Motilium, 1 mg/ml suspension 100 ml

Intestinal infections, reflux esophagitis, Abdominal bloating, GI motility disorders, Nausea, Vomiting, Meteorism, Heartburn, Hiccupsa) Complex of dyspeptic symptoms, often associated with delayed gastric emptying, gastroesophageal reflux, esophagitis:

– feeling of congestion in the epigastrium, feeling of bloating, pain in the upper abdomen;
– belching, flatulence;
– nausea, vomiting;
– heartburn, belching.

b) Nausea and vomiting of functional, organic, infectious origin, as well as caused by radiotherapy, drug therapy or violation of diet. A specific indication is nausea and vomiting caused by dopamine agonists when used in Parkinson’s disease (such as levodopa and bromocriptine).

Active ingredient

Domperidone

Composition

Active substance (per 1 ml of suspension):

Domperidone 1 mg.

Excipients (per 1 ml of suspension):

microcrystalline cellulose and sodium carmellose 12.0 mg,

sorbitol liquid uncrystallized 70% 455.4 mg,

methyl parahydroxybenzoate 1.8 mg, polysorbate 20 0,10 mg,

sodium hydroxide about 10 mcg*,

water up to 1.0 ml.

* From 0 to 30 µg.

How to take, the dosage

It is recommended to take Motilium® before meal, in case of taking it after meal absorption of domperidone slows down a little.

Adults and adolescents over 12 years old with body weight of 35 kg or more and children under 12 years old with body weight of 35 kg or more: 10 ml 3 times per day. The maximum daily dose is 30 ml (30 mg).

The dose should be determined very carefully taking into account the body weight and not exceeding the recommended maximum daily dosage.

In patients of all age categories usually for therapy of acute nausea and vomiting the maximum duration of continuous drug administration should not exceed one week. If nausea and vomiting last longer than one week, the patient should consult his or her physician again. For other indications, the duration of therapy is four weeks. If symptoms do not disappear within 4 weeks, the patient should be re-examined and the need for continuation of therapy should be assessed.

Use in patients with impaired renal function

Since the half-life of domperidone is longer in severe renal function disorders, during repeated use the frequency of Motilium® administration should be reduced to 1-2 times a day, depending on the severity of the disorders, a dose reduction may also be required. During long-term therapy, such patients should be examined regularly.

Use in patients with liver dysfunction

Motilium® use is contraindicated in patients with moderate (7 – 9 by Child-Pugh classification) or severe (> 9 by Child-Pugh classification) liver failure (see section “Contraindications”). No dose adjustment is required in patients with mild (5 – 6 Child-Pugh classification) hepatic impairment.

Interaction

Anticholinergic drugs may neutralize the effect of Motilium® EXPRESS.

Oral bioavailability of Motilium® EXPRESS decreases after previous intake of cimetidine or sodium hydrocarbonate. Antacids and antisecretory drugs should not be taken simultaneously with domperidone, because they reduce its bioavailability after oral administration (see section “Special Precautions”).

The CYP3A4 isoenzyme plays the main role in metabolism of domperidone. The results of in vitro studies and clinical experience show that concomitant use of drugs that significantly inhibit this isoenzyme may cause increased plasma concentrations of domperidone.

Strong inhibitors of CYP3A4 isoenzyme include:

– Asole antifungals such as fluconazole*, itraconazole, ketoconazole* and voriconazole*;
– Macrolide antibiotics such as clarithromycin* and erythromycin*;
– HIV protease inhibitors, such as amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir, and saquinavir;
– Calcium antagonists such as diltiazem and verapamil;
– Amiodarone*;
– Aprepitant;
– Nefazodone;
– Telithromycin*.

(Drugs marked with an asterisk also prolong the QTc interval (see

In several studies of the pharmacokinetic and pharmacodynamic interactions of domperidone with oral ketoconazole and oral erythromycin in healthy volunteers it has been shown that these drugs significantly inhibit the primary metabolism of domperidone by the CYP3A4 isoenzyme.

Concomitant administration of 10 mg domperidone 4 times daily and 200 mg ketoconazole 2 times daily resulted in prolongation of the QTc interval by an average of 9.8 ms during the entire observation period, at individual times the changes ranged from 1.2 to 17.5 ms. When concomitant administration of 10 mg domperidone 4 times daily and 500 mg erythromycin 3 times daily a prolongation of the QTc interval by 9.9 ms on the average during the whole period of observation was noted, at separate moments the changes ranged from 1.6 to 14.3 ms. In each of these studies the Cmax and AUC of domperidone were increased approximately threefold (see section “Contraindications”).

It is currently unknown what contribution increased plasma concentrations of domperidone make to QTc interval changes.

