miglustat

Action and Spectrum

Actions and Spectrum: 

• The mechanism of action of miglustat involves inhibiting the enzyme glucosylceramide synthase, which plays a vital role in the synthesis of glucocerebroside. By inhibiting this enzyme, miglustat reduces the production of glucocerebroside, thereby decreasing its accumulation in cells and tissues. 
• The spectrum of activity of miglustat is primarily focused on the management of Gaucher disease type 1. It is impractical for other types of Gaucher disease, such as types 2 and 3, which are more severe forms of the condition. Additionally, miglustat has been investigated for its potential use in other lysosomal storage disorders, such as Niemann-Pick disease type C. 

Drug Interaction

Adverse Reaction

Frequency not defined 

>10% 

Weight loss (66-70%) 

Flatulence (29-50%) 

Headache (21-22%) 

Nausea (8-22%) 

Visual disturbances (17%) 

Diarrhea (89-100%) 

Abdominal pain (18-67%) 

Dizziness (11%) 

Tremor (11-30%) 

Vomiting (4-11%) 

1-10% 

Vomiting (4%) 

Migraine (6%) 

Anorexia (7%) 

Thrombocytopenia (6-10%) 

Memory impairment (8%) 

Abdominal distension (8%) 

Epigastric pain (<6%) 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: miglustat should not be used in individuals with known hypersensitivity or allergy to the drug or its components. 
• Severe renal impairment: miglustat is primarily eliminated through the kidneys. Therefore, it is contraindicated in individuals with severe renal impairment (creatinine clearance less than 20 mL/min) due to the potential for increased drug accumulation and the risk of adverse effects. 
• Pre-existing advanced peripheral neuropathy: miglustat has been associated with peripheral neuropathy, a condition characterized by nerve damage in the extremities. If an individual has pre-existing advanced peripheral neuropathy, miglustat is contraindicated due to the potential to exacerbate the condition. 

Caution: 

• Gastrointestinal Symptoms: miglustat can cause gastrointestinal symptoms such as diarrhea, flatulence, and abdominal pain. These symptoms are common side effects and may require management.  
• Peripheral neuropathy: miglustat has been associated with peripheral neuropathy, a condition characterized by nerve damage that can cause numbness, tingling, and weakness in the extremities.  
• Liver Function Monitoring: miglustat can affect liver function, and periodic liver function tests may be recommended during treatment. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available. It is recommended to avoid miglustat use during pregnancy unless the potential benefits outweigh the risks. 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

The primary pharmacological action of miglustat is seen in treating Gaucher disease type 1, a lysosomal storage disorder characterized by the deficient activity of the enzyme glucocerebrosidase. In Gaucher disease, glucocerebroside accumulates in various organs and tissues, leading to organ dysfunction. By inhibiting glucosylceramide synthase and reducing the synthesis of glucocerebroside, miglustat helps to decrease substrate accumulation and potentially alleviate some of the symptoms associated with Gaucher disease type 1. 

Pharmacodynamics: 

miglustat’s primary pharmacodynamic effects are observed in treating Gaucher disease type 1, a lysosomal storage disorder characterized by deficient activity of the enzyme glucocerebrosidase. 

Pharmacokinetics: 

Absorption 

miglustat is well-absorbed after oral administration. Its bioavailability is high, approximately 97%. The peak plasma concentration is reached around 2-2.5 hours after oral dosing. 

Distribution 

miglustat has a large volume of distribution (Vd) ranging from 83-105 liters. This suggests that the drug is extensively distributed throughout the body tissues. miglustat does not bind significantly to plasma proteins, meaning it remains unbound mainly in the bloodstream. 

Metabolism 

miglustat is minimally metabolized in the body. The exact extent of metabolism is generally considered to undergo minimal hepatic metabolism. 

Elimination and Excretion 

miglustat is primarily excreted unchanged in the urine. The elimination half-life of miglustat is around 6-7 hours, indicating that it takes approximately 6-7 hours for half of the drug to be eliminated from the body. 

Adminstartion

Administration: 

• Food Intake: miglustat can be taken with or without food. However, taking miglustat at least 2 hours before or 2 hours after a meal is generally recommended to optimize its absorption. 
• Duration of Treatment: The duration of miglustat treatment will depend on the specific condition and the individual patient’s response. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: miglustat 

Why do we use miglustat? 

miglustat is primarily used in treating Gaucher disease type 1, a rare genetic disorder characterized by the deficiency of the enzyme glucocerebrosidase. It is indicated for treating mild to moderate type 1 Gaucher disease in adult and pediatric patients.