Sarozar Tablet

Saroglitazar is a potent and predominantly Peroxisome Proliferator-Activated Receptor (PPAR)-alpha agonist with moderate PPAR-gamma agonistic activity. PPARs are nuclear lipid-activated transcription factors that regulate the expression of various genes involved in the control of lipid and lipoprotein metabolism, glucose homeostasis and inflammatory processes.

PPARa activation by Saroglitazar increases the hepatic oxidation of fatty acids (FA) and reduces the synthesis and secretion of TG. This in turn increases diversion of FA from peripheral tissues (e.g. skeletal muscle and fat tissue) to the liver, and thereby decreasing both FA synthesis and delivery of TG to peripheral tissues. Saroglitazar also causes increased lipolysis and elimination of TG-rich particles from plasma by activating lipoprotein lipase (LPL) and reducing production of apolipoprotein C-lll (an inhibitor of LPL activity). Consistent with the above mechanism, Saroglitazar was also found to reduce plasma LDL cholesterol. PPARa activation by Saroglitazar also induces an increase in the synthesis of apolipoproteins A-l, A-ll and FIDL-cholesterol. Although Saroglitazar is predominantly a PPARa agonist, it also causes activation of PPARy and regulates the transcription of insulin-responsive genes involved in the control of glucose production, transport and utilization. Saroglitazar increases the expression of numerous PPARy-responsive genes involved in carbohydrate and lipid metabolism, including adiponectin, adipocyte fatty-acid-binding protein (aP2), LPL, fatty acid transport protein (FATP) and fatty acid translocase (CD36). By increasing the expression of these genes, Saroglitazar decreases the post prandial rise of plasma free fatty acids, improves post-absorptive insulin-mediated suppression of hepatic glucose output, reduces the metabolic burden on liver & muscle and promotes glucoseutilization. Robust anti-diabetic and insulin sensitizing effects of Saroglitazar were observed in preclinical models, in which hyperglycemia and/or impaired glucose tolerance is a consequence of insulin resistance in target tissues.

The recommended dose of Saroglitazar is two tablets of 2 mg once a day.

Pediatric Use: The safety and effectiveness of Saroglitazar in children less than 18 years of age have not been established.

Geriatric Use: Considering the comorbidity and concomitant medications in elderly patients, Saroglitazar should be used with caution in geriatric patients.

In vitro studies using recombinant human cytochrome P-450 (CYP) isozymes indicate that Sarozar does not significantly inhibit CYP1A2, 2C9, 2C19, 2D6 and 3A4 at concentrations of 10pM. Similarly, Sarozar did not show any potential for CYP3A4 enzyme induction when tested up to 100 pM concentration in a luciferase-based reporter assay in transiently transfected HepG2 cells. Although no clinical drug-drug interaction studies have been conducted with Sarozar so far, because the tested concentrations (10 pM and 100 pM) are several times higher than the mean C max of Sarozar, it can be inferred that Sarozar would not cause clinically significant drug-drug interactions related to the above-evaluated CYPs.

Hypersensitivity to Saroglitazar or any of the excipients used in the formulation.

In two controlled phase III clinical studies of 12 to 24 weeks treatment duration with Sarozar, the most common adverse events (AEs > 2%) reported were gastritis, asthenia and pyrexia. Most of the AEs were mild to moderate in nature and did not result in discontinuation of the study. Because clinical studies are conducted under widely varying conditions, AE rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Pregnancy Category C. The safety of Saroglitazar in pregnant women has not been established as there is no adequate and well-controlled study carried out in pregnant women. Women who become pregnant during Saroglitazar treatment should contact their physicians. Saroglitazar should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: Nursing mothers should not use Saroglitazar because it is not known whether Saroglitazar is excreted into breast milk.

Although clinical studies with Sarozar have not demonstrated any potential for myopathies or derangement of liver and/or renal function, Sarozar treatment should be initiated with caution in patients with abnormal liver or renal function, or history of myopathies.

Sarozar has not been studied in patients with established New York Heart Association (NYHA) Class III or IV heart failure. Sarozar should be initiated with caution in patients with type 2 diabetes having cardiac disease with episodic congestive heart failure and such patients should be monitored for signs and symptoms of congestive heart failure.

Although no significant weight gain and edema were reported with Sarozar during the clinical studies, patients who experience rapid increases in weight should be assessed for fluid accumulation and volume-related events such as excessive edema and congestive heart failure.

During clinical studies, no incidence of overdose with Sarozar has been reported. In case of overdose with Sarozar, general supportive care of the patient is indicated, including monitoring of vital signs and observation of clinical status.

Store below 25°C and dry place, away from light and moisture. Keep out of the reach of children.