Solitor 5

Solifenacin succinate (Solitor 5) 5 mg Film-Coated Tablet is a light-yellow colored, round, biconvex film coated tablets debossed with "78" on one side and plain on other side.
Each film-coated tablet contains: Solifenacin Succinate 5 mg.

Urological.
Pharmacology: Pharmacodynamics: Mechanism of action: Solifenacin is a competitive, specific cholinergic receptor antagonist.
The urinary bladder is innervated by parasympathetic cholinergic nerves. Acetylcholine contracts the detrusor smooth muscle through muscarinic receptors of which the M3 subtype is predominantly involved. In vitro and in vivo pharmacological studies indicate that solifenacin is a competitive inhibitor of the muscarinic M3 subtype receptor. In addition, solifenacin showed to be a specific antagonist for muscarinic receptors by displaying low or no affinity for various other receptors and ion channels tested.
Pharmacokinetics: Absorption: After oral administration of solifenacin tablets, peak plasma concentrations (Cmax) of solifenacin are reached after 3 to 8 hours. The tmax is independent of the dose. The Cmax and area under the curve (AUC) increase in proportion to the dose between 5 to 10 mg. Absolute bioavailability is approximately 90%. Food intake does not affect the Cmax and AUC of solifenacin succinate.
Distribution: The apparent volume of distribution of solifenacin following intravenous administration is about 600 L. Solifenacin to a great extent (approximately 98%) bound to plasma proteins, primarily α1-acid glycoprotein.
Biotransformation: Solifenacin is extensively metabolized by the liver, primarily by cytochrome P450 3A4 (CYP3A4). However, alternative metabolic pathways exist, that can contribute to the metabolism of solifenacin succinate. The systemic clearance of solifenacin succinate is about 9.39 L/h and the terminal half-life of solifenacin succinate is 45-68 hours. After oral dosing, one pharmacologically active (4R-hydroxy solifenacin) and three inactive metabolites (N-glucuronide, N-oxide and 4R-hydroxyl-N-oxide of solifenacin) have been identified in plasma in addition to solifenacin.
Elimination: After a single administration of 10 mg 14C-solifenacin succinate, about 69.2% of the radioactivity was detected in urine and 22.5% in feces over 26 days. Less than 15% (as mean value) of the dose was recovered in the urine as intact solifenacin. The major metabolites identified in urine were N-oxide of solifenacin, 4R-hydroxy solifenacin and 4R-hydroxy-N-oxide of solifenacin and in feces 4R-hydroxy solifenacin. In urine, approximately 11% of the radioactivity is recovered as unchanged active substance; about 18% as the N-oxide metabolite, 9% as the 4R-hydroxy-N-oxide metabolite and 8% as the 4R-hydroxy metabolite (active metabolite).
Linearity/non-linearity: Pharmacokinetics are linear in the therapeutic dose range.
Other special populations: Elderly: No dosage adjustment based on patient age is required. Studies in elderly have shown that the exposure to solifenacin, expressed as the AUC, after administration of solifenacin succinate (5 mg and 10 mg once daily) was similar in healthy elderly subjects (aged 65 through 80 years) and healthy young subjects (aged less than 55 years). The mean rate of absorption expressed as tmax was slightly slower in the elderly and the terminal half-life was approximately 20% longer in elderly subjects. These modest differences were considered not clinically significant.
The pharmacokinetics of solifenacin has not been established in children and adolescents.
Gender: The pharmacokinetics of solifenacin is not influenced by gender.
Race: The pharmacokinetics of solifenacin is not influenced by race.
Renal impairment: The AUC and Cmax of solifenacin in mild and moderate renally impaired patients, was not significantly different from that found in healthy volunteers. In patients with severe renal impairment (creatinine clearance ≤30 mL/min) exposure to solifenacin was significantly greater than in the controls with increases in Cmax of about 30%, AUC of more than 100% and t½ of more than 60%. A statistically significant relationship was observed between creatinine clearance and solifenacin clearance. Pharmacokinetics in patients undergoing hemodialysis have not been studied.
Hepatic impairment: In patients with moderate hepatic impairment (Child Pugh score of 7 to 9) the Cmax is not affected, AUC increased with 60% and t½ doubled. Pharmacokinetics of solifenacin in patients with severe hepatic impairment have not been studied.
Toxicology: Preclinical Safety Data: Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, fertility, embryo fetal development, genotoxicity, and carcinogenic potential. In the pre and postnatal development study in mice, solifenacin treatment of the mother during lactation caused dose dependent lower postpartum survival rate, decreased pup weight and slower physical development at clinically relevant levels. Dose related increased mortality without preceding clinical signs occurred in juvenile mice treated from day 10 or 21 after birth with doses that achieved a pharmacological effect and both groups had higher mortality compared to adult mice. In juvenile mice treated from postnatal day 10, plasma exposure was higher than in adult mice; from postnatal day 21 onwards, the systemic exposure was comparable to adult mice. The clinical implications of the increased mortality in juvenile mice are not known.

Symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency as may occur in patients with overactive bladder syndrome.

Posology: Adults, including the elderly: The recommended dose is 5 mg once daily. If needed, the dose may be increased to 10 mg once daily.
Pediatric population: The safety and efficacy of solifenacin in children have not yet been established. Therefore, Solifenacin should not be used in children.
Patients with renal impairment: No dose adjustment is necessary for patients with mild to moderate renal impairment (creatinine clearance >30 mL/min). Patients with severe renal impairment (creatinine clearance ≤30 mL/min) should be treated with caution and receive no more than 5 mg once daily.
Patients with hepatic impairment: Solifenacin is not recommended in patients with severe hepatic impairment. No dose adjustment is necessary for patients with mild hepatic impairment. Patients with moderate hepatic impairment (Child Pugh score of 7 to 9) should be treated with caution and receive no more than 5 mg once daily.
Potent inhibitors of cytochrome P450 3A4: The maximum dose of solifenacin should be limited to 5 mg when treated simultaneously with ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors e.g. ritonavir, nelfinavir, itraconazole.
Method of administration: Solifenacin should be taken orally and should be swallowed whole with liquids. It can be taken with or without food.

Symptoms: Over dosage with solifenacin succinate can potentially result in severe anticholinergic effects. The highest dose of solifenacin succinate accidentally given to a single patient was 280 mg in a 5-hour period, resulting in mental status changes not requiring hospitalization.
Treatment: In the event of overdose with solifenacin succinate the patient should be treated with activated charcoal. Gastric lavage is useful if performed within 1 hour, but vomiting should not be induced.
As for other anticholinergics, symptoms can be treated as follows: Severe central anticholinergic effects such as hallucinations or pronounced excitation: treat with physostigmine or carbachol.
Convulsions or pronounced excitation: treat with benzodiazepines.
Respiratory insufficiency: treat with artificial respiration.
Tachycardia: treat with beta-blockers.
Urinary retention: treat with catheterization.
Mydriasis: treat with pilocarpine eye drops and/or place patient in dark room.
As with other antimuscarinics, in case of overdosing, specific attention should be paid to patients with known risk for QT prolongation (i.e. hypokalemia, bradycardia and concurrent administration of medicinal products known to prolong QT interval) and relevant preexisting cardiac diseases (i.e. myocardial ischemia, arrhythmia, congestive heart failure).

Solifenacin succinate is contraindicated in patients with urinary retention, gastric retention, with uncontrolled narrow-angle glaucoma, and patients who are hypersensitive to solifenacin or to any of its excipients.

