Hot Topics in Drug Therapy: New products, new uses, new warnings

1
Hot Topics in Drug Therapy New products, new
uses, new warnings
Margaret A. Fitzgerald, DNP, FNP-BC, NP-C,
FAANP, CSP, FAAN, DCC President, Fitzgerald
Health Education Associates, Inc.North Andover,
MAFamily Nurse PractitionerGreater Lawrence
(MA) Family Health CenterEditorial Board, The
Nurse Practitioner Journal, Medscape Nursing,
The Prescribers Letter, American Nurse Today
Member, Pharmacy and Therapeutics
CommitteeNeighborhood Health Plan, Boston, MA
2
Objectives

• Upon completion of the program, the participant
  will be able to
• Describe recommendations for the use of new
  medications.
• Recognize new indications and cautions for
  established products.

3
What is hot? What is not?

• New products
• New warning
• New treatment recommendations

4
New Options for Weight Loss
5
Lorcaserin Hydrochloride (Belviq)

• What is it?
• Serotonin 2C receptor agonist
• Receptor that when activated significantly
  regulates mood, anxiety, feeding
• Clinical use
• First FDA approved weight loss medication in gt13
  years
• Source- http//us.eisai.com/package_inserts/Belviq
  PI.pdf, accessed 03.20.13.

6
Lorcaserin Hydrochloride (Belviq) (continued)

• Labeled use
• Adjunct to reduced-calorie diet and increased
  physical activity for chronic weight management
  in adults with initial body BMI of gt30 kg/m2 or
  27-29.9 kg/m2 in presence of gtone weight-related
  comorbid condition (hypertension, dyslipidemia,
  type 2 diabetes)

7
Lorcaserin Hydrochloride (Belviq) (continued)

• Labeled limitations of use
• Safety and efficacy of coadministration with
  other products for weight loss have not been
  established.
• The effect of medication on cardiovascular
  morbidity and mortality has not been established.

8
Lorcaserin Hydrochloride (Belviq) (continued)

• Dosing
• One, 10 mg tablet twice daily
• Discontinue if 5 weight loss is not achieved by
  week 12.
• Consistent with labeled advise with other weight
  loss medications

9
Drug Interaction Warning

• Do not use lorcaserin hydrochloride (Belviq)
  with any of the following
• Serotonergic drugs (SSRIs, SNRI, MAOIs, triptans,
  bupropion, dextromethorphan, St. Johns Wort,
  others).
• Reason
• Risk of serotonin syndrome

10
In Clinical Trials

• Lorcaserin hydrochloride (Belviq) 10 mg BID
• N3098, mean weight100.4 kg
• At end of 1 year, mean weight loss5.8 kg
• Placebo
• N3038, mean weight100.2 kg
• At end of 1 year, mean weight loss2.5 kg

11
Lorcaserin Hydrochloride (Belviq) Additional
Warnings

• Patient should be monitored for and advised to
  report any of the following
• Penile erectiongt4 hours, whether painful or not.
• Avoid pregnancy or breastfeeding while on the
  medication.

12
Phentermine and Topiramate Extended-release
(Qsymia)

• What is it?
• FDA-approved medication for chronic weight
  management in adults who are obese, or overweight
  with at least one weight-related comorbidity such
  as hypertension, type 2 diabetes mellitus, or
  dyslipidemia

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Phentermine/Topiramate (Qsymia)

• What is it?
• Phentermine/topiramate (Qsymia) is a once a day,
  proprietary, oral, controlled-release formulation
  of low dose phentermine and topiramate, which is
  believed to address both appetite and satiety -
  the two main mechanisms that impact eating
  behavior - in one capsule

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Phentermine/Topiramate (Qsymia) Doses

• 3.75 mg/23 mg
• Starting dose in AM X 2 weeks
• 7.5 mg/46 mg
• Use after 2 weeks of starting dose

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Phentermine/Topiramate (Qsymia) Doses
(continued)

• Higher doses allowable if weight loss not
  achieved with lower doses
• 11.25 mg/69 mg
• 15 mg/92 mg

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Typical Therapeutic Doses of Phentermine/Topiramat
e (Qsymia) Components

• Phentermine
• Up to 37.5 mg daily for weight loss
• Class IV controlled substance
• Topiramate
• Up to 400 mg daily for seizure control
• Up to 100 mg daily for migraine prophylaxis

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Weight Loss with Phentermine/Topiramate (Qsymia)
Use

• Percentage of patients losing greater than or
  equal to 5 body weight at end of 1 year
• 70
• Percentage of patients losing greater than or
  equal to 10 body weight at end of 1 year
• 40

18
Phentermine/Topiramate(Qsymia)

• Results from the two trials show that after one
  year of treatment with the recommended and
  highest daily dose of Qsymia, patients had an
  average weight loss of 6.7 percent and 8.9
  percent, respectively, over treatment with
  placebo.
• Source- http//www.fda.gov/NewsEvents/Newsroom/Pre
  ssAnnouncements/ucm312468.htm, accessed 03.20.13.

