2008-2009 New Drug Approvals

1,493 views

Published on

0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,493
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
20
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide

2008-2009 New Drug Approvals

  1. 1. 2008-2009 New Drug Approvals Samuel Gurevitz PharmD, CGP Assistant Professor Physician Assistant Program Butler University College of Pharmacy and Health Sciences
  2. 2. Financial Disclosure <ul><li>I have no actual or potential conflict of interest in relation to this program. </li></ul>
  3. 3. Educational Objectives <ul><li>After participating in this activity, pharmacists should be able to: </li></ul><ul><ul><li>Discuss the clinical indications, the various mechanisms of action of the drugs approved in 2008 and first quarter of 2009. </li></ul></ul><ul><ul><li>Recognize the clinically relevant drug interactions and common adverse effects as well as monitoring parameters. </li></ul></ul><ul><ul><li>Recognize the contraindications and precautions </li></ul></ul><ul><ul><li>Explain the dosing and recommended dosage adjustments </li></ul></ul><ul><ul><li>Compare to other members of the therapeutic class </li></ul></ul>
  4. 4. FDA Ratings: NDA Chemical Type <ul><li>1 = new molecular entity </li></ul><ul><li>2 = new ester, new salt </li></ul><ul><li>3 = new dosage form </li></ul><ul><li>4 = new combination </li></ul><ul><li>5 = new formulation or new manufacture </li></ul>
  5. 5. FDA Ratings: Review Classification <ul><li>P = priority review* </li></ul><ul><li>S = standard review </li></ul><ul><li>O = Orphan Designation </li></ul>*significant improvement compared to marketed products, in the treatment, diagnosis, or prevention of disease)
  6. 6. Desvenlafaxine (Pristiq ®) <ul><li>FDA rating: 1 S </li></ul><ul><li>MOA: selective serotonin and norepinephrine reuptake inhibitor (SNRI) </li></ul><ul><li>Indication: major depressive disorder </li></ul><ul><li>Pharmacokinetics </li></ul><ul><ul><li>metabolized by conjugation, 3A4 minor metabolic pathway </li></ul></ul><ul><ul><li>45% excreted unchanged in urine </li></ul></ul>Prestiq (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; February 2009
  7. 7. Desvenlafaxine (Pristiq ®) <ul><li>Precautions </li></ul><ul><ul><li>Should not be used with a hypersensitivity to desvenlafaxine (major metabolite) and venlafaxine </li></ul></ul><ul><ul><li>Concomitant use with monoamine oxidase inhibitor (MAOI) is contraindicated </li></ul></ul><ul><ul><ul><li>Should not be started within 14 days of stopping a MOAI </li></ul></ul></ul><ul><ul><ul><li>MAOI should not be started within 7 days of stopping desvenlafaxine </li></ul></ul></ul>Prestiq (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; February 2009
  8. 8. Desvenlafaxine (Pristiq ®) <ul><li>Precautions </li></ul><ul><ul><li>Increased risk of suicidal thinking and behavior in children, adolescents, and young adults </li></ul></ul><ul><ul><li>May cause sustained elevated blood pressure </li></ul></ul><ul><ul><li>May cause elevated total cholesterol and triglyceride </li></ul></ul>Prestiq (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; February 2009
  9. 9. Desvenlafaxine (Pristiq ®) <ul><li>Precautions </li></ul><ul><ul><li>Mania or hypomania </li></ul></ul><ul><ul><li>Seizures </li></ul></ul><ul><ul><li>Hyponatremia </li></ul></ul><ul><ul><li>Narrow angle glaucoma </li></ul></ul>Prestiq (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; February 2009
