Docstoc

cpe_part_3and4

Document Sample
cpe_part_3and4 Powered By Docstoc
					New Drugs of 2007
                                     Part 3
Presented by:    Sarah Rodriguez, PharmD

Drugs Covered:   azithromycin (Azasite®)
                 doripenem (Doribax™)
                 raltegravir (Isentress™)
                 maraviroc (Selzentry™)
                 temsirolimus (Torisel™)
Azithromycin
       Azasite ®
     Manufactured by: Inspire




                      www.prescribingreference.com
Azithromycin (Azasite®)

Therapeutic Class
• Ophthalmic antimicrobial


Indications
• Treatment of bacterial conjunctivitis caused by
       •   Haemophilius influenzae
       •   Staphylococcus aureus
       •   Streptococcus mitis
       •   Streptococcus pneumoniae
       • CDC coryneform group G
            Azasite® (Azithromycin) package insert. Durham, NC: Inspire. May 2007.
Azithromycin (Azasite®)

Mechanism of action                            Pharmacokinetics
  •   Interferes with                               •      Systemic absorption
      bacterial protein                                    is minimal
      synthesis by binding
      to the 50S ribosomal
      subunit




           Azasite® (Azithromycin) package insert. Durham, NC: Inspire. May 2007.
Azithromycin (Azasite®)
Dosing and Administration
  •    1 drop in the affected eye(s) twice daily for two
       days, then 1 drop daily for five days
Cost
  •    $66.25/bottle (AWP)




            Azasite® (Azithromycin) package insert. Durham, NC: Inspire. May 2007.
Azithromycin (Azasite®)
Contraindications & Precautions
     No contraindications
  •   Severe allergic reactions have been seen with
      systemic use of azithromycin
  •   Long-term use can result in resistant infections
      developing

Drug Interactions
  •   None identified

Adverse Effects
  •   Eye irritation most common
           Azasite® (Azithromycin) package insert. Durham, NC: Inspire. May 2007.
          Azithromycin (Azasite®)
Objective     Determine if azithromycin is efficacious in the treatment of
              bacterial conjunctivitis
Design        Randomized, double-blind, multi-center, vehicle controlled
              trial
Study Arms    Azithromycin or vehicle twice daily for the first 2 days, then
              once daily for 5 days

Results       Clinical resolution: 63% vs. 50%
              Microbiologic eradication: 88% vs. 66%

Conclusion    Azithromycin is an effective treatment for bacterial
              conjunctivitis


                       Azasite® (Azithromycin) package insert. Durham, NC: Inspire. May 2007.
            Azithromycin (Azasite®)
Objective     Compared the safety and tolerability of azithromycin to
              tobramycin for the treatment of bacterial conjunctivitis
Design        Randomized, double-blind, active-controlled, phase 3 trial
Study Arms    Patients with confirmed bacterial conjunctivitis
              randomized to azithromycin 1% or tobramycin 0.3%
Results       No significant differences between the groups with
              regards to safety
Conclusion    Azithromycin is as safe as tobramycin for the treatment of
              bacterial conjunctivitis


                      Protzko E, Bowman L, Abelson M, Shapiro A. Phase 3 Safety Comparisons for 1.0% Azithromycin
                      Polymeric Mucoadhesive Eye Drops versus 0.3% Tobramycin Eye drops for Bacterial Conjunctivitis.
                      Invest Ophthalmol Vis Sci. @007;48:3425-3429.
Azithromycin (Azasite®)

Patient Education
  •   Wash hands before using
  •   Avoid touching the tip of the bottle to the eye
  •   Important to complete full course of therapy
  •   Do not wear contact lenses
       Azithromycin (Azasite®)
Place in Therapy
   •    Less frequent dosing than other available treatments for bacterial
        conjunctivitis

          Drug                      Schedule                   Cost
       Azithromycin     1 drop twice daily for 2 days, then   $66.25
                             1 drop daily for 5 days
       Ciprofloxacin   1-2 drops every 2 hours for 2 days,    $63.00
                          then every 4 hours for 5 days
       Moxifloxacin     1 drop three times daily for 7 days   $69.44
       Gentamicin             1 drop every 4 hours            $9.61

Clinical Pearls
   •    Offers no therapeutic advantage over currently available products
        Question 1

Which of the following is an
advantage of azithromycin
   (Azasite®) over other
 treatments for bacterial
      conjunctivitis?
Answer now!                                                           15

1. It is much more
   efficacious than other
   available agents
2. Systemic absorption
   allows for eradication of
   the causative bacteria      25%                         25%
   elsewhere in the body
3. It requires less frequent
   dosing than other
   available agents            25%                         25%
4. It can be used in infants
   less than one year of
   age
                               Efficacy   Absorption   Dosing   Age
           Question 2

   A doctor calls the pharmacy
wishing to prescribe azithromycin
       (Azasite) for bacterial
   conjunctivitis. This agent is
 currently non-formulary at your
institution. Which of the following
      agents would be a valid
      therapeutic alternative?
                                                                    15
Answer now!

1. Meropenem               25% 25% 25% 25%
2. Gentamicin
3. Prednisolone
4. Ceftazidime




                                     n
                      em




                                                                e
                                                     e
                                       i




                                                               m
                                                     n
                                    ic




                                                  lo




                                                             di
                      en




                                   m



                                                so




                                                             zi
                                ta
                    op




                                                           ta
                                              ni
                            en
                  er




                                                         ef
                                             ed
                            G
                  M




                                                         C
                                           Pr
Doripenem
         Doribax™
    Manufactured by: Ortho-McNeil




                 www.prescribingreference.com
Doripenem (Doribax™)

Therapeutic Class
• Carbapenem antibiotic


Indications
• Complicated intra-abdominal infections
• Complicated urinary tract infections, including
  pyelonephritis




           Doripenem (Doribax®) Package Insert. Raritan, NJ: Ortho-McNeal. October, 2007.
           Doripenem (Doribax™)
              Mechanism of action                                        Pharmacokinetics
                    •     Binds to penicillin binding                            •   Distribution:
                          proteins                                                     • 8% protein bound
                    •     Inhibits synthesis of                                        • Concentrates in
                          bacterial cell wall                                             peritoneal fluid,
                    •     Bacteriocidal                                                   retroperitoneal fluid,
                                                                                          gallbladder, bile, and
                                                                                          urine
                                                                                 •   Metabolism:
                                                                                       • Metabolized to an
                                                                                          inactive, open ring
                                                                                          form by
                                                                                          dehydropeptidase-1
                                                                                       • Not a substrate for
                                                                                          CYP450
                                                                                 •   Elimination:
                                                                                       • Renal
Doripenem (Doribax®) Package Insert. Raritan, NJ: Ortho-McNeal. October, 2007.         • Half-life is 1 hour
Doripenem (Doribax™)
Dosing and Administration
  •    Complicated intra-abdominal infections
        • 500 mg infused over 1 hour every 8 hours for 5 – 14
          days
  •    Complicated urinary tract infections
        • 500 mg infused over 1 hour every 8 hours for 10 days
Cost
  •    $95.83/dose (AWP)




