Propiverine

G04B - Urologicals ATC G04BD06 Small molecule Natural product

JFDA label: Mictonorm XL

Mechanism of Action

Propiverine and three active metabolites account for pharmacologic effects; antispasmodic effect by inhibiting calcium influx and modulating intracellular calcium in bladder smooth muscle; also has anticholinergic activity leading to decreased intravesical pressure.

Indications

Approved

Overactive bladder

Contraindications

Source: Lexicomp

Hypersensitivity to propiverine or any component of the formulation Absolute
angle-closure glaucoma (uncontrolled) Absolute
children with rare hereditary problems of fructose intolerance or sucrose-isomaltase insufficiency Absolute
gastrointestinal obstructive disorder Absolute
intestinal atony Absolute
moderate or severe hepatic impairment Absolute
myasthenia gravis Absolute
rare hereditary problems of galactose intolerance, glucose-galactose malabsorption, or Lapp lactase deficiency Absolute
severe ulcerative colitis Absolute
significant degree of bladder outflow obstruction where urinary retention may be anticipated Absolute
tachyarrhythmias Absolute
toxic megacolon Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (11)

Not Known atrioventricular block · bradycardia · chest pain · extrasystoles · Fatigue · flushing · hypertension · palpitation · prolonged QT interval on ECG · tachycardia · ventricular tachycardia

Nervous system disorders (8)

Not Known confusion · delirium · Dizziness · hallucination · impaired consciousness · insomnia · paralysis · restlessness

Renal and urinary disorders (2)

Not Known Dysuria · urinary retention (Hematologic & oncologic: Leukopenia (0.1% to Hepatic: Increased serum alkaline phosphatase (0.1% to Hypersensitivity: Hypersensitivity

Metabolism and nutrition disorders (1)

Not Known Polydipsia

Gastrointestinal disorders (7)

Not Known abdominal distension · Abdominal pain · cleft palate · dysgeusia · intestinal obstruction · sore throat · stomatitis

Skin and subcutaneous tissue disorders (3)

Not Known erythema · Pruritus · Stevens-Johnson syndrome

Musculoskeletal and connective tissue disorders (7)

Not Known Back pain · dyskinesia · increased creatine phosphokinase · myalgia · rhabdomyolysis · tremor · weakness

Eye disorders (1)

Not Known Oculomotor disturbance, increased creatinine clearance, renal insufficiency

General disorders and administration site conditions (1)

Not Known Fever

Respiratory, thoracic and mediastinal disorders (1)

Not Known Increased bronchial secretions

Other (7)

Not Known Cough · dyschromia · leukocytosis · pain · reduced urine flow · tinnitus · upper respiratory tract infection

Dosing

Source: Lexicomp

Overactive bladder: Oral: Modified release: Initial: 30 mg once daily; may increase to a maximum of 45 mg once daily.

Overactive bladder: Children and Adolescents: Oral: Immediate release: 0.8 mg/kg/day in 2 divided doses or alternatively the following body weight adjusted dosing may be used: 12 to 16 kg: 5 mg two times daily 17 to 22 kg: 5 mg in the morning and 10 mg in the evening 23 to 28 kg: 10 mg two times daily 29 to 34 kg: 10 mg in the morning and 15 mg in the evening ≥35 kg: 15 mg two times daily (maximum: 30 mg/day) Note: Modified release capsules should not be used in pediatric patients.

Refer to adult dosing.

Mild to moderate impairment: No dosage adjustment necessary. Severe impairment: Maximum dose: 30 mg/day

Mild impairment: No dosage adjustments necessary. Moderate to severe impairment: Use is contraindicated.

Warnings & Precautions

Source: Lexicomp

CNS effects

May cause drowsiness and blurred vision, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Disease-related concerns:

Cardiovascular disease

Use with caution in patients with heart failure, tachycardia, and/or cardiac arrhythmias; may exacerbate condition. Use is contraindicated in patients with tachyarrhythmias. Monitor patients at risk for QTc prolongation during therapy (have not been studied).

Glaucoma

Use with caution in patients with glaucoma; may exacerbate condition. Use is contraindicated in patients with uncontrolled angle-closure glaucoma.

Hepatic impairment

Use with caution in patients with mild hepatic impairment. Monitor hepatic function closely and discontinue if transaminases and/or bilirubin are above normal limits. Use is contraindicated in patients with moderate or severe hepatic impairment.

Hiatal hernia

Use with caution in patients with hiatal hernia with reflux esophagitis.

Neuropathy

Use with caution in patients with autonomic neuropathy; may aggravate symptoms of decreased GI motility

Prostatic hyperplasia/urinary stricture

Use with caution in patients with prostatic hyperplasia and/or urinary stricture; may cause urinary retention

Renal impairment

Use with caution in patients with renal impairment; dosage adjustment may be required in severe impairment. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Other warnings/precautions:

Appropriate use

Prior to initiating therapy, rule out alternative causes of pollakiuria and nocturia (eg, organic bladder disease such as UTI or malignancy, heart failure).

Pregnancy & Lactation

Pregnancy

Adverse events have been reported in animal reproduction studies. Use is not recommended in pregnancy.

Lactation

Avoid

It is not known if propiverine is present in breast milk. Breastfeeding is not recommended by the manufacturer.

Monitoring

Clinical pearl	Hepatic function during long-term therapy; renal function; intraocular pressure in patients at risk of developing glaucoma; QTc interval (patients at risk for QTc prolongation)

Chemistry & Properties

Formula	C23H29NO3
Molecular weight	367.49 g/mol
IUPAC name	(1-methylpiperidin-4-yl) 2,2-diphenyl-2-propoxyacetate
CAS	60569-19-9
PubChem CID	4942
InChIKey	`QPCVHQBVMYCJOM-UHFFFAOYSA-N`
logP	3.99 (XLogP 4.7)
Polar surface area	38.77 Å²
H-bond acceptors / donors	4 / 0
Drug-likeness (QED)	0.69
Lipinski violations	0

SMILES

CCCOC(C(=O)OC1CCN(C)CC1)(c1ccccc1)c1ccccc1

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	0.485 h
Volume of distribution	2.609 L/kg
Protein binding	89.0%
BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP2B6	Inhibitor	—
CYP2B6	Substrate	—
CYP2C19	Substrate	—
CYP3A4	Inhibitor	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (3)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Mictonorm	Tablet 5 mg	28 tab	ORIENT DRUG STORE CO	7.700
Mictonorm XL	Capsule 30 mg	28 cap	ORIENT DRUG STORE CO	20.000
Mictonorm XL	Capsule 45 mg	28 cap	ORIENT DRUG STORE CO	22.780