Toviaz
Toviaz: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Toviaz
ATX code: G04BD11
Active ingredient: fesoterodine (Fesoterodine)
Producer: AESICA Pharmaceuticals, GmbH (Eisica Pharmaceuticals, GmbH) (Germany)
Description and photo update: 2019-10-07
Prices in pharmacies: from 689 rubles.
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Toviasis - M-anticholinergic antagonist.
Release form and composition
Dosage form - tablets of prolonged action, film-coated: oval, biconvex; at a dosage of 4 mg - light blue, with "FS" engraving on one side; at a dosage of 8 mg - blue, with "FT" engraving on one side; the cross section shows a white core (7 pieces in a blister, in a cardboard box 2, 3 or 8 blisters and instructions for the use of Toviaz).
Composition of 1 tablet:
- active substance: fesoterodine fumarate - 4 or 8 mg;
- auxiliary components: cellactose-100, glyceryl dibegenate or glyceryl tribegenate, hypromellose (methocel K4M), hypromellose (methocel K100), talc, xylitol;
- film coating: dosage 4 mg - Opadray light blue II 85G20426 (titanium dioxide, polyvinyl alcohol, talc, macrogol-3350, soy lecithin, indigo carmine aluminum varnish); dosage 8 mg - Opadry blue II 85G20427 (titanium dioxide, soy lecithin, macrogol-3350, polyvinyl alcohol, talc, indigo carmine aluminum varnish).
Pharmacological properties
Pharmacodynamics
Fesoterodine is a competitive specific muscarinic receptor antagonist. Once in the body, it is rapidly and intensively hydrolyzed by nonspecific blood plasma esterases to 5-hydroxymethyl derivative, which is the main pharmacologically active metabolite that determines the activity of fesoterodine.
The drug reduces the amount of urination and episodes of urge incontinence, and also increases the average volume during urination.
Activation of the postganglionic parasympathetic m-cholinergic receptors of the smooth muscles of the bladder causes the detrusor to contract. Fesoterodine inhibits these receptors in the bladder. It is assumed that it is this mechanism of action that causes the development of the corresponding pharmacological effects.
In therapeutic doses, fesoterodine increases the volume of the bladder by the time of the first contraction of the detrusor, and it also helps to increase the capacity of the bladder. These effects are proportional to the dose of Toviaz.
Toviasis does not affect the QT interval on the electrocardiogram.
Pharmacokinetics
Since fesoterodine undergoes rapid and intense hydrolysis by nonspecific esterases, it is not detected in blood plasma.
The bioavailability of the active metabolite is 52%. After taking Toviaz inside (single or multiple) in the dose range of 4-28 mg, plasma concentrations of the 5-hydroxymethyl derivative increase in proportion to the dose. The maximum plasma concentration (C max) is reached after about 5 hours. Therapeutic concentrations are reached after the first dose of the drug. Fesoterodine does not accumulate in the body with repeated doses.
The connection with plasma proteins (mainly albumin and alpha 1 -acid glycoprotein) of the active metabolite is approximately 50%.
After hydrolysis of fesoterodine, the active metabolite is further metabolized in the liver with the participation of isoenzymes CYP2D6 and CYP3A4 to carboxy-N-desisopropylated, N-desisopropylated and carboxylated metabolites, which have no significant antimuscarinic activity.
The average values of C max and AUC (areas under the concentration-time curve) of the active metabolite are approximately 1.7 and 2.1 times higher in patients who are slow metabolizers of the CYP2D6 isoenzyme, compared with rapid metabolizers.
The drug is excreted mainly (about 70%) through the kidneys: active metabolite - 16%, carboxy-N-desisopropylated metabolite - 18%, carboxylated metabolite - 34%, N-desisopropylated metabolite - 1%. Approximately 7% is excreted through the intestines.
The final half-life (T ½) of the active metabolite is about 7 hours.
