Download Express Scripts Drug Information & Wellness Center Drug Information Updates

October 2012
Volume 4 Issue 5
Express Scripts Drug Information & Wellness Center
Drug Information Updates
In the News
Special points of interest:
Prostate Specific Antigen Recommendations

The United States Preventive Services Task Force has now advised against PSA-based screening
in men of any age overturning its previous recommendation against testing in men ≥75 years.

Many physicians disagree and credit PSA testing with the 40% decrease in prostate cancer deaths
over the last 20 years.


 In the News
 Drug Recalls
 New Formulations and
Indications
A new study, the PIVOT trial, compared radical prostatectomy to observation alone and did not find
a significant improvement in mortality with prostatectomy. A sub-group analysis found that in men
 New Drug Approvals
with a PSA >10 ng/mL, prostatectomy did lower mortality.
PIVOT trial suggests it may be beneficial to conduct PSA screening in order to detect levels >10
ng/mL as treatment in these patients may prevent mortality.
 New Generic Approvals
 Drug Information Question
Topical Pain Relievers May Burn
The FDA reports that 43 cases of severe burns have occurred with the use of over the counter
topical pain relievers such as Icy Hot, Bengay, Flexall, Capzasin and Mentholatum.
FDA has the following advice for consumers using OTC topical muscle and joint pain relievers:
 Drug Shortages

Don’t apply to damaged or irritated skin

Don't apply bandages to the area where you've applied a topical muscle and joint pain reliever
 Recent Guideline Updates

Don't apply heat to the area in the form of heating pads, hot water bottles or lamps.

Don't allow these products to come in contact with eyes and mucous membranes

If you feel actual pain after applying a product, look for signs of blistering or burning. If you see any
of these signs, stop using the product and seek medical attention.

If you have any concerns about using one of these products, talk to a medical professional.

Report unexpected side effects from the use of OTC topical pain reliever to the FDA MedWatch
program