  10. 10. Desvenlafaxine (Pristiq ®) <ul><li>Drug interactions </li></ul><ul><ul><li>Other serotonergic drugs: serotonin syndrome </li></ul></ul><ul><ul><li>3A4 potent inhibitors: may result in higher concentrations </li></ul></ul><ul><li>Adverse effects </li></ul><ul><ul><li>Nausea, constipation, dizziness </li></ul></ul><ul><ul><li>Hyperhidrosis </li></ul></ul><ul><ul><li>Anxiety, Insomnia </li></ul></ul><ul><ul><li>Decreased appetite </li></ul></ul>Prestiq (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; February 2009
  11. 11. Desvenlafaxine (Pristiq ®) <ul><li>Dosage </li></ul><ul><ul><li>50 mg daily with or without food </li></ul></ul><ul><ul><ul><li>Do not crush </li></ul></ul></ul><ul><ul><ul><li>No additional benefit with a higher dose </li></ul></ul></ul><ul><ul><ul><li>50 mg daily in patients with CrCl 30-50 ml/min </li></ul></ul></ul><ul><ul><ul><li>50 mg every other day with CrCl < 30ml/min </li></ul></ul></ul><ul><ul><ul><li>Do not abruptly discontinue </li></ul></ul></ul><ul><li>Available: 50 and 100 mg extended-release tablets </li></ul>Prestiq (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; February 2009
  12. 12. Milnacipran (Savella ®) <ul><li>FDA rating: 1 S </li></ul><ul><li>MOA: selectively inhibits reuptake of serotonin and norepinephrine </li></ul><ul><li>Indication: fibromyalgia </li></ul><ul><ul><li>Exact MOA for reducing pain in patients with fibromyalgia is unknown </li></ul></ul><ul><li>Pharmacokinetics </li></ul><ul><ul><li>Eliminated primarily by renal excretion </li></ul></ul>Savella (package insert). St. Louis, MO: Forest Pharmaceuticals Inc; January 2009
  13. 13. Milnacipran (Savella ®) <ul><li>Precaution </li></ul><ul><ul><li>Increased risk of suicidal thinking and behavior in children, adolescents, and young adults </li></ul></ul><ul><ul><li>Concomitant use with monoamine oxidase inhibitor (MAOI) is contraindicated </li></ul></ul><ul><ul><ul><li>Should not be started within 14 days of stopping a MOAI </li></ul></ul></ul><ul><ul><ul><li>MAOI should not be started within 5 days of stopping milnacipran </li></ul></ul></ul>Savella (package insert). St. Louis, MO: Forest Pharmaceuticals Inc; January 2009
  14. 14. Milnacipran (Savella ®) <ul><li>Precaution </li></ul><ul><ul><li>Contraindicated in uncontrolled narrow angle glaucoma </li></ul></ul><ul><ul><li>May cause elevated blood pressure and heart rate </li></ul></ul><ul><ul><li>May cause increases in LFT </li></ul></ul><ul><ul><ul><li>Avoid in patients with substantial alcohol use or evidence of chronic liver disease </li></ul></ul></ul>Savella (package insert). St. Louis, MO: Forest Pharmaceuticals Inc; January 2009
  15. 15. Milnacipran (Savella ®) <ul><li>Precaution </li></ul><ul><ul><li>Use cautiously in patients with history of seizures </li></ul></ul><ul><ul><li>Hyponatremia </li></ul></ul><ul><ul><li>Abnormal bleeding </li></ul></ul>Savella (package insert). St. Louis, MO: Forest Pharmaceuticals Inc; January 2009
  16. 16. Milnacipran (Savella ®) <ul><li>Adverse Effects </li></ul><ul><ul><li>Nausea </li></ul></ul><ul><ul><li>Constipation </li></ul></ul><ul><ul><li>Hot flush </li></ul></ul><ul><ul><li>Hyperhidrosis </li></ul></ul><ul><li>Drug interactions </li></ul><ul><ul><li>Other serotonergic drugs; serotonin syndrome </li></ul></ul><ul><ul><li>Aspirin, NSAIDs and other drugs that affect coagulation; increased bleeding </li></ul></ul>Savella (package insert). St. Louis, MO: Forest Pharmaceuticals Inc; January 2009
  17. 17. Milnacipran (Savella ®) <ul><li>Dosage: 50 mg tablet twice a day with or without food; maximum dose 200 mg/day </li></ul><ul><ul><li>Start with 12.5 mg daily (day 1), 12.5 mg twice a day for days 2-3, 25 mg twice a day for days 4-7, and 50 mg twice a day on day 8 </li></ul></ul><ul><ul><li>CrCl 5 to 29 ml/min: maintenance dose reduced by 50% to 25 mg twice a day </li></ul></ul><ul><ul><li>Discontinuation: gradual dose reduction </li></ul></ul>Savella (package insert). St. Louis, MO: Forest Pharmaceuticals Inc; January 2009
  18. 18. Comparisons of SNRIs GAD = general anxiety disorder, SAD = social anxiety disorder, DPH = diabetic peripheral neuropathy Drug FDA-Approved Indications CYP 405 inhibition Comments Desvenlafaxine (Prestiq) Depression Not significant Monitor BP Potent 3A4 inhibitors may result in higher desvenlafaxine concentration Active metabolite of vanlafaxine Venlafaxine Depression, GAD SAD, Panic Disorder 2D6 (weak) Monitor BP Reduce dose by 25% for CrCl < 70ml/min Milnacipran (Savella) Fibromyalgia Not significant CrCl 5 to 29 ml/min: maintenance dose reduced by 50% to 25 mg twice a day Duloxetine (Cymbalta) Depression GAD, DPN, fibromyalgia 2D6 (moderate) Monitor BP Not recommended in CrCl < 30 ml/min
  19. 19. Fesoteridone (Toviaz ®) <ul><li>FDA rating: 1 S </li></ul><ul><li>MOA: muscarinic receptor antagonist </li></ul><ul><li>Indication: treatment of overactive bladder with symptoms or urinary incontinence, urgency, and frequency </li></ul><ul><li>Pharmacokinetics </li></ul><ul><ul><li>Fesoterodine is a prodrug. It is broken down into its active metabolite, 5-hydroxymethyl tolterodine, by plasma esterases </li></ul></ul><ul><ul><li>5-hydroxy-methyl tolterodine metabolized by 2D6 and 3A4 to inactive metabolites </li></ul></ul>Toviaz (package insert). New York, NY: Pfizer Labs; November 2008
  20. 20. Fesoteridone (Toviaz ®) <ul><li>Precautions </li></ul><ul><ul><li>Contraindicated in urinary retention, gastric retention, uncontrolled narrow angle glaucoma </li></ul></ul><ul><ul><li>Mild to moderate renal impairment, urinary obstruction </li></ul></ul><ul><ul><li>Myasthenia gravis </li></ul></ul><ul><ul><li>Extreme heat can induce hyperthermia </li></ul></ul>Toviaz (package insert). New York, NY: Pfizer Labs; November 2008
  21. 21. Fesoteridone (Toviaz ®) <ul><li>Drug interactions </li></ul><ul><ul><li>2D6 and 3A4 inhibitors may cause higher concentrations </li></ul></ul><ul><ul><ul><li>Do not exceed 4 mg with potent 3A4 </li></ul></ul></ul><ul><ul><li>Other anticholinergic/antimuscarinic drugs </li></ul></ul><ul><li>Adverse effects </li></ul><ul><ul><li>Anticholinergic effects </li></ul></ul><ul><ul><li>Increase in liver enzymes </li></ul></ul><ul><ul><li>QT prolongation, dose dependent increase heart rate </li></ul></ul>Toviaz (package insert). New York, NY: Pfizer Labs; November 2008
  22. 22. Fesoteridone (Toviaz ®) <ul><li>Dosage </li></ul><ul><ul><li>Starting dose 4 mg daily; based on response and tolerability can be increased to 8 mg daily </li></ul></ul><ul><ul><ul><li>Do not crush, chewed, or divided </li></ul></ul></ul><ul><ul><li>Should not receive more than 4 mg daily with a CrCl < 30 ml/min </li></ul></ul><ul><li>Available: 4 and 8 mg extended tablets </li></ul>Toviaz (package insert). New York, NY: Pfizer Labs; November 2008
  23. 23. Antimuscarinic Medications for Overactive Bladder Toviaz (package insert). New York, NY: Pfizer Labs; November 2008 Pharmacist Letter/Prescriber’s Letter: January 2008 Volume 24 Number 24018 Drug Muscarinic Receptor Specificty Incidence of Adverse Effects Comments Fesoterodine (Toviaz) M2 and M3 (?) Dry mouth 19% Constipation 4% Do not exceed 4 mg with 3A4 inhibitors and CrCl < 30 ml/mim Tolterodine (Detrol LA) M2 and M3 Dry mouth 23% Constipation 6% Lower dose with 3A4 inhibitors and CrCl < 30 ml/min Oxybutynin LA (patch, gel) Primarily M3 Dry mouth 61% Constipation 13% Lower Adverse effects with patch and gel Darifenacin (Enablex) M3 Dry mouth 20% Constipation 15% Do not exceed 7.5 mg with 3A4 inhibitors Solfenacin (Vesicare) Primarily M3 Dry mouth 10.9% Constipation 5.4% Do not exceed 5 mg with 3A4 inhibitors and CrCl < 30 ml/mim Trospium (Sanctura or Sacnctura XR) M2 and M3 Dry mouth 20% Constipation 10% Do not exceed 20 mg if CrCl < 30 ml/min
