Nausilium

Nausilium is a drug used to eliminate gastrointestinal dysfunction. It is a stimulant of intestinal peristalsis.

Indications Nausilium

It is used to eliminate vomiting and nausea that occur for a period of less than 48 hours.

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Release form

The medicine is released in tablets, 10 pieces per blister pack. The pack contains 1 or 3 such packs.

Pharmacodynamics

Domperidone is a dopamine antagonist with antiemetic action. This element weakly penetrates the BBB, with its use only rarely extrapyramidal symptoms are observed (especially in adults), although it stimulates the secretion of prolactin from the pituitary gland. The antiemetic effect of the drug probably develops due to a combination of peripheral action, and also antagonism of dopamine endings within the trigger region of chemoreceptors, located outside the BBB, in the posterior part (area postrema).

Animal tests, coupled with the low LS values observed inside the brain, indicate that domperidone has mainly only peripheral effects on dopamine endings.

Studies in humans have shown that after oral administration, domperidone increases the pressure level within the lower esophagus, and also improves antroduodenal motility and promotes gastric emptying.

The element does not affect the secretory function of the stomach.

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Pharmacokinetics

Domperidone is rapidly absorbed when taken orally (on an empty stomach). Peak plasma levels are observed after 0.5-1 hour. Low bioavailability values of the drug (about 15%) are due to extensive metabolic processes during the first pass through the liver and intestinal wall. In a healthy person, the bioavailability of the drug increases when taken after meals, but people with problems with the gastrointestinal tract should take Nausilium 15-30 minutes before meals.

Reduced gastric pH results in decreased absorption of domperidone. Bioavailability values after oral administration of the drug are reduced if baking soda or cimetidine is taken beforehand. If the tablet is taken orally after meals, its maximum absorption is slightly slowed down and the AUC value is slightly increased.

After oral use, domperidone does not accumulate and does not cause its own metabolic processes. Peak values in blood plasma after 1.5 hours (21 ng / ml) after 14 days of use in a portion of 30 mg / day were almost the same as the indicators after using the first portion (18 ng / ml). The drug is synthesized with blood plasma proteins by 91-93%.

Animal studies of drug distribution processes using a radiolabeled substance have shown that it is well distributed within tissues, although it has a low concentration within the brain. In addition, small amounts of the drug pass through the placenta in animals.

Hepatic metabolism of domperidone is rapid and extensive. It is carried out using hydroxylation processes, as well as N-dealkylation. In vitro metabolic process tests using a diagnostic inhibitor have revealed that the CYP3A4 element is the main form of hemoprotein P450 involved in N-dealkylation, and components of CYP3A4, as well as CYP1A2 and CYP2E1, participate in aromatic hydroxylation of the active substance of the drug.

Excretion with feces and urine is 66% and 31% of the dose taken orally, respectively. Only a small portion of the substance is excreted as an unchanged element - about 1% with urine and 10% with feces. The half-life of the drug from plasma when taken as a single dose is about 7-9 hours (healthy person). In people with severe renal failure, this period is longer.

Dosing and administration

The medicine should be taken before meals, because when taken after meals, there is a slight delay in its absorption. The duration of therapy using Nausilium can be a maximum of 7 days.

To relieve symptoms of vomiting with nausea, adolescents from 16 years of age and adults need to take 1 tablet (volume 10 mg) of LS three times a day. The maximum daily dose is exactly 3 tablets - 30 mg.

Without consulting a doctor, the medicine can only be taken for 48 hours.

Use Nausilium during pregnancy

There is limited post-marketing data on the use of Nausilium in pregnant women. Because of this, the drug is only approved for use when the physician believes that the benefit to the mother outweighs the risk of complications to the fetus.

Tests have shown that the drug can pass into breast milk. The amount of the substance that can pass into the body of a breastfed infant through the mother's milk is insignificant. The maximum possible relative portion for a breastfed infant is approximately 0.1% of the dosage taken by the mother, adjusted for weight.

There is no data on whether domperidone is harmful to the child, which is why it is recommended to stop breastfeeding while taking the drug.

Contraindications

Among the contraindications:

• the presence of intolerance to the drug or its auxiliary components;
• prolactinoma;
• the presence of renal or hepatic dysfunction;
• people who have prolongation of the QT interval, which is a major factor in heart disorders or diseases;
• presence of liver failure.

It is prohibited to use the medicine in cases where stimulation of gastric motility may be dangerous - for example, in the presence of bleeding in the gastrointestinal tract, perforation or mechanical obstruction.

