Livalo (Pitavastatin) is lipid reducing drug that is used to treat high cholesterol, LDL, apolipoprotein, and triglyceride levels. It also increases the HDL, reduces coronary plaque formation, has anticoagulant properties, improves high CRP levels and endothelial dysfunction.

Indications of Livalo (Pitavastatin):

• Primary hyperlipidemia and mixed dyslipidemia:

  • It is used as adjunctive therapy to diet to reduce elevated total cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo B), and triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C) in adults with primary hyperlipidemia or mixed dyslipidemia.

• Heterozygous familial hypercholesterolemia:

  • It is indicated to reduce elevated total cholesterol, LDL-C, and apo B in as adjunct therapy to diet in children and adolescents ≥8 years of age.

• Off Label Use of Pitavastatin in Adults:

  • Cardiac risk reduction for noncardiac surgery (perioperative therapy);
  • Secondary prevention of Non-cardioembolic stroke/Transient ischemic attack;
  • Primary and secondary prevention of atherosclerotic cardiovascular disease.

Livalo (Pitavastatin) dose in adults:

Livalo (Pitavastatin) dose in the treatment of primary hyperlipidemia and mixed dyslipidemia:

• Initial: 2 mg per oral once daily;
• 4 weeks after initiation or upon titration, analyze lipid levels and adjust dose accordingly
• The maintenance dose is 1 to 4 mg once daily
• The maximum dose is 4 mg/day per oral

Livalo (Pitavastatin) Dose in the Prevention of cardiovascular disease to reduce the risk of atherosclerotic cardiovascular disease (off-label):

• ACC/AHA Blood Cholesterol Guideline recommendations:

Note:

Risk of atherosclerotic cardiovascular disease (ASCVD) risk, risk-enhancing factors, the possibility for side effects, and drug interactions should be considered when starting therapy.

• Primary prevention:

  • LDL-C ≥190 mg/dL and age 20 to 75 years:

    • High-intensity therapy necessary;
    • use alternate statin therapy (eg, atorvastatin or rosuvastatin)

  • Diabetes, age 40 to 75 years and an estimated 10-year ASCVD risk <7.5%:

    • Moderate-intensity therapy: 2 to 4 mg per oral once daily.

  • Diabetes, age 40 to 75 years, and an estimated 10-year ASCVD risk ≥7.5%:

    • High-intensity therapy necessary;
    • use alternate statin therapy (eg, atorvastatin or rosuvastatin)

  • LDL-C 70 to 189 mg/dL, age 40 to 75 years, and an estimated 10-year ASCVD risk ≥7.5%:

    • Moderate to high-intensity therapy: 2 to 4 mg per oral once daily or consider using high-intensity statin therapy (eg, atorvastatin or rosuvastatin).

• Secondary prevention:

  • The patient has clinical ASCVD (eg, coronary heart disease, stroke/TIA, or peripheral arterial disease presumed to be of atherosclerotic origin) or is post-CABG  and:

    • Age ≤75 years:
      • High-intensity therapy necessary;
      • use alternate statin therapy (eg, atorvastatin or rosuvastatin).
    • Age >75 years:
      • Moderate- to high-intensity therapy: 2 to 4 mg per oral once daily or
      • consider using high-intensity statin therapy (eg, atorvastatin or rosuvastatin);
      • if moderate-intensity therapy is started and tolerated, increase to a high-intensity statin therapy within 3 months.

• US Preventive Services Task Force Recommendations:

  • Age 40 to 75 years, no history of CVD, with ≥1 CVD risk factor (dyslipidemia, diabetes, hypertension, or smoking), and calculated 10-year CVD event risk of ≥10%:

    • Primary prevention:

      • Low-intensity therapy: 1 mg per oral once daily
      • Moderate-intensity therapy: 2 to 4 mg per oral once daily

Note:

The treatment of patients with very high cholesterol levels (eg, LDL >190 mg/dL, familial hypercholesterolemia should be done on clinical judgment. In patients with a calculated 10-year CVD event risk of 7.5% to 10%, statin use may be considered based on patient characteristics.

• Dosage adjustment with concomitant medications:

  • Erythromycin:

    • Maximum pitavastatin dose: 1 mg/day per oral.

  • Rifampin:

    • Maximum pitavastatin dose: 2 mg/day per oral.

Livalo (Pitavastatin) Dose in Children:

The safety and efficacy of Pitavastatin in children are not established.

Pregnancy Risk Category: D

• Pitavastatin should not be used during pregnancy.
• Congenital defects may result from maternal use of HMGCoA reductase inhibitors during pregnancy.
• While pregnancy can lead to an increase in serum cholesterol and triglycerides, discontinuing lipid-lowering medication temporarily will not have any significant effect on long-term outcomes of primary hypercholesterolemia treatment.
• Pitavastatin should not be used if unplanned pregnancy occurs.
• Effective contraception should be used by females while on therapy.
• Those planning to have a baby should stop taking statins for at least 2 months before trying to conceive.

Use of pitavastatin while breastfeeding

• Breast milk contains pitavastatin, but it is not known if this substance is excreted in breast milk.
• Manufacturers have made it clear that breastfeeding mothers are not advised to use this product because of the risk of serious adverse reactions.

Dose adjustment in renal disease:

• GFR ≥60 mL/minute/1.73 m²:

  • There are no dosage adjustments provided in the manufacturer’s labeling.