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Phentermine/Topiramate (Qsymia) REMS

• Risk Evaluation and Mitigation Strategy (REMS)
  purpose
• To inform prescribers and females of reproductive
  potential about teratogenic potential (orofacial
  clefts) with topiramate use during 1st trimester
  pregnancy
• Outline need for highly effective contraception
  during phentermine/topiramate (Qsymia) use
• Source- http//www.qsymiarems.com, accessed
  03.20.13.

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New Addition to ED Drug Class
21
Avanafil (Stendra)

• What is it?
• Phosphodiesterase 5 (PDE5) inhibitor
• PDE5 is responsible for the degradation of cGMP,
  which produces smooth muscle relaxation in the
  corpus cavernosum and allows inflow of blood.
• Identical mechanism of action to other erective
  dysfunction (ED) medications

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Avanafil (Stendra) (continued)

• Dose
• For most, starting dose100 mg taken
  approximately 30 minutes before sexual activity,
  on an as needed basis
• No more than once a day
• Increase to 200 mg or decreased to 50 mg based on
  efficacy and/or tolerability
• Use lowest effective dose

23
Avanafil (Stendra) (continued)

• Precaution with use
• Can potentiate hypotensive effect of nitrates,
  alpha-blockers, antihypertensives, and alcohol
• Biotransformation
• CYP3A4 substrate

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Avanafil (Stendra) Drug Interaction

• Use 50 mg as maximum dose
• Not to exceed 1 dose in 24 h
• Concomitant use of moderate CYP3A4 inhibitors
  (erythromycin, amprenavir, aprepitant, diltiazem,
  fluconazole, fosamprenavir, and verapamil)

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Avanafil (Stendra) Drug Interaction
(continued)

• Do not use with
• Strong CYP3A4 inhibitors (ketoconazole,
  ritonavir, atazanavir, clarithromycin, indinavir,
  itraconazole, nefazodone, nelfinavir, saquinavir
  and telithromycin)

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Avanafil (Stendra)

• T ½5 h
• Sildenafil, vardenafil T ½4 to 5-h
• Tadalafil T ½17 to 20-h
• Onset of action
• 30 minutes post dose ingestion

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Avanafil (Stendra) (continued)

• Use in presence of renal impairment
• No dose adjustment is necessary for patients with
  mild to moderate renal impairment (creatinine
  clearance gt30 to less than 90 mL/min gt0.5 to
  less than 1.5 mL/s)
• Not studied in end-stage renal disease, dialysis,
  use not recommended

28
Avanafil (Stendra) Other Precautions and
Warnings

• Consistent with drug class
• Prolonged erection
• Avoid use with nitrates
• Limit alcohol use to no more than 3 drinks at a
  time while taking medication.

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New MedsReformulated Older Meds
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Zolpidem Tartrate (Intermezzo)

• What is it?
• Sublingual tablet formulation of zolpidem
  tartrate, a non-benzodiazepine hypnotic
• Indication
• PRN use for insomnia treatment when a
  middle-of-the-night awakening is followed by
  difficulty returning to sleep

• Source- Intermezzo Prescribing Information,
  available at http//app.purduepharma.com/xmlpublis
  hing/pi.aspx?idi, accessed 03.20.13.

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Zolpidem Tartrate (Intermezzo) (continued)

• Indication (cont.)
• Should only be taken if gt4 h patient of bedtime
  remaining before planned time of waking
• How supplied and used
• Sublingual tablet, allow to disintegrate
  completely before swallowing, do not swallow whole

• Source- Intermezzo Prescribing Information,
  available at http//app.purduepharma.com/xmlpublis
  hing/pi.aspx?idi, accessed 3.20.13.

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Zolpidem Tartrate (Intermezzo) (continued)

• Dose
• Men3.5 mg
• Women1.75 mg
• Only one dose per night, only if needed

• Source- Intermezzo Prescribing Information,
  available at http//app.purduepharma.com/xmlpublis
  hing/pi.aspx?idi, accessed 3.20.13.

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References for Intermezzo

• Intermezzo Prescribing Information, available at
  http//app.purduepharma.com/xmlpublishing/pi.aspx?
  idi, accessed 03.20.13.
• Roth T, Hull SG, Lankford DA, Rosenberg R, Scharf
  MB Intermezzo Study Group Low-dose sublingual
  zolpidem tartrate is associated with dose-related
  improvement in sleep onset and duration in
  insomnia characterized by middle-of-the-night
  (MOTN) awakenings. Sleep 2008 Sep31(9)1277-84.

