MICTONORM 15MG TABLET

Product Information

Registration Status: Active

MICTONORM 15MG TABLET is approved to be sold in Singapore with effective from 2007-02-22. It is marketed by PHARMAFORTE SINGAPORE PTE LTD, with the registration number of SIN13235P.

This product contains Propiverine 15mg in the form of TABLET,-COATED. It is approved for ORAL use.

This product is manufactured by Apogepha Arzneimittel GmbH in GERMANY.

It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.

Propiverine

Description

Propiverine is a widely used antimuscarinic drug with a mixed mode of action in the treatment of symptoms associated with overactive bladder (OAB) [A32576]. Overactive bladder (OAB) is a chronic condition of the lower urinary tract characterized by urinary urgency, increased frequency of urination, and nocturia (frequent waking during the night to urinate). OAB has a negative impact on quality of life and may lead to leakage and inconvenient urinary accidents [L2327], [L2328]. Overactive bladder syndrome affects millions of elderly individuals in the United States and shows equal prevalence in men and women. The impact of OAB on quality of life is sometimes devastating, especially to elderly patients with other medical conditions [L2328]. Propiverine hydrochloride is a bladder detrusor muscle relaxant drug with dual antimuscarinic and calcium-modulating properties for the treatment of OAB [L2317].

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 |


Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.

References

  1. Health Science Authority of Singapore - Reclassified POM
  2. Drugbank