Pharmacokinetics of Toviaz in special cases:
- old age and gender: changes in pharmacokinetic parameters depending on the age and gender of the patient have not been identified, so no dosage adjustment is required;
- children's age: the effect of the drug in children has not been studied;
- liver function: in case of violations of moderate severity (class B according to the Child-Pugh classification), C max increases 1.4 times, AUC increases 2.1 times. The pharmacokinetics of the drug in severe hepatic failure has not been studied;
- renal function: in case of mild and moderate impairment [creatinine clearance (CC) 30-80 ml / min] 1.5 times increases Cmax, 1.8 times - AUC, with severe impairments (CC <30 ml / min) the same indicators increase by 2 and 2.3 times, respectively.
Indications for use
Toviasis is intended for the symptomatic treatment of overactive bladder syndrome, which is manifested by frequent urination and / or urge to urinate, and / or urge urinary incontinence.
Contraindications
Absolute:
- conditions accompanied by urinary retention;
- myasthenia gravis;
- severe hepatic impairment (class C according to the Child-Pugh classification);
- toxic megacolon;
- ulcerative colitis;
- diseases of the gastrointestinal tract, accompanied by a delayed evacuation of stomach contents;
- galactose intolerance, lactase deficiency, glucose-galactose malabsorption;
- uncontrolled angle-closure glaucoma;
- age up to 18 years;
- lactation (or breastfeeding should be interrupted);
- pregnancy (there are no data on safety and effectiveness; in exceptional cases, the doctor may decide to prescribe Toviaz during gestation, but only if absolutely necessary, when the benefits to the mother significantly outweigh the possible risks to the fetus);
- concomitant administration of powerful inhibitors of the isoenzyme CYP3A4 or fesoterodine in patients with moderate to severe renal / hepatic impairment;
- hypersensitivity to soybeans, peanuts, any component of the drug.
Relative (Toviaz tablets should be used with caution):
- liver / kidney dysfunction;
- decreased gastrointestinal motility (eg, with severe constipation);
- gastroesophageal reflux;
- obstructive diseases of the gastrointestinal tract (eg, pyloric stenosis);
- obstructive diseases of the urinary system that cause urinary retention (eg, benign prostatic hyperplasia);
- controlled angle-closure glaucoma;
- neuropathy;
- pathologies from the heart, such as arrhythmias, myocardial ischemia, chronic heart failure;
- conditions accompanied by a risk of prolongation of the QT interval, for example, hypokalemia, bradycardia, combined use of drugs that can prolong the QT interval;
- Taking medications that can cause or intensify the manifestations of esophagitis (for example, oral bisphosphonates);
- simultaneous use of powerful inhibitors of the isoenzyme CYP2D6;
- joint use of CYP3A4 isoenzyme inhibitors of medium and high activity in patients with impaired renal / hepatic function.
Toviaz, instructions for use: method and dosage
Toviaz tablets should be taken orally, swallowed whole and washed down with a sufficient amount of liquid. Meal time does not matter.
The recommended starting dose is 4 mg once a day. If necessary, the dose can be increased to 8 mg (maximum daily dose).
The full therapeutic effect develops between the 2nd and 8th weeks of treatment, therefore, the effectiveness of therapy is recommended to be evaluated after 8 weeks of regular administration of the drug.
Dosing regimen correction
With the combined use of powerful inhibitors of the isoenzyme CYP3A4, the daily dose of Toviaz for patients with normal renal and liver function should not exceed 4 mg 1 time per day. When moderate inhibitors of this isoenzyme are prescribed, the response to therapy and drug tolerance are assessed individually.
Recommended daily doses of Toviaz for patients with impaired renal function:
- CC 50-80 ml / min: 4-8 * mg, with the simultaneous use of moderate inhibitors of CYP3A4 - 4 mg, strong inhibitors of CYP3A4 - the appointment of Toviaz should be avoided;
- CC 30-50 ml / min: 4-8 * mg, with the simultaneous use of moderate inhibitors of CYP3A4 - 4 mg, strong inhibitors of CYP3A4 - the appointment of Toviaz is contraindicated;
- CC <30 ml / min: 4 mg, with the simultaneous use of moderate inhibitors of CYP3A4 - the appointment of Toviaz should be avoided, strong inhibitors of CYP3A4 - the use of Toviaz is contraindicated.
