Peridon

Peridon belongs to the category of medicines that help stimulate intestinal peristalsis. Its main element is domperidone. This substance is a dopamine antagonist and has antiemetic effects.

It has been proven that after oral administration, domperidone increases the duration of duodenal and antral contractions, which makes it possible to increase the rate of bowel emptying. At the same time, domperidone does not affect the processes of gastric secretion. [1]

Indications Peridon

It is used to relieve signs of vomiting with nausea , lasting at least 2 days.

Release form

The release of the medication is realized in tablet form - 10 pieces inside the cell plate. There are 1 or 3 such plates inside the box.

Pharmacodynamics

The principle of the therapeutic effect of drugs is associated with the chemical and physical characteristics of the main active element - domperidone. It can overcome the BBB in small volumes.

The use of the drug occasionally causes the appearance of extrapyramidal negative symptoms, especially in an adult, but at the same time, domperidone can stimulate the pituitary secretion of prolactin. [2]

There is official information that small volumes of a substance determined inside the brain show that domperidone has a predominantly peripheral effect on dopamine endings.

The antiemetic activity of the drug is associated with a harmonious combination of gastrokinetic peripheral influence and antagonism in relation to dopamine endings, within the trigger region of chemoreceptors located outside the BBB in the posterior region.

Pharmacokinetics

Absorption.

Domperidone is absorbed at high speed after oral administration on an empty stomach, reaching the plasma Cmax after 0.5-1 hour. The low bioavailability of domperidone taken orally (about 15%) is associated with extensive metabolic processes during the 1st passage inside the liver and intestinal wall. Given that in a healthy person, the level of bioavailability of the substance increases when consumed after a meal, people with gastrointestinal disorders need to inject the medication 15-30 minutes before eating.

A decreased gastric pH impairs the absorption of domperidone. The bioavailability value after oral administration of drugs decreases with the previous use of cimetidine or baking soda.

The introduction of the drug inside after a meal slightly reduces the maximum absorption; at the same time, there is a slight increase in the AUC indicator.

Distribution processes.

After ingestion, there is no cumulation of domperidone and the induction of its own metabolism. Plasma Cmax after 1.5 hours (21 ng / ml) with a 2-week administration of 30 mg per day was almost the same as with the introduction of the first portion (18 ng / ml).

Protein synthesis of domperidone is 91-93%. Distribution tests carried out with animals (using drugs labeled with an isotope of the radioactive type) revealed a significant tissue distribution and low levels of the component inside the brain. A small amount of the drug in animals crosses the placenta.

Exchange processes.

Domperidone is extensively and at high speed involved in intrahepatic metabolic processes through hydroxylation as well as N-dealkylation. In vitro testing of metabolic processes using a diagnostic inhibitor revealed that CYP3A4 is the main type of P450 hemoprotein involved in N-dealkylation; at the same time, CYP3A4 with CYP1A2, as well as CYP2E1, are participants in the aromatic hydroxylation of the substance.

Excretion.

Excretion with feces and urine is equal to 66% and 31% of the dose taken orally. The unchanged substance is excreted in small quantities (10% with feces and about 1% with urine).

The term plasma half-life when administered as a single serving in volunteers is 7-9 hours; in persons with severe liver failure, it is lengthened.

Dosing and administration

To reduce the intensity of manifestations of vomiting with nausea, Peridon is consumed in 1 tablet 3 times a day. This portion is the maximum allowable per day (30 mg).

Without a medical prescription, therapy with this drug can last a maximum of 2 days. In the absence of the desired effect from taking it, you need to consult a doctor. In general, the treatment can last no more than 1 week.

• Application for children

It is forbidden to prescribe medicine to persons under the age of 16.

Use Peridon during pregnancy

The effect of the drug on pregnant patients has not been studied, therefore there is no data on the possible consequences of such use. Therefore, during pregnancy, Peridon is prescribed only in cases where the benefits of taking it are more likely than the risks of complications.

If there is a need for the use of drugs during breastfeeding, it is discontinued for the period of therapy.

Contraindications

Among the contraindications:

• severe intolerance to the elements that make up the drug;
• neoplasm in the pituitary gland associated with the release of prolactin (prolactinoma);
• renal or hepatic dysfunction;
• failure of the liver;
• diagnosed prolongation of the QT interval, which is the cause of cardiac dysfunction;
• phenylketonuria.

It is also not used in cases where vomiting occurs with motion sickness, mechanical blockage or perforation, and also bleeding inside the gastrointestinal tract.

It is forbidden to prescribe in combination with drugs that prolong the QT-gap, itraconazole, telithromycin, ritonavir and erythromycin, and in addition with clarithromycin, fluconazole, telaprevir and ketoconazole, as well as with amiodarone, saquinavir and posazaconazole with voriconazole.

Side effects Peridon

The main side signs:

• an allergy that could turn into anaphylaxis;
• an increase in prolactin indicators;
• dizziness, drowsiness, fatigue and nervousness, as well as headaches, thirst, convulsions, extrapyramidal disturbances and depression;
• tachycardia, edema, ventricular arrhythmia and sudden cardiac death;
• short-term spasms in the intestinal region, xerostomia, constipation, diarrhea, heartburn and nausea;
• rashes, Quincke's edema, itching and urticaria;
• swelling, pain and enlargement of the mammary glands, lactation disorder, amenorrhea, changes in the menstrual cycle and gynecomastia;
• increased urinary frequency, dysuria and asthenia;
• stomatitis or conjunctivitis.