            Doripenem (Doribax®) Package Insert. Raritan, NJ: Ortho-McNeal. October, 2007.
Doripenem (Doribax™)
Contraindications & Precautions
  •   Severe hypersensitivity reactions have occurred
  •   Clostridium difficile associated diarrhea
  •   Overuse can result in development of drug-resistant
      bacteria
  •   Cases of pneumonitis reported with inhalational use

Drug Interactions
  •   Valproic acid
  •   Probenecid




           Doripenem (Doribax®) Package Insert. Raritan, NJ: Ortho-McNeal. October, 2007.
Doripenem (Doribax™)

Adverse Reactions
 Headache
 Nausea
 Diarrhea
 Rash
 Phlebitis
 Seizure




         Doripenem (Doribax®) Package Insert. Raritan, NJ: Ortho-McNeal. October, 2007.
          Doripenem (Doribax™)
Objective    Compare clinical cure rates of patients with
             complicated intra-abdominal infections treated with
             meropenem or doripenem
Design       Randomized, double-blind, multi-center trials
Study Arms   Patients with complicated intra-abdominal infections
             randomized to treatment with doripenem 500 mg
             every 8 hours or meropenem 1 g every 8 hours
Results      Clinical cure:
             Study 1: 82.8% vs. 85.9%
             Study 2: 81% vs. 82.1%
Conclusion   Doripenem is not inferior to meropenem in the
             treatment of complicated intra-abdominal infections



                    Doripenem (Doribax®) Package Insert. Raritan, NJ: Ortho-McNeal. October, 2007.
            Doripenem (Doribax™)
Objective     Compare microbiological eradication rates in patients
              with complicated urinary tract infections treated with
              doripenem or levofloxacin
Design        Randomized, double-blind, multi-center trials
Study Arms    Patients randomized to treatment with doripenem 500
              mg every 8 hours or levofloxacin 250 mg daily
Results       Clinical cure: 82.1% vs. 83.4%

              Evaluation of the microbiological intent to treat patients
              also resulted in similar cure rates between the two
              groups
Conclusion    Doripenem is not inferior to levofloxacin in the treatment
              of complicated urinary tract infections

                       Doripenem (Doribax®) Package Insert. Raritan, NJ: Ortho-McNeal. October, 2007.
Doripenem (Doribax™)

Patient Education
  •   Possibility of severe allergic reactions
  •   Only used for the treatment of bacterial infections
  •   Full course of therapy should be completed
Doripenem (Doribax™)

Place in Therapy:
• Broad spectrum antibiotic
• Reserve for patients at high risk for serious, multi-drug
  resistant infections
• Effective against Pseudomonas aeruginosa and may be more
  potent in its activity than other carbapenems
        • No indication for Pseudomonal infections at this time
Clinical Pearls:
• Superiority over other carbapenems not established
• Pneumonia indication currently under review
    • Will require 4 hour infusion
  Zhanel GG, Wiebe R, Dilay L, et al. Comparative Review of the Carbapenems. Drugs 2007;67(7):1027 – 1052.
 Sakyo S, Tomita H, Tanimoto K, Fujimoto S, Ike Y. Potency of Carbapenems for the Prevention of Carbapenem-
                Resistant Mutants of Pseudomonas aeruginosa. J Antibiot 2006;59(4): 220-228.
        Question 3

Which of the following drugs
has the same mechanism of
   action as doripenem?
 Answer now!
                      15

1.Gentamicin
                25%
2.Colistin
                25%
3.Ceftriaxone
                25%
4.Tigecycline
                25%
       Question 4

   Which of the following
nosocomial pathogens does
  doripenem have activity
         against?
                                                            15
        Answer now!
1. Pseudomonas aeruginosa
2. Methicillin resistant
   Staphylococcus aureus
3. Vancomycin Resistant
   Enterococcus faecalis      25%            25%
4. Clostridium difficile


                              25%            25%



                            Pseudomona...   Methicilli...
                            Vancomycin...   Clostridiu...
Life Cycle of
     HIV:
Therapeutic
   Targets




 http://img.thebody.com/
Raltegravir
      Isentress™
      Manufactured by: Merck




                      www.prescribingreference.com
Raltegravir (Isentress™)

 Therapeutic Class
   • HIV integrase inhibitor


 Indications
   • Treatment of HIV-1 infection
                • Only used in combination with other agents
                • Patients with evidence of multi-drug resistance



Isentress (Raltegravir®) Package insert. Merck and Company, Whitehouse Station, NJ. October, 2007.
                    Raltegravir (Isentress™)
                      Mechanism of action                                   Pharmacokinetics
                           •     Inhibits HIV-1 integrase                        •               Absorption:
                                                                                                   • Bioavailability not
                                                                                                      known
                                                                                                   • AUC is increased by
                                                                                                      19% with a high-fat
                                                                                                      meal
                                                                                         •       Distribution:
                                                                                                   • 83% protein bound
                                                                                         •       Metabolism:
                                                                                                   • Glucuronidated by
                                                                                                      UGT1A1
                                                                                         •       Elimination:
                                                                                                   • 51% of the dose is
                                                                                                      excreted in the feces
Isentress (Raltegravir®) Package insert. Merck and Company, Whitehouse Station, NJ. October, 2007. • 32% in the urine

                                                                                                   • Half-life 9 hours
Raltegravir (Isentress™)
    Dosing and Administration
    • 400 mg twice daily with or without food

    Cost
    • $1,012.50/month (AWP)


    Contraindications & Precautions
    • No contraindications
    • Immune reconstitution syndrome to residual
      opportunistic infections
    • Pregnancy category C

Isentress (Raltegravir®) Package insert. Merck and Company, Whitehouse Station, NJ. October, 2007.
Raltegravir (Isentress™)
Drug Interactions
  •    Use caution in giving raltegravir with strong
      inducers of UGT1A1
        • Rifampin can decrease plasma concentrations
          of raltegravir through UGT1A1 induction
        • Tipranavir, ritonavir, and atazanavir also affect
          UGT1A1, but dose adjustment does not appear
          to be needed
  •   Increased risk of rhabdomyolysis with concurrent
      use of statins and fibrates




            Isentress (Raltegravir®) Package insert. Merck and Company, Whitehouse Station, NJ. October, 2007.
Raltegravir (Isentress™)
 Adverse Effects
 • Most Common
    • Diarrhea
    • Nausea
    • Headache
    • Fever
 • Myopathy
 • Elevated liver enzymes
    • Especially in those co-infected with Hepatitis B or C


Isentress (Raltegravir®) Package insert. Merck and Company, Whitehouse Station, NJ. October, 2007.
          Raltegravir (Isentress™)
Objective                  Evaluate the efficacy of raltegravir in patients with
                           triple-drug resistant HIV infection
Design                     Randomized, double-blind, placebo controlled,
                           multi-center trials
Study Arms                 Patients randomized to raltegravir 400 mg bid or
                           placebo plus optimized background therapy
Results                    At 16 weeks:
                           HIV RNA levels < 400: 77% vs. 41%
                           HIV RNA levels < 50: 61% vs. 36%
                           CD4 count increases: 86 cells/mm3 vs. 40 cells/mm3
Conclusion                 Raltegravir is a safe and effective treatment for HIV
                           in treatment-experienced patients with multi-drug
                           resistant HIV
     Jones, J, Taylor B, Wilkin TJ, Hammer SM. Advances in Antiretroviral Therapy. Top HIV Med 2007;15(2)48:82.
Raltegravir (Isentress™)