Recommended daily doses of Toviaz for patients with impaired liver function:
- class A according to the Child-Pugh classification: 4-8 * mg, with the simultaneous use of moderate inhibitors of CYP3A4 - 4 mg, strong inhibitors of CYP3A4 - the appointment of Toviaz should be avoided;
- class B according to Child-Pugh classification: 4 mg, with the simultaneous use of moderate CYP3A4 inhibitors - the appointment of Toviaz should be avoided, strong CYP3A4 inhibitors - the use of Toviaz is contraindicated;
- Child-Pugh class C: Toviasis is contraindicated.
* Caution should be exercised when increasing the dose to 8 mg.
Side effects
The side effects described below are classified by frequency of occurrence as follows: very often - ≥ 1/10, often - from ≥ 1/100 to <1/10, infrequently - from ≥ 1/1000 to <1/100, rarely - from ≥ 1 / 10,000 to <1/1000:
- from the gastrointestinal tract: very often - dryness of the oral mucosa; often - flatulence, abdominal pain, constipation, diarrhea, nausea, dyspepsia; infrequently - abdominal discomfort, gastroesophageal reflux;
- from the urinary system: often - dysuria; infrequently - difficult onset of urination, urinary retention (including urinary disorders, a feeling of incomplete emptying of the bladder);
- on the part of the organ of hearing and balance: infrequently - vertigo;
- on the part of the organ of vision: often - dry eyes; infrequently - blurred vision;
- from the nervous system: often - headache, insomnia, dizziness; infrequently - drowsiness, fatigue, taste perversion; rarely - confusion of consciousness;
- on the part of the cardiovascular system: infrequently - palpitations, tachycardia;
- from the respiratory system: often - dry throat; infrequently - dryness of the mucous membranes of the nasal cavity, cough, pain in the larynx and pharynx;
- on the part of the skin and subcutaneous tissue: infrequently - itching, dry skin, skin rashes; rarely - urticaria, angioedema;
- others: infrequently - urinary tract infections, increased activity of gamma-glutamyl transpeptidase (GGTP) and alanine aminotransferase (ALT) (an increase in the activity of enzymes in the liver while taking fesoterodine in clinical trials was recorded with the same frequency as in the placebo group).
Overdose
With an overdose of fesoterodine, like other M-anticholinergics, severe anticholinergic effects may develop. In clinical studies, the safety of the drug has been confirmed when used in daily doses up to 28 mg.
In case of taking an excessive dose of Toviaz, gastric lavage, intake of activated charcoal, symptomatic therapy, correction of the QT interval, monitoring of the electrocardiogram are recommended.
For severe central anticholinergic effects (eg, severe agitation or hallucinations), physostigmine is indicated. With pronounced agitation and convulsions, benzodiazepines are prescribed, for tachycardia, beta-blockers, and for mydriasis, eye drops containing pilocarpine. In case of development of respiratory failure, artificial ventilation of the lungs is carried out, with urinary retention - catheterization of the bladder.
special instructions
Before the appointment of Toviaz, an examination should be carried out in order to exclude the organic causes of the symptoms. It is also necessary to evaluate for other possible causes of frequent urination (for example, kidney disease or therapy for heart failure). If urinary tract infections are detected, appropriate antibiotic therapy is performed.
It was reported about the development of angioedema during the use of fesoterodine, including immediately after taking the first dose. In this case, Toviaz is canceled and appropriate treatment is carried out.
The efficacy and safety of Toviasis in neurogenic detrusor overactivity has not yet been established.
During treatment, it is necessary to monitor the condition of patients for the development of anticholinergic effects from the central nervous system, especially at the initial stage of therapy and during the period of increasing the dose. When such effects appear, a reduction in the dose of Toviaz or its complete cancellation is required.
Patients with clinically significant narrowing of the bladder outlet have an increased risk of urinary retention.
Influence on the ability to drive vehicles and complex mechanisms
Due to the likelihood of side effects that can reduce the rate of reactions and affect concentration (for example, dizziness, drowsiness, decreased clarity of visual perception), it is recommended to observe precautions during the period of taking Toviaz.
Application during pregnancy and lactation
Adequate and well-controlled clinical studies on the use of fesoterodine in pregnant and lactating women have not been conducted. Toviasis is contraindicated during pregnancy, except in cases of urgent need, when the patient desperately needs fesoterodine therapy, and the expected benefits of treatment definitely outweigh the potential risks.
