Solifenacin

When ATH:
G04BD08

Антагонист м-холинорецепторов. Solifenacin succinate is crystals or crystalline powder from white to pale yellowish-white. Easily soluble in water room temperature, in glacial acetic acid, demetilsulfoxide and methanol.

Pharmacological action.
Holinoliticheskoe, antispasmodic.

Application.

Emergency treatment (ymperatyvnoho) Incontinence, frequent urination and urgent (peremptory) the urge to urinate in patients with overactive bladder syndrome.

Hypersensitivity, acute and chronic urinary retention, severe gastrointestinal disease (including toxic megacolon), myasthenia gravis, zakrыtougolynaya glaucoma, severe liver failure, renal failure, severe or moderate liver failure while treating CYP3A4 inhibitors (for example, ketoconazole), hemodialysis.

Clinically significant infravezikal′naâ obstruction, leading to the risk of acute urinary retention; obstructive diseases of the digestive tract, risk of GASTROINTESTINAL motility, severe renal failure (creatinine clearance <30 ml / min) and mild hepatic impairment (dose for these patients should not exceed 5 mg), simultaneous reception of strong CYP3A4 inhibitors (for example, ketoconazole), hiatal hernia, gastroesophageal reflux and simultaneous preparations (for example, bisphosphonates), that can cause or enhance the development of the symptoms of esophagitis, autonomic neuropathy, childhood (safety and effectiveness in children have not been established). Patients with rare hereditary disorders of galactose tolerance, lactase deficiency the Lapps (the Saami), malabsorption of glucose-galactose should not take the drug.

Experimental studies, conducted on animals (mouse, rats, Rabbits), shown, that solifenacin passes through the placental barrier in mice. When mice solifenacin at doses 30 mg / kg / day (1,2 exposure when MRDC) There was no embryotoxicity and teratogenic effects. Introduction to pregnant mice doses 100 mg/kg/day and above (in 3,6 times higher than MRDC exposure) during fetal development and lactation led to a decrease in body weight of fruits, decrease in postnatal viability, delayed physical development (incl. disclosure of the eye); introduction of doses 250 mg/kg/day and above (in 7,9 times higher than MRDC exposure) led to an increase in the incidence of cleft palate. Revealed no embryotoxicity solifenacin in rats with doses up to 50 /mg / kg / day (<1 exposure when MRDC) and rabbits at doses up to 50 /mg / kg / day (1,8 times higher than MRDC exposure).

Assign with caution in pregnancy (adequate and well-controlled studies have been conducted).

Category actions result in FDA - C. (The study of reproduction in animals has revealed adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not held, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk.)

Not recommended during breastfeeding (penetrates into breast milk mice, data on the penetration of breast milk in humans are absent).

The most probable side effects, related to antiholinergicakim action of solifenacin is dry mouth, constipation, blurred vision (ccomodation), urinary retention, dry eyes. Undesirable effects often weak or moderate symptoms, their frequency depends on the dose. Four 12-week double-blind clinical trials it was noted 3 serious enteric cases of side effects in patients, receiving drug dose 10 mg: ileus, intestinal obstruction (obstruction of the intestines), coprostasia. Total frequency of serious side effects in double-blind trials was 2%. Angioneurotic edema was observed in one patient on the background 5 mg. The frequency and severity of side effects were similar in patients, treated with 12 Sun, and patients, treated to 12 Months. The most frequent reason for discontinuation of solifenacin was dry mouth (1,5%).

The following table shows side effects, regardless of their causes, registered in Randomized placebo-controlled clinical trials in patients, taking a daily dose of solifenacin 5 or 10 mg for 12 Sun (are the effects, with ≥ 1% and greater than placebo frequency).

Side effects, observed when conducting clinical trials of solifenacin

In post-marketing studies the following side effects have been recorded, associated with the acquisition of solifenacin:

General: hypersensitivity reactions, including angioedema, rash, itch, hives.

With concomitant treatment of HP with anticholinergic properties may increase the therapeutic actions and side effects (after discontinuation of solifenacin should take a break 1 weeks prior to the start of treatment with another drug antiholinergicakim). Therapeutic effect can be reduced while receiving holinergicakih receptors agonists. Solifenacin may reduce the effect of drugs, stimulating the motility of the gastrointestinal tract, for example metoclopramide and cisapride. Research in vitro shown, that solifenacin at therapeutic concentrations not ingibiruet isozyme human liver CYP1A1/2, CYP2С9, CYP2C19, CYP2D6, CYP3А4. Together with the use of ketoconazole in the dose 200 mg / day (CYP3A4 inhibitor) increases in AUC solifenacin in 2 times, dose 400 mg/cut-in 3 times; the maximum dose of solifenacin not exceed 5 mg, if the patient simultaneously receives ketoconazole or therapeutic doses of other CYP3A4 inhibitors (such as ritonavir, Nelfinavir, itraconazole). Co-administration of solifenacin and CYP3A4 inhibitor is contraindicated in patients with severe renal impairment or moderate hepatic impairment. Because solifenacin is metabolized by CYP3A4, pharmacokinetic interactions are possible with other CYP3A4 substrates with higher affinity (verapamil, diltiazem) and with CYP3A4 inducers (rifampicin, phenytoin, Carbamazepine). There were no pharmacokinetic interaction of solifenacin and a combined oral contraceptive (ethinyl estradiol / levonorgestrel). Simultaneous reception of solifenacin did not produce changes in the pharmacokinetics of R-warfarin or S-warfarin or their influence on POE. Simultaneous treatment of solifenacin had no effect on the pharmacokinetics of digoxin.

Overdose.

Symptoms (When administered solifenacin dose volunteers 100 mg dose): headache, dry mouth, dizziness, drowsiness, blurred vision. No cases of acute overdose have been reported.

Treatment: should appoint the activated carbon, gastric lavage, but do not induce vomiting. If necessary spend symptomatic therapy: with the heavy Central anticholinergic effects (hallucinations, hypererethism) — Physostigmine or carbachol; cramps or expressed excited — benzodiazepines; When respiratory failure-IVL; If tachycardia is beta-adrenoblokatora; acute delayed urine-bladder catheterization; When midriaze-instillation into the eye pilocarpina and/or placing the patient in a dark room.

As with other anticholinergic drugs overdose, special attention should be given to patients with established risk of QT prolongation (ie. if hypokalemia, bradycardia while taking drugs, causing QT prolongation) and patients with diseases of the cardiovascular system (myocardial ischemia, arrhythmia, congestive heart failure).

Inside (drinking plenty of fluids, regardless of the meal) by 5 mg 1 time / day. If necessary, the dose may be increased to 10 mg 1 time / day.

Before treatment should rule out other causes of urination. In case of detection of urinary tract infection should begin appropriate antibacterial therapy.

Solifenacin, like other anticholinergic drugs, It can cause blurred vision, as well as drowsiness and fatigue, so be careful when driving and working with machinery.