Toviaz fesoterodine

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Toviaz - fesoterodine

• Manufacturer Pfizer
• FDA Approval Date October 31, 2008

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Toviaz - fesoterodine Clinical Application

• Indications
• Overactive bladder (OAB) with symptoms of urge
  urinary incontinence, urgency, and frequency
• Place in therapy
• May be used first-line for patients with OAB or
  when other therapies have failed to improve
  symptoms
• Patients who have not responded to Detrol LA
  (tolterodine) are NOT likely to respond to
  Toviaz (fesoterodine)

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Toviaz - fesoterodine Clinical Application

• Contraindications
• Urinary retention
• Gastric retention
• Narrow angle glaucoma
• Hypersensitivity (to drug and/or ingredients)
• Precautions
• Use caution in patients with bladder outlet
  obstruction (BOO)
• Use caution in severe constipation
• Use caution in patients with myasthenia gravis
• Doses gt 4mg not recommended if patient is on a
  strong CYP3A4 inhibitor (ketoconazole,
  clarithromycin)

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Toviaz - fesoterodine Drug Facts

• Pharmacology
• Competitive muscarinic receptor antagonist
• Pro-drug
• Rapidly metabolized to 5-hydroxy methyl
  tolterodine
• The same active metabolite as Detrol LA
  (tolterodine)

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Toviaz - fesoterodine Pharmacology
tolterodine
fesoterodine
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Toviaz - fesoterodine Drug Facts

• Pharmacokinetics
• A Bioavailability of active metabolite 52
  Max plasma levels reached in 5 hrs
• D 50 bound to plasma proteins Vd 169L
• M Rapidly hydrolyzed to active metabolite then
  hepatic metabolism via CYP2D6 and CYP3A4
• E 70 of active metabolite excreted in urine
  terminal t1/2 after oral administration is 7 hrs

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Toviaz - fesoterodine Drug Interactions

• Drug Interactions Object Drugs
• No clinically significant interactions listed

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Toviaz - fesoterodine Drug Interactions

• Drug Interactions Precipitant Drugs
• CYP3A4 inhibitors ? exposure to fesoterodine and
  potentially ? side effects
• Keep fesoterodine dose at 4mg when given with
  strong inhibitors
• Antimuscarinic agents ? anticholinergic side
  effects
• Ex dry mouth, sedation, constipation, urinary
  retention

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Toviaz - fesoterodine Adverse Effects
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Toviaz - fesoterodine Monitoring Parameters

• Efficacy Monitoring
• Reduction in episodes of urge urinary
  incontinence
• Reductions in urinary frequency
• Toxicity Monitoring
• An overdose of fesoterodine may result in severe
  anticholinergic effects
• In the event of an overdose, ECG monitoring is
  recommended along with supportive care

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Toviaz - fesoterodine Prescription Information

• Dosing
• Usual dose - 4mg once daily
• May increase to 8mg once daily as tolerated
• Renal impairment
• Mild-moderate - No adjustment needed
• Severe - Max dose 4mg/day
• Hepatic impairment
• Mild-moderate - No adjustment needed
• Severe - NOT recommended (not studied)

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Toviaz - fesoterodineStudies Supporting Approval

• Two, randomized, double-blind, placebo controlled
  studies in subjects with OAB
• Inclusion criteria symptoms of OAB for gt 6
  months, at least 8 micturitions/day, at least 6
  urinary urgency episodes or 3 urge incontinence
  episodes per 3-day period
• Intervention N554 on placebo, N554 on
  fesoterodine 4mg, and N556 on fesoterodine 8mg
  all on therapy for 12-wks

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Toviaz - fesoterodine Results
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Toviaz - fesoterodine Conclusion

• Compared with placebo, fesoterodine at doses of
  4mg and 8mg reduces the number of urge
  incontinence episodes and number or micturitions
  per 24 hours and may also increase the voided
  volume per micturition.

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Toviaz - fesoterodine Summary

• Toviaz, fesoterodine, is a new competitive
  muscarinic receptor antagonist indicated for OAB
• At doses of 4 and 8mg daily, Toviaz may improve
  symptoms of urge urinary incontinence, urgency
  and frequency
• Monitor for anticholinergic SEs, especially in
  patients taking other anticholinergic medications
  or strong CYP3A4 inhibitors

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Toviaz - fesoterodine Place in Therapy

• Fesoterodine may be prescribed first-line for OAB
  or as an alternative for patients who have not
  responded to other medications
• However, fesoterodine is a pro-drug rapidly
  metabolized to the same active metabolite as that
  of Detrol LA (tolterodine)
• Patients who have not responded to tolterodine
  may not respond to fesoterodine

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Toviaz - fesoterodine References

• www.toviaz.com
• Toviaz package insert. Pfizer Labs. Oct. 2008.