Detrusitol
Detrusitol: 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. Drug interactions
- 14. Analogs
- 15. Terms and conditions of storage
- 16. Terms of dispensing from pharmacies
- 17. Reviews
- 18. Price in pharmacies
Latin name: Detrusitol
ATX code: G04BD07
Active ingredient: tolterodine (tolterodine)
Producer: Pfizer Italia SrL (Italy), Pharmacia Italia (Italy), Catalent Pharma Solutions Inc. (USA)
Description and photo update: 2019-26-08
Detrusitol is a competitive m-cholinergic receptor blocker, a drug that reduces the tone of the smooth muscles of the urinary tract.
Release form and composition
Detrusitol dosage forms:
- Sustained-release capsules: size No. 4, hard gelatinous, with a body and a blue-green lid, the number “2” is applied on the body in white ink, on the lid there is a symbol in the form of a man; contents - microspheres with a diameter of about 1 mm, white with a yellowish tinge (7 pcs. in blisters, in a cardboard box of 1, 4, 7, 12 or 40 blisters);
- Prolonged-release capsules: size No. 3, hard gelatinous, with a body and a blue cap, the number “4” is applied on the body in white ink, a symbol in the form of a man on the cap; contents - microspheres with a diameter of about 1 mm, white with a yellowish tinge (7 pcs. in blisters, in a cardboard box of 1, 4, 7, 12 or 40 blisters);
- Film-coated tablets: round, convex on both sides, white, letters "TO" are engraved on one side, arcs above and below them (14 pcs. In blisters, in a cardboard box 1, 2 or 4 blisters; each 60 pcs. In bottles, in a cardboard box 1 bottle);
- Film-coated tablets: round, convex on both sides, white, letters "DТ" are engraved on one side, arcs above and below them (14 pcs. In blisters, in a cardboard box 1, 2 or 4 blisters; each 60 pcs. In bottles, in a cardboard box 1 bottle).
The active substance of Detrusitol is tolterodine hydrotartrate:
- 1 capsule size No. 4 - 2 mg, which corresponds to the content of tolterodine - 1.37 mg;
- 1 capsule size No. 3 - 4 mg, which corresponds to the content of tolterodine - 2.74 mg;
- 1 tablet with an engraving "TO" - 1 mg, which corresponds to the content of tolterodine - 0.68 mg;
- 1 tablet with an engraving "DT" - 2 mg, which corresponds to the content of tolterodine - 1.37 mg.
Additional components of capsules:
- Excipients: hypromellose, sugar granules (corn starch and sucrose), Surelease E-7-19010 transparent (oleic acid, medium chain triglycerides, ethylcellulose);
- Shell composition: indigo carmine, gelatin, titanium dioxide, Opacode White S-1-7085 white ink (titanium dioxide, shellac, simethicone, propylene glycol), as well as iron dye yellow oxide - in capsules No. 4.
Excipients of tablets: sodium starch glycolate, calcium hydrogen phosphate dihydrate, magnesium stearate, microcrystalline cellulose, stearic acid, hypromellose, titanium dioxide, colloidal anhydrous silicon dioxide.
Pharmacological properties
Pharmacodynamics
The active substance of Detrusitol is tolterodine, a competitive antagonist of cholinergic muscarinic receptors, showing the highest selectivity in relation to the receptors of the bladder; The 5-hydroxymethyl derivative of tolterodine also has a high specificity for muscarinic receptors and does not significantly affect other receptors.
Thanks to tolterodine therapy, the contractile activity of the detrusor decreases, and salivation also decreases. The use of Detrusitol in excess of the recommended doses leads to an increase in the amount of residual urine and causes incomplete emptying of the bladder.
The development of the effect is noted after 4 weeks of treatment.
Tolterodine does not inhibit CYP2D6, 2C19, 1A2, or 3A4.
Pharmacokinetics
Tolterodine in the form of tablets from the gastrointestinal tract is absorbed faster than in the form of prolonged-release capsules. After taking Detrusitol in tablets or capsules, the serum concentration of the substance reaches a maximum in 1-2 or 2-6 hours, respectively.
In the range of therapeutic doses (from 1 to 4 mg), there is a linear relationship between the dose of the substance and the value of the peak serum concentration in the blood.
After oral administration, tolterodine is metabolized mainly in the liver by the polymorphic enzyme CYP2D6. As a result, a pharmacologically active 5-hydroxymethyl metabolite is formed, which is further metabolized to N-dealkylated 5-carboxylic acid and 5-carboxylic acid; The 5-hydroxymethyl metabolite has pharmacological properties similar to tolterodine and in most cases significantly enhances the action of Detrusitol.