In these studies, monotherapy with domperidone (10 mg four times daily) resulted in a 1.6 ms prolongation of the QTc interval (ketoconazole study) and 2.5 ms prolongation (erythromycin study), whereas ketoconazole monotherapy (200 mg twice daily) and erythromycin monotherapy (500 mg three times daily) resulted in 3.8 and 4.9 ms prolongation of the QTc interval respectively throughout the follow-up.

In another multiple-dose study in healthy volunteers, no significant prolongation of the QTc interval was found during steady-state monotherapy with domperidone (40 mg four times daily, total daily dose of 160 mg, significantly higher than the recommended maximum daily dose). At the same time plasma concentrations of domperidone were similar to those in the studies of domperidone interaction with other drugs.

Theoretically, as Motilium® EXPRESS has gastrokinetic effect, it could influence absorption of concomitantly used oral drugs, in particular, drugs with prolonged release of active substance or drugs coated with enteric coating. However, the use of domperidone in patients against the background of taking paracetamol or digoxin had no effect on the blood levels of these drugs.

Motilium® EXPRESS may be taken simultaneously with:

– neuroleptics, the effects of which it does not enhance;

– with dopaminergic receptor agonists (bromocriptine, levodopa), because it inhibits their unwanted peripheral effects, such as digestive disorders, nausea and vomiting, while not affecting their central effects.

Special Instructions

When Motilium® EXPRESS is used together with antacids or antisecretory drugs, the latter should be taken after meals, not before meals, i.e. they should not be taken simultaneously with Motilium® EXPRESS.

Motilium® EXPRESS oral tablets contain aspartame and therefore should not be used in patients with hyperphenylalaninemia.

Administration in children

Motilium® EXPRESS in rare cases may cause neurological side effects (see section “Side effects”). In this regard, the recommended dose should be strictly adhered to (see section “Dosage and administration”). Neurological undesirable effects may be caused in adolescents by overdose of the drug, but it is necessary to take into account other possible causes of such effects.

Application in diseases of the cardiovascular system.

In some epidemiological studies it has been shown that the use of domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden coronary death (see section “Side effects”). The risk may be more likely in patients over 60 years of age and in patients taking the drug in daily doses greater than 30 mg. Patients over 60 years of age should take Motilium® EXPRESS with caution.

Administration of domperidone and other drugs causing prolongation of QTc interval is not recommended in patients with conduction disorders, particularly prolongation of QTc interval, and in patients with significant electrolyte balance disorders (hypokalemia, hyperkalemia, hypomagnesemia) or with bradycardia, or in patients with concomitant cardiac diseases, such as congestive heart failure. It is known that against the background of electrolyte imbalance and bradycardia, the risk of arrhythmias increases.

In the case of signs or symptoms that may be associated with cardiac arrhythmias, therapy with Motilium® EXPRESS should be stopped and a doctor should be consulted.

Use in renal disease.

Since a very small percentage of the drug is excreted unchanged by the kidneys, correction of the single dose in patients with renal insufficiency is not required. However, when Motilium® EXPRESS is repeatedly prescribed, the frequency of administration should be reduced to once or twice a day, depending on the severity of renal impairment (see section “Dosage and administration”). During long-term therapy, patients should be monitored regularly.

Potential of drug interaction

The main pathway of domperidone metabolism is via CYP3A4 isoenzyme. In vitro data and results of studies in humans show that concomitant use of drugs that significantly inhibit this enzyme may be accompanied by increased plasma concentrations of domperidone. Concomitant use of domperidone with potent CYP3A4 isoenzyme inhibitors that are known to cause QT interval prolongation is contraindicated (see section “Contraindications”).

Caution should be exercised when combining domperidone with potent CYP3A4 isoenzyme inhibitors that do not cause QT interval prolongation, such as indinavir, and careful monitoring of patients for signs or symptoms of adverse reactions is required (see sect.

Caution should be exercised when combining domperidone with medicinal products that have been reported to cause QT interval prolongation, and patients should be closely monitored for signs or symptoms of cardiovascular adverse reactions.

Examples of such medications:

– Class IA antiarrhythmic drugs (e.g., disopyramide, quinidine);
– Class III antiarrhythmic drugs (e.g., amiodarone, dofetilide, dronedarone, ibutilide, sotalol);
– Certain antipsychotics (e.g., haloperidol, pimozide, sertindol);
– Certain antidepressants (e.g., citalopram, escitalopram);
– Certain antibiotics (e.g., levofloxacin, moxifloxacin);
– certain antifungal agents (e.g., pentamidine);
– certain antimalarials (e.g., halofantrine);
– certain gastrointestinal medications (e.g., dolasetron);
– certain anticancer drugs (e.g., toremifene, vandetanib);
– certain other drugs (e.g., bepridil, methadone).

