Instructions for use METOCLOPRAMIDUM

Composition and release form

The drug is dispensed in the form of tablets and solution for injection.

The active ingredient is metoclopramide hydrochloride. Excipients:

1. Saline.
2. Acetic acid.
3. Water for injections.
4. Sodium sulfite.
5. Edetate disodium.

Sold without a doctor's prescription. The cardboard package contains 1 bottle of clear liquid or 1-5 blisters of 10 tablets with attached instructions.

Shelf life 2 years. Optimal conditions are temperatures up to +25 C, in a dark place, away from children.

pharmachologic effect

Metoclopramide is a serotonin and dopamine receptor antagonist. It has a pronounced anti-hiccup, antiemetic and prokinetic effect. Stimulates intestinal motility in the upper section and regulates sphincter function.

The drug improves the tone of muscle contractions of the stomach, helps relax the duodenum and helps speed up the digestion process. It also has a positive effect on the functioning of the gallbladder, eliminating its disorder.

The antiemetic therapeutic effect is based on the suppression of dopamine receptors in the peripheral and central regions. Therefore, the medicine is effective in suppressing nausea and the gag reflex of various natures, namely due to anesthesia, chemotherapy, and taking certain groups of drugs when side effects occur.

The drug inhibits the effect of apomorphine, increasing the production of prolactin and increasing the content of aldosterone. Therefore, there is a temporary retention of fluid in the body.

When administered orally, the medicine is quickly absorbed into the bloodstream and reaches its maximum therapeutic effect after 1-2 hours. The overall bioavailability is 80%.

The half-life is 6 hours, in case of kidney disease it increases to 14 hours.

When the drug is administered by injection, the pharmacological effect is observed 1-3 minutes after intravenous administration and 15 minutes after intramuscular administration. Duration is 2 hours.

Instructions for use METOCLOPRAMIDUM tablets

In patients with a history of depression, especially moderate or severe depression, accompanied by suicidal tendencies, a relapse of the disease may occur during treatment with metoclopramide. Before starting treatment, it is necessary to weigh the ratio of the potential benefits of treatment to the possible risks.

In the first 24-48 hours of treatment with metoclopramide, extrapyramidal symptoms may appear in the form of disturbances in muscle tone, dystonic movements, paroxysmal dystonia, and spasmodic torticollis. These symptoms most often occur in children and people under 30 years of age, and also after using metoclopramide to prevent vomiting caused by cancer chemotherapy.

Within 6 months of treatment with metoclopramide, symptoms of parkinsonism may appear. These symptoms disappear 2-3 months after discontinuation of the drug product.

Elderly patients, especially women, treated with metoclopramide may experience dyskinesias, often irreversible. These symptoms are less common with short-term treatment using lower doses of the drug product.

In patients with impaired renal function, hypokalemia may occur during treatment with metoclopramide because the drug increases plasma aldosterone concentrations and decreases sodium excretion.

In patients with hypertension treated with MAO inhibitors, metoclopramide potentiates the effect of MAO inhibitors.

Metoclopramide causes a transient increase in plasma aldosterone levels. This can lead to fluid retention in the body, especially in patients with cirrhosis or congestive heart failure.

In vitro studies have shown that about 1/3 of breast tumors depend on prolactin levels. Metoclopramide increases prolactin levels, so the drug is contraindicated in patients with prolactin-dependent breast tumors.

The medicinal product contains lactose and should not be used in patients with rare hereditary galactose intolerance, lactase deficiency (Lapp type) or glucose-galactose malabsorption syndrome.

Impact on the ability to drive vehicles and operate machinery

Metoclopramide may cause undesirable CNS effects such as drowsiness and dizziness, which impair psychophysical performance. Therefore, it is necessary to inform the patient about the dangers associated with driving motor vehicles and servicing moving mechanisms.

Indications

Clinical conditions for which metoclopramide is indicated are:

1. Nausea.
2. Vomiting of various origins.
3. Dysfunction of the digestive system.
4. Atony and hypotension of the intestines and stomach.
5. Postoperative gastrointestinal disorders.
6. Increased gas formation.
7. The period of exacerbation of ulcerative pathology of the gastrointestinal tract.
8. Preparation for examination of the digestive system.
9. Diseases of the biliary tract.