  24. 24. Silodosin (Rapaflo ® ) <ul><li>FDA rating: 1 S </li></ul><ul><li>MOA: Alpha-1a antagonist </li></ul><ul><li>Indication: treatment of benign prostate hyperplasia </li></ul><ul><li>Pharmacokinetics: </li></ul><ul><ul><li>Metabolized by 3A4 </li></ul></ul><ul><ul><li>P-glycoprotein substrate </li></ul></ul>Rapaflo (package insert). Corona, CA: Watson Labs; October 2008
  25. 25. Silodosin (Rapaflo ® ) <ul><li>Precaution: patients with orthostatic hypotension and vertigo </li></ul><ul><li>Drug interactions </li></ul><ul><ul><li>Drugs that inhibit CYP 3A4 and P-glycoprotein: increase concentration </li></ul></ul><ul><ul><li>Concurrent antihypertensive therapy or phosphodiesterase-5 inhibitors: increase risk of orthostatic hypertension </li></ul></ul>Rapaflo (package insert). Corona, CA: Watson Labs; October 2008
  26. 26. Silodosin (Rapaflo ® ) <ul><li>Adverse effects: </li></ul><ul><ul><li>Dizziness, orthostatic hypotension </li></ul></ul><ul><ul><li>Diarrhea </li></ul></ul><ul><ul><li>Nasopharyngitis </li></ul></ul><ul><ul><li>Nasal congestion </li></ul></ul><ul><li>Dosage: 8 mg capsule daily with a meal </li></ul><ul><ul><li>CrCl 30 to 50 ml/min: 4 mg daily with a meal </li></ul></ul><ul><ul><li>CrCl < 30 ml/min: contraindicated </li></ul></ul>Rapaflo (package insert). Corona, CA: Watson Labs; October 2008
  27. 27. Comparison of Alpha1-Blockers Pharmacist Letter/Prescriber’s Letter: September 2003 Volume 19 Number 190909 Rapaflo (package insert). Corona, CA: Watson Labs; October 2008 Alfuzosin Doxazosin Silodosin Tamsulosin Terazosin FDA-Indication BPH BPH HTN BPH BPH BPH HTN Requires Dose Titration No Yes No Yes Yes Renal Precaution Yes No Yes No No Drug Interactions 3A4 inhibitors PDE-5 inhibitors PDE-5 inhibitors 3A4 inhibitors P-glycoprotein substrate PDE-5 inhibitors PDE-5 inhibitors PDE-5 inhibitors Affects QT Interval Yes No No No No Comments Selective for alpha-1a Nonselectivealpha-1 Selective for alpha-1a Selective for alpha-1a Nonselective for alpha-1
  28. 28. Lacosamide (Vimpat ®) <ul><li>FDA rating: 1 S </li></ul><ul><li>MOA </li></ul><ul><ul><li>Selectively enhances slow inactivation of voltage-gated channels and inhibits repetitive neuronal firing </li></ul></ul><ul><ul><li>Binds to collapsing response mediator protein-2 (CRMP-2) </li></ul></ul><ul><ul><ul><li>Phosphoprotein expressed in nervous system involved in neuronal differentiation and control of axonal outgrowth </li></ul></ul></ul>Vimpat (package insert). Smyrna, GA: UCB Inc; October 2008
  29. 29. Lacosamide (Vimpat ®) <ul><li>Indication: adjunctive treatment of partial-onset seizures in patients > 17 years </li></ul><ul><li>Pharmacokinetics </li></ul><ul><ul><li>IV and oral are bioequivalent </li></ul></ul><ul><li>Precautions </li></ul><ul><ul><li>Increased risk of suicidal thinking and behavior </li></ul></ul><ul><ul><li>Should be tapered slowly </li></ul></ul>Vimpat (package insert). Smyrna, GA: UCB Inc; October 2008
  30. 30. Lacosamide (Vimpat ®) <ul><li>Drug interactions </li></ul><ul><ul><li>No significant drug interactions </li></ul></ul><ul><ul><li>Caution with drugs that prolong the QT interval </li></ul></ul><ul><li>Adverse effects </li></ul><ul><ul><li>Dizziness, vertigo, ataxia </li></ul></ul><ul><ul><li>Blurred vision </li></ul></ul><ul><ul><li>Elevated liver enzymes </li></ul></ul>Vimpat (package insert). Smyrna, GA: UCB Inc; October 2008
