Usage
Levosulpiride is prescribed for the treatment of various gastrointestinal disorders, including functional dyspepsia (indigestion), gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), nausea, and vomiting. It also has some applications in managing certain psychiatric conditions like depression, anxiety disorders, schizophrenia, hallucinations, and vertigo. Additionally, it has been used in treating premature ejaculation. It’s pharmacological classification is as an atypical antipsychotic and prokinetic agent.
Levosulpiride’s mechanism of action involves two main aspects: In the gastrointestinal tract, it acts as a prokinetic by blocking dopamine D2 receptors, thereby increasing the frequency of muscular contractions in the stomach and intestines to improve food movement and reduce symptoms like nausea and vomiting. At lower doses, it also affects central dopamine D2 and D3 receptors in the brain, leading to its antipsychotic effects in conditions like schizophrenia and depression.
Alternate Names
While Levosulpiride is the established generic name, several brand names exist depending on the region and manufacturer. Some examples include: Dislep, Perk, Levogastrol.
How It Works
Pharmacodynamics: Levosulpiride primarily acts as a dopamine D2 receptor antagonist in both the central nervous system and the gastrointestinal tract. Its prokinetic effect stems from the blockade of peripheral D2 receptors in the enteric nervous system, leading to increased acetylcholine release and enhanced gastric motility and emptying. The antipsychotic effect is attributed to its action on central D2 receptors, particularly in the limbic system, which modulates dopaminergic neurotransmission involved in psychosis and mood regulation. At higher doses, it can also block postsynaptic D2 receptors.
Pharmacokinetics: Levosulpiride is readily absorbed after oral administration, with peak plasma concentrations achieved in approximately 1-2 hours. It undergoes minimal metabolism in the liver and is primarily eliminated through renal excretion, with a half-life of about 6-8 hours.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Levosulpiride’s primary mechanism is dopamine D2 receptor antagonism. It does not significantly interact with other receptors or enzymes, such as the cytochrome P450 system, making it less prone to certain drug interactions.
Elimination Pathways: Levosulpiride is primarily eliminated through renal excretion, with approximately 75% of an administered dose excreted unchanged in the urine within 24 hours.
Dosage
Standard Dosage
Adults:
The standard recommended dose for gastrointestinal issues is 25 mg three times a day, taken orally approximately 20-30 minutes before meals. For psychiatric conditions, dosages can range from 50 mg to 300 mg per day, divided into multiple doses, with the specific amount determined by the patient’s condition and response. The maximum recommended daily dose is typically 300 mg.
Children:
Levosulpiride is generally not recommended for use in children under 18 years of age due to insufficient data on safety and efficacy in this population.
Special Cases:
- Elderly Patients: Dose reduction is advised in elderly patients due to potential age-related decline in renal function. The starting dose should be lower, and titration should be done cautiously.
- Patients with Renal Impairment: Dose adjustment is necessary in patients with renal impairment as the drug is primarily excreted through the kidneys. The dose and frequency should be reduced based on the degree of renal dysfunction.
- Patients with Hepatic Dysfunction: Since levosulpiride undergoes minimal hepatic metabolism, significant dose adjustment is generally not required. However, caution is advised, and monitoring is recommended.
- Patients with Comorbid Conditions: Careful consideration and potential dose adjustment may be needed for patients with comorbid conditions such as heart disease, asthma, or a history of neuroleptic malignant syndrome.
Clinical Use Cases
The information on Levosulpiride does not describe dosing guidelines specifically for intubation, surgical procedures, mechanical ventilation, ICU use or emergency situations. Its primary use is for the treatment of gastrointestinal and psychiatric disorders mentioned above.
Dosage Adjustments
Dose adjustments may be necessary based on patient-specific factors like renal or hepatic dysfunction, metabolic disorders, age, and concomitant medications.
Side Effects
Common Side Effects
Headache, fatigue, drowsiness, dizziness, dry mouth, constipation, changes in menstrual cycle (amenorrhea, irregular periods), gynecomastia (breast enlargement in males), galactorrhea (nipple discharge), changes in libido, and weight fluctuations.
Rare but Serious Side Effects
Neuroleptic malignant syndrome (NMS), a rare but life-threatening adverse reaction characterized by high fever, muscle rigidity, altered mental status, autonomic instability; tardive dyskinesia, involving involuntary, repetitive movements, primarily of the face and mouth; extrapyramidal symptoms (EPS), like tremors, muscle rigidity, and restlessness; cardiac arrhythmias, including QT prolongation; hypersensitivity reactions; and hyperprolactinemia.
Long-Term Effects
Long-term use of Levosulpiride, especially at higher doses, can potentially increase the risk of tardive dyskinesia and other movement disorders. Regular monitoring is crucial for early detection and management.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include NMS, severe EPS, cardiac arrhythmias, and hypersensitivity reactions. These require immediate medical intervention.
