Last Updated on February 19, 2017 by Dr.Derek Fhisher
Most popular brand: Detrol
Active ingredient: Tolterodine
Available dosage forms: 1, 2, 4 mg
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Tolterodine general information
Using tolterodine with any of these medicines is mainly not recommended, but might be needed in some instances. Whenever you’re taking tolterodine, it’s especially important your healthcare professional know if you’re taking any one of the medicines given below. This information includes only the typical doses of tolterodine. Appropriate studies performed to date haven’t demonstrated geriatric-specific issues that would restrict the usefulness of tolterodine within the elderly.
Call your physician for medical advice regarding side effects. Only your doctor, nurse, or pharmacist can offer you advice on what exactly is safe and successful for you. In case your dose differs, don’t change it unless your own doctor directs you to achieve that. Remember to ask your physician about anything you don’t understand.
Take tolterodine at the similar time daily. To do so might increase the chance of side consequences. The aggregate of medicine you take is based on the strength of the medicine. Use Paxil as instructed by your doctor.
In deciding to utilize a medicine, the dangers of taking the medicine must certanly be weighed against the good it’ll do. Don’t take different medicines unless they’ve been discussed with your physician. Some side effects may happen that usually don’t need medical attention. It’s frequently used in hypertonic bladder.
It looks like camping trips create far better sleep schedules. Generally, 1 nap within the early afternoon is the greatest approach to adding napping to your own sleep cycle. Find outlets to lower your stress and you’re going to often find that better sleep comes because of this. To diminish the frequency of urination, medications including oxybutynin and tolterodine are frequently used.
To begin with, sleep debt is just a cumulative issue. Proceed to bed and awaken around precisely the same time daily. We welcome you to take a close look at our site to find out more or in case you have questions please don’t hesitate to contact us at the number above.
The use of exercise only grows more important with age. That’s because sleep is a critical component to our general mental as well as physical health. Others might suffer from one of a handful of diagnosable and frequently treatable sleep disorders. Cognitive skills weren’t affected.
DETROL LA has both advantages and hazards. There could be alternatives. Additionally, It suggests that a household camping trip before school starts might be considered a healthful family experience.
Difficulty in urinating, almost always, is gradually experienced by somebody. As a consequence, the individual experiences symptoms of overactive bladder. Doctors also run into certain neurological problems like Parkinson’s disease, and multiple sclerosis that could create the bladder to eventually become overactive. This condition may be caused due to disorders related to the nervous system.
Burning sensation while attempting to urinate. Frequent urination in little quantities. These pouches don’t empty out during urination. Drinking a great deal of water, at least 2-3 liters per day, will assist in increasing urination.
It would be a fantastic thought to be certain dietary changes. Forget the caffeine for some time, and see whether there are improvements. Making certain modifications to your lifestyle will even prove beneficial.
Bladder diverticulum is actually a condition that you can be born with or it could arise any moment. The condition is distinguished by a sudden and irresistible impulse to urinate even as soon as the bladder isn’t full. Clean skin is likewise a significant step in preventing infection. Cramps in the decrease abdomen.
Overactive bladder is actually a condition at which bladder isn’t able to hold urine for a very long duration. A house remedy to take care of difficulty in urination is really to apply some heat on the reduce abdomen and close to the pubic bone. The most important symptom is actually a sudden and robust desire to urinate, although the quantity of urine might not be as much as expected. Overactive bladder was attributed to improper performance of the bladder muscle.
Drug therapy is among the treatment alternatives. In cases, wherein, the individual may not answer conservative treatment techniques, surgery might be considered as an applicable option. Another treatment that is employed in the majority of cases is recognized as bladder training. It is exceedingly essential to finish the course. In the all-natural treatment I recommend below, a mix of lipid-free pumpkin seed extract together with soy germ extract is utilized to help keep a healthy bladder.
In a few people, this issue could result in involuntary loss of urine (incontinence), which might induce leakage of urine soon following the urge is felt. Within this condition, passing urine within the normal way has a tendency to become an issue and is sometimes painful. Eventually, your bladder will likely be trained to hold bigger levels of urine and you may not need to visit the bathroom more frequently. You also have to inform the physician about any other drugs that you may be using, in order to get rid of the chances of an adverse drug interaction. This really is because these products might cause complication, as well as their use needs to be limited, unless advised by a health professional. For this particular, a physical therapist might be appointed to work together with the patient.
Description of the active ingredient Tolterodine / Tolterodinum.