• GFR 15 to 59 mL/minute/1.73 m² (not receiving hemodialysis):

  • Initial: 1 mg once daily
  • maximum: 2 mg/day

• ESRD receiving hemodialysis:

  • Initial: 1 mg once daily
  • maximum: 2 mg/day

Dose adjustment in liver disease:

Pitavastatin is contraindicated in active liver disease or in patients with unexplained persistent elevations of serum transaminases.

Rare Side Effects of Livalo (Pitavastatin):

• Gastrointestinal:

  • Constipation
  • diarrhea

• Hepatic:

  • Increased serum alanine aminotransferase

• Neuromuscular & skeletal:

  • Back pain
  • myalgia

Livalo (Pitavastatin) Side effects - Frequency not known:

• Central nervous system:

  • Headache

• Dermatologic:

  • Pruritus
  • skin rash
  • urticaria

• Endocrine & metabolic:

  • Increased serum glucose

• Hepatic:

  • Increased serum alkaline phosphatase
  • increased serum bilirubin
  • increased serum transaminases

• Hypersensitivity:

  • Hypersensitivity reaction

• Infection:

  • Influenza

• Neuromuscular & skeletal:

  • Arthralgia
  • increased creatine phosphokinase in the blood specimen

• Respiratory:

  • Nasopharyngitis

Contraindications to Livalo (Pitavastatin):

• Hypersensitivity to pitavastatin and any component of this formulation
• Pregnancy/breastfeeding
• Active liver disease/transaminitis
• Combination therapy with Cyclosporine

Warnings and precautions

• Diabetes mellitus:

  • Pitavastatin may cause an increase of HbA or fasting glucose, but this therapy could be continued.
  • You can prevent it by exercising, weight control, and diet control.

• Hepatotoxicity:

  • Transaminitis can occur, which can be reversed by withholding treatment.
  • In the event of severe hepatotoxicity, such as jaundice or hyperbilirubinemia, the drug should be stopped immediately.
  • Avoid alcohol consumption as it can cause liver damage. Regular monitoring is necessary.

• Hypersensitivity

  • It is possible to experience hypersensitivity reactions like rash, pruritus and urticaria.

• Myopathy/Rhabdomyolysis:

  • Myopathy can be caused by statins with CPK >10x the ULN, rhabdomyolysis and acute renal failure.
  • Risk factors include combination therapy with fibrates, rifampicin, colchicine, erythromycin, niacin(doses >=1 g/day). Dose adjustment may be necessary.
  • It is not recommended for use with gemfibrozil or cyclosporine.
  • Patients at high risk for myopathies such as the elderly, uncontrolled hypothyroidism, or renal failure should not use it.
  • Rarely, it has been reported that immuno-mediated necrotizing myopathy is (IMNM) caused by HMG-CoA reductase inhibits.
  • Patients with undiagnosed myalgia, tenderness or weakness, brown urine, malaise, fever, or any other symptoms, must be monitored.
  • Patients at high risk for rhabdomyolysis (hypotension, shock, sepsis or trauma), should have therapy stopped.Patients with myopathy or markedly elevated CPK levels should be stopped from therapy.

• Hepatic impairment

  • Patients with transaminitis or active liver disease are not advised to use this medication.

• Renal impairment

  • It is not recommended to be used in cases of renal impairment, as it may cause myopathy.
  • Patients with GFR 60mL/minute/1.73m, including patients receiving hemodialysis, will need to adjust their dosage.

Pitavastatin: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

ACC/AHA Blood Cholesterol Guideline recommendations:

• Lipid profile:
  • Lipid profile (fasting or nonfasting) at baseline, then 12 weekly after starting therapy and every 3 to 12 months, thereafter.
  • The dose should be reduced if 2 consecutive LDL levels are <40 mg/dL.
• Hepatic function tests:
  • Hepatic function tests should be measured at baseline and in the case of anorexia, abdominal pain, jaundiced sclera, unusual fatigue or weakness, and dark-colored urine during therapy.
• CPK:
  • CPK is measured in patients with a family history of statin intolerance or muscle disease, combination therapy that may increase the risk of myopathy, or showing signs of myopathy.
• Blood glucose:
  • It should be checked during therapy and if diabetes occurs, therapy should be continued with diet and weight control, exercise.

How to administer Livalo (Pitavastatin)?

It should be taken orally with or without food without regard to the time of day.

Mechanism of action of Livalo (Pitavastatin):

Pitavastatin is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis (reduces the production of mevalonic acid from HMG-CoA), resulting in a compensatory increased LDL receptor expression on hepatocyte membranes in addition to LDL catabolism stimulation. It has pleiotropic qualities, such as improved endothelial function and reducing coronary plaque inflammation.

Protein binding:

• >99%, primarily to albumin and alpha 1-acid glycoprotein

Metabolism:

• Occurs in the liver via UGT1A3 and UGT2B7; minimal metabolism via CYP2C9 and CYP2C8

Bioavailability:

• 51%

Half-life elimination:

• 12 hours

Time to peak, plasma:

• 1 hour

Excretion:

• Feces (79%)
• urine (15%)

International Brands of Pitavastatin:

• Livalo
• Zypitamag
• Alipza
• Fadrinarex
• Flovas
• Guan Shuang
• Lip Loss
• Lipidalon
• Livalo
• Livazo
• Pavigard
• Pitalip
• Pitasor 2
• Pitator
• Pitava
• Pitavas
• Pivalo
• Redevant
• Statrival
• Trolis

Pitavastatin Brands in Pakistan: