Challenges in Drug Decision Making

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Challenges in Drug Decision Making

• Julienne Kirk, Pharm.D., CDE
• Associate Professor
• Department of Family and
• Community Medicine

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1x a week, 1x a month, 1x a year?

• 66 year old full professor at WFU comes in and
  states she received the results from her recent
  DEXA scan
• Her Z score is -2.5 at her hip
• She is post-menopausal and reports intolerance to
  weekly Fosomax
• What are her options and she wants details

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Bisphonsphonates for Osteoporosis

• Alendronate (Fosamax) 10 mg daily 1127 or 70 mg
  weekly 1090, Fosomax Plus D 70 mg witj 2800
  units D3 1097, 5600 imots 1084
• Ibandronate (Boniva) 2.5 mg daily 1077, or 150
  mg monthly 1030 or 3mg IV every 3 mo. 1911
• Risedronate (Actonel) 5mg daily (1077), 35 mg
  weekly 1076, or 75 mg x 2 days monthly 1078
  Actonel 35 mg weekly with Calcium 500 mg other
  days of the week 1074
• Reclast IV infusion

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Zoledronic acid (Reclast)

• Indications
• Treatment of osteoporosis in postmenopausal women
• Treatment of Pagets disease of bone in men and
  women
• MOA
• Bisphosphonate
• Inhibits osteoclast-mediated bone resorption

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Zoledronic acid (Reclast)

• Efficacy HORIZON Recurrent Fracture Trial
• n2100 post-surgical repair of hip fracture
• 5 mg yearly, follow-up 2 years
• New fractures
• Zoledronic acid 8.6
• Placebo 13.9 (35 reduction)
• Hip
• Zoledronic acid 2.0
• Placebo 3.5 (30 reduction)

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Zoledronic acid (Reclast)

• Efficacy HORIZON Recurrent Fracture Trial
• Vertebral
• Zoledronic acid 1.7
• Placebo 3.8 (46 reduction)
• Death
• Zoledronic acid 9.6
• Placebo 13.3

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Zoledronic acid (Reclast)

• Adverse effects
• Infusion reaction fever, flu-like symptoms,
  headache, arthralgia/myalgia
• Other muscle pain
• GI disturbances
• Jaw osteonecrosis (one patient high dose
  bisphophonate was used)
• Atrial fibrillation
• IV bisphosphonates have been associated with
  renal impairment
• Transient decreases in calcium

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Zoledronic acid (Reclast)

• Dosage / Administration
• Osteoporosis
• 5 mg once yearly, IV over 15 minutes
• Daily requirement of calcium 1200 mg /
• vitamin D 400-800 IU
• Pagets Disease
• 5 mg IV over 15 minutes
• Daily requirement of calcium 1500 mg
• vitamin D 800 IU, esp for 2 weeks
• Not recommended in severe renal impairment
• Patient should be sufficiently hydrated

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My Child is Coughing

• Mom comes in with her 3 year old and states that
  she can no longer buy OTC cough and cold
  medicines
• She wants to know how to get a good night sleep
  tonight
• Mom went to the pharmacy and they told her all
  infant and cold meds have been withdraw because
  of questions about efficacy and safety issues

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Alternatives

• Saline Nasal Spray if used in kids, the first
  dose loosens the mucus and reapplication will be
  necessary
• Humidifiers and vaporizers can moisten the air
  but must be cleaned often
• If parents are using camphor, menthol or
  eucalyptus for cough or congestion then do not
  allow inhalation (worry about absorption and
  liver damage
• Honey may help to relieve cough

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Allergy Dilemma

• 64 year old female with hay fever. Other meds
  include Ditropan, Diazepam, Tramadol,
  Cyclobenzaprine, Aspirin and Lisinopril.
• She states she is highly allergic to dust
• Xyzal is what her friend uses and she wants a
  prescription for this new drug
• She also want to know about nasal steroids and if
  they will have an affect on blood sugar

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Allergy Case Dilemma

• 40 million people suffer from allergic rhinitis
• 56 have nasal allergies throughout the year
• Xyzal (levocetirizine) has a 2 fold greater
  affinity for H1 receptors than cetirizine
• Onset at 60 minutes, efficacy demonstrated at 24
  hours
• Side effects include somnolence (5),
  nasopharangitis (5), dry mouth 2-3

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Allergy Case Discussion

• Xyzal (levocetirizine) son of Zyrtec
  indicated in the relief o symptoms associated
  with allergic rhinitis (seasonal and perennial)
  and the symptoms of uncomplicated idiopathic
  urticaria in adults and children 6 years old
• Dosage 5 mg daily for 12 years, pediatric
  patients 2.5 mg daily at bedtime

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Allergic Rhinitis Treatment

• Mainstay oral antihistamines
• irritative symptoms
• First vs Second-generation drugs
• Oral decongestants for obstructive sx
• Topical decongestants for temporary relief
• Topical steroids
• major impact on obstructive nasal sx, less on
  irritative
• most effective per guidelines
• Ipratropium useful for watery rhinorrhea

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Dosage

• Levocetirizine (Xyzal)
• 12 yo 5 mg q PM
• 6 11 yo 2.5 mg q PM
• Fluticasone furoate (Veramyst 27.5 mcg/spray)
• 12 yo 2 sprays each nostril daily
• 2 11 yo 1 spray each nostril daily

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Allergy Medicine Cost

• Cost of antihistamines
• OTC products and competition
• 4 WalMart Loratidine 10 mg 30
• Insurance coverage Xyzal 3rd copay 50
• Fexofendine 40
• Cost of intranasal steroids
• Flovent 86 Fluticasone 60
• Nasacort 88
• Rhinocort 91
• Vancenase/Beconase 118
• Veramist

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Typical Short Visit

• 61 year old male with a PMH of HTN, type 2
  diabetes, gall stones, gout and hyperlipidemia.
  His A1C is 8.8 and BP is 150/88, cholesterol
  profile showed a TC of 305, LDL 165, HDL 42 and
  TG 339. His height is 510 and he weighs 244
  lbs.
• What should you think about for pharmacotherapy
  treatment regimen. Current medications include
  Lipitor 10 mg daily, lopressor 25 mg bid, and
  metformin 1000 mg bid and Avandia 4 mg daily.
• His has CHD in his family and his daughter who is
  in medical school has several questions one is
  about Avandia and CV data?

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Cardiovascular Drug Issues

• Do you add an aspirin today?
• Do you add an ACEI?
• Do you leave the beta-blocker?
• What you do about Avandia?
• What evidence do you have to support your
  decisions in this 15 minute visit today?
• Is there evidence to support monitoring his blood
  glucose daily for better A1c control?
• What labs do you want and why)

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Aspirin Guidelines

• ADA recommends all patients take a daily aspirin
  for CV protection
• Contraindications include allergy, AAA, severe GI
  bleed
• Document on medical history
• Blood pressure should be controlled before you
  start aspirin therapy because of the risk of
  hemorragic stroke in the face of high BP
• Have BP

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ADA and EASD Treatment Algorithm

• Lifestyle Intervention and metformin are
  recommended for initial therapy
• Meta-analysis (Nissen et al. 2007, NEJM) found a
  30 to 40 relative increase in risk for MI
• Another meta-analysis using a similar data set
  showed no increaser risk of CV mortality (Lago et
  al. 2007 Lancet)
• RECORD (Rosiglitazone Evaluation for Cardiac
  Outcomes and Regulation of Glycemia in Diabetes
  showed no significant increase in MI

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Avandia vs. Actos

• Label Changes No longer indicated as a diabetes
  treatment in combination with insulin however, it
  is not contraindicated
• Initiation of TZD in NYHA III or IV heart failure
  is CONTRAINDICATED
• TZD can cause or exacerbate CHF evaluate
  patient of rapid weight gain, dyspnea, and or
  edema
• Pioglitazone (Actos) has 19 randomized studies of
  16,900 patients ranging 4 months to 3.5 years.
  MI, stroke or death occurred in 375 (4.4) of
  8,544 patients vs. 450 (5.7) of 7,836 patients
  on control theapy

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To TZD of not to TZD?

• Both TZDs have been associated with an increased
  risk for fractures, particularly in women (distal
  forearm, hand, and wrist) or lower limb (foot,
  ankle, fibula, and tibia)
• ADA and EASD Treatment Algorithm states that TZD
  are 2nd line and notes that they are associated
  with an increased risk of fluid retention, CHF
  and fractures.
• Rosilgitazone has been associated with macular
  edema

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B-Blocker for Hypertension

• Cochrane Review 2007, Issue 1 Wisonge et al.
• Objective of review was to evaluate the
  effectiveness and safety of B-blockers on
  morbidity and mortality endpoints in adults with
  hypertension
• 13 RCT (n91,561) in comparison with thiazides,
  CCB, RAS inhibitors showed that B-blockers did
  not reduce stroke and had an absence of overall
  effect on CHD when compared to the other agents
• Atenolol was the primary B-blocker in these trials