  31. 31. Lacosamide (Vimpat ®) <ul><li>Dosage </li></ul><ul><ul><li>Starting dose is 50 mg twice a day, may be increased weekly by 100 mg until recommended dose of 200 to 400 mg/day </li></ul></ul><ul><ul><ul><li>Maximum dose of 300 mg/day recommended for severe renal impairment or mild to moderate hepatic impairment </li></ul></ul></ul><ul><li>Available: 50, 100, 150, and 200 mg tablets </li></ul>Vimpat (package insert). Smyrna, GA: UCB Inc; October 2008
  32. 32. Methylnaltrexone (Relistor ®) <ul><li>FDA rating: 1 S </li></ul><ul><li>MOA: peripheral selective mu-opioid antagonist </li></ul><ul><ul><li>Does not cross the blood-brain barrier </li></ul></ul><ul><ul><li>Does not impact the opioid mediated analgesic effects </li></ul></ul><ul><li>Indications: treatment of mediated opioid-induced constipation, when response to laxatives has not been sufficient </li></ul>Relistor (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; April 2008 Guay DRP. Consultant Pharmacist 2009;24:210-26
  33. 33. Methylnaltrexone (Relistor ®) <ul><li>Precautions: suspected GI obstruction (do not use) </li></ul><ul><li>Adverse effects: </li></ul><ul><ul><li>Abdominal pain </li></ul></ul><ul><ul><li>Flatulence </li></ul></ul><ul><ul><li>Nausea </li></ul></ul><ul><ul><li>Dizziness </li></ul></ul><ul><ul><li>Diarrhea </li></ul></ul>Relistor (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; April 2008 Guay DRP. Consultant Pharmacist 2009;24:210-26
  34. 34. Methylnaltrexone (Relistor ®) <ul><li>Dosage: Usual schedule is one dose subcutaneous every other day as needed </li></ul><ul><ul><li>Patients 38 to less than 62 kg: 8mg </li></ul></ul><ul><ul><li>Patients 62 to 114 kg: 12 mg </li></ul></ul><ul><ul><li>Patients < 38 or > 114 kg: 0.15 mg/kg </li></ul></ul><ul><ul><li>Patients with CrCl < 30 ml/min dosage should be reduced by 50% </li></ul></ul><ul><ul><li>Use beyond 4 months has not been studied </li></ul></ul><ul><li>Available: 12mg/0.6ml single use vial </li></ul>Relistor (package insert). Philadelphia, PA: Wyeth Pharmaceuticals Inc; April 2008 Guay DRP. Consultant Pharmacist 2009;24:210-26
  35. 35. Tetrabenazine (Xenazine ®) <ul><li>FDA rating: 1 P O </li></ul><ul><li>MOA: centrally acting depletor of monoamines (dopamine, serotonin, norepinephrine, and histamine) from nerve terminals </li></ul><ul><ul><li>It inhibits vesicular monoamine transporter type 2, resulting in decreased uptake of monoamines in synaptic vesicles and depletion of monoamine stores </li></ul></ul>T.Yero, et al. P&T. 2008;33:690-94 Xenazine (pakage insert). Deerfield, IL: Ovation Pharmaceuticals Inc.; September 2008
  36. 36. Tetrabenazine (Xenazine ®) <ul><li>Indications: Treatment of chorea associated with Huntington’s disease </li></ul><ul><li>Pharmacokinetics: </li></ul><ul><ul><li>Metabolized by 2D6 </li></ul></ul><ul><li>Precautions </li></ul><ul><ul><li>Contraindicated in patients treated inadequately for depression </li></ul></ul><ul><ul><li>Should not be used in patients taking monoamine oxidase inhibitors or reserpine </li></ul></ul>T.Yero, et al. P&T. 2008;33:690-94 Xenazine (pakage insert). Deerfield, IL: Ovation Pharmaceuticals Inc.; September 2008
  37. 37. Tetrabenazine (Xenazine ®) <ul><li>Precautions </li></ul><ul><ul><li>Contraindicated in patients treated inadequately for depression </li></ul></ul><ul><ul><li>Should not be used in patients taking monoamine oxidase inhibitors or reserpine </li></ul></ul><ul><ul><li>Avoid in patients with long QT syndrome or other drugs that prolong QTc interval </li></ul></ul><ul><li>Adverse Effects: depression, akathisia, sedation, anxiety, insomnia </li></ul>T.Yero, et al. P&T. 2008;33:690-94 Xenazine (pakage insert). Deerfield, IL: Ovation Pharmaceuticals Inc.; September 2008
