Rapaflo silodosin

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Rapaflo - silodosin

• Manufacturer Watson
• FDA Approval Date October 8, 2008

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Rapaflo - silodosin Clinical Application

• Indications
• BPH
• Place in therapy
• Could be an alternative to other similar agents
  due to having fewer drug interactions

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Rapaflo - silodosin Clinical Application

• Contraindications
• Severe renal impairment (CrCl lt 30 mL/min)
• Severe hepatic impairment (Child-Pugh score 10)
• Concomitant administration with 3A4 inhibitors
  (e.g. ketoconazole, clarithromycin, itraconazole,
  ritonavir)
• Warnings
• Orthostatic hypotension
• Precautions
• Prostate carcinoma
• Intraoperative Floppy Iris Syndrome (IFIS)

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Rapaflo - silodosin Drug Facts

• Pharmacology
• a-1 blocker leading to smooth muscle relaxation
  allowing for increased urine flow and reduction
  in BPH symptoms

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Rapaflo - silodosin Drug Facts

• Pharmacokinetics
• A Bioavailability of 32
• D Vd 49.5 L/kg 97 protein binding
• M Primarily CYP3A4
• E t1/2 13 hours 55 feces 34 urine

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Rapaflo - silodosinDrug Interactions

• Drug Interactions Object Drugs
• None

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Rapaflo - silodosin Drug Interactions

• Drug Interactions Precipitant Drugs
• Moderate and Strong 3A4 inhibitors
• ? AUC 3 fold
• P-gp Inhibitors
• ?

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Rapaflo - silodosin Adverse Effects

• Common Adverse Effects
• Serious Adverse Events

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Rapaflo - silodosin Monitoring Parameters

• Efficacy Monitoring
• Blood pressure (supine and standing), urine flow,
  symptom improvement
• Toxicity Monitoring
• None

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Rapaflo - silodosin Prescription Information

• Dosing
• 8 mg with food
• 4 mg with food
• Moderate impairment (CrCl 30-50 mL/min)
• Cost
• Currently unavailable

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Rapaflo - silodosin Trial Information

• Early efficacy of silodosin in patients with
  lower urinary tract symptoms suggestive of benign
  prostatic hyperplasia.
• Int J Urol 200815992-6
• Objective To evaluate the early efficacy of
  silodosin (i.e. in the first 1-2 weeks) in the
  treatment of BPH/LUTS patients.
• Treatment Group Included patients gt65 y/o who
  complained of LUTS suggestive of BPH according to
  the judgment of a physician they recruited, had
  an IPSS 8 and a QOL index of 2
• Average patient was 68 y/o with total IPSS of 19
  (almost severe 36 pts had a severe score) with a
  QOL score of 4.7 and a prostate volume of 32.6 mL

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Rapaflo - silodosin Trial Information

• Treatment Group Excluded pts suffering from
  neurogenic bladder dysfunction, bladder neck
  contracture, urethral stricture, bladder
  calculus, chronic bacterial prostatitis, active
  UTIs, prostate cancer, h/o pelvic radiotherapy,
  prostatectomy, clinically significant CV disease,
  severe renal dysfunction, severe hepatic
  illnesses, pts receiving concomitant
  alpha-blockers, anti-cholinergics,
  antidepressants, sex hormone agents

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Rapaflo - silodosin Trial Information

• Comments about a priori assumptions and analysis
  type alpha 0.05
• What is the intervention? Phase III study all
  pts given 4 mg BID (no placebo) pts given IPSS
  and QOL modified indexes during treatment
• How long was the treatment? 28 days

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Rapaflo - silodosin Trial Information

• Primary Endpoint change in IPSS, QOL score
• Secondary Endpoints

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Rapaflo - silodosin Trial Information

• Adverse Effect Analysis 6 pts experienced AE- 2
  with abnormal ejaculation, 2 with diarrhea, 1
  with tinnitus, 1 with lightheadedness all
  resolved after silodosin was stopped
• Study Limitations only informational for how
  quickly pt responded to therapy, no comparison to
  other alpha blockers or a placebo (not a
  randomized controlled trial) severe group of
  men no urodynamics performed

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Rapaflo - silodosin Trial Information

• Conclusion Total IPSS decreased at day 1 and
  continued to decline throughout the 4 weeks.
• At day 3 45.6 (31/68) good responders, 54.4
  (37/68) bad responders
• Of these at day 28 80.6 (or 25/31) continued to
  respond well and 54.1 (or 20/37) continued to
  respond badly
• At day 7 62 (42/68) good responders, 38
  (26/68) bad responders
• Of these at day 28 78.6 (or 33/42) continued to
  respond well and 65.4 (or 17/26) continued to
  respond badly

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Rapaflo - silodosin Summary

• Rapaflo? (silodosin) is a new non-selective
  alpha-blocker with no significant benefit over
  other alpha-blockers in BPH treatment.
• Silodosin requires no dose titration and has very
  little orthostatic hypotension, but the high
  incidence of retrograde ejaculation (28) is
  concerning.
• One potential advantage of silodosin is the few
  drug interaction. It could be seen as an option
  for patients using multiple medications.

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Rapaflo - silodosin References

• Rapaflo PI. Watson Pharmaceuticals, Inc. Revised
  September 2008.
• Takao T, et al. Early efficacy of silodosin in
  patients with lower urinary tract symptoms
  suggestive of benign prostatic hyperplasia. Int J
  Urol 200815992-6.