Guidelines

Guidelines

Patients who may be appropriate for Zypitamag (pitavastatin)

Patients who may be appropriate for Zypitamag (pitavastatin)

Pitavastatin is recommended in the most recent ACC/AHA Statin Intensity Guidelines as a moderate intensity statin (2 mg and 4 mg).1

Patients who may be appropriate for Zypitamag (pitavastatin) Table

Boldface type indicates specific statins and doses that were evaluated in RCTs. All of these RCTs demonstrated a reduction in major cardiovascular events. Italic type indicates statins and doses that have been approved by the FDA but were not tested in the RCTs reviewed.

BID indicates twice daily; FDA, Food and Drug Administration; LDL-C, low-density lipoprotein cholesterol; and RCTs, randomized controlled trials.

Individual responses to statin therapy varied in the RCTs and should be expected to vary in clinical practice. There might be a biological basis for a less-than-average response.

†Evidence from 1 RCT only: down-titration if unable to tolerate atorvastatin 80 mg in the IDEAL (Incremental Decrease through Aggressive Lipid Lowering) study.

‡Although simvastatin 80 mg was evaluated in RCTs, the Prescribing Information for simvastatin restricts dosing for 80 mg due to the increased risk of myopathy, including rhabdomyolysis.2

References:

1) Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 suppl 2):S13.

2) ZOCOR [prescribing information]. Whitehouse Station, NJ; Merck & Co., Inc.; February 2018.

IMPORTANT SAFETY INFORMATION FOR ZYPITAMAG™ (pitavastatin)

INDICATIONS & USAGE

Drug therapy should be one component of multiple-risk-factor intervention in individuals who require modifications of their lipid profile. Lipid-altering agents should be used in addition to a diet restricted in saturated fat and cholesterol only when the response to diet and other nonpharmacological measures has been inadequate.

Primary Hyperlipidemia and Mixed Dyslipidemia: Zypitamag is indicated as an adjunctive therapy to diet to reduce elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C) in adult patients with primary hyperlipidemia or mixed dyslipidemia.

Limitations of Use: Doses of Zypitamag greater than 4 mg once daily were associated with an increased risk for severe myopathy in premarketing clinical studies. Do not exceed 4 mg once daily dosing of Zypitamag. The effect of Zypitamag on cardiovascular morbidity and mortality has not been determined. Zypitamag has not been studied in Fredrickson Type I, III, and V dyslipidemias.

CONTRAINDICATIONS

Zypitamag is contraindicated in patients with a known hypersensitivity to product components, in patients with active liver disease (which may include unexplained persistent elevations in hepatic transaminase levels), in women who are pregnant or may become pregnant, in nursing mothers or in coadministration with cyclosporine.

WARNINGS & PRECAUTIONS

Skeletal Muscle Effects: Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors, including pitavastatin.

  • These risks can occur at any dose level, but increase in a dose-dependent manner, with advanced age (≥ 65 years), renal impairment, and inadequately treated hypothyroidism; administer with caution in these patients, or when used concomitantly with fibrates or lipid-modifying doses of niacin, or colchicine. Avoid concomitant administration with gemfibrozil.
  • Advise patients to promptly report unexplained and/or persistent muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever; discontinue Zypitamag.
  • If muscle signs and symptoms persist after discontinuation, this may be a sign of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy associated with statin use, requiring immediate medical attention. IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; muscle biopsy showing necrotizing myopathy without significant inflammation; improvement with immunosuppressive agents.
  • Zypitamag should be discontinued if markedly elevated creatine kinase levels occur or myopathy is diagnosed or suspected.
  • Zypitamag should also be temporarily withheld in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g., sepsis, hypotension, dehydration, major surgery, trauma, severe metabolic, endocrine, and electrolyte disorders, or uncontrolled seizures).

Liver Enzyme Abnormalities:

  • Persistent elevation in hepatic transaminases can occur. Check liver enzymes before initiating therapy and if signs or symptoms of liver injury occur; advise patients to report fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.
  • Fatal and non-fatal hepatic failure can occur. Interrupt Zypitamag if serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs. If an alternate etiology is not found do not restart Zypitamag.
  • Use Zypitamag with caution in patients who consume substantial quantities of alcohol and/or have a history of chronic liver disease. Do not use Zypitamag if patient has active liver disease, which may include unexplained persistent transaminase elevations.

Endocrine Function:

  • Increases in HbA1c and fasting serum glucose levels have been reported.

COMMON ADVERSE REACTIONS

Myalgia, back pain, diarrhea, constipation and pain in extremity (rate ≥ 2% in at least one marketed dose). This is not a complete list of all reported adverse events.

For additional information, refer to full Prescribing Information.

You are encouraged to report negative side effects of prescription drugs to the FDA.

Visit www.FDA.gov/medwatch
or call 1-800-FDA-1088