If the product has expired or has passed its expiration date – do not throw it down the drain or into the street! Place the medication in a bag and put it in a trash container. These measures will help protect the environment!

Synopsis

White homogeneous suspension

Contraindications

• Excessive sensitivity to domperidone or any of the drug components;
• prolactin-secreting pituitary tumor (prolactinoma);
• .concomitant use of oral forms of ketoconazole, erythromycin, or other potent CYP3A4 isoenzyme inhibitors that cause QTc interval prolongation, such as clarithromycin, itraconazole, fluconazole, posaconazole, ritonavir, saquinavir, amiodarone, telithromycin, telaprevir, and voriconazole (see “Dangerous Instructions”).
• in cases where stimulation of gastric motility may be dangerous, such as gastrointestinal bleeding, mechanical obstruction, or perforation;
• Moderate to severe hepatic dysfunction.
• children under 12 years of age at body weight < 35 kg

With caution

• disorders of renal function;

.

Side effects

According to clinical trials

Adverse reactions observed in ≥ 1% of patients taking MOTILIUMÒ: depression, anxiety, decreased or absent libido, headache, somnolence, akathisia, diarrhea, rash, itching, breast enlargement/gynecomastia, breast pain and sensitivity, galactorrhea, menstrual disorders and amenorrhea, lactation disorders, asthenia.

Adverse reactions observed in < 1% of patients taking MOTILIUMÒ: hypersensitivity, urticaria, mammary gland swelling, mammary gland discharge.

The following adverse effects were classified as follows: very frequently (≥10%), frequently (≥1% but < 10%), infrequently (≥0.1% but < 1%), rarely (≥0.01% but < 0.1%), and very rarely (< 0.01%), including individual cases.

According to spontaneous reports of adverse events.

Immune system disorders. Very rare: anaphylactic reactions, including anaphylactic shock. Psychiatric disorders. Very rarely: increased excitability, nervousness, irritability.

Nervous system disorders. Very rarely: somnolence, headache, dizziness, extrapyramidal disorders and seizures.

Cardiovascular system disorders. Frequency is unknown: ventricular arrhythmia*, ventricular tachycardia by type “pirouette”, sudden coronary death*.

Skin and subcutaneous tissue disorders. Very rarely: urticaria, angioedema.

Renal and urinary tract disorders. Very rarely: urinary retention.

Laboratory and instrumental data. Very rarely: abnormal laboratory parameters of liver function, hyperprolactinemia.

Adverse reactions detected during post-registration clinical studies

Immune system disorders. Frequency unknown: anaphylactic reactions, including anaphylactic shock. Mental disorders. Infrequent: increased excitability, nervousness.

Nervous system disorders. Often: dizziness. Rare: seizures. Frequency unknown: extrapyramidal disorders.

Cardiovascular system disorders. Frequency unknown: ventricular arrhythmia*, pirouette-type ventricular tachycardia, sudden coronary death*.

Gastrointestinal disorders. Frequency unknown: dry mouth.

Skin and subcutaneous tissue disorders. Frequency unknown: angioedema.

Renal and urinary tract disorders. Infrequent: urinary retention.

Laboratory and instrumental data. Infrequent: abnormal laboratory indexes of liver function. Rare: hyperprolactinemia.

* In some epidemiological studies it has been shown that domperidone use may be associated with an increased risk of serious ventricular arrhythmias or sudden death.

The risk of these phenomena is more likely in patients over 60 years of age and in patients taking the drug in a daily dose greater than 30 mg.

It is recommended to use domperidone in the lowest effective dose in adults and children.

Overdose

Symptoms

Cases of overdose have been noted mainly in infants and older children. Symptoms of overdose may include increased agitation, altered consciousness, seizures, disorientation, somnolence and extrapyramidal reactions.

Treatment

There is no specific antidote for domperidone. In case of overdose, gastric lavage within 1 hour of taking the drug and use of activated charcoal is recommended. It is recommended to closely monitor the patient’s condition and provide supportive therapy. Anticholinergic agents and drugs used to treat parkinsonism may be effective in stopping extrapyramidal reactions that have occurred.

Pregnancy use

Pregnancy

There are insufficient data on the use of domperidone during pregnancy. To date, there are no data on an increased risk of malformations in humans. Nevertheless, Motilium® should be prescribed during pregnancy only if its use is justified by the expected therapeutic benefit.

Lactation

The amount of domperidone that may enter the child with breast milk is small. The maximum relative dose for infants (%) is estimated to be about 0.1% of the dose taken by the mother per body weight. It is not known whether this level has an adverse effect on newborns. In this regard, breastfeeding should be discontinued when using Motilium® during lactation.

Similarities

Motilium, Passazhix, Motilac, Domperidon-Teva, Motonium, Domperidon, Motilium Express, Motogastric