Formula: C22H31NO, chemical name: (+) – (R) – 2 – [alpha – [2 – (diisopropylamino) ethyl] benzyl] – p – cresol
Pharmacological group: Wegetotropona funds / funds holinoliticheskie / m – anticholinergics
Mode of action: antispasmodic, holinoliticheskoe.
Tolterodine is a competitive antagonist of m – cholinergic receptors, which are located in salivary glands and bladder. Tolterodine to its active 5 – hydroxymethyl metabolite are highly specific for muscarinic receptors and does not affect other receptors, and they possess receptor selectivity for the urinary bladder as compared to receptors located in the salivary glands. Tolterodine reduces the contractile activity of the bladder and salivation. Tolterodine suppress the involuntary discharge of urine, reduces the detrusor pressure and increases the volume of urine increases interval between urination, it contributes to the weakening or disappearance of urgency. At doses that exceed therapeutic, tolterodine causing incomplete emptying of the bladder and increases the amount of residual urine. After 4 weeks, the therapeutic effect is achieved
tolterodine When using rats and mice at doses in 9 -. 14 times the maximum recommended human dose, increasing the risk of developing tumors were found
The Ames test (p. using two strains of Escherichia coli and Salmonella typhimurium strains), chromosome aberration test with human lymphocytes, the test for gene mutations in mice lymphoma cells, micronucleus test in the mutagenic effects of mice bone marrow cells of tolterodine is not revealed.
The introduction of female mice not marked effect on fertility and reproductive activity – 20 mg / kg tolterodine daily for 14 days before mating (time exposure system in animals is 15 times higher than in humans, based on the area under the concentration curve). Introduction of male mice of 30 mg / kg per day to tolterodine fertility disorders not caused
At high concentrations of tolterodine and its main metabolite. (50 – 100 times higher than the therapeutic concentration) was observed in dogs lengthening the interval QT. In clinical observations in a large representative sample of patients when used in recommended doses of tolterodine long QT interval is detected.
Tolterodine ingestion rapidly absorbed. The maximum concentration is usually reached within 1 – 3 h. The maximum concentration at a dosage range from 1 mg to 4 is increased in proportion to dose. Bioavailability tolterodine in most patients is 17% in people with CYP2D6 failure – 65%. Tolterodine is extensively metabolized in the liver, primarily involving isozyme CYP2D6, thereby forming the pharmacologically active 5 – hydroxymethyl metabolite, which is further metabolized to 5 – carboxylic acid and N – dezalkilirovannoy 5 – carboxylic acid. Tolterodine not inhibit of CYP2D6, CYP2C19, CYP3A4 and CYP1A2. Systemic clearance of tolterodine is approximately 30 liters per hour. The half-life of tolterodine is 2 – 3 hours. The half-life of 5 – hydroxymethyl metabolite is 3 – 4 hours. People with reduced metabolism (with CYP2D6 deficiency, these people are also called “weak metabolizantami”, which make up about 7% of the population, as opposed to another, which is called “extensive metabolizantami”) tolterodine dezalkiliruetsya with the participation of CYP3A4 to form a pharmacologically inactive N – dezalkilirovannogo tolterodine. Decreasing clearance and increase in half-life (approximately 10 hours) in humans with decreased metabolism leads to higher tolterodine concentrations (approximately 7 times). Food does not affect the exposure of unbound tolterodine and the active 5 – hydroxymethyl metabolite in patients with an increased metabolism, but its concentration increases at the reception during the meal. Tolterodine plasma protein binds to 96,3% (mainly alpha-1 acid – glycoprotein), 5 – hydroxymethyl metabolite binds to 64%. Tolterodine and the 5 – hydroxymethyl metabolite bind preferentially to orosomucoid. The unbound fraction of 3.7 and 36%, respectively. Since the binding of tolterodine and its active metabolite with a different protein, the total free plasma concentration at equilibrium and are similar in extensive metabolizantov weak. The volume of distribution when administered intravenously at a dose of 1.28 mg 86.3 – 139.7 (about 113) liters. Tolterodine is excreted in the feces (17%) and urine (77%). The unchanged output of less than 1%, in the form of 5 – hydroxymethyl metabolite derived 5 – 14%. 5 – carboxylic acid and N – dezalkilirovannaya 5 – carboxylic acid are respectively 51% and 29% of the amount that is excreted in urine. At insufficiency of CYP2D6 isoenzyme in unchanged form stands out less than 2.5%, in the form of 5 – hydroxymethyl metabolite – less than 1%
In patients with cirrhosis of the liver area under the concentration value of -. Time of tolterodine and the active 5 – hydroxymethyl metabolite increases about 2 times
The average value of the area under the concentration -. time of tolterodine and its 5 – hydroxymethyl metabolite 2-fold higher in patients with severe renal function (glomerular filtration rate less than 30 mL / min). other blood serum concentration of metabolites in these patients is much higher (12 times). The clinical significance of increasing the area under the concentration -. Time of these metabolites is unknown
Hyperactivity (hyperreflexia, instability) of the bladder, which is manifested urinary incontinence, frequent urination or frequent urination imperative.
