METOCAI

Uses

Intubation of the small intestine, Premedication for radiologic examination of the upper gastrointestinal tract, Prophylaxis of chemotherapy-induced nausea and vomiting, Nausea and vomiting associated with cancer chemotherapy or radiotherapy, Diabetic gastric stasis, Gastro-oesophageal reflux disease, Diabetic gastric stasis, Prophylaxis of postoperative nausea and vomiting

METOCAI is also used to associated treatment for these conditions: Chemotherapy-Induced Nausea and Vomiting (CINV), Diabetic Gastroparesis, Dyspepsia, Flatulence, Gastroesophageal Reflux, Gastroparesis, Hiccups, Hyperacidity, Migraine, Nausea and vomiting, Post Operative Nausea and Vomiting (PONV), Acute, recurrent Diabetic Gastroparesis, Gastric bezoar, Radiation therapy induced nausea and vomiting, Facilitation of small bowel intubation therapy, Gastric emptying for radiologic procedures

How METOCAI works

METOCAI causes antiemetic effects by inhibiting dopamine D2 and serotonin 5-HT3 receptors in the chemoreceptor trigger zone (CTZ) located in the area postrema of the brain. Administration of this drug leads to prokinetic effects via inhibitory actions on presynaptic and postsynaptic D2 receptors, agonism of serotonin 5-HT4 receptors, and antagonism of muscarinic receptor inhibition. This action enhances the release of acetylcholine, causing increased lower esophageal sphincter (LES) and gastric tone, accelerating gastric emptying and transit through the gut. METOCAI antagonizes the dopamine D2 receptors. Dopamine exerts relaxant effect on the gastrointestinal tract through binding to muscular D2 receptors.

Dosage

METOCAI dosage

Intravenous-Intubation of the small intestine, Premedication for radiologic examination of the upper gastrointestinal tract:

• Adult: 10 mg as a single dose by slow inj over 1-2 min.
• Child: <6 yr 0.1 mg/kg as a single dose; 6-14 yr 2.5-5 mg as a single dose.

Prophylaxis of chemotherapy-induced nausea and vomiting:

• Adult: For highly emetogenic drugs/regimens: Initially, 2 mg/kg by slow inj over at least 15 min, 30 min before chemotherapy. Repeat 2 hrly for 2 doses, then 3 hrly for 3 doses. For less emetogenic drugs/regimens: 1 mg/kg may be used. Max duration: 5 days.

Oral-

Nausea and vomiting associated with cancer chemotherapy or radiotherapy:

• Adult: 10 mg, up to tid. Max duration: 5 days.

Diabetic gastric stasis:

• Adult: 10 mg 4 times daily for 2-8 wk.

Gastro-oesophageal reflux disease:

• Adult: 10-15 mg 4 times daily, depending on severity of symptoms. If symptoms are intermittent, may give single doses of 20 mg prior to provoking situation. Max duration: 12 wk.
• Elderly: 5 mg/dose.

Parenteral-

Diabetic gastric stasis:

• Adult: 10 mg 4 times daily by IM inj or slow IV inj over 1-2 min for up to 10 days. Convert to oral admin when symptoms subside sufficiently.

Prophylaxis of postoperative nausea and vomiting:

• Adult: 10 mg as a single dose by IM or slow IV inj over at least 3 min.
• Child: 1-3 yr 10-14 kg: 1 mg tid; >3-5 yr 15-19 kg: 2 mg tid; >5-9 yr 20-29 kg: 2.5 mg tid; >9-18 yr 30-60 kg: 5 mg tid. Max duration: 48 hr.

Should be taken on an empty stomach. Take ½ hr before meals.

Side Effects

Extrapyramidal symptoms (usually acute dystonic reactions); parkinsonism; tardive dyskinesia; restlessness, drowsiness, dizziness, anxiety, confusion, tremor; hallucinations (rare); depression w/ suicidal ideation; hypotension, HTN, GI disturbances, dyspnoea, visual disturbances, urinary frequency and incontinence, headache; hypersensitivity reactions (rash, bronchospasm, angioedema); galactorrhoea or related disorders; blood disorders; transient increase in plasma-aldosterone concentration. IV: Cardiac conduction disorders, transient flushing of face and upper body (high dose).

Toxicity

The rat oral LD50 of metoclopramide is 750 mg/kg.

Some symptoms of an overdose with metoclopramide include drowsiness, disorientation, and extrapyramidal reactions. Drugs that manage Parkinson's disease or anticholinergic drugs or antihistamines with anticholinergic properties should be employed to treat extrapyramidal symptoms. Normally, these symptoms subside within 24 hours. Unintentional overdose in infants receiving the oral solution of metoclopramide resulted in seizures, extrapyramidal symptoms, in addition to a lethargic state.