Nausea and vomiting. Practical recommendations for treatment

Definitions

Nausea is an unpleasant subjective sensation, often accompanied by vegetative symptoms (salivation, cold sweat, tachycardia, etc.);
can be both a precursor to vomiting and an independent clinical manifestation. Gagging is a rhythmic, painful spasmodic movement of the diaphragm and abdominal muscles, usually accompanying nausea and ending in vomiting.

Vomiting is the forced ejection of stomach contents through the mouth, which does not always occur after previous nausea. Nausea brings more discomfort to the patient, who may well tolerate vomiting 2-3 times a day, while chronic nausea can be a serious debilitating symptom that significantly reduces the quality of life.

Frequency – 50–60% of incurable cancer patients experience nausea and vomiting (up to 40% in the terminal period of other incurable diseases).

Causes : stomach irritation, gastrostasis, uremia, obstruction of the large intestine, prolonged constipation, infections, cough, psychogenic factors, medications, biochemical and metabolic disorders.

Pathogenesis

The pathogenesis of nausea and vomiting is a complex process. Nausea is a consequence of autonomic stimulation, while gagging and vomiting are carried out by the somatic part of the nervous system (Fig. 1).

Nausea is associated with atony of the upper gastrointestinal tract: the stomach, lower esophageal sphincter and pylorus, resulting in retrograde reflux of contents.

Vomiting is caused by the coordinated action of the gastrointestinal tract, diaphragm and abdominal muscles. The act of vomiting is caused by contraction of the respiratory muscles and abdominal muscles, pushing the contents out of the atonic upper parts of the gastrointestinal tract.

The vomiting center of the nervous system regulates a complex physiological process, receiving and combining signals from many sources.

Abbreviations for the names of receptor types: AChm = muscarinic cholinergic; α2 = α2adrenergic; D2 = dopamine type 2; GABA = gamma-aminobutyric acid; 5HT, 5HT2, 5HT3 = 5-hydroxytryptamine (serotonin) unspecified, type 2, type 3; H1 = histamine type 1; NK1 = neurokinin type 1. Antiemetic drugs act as antagonists of these receptors, with the central antiemetic effects of clonidine and opioids being agonistic. Area postrema is part of the rhomboid fossa in the medulla oblongata.

Grade

Collection and analysis of anamnesis usually allows us to establish the possible cause of nausea and vomiting, which determines treatment tactics.

Basic principles of drug treatment

The choice of drugs in palliative care depends on the identified causes of nausea and vomiting, the mechanisms of action of the drugs (Fig. 1, Table 1, Scheme 1), side effect profile and possible routes of administration. If possible, it is necessary to influence aggravating factors, such as taking medications, severe pain, cough, infectious complications, hypercalcemia.

Stage 1. Antiemetic etiological drugs

A. Gastritis, gastrostasis, functional obstruction (motility disorders) of the large intestine

Prokinetic agent with antiemetic effect:

• Metoclopramide/Cerucal:

● orally 10 mg 3–4 times a day (daily) and 10 mg as needed;

● continuous subcutaneous infusion (NPI, international experience in administering the drug) 30–40 mg/24 hours and 10 mg subcutaneously as needed;

● po, NPI, usually maximum 100 mg/24 hours.

• Domperidone/Motilium:

● po 10 mg 2–3 times a day.

b. Biochemical causes (morphine intake, hypercalcemia, renal failure)

Antiemetic drugs acting on the chemoreceptor trigger zone:

• haloperidol:

● po 0.5–1.5 mg at night and as needed;

● SC/NPI 2.5–5 mg/24 hours and 1 mg SC as needed;

● p/o, sc, NPI, usually maximum 10 mg/24 hours.

V. Cerebral causes (increased intracranial pressure, tumor compression, vestibular disorders)

Antiemetic drugs acting on the vomiting center:

• thiethylperazine/Torecan:

● p/o 1 tablet 6.5 mg 1–3 times a day;

● or rectally, 1 suppository 6.5 mg 1–3 times a day IM, subcutaneously 1 ml (6.5 mg/ml) 1–3 times a day. Prescribed in combination with dexamethasone

d. Mechanical obstruction of the large intestine, colic and/or the need to reduce secretion in the gastrointestinal tract

Antiemetic with antispasmodic and antisecretory effects:

• Hyoscine butyl bromide/ Buscopan:

● by NPI 60–120 mg/24 hours and 20 mg subcutaneously if necessary, the usual maximum dose is 300 mg/24 hours.

