Peridone

Peridone is a drug that helps stimulate intestinal peristalsis. Its main ingredient is domperidone. This substance is a dopamine antagonist and has an antiemetic effect.

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

Indications Peridone

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

Release form

The drug is released in tablet form - 10 pieces inside a cell plate. Inside the box - 1 or 3 such plates.

Pharmacodynamics

The principle of the therapeutic effect of the drug is associated with the chemical and physical properties 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 adults, but at the same time domperidone can stimulate the pituitary secretion of prolactin. [ 2 ]

There is official information that small amounts of the substance determined inside the brain indicate 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 area 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 level after 0.5-1 hour. The low bioavailability of orally administered domperidone (about 15%) is associated with extensive metabolic processes during the first pass through the liver and intestinal wall. Although in a healthy person the level of bioavailability of the substance increases when taken after meals, people with gastrointestinal disorders should take the medication 15-30 minutes before meals.

Reduced gastric pH reduces the absorption of domperidone. The bioavailability value after oral administration of the drug is reduced by previous use of cimetidine or baking soda.

Administration of the drug orally after meals slightly reduces the maximum absorption; however, a slight increase in the AUC is observed.

Distribution processes.

After oral administration, there is no accumulation of domperidone and no induction of its own metabolism. The plasma Cmax value after 1.5 hours (21 ng/ml) with a 2-week administration of 30 mg per day was almost identical to the level with the administration of the first portion (18 ng/ml).

Protein synthesis of domperidone is 91-93%. Animal drug distribution studies (using a radioactively labeled drug) have shown significant tissue distribution and low levels of the component within the brain. Little of the drug crosses the placenta in animals.

Exchange processes.

Domperidone is extensively and rapidly involved in intrahepatic metabolic processes via hydroxylation and N-dealkylation. In vitro metabolic assays using a diagnostic inhibitor have shown that CYP3A4 is the major type of P450 hemoprotein involved in N-dealkylation; CYP3A4 with CYP1A2 and CYP2E1 are involved in aromatic hydroxylation of the substance.

Excretion.

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

The plasma half-life after administration of a single dose in volunteers is 7-9 hours; in individuals with severe liver dysfunction it is prolonged.

Dosing and administration

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

Without a doctor's prescription, therapy with this drug can last a maximum of 2 days. If there is no desired effect from taking it, you must consult a doctor. In general, treatment can last no more than 1 week.

• Application for children

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

Use Peridone during pregnancy

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

If there is a need to use the drug during breastfeeding, it is stopped for the duration of therapy.

Contraindications

Among the contraindications:

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

It is also not used in cases where vomiting occurs due to motion sickness, mechanical obstruction or perforation, as well as bleeding within the gastrointestinal tract.

It is prohibited to prescribe in combination with substances that prolong the QT interval, itraconazole, telithromycin, ritonavir and erythromycin, as well as with clarithromycin, fluconazole, telaprevir and ketoconazole, as well as with amiodarone, saquinavir and posaconazole with voriconazole.

Side effects Peridone

Main side effects:

• allergy that could develop into anaphylaxis;
• increased prolactin levels;
• dizziness, drowsiness, fatigue and nervousness, as well as headaches, thirst, convulsions, extrapyramidal disorders and depression;
• tachycardia, edema, ventricular arrhythmia and sudden cardiac death;
• short-term spasms in the intestinal area, 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 urination, dysuria and asthenia;
• stomatitis or conjunctivitis.

If atypical negative symptoms appear after using the medication, you should consult with your doctor regarding a possible change in the therapeutic regimen.

Overdose

In case of poisoning with the drug, drowsiness and disorientation, agitation, convulsions, disturbance of consciousness and extrapyramidal symptoms may be observed.

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

To control extrapyramidal manifestations, anticholinergic drugs can be used.

Interactions with other drugs

Anticholinergic agents can neutralize the antidyspeptic effect of domperidone.

It is prohibited to use antisecretory medications and antacids in combination with the drug, because they reduce its bioavailability.

The metabolic processes of domperidone are mainly realized through CYP3A4. In vitro data and information obtained during testing revealed that the administration of the drug together with drugs that significantly inhibit the specified enzyme may provoke an increase in plasma indicators of domperidone.

Separate in vivo pharmacokinetic/dynamic interaction studies with combined oral administration of erythromycin or ketoconazole in volunteers confirmed that these substances significantly inhibit the CYP3A4-associated presystemic metabolism of domperidone.

Administration of domperidone 10 mg orally 4 times daily and ketoconazole 0.2 g orally 2 times daily resulted in prolongation of the QTc interval by 9.8 msec (mean value); individual values ranged from 1.2 to 17.5 msec. Administration of domperidone 10 mg 4 times daily with erythromycin 0.5 g 3 times daily resulted in prolongation of the QTc interval by 9.9 msec (mean value), with individual values ranging from 1.6 to 14.3 msec.

Steady-state Cmax and AUC levels of the drug were increased approximately threefold during each of these interaction tests. The contribution of increased plasma domperidone values to the observed QTc effect is not known. In such tests, when domperidone was given alone (10 mg 4 times daily), the QTc interval was prolonged by 1.6 msec (ketoconazole) or 2.5 msec (erythromycin); when ketoconazole (0.2 g twice daily) or erythromycin (0.5 g three times daily) were given alone, the QTc interval was prolonged by 3.8 and 4.9 msec, respectively.

In theory, because the drug has a prokinetic effect relative to the stomach, it can affect the absorption of orally administered drugs - for example, enteric-coated or prolonged-release forms. However, in individuals whose condition was normalized after using paracetamol or digoxin, combined administration of domperidone did not change the blood levels of these drugs.

Among the potent inhibitors of the CYP3A4 element with which it is prohibited to combine Peridon are:

• azole antimycotics – itraconazole, fluconazole* with ketoconazole* and voriconazole*;
• nefazodone;
• macrolides – erythromycin* with clarithromycin*;
• drugs that inhibit 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 prolong the QTc interval.

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

Possible interactions with other medications.

The main pathway of domperidone metabolism is associated with the action of CYP3A4. Data obtained from in vitro testing, as well as in humans, show that a combination of drugs that significantly inhibit this enzyme can provoke an increase in plasma levels of domperidone. It is prohibited to administer the drug with substances that significantly slow the action of CYP3A4 and can provoke prolongation of the QT interval.

Domperidone should be combined with caution with drugs that strongly inhibit CYP3A4 action but do not prolong the QT interval (eg, indinavir), and patients should be monitored for the development of adverse effects.

Caution is also required when using with drugs that prolong the QT interval, and it is also necessary to closely monitor the patient's condition in the event of adverse reactions associated with the cardiovascular system. Among these are:

• antiarrhythmic drugs of subtype IIA or III;
• certain neuroleptics, antibiotics or antidepressants;
• individual antifungal agents;
• certain drugs that have effects on the gastrointestinal tract or that have antimalarial effects;
• some medications used in oncological pathologies;
• certain other medicinal products.

Storage conditions

Peridon must be stored at temperatures no higher than 25°C.

Shelf life

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

Analogues

Analogues of the drug are the following medications: Limzer, Rabirid and Motinol with Bryulium Linguatabs, Motorix and Lancid with Gastrop-Apo, and in addition Perilium, Motinorm with Domidon and Motoricum. In addition, the list includes Domrid, Peridonium with Motilium, Cinnaridone with Nausilium.