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GregoryRx Press
Lloyd L. Gregory School of Pharmacy
September 2014
Volume 9 Issue 3
Rescheduling of Hydrocodone Combination Products
Inside This Issue
Beginning October 6, 2014, all hydrocodone combination products will be switched from a
controlled scheduled III classification to a schedule II classification. Hydrocodone is a semi Rescheduling of
synthetic opioid derived from codeine and has high risk for abuse with the potential to
Hydrocodone
cause both physical and psychological dependence. These medications are often
Combination Products
prescribed for patients suffering from certain conditions that may induce moderate to
 New Drug Approval:
Suvorexant
severe pain from various primary conditions. According to the DEA, in 2013,
(Belsomra®)
approximately 137 million prescriptions containing combination hydrocodone and either
 Medication Review
acetaminophen or an antitussive agent were dispensed. Prior to this new rule, only
Spotlight: fluticasone
hydrocodone bitrate as a single entity was classified as a schedule controlled II substance
furoate/vilanterol
under the Controlled Substances Act (CSA) that passed in 1971. Although the DEA stands
(BREO ELLIPTA®)
firm that this solution will most likely decrease hydrocodone’s abuse, overdose, and
 Medication Review
emergency room visits, the American Pharmacist Association (APhA) has a different
Spotlight: Ceftaroline
viewpoint on this decision stating that “stricter requirements for Schedule II drugs related
fosamil (Teflaro®)
to prescribing and dispensing would restrict patient access and delay relief of pain.” APhA
postulates that this change will introduce discrepancies in healthcare due to stricter
storage and handling laws for Schedule II substances. With these new changes taking place, the decision to prescribe
and dispense hydrocodone combination products by health professionals may be a difficult one to make. It is
imperative that clinicians continue to exercise sound medical judgment for appropriate medical use according to
practice standards to ensure optimal care for pain control. Below are tables which describe reasons for the scheduling
change, updates practitioners on how these changes will affect practice, and reviews commonly available combination
hydrocodone products. For detailed information on the ruling, review the final DEA Rule.
Table 1. What are the Reasons for Schedule Change?
Diversion or misuse of the drug
High addictive potential
Impacts the health and safety of surrounding communities
Increased abuse and overdose
Widespread prescribing in high quantities
Table 2. How Does this New Rule Change Practice?
Call in prescriptions will not be allowed (exemptions apply in emergency situations)
Certain states only accept schedule II prescriptions on triplicate forms that are only
provided by the department of justice.
Every prescription must be accounted for by the pharmacist and entered separately into
systems (technicians in some state are legally not allowed to perform these tasks)
Faxing prescriptions will not be allowed (exemptions apply)
Inventory on the drug will be strictly checked and monitored with required record
keeping
More storage space will be needed for these products to be secured with other existing
scheduled II’s
Prescriptions will allow a 30 day supply with no refills with up to a 90 day supply with
multiple prescriptions and no refills
Patients may require more frequent visits to physician’s offices to obtain new written
prescriptions
All remaining valid refills for hydrocodone combinations written before October 6, 2015
may be granted before April 28, 2015 per DEA regulations
Table 3. A Review of Common Hydrocodone Combination Products
Generic
Brand
Hydrocodone Bitartrate/Acetaminophen Oral
Anexsia®, Lorcet®, Lortab®, Vicodin
HP®, Maxidone®, Norco®, Zydone
Ceta Plus®
Hydrocodone Bitartrate/Chlorpheniramine Maleate
Vituz®
Hydrocodone Bitartrate/Homatropine Methylbromide
Hycodan®, Hydromet®, Tussigon®
Hydrocodone Bitartrate/Ibuprofen
Ibudone®,Reprexain®, Vicoprofen®
Hydrocodone Bitartrate/Pseudoephedrine
Hydrochloride
Pancof HC®, Rezira®
Hydrocodone/Chlorpheniramine/Pseudoephedrine
Hydron PSC®, Hyphed®, NotussForte®, Zutripro®
Hydrocodone Polistirex/Chlorpheniramine Polistirex
Oral
Pennkinetic®, TussiCaps®, Tussionex®
Micromedex 2014. Drug Enforcement Administration 2014. Federal Register Daily Journal of the United States Govt. 2014. American Pharmacist Association 2014.
