Trospium chloride

Pharmacological properties

trospium chloride is a quaternary ammonium base derived from nortropanol and belongs to the group of parasympatolytics or anticholinergics. depending on the concentration of the drug, it competes with endogenous acetylcholine transmitters at the postsynaptic level. It is a competitive acetylcholine antagonist on the postsynaptic membrane membranes of smooth muscles, has a high affinity for m1- and m3-cholinergic receptors, and a lower affinity for m2-cholinergic receptors, and binds to nicotinic receptors at a slightly low level. m-anticholinergics act on peripheral m-cholinergic receptors. The mechanism of action is the competitive inhibition of acetylcholine at the postsynaptic membrane receptors of the smooth muscles of the gastrointestinal tract and the genitourinary system. the drug reduces the tone of the smooth muscles of the urinary tract and weakens the bladder detrusor both due to the anticholinergic effect and due to the direct antispastic effect.

It has a ganglion blocking effect. It inhibits the secretion of salivary and sweat glands, paralyzes accommodation. It has a dose-dependent effect on heart rate, accelerating it.

Pharmacokinetics When taken orally C_max in plasma reached after 4-6 hours. T_½ varies from 5 to 18 hours. It does not accumulate in the body, binds to blood plasma proteins up to 50–80%.

When using a single dose in the range of 20-60 mg, its concentration in the blood plasma increases in proportion to the dose taken. It is excreted by the kidneys, most of it is unchanged, less (about 10%) is in the form of cyclic alcohols, the metabolite is formed by hydrolysis of ether. It does not penetrate the BBB (does not cause side effects from the central nervous system).

There are no pharmacokinetic differences in patients of different ages and sex.

The role of hepatic metabolism in elimination is limited.

Indications

Symptomatic treatment of idiopathic detrusor hyperactivity or neurological detrusor hyperactivity, accompanied by symptoms of pollakiuria, impaired bladder function (urinary incontinence and imperative urination).

Application

Used in adults. taken orally on an empty stomach (before meals), without chewing, drinking plenty of water.

The dosage regimen and duration of treatment are determined by the doctor individually for each patient, depending on the clinical picture and severity of the disease.

For the treatment of idiopathic hyperactivity of the detrusor, 10–15 mg of trospium chloride is prescribed 3 times a day (30–45 mg / day).

For the treatment of neurological hyperactivity of the detrusor, 20 mg of trospium chloride is prescribed 2 times a day in the morning and evening (40 mg / day).

In patients with renal failure (creatinine clearance of 10-30 ml / min / 1.73 m²) The daily dose of trospium chloride should not exceed 20 mg.

Contraindications

Hypersensitivity to the components of the drug; urinary retention; glaucoma; tachyarrhythmia; myasthenia gravis; severe chronic inflammatory bowel disease (ulcerative colitis and Crohns disease); toxic megacolon; renal failure requiring dialysis (creatinine clearance 10 ml / min / 1.73 m2); prostatic hyperplasia; urinary tract infections; impaired liver function; During pregnancy and breastfeeding; childhood.

Side effects

The trospium chloride observed during use is systematized according to the classes of organs and systems and the frequency of occurrence: very often (≥1 / 10), often (≥1 / 100, 1/10), infrequently (≥1 / 1000, 1/100), rarely (≥1 / 10,000, 1/1000), very rarely (1/10 000), including isolated cases.

From the digestive system: often - dry mouth, dyspepsia, abdominal pain, nausea, constipation; infrequently - diarrhea, flatulence.

On the part of the immune system: rarely - angioedema, anaphylaxis.

From the side of the organ of vision: infrequently - violation of accommodation (especially in patients with farsightedness and insufficient vision correction).

From the cardiovascular system: infrequently - tachycardia, rarely - tachyarrhythmia.

From the respiratory system: infrequently - shortness of breath.

From the liver and biliary tract: rarely - an increase in the level of individual laboratory parameters (slight or moderate increase in transaminase).

On the part of the skin: infrequently - a rash on the skin.

From the kidneys and urinary tract: infrequently - impaired urination, rarely - urinary retention.

From the side of the nervous system: infrequently - headache, dizziness.

From the musculoskeletal system: rarely - arthralgia (joint pain), very rarely - myalgia (muscle pain).

Other: infrequently - weakness, chest pain, asthenia.

special instructions

Before starting treatment, the presence of infections and organic etiology should be excluded (impaired renal function, heart, polydipsia, malignant neoplasms, carcinomas of the urinary system).

The drug contains lactose monohydrate as an auxiliary substance, therefore, patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome cannot use the drug.

Use the drug with caution with:

• gastrointestinal obstruction (e.g. pyloric stenosis);
• obstructive outflow of urine with a risk of having final urine;
• autonomic (autonomous) neuropathy;
• hernia of the esophageal opening of the diaphragm, accompanied by reflux esophagitis.

It is used with extreme caution in patients with coronary heart disease and heart failure, impaired renal function.

When prescribing the drug to patients with impaired bladder detrusor function, the ability to completely empty the bladder (including catheterization) should be provided.

Use during pregnancy and lactation

Pregnancy. The safety of use during pregnancy has not been established, therefore, data on the effect of the drug on pregnancy and / or embryonic development, fetal development, childbirth and postnatal development are insufficient. In this regard, Spazmeks are not used during pregnancy.

The period of breastfeeding. The drug is not recommended for use during lactation.

Children. The drug is not prescribed for children.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. For the treatment period, it is recommended to refrain from driving vehicles and engaging in potentially hazardous activities that require increased attention and speed of psychomotor reactions, since there is a risk of accommodation disturbance.

Interactions

With simultaneous use, it enhances the anticholinergic effect of amantadine, tricyclic antidepressants, quinidine, n1-histamine receptor blockers, disopyramide.

When taken simultaneously with β-adrenergic agonists, enhances heart rate.

With simultaneous use with prokinetics (metoclopramide and cisapride) reduces the severity of the effect of prokinetics.

With simultaneous use with drugs containing guar, colestyramine and colestipol, the resorption of trospium chloride decreases, so the simultaneous use of these drugs is not recommended.

Trospium chloride does not change the activity of the enzyme system of cytochrome P450, so it can be taken simultaneously with drugs metabolized by this system.

Overdose

Symptoms: anticholinergic manifestations, such as visual disturbances, dry mouth, tachycardia, flushing of the skin.

Treatment: drug withdrawal, gastric lavage, intake of adsorbents (activated charcoal), symptomatic and supportive therapy, catheterization with urinary retention; in patients with glaucoma, pilocarpine in the form of eye drops is used. In severe cases, cholinomimetics are prescribed (e.g. neostigmine).

In tachycardia and circulatory disorders, β-adrenoreceptor blockers are injected iv (for example, 1 mg iv propranolol under the control of ECG and blood pressure).

Storage conditions

In the original packaging at a temperature not exceeding 25 ° C.