There is no information on the release of fesoterodine in mother's milk, so you should stop taking Toviaz or stop breastfeeding.
Pediatric use
Toviaz is contraindicated in children and adolescents under 18 years of age.
With impaired renal function
Caution should be exercised when treating patients with impaired renal function with the drug.
For violations of liver function
Severe hepatic impairment (class C according to the Child - Pugh classification) is a contraindication to the appointment of Toviasis, since the pharmacokinetics of fesoterodine in this category of patients has not been studied.
Caution should be exercised in mild to moderate hepatic impairment (Child-Pugh grades A and B).
Use in the elderly
Changes in pharmacokinetic parameters in elderly patients have not been identified, therefore, correction of the dosage regimen of Toviaz is not required.
Drug interactions
The combined use of other M-anticholinergics (for example, tricyclic antidepressants, amantadine, some neuroleptics) is associated with an increase in the therapeutic effect and an increased risk of developing adverse reactions, in particular, dryness of the oral mucosa, constipation, urinary retention, drowsiness. When using them simultaneously, special care is required.
Fesoterodine is able to reduce the effect of drugs that stimulate the motility of the gastrointestinal tract, including metoclopramide.
At therapeutic concentrations, the active metabolite of fesoterodine does not inhibit the activity of isoenzymes CYP1A2, ZA4, 2D6, 2E1, 2C9, 2C8, 2C19 and 2B6. Does not induce the activity of isoenzymes CYP1A2, ZA4, 2C9, 2B6 and 2C19. Therefore, it is expected that the effect of Toviaz on the clearance of drugs metabolized with the participation of the listed enzymes is insignificant.
The C max and AUC of fesoterodine increase potent inhibitors of the CYP3A4 isoenzyme, such as ritonavir (and all ritonavir boosted protease inhibitor antiretroviral regimens), clarithromycin, ketoconazole, nelfinavir, itraconazole, indinavir, nefakvironavirin, atraconazole With their simultaneous use, the maximum daily dose of Toviaz should not exceed 4 mg.
No studies have been conducted on the effect of moderately active CYP3A4 isoenzyme inhibitors such as verapamil, diltiazem, aprepitant, fosamprenavir, amprenavir, fluconazole, erythromycin, and grapefruit juice on the pharmacokinetics of fesoterodine. However, it is expected that with their simultaneous use there will also be an increase in the active metabolite of fesoterodine, albeit to a lesser extent than when using potent inhibitors of the isoenzyme CYP3A4.
C max and AUC of fesoterodine reduce powerful inducers of the isoenzyme CYP3A4, such as rifampicin, phenytoin, phenobarbital, carbamazepine, St. John's wort preparations. Their simultaneous appointment is not recommended.
Potent inhibitors of the isoenzyme CYP2D6 can increase exposure and the risk of side effects of fesoterodine. With their simultaneous use, it may be necessary to reduce the daily dose of Toviaz to 4 mg.
Fesoterodine does not alter the plasma concentrations of the components of combined oral contraceptives containing levonorgestrel and ethinyl estradiol, nor does it interfere with the suppression of ovulation caused by them.
Analogs
Analogs of Toviaz are: Avisan, Vesikar, Driptan, Novitropan, Roliten, Spazmex, Spazmolit, Urotol, Uroflex, Enablex.
Terms and conditions of storage
Store in a dry, dark place at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Toviaz
There are no reviews of Toviaz on specialized medical sites and forums, so today there is no way to assess the degree of effectiveness and safety of the drug from the point of view of the consumer.
Price for Toviaz in pharmacies
The price of Toviaz depends on the dosage of the drug, the region of its sale and the pharmacy chain. The approximate cost of a package (28 pcs.) Of prolonged-release tablets in a dosage of 4 mg is 648–770 rubles, in a dosage of 8 mg - 948–1190 rubles.
Toviaz: prices in online pharmacies
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Drug name Price Pharmacy |
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Toviaz 4 mg prolonged release tablets 28 pcs. 689 r Buy |
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Toviaz 8 mg prolonged release tablets 28 pcs. 896 r Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