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Older drugNewer form and status
35
Oxybutynin in a Sustained Release Patch Form

• Oxytrol for women
• AboveFull branded name for this indication
• IndicationOAB
• Identical dose as the Rx formulation
• Labeling restricted to women due to licensing
• Safety, efficacy data presented to FDALimited to
  woman

36
The Original Federal Food, Drug, and Cosmetic Act
of 1938

• No clear-cut distinction between prescription and
  OTC drugs
• In 1951, Durham-Humphrey amendments to the act
  set up specific standards for classification
• Source- http//www.fda.gov/Drugs/ResourcesForYou/C
  onsumers/ucm143547.htm, accessed 3.20.13.

37
What is the difference between Rx and OTC drugs?

• Drugs only by prescription
• KeyHCP input needed for diagnosis and monitoring
  
• Antimicrobials
• Medications requiring monitoring of underlying
  condition (HTN, DM, etc.)
• Potentially toxic or habit-forming, with
  significant adverse effects

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What is the difference between Rx and OTC drugs?
(continued)

• Drugs available OTC
• KeyConsumer can self-diagnose condition
• Non habit-forming
• Generally safe with minimum risk of toxicity when
  used as directed with minimum adverse effects

39
Rx-to-OTC Switch?

• Per FDA
• When considering an Rx-to-OTC switch, the key
  question for the FDA is whether patients alone
  can achieve the desired medical result without
  endangering their safety.

40
OTC Direct-to-Consumer Advertising

• Under the law
• OTC drugs able to be advertised directly to
  consumers without the many restrictions placed on
  prescription products

41
New Option to Avoid Product Misuse
42
Oxycodone (Oxecta)

• What is it?
• Immediate release tablet formulation of opioid
  analgesic oxycodone HCl
• Formulation developed to limit or impede opioid
  abuse via intravenous injection of dissolved
  tablets and nasal snorting of crushed tablets
• Source- http//labeling.pfizer.com/showlabeling.as
  px?id620, accessed 3.20.13.

43
True or false?

• The current formulation of sustained release
  oxycodone (OxyContin) limits ability for the
  tablets to be crushed or dissolved for injection
  or snorting.
• A growing problem is former sustained release
  oxycodone users who have now gravitated to heroin
  use.
• Source- http//www.chicagotribune.com/health/sns-r
  t-us-usa-health-painkillersbre86a1aw-20120711,0,71
  9700.story, accessed 03.20.13.

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Sumatriptan Transdermal (Zecuity)

• Delivers 6.5 mg of sumatriptan transdermally over
  4 hours via patient activated system
• Once applied, activation button must be pushed,
  red light emitting diode (LED) turns on

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Sumatriptan Transdermal (Zecuity) (continued)

• Best suited
• Patient with migraine and significant GI upset
• Compare dose
• Up to 100 mg PO
• 6 mg in subcutaneous form
• 6.5 mg transdermal form

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Established Drugs, New Indications
47
Established Drugs, New Indications (continued)

• Pregabalin (Lyrica)
• Neuropathic pain associated with spinal cord
  injury
• Estradiol valerate and estradiol
  valerate/dienogest (Natazia)
• Heavy menstural bleeding

48
New Warning About a Commonly Prescribed Medication
49
Azithromycin and the Risk of Cardiovascular Death
Wayne A. Ray, Ph.D., Katherine T. Murray, M.D.,
Kathi Hall, B.S., Patrick G. Arbogast, Ph.D., and
C. Michael Stein, M.B., Ch.B.
N Engl J Med Volume 366(20)1881-1890 May 17, 2012
50
Background Information

• Macrolide antibiotics
• Azithromycin, clarithromycin, erythromycin
• Clarithromycin, erythromycin
• Long known to have proarrhythmic potential, use
  increases risk of serious ventricular
  arrhythmias, associated with increased risk of
  sudden cardiac death

51
Background Information (continued)

• Azithromycin
• Thought relatively free of cardiotoxic effects
• The FDAs Adverse Event Reporting System includes
  at least 20 reports of torsades de pointes
  associated with azithromycin use.

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For Additional Information, http//www.qtdrugs.or
g

• True or false?
• The risk of torsades de pointe with erythromycin
  or clarithromycin is greater in females than in
  males.

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Torsades de Ponte
54
Study Conclusion

• In conclusion, during 5 days of azithromycin
  therapy, there was a small absolute increase in
  cardiovascular deaths.

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Study Conclusion (continued)

• As compared with amoxicillin, there were 47
  additional cardiovascular deaths per 1 million
  courses of azithromycin therapy. For patients in
  the highest decile of baseline risk of
  cardiovascular disease, there were 245 additional
  cardiovascular deaths per 1 million courses.