Patient Education
  •   Not a cure for HIV
  •   Importance of compliance with antiretroviral
      regimens
  •   Report any unusual muscle pain or weakness
Raltegravir (Isentress™)
Place in Therapy:
• Novel mechanism of action shown to be efficacious even in
  patients with very resistant HIV infections
• Studies ongoing in treatment naïve patients
• Low pill burden


Clinical Pearls:
• May be particularly effective when given in combination with
  darunavir and enfuvirtide


    Jones, J, Taylor B, Wilkin TJ, Hammer SM. Advances in Antiretroviral Therapy. Top HIV Med 2007;15(2)48:82.
    Correll T, Klibanov OM. Integrase Inhibitors: A New Treatment Option for Patients with Human
    Immunodeficiency Virus Infection. Pharmacotherapy 2008, 28(1):91 – 100.
         Question 5

 Which of the following co-
morbidities in an HIV positive
   patient may increase the
 likelihood of toxicity when
   treated with raltegravir?
                                                                            15

       Answer now!
1. Hepatitis C                      25% 25% 25% 25%
2. Diabetes mellitus
3. Chronic renal
   insufficiency
4. Kaposi’s sarcoma




                                               s
                                C




                                                                        a
                                                           .
                                                u




                                                                       m
                                                           .
                                s




                                                        fi.
                                             lit
                             iti




                                                                        o
                                                      uf
                                           el




                                                                     rc
                           at




                                                      ns
                                       m




                                                                 sa
                       ep




                                                    li
                                      es




                                                                ’s
                       H




                                                 na
                                    et




                                                               i
                                                            os
                                               re
                                  b
                               ia




                                                           ap
                                             ic
                              D




                                                       K
                                         on
                                       hr
                                      C
           Question 6
 A patient in your unit comes in
with new onset of shingles. Upon
  reviewing his history, you find
    that he is HIV positive and
 recently underwent a change in
his antiretroviral medications. His
 physician wants to discontinue
  the new therapy since it is not
  working. What is your advice?
           Answer now!                                                          20
1. Agree with the MD and
     discontinue all antiretroviral
     therapy immediately
2.   Discontinue all of his
     antiretroviral agents but one to
     keep his HIV under control until
     you figure out what his new
     regimen will be
3.   Advise the MD to continue the      25%                             25%
     patient’s current therapy and
     add on raltegravir to maintain
     better control of his HIV
4.   Advise the MD that the patient     25%                             25%
     just had a change in his
     antiretroviral medications and
     his symptoms may be due to
     immune reconstitution
     syndrome
                                        Agree   All but one   Add raltegravir   IRS
Maraviroc
     Selzentry™
     Manufactured by: Pfizer




       www.prescribingreference.com
Maraviroc (Selzentry™)

Therapeutic Class
• CCR5 co-receptor antagonist


Indications
• Treatment of CCR5-tropic HIV-1 infection
          • Only in combination with other antiretroviral agents
          • Treatment experienced patients who have evidence
            of multi-drug resistance



   Selzentry® (Maraviroc) Package Insert. Pfizer Labs, New York, NY. August, 2007.
  Maraviroc (Selzentry™)

Mechanism of action                    Pharmacokinetics
  •   Antagonizes the                        •      Absorption:
      interaction between                              • Low bioavailability
      CCR5 and HIV gp120                               • AUC is decreased by high-fat
  •   Prevents HIV from                                  meal
      entering the cell                                • Maraviroc is also a substrate for
                                                         P-glycoprotein
                                             •      Distribution:
                                                       • 76% protein bound
                                             •      Metabolism:
                                                       • CYP450 3A4 substrate
                                             •      Elimination:
                                                       • 76% of the dose is excreted in
                                                         the feces
                                                       • 20% in the urine
                                                       • Half-life of 18 hours

              Selzentry® (Maraviroc) Package Insert. Pfizer Labs, New York, NY. August, 2007.
        Maraviroc (Selzentry™)
               Concomitant Medications                                                         Dose
                   CYP450 3A4 inhibitors                                            150 mg twice daily
      Other medications including tipranavir/ritonavir,                             300 mg twice daily
           nevirapine, all NRTIs and enfuvirtide
      CYP450 3A4 inducers (without a strong CYP3A4                                  600 mg twice daily
                       inhibitor)

Cost
  •     $1087.50/bottle (AWP)
  •     Does not differ with strength




                            Selzentry® (Maraviroc) Package Insert. Pfizer Labs, New York, NY. August, 2007.
      Maraviroc (Selzentry™)
Contraindications & Precautions
  •   Black box warning for hepatotoxicity
        • Preceded by allergic symptoms including rash, eosinophilia, and
          elevated IgE
        • Discontinue immediately if patient develops symptoms of hepatitis
          or elevated liver enzymes
        • Little data in patients with Hepatitis B, Hepatitis C, or other forms
          of liver impairment
  •   Cardiovascular events including myocardial infarction and ischemia
  •   Immune reconstitution syndrome to residual opportunistic infections
  •   Increased risk of infection
  •   Increased risk of malignancy




                         Selzentry® (Maraviroc) Package Insert. Pfizer Labs, New York, NY. August, 2007.
Maraviroc (Selzentry™)
Drug Interactions
• Caution in patients with a history of postural hypotension or in
    those receiving anti-hypertensive medications due to increased
    risk of symptomatic hypotension
•   CYP3A4 inducers and inhibitors

Adverse Effects
   Cough
   Fever
   Upper respiratory tract infections
   Rash
   Musculoskeletal pain
   Abdominal pain
   Dizziness
   Hepatotoxicity, especially in patients with pre-existing hepatic
    dysfunction
                   Selzentry® (Maraviroc) Package Insert. Pfizer Labs, New York, NY. August, 2007.
          Maraviroc (Selzentry™)
Objective     Determine the safety and efficacy of maraviroc in
              combination with usual therapy
Design        Double-blind, randomized, multi-center trial
Study Arms    3 class experienced patients with CCR5 tropic HIV-1
              randomized to best available therapy plus placebo,
              maraviroc 150 mg daily, or maraviroc 150 mg bid
Results       Approximately 70% of patients responded to therapy
              HIV RNA < 400: 60.8% vs. 27.8%
              HIV RNA < 50: 45.3%
              CD4 count increases: 106.3 cells/mm3 in maraviroc
              twice daily group vs. 57.4 cells/mm3 in maraviroc
              once daily group
Conclusion    Maraviroc was found to be an effective treatment for
              multi-drug resistant HIV at 24 week analysis
                         Jones, J, Taylor B, Wilkin TJ, Hammer SM. Advances in Antiretroviral Therapy.
                                                  Top HIV Med 2007;15(2)48:82.
Maraviroc (Selzentry™)

