Singapore Drugs Database

Indication

Indicated for symptomatic treatment of urinary incontinence and/or increased urinary frequency and urgency in patients with overactive bladder (OAB) [L2315]. Propiverine may also be used in patients with neurogenic bladder as a result of spinal cord injury [A32581].

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 [L2315]. 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 [L2332]. 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 [L2334].

Pharmacokinetics

Absorption

Propiverine is rapidly absorbed from the gastrointestinal tract with maximum plasma concentrations attained after 2.3 hours. the mean absolute bioavailability of mictonorm 15 mg tablets (propiverine) is 40.5 %. It undergoes heavy first-pass metabolism in the liver [L2315].

Distribution

In one study, the volume of distribution was calculated in 21 healthy volunteers after intravenous (IV) administration of propiverine hydrochloride was measured to range from 125 to 4731 (average 2791) indicating, that a large amount of available propiverine is distributed to peripheral compartments [L2324].

Metabolism

The major metabolites were found to be as follows; 4-piperidyl diphenylpropoxyacetate (DM-P-4), 1-methyl-4-piperidyl benzilate (Dpr-P-4) and 1-methyl-4-piperidyl diphenyl-(2 carboxy) ethoxyacetate (ω-COOH-P-4) in the liver, Dpt-p-4, DM-P-4 in the kidney, and DM-P-4, DPr-P-4 in the lung [L2323]. In the same pharmacokinetic study, All pharmacologically active compounds such as the unchanged compound, 1-methyl-4-piperidyl benzilate N-oxide (DPr-P-4 (N→O)), Dpt-p-4 and 1-methyl-4-piperidyl diphenylpropoxyacetate N-oxide (P-4 (N→O)) were present in the urinary bladder, a target organ for P-4, at higher concentrations than in the plasma [L2323]. Propiverine is metabolized by both intestinal and hepatic enzymes. The main metabolic pathway involves the oxidation of the _piperidyl-N _and is mediated by _CYP 3A4_ and _flavin-containing monooxygenases (FMO) _1 and 3 and results in the formation of the second main metabolite M-5, the plasma concentration of which is greater in concentration that of the parent substance propiverine. Four metabolites have been identified in the urine following propiverine ingestion; 3 them are pharmacologically active metabolites that may contribute to its therapeutic effect (M-5, M-6, M-23) [L2325]. The mean absolute bioavailability of propiverine IR 15 mg is 40.5% [L2315].

Elimination

Clearance

Mean total clearance after single dose administration of 30 mg is 371 mL/min (191 – 870 mL/min) [L2315].

Toxicity

The most common adverse reactions reported in patients treated with propiverine include dry mouth, headache, accommodation disorder, constipation, abdominal pain, dyspepsia and fatigue [L2315]. Propiverine may cause drowsiness and blurred vision. This may impair the ability to exert activities that require mental alertness such as operating a motor vehicle or other machinery, or to perform hazardous work while taking this drug [L2315]. There have been reports of QT interval prolongation with antimuscarinic medications in the same class of drugs of propiverine hydrochloride. Some drugs that may cause QT/QTc interval prolongation may increase the risk of a rare, but serious ventricular arrhythmia called _torsades de pointes_. Patients at risk for QT/QTc interval prolongation, such as those with diagnosed heart failure, long QT syndrome, recent significant hypokalemia episodes or receiving other drugs known to prolong QT/QTc, should be closely monitored while treated with propiverine. Patients who experience prolonged QT/QTc or symptoms of possible arrhythmias including dizziness, palpitations or fainting should be electrocardiographically evaluated and monitored for electrolyte disturbances [L2315]. Propiverine, like other anticholinergics, induces mydriasis. Therefore, the risk to induce acute angle-closure glaucoma in individuals predisposed with narrow angles of the anterior chamber may be increased. Drugs of this class, including propiverine, have been reported to induce or precipitate acute angle-closure glaucoma [L2315]. No clinical data are available on the use of propiverine in pregnant women. Studies in animals have shown reproductive toxicity [L2315].

Active Ingredient/Synonyms

Propiverine | Propiverine |