Cerulan (Tablets, Solution) Instructions for Use

ATC Code

A03FA01 (Metoclopramide)

Active Substance

Metoclopramide (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

Antiemetic agent, helps reduce nausea, hiccups; stimulates gastrointestinal tract peristalsis.

The antiemetic effect is due to the blockade of dopamine D₂ receptors and an increase in the threshold of chemoreceptors in the trigger zone; it is also a serotonin receptor blocker.

It is believed that Metoclopramide inhibits the relaxation of gastric smooth muscle induced by dopamine, thereby enhancing cholinergic responses of the gastrointestinal tract smooth muscle.

It promotes accelerated gastric emptying by preventing relaxation of the gastric body and increasing the activity of the gastric antrum and upper small intestine.

It reduces the reflux of contents into the esophagus by increasing the resting pressure of the lower esophageal sphincter and enhances acid clearance from the esophagus by increasing the amplitude of its peristaltic contractions.

Metoclopramide stimulates prolactin secretion and causes a transient increase in the level of circulating aldosterone, which may be accompanied by short-term fluid retention.

Pharmacokinetics

After oral administration, it is rapidly absorbed from the gastrointestinal tract. Plasma protein binding is about 30%. It is biotransformed in the liver. It is excreted mainly by the kidneys, both unchanged and as metabolites. T_1/2 ranges from 4 to 6 hours.

Indications

Vomiting, nausea, hiccups of various origins. Atony and hypotension of the stomach and intestines (including postoperative); biliary dyskinesia; reflux esophagitis; flatulence; as part of complex therapy for exacerbations of gastric and duodenal ulcers; acceleration of peristalsis during X-ray contrast studies of the gastrointestinal tract.

ICD codes

Dosage Regimen

Tablets, Solution

Adults: orally – 5-10 mg 3-4 times/day. For vomiting, severe nausea, Metoclopramide is administered intramuscularly or intravenously at a dose of 10 mg. Intranasally – 10-20 mg into each nostril 2-3 times/day.

Maximum doses: single dose when taken orally – 20 mg; daily – 60 mg (for all routes of administration).

The average single dose for children over 6 years old is 5 mg 1-3 times/day orally or parenterally. For children under 6 years of age, the daily dose for parenteral administration is 0.5-1 mg/kg, frequency of administration – 1-3 times/day.

Adverse Reactions

From the digestive system: at the beginning of treatment, constipation, diarrhea are possible; rarely – dry mouth.

From the central nervous system: at the beginning of treatment, feeling of fatigue, drowsiness, dizziness, headache, depression, akathisia are possible. The occurrence of extrapyramidal symptoms is possible in children and young persons (even after a single use of metoclopramide): spasm of facial muscles, hyperkinesis, spasmodic torticollis (as a rule, they disappear immediately after discontinuation of metoclopramide). With prolonged use, more often in elderly patients, manifestations of parkinsonism, dyskinesia are possible.

From the hematopoietic system: at the beginning of treatment, agranulocytosis is possible.

From the endocrine system: rarely, with prolonged use in high doses – galactorrhea, gynecomastia, menstrual cycle disorders.

Allergic reactions: rarely – skin rash.

Contraindications

Gastrointestinal bleeding, mechanical intestinal obstruction, perforation of the stomach or intestines, pheochromocytoma, extrapyramidal disorders, epilepsy, prolactin-dependent tumors, glaucoma, pregnancy, lactation, simultaneous use of anticholinergic drugs, hypersensitivity to metoclopramide.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy.

When used during lactation (breastfeeding), it should be taken into account that Metoclopramide penetrates into breast milk.

Experimental studies have not established an adverse effect of metoclopramide on the fetus.

Use in Hepatic Impairment

Use with caution in patients with impaired liver function.

Use in Renal Impairment

Use with caution in patients with impaired renal function.

Pediatric Use

Should be used with particular caution in children, especially young children, because they have a significantly higher risk of dyskinetic syndrome.

Geriatric Use

When used in elderly patients, it must be borne in mind that with prolonged use of metoclopramide in high or medium doses, the most common side effect is extrapyramidal disorders, especially parkinsonism and tardive dyskinesia.

Special Precautions

Use with caution in patients with bronchial asthma, arterial hypertension, impaired liver and/or kidney function, with Parkinson’s disease.

Should be used with particular caution in children, especially young children, because they have a significantly higher risk of dyskinetic syndrome. Metoclopramide in some cases may be effective for vomiting caused by cytostatics.

When used in elderly patients, it must be borne in mind that with prolonged use of metoclopramide in high or medium doses, the most common side effect is extrapyramidal disorders, especially parkinsonism and tardive dyskinesia.

During the use of metoclopramide, distortions of laboratory data on liver function and determination of aldosterone and prolactin concentrations in blood plasma are possible.

Influence on the ability to drive vehicles and mechanisms

During the treatment period, potentially hazardous activities requiring increased attention and rapid psychomotor reactions should be avoided.

Drug Interactions

With simultaneous use with anticholinergic agents, mutual weakening of effects is possible.

With simultaneous use with neuroleptics (especially phenothiazine derivatives and butyrophenone derivatives), the risk of extrapyramidal reactions increases.

With simultaneous use, the absorption of acetylsalicylic acid, paracetamol, and ethanol is enhanced.

Metoclopramide with intravenous administration increases the rate of absorption of diazepam and increases its maximum plasma concentration.

With simultaneous use with a slow-release dosage form of digoxin, a decrease in the serum concentration of digoxin by 1/3 is possible. No interaction was noted with simultaneous use with digoxin in a liquid dosage form or in the form of a rapidly soluble dosage form.

With simultaneous use with zopiclone, the absorption of zopiclone is accelerated; with cabergoline – a decrease in the effectiveness of cabergoline is possible; with ketoprofen – the bioavailability of ketoprofen decreases.

Due to antagonism towards dopamine receptors, Metoclopramide may reduce the antiparkinsonian effect of levodopa, while an increase in the bioavailability of levodopa is possible due to the acceleration of its evacuation from the stomach under the influence of metoclopramide. The results of the interaction are ambiguous.

With simultaneous use with mexiletine, the absorption of mexiletine is accelerated; with mefloquine – the rate of absorption of mefloquine and its plasma concentration increase, while a decrease in its side effects is possible.

With simultaneous use with morphine, the absorption of morphine when taken orally is accelerated and its sedative effect is enhanced.

With simultaneous use with hymecromone, mutual weakening of effects is observed.

With simultaneous use with nitrofurantoin, the absorption of nitrofurantoin decreases.

When using metoclopramide immediately before the administration of propofol or thiopental, a reduction in their induction doses may be required.

In patients receiving Metoclopramide, the effects of suxamethonium chloride are enhanced and prolonged.

With simultaneous use with tolterodine, the effectiveness of metoclopramide decreases; with fluvoxamine – a case of extrapyramidal disorders has been described; with fluoxetine – there is a risk of developing extrapyramidal disorders; with cyclosporine – the absorption of cyclosporine increases and its plasma concentration increases.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.