Patient Education
  •   Not a cure for HIV
  •   Importance of compliance with antiretroviral
      regimens
  •   Notify physician immediately if symptoms of
      hepatitis develop such as yellowing of the skin or
      eyes, abdominal pain, dark urine, or vomiting
Maraviroc (Selzentry™)
Place in Therapy:
• Novel mechanism of action
• Has been shown to only be effective in patients with
  CCR5 tropic HIV-1 and is not effective in those who
  demonstrate dual or mixed tropism

Clinical Pearls:
• High rate of co-infection with Hepatitis B and C in this
  population, which warrants extreme caution using
  maraviroc
• Ongoing trials needed to determine cardiovascular
  effects and increased rates of malignancy
Jones, J, Taylor B, Wilkin TJ, Hammer SM. Advances in Antiretroviral Therapy. Top HIV Med 2007;15(2)48:82.
              Selzentry® (Maraviroc) Package Insert. Pfizer Labs, New York, NY. August, 2007.
        Question 7

Patients receiving maraviroc
   (Selzentry™) should be
 counseled on which of the
         following?
                                                                          15
         Answer now!
1. Decreased bioavailability
   when taken with food
2. Muscle pain and weakness,
   especially in combination
   with other agents
                                          25%                25%
3. Signs and symptoms of
   increased blood sugar
4. Signs and symptoms of
   hepatotoxicity
                                          25%                25%



                               No food   Muscle pain   Blood sugar   Hepatotoxicity
        Question 8

Which of the following has a
 drug-drug interaction with
  maraviroc (Selzentry™)?
Answer now!
                          15

1.Divalproic acid
                    25%
2.Pravastatin
                    25%
3.Itraconazole
                    25%
4.Enoxaparin
                    25%
Temsirolimus
       Torisel ™
     Manufactured by: Wyeth




                     www.prescribingreference.com
 Temsirolimus (Torisel™)

  Therapeutic Class
    • Mammalian target of rapamycin (mTOR) inhibitor


  Indications
    • Treatment of advanced renal cell carcinoma




Torisel™ (temsirolimus) package insert. Wyeth Pharmaceuticals Incorporated, Madison, NJ. May, 2007.
     Temsirolimus (Torisel™)

Mechanism of action
• Inhibits mTOR by
  binding FKBP-12
• Forms complex that
  inhibits mTOR
• Inhibition of mTOR
  results in arrest of the
  cell cycle and decreases
  angiogenesis


                             http://professional.cancerconsultants.com
 Temsirolimus (Torisel™)
  Pharmacokinetics
  • Absorption: Following intravenous administration, Cmax is 585
      ng/mL and AUC was 1627 ng*h/mL.
  •   Distribution: extensively distributed in blood with a volume of
      distribution of 172L
  •   Metabolism: Metabolized by CYP450 3A4 to 5 different
      metabolites, including sirolimus
  •   Elimination: Eliminated primarily in the feces. The half-life of
      the parent compound is 17.3 hours and is 54.6 hours for
      sirolimus

  Dosing and Administration
        •      25 mg IV weekly
        •      Only stable for 6 hours after final dilution

  Cost
        •      $1400/25 mg vial (AWP)

Torisel™ (temsirolimus) package insert. Wyeth Pharmaceuticals Incorporated, Madison, NJ. May, 2007.
 Temsirolimus (Torisel™)
  Contraindications & Precautions
        •      Severe hypersensitivity reactions
        •      Increase in serum glucose that may require insulin
               or oral hypoglycemic therapy
        •      Interstitial lung disease - may result in death
        •      Increased total cholesterol and triglycerides
        •      Bowel perforation
        •      Acute renal failure independent of disease
               progression


Torisel™ (temsirolimus) package insert. Wyeth Pharmaceuticals Incorporated, Madison, NJ. May, 2007.
 Temsirolimus (Torisel™)

        Contraindications/Precautions (Cont.)
        •      Abnormal wound healing
        •      Patients with central nervous system tumors or
               those receiving anticoagulants are at risk of
               intracerebral hemorrhage
        •      Concomitant use with sunitinib has resulted in
               increased risk for severe rash, gout, and cellulitis
        •      Use of live vaccines should be avoided
        •      Pregnancy category D



Torisel™ (temsirolimus) package insert. Wyeth Pharmaceuticals Incorporated, Madison, NJ. May, 2007.
 Temsirolimus (Torisel™)
  Drug Interactions:
  • Dose adjustments required when given with strong
      inhibitors or inducers of CYP450 3A4

  Adverse Reactions:
      •Rash                                                •Hyperglycemia
      •Asthenia                                            •Hyperlipidemia
      •Mucositis                                           •Lymphopenia
      •Nausea                                              •Elevated serum
      •Edema                                               creatinine
      •Anorexia                                            •Elevated liver enzymes
      •Anemia                                              •Hypophosphatemia
Torisel™ (temsirolimus) package insert. Wyeth Pharmaceuticals Incorporated, Madison, NJ. May, 2007.
                   Temsirolimus (Torisel™)
Objective                  Compare efficacy and tolerability of temsirolimus alone or
                           temsirolimus plus interferon alfa-2a with interferon alfa-2a
                           alone in metastatic renal cell carcinoma
Design                     Phase III, open label, randomized, multi-center trial
Study Arms                 Patients randomized to temsirolimus, temsirolimus plus
                           interferon alfa-2a, or interferon alfa-2a alone
Results                    Overall survival: 10.9 months vs. 7.3 months

                           Progression free survival: 5.5 months over 3.1 months

Conclusion                 Treatment with temsirolimus increases overall survival in
                           patients with metastatic renal cell carcinoma



Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, Interferon Alfa, or Both for Advanced Renal-Cell Carcinoma. N Engl J Med 2007;356:2271-2281.
 Temsirolimus (Torisel™)
Patient Education
  •   Risks of severe allergic reaction, renal failure,
      interstitial lung disease, bowel perforation, and
      intracerebral hemorrhage
  •   Increased urination or thirst, increased or new
      respiratory symptoms, or blood in the stool
  •   Increased susceptibility to infection
  •   Risk of serious drug interactions
  •   Patients of child-bearing age should use
      contraception throughout therapy and for three
      months after treatment

               Torisel™ (temsirolimus) package insert. Wyeth Pharmaceuticals Incorporated, Madison, NJ. May, 2007.
        Temsirolimus (Torisel™)

Place in Therapy
• First line monotherapy in patients with relapsed or unresectable stage IV
    renal cancer


Clinical Pearls
• Treatment extends overall survival and provides some clinical benefit, but
    prognosis for patients with advanced renal cell carcinoma is still poor
•   Still being studied in combination with interferon-alfa 2a
•   Also being studied in mantle cell lymphoma, breast cancer, and
    glioblastoma
•   New oral mTOR inhibitor, everolimus, currently in development
                      Motzer RJ, Bolger GB, Boston B. et al. NCCN Clinical Practice Guidelines in Oncology™ Kidney Cancer,
                      Version 1.2008. Available at: http://www.nccn.org/physician_gls/index.html.
                      Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, Interferon Alfa, or Both for Advanced Renal-Cell
                      Carcinoma. N Engl J Med 2007;356:2271-2281.
        Question 9

  Which of the following
serious adverse effects has
   been associated with
 temsirolimus treatment?
                                                                             15
        Answer now!
1. Congestive heart failure
2. Interstitial lung disease
3. Aplastic anemia
                               25%                               25%
4. Liver failure