  38. 38. Tetrabenazine (Xenazine ®) <ul><li>Drug interactions </li></ul><ul><ul><li>2D6 inhibitors (Paroxetine and fluoxetine) </li></ul></ul><ul><ul><ul><li>Increase concentrations dose should be reduced by 50% </li></ul></ul></ul><ul><ul><li>Drugs known to prolong QTc interval </li></ul></ul>T.Yero, et al. P&T. 2008;33:690-94 Xenazine (pakage insert). Deerfield, IL: Ovation Pharmaceuticals Inc.; September 2008
  39. 39. Tetrabenazine (Xenazine ®) <ul><li>Dosage: recommended maximum dose is 25 mg tablet daily; doses above 100 mg not recommended </li></ul><ul><ul><li>Starting dose 12.5 mg daily, after one week 12.5 mg twice a day, titrate weekly by 12.5 mg until desired effect </li></ul></ul><ul><ul><li>If 37.5 to 50 mg/day is needed, it should be given in three divided doses </li></ul></ul><ul><ul><li>Patients requiring greater than 50 mg/day should undergo genotyping for CYP2D6 </li></ul></ul>T.Yero, et al. P&T. 2008;33:690-94 Xenazine (pakage insert). Deerfield, IL: Ovation Pharmaceuticals Inc.; September 2008
  40. 40. Febuxostat (Uloric ®) <ul><li>FDA rating: 1 S </li></ul><ul><li>MOA: inhibits xanthine oxidase </li></ul><ul><li>Indication: chronic management of hyperuricemia inpatients with gout </li></ul><ul><ul><li>Not recommended for asymptomatic hyperuricemia </li></ul></ul>Uloric (pakage insert). Deerfield, IL: Takeda Pharmaceuticals America Inc.; February 2009
  41. 41. Febuxostat (Uloric ®) <ul><li>Pharmacokinetics </li></ul><ul><ul><li>Metabolized </li></ul></ul><ul><ul><ul><li>Conjugation by uridine diphosphate glucuronosyltransferase </li></ul></ul></ul><ul><ul><ul><li>CYP1A2, 2C8, and 2C9 </li></ul></ul></ul><ul><li>Adverse Effects </li></ul><ul><ul><li>Liver function abnormalities, arthralgia (joint pain), and rash </li></ul></ul>Uloric (pakage insert). Deerfield, IL: Takeda Pharmaceuticals America Inc.; February 2009
  42. 42. Febuxostat (Uloric ®) <ul><li>Precautions </li></ul><ul><ul><li>Gout flares </li></ul></ul><ul><ul><li>Cardiovascular thromboembolic events </li></ul></ul><ul><ul><ul><li>Compared to allopurinol and febuxostat 80 mg </li></ul></ul></ul><ul><ul><li>Increase in liver enzymes </li></ul></ul><ul><ul><li>Contraindicated in patients being treated with azathioprine, mercaptopurine, or theophylline </li></ul></ul>Uloric (pakage insert). Deerfield, IL: Takeda Pharmaceuticals America Inc.; February 2009
  43. 43. Febuxostat (Uloric ®) <ul><li>Dosage: recommended at 40 to 80 mg daily </li></ul><ul><ul><li>Start at 40 mg tablet daily </li></ul></ul><ul><ul><li>Patients not achieving a serum uric acid less than 6 mg/dL after 2 weeks with 40 mg increase to 80 mg daily </li></ul></ul><ul><ul><li>Caution in patients with CrCl < 30 ml/min </li></ul></ul>Uloric (pakage insert). Deerfield, IL: Takeda Pharmaceuticals America Inc.; February 2009
  44. 44. Comparison: Allopurinol and Febuxostat Uloric (pakage insert). Deerfield, IL: Takeda Pharmaceuticals America Inc.; February 2009 Pharmacist’s letter/Prescriber’s Letter. April 2009: Volume 25; Number 250413 Allopurinol Febuxostat MOA Inhibits xanthine oxidase Inhibits xanthine oxidase (more selective) Cost (month) < $16.00 $160 Uric acid < 6 mg/dL 36% - 42% (300 mg) 45% (40mg) 67% - 74% (80 mg) Renal adjustment Yes CrCl 10-20 ml/min; 200mg CrCl < 10 ml/min; 100mg No (caution in CrCl <30 ml/min) Comments 600mg reduced uric acid (< 6mg/dL) by 85% Offers an alternative to allopurinol Discontinuation due to LFTs greater than allopurinol Febuxostat 40mg (1.8%), 80mg (1.2%) vs Allopurinol (0.9%)
