PLASIL ® Metoclopramide

PLASIL ® is a drug based on metoclopramide monohydrochloride monohydrate.

THERAPEUTIC GROUP: Drugs for functional gastrointestinal disorders - prokinetics.

IndicationsAction mechanismStudies and clinical effectiveness Usage and dosage instructionsWarnings Pregnancy and lactationInteractionsContraindicationsUndesirable effects

Indications PLASIL ® Metoclopramide

PLASIL ® is used, due to its therapeutic properties, in the treatment of functional disorders of the gastro-intestinal tract due to prolonged drug therapies, gastritis and peptic ulcers, dyspeptic syndromes, surgical and radiological therapies.

PLASIL ® is also widely used in the treatment of nausea and vomiting of various origins (for example associated with headaches, anxiety disorders, anesthetic treatment, etc.).

Mechanism of action PLASIL ® Metoclopramide

Metoclopramide is a basic, fat-soluble molecule, which is why it is effectively absorbed at the intestinal level following oral administration and subsequently distributed to various tissues linked to plasma proteins. The bioavailability observed is subject to important individual variations which are more accentuated when the drug is taken intramuscularly (increased bioavailability and maximum concentration).

Its therapeutic action is linked to the different modulating properties exerted on various receptor structures present at the level of the gastro-intestinal tract, important in coordinating and regulating the peristaltic, contractile and tonic capacities of the intestinal musculature. More precisely, there is an increase in the tone and amplitude of the gastroduodenal peristaltic contractions, which tends to progressively decrease from the most proximal end towards the distal one, allowing a progression of the intestinal contents towards the colon thus avoiding any kind of reflux.

The latter type of activity also appears to be supported by the tonic action that metoclopramide exerts against the musculature of the distal part of the esophagus, therefore also of the esophageal sphincter.

From the molecular point of view, all the aforementioned functions are justified by a coordinative action of the active ingredient contained in PLASIL ® able to antagonize the effects of dopamine D1 and 5-HT3 receptors of serotonin, and enhance the activation of 5-HT4 receptors, responsible for cholinergic stimulation.

After its action, after about 3-5 hours, the metoclopramide, undergoes a slight hepatic metabolism, being subsequently eliminated through the urine.

Studies carried out and clinical efficacy

1. METOCLOPRAMIDE IN PREGNANCY

Nausea and vomiting are two very frequent disorders in pregnancy, which significantly worsen the quality of life of future mothers during the entire gestational period. Among the first choice antiemetics, in different countries, there is metaclopramide, which is not recommended in the first quarter. However, this recent study focuses on statistics, arguing that the incidence of congenital abnormalities, perinatal death, low birth weight or preterm pregnancies is not particularly high in women who have taken metoclopramide. Nevertheless, however, it is possible to observe a slight trend, such as to justify the request for more clinical studies useful to clarify the real danger of this drug when taken during pregnancy.

2. METOCLOPRAMIDE AND ACUTE MIGRAINE

The rapid administration of metoclopramide, today represents one of the possible therapies useful in the treatment of acute migraine. Although it has long been used in common clinical practice, optimal dosage does not yet exist. For this reason, the intravenous administration of 10, 20 and 40 mg of active ingredient was tested, evaluating its effectiveness. Studies seem to agree that dosages above 10mg do not result in a significant improvement in symptoms.

3. THE INFFICACY OF METOCLOPRAMID IN PREVENTING NAUSEA AND POST-INTERVENTION VOMITING

Nausea and vomiting are among the most frequently observed reactions following a surgical procedure with relative sedation, which makes the post-operative course particularly annoying. Among the drugs used in the treatment of this condition it is possible to include metoclopramide, which however, despite its wide use, seems to be the least effective in the prevention of these disorders.

Method of use and dosage

The recommended doses for the use of PLASIL ® are:

PLASIL ® tablets of 10.5 mg of metoclopramide monohydrochloride monohydrate: one tablet 3 times a day before meals;
PLASIL ® is about 10.5 mg of metoclopramide monohydrochloride monohydrate: 10ml of syrup 3 times a day, before meals;
PLASIL ® vial for solution for injection of 10.5 mg of metoclopramide monohydrochloride monohydrate: a vial intramuscularly or intravenously (slow release). In the latter case the administration should be guaranteed by expert personnel.

The intake of PLASIL ® must take place under strict medical supervision, and any adjustments of the dosage, necessary for example in patients with liver and kidney diseases, should necessarily be established by the doctor, after a careful evaluation of the physical condition of the patient.

Warnings PLASIL ® Metoclopramide

Given the hepatic metabolism and subsequent renal elimination of metoclopramide monohydrochloride monohydrate, PLASIL ® should be taken with particular care in patients with reduced liver and kidney function.

The same precaution should be respected even in the case of depressed and epileptic patients, given the ability of the active principle to lower the relative thresholds of symptom onset.

The onset of fever, extrapyramidal disorders, increased serum concentrations of muscle enzymes, increased prolactin blood concentrations in patients with breast cancer or pituitary adenoma, could occur following the discontinuation of PLASIL ® in this case, could be sufficient to stop the symptoms.

The presence of alcohol and side effects such as drowsiness, dizziness and loss of perceptive ability after taking PLASIL ® could make driving cars or using machinery dangerous.

PREGNANCY AND BREASTFEEDING

During pregnancy and lactation it is important to ask your doctor or pharmacist for advice before taking any medicine.

Pregnancy

A vast amount of data on pregnant women (more than 1, 000 exposure outcomes) indicates no malformative toxicity and fetotoxicity. If clinically necessary, metoclopramide can be used during pregnancy. Due to the pharmacological properties (as for other neuroleptics), extrapyramidal syndrome in the newborn cannot be excluded in the case of metoclopramide administration at the end of pregnancy. Metoclopramide should be avoided at the end of pregnancy. If metoclopramide is used, neonatal monitoring should be instituted.

Feeding time

Metoclopramide is excreted in breast milk at low levels. Adverse reactions in the breast-fed child cannot be excluded. Therefore metoclopramide is not recommended during breastfeeding. Discontinuation of metoclopramide in breast-feeding women should be considered.

Interactions

The effects of the active ingredient contained in PLASIL ® could be enhanced by the concomitant administration of alcohol, drugs with inhibitory action on the central nervous system, and inhibited by the simultaneous intake of levodopa, anticholinergics and morphine and derivatives.

The prokinetic action of metoclopramide monohydrochloride monohydrate, could instead cause an alteration of the pharmacokinetic properties of different active principles when taken simultaneously.

Contraindications PLASIL ® Metoclopramide

PLASIL ® is contraindicated in patients with glaucoma, pheochromocytoma, epileptic disease, Parkinson's syndrome, extrapyramidal pathologies and in patients under drug treatment with anticholinergics, levodopa or drugs capable of determining extrapyramidal reactions.

The intake of this drug is also contraindicated in case of hypersensitivity to the active ingredient or to one of its components, in the first trimester of pregnancy, and in all those cases in which the increase in peristalsis and intestinal motility could aggravate the conditions of patient health (gastro-intestinal bleeding, perforation and intestinal obstruction).

Undesirable effects - Side effects

The intake of PLASIL ® especially when prolonged over time, may be associated with extrapyramidal syndromes such as tremor, acute dystonia and dyskinesia, drowsiness, hallucinations, confusions, alteration of personality, convulsions and depression.

Clinical trials and post-marketing monitoring also described the possible incidence of diarrhea, methaemoglobinaemia, hyperprolactinaemia in patients at risk, hypotension and allergic reactions.