                               25%                               25%



                               Congestive heart ...   Interstitial lung...
                               Aplastic anemia        Liver failure
      Question 10

Which treatment should be
    given along with
     temsirolimus?
                                                                               15

       Answer now!
1. Antihistamines               25% 25% 25% 25%
2. Corticosteroids
3. Darbepoetin
4. IV fluids




                                                                           s
                               s




                                                 s




                                                              in




                                                                        id
                                e




                                                  d



                                                            et
                             in




                                               oi




                                                                    flu
                                                          po
                            m




                                            er
                         ta




                                                                   IV
                                          t



                                                        be
                                       os
                         is




                                                      ar
                                      tic
                       ih




                                                      D
                     nt




                                    or
                     A




                                C
       New Drugs of 2007
                                  Part 4
Presented by: Sharla Tajchman, PharmD

Drugs Covered: Ixabepilone (Ixempra™)
               Rotigotine (Neupro®)
               Armodafinil (Nuvigil™)
               Lapatimib (Tykerb®)
               Lisdexamfetamine (Vyranse®)
Ixabepilone
        Ixempra™
Manufacterur: Bristol-Myers Squibb
                              Ixabepilone (Ixempra™)
       Therapeutic Class
          • Antineoplastic agent

       Indications
          • Metastatic or locally advanced breast
            cancer
          • Failed prior therapy with an anthracycline
            and a taxane
                          -       In combination with capecitabine
                          -       As monotherapy, if failed prior therapy
                                  with capecitabine


Product Information: Ixempra™ IV injection, ixabepiline IV injection. Bristol-
Myers Squibb Company, Princeton, NJ, 2007.
                             Ixabepilone (Ixempra™)
       Mechanism of                                                              Pharmacokinetics
         action                                                                  • Absorption: Maximum
       • Microtubule                                                               concentration at
            inhibitor
                                                                                   completion of infusion
                                                                                 • Distribution: Protein
                                                                                   binding 67% to 77%
                                                                                 • Metabolism: CYP3A4
                                                                                   -   No active metabolites
                                                                                 • Elimination: Fecal
                                                                                   -   Terminal half-life 52 hrs

Product Information: Ixempra™ IV injection, ixabepiline IV injection. Bristol-
Myers Squibb Company, Princeton, NJ, 2007.
                             Ixabepilone (Ixempra™)
       Dosing and Administration
       • 40 mg/m2 infused intravenously over 3
         hours every 3 weeks
       • Dose Adjustments

       Cost (AWP)
       • Ixempra™ 15 mg vial $1,152.45
       • Ixempra™ 45 mg vial $3,457.36

       Formulary status: Nonformulary
       Formulary alternatives: None
Product Information: Ixempra™ IV injection, ixabepiline IV injection. Bristol-
Myers Squibb Company, Princeton, NJ, 2007.
                             Ixabepilone (Ixempra™)
         Contraindications
         • Severe hypersensitivity to Cremophor EL
         • Neutrophil count < 1500 cells/mm3 or platelet
              count < 100,000 cells/mm3
         •    In combination with capecitabine in patients with
              AST or ALT > 2.5 x UNL or bilirubin > 1 x UNL

         Precautions
         • Caution in hepatic impairment
         • Peripheral neuropathy, myelosuppression,
              cardiac adverse reactions
         •    Cognitive impairment
         •    Pregnancy Category D
Product Information: Ixempra™ IV injection, ixabepiline IV injection. Bristol-
Myers Squibb Company, Princeton, NJ, 2007.
          Ixabepilone (Ixempra™)
Drug Interactions
• CYP3A4 inhibitors
  •   Decrease dose to 20 mg/m2

Adverse Effects
• Nonhematologic
  •   Peripheral neuropathy, myalgia/arthritis,
      musculoskeletal pain
  •   Fatigue, edema, chest pain
  •   Nausea, vomiting, diarrhea, constipation
  •   Stomatitis/mucositis, alopecia, skin rash
• Hematologic:
  •   Neutropenia, leukopenia, anemia,
      thrombocytopenia        Product Information: Ixempra™ IV injection, ixabepiline IV injection. Bristol-
                                                     Myers Squibb Company, Princeton, NJ, 2007.
             Ixabepilone (Ixempra™)
     Perez EA, Lerzo G, Pivot X, et al. J Clin Oncol. 2007; 25: 3407.
Objective     Determine the safety and efficacy of ixabepilone
              monotherapy
Design        Prospective, multicenter, single-arm, phase II clinical
              trial
Study Arm     Ixebepilone 40mg/m2 monotherapy administered on
              day 1 of a 21 day chemotherapy cycle
Results       Overall response rate (ORR) was 19% and 50% of
              patients had stable disease, 14% for 6 months or
              longer
              The median length of response duration and overall
              survival were 5.7 and 8.6 months, respectively.
Conclusion    Ixabepilone demonstrated efficacy and safety in
              patients with metastatic breast cancer who were
              refractory to anthracycline and taxane therapy.
              Ixabepilone (Ixempra™)
        Thomas, ES, Gomez, HL, Li, RK, et al. J Clin Oncol 2007; 25:5210.

Objective      Determine the safety and efficacy of ixabepilone in
               combination with capecitabine
Design         International, prospective, randomized, open label, phase
               III clinical trial
Study          Ixabepilone plus capecitabine (combo group), or
Arms           capecitabine as monotherapy (mono group)

Results        Prolonged progression-free survival in combo group
               compared to mono group (median, 5.8 versus 4.2 months)
               25% reduction in the risk of disease progression (p < 0.01)
               ORR was also increased (35% versus 14%; p < 0.0001)
Conclusion Ixabepilone plus capecitabine is superior to capecitabine
               monotherapy in patients with metastatic breast cancer
               refractory to anthracyclines and taxanes
                             Ixabepilone (Ixempra™)
       Patient Education
       • Numbness or tingling
       • Fever of 100.5°F or greater or evidence of
            potential infection
       •    Contraception
       •    Avoid nursing
       •    Chest pain, difficulty breathing, palpitations
            or unusual weight gain



Product Information: Ixempra™ IV injection, ixabepiline IV injection. Bristol-
Myers Squibb Company, Princeton, NJ, 2007.
                             Ixabepilone (Ixempra™)
       Place in Therapy
        Metastatic or locally advanced breast cancer
            refractory to anthracycline or taxane-based
            chemotherapy regimens


       Clinical Pearls
       • Premedication – similar to paclitaxol infusions
       • Contains alcohol
       • If given in combination with capecitabine,
            consider BOTH medications when counseling
Product Information: Ixempra™ IV injection, ixabepiline IV injection. Bristol-
Myers Squibb Company, Princeton, NJ, 2007.
What is the mechanism of
  action of Ixempra™?
                       Answer Now!                         :15

1. Cross-links to DNA by
     alkylating the N7 position
     of guanine, resulting in       20%   20%   20%   20%    20%
     DNA strand breakage
2.   Inhibits microtubules,
     halting cell division in the
     mitotic phase resulting in
     cell death
3.   Inhibits topoisomerase II,
     resulting in DNA strand
     breakage
4.   Inhibitor of dihydrofolate
     reductase, causing an
     intracellular deficiency of     1    2      3     4         5


     folate
5.   Dual tyrosine-kinase
Ixempra™ is contraindicated
  in which of the following:
                     Answer Now!                       :15