  45. 45. Tapentadol (Nucynta ®) <ul><li>FDA rating: 1 S </li></ul><ul><li>MOA: two mechanisms of action </li></ul><ul><ul><li>Binds to and activates mu-opioid receptors in the CNS </li></ul></ul><ul><ul><li>Norepinephrine reuptake inhibitor; inhibits transmission of pain from spinal cord and affect activity at parts of the brain that control how pain is perceived </li></ul></ul><ul><li>Indication: relief of moderate to severe pain in adults 18 yrs or older </li></ul>www.clinicalpharmacology.com www.jnj.com/connect/news/all/20080509
  46. 46. Tapentadol (Nucynta ®) <ul><li>Pharmacokinetics </li></ul><ul><ul><li>No active metabolites; metabolized by glucuronidation </li></ul></ul><ul><ul><li>3% renally excreted unchanged </li></ul></ul><ul><ul><li>69% renally excreted as conjugates </li></ul></ul><ul><li>Adverse effects </li></ul><ul><ul><li>Nausea, vomiting, dizziness, somnolence </li></ul></ul>www.clinicalpharmacology.com www.jnj.com/connect/news/all/20080509
  47. 47. Tapentadol (Nucynta ®) <ul><li>Precautions </li></ul><ul><ul><li>Elderly </li></ul></ul><ul><ul><li>COPD, sleep apnea </li></ul></ul><ul><ul><li>Patients with head injury </li></ul></ul><ul><ul><li>Patients with biliary tract disease </li></ul></ul><ul><li>Drug Interactions </li></ul><ul><ul><li>Serotonergic drugs: Serotonin syndrome </li></ul></ul><ul><li>Available: 50 mg, 75 mg, 100 mg dose </li></ul>www.clinicalpharmacology.com www.jnj.com/connect/news/all/20080509
  48. 48. Degarilex (No Trade Name) <ul><li>FDA rating: 1 S </li></ul><ul><li>MOA: GnRH receptor antagonists </li></ul><ul><ul><li>It binds reversibly to the pituitary GnRH receptors, thereby reducing the release of gonadotropins and consequently testosterone </li></ul></ul><ul><li>Indication: Treatment of patients with advanced prostate cancer </li></ul><ul><li>Pharmacokinetics: not a substrate, inducer, or inhibitor of CYP450 </li></ul>Degarilex (pakage insert). Saint-Prex, Switzerland : Ferring Pharmaceuticals Inc.; December 2008
  49. 49. Degarilex <ul><li>Adverse effects </li></ul><ul><ul><li>Injection site reactions </li></ul></ul><ul><ul><li>Hot flashes </li></ul></ul><ul><ul><li>Increased weight </li></ul></ul><ul><ul><li>Increase LFTs and gamma-glutamyltranferase </li></ul></ul><ul><li>Drug interactions: unlikely </li></ul><ul><li>Precautions: </li></ul><ul><ul><li>QT prolongation </li></ul></ul>Degarilex (pakage insert). Saint-Prex, Switzerland : Ferring Pharmaceuticals Inc.; December 2008
  50. 50. Degarilex <ul><li>Dosage: Treatment started with 240mg given as two subcutaneous injections of 120mg each </li></ul><ul><ul><li>Followed by 80 mg administered every 28 days </li></ul></ul><ul><ul><li>Available in 80 mg/vial and 120mg/vial </li></ul></ul>Degarilex (pakage insert). Saint-Prex, Switzerland : Ferring Pharmaceuticals Inc.; December 2008
  51. 51. Other GnRH Antagonists and Agonist used for Prostate Cancer <ul><li>Aberilex (Plenaxis ®): antagonists </li></ul><ul><li>Leuprolide: agonist </li></ul><ul><li>Goserelin (Zoladex®): agonist </li></ul><ul><li>Advantage of these agents over GnRH agonists (goserelin, leuprolide) would be they lack initial flare stimulation and induce quickly a hypogonadal situation </li></ul>
  52. 52. Degarelix vs Leuprolide Percentage Attaining Testosterone < 50 ng/dL within the First 28 Days Klotz L, et al. BJU Int. 2008. 102:1531-8 Degarelix (240/160 mg) N=202 Degarelix (240/160 mg) N=207 Leuprolide (7.5 mg ) N=201 Day 1 44% 52% 0% Day 3 96% 96% 0% Day 7 99% 99% 1% Day 14 99% 99% 18% Day 28 99% 100% 100%
