DETRUSITROL SR 4MG

Indications

• Overactive bladder
• Urinary incontinence
• Urgency and frequency of urination

Dosage

Children: Refer to the BNF for Children.

Adults: The usual starting dose is 2 mg twice daily, which may be increased to a maximum of 4 mg per day based on individual response.

Mechanism of action

Tolterodine and its active metabolite, 5-hydroxymethyltolterodine, function as competitive antagonists at muscarinic receptors. This antagonism leads to inhibition of bladder contraction, a decrease in detrusor pressure, and incomplete bladder emptying.

Pharmacodynamics

As a competitive muscarinic receptor antagonist, tolterodine specifically inhibits cholinergic activity in the bladder, resulting in reduced urinary urgency and frequency. After oral administration, tolterodine is metabolized in the liver to form its active metabolite, which has similar antimuscarinic properties. This mechanism contributes to increased residual urine and decreased detrusor pressure.

Pharmacokinetics

Tolterodine is well absorbed after oral administration, with peak plasma concentrations occurring within 1-2 hours. It undergoes extensive first-pass metabolism in the liver, predominantly via CYP2D6 and CYP3A4 enzymes, leading to the formation of its active metabolite. The elimination half-life is approximately 2-4 hours for tolterodine and longer for its metabolite. Excretion occurs mainly through urine.

Contra-indications

• Urinary retention
• Severe gastric retention
• Uncontrolled narrow-angle glaucoma
• Hypersensitivity to tolterodine or any of its components

Adverse effects

• Dry mouth
• Constipation
• Dizziness
• Somnolence
• Blurred vision
• Nausea
• Abdominal pain

Interactions

• dacomitinib+tolterodine: Severe (increases exposure)
• clarithromycin+tolterodine: Severe (increases exposure)
• eliglustat+tolterodine: Moderate (increases exposure)
• clozapine+tolterodine: Unknown (additive effect)
• cobicistat+tolterodine: Unknown (increases exposure)
• idelalisib+tolterodine: Unknown (increases exposure)
• antipsychotics, second generation+tolterodine: Unknown (additive effect)

Precautions

• Use with caution in patients with hepatic impairment
• Caution is advised in patients with a history of urinary retention
• Consider monitoring in elderly patients due to increased sensitivity to antimuscarinic effects

Pregnancy

Tolterodine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. There is limited data on its use in pregnant women.

Breast-feeding

Tolterodine is excreted in breast milk. Caution should be exercised when administering tolterodine to breastfeeding women.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Formulations

• Immediate-release tablets
• Extended-release capsules

Indications

• Urinary frequency
• Urgency
• Incontinence associated with overactive bladder
• Neurogenic bladder instability

Dosage

Children: The use of tolterodine in children is not well-established; refer to the BNF for Children for specific dosing information.

Adults: For immediate-release tablets, the usual starting dose is 2 mg taken twice daily, which may be increased to a maximum of 4 mg twice daily if necessary. For modified-release capsules, the recommended dose is 4 mg once daily, which may be increased to a maximum of 8 mg once daily depending on clinical response.

Mechanism of action

Tolterodine selectively antagonizes muscarinic receptors, primarily M2 and M3 subtypes, which are involved in the contraction of the detrusor muscle of the bladder. By inhibiting these receptors, tolterodine reduces involuntary bladder contractions and increases bladder storage capacity.

Pharmacodynamics

The pharmacodynamic effects of tolterodine include reduced urinary urgency and frequency. It improves bladder control and decreases the episodes of incontinence. The onset of action generally occurs within a few hours after administration, with a peak effect seen within 1-2 hours for immediate-release formulations.

Pharmacokinetics

Tolterodine is well-absorbed after oral administration, with peak plasma concentrations achieved within 1-2 hours. It undergoes hepatic metabolism via CYP2D6 and CYP3A4, with a resultant half-life of approximately 2-3 hours for immediate-release forms and up to 6-8 hours for extended-release forms. The drug is primarily excreted in urine as metabolites, with less than 10% excreted unchanged.

Contra-indications

• Hypersensitivity to tolterodine or any excipients in the formulation
• Severe hepatic impairment
• Urinary retention
• Uncontrolled narrow-angle glaucoma

Adverse effects

• Dry mouth
• Constipation
• Dizziness
• Fatigue
• Nausea
• Abdominal pain
• Headache
• Taste disturbances
• Anaphylactic reactions (rare)

Interactions

• Caution with other anticholinergic drugs
• May enhance the effects of drugs that prolong the QT interval
• Use with caution with CYP3A4 inhibitors (e.g., ketoconazole, erythromycin)
• Antimuscarinic agents may have additive effects

Precautions

• Caution in patients with a history of urinary retention
• Caution in patients with bladder outflow obstruction
• Caution in elderly patients
• Monitor for signs of anticholinergic toxicity

Pregnancy

Manufacturer advises caution due to lack of human data; animal studies have shown adverse effects.

Breast-feeding

Manufacturer advises avoiding use; present in animal milk studies.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tolterodine tartrate 1 mg tablets
• Tolterodine tartrate 2 mg tablets
• Tolterodine tartrate 4 mg modified-release capsules
• Tolterodine tartrate oral solution 1 mg per 1 ml

Mechanism of action

Both tolterodine and its active metabolite, 5-hydroxymethyltolterodine, act as competitive antagonists at muscarinic receptors. This antagonism results in inhibition of bladder contraction, decrease in detrusor pressure, and an incomplete emptying of the bladder.

Pharmacodynamics

Tolterodine is a competitive muscarinic receptor antagonist. Both urinary bladder contraction and salivation are mediated via cholinergic muscarinic receptors. After oral administration, tolterodine is metabolized in the liver, resulting in the formation of the 5-hydroxymethyl derivative, a major pharmacologically active metabolite. The 5-hydroxymethyl metabolite, which exhibits an antimuscarinic activity similar to that of tolterodine, contributes significantly to the therapeutic effect. Both tolterodine and the 5-hydroxymethyl metabolite exhibit a high specificity for muscarinic receptors, since both show negligible activity or affinity for other neurotransmitter receptors and other potential cellular targets, such as calcium channels. Tolterodine has a pronounced effect on bladder function. The main effects of tolterodine are an increase in residual urine, reflecting an incomplete emptying of the bladder, and a decrease in detrusor pressure, consistent with an antimuscarinic action on the lower urinary tract.