1. Concomitant use with        20%   20%   20%   20%   20%
     capecitabine
2.   Pregnancy
3.   Concomitant use with
     CYP3A4 inhibitors
4.   Absolute neutrophil
     count of less than 1500
     cells/mcL
5.   Primary treatment of
     breast cancer
                               1     2      3     4     5
Rotigotine
     Neupro®
 Manufacterur: UCB S.A.
                                 Rotigotine (Neupro®)
       Therapeutic Class
         • Antiparkinsonian, dopamine agonist


       Indications
          Treatment of early-stage idiopathic
           Parkinson’s disease




Product information: Neupro ® Transdermal Patch, rotigotine transdermal
patch, Schwarz Pharma, Co Claire, Ireland, 2007.
                                 Rotigotine (Neupro®)
       Mechanism of                                                       Pharmacokinetics
         action                                                           • Absorption: 3 hrs
        Non-ergolinic           after application
           dopamine (D3/D2/D1) • Distribution: Protein
           receptor agonist      binding 92%
                               • Metabolism:
                                 Conjugation and N-
                                 dealkylation
                               • Elimination: Primarily
                                 excreted in urine
                                                                            -   Half-life 5 to 7 hours
Product information: Neupro ® Transdermal Patch, rotigotine transdermal
patch, Schwarz Pharma, Co Claire, Ireland, 2007.
                                 Rotigotine (Neupro®)
       Dosing and Administration
       • Initiation therapy at 2 mg/24 hrs
       • Highest recommended dose is 6 mg/24 hrs

       Cost
       • Currently unavailable due to reformulation of
           product

       Formulary status: Nonformulary
       Formulary Alternatives: None

Product information: Neupro ® Transdermal Patch, rotigotine transdermal
patch, Schwarz Pharma, Co Claire, Ireland, 2007.
                                 Rotigotine (Neupro®)
       Contraindications
       • Hypersensitivity to rotigotine
       • Sulfa allergy

       Precautions
       • Sedation
       • Symptomatic hypotension, syncope, elevation of
           heart rate and blood pressure, weight gain and
           fluid retention
       •   Pregnancy Category C

Product information: Neupro ® Transdermal Patch, rotigotine transdermal
patch, Schwarz Pharma, Co Claire, Ireland, 2007.
                                 Rotigotine (Neupro®)
       Drug Interactions
       • Metabolized by CYP isoforms
       • Displacement of highly protein bound drugs
       • Dopamine antagonists

       Adverse Effects
       • Cardiovascular
       • Dermatologic
       • Gastrointestinal
       • Neurologic
       • Opthalmic
       • Psychiatric
Product information: Neupro ® Transdermal Patch, rotigotine transdermal
patch, Schwarz Pharma, Co Claire, Ireland, 2007.
            Rotigotine (Neupro®)
            Watts RL, et al. Neurology. 2007; 68, 272-6.

Objective    Compare the safety and efficacy of transdermal
             rotigotine versus placebo in Parkinson’s disease
Design       Multicenter, randomized, double-blinded, phase III
             clinical trial
Study        Patients received placebo or rotigotine patch once-
Arms         daily and maintained for 6 months
Results      Change in UPDS scores of 5.28 lower than patients
             receiving placebo (p < 0.0001)
             More patients respond to drug therapy than placebo
             (48% vs 19%, p < 0.0001)
Conclusion Transdermal rotigotine was effective for the
           treatment of early-stage Parkinson’s disease when
           titrated up to a dosage of 6 mg/hr once daily
                                 Rotigotine (Neupro®)
       Patient Education
       • Sedating effects
       • Magnetic resonance imaging or cardioversion
       • Do not cut
       • Sun exposure may lead to skin color changes
       • Intense urges to gamble and increased sexual
           urges




Product information: Neupro ® Transdermal Patch, rotigotine transdermal
patch, Schwarz Pharma, Co Claire, Ireland, 2007.
        Rotigotine (Neupro®)
Place in Therapy
• Early-stage Parkinson’s disease (FDA
  approved)
• Moderate to severe Parkinson’s disease,
  adjunct to levodopa, COMT inhibitors or MAOIs
  in advanced disease (Not FDA approved)


Clinical Pearls
• Under evaluation for restless leg syndrome
• Valvular heart disease
• Recalled
                            Product information: Neupro ® Transdermal Patch, rotigotine transdermal
                            patch, Schwarz Pharma, Co Claire, Ireland, 2007.
Which of the following patient
   populations should use
   Neupro® with caution?
                      Answer Now!                        :15

1. Patients with hepatic
     insufficiency due to
     inability to metabolize     20%   20%   20%   20%   20%

     drug
2.   Patients with renal
     insufficiency due to
     inability to excrete drug
3.   Patients with bipolar
     disorder as it may
     exacerbate symptoms
     of depression or mania
4.   Ischemic heart disease
     patients as it may          1     2      3     4     5

     worsen symptoms of
     angina
5.   CHF patients due to
 Neupro® is titrated up to
stronger doses how often?
                 Answer Now!                                    :15


1.   Daily              20%     20%      20%       20%       20%

2.   Weekly
3.   Every 2 weeks
4.   Monthly
5.   Every 6 weeks




                        Daily   Weekly   Every 2   Monthly   Every 6
                                         weeks               weeks
Armodafinil
     Nuvigil™
 Manufacterur: Cephalon
                                Armodafinil (Nuvigil™)
        Therapeutic Class Indications
           Amphetamine related, CNS stimulant


        Indications
           Improve wakefulness in patients with
            excessive sleepiness associated with
            obstructive sleep apnea/hypopnea syndrome
            (OSAHS), narcolepsy and shift work sleep
            disorder (SWSD)



Product information: Nuvigil oral tablets, armodafinil oral tablets,
Cephalon, Frazer, PA, 2007.
                                Armodafinil (Nuvigil™)
        Mechanism of                                                   Pharmacokinetics
          action                                                       • Absorption: Maximum
        • R-enantiomer of                                                concentration in 2 hrs
            modafinil                                                  • Distribution: 60% bound
        •   Exact mechanism                                              to albumin
            unknown                                                    • Metabolism: Liver
                                                                         -   Amine hydrolysis
                                                                       • Elimination: Urine
                                                                         -   Terminal half-life 15 hrs




Product information: Nuvigil oral tablets, armodafinil oral tablets,
Cephalon, Frazer, PA, 2007.
        Armodafinil (Nuvigil™)
Dosing and Administration
• Narcolepsy: 150mg or 250mg in the morning
• Obstructive sleep apnea: 150mg or 250mg in
  the morning
• Shift work sleep disorder: 150mg orally daily
  approximately 1 hour prior to start of work shift
• Dose Adjustments: Elderly and severe hepatic
  impairment

Cost
• Unavailable
Formulary status: Nonformulary          Product information: Nuvigil oral tablets,
                                        armodafinil oral tablets, Cephalon, Frazer, PA,
Formulary Alternatives: Modafinil       2007.



