Maxocol

Approved Indications:

A. Gastrointestinal Disorders

• Gastroparesis (Diabetic origin): Relief of symptoms such as nausea, vomiting, bloating, and early satiety.
• Gastroesophageal Reflux Disease (GERD): Short-term treatment (4–12 weeks) of adults who fail to respond to conventional therapy.
• Prevention of Nausea and Vomiting: Including postoperative, chemotherapy-induced, and radiation-induced nausea and vomiting.
• Facilitation of small bowel intubation: In radiologic or endoscopic procedures.

B. Diagnostic Aid

• Radiological examination of the upper GI tract: To accelerate gastric emptying and improve visualization.

C. Off-label / Clinically Accepted Uses

• Migraine-associated nausea and vomiting
• Hiccup (persistent, intractable)
• Prevention of aspiration pneumonitis in surgical or labor patients
• Augmentation of lactation (limited evidence; not routinely recommended due to safety concerns)

Route: Oral (tablet, syrup), Intravenous (IV), Intramuscular (IM)

Adults:

• Diabetic Gastroparesis:
• Oral: 10 mg up to 4 times daily, 30 minutes before meals and at bedtime, for 2–8 weeks
• GERD (short-term):
• Oral: 10–15 mg up to 4 times daily, before meals and at bedtime
• Prevention of Chemotherapy-Induced Nausea/Vomiting (CINV):
• IV: 1–2 mg/kg 30 minutes before chemotherapy; may repeat every 2 hours for 2 doses, then every 3 hours for 3 doses
• Postoperative Nausea/Vomiting:
• IV/IM: 10–20 mg near the end of surgery
• Radiologic examination / Small bowel intubation:
• IV: 10 mg over 1–2 minutes 10 minutes before procedure
• Migraine (off-label):
• IV: 10 mg given slowly over 1–2 minutes

Pediatrics:

• Chemotherapy-Induced Nausea/Vomiting:
• IV: 0.1–0.15 mg/kg/dose every 6–8 hours (max: 10 mg/dose)
• Other GI indications:
• Oral: 0.1–0.2 mg/kg/dose 3–4 times daily (max: 0.5 mg/kg/day)

⚠ Pediatric use should be limited to short durations due to risk of extrapyramidal reactions.

Elderly:

• Use the lowest effective dose.
• Increased risk of tardive dyskinesia—avoid long-term use.

Renal Impairment:

• CrCl <40 mL/min: Reduce dose by 50%
• CrCl <10 mL/min: Reduce dose by 75%

Hepatic Impairment:

• Use with caution; monitor for adverse CNS effects

Administration Notes:

• Administer oral doses 30 minutes before meals and at bedtime.
• IV doses should be infused slowly (over at least 1–2 minutes).

Metoclopramide is a dopamine D2 receptor antagonist with additional serotonergic properties. In the gastrointestinal tract, it enhances the response of tissues to acetylcholine, increasing lower esophageal sphincter tone, accelerating gastric emptying, and improving duodenal peristalsis. It antagonizes D2 receptors centrally in the chemoreceptor trigger zone (CTZ), which contributes to its antiemetic action. At higher doses, it also antagonizes 5-HT3 receptors in the CNS and GI tract, enhancing anti-nausea effects. These actions make it effective for nausea, vomiting, and gastroparesis.

• Absorption: Rapid and well absorbed orally
• Bioavailability: ~80%
• Onset of Action:
• Oral: ~30–60 minutes
• IV: 1–3 minutes
• IM: 10–15 minutes
• Peak Plasma Concentration: ~1–2 hours (oral)
• Distribution: Vd ~3.5 L/kg; crosses blood-brain barrier and placenta; found in breast milk
• Protein Binding: ~30%
• Metabolism: Hepatic metabolism primarily via sulfation and glucuronidation
• Half-life: 5–6 hours (longer in renal impairment)
• Excretion: ~80% renal (unchanged and metabolites); requires dose adjustment in renal dysfunction

• Pregnancy: Category B (FDA). No known teratogenic risk. Widely used during pregnancy for nausea and vomiting, including hyperemesis gravidarum. Use only when clearly needed.
• Lactation: Excreted into breast milk in small amounts. Considered generally safe, but caution advised due to potential for infant sedation or extrapyramidal symptoms. Monitor infants if prolonged maternal use is necessary.

• Primary Class: Antiemetic and Gastroprokinetic Agent
• Subclass: Dopamine D2 receptor antagonist with serotonin (5-HT3) antagonism at higher doses

• Hypersensitivity to metoclopramide or any component
• History of tardive dyskinesia or drug-induced movement disorders
• Pheochromocytoma (risk of hypertensive crisis)
• Epilepsy or patients on drugs that lower seizure threshold
• GI hemorrhage, mechanical obstruction, or perforation
• Parkinson’s disease (can worsen symptoms)

• Tardive Dyskinesia: Risk increases with treatment duration and dose. May be irreversible. Avoid use longer than 12 weeks.
• Extrapyramidal Symptoms (EPS): Dystonia, akathisia, and parkinsonism—more common in children and young adults
• Neuroleptic Malignant Syndrome (NMS): Rare but potentially fatal; discontinue immediately if suspected
• Depression and Suicidal Ideation: Use with caution in patients with a history of mental illness
• Renal Impairment: Risk of drug accumulation and toxicity
• Pediatric Use: Increased risk of dystonic reactions—limit use

Common:

• CNS: Drowsiness, fatigue, restlessness, insomnia, dizziness
• GI: Nausea, diarrhea
• Endocrine: Galactorrhea, gynecomastia, menstrual irregularities (due to elevated prolactin)

Serious/Rare:

• Neurological: Tardive dyskinesia (involuntary movements), Parkinsonian symptoms, dystonia, akathisia
• Psychiatric: Depression, suicidal thoughts
• Cardiovascular: Hypotension, hypertension, arrhythmias (rare)
• Allergic: Rash, bronchospasm, anaphylaxis (rare)
• Hematologic: Methemoglobinemia (especially in neonates and G6PD-deficient patients)

Timing: Neurological symptoms may appear within days to weeks. Tardive dyskinesia is more likely with prolonged use.

• CNS Depressants (e.g., opioids, benzodiazepines): Additive sedative effects
• Antipsychotics (e.g., haloperidol): Increased risk of extrapyramidal symptoms
• Levodopa & Dopamine Agonists: Antagonistic effects—avoid concurrent use
• MAO Inhibitors: Risk of hypertensive crisis (with pheochromocytoma)
• Cyclosporine: Increased cyclosporine levels due to enhanced GI motility
• Digoxin: Decreased absorption due to accelerated gastric emptying

Enzyme System: Primarily metabolized via conjugation; not heavily reliant on CYP450 enzymes, but may involve minor CYP2D6 pathways

• FDA Black Box Warning: Reinforced risk of tardive dyskinesia; limit use to ≤12 weeks
• EMA and WHO Guidelines: Recommend caution in pediatric populations and advise against long-term use
• New Formulation Guidance: Oral disintegrating tablets now available for rapid onset without swallowing

• Oral Tablets & Syrup:
• Store at 20°C to 25°C (68°F to 77°F)
• Protect from moisture and light
• Do not refrigerate syrup unless specified by manufacturer
• Injectables (IV/IM):
• Store vials at 20°C to 25°C
• Protect from freezing
• Use reconstituted solution within manufacturer-specified time (usually within 24 hours if refrigerated)