Solifenacin Pharmacology

Solifenacin is a bladder antimuscarinic medication most commonly used for overactive bladder (OAB) with symptoms of urinary frequency, urgency, and urge incontinence. Like other agents in its class, understanding the pharmacology can help anticipate potential side effects, drug interactions, and downstream prescribing problems.

Mechanism of Action

Solifenacin selectively blocks muscarinic M3 receptors in the bladder detrusor muscle. Inhibiting these receptors reduces involuntary bladder contractions, increases bladder capacity, and delays the urge to void. While M3 selectivity may theoretically reduce side effects compared to nonselective antimuscarinics, in clinical practice, many anticholinergic effects still occur.

Adverse Effects

Because muscarinic receptors are present throughout the body, solifenacin can lead to a range of anticholinergic adverse effects:

  • Dry mouth – among the most common, can be significant enough to cause dental issues with long-term use.
  • Constipation – especially problematic in older adults; severe cases may require hospitalization.
  • Blurred vision – due to impaired accommodation.
  • Cognitive impairment – increased risk in older adults, particularly with cumulative anticholinergic burden.
  • Urinary retention – paradoxical worsening in patients with bladder outlet obstruction.

Drug Interactions

  • CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir) can increase solifenacin plasma concentrations, raising the risk of side effects.
  • Other anticholinergics (e.g., diphenhydramine, tricyclic antidepressants, other bladder antimuscarinics) can result in additive toxicity and higher anticholinergic burden.
  • QT-prolonging drugs (e.g., amiodarone, certain fluoroquinolones) may have additive cardiac risk since solifenacin has been associated with QT prolongation in rare cases.

Prescribing Cascade Examples

  1. Constipation → Laxative initiation – A patient starts solifenacin for OAB and develops severe constipation, leading to chronic use of stimulant laxatives like senna or bisacodyl.
  2. Dry mouth → Mouth rinse prescription – Dry mouth is treated with saliva substitutes or prescription rinses, instead of reassessing the anticholinergic therapy.
  3. Cognitive decline → Donepezil initiation – In older adults, cognitive impairment may be mistaken for dementia progression, leading to cholinesterase inhibitor prescribing—directly counteracting the anticholinergic effects of solifenacin.

Solifenacin can be an effective treatment for OAB, but the risk of adverse effects and prescribing cascades—especially in older adults—cannot be ignored. Healthcare professionals should regularly review the indication, monitor for anticholinergic burden, and look for opportunities to deprescribe when appropriate.

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Darifenacin Pharmacology Podcast – Episode 308

On this podcast episode, I discuss darifenacin pharmacology, adverse effects, drug interactions and much more.

CYP3A4 and CYP2D6 are important enzymes in relation to darifenacin. I breakdown the importance of these enzymes and how they can impact drug therapy.

Darifenacin has anticholinergic activity but affects the central nervous system less than other agents in its class such as oxybutynin and tolterodine.

Darifenacin’s pharmacology is selective for the Muscarinic-3 (M3) receptor in bladder tissue which helps reduce the risk for CNS adverse effects.

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Alfuzosin Pharmacology Podcast

On this podcast episode, I discuss alfuzosin pharmacology, adverse effects, drug interactions, and much more!

Alfuzosin is an alpha blocker used to help relieve the symptoms of BPH.

Low blood pressure is a possible adverse effect of alfuzosin and is more likely when combined with PDE-5 inhibitors like sildenafil.

CYP3A4 is an important enzyme in the metabolism of alfuzosin. Inhibitors of CYP3A4 can raise concentrations and increase the chance of alfuzosin toxicity.

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Vibegron Pharmacology Podcast

On this episode of the Real Life Pharmacology podcast, I discuss vibegron pharmacology, adverse effects, drug interactions and more!

I spend some time comparing and contrasting vibegron to mirabegron. Both are beta-3 agonists used for overactive bladder.

Vibegron dosing is very simple. It is dosed once daily with no alternative dosage forms available. The starting dose is the target dose.

Being primarily excreted in the feces and urine, vibegron doesn’t have many drug interactions.

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Trospium Pharmacology

On this episode, I discuss trospium pharmacology, adverse effects, and important drug interactions you should know.

Trospium chloride (Sanctura) is a bladder antimuscarinic or anticholinergic. It blocks the action of acetylcholine in bladder smooth muscle. It is used for urinary frequency and overactive bladder. The immediate-release formulation is taken twice a day. There is an extended-release version that is more expensive.

As its classification suggests it is going to have anticholinergic effects that include dry eyes, dry mouth, constipation, urinary retention, GI tract slowing down, CNS sedation, and increased risk of falls. Compared to older bladder anticholinergics such as oxybutynin or tolterodine there is less CNS penetration. Hopefully, this will cause the patient to experience fewer CNS side effects. A downside to this being a newer medication is that it costs more.

Trospium is on the BEERS list. Look for medications started after the trospium that indicate anticholinergic side effects such as saliva substitutes, an increase in BPH medications, artificial tears, or constipation medications.

It should be administered on an empty stomach as food can block absorption. If the patient is currently taking it with food and seeing results there is no need to change how they are taking it.

Trospium is not metabolized by CYP enzymes minimizing drug interactions. Most interactions occur because of additive effects. Avoid using it with other medications on the BEERS list, especially other anticholinergic medications. Be cautious using other medications with sedative effects and CNS depression (benzodiazepines, sleep medications, opioids, alcohol) as they may have additive effects.

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Phenazopyridine Pharmacology

On this episode, I discuss phenazopyridine pharmacology, adverse effects, and potential drug interactions.

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Oxybutynin Pharmacology

On this episode, I discuss oxybutynin pharmacology, drug interactions, and adverse effects.

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Tamsulosin Pharmacology

On this episode of the RLP podcast, I discuss tamsulosin pharmacology.

Tamsulosin inhibits alpha receptors which helps improve urine flow in patients with BPH.

As an off-label use, you may see tamsulosin used to try to aid in the passage of renal stones.

Tamsulosin concentrations may be increased by CYP3A4 inhibitors and reduced by CYP3A4 inducers.

I discuss important drug interactions on the podcast, be sure to check out my latest project which is a 200+ page book on managing drug interactions in primary care.

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Mirabegron Pharmacology

Mirabegron is a beta-3 agonist that can help relax bladder smooth muscle and manage symptoms of overactive bladder.

Mirabegron inhibits CYP2D6 which can negatively impact the effectiveness of tamoxifen. I discuss this in greater detail in the podcast.

Tramadol and codeine effectiveness can be impacted by mirabegron. Be aware of this when using this medication.

By inhibiting CYP2D6, mirabegron can increase the concentrations of many psychotropic medications such as fluoxetine, aripiprazole, clozapine, and paroxetine. I discuss this further in this episode of the podcast.

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