Federally controlled substance (C-IV)
        Armodafinil (Nuvigil™)
Contraindications
• Hypersensitivity to modafinil and
 armodafinil


Precautions
• Rash, Steven Johnson’s Syndrome (SJS),
  angioedema and anaphylaxis reactions,
• Elderly and severe hepatic impairment with
  or without cirrhosis
• Left ventricular hypertrophy or mitral valve
  prolapse
• Pregnancy Category C          Product information: Nuvigil oral tablets, armodafinil oral tablets,
                                Cephalon, Frazer, PA, 2007.
                                Armodafinil (Nuvigil™)
        Drug Interactions
        • CYP3A4 inhibitors or inducers
        • Moderate inhibition of CYP2C19

        Adverse Effects
        • Cardiovascular
        • Dermatologic
        • Gastrointestinal
        • Neurological
        • Psychiatric
        • Other
Product information: Nuvigil oral tablets, armodafinil oral tablets,
Cephalon, Frazer, PA, 2007.
                Armodafinil (Nuvigil™)
          Hirshkowitz M, et al. Respiratory Medicine. 2007; 101: 616-27.
Objective        Evaluate the efficacy of armodafinil as adjunct
                 treatment to (nCPAP) in patients with OSAHS
Design           Multicenter, randomized, double-blind, placebo-
                 controlled, parallel-group clinical trial
Study Arms       Armodafinil 150 mg or placebo once daily
Results          Maintenance of Wakefulness Test (MWT) sleep latency
                 increased in the armodafinil group and decreased in
                 placebo group (p = 0.0003)
                 Improved clinical condition (p = 0.0069), episodic
                 secondary memory (p = 0.0102) and reduced fatigue (p
                 < 0.05) compared to placebo
Conclusion       Adjunct treatment with armodafinil significantly
                 improved alertness and the impact of sleepiness on
                 daily activities.
                                Armodafinil (Nuvigil™)
        Patient Education
        • Effects on level of wakefulness
        • Rash, depression, anxiety or signs of
            psychosis or mania
        •   Past history of drug abuse




Product information: Nuvigil oral tablets, armodafinil oral tablets,
Cephalon, Frazer, PA, 2007.
                                Armodafinil (Nuvigil™)
        Place in Therapy
         Adjunct to standard treatments to improve
            wakefulness in patients with excessive
            sleepiness due to OSAHS, narcolepsy or
            SWSD


        Clinical Pearls
         Cephalon about to lose modafinil patent


Product information: Nuvigil oral tablets, armodafinil oral tablets,
Cephalon, Frazer, PA, 2007.
In which of the following
  conditions would dose
 reduction of Nuvigil™ be
     recommended?
                  Answer Now!                     :15


1. Severe renal          20%    20%   20%   20%   20%
     impairment
2.   Severe hepatic
     impairment
3.   Elderly
4.   1 and 2
5.   2 and 3




                          1     2      3     4     5
What is the DEA schedule of
          Nuvigil™?
            Answer Now!                      :15


1.   CII            20%   20%    20%   20%   20%
2.   CIII
3.   CIV
4.   CV
5.   CVI




                    CII   CIII   CIV    CV    CVI
 Lapatinib
         Tykerb®
Manufacterur: GlaxoSmithKline
         Lapatinib (Tykerb®)
Therapeutic Class
• Antineoplastic agent

Indications
• Breast cancer, advanced or metastatic, HER2
  overexpression, in combination with capecitabine
  after prior therapies




                                   Product Information: Tykerb® oral tablets, lapatinib
                                   oral tablets. GlaxoSmithKline, Research Triangle
                                   Park, NC, 2007.
           Lapatinib (Tykerb®)
Mechanism of action       Pharmacokinetics
• Tyrosine kinase         • Absorption:
 inhibitor of epidermal     Bioavailability
 growth factor receptor     incomplete and variable
 (EFGR, HER1) and         • Distribution: Protein
 human epidermal            bound > 99% to
 receptor type 2 (HER2)     albumin and alpha-1
                            acid glycoprotein
                          • Metabolism: CYP3A4,
                            CYP3A5, CYP2C19 and
                            CYP2C8
                          • Elimination: 27% fecal,
                            < 2% renal
                             • Elimination half-life
                                24 hours at steady
                                state
                                       Lapatinib (Tykerb®)
       Dosing and Administration
       • 1250 mg orally once daily in combination
         with capecitabine 2000 mg/m2/day orally
       • Dose Adjustments:
               •       Left ventricular ejection fraction (LVEF) <
                       40%
               •       Hepatic Impairment
               •       Strong CYP3A4 Inhibitors/Inducers
               •       Other toxicities

       Cost (AWP)
       • Tykerb® 250 mg tablet, 150 count $3,625.00
       Formulary status: Nonformulary
Product Information: Tykerb® oral tablets, lapatinib oral tablets.

       Formulary alternatives: None
GlaxoSmithKline, Research Triangle Park, NC, 2007.
                                       Lapatinib (Tykerb®)
       Contraindications
       • Specific contraindications have not been
         determined

       Precautions
       • CYP3A4 inhibitors or inducers
       • Hepatic impairment
       • Interstitial lung disease or pneumonitis
       • Decreases in LVEF
       • QT prolongation
Product Information: Tykerb® oral tablets, lapatinib oral tablets.
GlaxoSmithKline, Research Triangle Park, NC, 2007.
                                       Lapatinib (Tykerb®)
       Drug Interactions
       • CYP3A4 inhibitors/inducers

       Adverse Effects
       • Cardiovascular
       • Gastrointestinal
       • Skin and subcutaneous tissue
       • Musculoskeletal
       • Respiratory
       • Psychiatric
       • Hematologic
       • Hepatic
Product Information: Tykerb® oral tablets, lapatinib oral tablets.
GlaxoSmithKline, Research Triangle Park, NC, 2007.
              Lapatinib (Tykerb®)
 Geyer CE, Forster J, Lindquist D, et al. N Engl J Med. 2006; 355: 2733.

Objective     Evaluate the efficacy of lapatinib in combination
              with capecitabine versus capecitabine monotherapy
              in women with HER2-positive, trastuzumab-
              refractory metastatic breast cancer
Design        Prospective, randomized, open-label, phase III
              clinical trial
Study Arms    Lapatinib plus capecitabine or capecitabine alone
Results       Median time to disease progression was 8.4 versus
              4.4 months in combination therapy versus
              monotherapy
Conclusion    Lapatinib therapy with capecitabine is superior to
              capecitabine monotherapy in patients with
              refractory, HER2-positive advanced breast cancer
                                       Lapatinib (Tykerb®)
       Patient Education
       • Shortness of breath, palpitations and/or fatigue
       • Take at least 1 hour before or 2 hours after a meal
            and as a single dose and never as a divided dose