Pharmacist’s Letter 2014;30(10):301001.
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New Drug Approval: Suvorexant (Belsomra®) For the Treatment of Insomnia
On August 13, 2014, suvorexant (Belsomra ®) was FDA
approved for the treatment of insomnia, defined as
difficulties with sleep onset or sleep maintenance.
Suvorexant is the first and only drug in the novel class of
orexin receptor antagonists. The orexin neuropeptide is
located in the hypothalamus. The orexin function is to
promote wakefulness by blocking the wake-promoting
neuropeptides orexin A and orexin B to receptors OX1R
and OX2R. When the orexin receptor is blocked by
suvorexant, it facilitates the transition from wake to
sleep. Current medications for insomnia affect the
inhibitory neurotransmitter gamma-aminobutyric acid
(GABA). This results in a decrease in neuronal excitability
leading to sedative effects. According to Institute of
Medicine, insomnia is the most prevalent sleep disorder
in the general population. An estimated 50 to 70 million
adults in the US have sleep or
wakefulness disorders. The FDA
approval was based on the results
of two similarly designed phase III,
multicenter, randomized, doubleblind, placebo controlled, parallel
group studies to evaluate the
efficacy of suvorexant in patients
with primary insomnia. The two
trials compared the change from
baseline in subjective total sleep time in minutes (sTSTm)
and time to sleep onset in minutes(sTSOm), wake time
after persistent sleep onset (WASO), and latency to onset
of persistent sleep (LPS). Patients were randomized to
receive suvorexant 20 mg or placebo. Those randomized
to the suvorexant group who were classified as elderly
who were 65 years of age or older received a 15 mg dose.
Patients were included if they were diagnosed with
primary insomnia and reported having difficulty initiating
and maintain sleep 4 weeks prior to visit 1. Patients with a
history or diagnosis of another sleep disorder or having
difficulty sleeping due to a medical condition were
excluded. Results from one study showed mean baseline
of LPS in suvorexant and placebo were 69 minutes and 66
minutes, respectively, with a change in baseline of -35
and -27 with a difference of -8 minutes (p<0.01). Baseline
scores of time to sleep onset were 64 minutes and 67
minutes in suvorexant and placebo groups, respectively.
Results of sTSOm showed a decrease from baseline of -23
and -17 with a difference of -5 (p<0.05). The most
common side effects observed in the clinical trials were
somnolence, headache, and dizziness. In July 2013, the
FDA rejected suvorexant approval due to safety concerns
with higher doses. These doses led to potential major
safety concerns which include daytime somnolence,
impaired driving ability, unconscious nighttime behaviors,
suicidal ideation and narcolepsy-like syndrome. Merck
suggested adults start on 20 mg and increase to 40 mg if
needed and elderly start on 15 mg and increase to 30 mg
if needed. The FDA concluded that 30 mg and 40 mg were
not safe. Currently suvorexant is approved in four
different strengths: 5, 10, 15, and 20
mg. The recommended dose is 10 mg
for most patients. The FDA stated if 10
mg dose is tolerated but not effective
then 15 mg and 20 mg doses would be
acceptable. The maximum dosage in a
24 hour period is 20 mg. Patients
receiving concomitant therapy that
inhibit the cytochrome P-450 enzyme
should take a 5 mg dose and take no
more than 10 mg per night. Suvorexant should be taken
within 30 minutes of going to bed and should only be
taken for those planning to sleep for at least 7 hours.
Suvorexant is contraindicated in patients with narcolepsy
and is labeled as a pregnancy category C. It should also be
noted that suvorexant will be classified as a Schedule IV
controlled substance, along with other insomnia
medications: Ambien®, Lunesta®, and Sonata®.
Pharmacists dispensing this new medication should also
counsel patients on the importance of good sleep hygiene
habits such as minimizing nicotine, caffeine, large meals
before bed, avoid napping during the day, and encourage
exercise in their daily routine. Belsomra [package insert]. Merck &
Co., Inc. Whitehouse Station, NJ, 2014
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Medication Spotlight: BREOELLIPTA ® and Teflaro®
Fluticasone furoate/vilanterol (FF/VI)
(BREO ELLIPTA®)
Ceftaroline Fosamil (Teflaro®)
Therapeutic class