In addition, methemoglobinemia has been found to occur in premature and full-term neonates after a metoclopramide overdose. Intravenous methylene blue may treat metoclopramide-associated methemoglobinemia. It is important to note that methylene blue administration may lead to hemolytic anemia in patients who suffer from G6PD deficiency, which can result in fatality. Dialysis has not been shown to be effective in sufficiently eliminating metoclopramide in an overdose situation due to low plasma distribution of this drug.

Precaution

Patients with underlying neurological conditions, cardiac conduction disturbances, uncorrected electrolyte imbalance, bradycardia. Renal and hepatic impairment. Elderly, childn. Pregnancy and lactation.

Interaction

Antagonistic effect with anticholinergics and morphine derivatives. Potentiation of sedative effects with CNS depressants. Additive effect with other neuroleptics on the occurrence of extrapyramydal disorders. May increase the risk of serotonin syndrome with serotonergic drugs (e.g. SSRIs). May decrease digoxin bioavailability. May increase ciclosporin bioavailability. May prolong the neuromuscular blocking effect of mivacurium and suxamethonium. Increased exposure levels with strong CYP2D6 inhibitors (e.g. fluoxetine). May reduce plasma concentration of atovaquone.

Food Interaction

• Avoid alcohol.
• Take before a meal. Co-administration with food decreases bioavailability - take 30 minutes before meals.

[Moderate] GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.

Use in combination may result in additive central nervous system depression and
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol.

Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

METOCAI Hypertension interaction

[Moderate] In a study involving patients with essential hypertension, intravenously administered metoclopramide was shown to induce the release of catecholamines.

Therapy with metoclopramide should be administered cautiously in patients with hypertension because of potential increases in blood pressure.

METOCAI Drug Interaction

Moderate: diphenhydramine, duloxetine, pregabalin, alprazolamMinor: aspirin, acetaminophen, acetaminophenUnknown: omega-3 polyunsaturated fatty acids, insulin glargine, furosemide, atorvastatin, metoprolol, metoprolol, polyethylene glycol 3350, esomeprazole, montelukast, cyanocobalamin, ascorbic acid, cholecalciferol, ondansetron

METOCAI Disease Interaction

Major: depression, gastrointestinal disorders, NMS, pheochromocytoma, seizures, tardive dyskinesiaModerate: fluid retention, hypertension, parkinsonism, renal dysfunction

Volume of Distribution

The volume of distribution of metoclopramide is approximately 3.5 L/kg. This implies a high level of tissue distribution. METOCAI crosses the placental barrier and can cause extrapyramidal symptoms in the fetus.

Elimination Route

METOCAI is rapidly absorbed in the gastrointestinal tract with an absorption rate of about 84%. The bioavailability of the oral preparation is reported to be about 40.7%, but can range from 30-100%.

Nasal metoclopramide is 47% bioavailable. A 15mg dose reaches a C_max of 41.0 ng/mL, with a T_max of 1.25 h, and an AUC of 367 ng*h/mL.

Half Life

The mean elimination half-life of metoclopramide in people with healthy renal function ranges from 5 to 6 hours but is prolonged in patients with renal impairment. Downward dose adjustment should be considered.

Clearance

The renal clearance of metoclopramide is 0.16 L/h/kg with a total clearance of 0.7 L/h/kg. Clinical studies showed that the clearance of metoclopramide may be reduced by up to 50% in patients with renal impairment. After high intravenous doses, total metoclopramide clearance ranged from 0.31 to 0.69 L/kg/h.

Elimination Route

About 85% of an orally administered dose was measured in the urine within 72 hours during a pharmacokinetic study. An average of 18% to 22% of 10-20 mg dose was recovered as free drug within 3 days of administration.

Pregnancy & Breastfeeding use

Category B: Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).

Contraindication

GI haemorrhage, mechanical obstruction or GI perforation; confirmed or suspected pheochromocytoma; history of neuroleptic or metoclopramide-induced tardive dyskinesia; epilepsy, Parkinson's disease; history of methaemoglobinaemia with metoclopramide or of NADH cytochrome-b5 deficiency. Concomitant use with levodopa or dopaminergic agonists.

Acute Overdose

Symptoms: Extrapyramidal disorders, drowsiness, decreased level of consciousness, confusion, hallucination, cardiorespiratory arrest.

Management: Symptomatic treatment with continuous monitoring of CV and resp functions. In case of extrapyramidal symptoms, treatment is symptomatic (benzodiazepines in childn and/or anticholinergic antiparkinsonian medicinal products in adults).

Storage Condition

Store between 20-25°C. Protect from light.

Innovators Monograph

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