If frequent vomiting is present or nausea persists, it is recommended to administer drugs subcutaneously or by NPI (this method is still of little use in Russian practice, although it is used in many countries). To ensure the desired effect, you should begin with an emergency administration of the starting dose “as needed”, followed by titration to a regular dose. It must be monitored daily and attention must be paid to extradoses “as needed.”

If the therapy is ineffective, the possible causes should be reconsidered, the choice of antiemetic drug and the method of its administration should be analyzed. If therapy is ineffective, it is recommended to switch to broad-spectrum antiemetic drugs; in the absence of a positive response, to two-component therapy.

Stage 2. Broad spectrum drugs:

• levomepromazine:

● p/o, sc (international experience): 6–6.25 mg at night and as needed;

● the usual maximum dose is 50 mg/24 hours - either once at night or 25 mg twice a day;

● NPI should be considered.

Step 3. Two-component therapy (combination of antiemetic drugs with different mechanisms of action):

• haloperidol + 5HT3 antagonist , for example: Ondasentron 6 mg SC qd or NPI, or ondansetron 16 mg/24 hours NPI, when there is a massive release of 5HT/serotonin from intestinal enterochromaffin cells or platelets, for example: during radiation therapy on abdominal area, colon distension, kidney failure;
• levomepromazine + benzodiazepine , for example: lorazepam 0.5‒1 mg sublingually 2 times a day or midazolam 10 mg/24 hours NPI, especially with nausea due to increased anxiety or nausea of ​​anticipation;
• levomepromazine + dexamethasone 8–16 mg p/o, sc, emergency dose and 1 r/d when nothing else helps; if there is no effect, stop using dexamethasone within one week by reducing the dosage daily; otherwise, reduce the dose by 2 mg per week to the minimally effective dose.

The simultaneous use of prokinetics (act through the cholinergic system) and M-cholinergic blockers (act competitively antagonistically) should be avoided.

Nausea may be a manifestation of seizures (eg, in meningeal carcinomatosis), in which case anticonvulsants or benzodiazepines should be used.

In the absence of mechanical obstruction of the large intestine, consider switching to oral administration of drugs three days after achieving a positive effect from NPI or subcutaneous administration. If the patient's condition improves, the dual-component therapy regimen can be simplified after 1–2 weeks by gradually reducing the dose of one or two antiemetic drugs. The algorithm for choosing a drug to relieve vomiting is also presented in Appendix 1.

Useful tips

• Even if the patient is not vomiting, ask if he is bothered by nausea - patients rarely talk about this themselves.
• The central genesis of vomiting may be indicated by the presence of a concomitant process in the brain, an increase in intracranial pressure; involvement of the vestibular apparatus in the process; psychogenic arousal (fear, anxiety). Neurogenic vomiting is usually not associated with food intake, it occurs in the morning, it is provoked by the movement of the patient, head movements, and is combined with pale skin or facial flushing.
• Prokinetics should be prescribed very carefully in case of intestinal obstruction, because they can worsen intestinal colic and provoke severe abdominal pain.
• Octreotide and ondansetron promote constipation.
• Discontinue medications if the cause of symptoms is eliminated. For example, opioids are initially associated with nausea, so prokinetics should be given concomitantly. After 7–10 days, nausea stops and prokinetics can be discontinued.
• We should not forget about the need for careful oral care.
• Nausea may be completely relieved or significantly reduced; Vomiting once a day may be acceptable for intestinal obstruction.
• Ensure that the patient and caregivers are aware that antiemetic medications must be taken regularly or as needed; Discuss your treatment plan with them.
• Suggest dietary changes in favor of small, frequent snacks.
• Explain the need to avoid odors that are unpleasant to the patient.

Important
Try to help the patient to move him from a state of exhaustion to a state of being able to control the symptom!

Thank you for your help in preparing the materials:

Kravchenko T.V. (Chief Physician of the State Budgetary Healthcare Institution, Center for Emergency Medicine, Department of Healthcare),

Gurkin S.P. (Deputy Chief Physician for the organization of inpatient care of the State Budgetary Healthcare Institution of the Central Clinical Hospital of the Department of Healthcare),

Ibragimova A. N. (Head of the branch of the First Moscow Hospice named after Vera Millionshchikova, State Budgetary Healthcare Institution of the Center for Emergency Medicine of the Department of Healthcare).