If atypical negative signs appear after using the medication, you need to consult with your doctor about a possible change in the therapeutic regimen.

Overdose

In case of drug poisoning, drowsiness and disorientation, agitation, seizures, disturbances of consciousness and extrapyramidal symptoms may occur.

There is no antidote. Gastric lavage is performed (in the first 60 minutes after intoxication), the use of enterosorbents and symptomatic actions.

To control extrapyramidal manifestations, anticholinergic medications can be used.

Interactions with other drugs

Anticholinergic substances are able to neutralize the antidispeptic effect of domperidone.

It is forbidden to use antisecretory medicines and antacids in combination with a medicine, because they reduce the values of its bioavailability.

The metabolic processes of domperidone are mainly realized through CYP3A4. In vitro information and information obtained during testing revealed that the introduction of drugs together with drugs that significantly inhibit this enzyme can provoke an increase in plasma levels of domperidone.

Separate tests of pharmacokinetic / -dynamic interactions in vivo in the case of combined oral administration with erythromycin or ketoconazole in volunteers confirmed that these substances significantly inhibit the presystemic metabolic processes of domperidone associated with CYP3A4.

The introduction of 10 mg of domperidone orally 4 times per day, as well as 0.2 g of ketoconazole (orally, 2 times per day) led to a prolongation of the QTc-interval by 9.8 ms (average); at the same time, individual marks varied in the range of 1.2-17.5 ms. After 4 times a day use of 10 mg of domperidone with 3 times a day of 0.5 g of erythromycin, the QTc interval was prolonged by 9.9 ms (mean value), the intervals of individual indicators ranged from 1.6 to 14, 3 ms.

The equilibrium drug Cmax and AUC levels rise approximately threefold during each of these interaction tests. What part of the effect of increased plasma domperidone values relative to the observed QTc effect has not been determined. During such tests, with monotherapy using domperidone (4-fold intake of 10 mg per day), the QTc-interval was prolonged by 1.6 ms (administration of ketoconazole) or 2.5 ms (administration of erythromycin); at the same time, the use of exclusively ketoconazole (0.2 g 2 times a day) or erythromycin (0.5 g 3 times a day) caused the QTc interval to be prolonged by 3.8 and 4.9 ms, respectively.

In theory, because the drug has a prokinetic effect on the stomach, it can affect the absorption of drugs taken orally - for example, enteric coated or prolonged release forms. But in persons whose condition returned to normal after using paracetamol or digoxin, the combined administration of domperidone did not change the blood values of these drugs.

Among the powerful inhibitors of the CYP3A4 element, with which it is forbidden to combine Peridon:

• azole antimycotics - itraconazole, fluconazole * with ketoconazole * and voriconazole *;
• nefazodone;
• macrolides - erythromycin * with clarithromycin *;
• drugs that slow down the action of HIV protease - ritonavir, amprenavir and nelfinavir with atazanavir, as well as indinavir and fosamprenavir with saquinavir;
• amrepitant;
• Ca antagonists - verapamil with diltiazem;
• amiodarone *;
• telithromycin *.
• * also lengthen the QTc-gap.

The drug can be combined with antipsychotics, whose activity it potentiates, as well as with dopamine agonists (bromocriptine or L-dopa), the negative effect of which (nausea, digestive disorders and vomiting) it inhibits, without neutralizing their main effects.

Possible interactions with other medications.

The main pathway of domperidone metabolic processes is associated with the action of CYP3A4. Information obtained from in vitro testing, as well as in humans, shows that a combination of drugs that significantly inhibit this enzyme can provoke an increase in plasma values of domperidone. It is forbidden to administer a medicine with substances that greatly slow down the action of CYP3A4 and can provoke a prolongation of the QT interval.

It is necessary to carefully combine domperidone with drugs that strongly slow down the action of CYP3A4 and do not cause prolongation of the QT interval (for example, indinavir). At the same time, the condition of patients must be monitored in order to notice the development of side symptoms.

Caution is also required when used with medications that prolong the QT interval, and it is also necessary to carefully monitor the patient's condition in the development of negative reactions associated with CVS. Among those:

• antiarrhythmic substances of subtype IIA or III;
• certain antipsychotics, antibiotics, or antidepressants;
• certain antimycotics;
• certain drugs associated with exposure to the gastrointestinal tract, or with antimalarial effects;
• some medicines used for oncological pathologies;
• certain other drugs.

Storage conditions

The periodon must be kept at temperatures up to a maximum of 25 ° C.

Shelf life

Peridon can be used within a 5-year period from the date of manufacture of the pharmaceutical substance.

Analogs

Analogs of drugs are the medicines Limser, Rabirid and Motinol with Brulium Lingvatabs, Motorix and Lancid with Gastropom-Apo, and in addition to this Perilium, Motorinorm with Domidon and Motoricum. In addition, the list includes Domrid, Peridonium with Motilium, Cinnaridon with Nausilium.