The systemic clearance of tolterodine in serum in most patients is approximately 30 l / h, the terminal T 1/2 (half-life) after taking Detrusitol tablets is in the range from 2 to 3 hours, the T 1/2 of the 5-hydroxymethyl metabolite is 3 hours … T 1/2 of tolterodine and 5-hydroxymethyl metabolite after taking the drug in capsules is approximately 6 hours.
In patients with a deficiency of the CYP2D6 isoenzyme, tolterodine undergoes dealkylation with CYP3A4 isoenzymes, subsequently N-dealkylated tolterodine is formed (it has no pharmacological activity). T 1/2 of the substance in such patients after taking Detrusitol in any form of release is approximately 10 hours.
A decrease in the clearance of the parent compound in CYP2D6 deficiency leads to a significant increase in the concentration of tolterodine (about 7 times) against the background of undetectable concentrations of the 5-hydroxymethyl metabolite. Due to the difference in protein binding of tolterodine and 5-hydroxymethyl metabolite, the AUC (area under the concentration-time curve) of unbound tolterodine in patients with CYP2D6 deficiency is approximately equal to the sum of the AUC of unbound tolterodine and 5-hydroxymethyl metabolite in most patients at the same dosage …
Tolerability, safety and therapeutic efficacy of Detrusitol do not depend on CYP2D6 activity. Stationary concentrations after taking the drug in tablets or capsules are achieved in 2 or 4 days, respectively.
The absolute bioavailability of tolterodine is: the majority of patients - 17%, patients with CYP2D6 deficiency - 65%. Food does not affect the bioavailability of the drug, although the concentration of the substance after taking Detrusitol with meals increases.
Tolterodine and the 5-hydroxymethyl metabolite bind primarily to orosomucoid. The share of unbound fractions is 3.7 and 36%, respectively. V d (volume of distribution) tolterodine - 113 liters. About 17% of tolterodine is excreted in the feces, 77% in the urine. Up to 1% of the dose is excreted unchanged, approximately 4% - in the form of a 5-hydroxymethyl metabolite. N-dealkylated 5-carboxylic acid and 5-carboxylic acid make up about 29 and 51% of the volume that is excreted in the urine, respectively.
In patients with liver cirrhosis, the AUC of unbound tolterodine and 5-hydroxymethyl metabolite is approximately 2 times higher.
In severe renal impairment (at a glomerular filtration rate of insulin of 30 ml / min), the average AUC of unbound tolterodine and 5-hydroxymethyl metabolite doubles. The plasma content of other metabolites in these patients is significantly higher (about 12 times). The clinical significance of an increase in the AUC of these metabolites has not been studied.
Indications for use
According to the instructions, Detrusitol is a drug for the treatment of overactive bladder, manifested by increased urination, frequent and urgent urge to urinate and / or urinary incontinence.
Contraindications
- Frequent and urgent urge to urinate, caused by organic reasons;
- Delay in urination;
- Severe ulcerative colitis;
- Myasthenia gravis;
- Megacolon;
- Slowing stomach emptying;
- Refractory angle-closure glaucoma;
- Glucose-galactose malabsorption, rare hereditary disorders of fructose tolerance, sucrase-isomaltase deficiency (for capsules);
- Age under 18;
- Lactation;
- Hypersensitivity to the drug.
With caution, Detrusitol is prescribed in the following cases:
- Severe obstruction of the lower urinary tract;
- Risk of delayed gastric emptying, including obstructive gastrointestinal disease (eg, pyloric stenosis);
- Renal or hepatic impairment (the daily dose of Detrusitol should not exceed 2 mg);
- Hernia of the esophageal opening of the diaphragm;
- Neuropathy;
- Congenital or acquired lengthening of the QT interval;
- Concomitant use of class IA antiarrhythmic drugs (procainamide, quinidine) or class III (sotalol, amiodarone).
During pregnancy, Detrusitol can only be prescribed for health reasons, if the intended benefits outweigh the potential risks.
Instructions for the use of Detrusitol: method and dosage
Detrusitol is taken orally, without reference to meals.
The daily dose of the drug is 4 mg: prolonged-release capsules - 4 mg once a day, coated tablets - 2 mg 2 times a day.
Depending on the tolerance of Detrusitol, the daily dose may be reduced to 2 mg.
The recommended daily dose for patients with impaired renal and / or liver function, patients receiving ketoconazole or other strong inhibitors of CYP3A4, is 2 mg: capsules - 2 mg once a day, tablets - 1 mg twice a day.
