What are the differences between oxybutynin (Ditropan) extended release and immediate release formulations?

Oxybutynin Extended Release vs. Immediate Release Formulations

Oxybutynin extended release (ER) is marketed as Ditropan XL or Lyrinel XL, while the immediate release (IR) formulation is known as Ditropan, with the ER formulation offering once-daily dosing compared to multiple daily doses required with IR.

Formulation Differences

Extended Release (ER)

• Brand names: Ditropan XL, Lyrinel XL 1
• Dosing frequency: Once daily 1, 2
• Technology: Uses OROS (Osmotic Release Oral System) technology 2, 3
• Mechanism: Osmotic pressure delivers drug at controlled rate over 24 hours 3
• Available doses: 5-30 mg once daily (greater dosing flexibility) 1

Immediate Release (IR)

• Brand name: Ditropan 2
• Dosing frequency: Multiple times daily (typically 3-4 times daily) 4, 5
• Technology: Standard tablet formulation 3
• Available doses: Typically 5 mg tablets taken multiple times per day 5

Pharmacokinetic Differences

Plasma Concentration Profiles

• ER formulation:

  • Slow rise in plasma concentration over 4-6 hours 3
  • Maintains steady concentrations for up to 24 hours 3
  • Lower peak plasma concentrations (Cmax) 4
  • Reduced fluctuation between peak and trough levels (78% vs 371% with IR) 5

• IR formulation:

  • Rapid rise in plasma concentration within first hour 5
  • Higher peak concentrations (Cmax) 4
  • Significant fluctuations between doses 5

Bioavailability

• ER formulation has 153% higher bioavailability of parent drug (oxybutynin) compared to IR 5
• ER formulation has 69% lower bioavailability of the metabolite N-desethyloxybutynin compared to IR 5
• The difference in bioavailability is likely due to reduced first-pass metabolism with ER formulation 4, 5

Clinical Implications

Efficacy

• Both formulations show similar efficacy in reducing urinary urge incontinence episodes 1, 2
• Both effectively decrease weekly total incontinence episodes and micturition frequency 1

Tolerability

• ER formulation is associated with fewer anticholinergic side effects, particularly dry mouth 4, 5
• The reduced side effect profile is likely due to lower metabolite (N-desethyloxybutynin) exposure, as the metabolite appears to contribute significantly to dry mouth 4
• Both formulations have typical anticholinergic side effects (dry mouth, constipation, somnolence, blurred vision) 3

Adherence

• Once-daily dosing with ER formulation may improve medication adherence, particularly in elderly patients on multiple medications 3
• Approximately two-thirds of patients prescribed ER oxybutynin continue taking the medication after 6 months 2

Mechanism of Action (Both Formulations)

Both formulations contain oxybutynin chloride, which:

• Exerts direct antispasmodic effect on smooth muscle 6
• Inhibits muscarinic action of acetylcholine on smooth muscle 6
• Increases bladder capacity 6
• Diminishes frequency of uninhibited detrusor muscle contractions 6
• Delays initial desire to void 6

Practical Considerations

• ER formulation is particularly beneficial for patients who:
  • Experience significant dry mouth with IR formulation
  • Have difficulty adhering to multiple daily dosing schedules
  • Are elderly or on multiple medications
• IR formulation may be preferred when:
  • More flexible dosing is needed
  • Cost is a significant concern
  • Rapid onset of action is desired

The choice between ER and IR formulations should consider the patient's tolerance of side effects, dosing preference, and cost considerations, with the ER formulation generally offering better tolerability and convenience.