.m.
(618) 650-5142
Page 4
Volume 5 Issue 3
Drug Information Question
Is there any benefit of switching birth controls from Ortho Tri Cyclen Lo to Yaz or Yasmin to stop hair loss due to the anti-androgenic effects of
drosperinone? What are the recommendations regarding what is the best birth control product(s) to decrease the occurrence of alopecia?
According to Facts & Comparisons1, a common cause of hair loss due to oral contraceptive use is an excess of progesterone. Micromedex2 describes the
issue as slight and temporary in practice and that diffuse loss of scalp hair is possible with any combination oral contraceptive. Micromedex also goes on to say
that while current formulations have low androgenic potential, limiting the progestin-like effects of combination contraceptives may decrease hair loss.
Meyler’s Side Effect of Drugs3 states that all oral hormonal contraceptives have the potential to cause hair loss due to the fact that their mechanism of action
is to induce pseudo pregnancy and pregnancy is known to cause hair loss. However, the link between hormonal therapies and hair has been shown to go both
directions as in addition to hair loss, some case reports indicate an improvement in hair quality.
The package inserts for Ortho Tri-Cyclen Lo4, NuvaRing5, Depo provera6, Implanon7, Mirena8, and Ortho Evra patches9 all state that loss of scalp hair is a
possible adverse effect. The prescribing information for both Yaz10 and Yasmin11 fail to mention hair loss. The progestin in Yaz/Yasmin is drospirenone, a spironolactone analog, and is thought to have the lowest progestin activity on the market, in addition to being an “antiandrogen.” According to the American Hair Loss
Association, spironolactone is a treatment option for female hair loss due to its antiandrogenic effects, which it shares with drospirenone.12 Three mg of drospirenone, the dose found in oral contraceptives, is equal to 25 mg of spironolactone. When used in the treatment of androgenic alopecia, spironolactone is recommended in divided doses of 100-200 mg daily.13 Information about the incidence of alopecia for contraceptive devices is presented below.
Device (Progestin released by device)
Mirena (Levonorgestrel)
Implanon (Etonogestrel)
Depo Provera (Medroxyprogesterone)
NuvaRing (Etonogestrel)
Ortho Evra Patch (Norelgestromin)
Below is a table comparing the progestin and androgen
effects of typical progestin components of oral contraceptives. This table shows the overall androgen effect of
the progestin since that has been linked to alopecia.
++++ – pronounced effect; +++ – moderate effect; ++ –
low effect; + – slight effect; 0 – no effect.1
Progestin
Desogestrel
Levonorgestrel
Norgestrel
Ethynodiol diacetate
Norgestimate
Norethindrone
Norethindrone acetate
Drospirenone
Progestin Activity
Androgen Activity
++++
++++
+++
++
++
++
++
N/A
+++
++++
+++
+
++
++
++
0
Incidence
0.18% - 15.7%15
1.7%16
Transient, estimated up to 15% 17
Possible, no incidence given5
Possible, no incidence given9
In summary, all oral contraceptives have the possibility to change the growth
and quality of scalp hair. Using a combination with the lowest possible progesterone and
andgrogenic effects will have the best chance to reduce or minimize the potential for hair
loss. Patches, intrauterine devices, and other implantable devices also have some
chance of hair loss associated with them, when they release a progestin into systemic
circulation. All contraceptives have different risks and benefits, including the potential for
serious adverse events, and as such should be discussed fully with a healthcare provider.
References
1.Contraceptives, Oral. Comparative Efficacy. Drug Facts and Comparisons. Facts & Comparisons [database online]. St. Louis, MO: Wolters Kluwer Health, Inc;
March 2005. Accessed June 17, 2013.
2.Contraceptive Combinations. In: Drugdex System [Internet Database]. Greenwood Village, Colo: Thomson Reuters [Healthcare] Inc. Updated Periodically.
3.Hormonal Contraceptives – Oral. Meyler's side effects of drugs, 15th edition. Edited by JK Aronson. Elsevier Science, Amsterdam, 2006.
4.Ortho Tri-Cyclen Lo. Prescribing Information. Raritan, NJ. Ortho-McNeil-Janssen Pharmaceuticals Inc; June 2010.
5.NuvaRing. Prescribing Information. Whitehouse Station, NJ. Merck & Co., Inc; May 2012.
6.Depo Provera. Prescribing Information. New York, NY. Pfizer. May 2006.
7.Implanon. Prescribing Information. Whitehouse Station, NJ. Merck & Co., Inc; May 2012.
8.Mirena. Prescribing Information. Wayne, NJ. Bayer Healthcare. February 2013.
9.Yaz. Prescribing Information. Wayne, NJ. Bayer Healthcare. April 2012.
10.Yasmin. Prescribing Information. Wayne, NJ. Bayer Healthcare. April 2012.
11.Ortho Evra. Prescribing Information. Titusville, NJ. Janssen Pharmaceuticals. August 2012.
12.Women’s Hair Loss Treatment. American Hair Loss Association [Internet]. Accessed June 18, 2013. Available at: http://www.americanhairloss.org/
women_hair_loss/treatment.asp.
13.Androgenic Alopecia. Family Practice Notebook [Internet]. Accessed June 18, 2013. Available at: http://www.fpnotebook.com/Derm/Hair/AndrgncAlpc.htm.
14.ParaGard. Prescribing Information. Sellerville, PA. Teva.
15.Paterson, H. Clifton, J. Miller, D. et al. Hair Loss with Use of the Levonorgestrel Intrauterine Device. Contraception. 2007;76:306–309.
16.Lee, D. Ewer, K. Implanon and Alopecia. J Fam Plann Reprod Health Care 2006;32:255.
17.Archer, B. Irwin, D. Jensen, K. et al. Depot Medroxyprogesterone: Management of side effects commonly associated with its contraceptive use. Journal of
Nurse-Midwifery. 1997;42:104-11.