List of sources:

1. Abuzarova G.R. Nevzorova D.V. Pain management in palliative care. Practical guide for the doctor. Moscow, 2021.
2. Chronic pain syndrome (CPS) in adult patients requiring palliative care, 2021. ICD 10: R52.1/ R52.2.
3. Introducing Palliative Care Fifth Edition. Editors Twycross R., Wilcock A., 2021.
4. Hospice and Palliative Care Training for Physicians. Unipac Self-Study Program, 2008.
5. Lanarkshire Palliative Care Guidelines, 2012.
6. ProCare HospiceCare. Hospice Medication Utilization Guidelines. Eds. S. Shah, M. Madison. www.ProCareHospiceCare.com

You can download the leaflet “Nausea and vomiting in palliative care” in pdf format here:
Practical_guide_nausea_and_vomiting.pdf

Mode of application

Depending on the form of the drug, Metoclopramide has some application features:

1. Oral method - take half an hour before meals, do not chew the tablets, be sure to wash them down with water. The maximum duration of treatment for vomiting and nausea is up to 5 days. Intervals between doses of the drug should be at least 6 hours. The dosage of the drug is calculated individually, according to age, body weight and pronounced clinical picture. Do not exceed the amount of medication above 0.5 mg/kg. The optimal adult dosage is 10 mg 3 times a day.
2. Injection method - the drug is prescribed for a course of 5 days. The solution is administered intravenously or intramuscularly over 3 minutes. Dosage for adults: 10 mg once or 30 mg 3 times a day.

In childhood, the use of Metoclopramide is possible from 2 years of age. If you weigh less than 60 kg, 0.1-0.15 mg/kg of the drug is indicated three times a day. Children over 15 years old weighing more than 60 kg are prescribed 10 mg 3 times a day.

Elderly people should reduce the therapeutic dose, taking into account the deterioration of the liver and excretory system.

Patients with kidney pathologies should use the drug with caution. The dose is reduced by 75% or 50% depending on the condition.

If liver function is impaired, take 10 mg once, or reduce the dosage by half.

Buy Metoclopramide solution intravenously and intramuscularly 5mg/ml 2ml No. 10 in pharmacies

Instructions for use Metoclopramide solution IV and IM 5mg/ml 2ml No. 10 Dosage forms solution for injection 5mg/ml 2ml Synonyms Vero-Metoclopramide Metoclopramide-Akri Metoclopramide-Promed Cerucal Cerulan Group Antiemetics International nonproprietary name Metoclopramide Composition Active substance - metoclopramide. Manufacturers: Biokhimik OJSC (Russia), Moscow Endocrine Plant (Russia), Novosibkhimpharm (Russia), Polpharma Pharmaceutical Plant (Poland), Promed Exports Pvt.Ltd (India), Sotex PharmFirma (Russia) Pharmacological action Pharmacological action - antiemetic, antihiccup. Stimulates the motor activity of the upper gastrointestinal tract and normalizes its motor function. Strengthens the tone and amplitude of gastric contractions, relaxes the pyloric sphincter and duodenal bulb, increases peristalsis and accelerates gastric emptying. It is a dopamine antagonist, suppresses the central and peripheral effects of apomorphine, increases the secretion of prolactin, aldosterone levels, and tissue sensitivity to acetylcholine. It is quickly and well absorbed, the maximum concentration is reached 1-2 hours after taking a single dose. Easily passes through histohematic barriers and penetrates tissues. Excreted in the urine after 72 hours. Side effects Dry mouth, constipation or diarrhea, drowsiness, depression, extrapyramidal disorders (convulsive twitching of the facial muscles, impaired movement of the eyeballs, protruding tongue), edema, galactorrhea, hyperprolactinemia, menstrual irregularities, mucosal hyperemia nasal membranes, skin rashes. Indications for use Nausea, vomiting, functional digestive disorders, reflux esophagitis, atony and hypotension of the stomach and duodenum; preparation for diagnostic studies of the gastrointestinal tract. Contraindications Hypersensitivity, glaucoma, pheochromocytoma, epilepsy, Parkinson's disease and other extrapyramidal disorders, pregnancy (first trimester), breastfeeding (breastfeeding should be stopped during treatment). Directions for use and dosage : Inside. Adults: 5-10 mg (1-2 teaspoons of solution) 3 times a day before meals or 2 ml intramuscularly. Children - 0.5 doses for adults; newborns are prescribed in the form of drops. Overdose Symptoms: hypersomnia, disorientation, extrapyramidal disorders. Treatment: usually go away on their own within 24 hours after discontinuation of the drug; if necessary, prescribe anticholinergic and antiparkinsonian drugs. Interaction The effect of the drug can be weakened by anticholinesterase drugs. Antipsychotics increase (mutually) the likelihood of developing extrapyramidal disorders. Strengthens the sedative effect of sleeping pills and alcohol. Slows down the absorption of digoxin, accelerates the absorption of paracetamol, tetracycline, levodopa, ethanol. Special instructions The possibility of decreased concentration and increased reaction time during treatment should be taken into account (it is better to avoid driving a car and working with potentially dangerous equipment). During the treatment period, alcohol consumption is not recommended. The injection solution must not be mixed with alkaline infusion solutions. Storage conditions List B. Store at room temperature in a dry place.