Side effects
Classification of side effects: often - more than 10% of cases, sometimes - from 1 to 10%, rarely - less than 1%:
- Digestive system: sometimes - abdominal pain, constipation, vomiting, flatulence, dyspepsia; rarely - gastroesophageal reflux;
- Central and peripheral nervous system: sometimes - vertigo, drowsiness, headache, visual disturbances, nervousness, weakness, fatigue; rarely - hallucinations, confusion;
- Urinary system: sometimes - dysuria;
- Cardiovascular system: rarely - hot flushes of blood to the skin, palpitations, tachycardia, peripheral edema;
- Allergic reactions: rarely - anaphylactic reactions, incl. angioneurotic edema;
- Side effects associated with anticholinergic action: often - dryness of the oral mucosa; sometimes - xerophthalmia (decreased lacrimation), accommodation disorders; rarely - urinary retention;
- Side effects caused by taking Detrusitol tablets: sometimes - weight gain, dry skin, chest pain, bronchitis;
- Side effects caused by taking Detrusitol capsules: sometimes - sinusitis.
Overdose
The main symptoms are: difficulty urinating and disturbance of accommodation, strong agitation, hallucinations, convulsions, urinary retention, dilated pupils, respiratory failure, tachycardia are also possible.
Therapy: gastric lavage, intake of activated charcoal, measures aimed at lengthening the QT interval.
Symptomatic treatment:
- urinary retention: bladder catheterization;
- hallucinations, severe agitation: physostigmine;
- mydriasis: pilocarpine (in the form of eye drops) and / or transferring the patient to a dark room;
- convulsions or severe agitation: benzodiazepine anxiolytics;
- tachycardia: β-blockers;
- respiratory failure: artificial respiration.
special instructions
Before prescribing Detrusitol, it is necessary to examine the patient in order to exclude the presence of organic causes of frequent and urgent urge to urinate.
The daily dose of the drug should be reduced to 2 mg if necessary for the simultaneous use of CYP3A4 inhibitors, such as antibiotics of the macrolide group (clarithromycin, erythromycin), antifungal agents (itraconazole, miconazole, ketoconazole).
Detrusitol is not recommended for children, since the safety of its use in this age group of patients has not been studied.
Women of childbearing age need to use reliable contraceptive methods during treatment.
Influence on the ability to drive vehicles and complex mechanisms
Detrusitol can reduce the rate of psychophysical reactions and cause disturbances in accommodation, in connection with which, during treatment, one should refrain from driving vehicles and performing potentially hazardous types of work that require increased attention and speed of reactions.
Application during pregnancy and lactation
- pregnancy: Detrusitol can only be used for health reasons after assessing the benefit / risk ratio (the safety profile has not been studied);
- lactation period: therapy is contraindicated.
Pediatric use
The drug is not registered for use in pediatrics. Detrusitol therapy is not prescribed for patients under 18 years of age, since there is no data on the safety / efficacy of the drug in this category of patients.
With impaired renal function
In renal failure, therapy should be carried out under medical supervision in a reduced dose (no more than 2 mg / day).
For violations of liver function
In liver failure, therapy should be carried out under medical supervision in a reduced dose (no more than 2 mg / day).
Drug interactions
- Anticholinergic drugs: the therapeutic effect of Detrusitol and its undesirable effects is enhanced;
- M-cholinomimetics: the therapeutic effect of Detrusitol decreases;
- Metoclopramide, cisapride: their effect is weakened;
- Fluoxetine: a slight increase in the total concentration of tolterodine and its active 5-hydroxymethyl metabolite (not accompanied by clinically significant reactions).
Possible pharmacokinetic interaction with drugs that are metabolized by isoenzymes 2D6 or 3A4 of the cytochrome P450 system, or are inducers or inhibitors of these isoenzymes.
Patients with CYP2D6 deficiency should avoid the simultaneous use of Detrusitol with strong inhibitors of CYP3A4, such as macrolide antibiotics (clarithromycin and erythromycin), antifungal agents (miconazole, itraconazole, ketoconazole), because an increase in the concentration of tolterodine in the blood serum and an increase in the risk of overdose are possible.
Tolterodine does not interact with combined oral contraceptives (containing levonorgestrel or ethinyl estradiol) and warfarin.
Analogs
Detrusitol analogs are: Roliten, Urotol, Uroflex.
Terms and conditions of storage
Store at temperatures up to 25 ºС in a place protected from light and out of reach of children.
The shelf life of capsules is 2 years, of tablets - 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews of Detrusitol
Reviews of Detrusitol are few. Most of them indicate the effectiveness of the drug. It is noted that when using capsules of prolonged action in comparison with therapy with tablets, the therapeutic effect is more pronounced. The development of side effects is rarely reported. Dry mouth (the most common disorder during therapy) is usually mild.
The price of Detrusitol in pharmacies
The price of Detrusitol is unknown because the drug is not available in pharmacies.
The approximate cost of analogues: Urotol - 531–666 rubles (56 tablets of 1 mg) or 647–723 rubles (56 tablets of 2 mg), Roliten (30 tablets of 2 mg) - 447–485 rubles.
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!
