Pitavastatin Calcium

• Approved Indications:
• Hypercholesterolemia: Primary treatment for elevated total cholesterol, LDL cholesterol, and triglycerides in patients with primary hyperlipidemia or mixed dyslipidemia.
• Prevention of cardiovascular disease (CVD) in patients at high risk, including those with type 2 diabetes mellitus and other risk factors.
• Adjunct to diet and lifestyle modifications to reduce cholesterol levels and associated risks.
• Off-label/Clinically Accepted Uses:
• Treatment of atherosclerotic cardiovascular disease (ASCVD) risk reduction.
• Occasionally used in patients intolerant to other statins.

• Route: Oral tablets.
• Adults:
• Initial dose: 1 mg once daily, taken orally with or without food.
• Maintenance dose: 2 mg once daily; may increase up to 4 mg once daily based on lipid response and tolerability.
• Elderly:
• Start with 1 mg daily; titrate cautiously.
• Renal impairment:
• No dose adjustment necessary in mild to moderate renal impairment. Use with caution in severe impairment.
• Hepatic impairment:
• Use contraindicated in active liver disease or unexplained persistent elevations of serum transaminases.
• Duration:
• Long-term therapy recommended; treatment continuation based on clinical response and lipid levels.

Pitavastatin is a selective inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis in the liver. By competitively inhibiting this enzyme, pitavastatin decreases the conversion of HMG-CoA to mevalonate, an essential precursor of cholesterol. This leads to a reduction in intrahepatic cholesterol concentration, which upregulates LDL receptor expression on hepatocytes, enhancing clearance of LDL cholesterol from the bloodstream, thereby lowering plasma LDL and total cholesterol levels.

• Absorption: Rapid and well absorbed orally; peak plasma concentration reached within 1 hour; bioavailability approximately 60%.
• Distribution: Approximately 96% bound to plasma proteins.
• Metabolism: Primarily metabolized by liver enzyme UGT1A3 and UGT2B7 via glucuronidation; minor metabolism by CYP2C9 and CYP2C8; does not significantly involve CYP3A4.
• Elimination: Excreted mainly via bile and feces; less than 2% excreted unchanged in urine.
• Half-life: Approximately 11 hours.
• Onset: LDL reduction noticeable within 2 weeks, maximal effect by 4 weeks.

• Pregnancy: FDA category X – contraindicated in pregnancy due to potential teratogenicity and fetal harm; statins should be discontinued prior to conception.
• Lactation: Excretion in human milk unknown; breastfeeding is not recommended during treatment.

• Lipid-lowering agent
• HMG-CoA reductase inhibitor (Statin)

• Known hypersensitivity to pitavastatin or any excipients.
• Active liver disease or unexplained persistent elevations of serum transaminases.
• Pregnancy and breastfeeding.
• Concurrent use with cyclosporine.
• Severe renal impairment without close monitoring.

• Monitor liver function tests before initiation and periodically during treatment.
• Risk of myopathy and rhabdomyolysis, especially in patients with predisposing factors (e.g., renal impairment, concomitant fibrate use).
• Use with caution in elderly patients.
• Avoid concomitant use of strong OATP1B1 inhibitors (e.g., cyclosporine) due to increased pitavastatin plasma levels.
• Patients should report unexplained muscle pain, tenderness, or weakness promptly.
• Caution in patients with a history of liver disease or excessive alcohol intake.

• Common:
• Headache, myalgia, abdominal pain, constipation, diarrhea, nausea.
• Serious (rare):
• Myopathy, rhabdomyolysis, elevated liver enzymes, hypersensitivity reactions, new-onset diabetes mellitus.
• Side effects typically occur within the first months of therapy and are dose-dependent.

• Minimal involvement of CYP3A4 reduces risk of CYP450-mediated interactions.
• Increased risk of myopathy with concomitant use of fibrates, niacin, or other statins.
• Cyclosporine markedly increases pitavastatin plasma concentration; coadministration contraindicated.
• May interact with drugs inhibiting OATP1B1 transporter (e.g., rifampin) altering pitavastatin levels.
• No significant food interactions; can be taken with or without food.

• Current clinical guidelines endorse pitavastatin as an effective statin for hypercholesterolemia management and cardiovascular risk reduction.
• Emphasis on its lower potential for drug interactions due to minimal CYP3A4 metabolism.
• Ongoing studies evaluate cardiovascular benefits and safety in diverse populations.
• No recent major changes in dosing or safety warnings.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep in a tightly closed container.
• Do not freeze.
• Keep out of reach of children.