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Side effects Nausilium

Use of the drug may cause the following side effects:

• immune disorders: signs of allergy appear sporadically, including anaphylaxis and hypersensitivity;
• disorders of the endocrine system: occasionally an increase in prolactin levels is observed;
• mental disorders: occasional feelings of excitement, nervousness, anxiety or irritability, as well as a state of depression and a weakening or complete disappearance of libido;
• problems with the nervous system function: occasional feelings of thirst, lethargy or drowsiness, dizziness, migraine, insomnia, akathasia, headaches and extrapyramidal symptoms;
• symptoms from the cardiovascular system: isolated development of edema, severe ventricular arrhythmia, palpitations, prolongation of the QT interval, changes in the rhythm of heart contractions and heart rate, and also an increase in blood pressure and systolic blood pressure;
• Gastrointestinal disorders: gastrointestinal disorders are occasionally observed, including regurgitation, abdominal pain, burning sensation, nausea, constipation and changes in appetite. Occasionally, short-term spasms in the intestines or stomach, diarrhea, dry mouth and belching occur;
• visual impairment: possible development of oculogyric crisis;
• lesions of the subcutaneous layers and epidermis: rashes or itching appear sporadically. Quincke's edema or urticaria may appear;
• problems affecting reproductive function and the mammary glands: gynecomastia, galactorrhea, increased sensitivity of the mammary glands, pain and swelling in their area or discharge from them, as well as hot flashes, lactation disorders, amenorrhea and an unstable menstrual cycle are occasionally observed;
• damage to the function of the musculoskeletal system and connective tissues: occasionally there is pain in the legs;
• urinary disorders: painful and frequent urination or delayed urination are observed sporadically, as well as dysuria;
• systemic disorders: asthenia occasionally develops;
• others: development of stomatitis, chills, conjunctivitis, hyperhidrosis, and in addition, cramps in the calf muscles;
• changes in laboratory test results: cholesterol, AST or ALT values increase occasionally. Occasionally, the prolactin level in the blood increases and deviations from normal values of functional liver tests are noted.

Since the pituitary gland is located outside the BBB, domperidone can provoke an increase in prolactin levels. Rarely, such hyperprolactinemia can cause neuroendocrine side effects (amenorrhea, galactorrhea, or gynecomastia).

At the stage of post-marketing tests, no differences were found between the safety profiles of drug use in adolescents and adults (except for extrapyramidal disorders and other signs, agitation and seizures associated with CNS function, and observed mainly in adolescents).

Overdose

Signs of poisoning include agitation, seizures, feelings of disorientation or drowsiness, altered consciousness, and extrapyramidal disturbances.

Domperidone has no antidote, so in case of severe intoxication, gastric lavage should be performed (within 60 minutes after taking the drug) and activated carbon should be given to the patient. In addition, constant monitoring of the victim and supportive measures will be required. Anticholinergic drugs and drugs that help with Parkinson's disease are effective in controlling extrapyramidal symptoms.

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Interactions with other drugs

It is prohibited to combine Nausilium with erythromycin, ketoconazole and other potent drugs that slow down the activity of the CYP3A4 element, as well as drugs that prolong the QT interval (including posaconazole, itraconazole with fluconazole, as well as ritonavir, telaprevir, telithromycin, saquinavir with clarithromycin, voriconazole and amiodarone).

Anticholinergic drugs can neutralize the antidyspeptic effect of domperidone.

If combined use with antisecretory agents or antacids is required, it is recommended to take them after meals, not before (concomitant use with domperidone is prohibited, because these medications reduce its bioavailability when taken orally).

Domperidone can be combined with the following drugs:

• neuroleptics, as it potentiates their properties;
• dopaminergic agonists (such as bromocriptine and L-dopa), because it inhibits their negative peripheral effects (such as digestive disorders and vomiting with nausea), without neutralizing their main effect.

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Storage conditions

Nausilium should be kept in a place out of reach of small children, at temperatures not exceeding 30°C.

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Shelf life

Nausilium can be used for 3 years from the date of release of the drug.

Application for children

The medication is prohibited for use in children under 16 years of age.

Domperidone for children is prescribed only in the minimum effective doses.

Analogues

Analogues of the drug are such drugs as Metoclopramide, Cerucal and Itomed with Motilium, Motilak and Passazhiks.

Reviews

Nausilium is considered a very good antiemetic. Most reviews of it note its high effectiveness in stopping nausea and vomiting that cannot be stopped with other drugs.