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Hypertension 4 Examples

• Atenolol 25 mg 30
• Chlorthalidone 25 mg 30
• Diltiazem 60 mg 60
• Lisinopril 10 mg 30
• Furosemide 40 mg 30
• Metoprolol 50 mg 60
• Spironolactone 25 mg 30
• Propanolol 20 mg 60

www.target.com / www.walmart.com
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Cardiology Survival Tips Adult Dosing Guide

• Common drugs used in the adult cardiovascular
  setting including PK parameters such as age,
  gender, comorbidties, phenotype, weight and
  interacting drugs
• In general, steady-state drug levels are reached
  within 3-5 half-lives
• Last up-dated 6/07

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CAP In Patient vs. Out Patient

• 59 year old female with a PMH significant for
  COPD, Afib, depression and high cholesterol. Now
  6 day h/o productive cough, fever with
  occasional chills. She smokes 1 PPD. Some
  weakness, but no respiratory distress. - nv,
  headache, MS change or diarrhea. PE. - VS - RR-
  22 (unlabored) bp-120/60 p-108 temp- 101. Pulse
  ox. 91
• Medications Atrovent and Advair Inhalers, Zocor
  40 mg daily, Zoloft 100 mg daily, and Coumadin 5
  mg daily and Amlodipine 5 mg daily
• Chest - rales at lung bases RL. No wheezing,
  scattered rhonchi, CXR - Patchy RLL pneumonia

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WFUBMC Empiric Antibiotic Recommendations for
Infections with and without Sepsis

• CAP Ceftriaxone Azithromycin
• Pneumonia in LTCF, Assisted Living,
  Aspiration, AECB and Pen Allergy alternatives
• Skin, Soft Tissue and Bone Infections
• Abdominal Infection
• UTI
• Catheter Related Infection
• Fever and Neutropenia

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IDSA Guidelines - CAP in Outpatients

• Recommended treatments for CAP in outpatients
  are
• Previously healthy
• No recent antibiotic therapy macrolide or
  doxycycline
• Recent antibiotic therapy a respiratory
  fluoroquinolone, an advanced macrolide plus high
  dose amoxicillin, or an advanced macrolide plus
  high dose amoxicillin-clavulanate

Adapted from Mandell LA et al. Clin Infect Dis.
2006 1405-1433
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IDSA Guidelines - CAP in Outpatients

• Recommended treatments for CAP in outpatients
  are
• Comorbidities (COPD, malignancy, diabetes, renal
  or CHF)
• No recent antibiotic therapy an advanced
  macrolide or respiratory fluoroquinolone
• Recent antibiotic therapy a respiratory
  quinolone alone or an advanced macrolide plus
  beta-lactam
• Suspected aspiration with infection Augmentin
  or clindamycin
• Influenza with bacterial superinfection a
  beta-lactam or respiratory fluoroquinolone

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Respiratory Med Cost

• Cost of current medications
• Advair 250/50 185.22
• Atrovent 0.03 64.63
• Advair (Salmeterol/Fluticasone) HFA
• --45/21 165
• --115/21 170
• --230/21 229
• Symbicort 160/4.5ug - 120 dose
  -Budesonide/Formoterol
• Symbicort 80/4.5 135

Prices www.walgreens.com / www.drugstore.com
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Cost of Antibiotics

• Cost of treatment for CAP
• No recent antibiotic therapy
• Azithromycin 500 mg daily x 7 days 151
• Clarithromycin XL 500 mg pack 234
• Doxycycline 100 mg BID x 10 days 4.00
• Recent Antibiotic therapy
• Moxifloxacin 400 mg daily for 7-14 days 327
• Amoxicillin 1 gram TID 10-14 days 16
• Augmentin XR (1000/62.5) Two 1000 mg tablets
  every 12 hours for 7-10 days 96

Prices www.walgreens.com / www.drugstore.com
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Antibiotics 4 Examples

• Amoxicillin 500 mg 30
• Cephalexin 500 mg 30
• Ciprofloxacin 500 mg 30
• Metronidazole 500 mg 14
• Penicillin VK 250 mg 28
• SMZ/TMP DS 800/160 20
• Tetracycline 500 mg 60

www.target.com / www.walmart.com
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Antidepressant 4 Examples

• Amitriptyline 75 mg 30
• Citalopram 40 mg 30
• Fluoxetine 10 mg 30
• Paroxetine 20 mg 30
• Trazodone 100 mg 30
• Doxepin 25 mg 30

www.target.com / www.walmart.com
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Retapamulin ointment (Altabax)

