DETRUNORM XL

Indications

• Overactive bladder
• Idiopathic detrusor muscle overactivity
• Neurogenic detrusor overactivity

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing guidelines.

Adults: Refer to the BNF for specific adult dosing guidelines.

Mechanism of action

Propiverine demonstrates both anticholinergic and calcium-modulating properties. It inhibits the pelvic nerve's efferent connection, leading to relaxation of bladder smooth muscle. By blocking calcium ion influx and modulating intracellular calcium levels in urinary bladder smooth muscle cells, propiverine inhibits muscle spasms. It competitively inhibits the binding of acetylcholine at muscarinic receptors on detrusor muscle cells and other structures within the bladder wall, particularly showing high occupancy of M-2 muscarinic receptors in the bladder.

Pharmacodynamics

Propiverine hydrochloride effectively inhibits abnormal contractions of bladder smooth muscle in vivo, demonstrating both anticholinergic and calcium antagonistic activities. It relieves symptoms of overactive bladder by decreasing intravesical pressure and increasing bladder capacity. Clinical studies indicate dose-dependent efficacy and tolerability in patients with idiopathic detrusor muscle overactivity and neurogenic detrusor overactivity.

Pharmacokinetics

The pharmacokinetics of propiverine involve absorption, distribution, metabolism, and excretion, but specific values such as half-life, clearance, and volume of distribution are not provided in the available data. It is important to refer to detailed pharmacokinetic studies for precise information.

Adverse effects

• dry mouth
• constipation
• blurred vision
• dizziness
• headache
• nausea

Interactions

• clozapine+propiverine: Unknown (additive effect)
• propiverine+lomitapide: Unknown (increases exposure)
• clarithromycin given with carbimazole+propiverine: Unknown (increases exposure)
• antipsychotics, second generation+propiverine: Unknown (additive effect)

Precautions

• Use with caution in patients with glaucoma
• Use with caution in patients with urinary retention
• Caution in elderly patients due to potential for increased sensitivity to side effects

Pregnancy

There is limited data on the use of propiverine during pregnancy. Use only if clearly needed and the benefits outweigh the risks.

Breast-feeding

It is not known whether propiverine is excreted in human milk. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• tablets
• sustained-release tablets

Indications

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

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing guidelines.

Adults: 15 mg 1–2 times a day, increased if necessary to a maximum of 15 mg 3 times a day. For modified-release capsules, 30 mg once daily.

Mechanism of action

Propiverine hydrochloride acts as a competitive antagonist of muscarinic receptors in the bladder. This activity reduces the frequency of detrusor muscle contractions, decreasing the sensation of urgency and increasing bladder capacity. It may also have some effect on calcium channels, contributing to its antispasmodic properties.

Pharmacodynamics

The pharmacodynamic effects of propiverine hydrochloride include a reduction in bladder overactivity, leading to decreased urinary urgency and frequency. The drug's antimuscarinic properties help to relax the smooth muscle of the bladder, which allows for improved urinary retention and control.

Pharmacokinetics

Propiverine hydrochloride is well absorbed after oral administration, with peak plasma concentrations occurring approximately 1 to 2 hours post-dose. The bioavailability may be influenced by food intake. It is extensively metabolized by the liver, primarily via cytochrome P450 enzymes, and has a relatively long half-life, allowing for once or twice-daily dosing. Renal and hepatic impairments may affect its clearance, necessitating dose adjustments in these populations.

Contra-indications

• Hypersensitivity to propiverine hydrochloride or any excipients
• Severe hepatic impairment
• Severe renal impairment
• Narrow-angle glaucoma

Adverse effects

• Abdominal pain
• Fatigue
• Altered taste
• Tremor
• Restlessness
• Hallucinations
• Delirium
• Dysphonia
• Muscle weakness
• QT interval prolongation
• Anaphylactic reaction

Interactions

• Anticholinergic agents may enhance the effects and side effects of propiverine
• Caution with drugs that prolong the QT interval
• Potential interactions with other medications metabolized by liver enzymes

Precautions

• Use with caution in patients with gastrointestinal disorders
• Monitor patients with a history of arrhythmias
• Caution in elderly patients due to the risk of side effects
• Assess renal function before prescribing, particularly in patients with creatinine clearance less than 30 mL/minute

Pregnancy

Manufacturer advises caution due to lack of information on use in pregnancy. Risk of skeletal development impairment in animal studies.

Breast-feeding

Manufacturer advises avoiding use as propiverine is present in milk in animal studies.

Storage

Store below 25°C in a dry place. Protect from light.

Formulations

• Immediate-release tablets: 15 mg
• Modified-release capsules: 30 mg, 45 mg
• Oral solution: 1 mg/ml

Mechanism of action

Propiverine demonstrates both anticholinergic and calcium-modulating properties. The efferent connection of the pelvic nerve is inhibited due to the anticholinergic action exerted by this drug, leading to relaxation of bladder smooth muscle. Propiverine blocks calcium ion influx and modulates the intracellular calcium in urinary bladder smooth muscle cells, resulting in the inhibition of muscle spasm. The bladder contains several muscarinic receptors. Acetylcholine is the main contractile neurotransmitter in the human bladder detrusor muscle, and antimuscarinics such as propiverine exert their effects by competitively inhibiting the binding of acetylcholine at muscarinic receptors on detrusor smooth muscle cells and other structures within the bladder wall. In one study, After oral treatment with propiverine, the bladder showed the highest concentration of M-2, indicating a targeted distribution of this metabolite into the bladder. Therefore, muscarinic receptor-2 may highly contribute to the relatively selective and long-lasting occupation of bladder muscarinic receptors after oral ingestion of propiverine.

Pharmacodynamics

Propiverine hydrochloride inhibits abnormal contractions of bladder smooth muscle in vivo through not only its anticholinergic activity but also its concurrent calcium antagonistic activity. Through the above-mentioned mechanism, propiverine is able to relieve the symptoms of overactive bladder. In animal models, this administration of this drug leads to a dose-dependent decrease in intravesical pressure of the bladder and an increase in bladder capacity. In patients with symptoms of OAB resulting from idiopathic detrusor muscle overactivity (IDO) or neurogenic detrusor overactivity (NDO), propiverine showed dose-dependent efficacy and tolerability.