How to use and dosage of tolterodine
Tolterodine taken orally, regardless of the meal, 2 times a day to 2 mg. Based on individual tolerability, the total dose may be reduced to 2 mg per day. Duration of treatment was 2 – 3 months, followed by evaluate the effectiveness and the need for further therapy
When liver and / or kidney failure, joint use with potent inhibitors of CYP3A4, as well as the development of side reactions reduce the dose to 1 mg 2. times a day.
Before starting therapy should exclude organic causes of mandatory and frequent urge to urinate.
When you save a dryness in the mouth for more than two weeks in patients receiving tolterodine is necessary to consult a dentist.
studies have It found that the effect of tolterodine on QT interval was more pronounced when using a dose that is greater than 8 mg per day (this dose of 2 times the therapeutic dose – 4 mg), and patients who have a decreased activity of the isozyme CYP2D6. With simultaneous use of tolterodine and moxifloxacin 8 mg per day, tolterodine effect on QT interval was less pronounced when compared to tolterodine four-treatment, but the reliability of said data is not proven. Therefore you must be very careful when using tolterodine patients who have congenital or acquired prolongation of the interval the QT, electrolyte disturbances (such as hypomagnesemia, hypokalemia, hypocalcemia), bradycardia, presence of diseases and pathological changes in the heart (eg, myocardial ischemia, cardiomyopathy, congestive heart failure, arrhythmia), as well as those patients taking antiarrhythmic drugs of class IA (e.g., procainamide, quinidine) or a class III (e.g., sotalol, amiodarone).
women of reproductive age tolterodine should only be provided using reliable contraception.
currently, the safety and efficacy of using the drug in children has not been studied.
During treatment with tolterodine should refuse to perform activities that require high concentration and speed of psychomotor reactions (including means of transport management, work with mechanisms).
Hypersensitivity, myasthenia gravis, urinary retention, angle-closure glaucoma, megacolon, severe ulcerative colitis, pregnancy, breastfeeding, age 18 years (effectiveness and safety are not defined).
Restrictions on the use
obstructive lesions of gastro – intestinal tract (eg pyloric stenosis), an increased risk of reduced motility of the gastro – intestinal tract, a significant obstruction of the tract urinary outflow from the risk of urinary retention, liver and / or renal insufficiency (daily dose should not exceed 2 mg) , irreducible hernia, hiatal hernia, neuropathy, congenital or acquired prolongation of the interval the QT, bradycardia, electrolyte disturbances (such as hypomagnesemia, hypokalemia, hypocalcemia), heart disease (eg, myocardial ischemia, cardiomyopathy, congestive heart failure, arrhythmia), the use of antiarrhythmic drugs of class IA agents (e.g., procainamide, quinidine) or a class III (e.g., sotalol, amiodarone).
Pregnancy and breastfeeding
In studies on mice showed that pregnant females tolterodine in doses of 20 mg / kg per day, malformations or abnormalities were observed by oral administration. High doses (30 – 40 mg / kg per day, about 20 – 25 times higher human dosage, based on the area under the concentration – time) cause weight reduction embryos body embrioletalnost, increase the frequency of embryonic malformations (finger anomalies cleft fall, intra-abdominal hemorrhage, reduction of primary ossification, skeleton anomalies). There was no embryotoxic and teratogenic in pregnant rabbits that received tolterodine subcutaneously at a dose of 0.8 mg / kg per day. Strictly controlled and adequate studies in pregnant women have not performed. In pregnancy, the use of tolterodine is possible only on prescription, if the expected benefit to the mother above the possible risk to the fetus. Women of reproductive age tolterodine should be used only when the use of reliable contraception.