Other causes of frequent urination (heart failure or renal disease) should be assessed before treatment with solifenacin succinate. If urinary tract infection is present, an appropriate antibacterial therapy should be started.
Solifenacin succinate should be used with caution in patients with: Clinically significant bladder outflow obstruction at risk of urinary retention.
Gastrointestinal obstructive disorders and decreased gastrointestinal motility.
Reduced renal function, doses of solifenacin succinate greater than 5 mg are not recommended in patients with severe renal function.
Reduced hepatic function, doses of solifenacin succinate greater than 5 mg are not recommended in patients with moderate hepatic impairment.
Hiatus hernia/gastro-esophageal reflux and/or who are concurrently taking medicinal products (such as bisphosphonates) that can cause or exacerbate esophagitis.
Autonomic neuropathy.
Myasthenia Gravis.
QT prolongation and Torsade de Pointes have been observed in patients with risk factors, such as preexisting long QT syndrome and hypokalemia.
Angioedema with airway obstruction has been reported in some patients on solifenacin succinate. If angioedema occurs, solifenacin succinate should be discontinued and appropriate therapy and/or measures should be taken.
Anaphylactic reaction has been reported in some patients treated with solifenacin succinate. In patients who develop anaphylactic reactions, solifenacin succinate should be discontinued and appropriate therapy and/or measures should be taken.
Effects on Ability to Drive and Use Machines: Since solifenacin, like other anticholinergics may cause blurred vision, and, uncommonly, somnolence and fatigue, the ability to drive and use machines may be negatively affected.

Pregnancy: There is no adequate and well-controlled data from the use of solifenacin succinate in pregnant women. It should be used in pregnancy only if potential benefit justifies the potential risk of the fetus.
Lactation: Solifenacin succinate should not be administered during nursing.

Summary of the safety profile: Due to the pharmacological effect of solifenacin, solifenacin may cause anticholinergic undesirable effects of (in general) mild or moderate severity. The frequency of anticholinergic undesirable effects is dose related. The most commonly reported adverse reaction with solifenacin was dry mouth. It occurred in 11% of patients treated with 5 mg once daily, in 22% of patients treated with 10 mg once daily and in 4% of placebo treated patients. The severity of dry mouth was generally mild and did only occasionally lead to discontinuation of treatment. In general, medicinal product compliance was very high (approximately 99%) and approximately 90% of the patients treated with solifenacin completed the full study period of 12 weeks treatment.
Tabulated list of adverse reactions: See table.

Click on icon to see table/diagram/image

Drugs Metabolized by Cytochrome P450: Pharmacokinetic interactions: in vitro studies have demonstrated that at therapeutic concentrations, solifenacin does not inhibit CYP1A1/2, 2C9, 2C19, 2D6, or 3A4 derived from human liver microsomes. Therefore, solifenacin succinate is unlikely to alter the clearance of drugs metabolized by these CYP enzymes.
CYP3A4 Inhibitors: Solifenacin is metabolized by CYP3A4. Simultaneous administration of ketoconazole (200 mg/day), a potent CYP3A4 inhibitor, resulted in a two-fold increase of the AUC of solifenacin, while ketoconazole at a dose of 400 mg/day resulted in a threefold increase of the AUC of solifenacin. Therefore, the maximum dose of solifenacin succinate should be restricted to 5 mg, when used simultaneously with ketoconazole or therapeutic doses of other potent CYP3A4 inhibitors (e.g. ritonavir, nelfinavir, itraconazole).
Oral Contraceptives: Intake of solifenacin succinate showed no pharmacokinetic interaction of solifenacin on combined oral contraceptives (ethinylestradiol/levonorgestrel both CYP34A substrates).
Warfarin: Intake of solifenacin succinate did not alter the pharmacokinetics of R-warfarin (substrate of CYP34A) or S-warfarin (substrate of CYP2C9) or their effect on prothrombin time.
Digoxin: Intake of solifenacin succinate showed no effect on the pharmacokinetics of digoxin (0.125 mg/day) in healthy subjects.

Store at temperatures not exceeding 30°C.

Drugs for Bladder & Prostate Disorders

G04BD08 - solifenacin ; Belongs to the class of urinary antispasmodics.

Rx