Saroglitazar Magnesium

Approved Indications:

• Type 2 Diabetes Mellitus with Dyslipidemia or Hypertriglyceridemia:
  As an adjunct to diet and exercise to improve glycemic control and correct lipid abnormalities in patients with Type 2 Diabetes Mellitus, particularly those not adequately controlled on statins alone.

Clinically Accepted Off-Label or Investigational Uses:

• Non-Alcoholic Fatty Liver Disease (NAFLD)
• Non-Alcoholic Steatohepatitis (NASH)
  Emerging data supports its hepatoprotective and lipid-lowering effects in patients with NAFLD/NASH, though formal regulatory approval is pending.

Adults:

• Recommended Dose: 4 mg once daily orally, with or without food.
• Initiation in Specific Cases: A starting dose of 2 mg once daily may be considered in patients with mild renal or hepatic impairment.

Pediatrics:

• Safety and efficacy not established in patients below 18 years; use is not recommended.

Elderly:

• No dose adjustment typically required, but monitor renal and hepatic function.

Renal Impairment:

• Mild to Moderate: Use with caution.
• Severe Impairment/ESRD: Use not recommended due to limited data.

Hepatic Impairment:

• Mild: May use with caution.
• Moderate to Severe: Contraindicated.

Route of Administration: Oral
Frequency: Once daily
Duration: Chronic, long-term use as directed by healthcare provider.

Saroglitazar Magnesium is a dual agonist of Peroxisome Proliferator-Activated Receptors (PPARs), with predominant activity on PPAR-α and moderate activity on PPAR-γ.

• PPAR-α activation enhances lipid metabolism by increasing fatty acid oxidation and reducing hepatic triglyceride production, resulting in decreased plasma triglyceride levels and improved HDL cholesterol.
• PPAR-γ activity improves insulin sensitivity by modulating glucose uptake in adipose tissue and skeletal muscle.
  Together, this dual action improves both dyslipidemia and glycemic control in patients with diabetic dyslipidemia and related metabolic disorders.

• Absorption: Rapid and well absorbed after oral administration.
• Bioavailability: High; food does not significantly affect absorption.
• Tmax (Time to peak): Approximately 1 to 2 hours post-dose.
• Distribution: Widely distributed; highly protein-bound in plasma.
• Metabolism: Extensively metabolized in the liver via oxidation and conjugation pathways.
• Elimination Half-life: ~5 to 7 hours.
• Excretion: Predominantly via feces; minimal renal excretion.
• Steady State: Reached within 7 days of once-daily administration.

• Pregnancy: No official FDA pregnancy category assigned. Animal studies show fetal risk at high doses. Use during pregnancy only if potential benefits justify the potential risk to the fetus.
• Lactation: Unknown whether excreted in human breast milk. Due to the potential for serious adverse reactions in nursing infants, breastfeeding is not advised during treatment.
• Recommendation: Use with caution in women of childbearing potential and advise effective contraception during therapy.

• Primary Class: Dual PPAR Agonist
• Subclass: PPAR-α/γ Agonist (Glitazar Class)
• Therapeutic Area: Antidiabetic and Hypolipidemic Agent

• Known hypersensitivity to Saroglitazar or any component of the formulation
• Moderate to severe hepatic impairment
• Severe renal impairment or end-stage renal disease
• Active or history of bladder cancer (precautionary, due to PPAR-γ activity)
• Pregnancy and lactation (unless clearly indicated)
• Pediatric use (under 18 years)

• Liver Function: Monitor ALT, AST, and other hepatic enzymes periodically; discontinue if significant liver injury is suspected.
• Fluid Retention & Edema: May occur due to PPAR-γ effect; use cautiously in patients with cardiac disease or at risk of heart failure.
• Weight Gain: May occur, especially when combined with insulin or sulfonylureas.
• Fracture Risk: Long-term PPAR-γ activity may increase risk of bone fractures.
• Bladder Cancer Risk: Although not established, use caution in patients with risk factors.
• Combination Therapy: Not a substitute for statins; may be used as add-on therapy in uncontrolled dyslipidemia.
• Monitoring: Regular lipid panels, liver function tests, and renal parameters should be monitored during prolonged therapy.

Common Adverse Effects:

• Gastrointestinal: Abdominal discomfort, nausea, flatulence, dyspepsia
• Metabolic: Weight gain, increased appetite
• Hepatic: Elevated liver enzymes
• General: Headache, fatigue, back pain

Serious and Rare Adverse Effects:

• Hepatotoxicity or cholestatic jaundice
• Fluid retention leading to peripheral edema or exacerbation of heart failure
• Possible hypoglycemia when used with other antidiabetics
• Increased creatinine in susceptible individuals

Timing & Severity:

• Most side effects are mild to moderate and appear within the first few weeks.
• Hepatic effects may be delayed; routine lab monitoring is advised.

• Statins: No significant interaction; may be safely co-administered to enhance lipid control.
• Insulin and Sulfonylureas: Increased risk of hypoglycemia when combined.
• CYP450 Involvement: Minimal interaction with CYP450 enzymes; low risk for major metabolic drug interactions.
• Food Interactions: No significant interaction with food.
• Alcohol: Caution advised due to potential hepatic stress.

• Indian Regulatory Approval: Widely approved and used in India for diabetic dyslipidemia.
• Guidelines: Included in some regional dyslipidemia management protocols as adjunct therapy in patients inadequately controlled by statins.
• NAFLD/NASH Research: Recent clinical trials show promising results in improving liver enzymes and hepatic steatosis; broader global recognition is under evaluation.
• Global Approval Status: Not yet approved by US FDA or EMA; under clinical development in various international regions.

• Temperature: Store below 30°C (86°F).
• Humidity: Keep in a dry place; protect from moisture.
• Light: Store in original packaging to protect from light.
• Handling: Do not use damaged or discolored tablets.
• No refrigeration or reconstitution required.