Inhaled corticosteroid (ICS)/Long-acting beta-2 
adrenergic agonist (LABA)
Date of approval

May 10, 2013

October 29, 2010
Indications


COPD maintenance treatment
Reduce COPD exacerbations

Medications for Same
Indication per Current
Clinical Practice
Guidelines

Advair 250/50 mg bid

Dosage/Frequency

Acute Bacterial Skin and Soft skin
Infections (ABSSSI)
Community Acquired Bacterial
Pneumonia (CABP)
ABSSSI w/ MRSA
Vancomycin, Linezolid, Clindamycin,
Daptomycin, Cefaroline, Doxycycline,
Minocycline, TMP-SMX
CABP (inpatient)
Cefotaxime, ceftriaxone, or
ampicillin-sulbactam + azithryomycin
or a fluoroquinolone, add
vancomycin or linezolid for MRSA
I.V.: 600 mg every 12 hrs
Renal Dosing
o No adj forCrCL >50ml/min
o CrCl>30-50ml/min:
400mg every 12 hrs
o CrCl 15-30ml/min:
300mg every 12 hrs
o CrCl<15ml/min:
200mg every 12hrs
Compatible with
o Dextrose 2.5 or 5% in water
o Ringers injected , lactated
o Sodium Chloride
Diarrhea
Nausea
Hypersensitivity


One inhalation powder FF 100 mcg/VI 25 mcg
once daily



Common Adverse
Drug Reactions



Headache
Nasopharyngitis
Hypertension
Black Box Warning

Asthma related deaths: LABAs increase the risk 
of asthma related death
Drug Interactions

Avoid strong CYP 3A4 inhibitors: increases
systemic corticosteroid and CV ADR can occur
Concomitant MAOIs and TCAs: may prolong
QTC interval
Concomitant beta blocker: may block FF/VI
effects and cause bronchospasm
Concomitant non-potassium-sparing diuretics:
can worsen hypokalemia and/or ECG changes

Probenecid may increase the serum
concentration of cephalosporin
Inhale and hold breathe for 3-4 seconds, after

Do not use longer or less than told by



Pharmacist




Cephalosporin
Known hypersensitivity to this or any
cephalosporin
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Counseling Points
and Clinical pearls


Clinical relevance

exhaling, rinse mouth with water and spit
(reduce risk of oral candidiasis)
Do not shake the inhaler
Discard inhaler within 6 weeks of opening foil
or when counter reaches zero
Advair 250/50 BID is currently used for
maintenance therapy, FF/VI is a more
convenient once daily alternative




prescriber to prevent re-infection
Do not use if solution is cloudy, leaking or
has particles, or changes color
If missed dose take dose as soon as you
remember, or if close to time for next
dose skip missed dose and go back to
normal schedule
Do not take 2 doses for missed dose
Has better binding affinity compared to
ceftriaxone, cefotaxime, oxacillin, and
penicillin G for penicillin-binding proteins
in MSSA, MRSA and S. pneumoniae
References: Lexi-Comp, 2014. Micromedex, 2014. IDSA Guidelines Management of Skin and Soft Tissue 2014. IDSA Guidelines Management of Community-Acquired
Pneumonia in Adults. Breo Ellipta [package insert]. GOLD Guidelines Management of COPD 2013.
Philippians 4:6 (NIV)
“Do not be anxious about anything, but in every situation, by prayer and petition, with thanksgiving, present your requests to God.”
The Drug Information Center is operated as a training site for experiential purposes. Students, under supervision of a pharmacy
faculty member, answer questions from preceptors. The GSOP DIC currently partners with Wellington Regional Medical Center.
The Center is open Monday to Friday, 8:30 am to 4:30 pm. Phone: 561-803-2728. You can also e-mail your questions to:
[email protected].
This issue was written by Steven Sabatell and JohnPaul Ramirez, PharmD Candidates 2015
Edited by Faculty Preceptor: Krisy Thornby, PharmD
Thank you to Leonid Slobodskoy, PharmD, Victoria Scott, PharmD, and the pharmacy team at WRMC for the generation of
newsletter topics!
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