Tolterodine is a tertiary amine and serves as an antimuscarinic medication indicated in patients with an overactive bladder (OAB), including increased urgency and frequency to urinate.[1] This drug serves as a gold standard treatment for OAB, is regarded as the third most favorable antimuscarinic, and has a decreased level of adverse effects when compared to other alternatives, such as oxybutynin.[2][3] Patient tolerance of tolterodine is significantly better oxybutynin, with regards to the incidence and severity of dry mouth. Also, fewer dropouts of patients occur with tolterodine as compared to oxybutynin. Clinical studies have shown that combination therapy of tolterodine with an alpha-blocker, such as tamsulosin, significantly improves symptoms.[4] Compared to placebo, tolterodine 4 mg did not prove to be effective in reducing nocturia episodes.[5] In comparison to tolterodine, a β-adrenoceptor agonist called mirabegron is better tolerated by patients. It has a higher patient preference and shows better improvements in symptoms of OAB. Although both treatments are well tolerated, the anticholinergic side effects of tolterodine were higher than those of mirabegron.[1]

Tolterodine is an antimuscarinic medication that selectively and competitively binds to muscarinic M3 receptors in the bladder, thereby decreasing bladder contraction by decreasing in detrusor muscle tone and increasing internal urethral sphincter tone. Upon administration, it undergoes first-pass metabolism, where CYP2D6 metabolizes the drug to its active form, 5-hydroxymethyl.[6]

Tolterodine administration occurs in two different ways – orally or transdermally as a topical gel formulation (proniosomes).

Oral

Orally, it is available in two forms: immediate-release (IR) and extended-release (ER) (i.e., administering tolterodine ER 4mg once daily is pharmacokinetically equivalent to tolterodine ER 2mg twice daily). 

Adults

The initial dosage for IM begins at 2mg, twice daily, and has shown to decrease the number of micturition every 24 hours, whereas EM is given as 4mg once a day.[7] The IM and ER dose can be decreased to 1mg twice a day and 2mg once a day, respectively, depending on the individual reaction to the drug and tolerability.  

A clinical study regarding male overactive bladder symptoms shows an increased effect of tolterodine ER in comparison to tolterodine IM.[3] Tolterodine EM also manifests less adverse effects.[2]

Pediatric

Doses from 0.03 to 0.12mg/kg is considered to be safe for children from the ages of 1 month to 15 years. A clinical study showed that the drug was well-tolerated, and there was no relationship between the dose levels and adverse events; however, complete safety and efficacy have not been established.[8]

Transdermal, topical gel formation (proniosomes)

A study on transdermal patches shows evidence of having similar effects as the oral dose form, but it improved upon to decrease the adverse effects of the drug, such as dry mouth and constipation. Both transdermal and oral administration of tolterodine had a similar level of inhibitory effects in the bladder.[9] Additionally, this method of administration was effective for over 72 hours after the application because of the constant entry into the systemic circulation through the patch.

Adverse effects of tolterodine are significantly lower than that of other antimuscarinic drugs indicated for the same use.  

However, the following effects are still present:

• Dry mouth
• Dry eyes
• Constipation
• Headache
• Blurred vision
• Drowsiness

Elderly patients who use multiple medications are more at risk for adverse effects because of drug-to-drug interactions.

Considering more clinically relevant adverse effects, tolterodine has the potential to cause disturbances in the cardiac and central nervous systems. Because of muscarinic receptors in the heart, low doses of tolterodine can cause an increase in heart rate by acting on M1 and leading to tachycardia, palpitations, and cardiac rhythm disorders. Due to this potential adverse effect, the suggestion is that those with any heart-related problems use caution when taking this drug. In the central nervous system, all five subtypes of the muscarinic receptors are present, and because of the lipophilicity of tolterodine, it can cross the blood-brain barrier. This situation can give rise to CNS problems such as depression, cognitive impairment, confusion, or the most common effect, dizziness. Therefore, any patients with pre-existing neurological conditions should be cautious, and further advisement from their physician is strongly recommended. 

Tolterodine, along with other OAB drugs, is contraindicated in patients who are at risk for or currently have gastric retention or uncontrolled angle-closure glaucoma. It is also not for use in patients with myasthenia gravis, severe constipation, intestinal atony, ulcerative colitis, or those with bladder outflow obstructions.[10]

Because of its tertiary property, tolterodine should be monitored and used with caution if the patient has a neurological disorder or neurodegenerative disease. Additionally, if a patient is about to perform a potentially dangerous task, then this medication should not be administered, as it can cause drowsiness and blurred vision.