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Excess Risk of Cardiovascular Death with
Azithromycin as Compared with Amoxicillin,
According to Decile of Cardiovascular Risk Score
Ray WA et al. N Engl J Med 20123661881-1890
57
What about treating the older adult with COPD
exacerbation, typically a group with significant
cardiovascular risk, in need of antimicrobial
therapy?
58
Sanford Guide Recommendation for Antimicrobial
Therapy
Mild to moderate COPD exacerbation/ acute exacerbation of chronic bronchitis Antimicrobial therapy usually not indicated. If prescribed, consider using the following agents Amoxicillin Cephalosporin TMP-SMX Doxycycline
Source- Gilbert, D., Moellering R., Eliopoulos,
G., Chambers, H., Saag, M. (2012) The Sanford
Guide to Antimicrobial Therapy (41th ed.).
Sperryville, VA Antimicrobial Therapy, Inc.
59
Sanford Guide Recommendation for Antimicrobial
Therapy
More severe COPD exacerbation/ acute exacerbation of chronic bronchitis One of the following Amoxicillin-clavulanate Cephalosporin Azithromycin Clarithromycin Fluoroquinolone with activity against DRSP (Moxi-, gemi-, levofloxacin)
Source- Gilbert, D., Moellering R., Eliopoulos,
G., Chambers, H., Saag, M. (2012) The Sanford
Guide to Antimicrobial Therapy (41th ed.).
Sperryville, VA Antimicrobial Therapy, Inc.
60
Update to CDC's Sexually Transmitted Diseases
Treatment Guidelines, 2010 Oral Cephalosporins
No Longer a Recommended Treatment for Gonococcal
Infections

• Available at http//www.cdc.gov/mmwr/preview/mmwrh
  tml/mm6131a3.htm?s_cidmm6131a3_w, accessed
  03.20.13.

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ceftriaxonethe last antimicrobial that is
recommended and known to be highly effective in a
single dose for treatment of gonorrhea at all
anatomic sites of infection.

• Source- http//www.cdc.gov/mmwr/preview/mmwrhtml/m
  m6131a3.htm?s_cidmm6131a3_w, accessed 03.20.13.

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Uncomplicated Gonococcal Infections of the
Cervix, Urethra, and Rectum

• CDC recommendations as of August 2012
• Ceftriaxone 250 mg IM as 1 X dose
• Plus
• Azithromycin 1 g PO X 1 dose or doxycycline 100
  mg PO BID X 7 d

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Uncomplicated Gonococcal Infections of the
Cervix, Urethra, and Rectum (continued)

• Option 1

• Alternative when ceftriaxone unable to be used
• Return 1 week after treatment for TOC at site of
  infection

• Cefixime 400 mg orally plus either azithromycin 1
  g PO X 1 or doxycycline 100 mg PO BID X 7 d

64
Uncomplicated Gonococcal Infections of the
Cervix, Urethra, and Rectum (continued)

• Option 2

• Return 1 week after treatment for TOC at site of
  infection

• Azithromycin 2 g orally in a single dose if
  ceftriaxone cannot be given because of severe
  allergy

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Neisseria gonorrhoeae Pharyngeal Infection

• Ceftriaxone 250 mg IM X 1 dose
• Plus
• Azithromycin 1 g PO X 1 in or doxycycline 100 mg
  PO BID X 7 d
• Plus
• TOC in 1 week

66
Expedited Partner Therapy (EPT)

• Defined
• Clinical practice of treating the sex partners of
  patients diagnosed with certain STI by providing
  prescriptions or medications to the patient to
  take to his/her partner without the health care
  provider first examining the partner.
• Source- http//www.cdc.gov/std/ept/default.htm,
  accessed 03.20.13.

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EPT Q and A

• According to the CDCs recommendations, EPT can
  be use in the treatment of
• Chlamydia.
• Gonorrhea.
• Chlamydia and gonorrhea.
• All clinically documented STIs.

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EPT Allowed or not?

• Prohibited
• Arkansas
• Florida
• Kentucky
• Michigan
• Ohio
• Oklahoma
• West Virginia

• Permissible in 32 states
• All New England states, NY
• Potentially allowable in 11 states, DC, and
  Puerto Rico
• Source- http//www.cdc.gov/std/ept/legal/default.h
  tm, accessed 03.20.13.

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True or false?

• For all patients with gonorrhea, every effort
  should be made to ensure that the patients' sex
  partners from the preceding 60 days are evaluated
  and treated for N. gonorrhoeae with a recommended
  regimen.

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With All STIs

• Concomitant testing
• Syphilis
• HIV
• HBV, consider HCV
• Immunization considerations
• HAV, HBV
• HPV

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End of Presentation

• Thank you for your time and attention.
• Margaret A. Fitzgerald, DNP, FNP-BC, NP-C,
  FAANP, CSP, FAAN, DCC
• www.fhea.com, E-mail cs_at_fhea.com