Product Information: Tykerb® oral tablets, lapatinib oral tablets.
GlaxoSmithKline, Research Triangle Park, NC, 2007.
          Lapatinib (Tykerb®)
Place in Therapy
• In metastatic breast cancer with HER2
  overexpression after failure of an anthracycline and
  taxane-based chemotherapy regimen in
  combination with capecitabine
• Non-FDA approved uses
   • Breast cancer, Inflammatory, relapsed or
     refractory
   • Metastatic breast cancer, HER2 overexpression,
     first-line
   • Metastatic breast cancer, HER2 overexpression,
     refractory, monotherapy
   • Metastatic breast cancer, HER2 overexpression
     - Secondary malignant neoplasm of brain
                              Product Information: Tykerb® oral tablets, lapatinib oral tablets.
                              GlaxoSmithKline, Research Triangle Park, NC, 2007.
                                       Lapatinib (Tykerb®)
       Clinical Pearls
       • “The Value Meal”
       • Administer as a single dose
       • Since usually given in combination with
            capecitabine, one must consider BOTH
            medications when counseling




Product Information: Tykerb® oral tablets, lapatinib oral tablets.
GlaxoSmithKline, Research Triangle Park, NC, 2007.
In which patient population is
  Tykerb® indicated for use?
                      Answer Now!                          :15

1. Patients with breast cancer
     as monotherapy
2.   Colorectal cancer patients    20%   20%   20%   20%   20%
     with metastases
3.   Patient with breast cancer
     with brain metastases
4.   Liver cancer patients
     currently receiving
     chemotherapy with
     capcitabinne
5.   Patients with advanced or
     metastatic breast cancer,
     HER2 overexpression
     receiving chemotherapy with
     capcitabine

                                   1     2      3     4     5
Tykerb® is dispensed as
 which of the following
     formulations?
                   Answer Now!                     :15


1. Oral solution          20%   20%   20%   20%   20%
2. Tablet
3. Intramuscular
     injection
4.   Patch
5.   Intravenous
     infusion




                          1      2     3     4     5
Lisdexamfetamine
       Vyvanse®
     Manufacterur: Shire
              Lisdexamfetamine (Vyvanse®)
       Therapeutic Class
         • Amphetamine, CNS stimulant


       Indications
          Treatment of ADHD


       Mechanism of action
         • Prodrug of dextroamphetamine
         • Inhibits reuptake of and increases the release of
           norepinephrine and dopamine
Product Information: Vyvanse ® capsule, lisdexamfetamine
capsules, Shire Inc, Wayne, PA, 2007.
     Lisdexamfetamine (Vyvanse®)
Pharmacokinetics
• Absorption: Rapidly absorbed
• Metabolism: Converted to dextroamphetamine and L-
    lysine in first pass metabolism
•   Elimination: 96% urine as 42% amphetamine

Dosing and Administration
• Initiate therapy at 30 mg/day for children 6 to 12
     • Increased by 20 mg/day weekly
     • Maximum daily dose in children is 70 mg/day
•   May be taken with or without food
•   Capsule contents may be dissolved in a glass
    of water
                                 Product Information: Vyvanse ® capsule, lisdexamfetamine
                                 capsules, Shire Inc, Wayne, PA, 2007.
              Lisdexamfetamine (Vyvanse®)
       Cost (AWP)
       • Vyvanse® 30 mg capsule, 100 capsules: $426.68
       • Vyvanse® 50 mg capsule, 100 capsules: $426.68
       • Vyvanse® 70 mg capsule, 100 capsules: $426.68

       Formulary status: Nonformulary
       Formulary Alternatives: Methylphenidate
       Federally controlled substance (CII)



Product Information: Vyvanse ® capsule, lisdexamfetamine
capsules, Shire Inc, Wayne, PA, 2007.
              Lisdexamfetamine (Vyvanse®)
       Contraindications
       • Advanced arteriosclerosis or symptomatic
           cardiovascular disease, moderate to severe
           hypertension
       •   Hyperthyroidism
       •   Hypersensitivity to sympathetic amines
       •   Glaucoma
       •   History or drug abuse
       •   Within 14 days following administration of
           monoamine oxidase inhibitors



Product Information: Vyvanse ® capsule, lisdexamfetamine
capsules, Shire Inc, Wayne, PA, 2007.
              Lisdexamfetamine (Vyvanse®)
       Precautions
       • Cardiac concerns
       • Sudden death, stroke and myocardial
           infarction
       •   Increases in blood pressure and heart rate
       •   May exacerbate pre-existing psychosis or
           bipolar disorder
       •   Pregnancy Category C



Product Information: Vyvanse ® capsule, lisdexamfetamine
capsules, Shire Inc, Wayne, PA, 2007.
    Lisdexamfetamine (Vyvanse®)
Drug Interactions
• Inhibits monoamine oxidase
• May potentiate the analgesic effects of meperidine
    and adrenergic effects of norepinephrine
•   Chlorpromazine, lithium carbonate and haloperidol
    will inhibit amphetamines

Adverse Effects
• Cardiovascular
• Central nervous system
• Gastrointestinal
• Allergic
• Endocrine
                                Product Information: Vyvanse ® capsule, lisdexamfetamine
                                capsules, Shire Inc, Wayne, PA, 2007.
      Lisdexamfetamine (Vyvanse®)
     Biederman J, et al. Clinical Therapeutics. 2007; 29: 450-63.

Objective     Assess the efficacy and tolerability of
              lisdexamfetamine in school-aged children with ADHD
Design        Prospective, multicenter, randomized, double-blind,
              forced dose, parallel group phase III clinical study
Study Arms    Lisdexamfetamine 30, 50 or 70 mg or placebo once
              daily for 4 weeks
Results       Significant improvements in ADHD-RS-IV scores were
              seen with all doses of lisdexamfetamine as compared
              to placebo (p < 0.001)
Conclusion    Once-daily treatment with lisdexamfetamine in school-
              aged children was effective and was as tolerable as
              other currently marketed extended-release products
              Lisdexamfetamine (Vyvanse®)
       Patient Education
       • Heart-related issues
       • Psychiatric disorders
       • May lead to dependence and/or abuse
       • Slowing of growth (height and weight) in children
       • Seizures
       • Vision changes



Product Information: Vyvanse ® capsule, lisdexamfetamine
capsules, Shire Inc, Wayne, PA, 2007.
              Lisdexamfetamine (Vyvanse®)
       Place in Therapy
       • Treatment of ADHD
             •       Long-term effects of amphetamines have not
                     been established


       Clinical Pearls
       • Reevaluation of ADHD



Product Information: Vyvanse ® capsule, lisdexamfetamine
capsules, Shire Inc, Wayne, PA, 2007.
Vyvanse® is contraindicated
  with use of the following
       drug classes?
                   Answer Now!                      :15


1. Monoamine oxidase
                           20%   20%   20%   20%   20%
     inhibitors
2.   Selective serotonin
     reuptake inhibitors
3.   HMG CoA reductase
     inhibitors
4.   Beta-2 agonists
5.   Alpha-2 agonists


                           1     2      3     4     5
Food has which of the
 following effects on
Vyvanse® absorption?
                  Answer Now!                         :15

1. Increases systemic
     absorption, increasing
     systemic drug            20%   20%   20%   20%   20%
     exposure
2.   Inhibits drug
     absorption, decreasing
     systemic drug
     exposure
3.   Prolongs time to
     maximum serum
     concentrations by 1
     hour
4.   Increases serum          1     2      3     4     5



     concentration levels

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:31
posted:5/16/2010
language:English
pages:138