 Apps of the Month
Drug Recalls
Nimodipine 30 mg capsules, by Sun Pharmaceuticals (09/03/12)
Reason/Problem:
 Lot 3305.039A with NDC 5766413565 and lot 3305.039B with NDC 5766413564 (distributed between January 19, 2012 and April 24, 2012) were voluntarily recalled as a precautionary measure
because of the presence of crystals of nimodipine within the capsule solution. The crystallization
of nimodipine could adversely affect bioavailability
Hydrocodone bitartrate and acetaminophen 10 mg/500 mg tablets, by Qualitest (09/10/12)
Reason/Problem:
 Lot C1440512A within NDC 0603388821 (expiration December 2013) was voluntarily recalled
because of the potential for oversized tablets which could be more potent.
Hydrocodone bitartrate and acetaminophen 10 mg/500 mg tablets, by Watson (09/23/12)
Reason/Problem:
 Lots 519406A and 521759A (expiration April 2014) were voluntarily recalled because of the potential for oversized and superpotent tablets.
Created by: Brooke Hasquin, Deborah Helmink, and Amanda Peterson,
PharmD Candidates
Page 2
Volume 4 Issue 5
Express Scripts Drug Information & Wellness Center
New Formulations and Indications
Qsymia (phentermine and topiramate) tablets by Vivus
Class: combination anorectic and antiepileptic
Indication: adjunct to reduced-calorie diet and increased physical activity
for chronic weight management in adults with a BMI over 30 and those
with a BMI over 27 with at least one weight-related comorbidity such as
hypertension, Type 2 diabetes mellitus, or dyslipidemia
MOA: Phentermine’s exact mechanism of action is not know but it likely
acts by release of catecholamines in the hypothalamus, resulting in reduced appetite and decreased food consumption. Topiramate’s mechanism of action on chronic weight management is not known but it may be
due to its effects on both appetite suppression and satiety enhancement
NOTE: Qsymia is only available by mail order through certified pharmacies in the Qsymia Home Delivery Network
New Formulation: Combination product for weight loss
Nucynta ER (tapentadol) by Janssen
Class: Adrenal Glucocorticoid
Indication: relief of moderate-to-severe chronic pain or neuropathic pain
when continuous around the clock analgesia is necessary for an extended
time period
MOA: Nucynta ER binds to mu-opiate receptors in the CNS causing inhibition of ascending pain pathways altering the perception of and response
to pain
New Indication: management of neuropathic pain associated with diabetic
peripheral neuropathy in adults
Exelon patch (rivastigmine transderm) by Novartis
Class: Acetylcholinesterase inhibitor
Indication: Mild-to-moderate dementia associated with Alzheimer’s disease or Parkinson’s disease
MOA: Exelon increases acetylcholine in the CNS through reversible inhibition of its hydrolysis by cholinesterase
New Dose: 13.3 mg per 24 hours
New Drug Approvals
Aubagio (teriflunomide) by Sanofi: (09/13/12)
Class: pyrimidine synthesis inhibitor
Indication: relapsing forms of multiple sclerosis
MOA: Aubagio’s exact mechanism in multiple sclerosis is unkown
however, it may involve a reduction in the number of activated
lymphocytes in the CNS.
Dosing: 7 mg or 14 mg orally once daily
Linzess (linaclotide) by Ironwood: (08/29/12)
Class: guanylate cyclase-C (GC-C) agonist
Indication: irritable bowel syndrome with constipation (IBS-C)
MOA: Linzess and its active metabolite bind to GC-C and act
locally on the luminal surface of the intestinal epithelium which
results in an increase in both intracellular and extracellular cGMP
resulting in increased intestinal fluid and accelerated transit
Dosing: 290 mcg orally once daily on empty stomach 30 minutes
prior to first meal of the day
Tudorza Pressair (aclidinium bromide) by Forest Laboratories: (07/23/12)
Class: long acting anticholinergic
Indication: long-term COPD maintenance
MOA: Tudorza inhibits the M3 receptor at the smooth muscle
leading to brochodilation
Dosing: one oral inhalation of 400 mcg twice daily
.
New Generic Approvals
Generic
Montelukast
Pioglitazone
Lidocaine Topical Patch 5%
Xopenex
Valsartan and Hydrochlorothiazide
Aripeptant
Amlodipine besylate, HCTZ, and Valsartan
Approval Date
08/03/12
08/17/12
08/23/12
08/28/12
09/21/12
09/24/12
09/25/12
Brand
Singulair
Actos
Lidoderm
Levalbuterol HCl
Diovan HCT
Emend
Exforge
Page 3
Drug Information Question
Does sulindac affect renal function less than other NSAIDs?
NSAIDs act by preventing the formation of prostaglandins produced in response to painful stimuli which decreases the number of pain impulses
received by the CNS.1 Prostaglandins within the kidneys help to diminish vascular resistance, dilate renal vascular beds and enhance organ perfusion. If this process is inhibited, renal profusion is decreased and blood flow is redistributed to the cortex which leads to acute renal dysfunction.2
Other NSAIDs are thought to be excreted as the active compound. Sulindac is excreted in the urine primarily as the inactive form which may possibly affect renal function less than other NSAIDs but renal adverse experiences have been reported.3
A prospective randomized crossover trial published in 1990, compared the renal effects of ibuprofen, piroxicam, and sulindac. Ibuprofen was given
at a dose of 800 mg three times daily, piroxicam was dosed at 20 mg daily, and sulindac was dosed at 200 mg twice daily. Twelve female patients
with asymptomatic, mild but stable chronic renal failure were included in this study. Each medication was given for an 11 day period followed by a
one month washout period. This study did not find a significant change in renal function from baseline in patients who were taking sulindac. They
went on to state that an 11-day course may not have been long enough to induce acute renal deterioration based on sulindac’s half-life.4
A study published in 1989 evaluated the renal effects of sulindac in 12 women. Urinary prostaglandin E2 excretion was decreased on day 4 from
baseline from 23.8 ng/hr to 7.7 ng/hr (p<0.02).5 A decrease in prostaglandin excretion confirms prostaglandin inhibition. A case series published
in 1995 involving 8 patients with renal impairment after diclofenac (n=1), naproxen (n=2), and sulindac (n=5) overdoses. These patients presented
with lumbar pain, oliguria, and protein and erythrocytes in the urine. Serum creatinine was increased to a maximum of 2.15 mg/dL to 10.5 mg/dL.6
In summary, initially, it was thought that sulindac decreased prostaglandin inhibition within the kidneys, compared to other NSAIDs, which is a primary factor in NSAID induced renal dysfunction. No substantial clinical evidence was found confirming that sulindac is better at preserving renal
function than other NSAIDs.
References:
1. Baumann T, Strickland J, Herndon C. Pain Management. In: DiPiro J, Talbert R, Yee G et al, eds. Pharmacotherapy: A Pathophysiologic
Approach. 8th ed. New York, NY: McGraw-Hill; 2011: 1048.
2. Whelton A. Nephrotoxicity of Nonsteroidal Anti-inflammatory Drugs: Physiologic Foundations and Clinical Implications. Am J Med. 1999;
106(5B): 13S – 24S.
3. Sulindac package insert. Corona, CA: Watson Pharma, Inc.: June 2009
4. Whelton A, Stout R, Spilman P, Klassen D. Renal Effects of Ibuprofen, Piroxicam, and Sulindac in Patients with Asymptomatic Renal Failure.
Ann Intern Med. 1990;112:568-576.
5. Klassen D, Stout R, Spilman P, Whelton A. Sulindac kinetics and effects on renal function and prostaglandin excretion in renal insufficiency.
J Clin Pharmacol. 1989; 29:1037-1042
6. Kulling P, Backman E, Beckman E. Renal impairment after acute diclofenac, naproxen, and sulindac overdoses. J Toxicol Clin Toxicol.
1995;33(2):173-177.
Drug Shortages
Boniva Injection by Genentech
 Products: Boniva 3 mg/ml
 Reason: Compliance issue with IV infusion set that is enclosed in
product kit and supplied by a third-party vendor
 Related information: Genentech expects current backlog to continue until early October
Metoclopramide Injection by Hospira and Teva
 Products: Metoclompramide 5 mg/ml
 Reason: Demand increase for drug
 Related information: Hospira expects next delivery in October
Cetrorelix Acetate for Injection by EMD Serono
 Products: Cetrorelix Acetate 0.25 mg
 Reason: Demand increase for drug
 Related information: Product is currently available on an allocated
basis
Dextroamphetamine Tablets by Teva
 Products: Dextroamphetamine 10 mg
 Reason: Delay in shipping of drug
 Related information: Low inventory, possible backorders through
October
Express Scripts
Drug Information & Wellness Center
Southern Illinois University Edwardsville
Monday — Friday
8 a.m. — 4 p.m.
(618) 650-5142
Page 4
Apps of the Month
The following applications have been reviewed and critiqued by students and pharmacists:
Name
APhA Drug Info
Line
Skyscape
Cost
Content
Free
New drug approvals, supplemental approvals, alerts
and recalls, product withdrawals, as well as new
updates in care
Free
Rating (1-5)
Drug information including interactive dosing calculators, formulary and pricing information, pill image
information, outlines of disease states and more
than 200 medical calculators and tools.
Recent Guideline Updates
The American College of Rheumatology has released updated guidelines for screening, treatment, and management of
lupus nephritis.
The general recommendations include the following:

Induction therapy should include either mycophenolate mofetil or cyclophosphamide, both in addition to a glucocorti-
coid.


Maintenance therapy should include either mycophenolate mofetil or azathioprine plus a glucocorticoid.
In patients who are planning to become pregnant, azathioprine is the recommended therapy.
The International Aniviral Society-USA has updated evidence-based recommendations for the management of HIV in
adult patients. The recommendations include the following:


Anti-retroviral therapy (ART) should be initiated as soon as possible regardless of CD4 cell count
Initial therapy continues to be based on a combination of 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs)
and a potent third agent, generally a nonnucleoside reverse transcriptase inhibitor (NNRTI), a ritonavir-boosted protease inhibitor (PI/r), an integrase strand transfer inhibitor (InSTI), or, rarely, an agent that blocks the CC chemokine receptor 5 (CCR5).

Recommended Regimens:
NNRTI + NRTIs:
Efavirenz/tenofivir/emtricitabine efavirenz + abacavir/lamivudine
PI/r + NRTIs:
Darunivir/r + tenofivir/emtricitabine
Atazanavir/r + tenofivir/emtricitabine
Atazanavir/r + abacavir/lamivudine
InSTI + NRTIs:
Raltegravir + tenofivir/emtricitabine
The Infectious Diseases Society of America (IDSA) has released updated guidelines on the diagnosis and management of
Group A Streptococcal (GAS) Pharyngitis. The recommendations include the following:

For diagnosis of GAS Pharyngitis, it is recommended to swab the throat by rapid antigen detection test (RADT) and/or
culture should be performed since clinical features alone do not reliably discriminate between GAS and viral pharyngitis.




In children and adolescents, negative RADT tests should be backed up by a throat culture.

Treatment of GAS pharyngitis in penicillin allergic individuals should include a first generation cephalosporin such as
cephalexin or cefadroxil (strong recommendation, high-quality evidence) for 10 days, clindamycin or clarithromycin for 10
days, or azithromycin for 5 days (strong, moderate).
Positive RADTs do not necessitate a back-up culture because they are highly specific.
Routine use of back-up throat cultures for those with negative RADT is not necessary for adults in usual circumstances.
For patients with acute GAS pharyngitis, the recommended therapy includes penicillin or amoxicillin for a duration of 10
days.