Tolterodine is excreted in breast milk in mice. Introduction tolterodine during lactation mice at a dose of 20 mg / kg per day resulted in a slight decrease in body weight gain in the offspring, but the weight recovered maturation phase. During therapy, tolterodine should stop breast-feeding (it is not known whether tolterodine in breast milk of women stands out).
Side effects of tolterodine
The nervous system and sensory organs: dizziness, headache, drowsiness, fatigue, nervousness, confusion, impaired consciousness, hallucinations, paresthesia, dry sclera, blurred vision, disturbance of accommodation, xerophthalmia
Digestive system: dryness of the oral mucosa, dyspepsia, nausea, abdominal pain, constipation, vomiting, gastro-oesophageal reflux, diarrhea, flatulence
Urogenital system:. urinary tract infection, urinary urgency, painful, difficult urination, urinary retention, hematuria, leucocyturia, dysuria, edema peripheral
The respiratory system:. bronchitis, sinusitis
Other:. flu-like symptoms, pain in joint pain, allergic reactions (including anaphylaxis, angioedema, angioedema, and others), weakness, fatigue, fatigue, dry skin, weight gain, breast pain, hot flushes in the face.
tolterodine Interaction with other substances
When combined with tolterodine anticholinergic drugs enhanced the therapeutic effect of tolterodine and increased risk of adverse reactions.
Tolterodine reduces the effect of prokinetic (cisapride, metoclopramide).
The effect of tolterodine reduce muscarinic cholinergic receptor agonists.
No tolterodine interaction with warfarin, and combined oral contraceptives that contain levonorgestrel and ethinyl estradiol
Perhaps tolterodine pharmacokinetic interaction with drugs that are metabolized by cytochrome P450 -. CYP3A4 or CYP2D6 (inhibitors and / or inducers)
. When used together, tolterodine and fluoxetine (a potent inhibitor of CYP2D6, metabolised to norfluoxetine, which is an inhibitor of CYP3A4) in extensive metabolizantov significantly inhibited the metabolism of tolterodine (increase in the area under the concentration – time tolterodine 4.8 times, reduction of area under the concentration – time and maximum concentration of the active 5 – hydroxymethyl metabolite 20 and 52%, respectively, with the total concentration of the unbound fraction of tolterodine and 5 – hydroxy – metabolite is increased by 25%), but did not change the dosing regimen required
avoid use with tolterodine. potent inhibitors of CYP3A4, such as antifungal agents (itraconazole, ketoconazole, miconazole), or macrolide antibiotics (clarithromycin, erythromycin).
When sharing tolterodine 2 mg 2 times a day duloxetine and 40 mg 2 times a day (moderate CYP2D6 inhibitor ) increases the stable part of the area under the concentration – time tolterodine at 71%, but the effect on the pharmacokinetics of 5 – gidroksilmetabolita not provided; . Care must be taken
When used together, tolterodine and amantadine is synergistic effect holinolitichesky; caution is needed.
When used together, tolterodine and haloperidol increases the risk of increased intraocular pressure.
tolterodine, relaxing salivation and causing dry mouth, difficult absorption of sublingual nitroglycerin.
When used together, tolterodine and ipratropium bromide, promethazine mutually enhanced anticholinergic effects; caution is needed.
When used together, tolterodine and oxybutynin mutually increase the frequency and / or severity of anticholinergic side effects (constipation, dry mouth, drowsiness, and other).
pilocarpine eye drops when used in conjunction with a one-tolterodine education enhances the reduction of intraocular fluid. Against the background of systemic effects of pilocarpine increases the risk of conduction disturbances.
Tolterodine is not an inhibitor of CYP2D6, CYP2C19, CYP3A4, CYP1A2, therefore at a joint reception with tolterodine is not expected to increase the plasma concentrations of drugs that are metabolized by these isoenzymes.
symptoms. When tolterodine overdose develop strong excitation, hallucinations, convulsions, paresis of accommodation, mydriasis, tachycardia, prolongation of the interval QT, respiratory failure, tenesmus, urinary retention.
Treatment: gastric lavage, activated charcoal; symptomatic treatment; bladder catheterization – with urinary retention; physostigmine – with strong central anticholinergic effects. benzodiazepines (diazepam, lorazepam) – with an excited expression or cramps; mechanical ventilation – at which developed respiratory failure; beta – blockers – tachycardia; with pilocarpine eye drops and / or transfer of the patient in a dark room – with mydriasis; in connection with the possible prolongation of the QT interval is necessary to conduct monitoring and electrocardiography.