Passagix^® (Tablets) Instructions for Use

ATC Code

A03FA03 (Domperidone)

Active Substance

Domperidone (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Centrally acting antiemetic drug blocking dopamine receptors

Pharmacotherapeutic Group

Antiemetic agent – central dopamine receptor antagonist

Pharmacological Action

The drug has a prokinetic and antiemetic effect and normalizes the function of the gastrointestinal tract. It is a dopamine D₂ receptor blocker.

The prokinetic properties are associated with the blockade of peripheral dopamine receptors and the elimination of the inhibitory effect of dopamine on gastrointestinal functions. It increases the duration of peristaltic contractions of the antrum of the stomach and duodenum, accelerates gastric emptying in case of its delay, increases the tone of the lower esophageal sphincter, and prevents the development of nausea and vomiting.

Domperidone poorly penetrates the blood-brain barrier, therefore the use of domperidone is rarely accompanied by extrapyramidal side effects, especially in adults, but Domperidone stimulates the release of prolactin from the pituitary gland. The antiemetic effect is possibly due to a combination of peripheral (gastrokinetic) action and antagonism to dopamine receptors in the chemoreceptor trigger zone. Domperidone does not affect gastric secretion.

Pharmacokinetics

Absorption

After oral administration, Domperidone is rapidly absorbed. It has low bioavailability (about 15%). A decrease in gastric juice acidity reduces the absorption of domperidone. C_max in plasma is reached after 1 hour.

Distribution

Domperidone is widely distributed in various tissues; its concentration in brain tissue is low. Plasma protein binding is 91-93%.

Metabolism

It undergoes intensive metabolism in the intestinal wall and liver.

Excretion

It is excreted through the intestines (66%) and kidneys (33%), unchanged – 10% and 1% of the dose, respectively. T_1/2 is 7-9 hours.

Pharmacokinetics in special clinical cases

In severe renal failure, T_1/2 is prolonged.

Indications

1) A complex of dyspeptic symptoms, often associated with delayed gastric emptying, gastroesophageal reflux, esophagitis

• Feeling of fullness in the epigastrium, sensation of abdominal bloating, pain in the upper abdomen;
• Belching, flatulence;
• Heartburn with or without regurgitation of gastric contents into the oral cavity.

2) Nausea and vomiting of functional, organic, infectious origin, caused by radiotherapy, drug therapy or dietary disturbances, as well as during the use of dopamine agonists in Parkinson’s disease (such as levodopa and bromocriptine).

ICD codes

Dosage Regimen

Tablets

The drug is taken orally, preferably before meals. When taken after meals, absorption is somewhat slowed down.

Chronic dyspepsia

Adults are prescribed 10 mg (1 tablet) 3 times/day, 15-30 minutes before meals and, if necessary, before bedtime.

Children over 5 years old – 2.5 mg per 10 kg of body weight 3 times/day, before meals and, if necessary, before bedtime.

If necessary, the indicated dose can be doubled.

Acute and subacute conditions (primarily nausea and vomiting)

Adults are prescribed 20 mg (2 tablets) 3-4 times/day, before meals and before bedtime.

Children over 5 years old – 5 mg per 10 kg of body weight, 3-4 times/day, before meals and before bedtime.

In renal failure, a reduction in the frequency of drug administration is recommended. In patients with severe renal failure (serum creatinine >6 mg/100 ml, i.e. >0.6 mmol/l), the T_1/2 of domperidone increased from 7.4 to 20.8 hours, but plasma concentrations of the drug were lower than in healthy volunteers.

Since a very small percentage of the drug is excreted by the kidneys unchanged, correction of a single dose in patients with renal failure is hardly necessary. However, with repeated administration, the frequency of administration should be reduced to 1-2 times/day depending on the severity of renal failure, and a dose reduction may also be necessary. During long-term therapy, patients should be under regular supervision.

Considering the metabolism of domperidone in the liver, the drug should be prescribed with caution to patients with hepatic impairment.

Adverse Reactions

Side effects are rare.

Allergic reactions rarely – rash, urticaria.

From the digestive system exceptional cases of transient intestinal spasms have been noted.

From the nervous system extrapyramidal reactions are observed in children and with increased permeability of the blood-brain barrier, which are completely reversible and disappear spontaneously after discontinuation of treatment.

From the endocrine system the drug can induce an increase in plasma prolactin levels (because the pituitary gland is outside the blood-brain barrier). In rare cases, hyperprolactinemia can stimulate the appearance of galactorrhea, gynecomastia and dysmenorrhea.

Contraindications

• Established intolerance to the drug;
• Prolactin-secreting pituitary tumor (prolactinoma);
• Children under 5 years of age.

Passagix^® should not be used when stimulation of gastric motility may be dangerous, including in gastrointestinal bleeding, mechanical obstruction or perforation.

Use in Pregnancy and Lactation

When administered to animals in doses up to 160 mg/kg/day, Domperidone had no teratogenic effect. However, like most medications, the drug should be prescribed in the first trimester of pregnancy only if its use is justified by the expected therapeutic benefit. To date, there is no data on an increased risk of developmental defects in humans.

In women, the concentrations of domperidone in breast milk are 4 times lower than the corresponding concentrations in plasma. It is not known whether this level has a negative effect on newborns. Therefore, if the mother is taking Passagix^®, breastfeeding is not recommended, except when the expected benefit justifies the potential risk.

Use in Hepatic Impairment

Considering the metabolism of domperidone in the liver, the drug should be prescribed with caution to patients with hepatic impairment.

Use in Renal Impairment

Since a very small percentage of the drug is excreted by the kidneys unchanged, correction of a single dose in patients with renal failure is hardly necessary. However, with repeated administration, the frequency of administration should be reduced to 1-2 times/day, depending on the severity of the insufficiency, and a dose reduction may also be necessary.

Pediatric Use

The use of the drug is contraindicated in children under 5 years of age.

Special Precautions

When using Passagix^® concomitantly with antacid or antisecretory drugs, the latter should be taken after meals, not before meals, i.e., they should not be taken simultaneously with Passagix^®.

Effect on the ability to drive vehicles and operate machinery

Domperidone does not impair the speed of psychomotor reactions.

Overdose

Symptoms drowsiness, disorientation and extrapyramidal reactions, especially in children.

Treatment administration of activated charcoal and careful observation are recommended. Anticholinergic agents, drugs used to treat parkinsonism, or antihistamines may be effective if extrapyramidal reactions occur.

Drug Interactions

With simultaneous use, anticholinergic drugs can neutralize the effect of Passagix^®.

With simultaneous use with Passagix^®, antacid and antisecretory drugs reduce its bioavailability.

Based on in vitro studies, it can be assumed that with simultaneous use with Passagix^® of drugs that significantly inhibit CYP3A4 (azole antifungals, macrolide antibiotics, HIV protease inhibitors, the antidepressant nefazodone), an increase in the plasma concentration of domperidone may be observed.

The drug does not affect the blood concentration of paracetamol and digoxin.

It is possible that Passagix^® may affect the absorption of concomitantly administered oral drugs with delayed release of the active substance or enteric-coated drugs.

Storage Conditions

The drug should be stored out of the reach of children, in a dry, light-protected place at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is approved for use as an over-the-counter product.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.