• Indication topical treatment of impetigo
• Up to 100 cm2 (adults) or 2 total BSA (children)
• Caused by Staphylococcus aureus or Streptococcus
  pyogenes
• MOA
• interacts with 50S subunit of the bacterial
  ribosome

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Impetigo

• Usually affects children
• Transmitted via direct contact
• Types nonbullous bullous
• Prognosis
• Guidelines
• Topical treatment for limited disease
• Oral antibiotics for more severe disease

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Retapamulin ointment (Altabax)

• Efficacy
• 85, versus 50 placebo
• 90 for both retapamulin vs cephalexin po
• Safety
• Application site irritation (1.5)
• Drug interactions none clinically important

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Treatment of Impetigo
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Paliperidone (Invega)

• Indication acute and maintenance treatment of
  schizophrenia
• MOA
• 9-hydroxyrisperidone
• Central dopamine Type 2 (D2) and serotonin Type 2
  (5HT2A) receptor antagonism

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Paliperidone (Invega)

• Pharmacokinetics
• Osmotic delivery (OROSTM)once daily interval
• Metabolism limited role of CYP2D6 3A4
• Elimination 80 urine, 10 feces
• Drug interactions
• Caution with other centrally-acting drugs
• May lessen effects of levodopa / dopamine
  agonists
• Avoid drugs prolonging QT interval

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Paliperidone (Invega)

• Adverse effects
• tachycardia, headache, sedation, anxiety
• QT prolongation (4)
• dizziness, nausea, tremor
• Other class labeling with regard to
• neuroleptic malignant syndrome
• orthostatic hypotension
• tardive dyskinesia
• seizure risk
• ?ed mortality in elderly with dementia-related
  psychosis

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Second Generation Antipsychotics Comparative
Adverse Effects
Limited experience, likely similar to risperidone
Med Lett Drug Ther 20074921
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Paliperidone (Invega)

• Dosage / Administration
• 6 mg daily range 3 12 mg
• 3, 6, 9 mg available
• No titration necessary
• Renal impairment
• CrCL 50-79 mL/min 6 mg max
• CrCL 10-49 mL/min 3 mg max
• Do not crush
• Insoluble core eliminated in stool

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2nd Generation AntipsychoticsComparative Cost
Adapted from Med Lett Drug Ther 20074922
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Paliperidone (Invega)

• Summary
• Major metabolite of risperidone
• Effective compared to placebo
• No current comparisons to other active drugs
• Similar adverse effects, expected fewer drug
  interactions
• Fewer indications and dosage forms
• Generic risperidone to come

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Rotigotine (Neupro)

• Indication treatment of signs/symptoms of
  early-stage idiopathic Parkinsons disease
• MOA
• Non-ergot dopamine agonist
• Matrix patch

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Parkinsons Disease

• Cardinal features
• Tremor, rigidity, bradykinesia
• Postural instability
• Symptom control challenges
• Wearing-off
• On-off
• Dyskinesias

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Parkinsons Disease

• Cardinal features
• Tremor, rigidity, bradykinesia
• Postural instability
• Symptom control challenges
• Wearing-off
• On-off
• Dyskinesias

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Rotigotine (Neupro)

• Efficacy
• Early PD
• Versus placebo ? improvements in motor and
  daily living scores
• Versus ropinirole both drugs vs placebo
• Advanced PD (2.5 hrs off time)
• Versus placebo 1-2 hrs more improvement
• Versus pramipexole both drugs 2 hrs vs
  placebo
• Restless Legs
• Versus placebo

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Rotigotine (Neupro)

• Availability 2-, 4-, 6-mg/24 hr patches
• Dosage / Administration
• Initial 2 mg / 24 hr
• Titrate in weekly intervals, taper on d/c
• Apply to abdomen, hip, thigh, flank, shoulder, or
  upper arm
• Rotate sites over 14-day period
• Avoid direct heat
• Contains aluminum

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Rotigotine (Neupro)

• Adverse effects
• Application site reactions
• Nausea, somnolence, dizziness
• Sudden sleep onset
• Hallucinations, abnormal dreaming
• Postural hypotension
• Weight gain, peripheral edema
• Contains sodium metabisulfite

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Rotigotine (Neupro)

• Summary
• Initial therapy for Parkinsons
• Levodopa vs anticholinergic vs dopamine agonist
  vs selegiline
• Once daily administration
• Similar adversities to dopaminergic agents
• Unclear benefit to continuous dopaminergic
  stimulation
• Cost