  53. 53. Dexlansoprazole (Kapidex ® ): Comparison to Other Proton Pump Inhibitors Patients treated with proton pump inhibitors and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time Drug Formulation Drug Interactions Dexlansoprazole Dual Delayed Release (1 st peak 1 to 2 hrs after and 2 nd peak within 4 to 5 hrs) Inhibits absorption: iron salts, ketoconazole; Do not use Atazanavir Lansoprazole Delayed Release Peaks at 1.7 hrs Inhibits absorption: iron salts, ketoconazole; Do not use Atazanavir Esomeprazole Delayed Release Peaks at 1.5 hrs Inhibits absorption: iron salts, ketoconazole; Do not use Atazanavir Omeprazole Zegerid Delayed Release 0.5 – 3 hrs Peaks 10 – 90 min (30 min) Inhibits absorption: iron salts, ketoconazole, Atazanavir (do not use) Inhibits metabolism: Diazepam Pantoprazole Delayed Release Peaks at 2.5 hrs Inhibits absorption: iron salts, ketoconazole; Do not use Atazanavir Rabeprazole Delayed Release Peaks 2 – 5 hrs Inhibits absorption: iron salts, ketoconazole; Do not use Atazanavir
  54. 54. Comparison of Clevidipine vs Other IV Agents to Lower Blood Pressure Phung OJ, et al. Formulary 2009;44:102-7 Characteristics Clevidipine Nicardipine NTG Esmolol Labetalol MOA DHP CCB DHP CCB Vasodilator B-Blocker B-blocker and alpha-blocker Onset of Action 2-4 min 5-10 min 1-5 min 1-2 min 5-10 min Duration of Action 5-15 min 1-4 h 3-5 min 10-20 min 3-6 h Adverse Effects HA, tachycardia hypotension N & V HA, N & V edema, tachycardia flushing HA, vomiting, tachycardia Methemoglobin-emia Bronchospasm, bradycardia, hypotension Bronchospasmbradycardia, hypotension
  55. 55. Other New Approvals Drugs @ FDA : Information about FDA-approved prescription, over-the-counter, and discontinued drug products www.accessdata.fda.gov/scripts/cder/drugsatfda Drug FDA Category MOA Indication Alvimopan* (Entereg) * Hospital use only 1S Peripheral acting mu-opioid receptor antagonist Acceleration of the time to upper and lower GI recovery following partial large or small bowel resection with primary anastomosis Bendamustine (Treanda) 1P,O Akylating agent Chronic lymphocytic leukemia Clevidipine Cleviprex) 1S Dihydropyrydine calcium channel blocker Hypertension when oral therapy is not possible or desirable Difluprednate (Durezol) 1P Topical corticosteroid Inhibits inflammation Treatment of inflammation and pain associated with ocular surgery
  56. 56. Other New Approvals Drugs @ FDA : Information about FDA-approved prescription, over-the-counter, and discontinued drug products www.accessdata.fda.gov/scripts/cder/drugsatfda Drug FDA Category MOA Indication Eltrombopag (Promact) 1P, O Thrombopoietin receptor agonist, stimulates platelet production Treatment of chronic immune thrombocytopenia purpura (ITP) in patients with insufficient response to corticosteroids, immunoglobulins, or splenectomy Romiplostim (Nplate) 1P, O Thrombopoietin receptor agonist, stimulates platelet production Treatment of chronic immune thrombocytopenia purpura (ITP) in patients with insufficient response to corticosteroids, immunoglobulins, or splenectomy
  57. 57. Other New Approvals Drugs @ FDA : Information about FDA-approved prescription, over-the-counter, and discontinued drug products www.accessdata.fda.gov/scripts/cder/drugsatfda Drug FDA Category MOA Indication Etravirine 1P Non-nucleoside reverse transciptase In combination with other antiretovirals for HIV-1 among treatment experienced adults who have evidence of resistance Certolizum Pegol (Cimzia) 1S Humanized monoclonal antibiody Fab’ fragment that binds and neutralizes TNF-alpha Reducing signs and symptoms of Crohn’s disease and maintaining clinical response in moderate to severe disease when conventional therapy fails Rufinamide (Banzel) 1S Modulates sodium channels, prolonging the inactive state of the channel Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome
  58. 58. Questions or Comments

×