Side effects

The antiemetic may cause the following side effects:

1. Constipation, dry mouth, profuse diarrhea.
2. Feelings of drowsiness, malaise, headache and dizziness during the initial period of therapy.
3. Tension of the facial muscles.
4. Symptoms of parkinsonism and dyskinesia with prolonged use.
5. Hormonal imbalance.
6. Allergic manifestations.

Metoclopramide

The frequency of adverse reactions is given according to the classification: very often (≥ 1/10); often (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000); frequency unknown (frequency cannot be estimated from available data).

Blood and lymphatic system disorders:

frequency unknown - methemoglobinemia, probably associated with deficiency of the enzyme NADH-dependent cytochrome b5 reductase (especially in newborns), sulfhemoglobinemia (most often with the simultaneous use of high doses of sulfur-containing drugs).

Cardiac disorders:

infrequently - bradycardia; frequency unknown - cardiac arrest, which may be caused by bradycardia, atrioventricular block, sinus node block, prolongation of the QT interval on the electrocardiogram, ari.

Vascular disorders:

often - decreased blood pressure, frequency unknown - cardiogenic shock, acute increase in blood pressure in patients with pheochromocytoma.

Endocrine system disorders*

: infrequently - amenorrhea, hyperprolactinemia; rarely - galactorrhea; frequency unknown - gynecomastia.

* Endocrine disorders during long-term treatment are associated with hyperprolactinemia (amenorrhea, galactorrhea, gynecomastia).

Gastrointestinal disorders:

often - diarrhea; rarely - dry mouth.

Immune system disorders:

uncommon - hypersensitivity reactions; frequency unknown - anaphylactic reactions (including anaphylactic shock).

Nervous system disorders:

very often - drowsiness; often - extrapyramidal disorders (especially in children and young patients and/or when recommended doses of the drug are exceeded, even after a single administration), parkinsonism, akathisia; infrequently - dystonia, dyskinesia, impaired consciousness; rarely - seizures, especially in patients with epilepsy; frequency unknown - tardive dyskinesia, sometimes persistent, during or after long-term treatment, especially in elderly patients, neuroleptic malignant syndrome.

Mental disorders:

often - depression; infrequently - hallucinations; rarely - confusion.

General disorders and disorders at the injection site:

often - asthenia.

Adverse reactions that are most common when using high doses of the drug:

— Extrapyramidal symptoms: acute dystonia and dyskinesia, parkinsonism syndrome, akathisia developed even after using a single dose of the drug, especially in children and young patients (see section “Special instructions”),

- Drowsiness, decreased level of consciousness, confusion, hallucinations.

Overdose

In case of non-compliance with the therapeutic dose, an overdose is possible. It manifests itself with a pronounced clinical picture in the form of nervous disorders. Hallucinations and unclear consciousness are noted.

Rarely - deterioration of the cardiovascular system with a decrease in blood pressure, the appearance of bradycardia, even cardiac arrest.

Signs of an overdose last a day after starting to take the drug.

Treatment based on symptoms, medication with monitoring of cardiac and respiratory function.