Contraindications
Levosulpiride is contraindicated in patients with hypersensitivity to the drug, pheochromocytoma (adrenal gland tumor), prolactin-dependent tumors (e.g., pituitary prolactinomas, breast cancer), epilepsy, and during mania or manic phase of bipolar disorder. It is also contraindicated in patients with gastrointestinal bleeding, mechanical obstruction, or perforation.
Drug Interactions
Levosulpiride can interact with several medications: Dopamine agonists (e.g., levodopa) may have antagonistic effects, reducing the efficacy of both drugs; Drugs that prolong the QT interval (e.g., some antiarrhythmics, certain antibiotics) can increase the risk of cardiac arrhythmias; Anticholinergic drugs may exacerbate anticholinergic side effects; Antacids and sucralfate can reduce levosulpiride absorption; Alcohol can increase sedation.
Pregnancy and Breastfeeding
Levosulpiride is generally not recommended during pregnancy due to the potential risk of fetal harm, although limited data is available. It is also not recommended during breastfeeding as it can be excreted in breast milk and may affect the nursing infant.
Drug Profile Summary
- Mechanism of Action: Dopamine D2 receptor antagonist (both peripherally and centrally).
- Side Effects: Common: Headache, fatigue, drowsiness, constipation, menstrual changes, gynecomastia, galactorrhea. Serious: NMS, tardive dyskinesia, EPS, cardiac arrhythmias.
- Contraindications: Hypersensitivity, pheochromocytoma, prolactin-dependent tumors, epilepsy, mania, GI bleeding/obstruction.
- Drug Interactions: Levodopa, QT-prolonging drugs, anticholinergics, antacids, alcohol.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: 25 mg thrice daily (GI); 50-300 mg/day (psychiatric). Elderly: Dose reduction advised. Renal impairment: Dose adjustment necessary.
- Monitoring Parameters: Liver function tests, blood prolactin levels, electrocardiogram (ECG), and monitoring for extrapyramidal symptoms.
Popular Combinations
Levosulpiride is sometimes used in combination with other medications for specific conditions, but no “popular combinations” are consistently mentioned in the provided material. Any combined use should be carefully considered by a healthcare professional.
Precautions
- General Precautions: Pre-screening for allergies, existing medical conditions (especially renal/hepatic impairment, cardiac disease, psychiatric history), and concomitant medications is crucial.
- Specific Populations: Use with caution in the elderly. Not recommended for children. Avoid or use with extreme caution during pregnancy and breastfeeding.
- Lifestyle Considerations: Alcohol should be avoided due to increased sedation risk. Smoking may affect drug metabolism. Caution is advised when operating machinery or driving due to potential drowsiness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Levosulpiride?
A: The recommended dosage varies depending on the indication. For gastrointestinal issues, the standard dose is 25 mg three times a day. For psychiatric conditions, it ranges from 50 mg to 300 mg/day, divided into multiple doses. Dosage adjustments are necessary for elderly patients and those with renal impairment. It’s not recommended for children.
Q2: What are the primary uses of Levosulpiride?
A: Levosulpiride is primarily used to treat gastrointestinal disorders like functional dyspepsia, GERD, and IBS. It’s also used in some psychiatric conditions like depression, anxiety, and schizophrenia.
Q3: What are the common side effects of Levosulpiride?
A: Common side effects include headache, fatigue, drowsiness, constipation, menstrual changes, gynecomastia, galactorrhea, and libido changes.
Q4: What are the serious side effects of Levosulpiride?
A: Serious side effects include neuroleptic malignant syndrome (NMS), tardive dyskinesia, extrapyramidal symptoms (EPS), and cardiac arrhythmias.
Q5: Is Levosulpiride safe during pregnancy and breastfeeding?
A: Levosulpiride is generally not recommended during pregnancy and breastfeeding due to potential risks to the fetus/infant.
Q6: Can I take Levosulpiride with antacids?
A: Antacids can reduce the absorption of Levosulpiride. If antacids are necessary, they should be taken at least 2 hours apart from Levosulpiride.
Q7: What is the mechanism of action of Levosulpiride?
A: Levosulpiride is a dopamine D2 receptor antagonist. In the gut, this blockade increases motility. In the brain, it influences mood and behavior.
Q8: How is Levosulpiride eliminated from the body?
A: Levosulpiride is primarily eliminated through the kidneys. Dose adjustment is necessary in patients with renal impairment.
Q9: Can Levosulpiride interact with other medications?
A: Yes, Levosulpiride can interact with several medications, including levodopa, QT-prolonging drugs, anticholinergics, and alcohol. Consult with a physician or pharmacist before combining Levosulpiride with other medications.
Q10: What precautions should be taken while using Levosulpiride?
A: Pre-screening for allergies and other medical conditions is essential. Caution is advised in elderly patients. It’s important to avoid alcohol and to be cautious when driving or operating machinery due to potential drowsiness. Close monitoring for side effects is recommended, especially during long-term use.
