Zypitamag

General Dosing Information

The dose range for Zypitamag is 1 mg to 4 mg orally once daily at any time of the day with or without food. The recommended starting dose is 2 mg and the maximum dose is 4 mg. The starting dose and maintenance doses of Zypitamag should be individualized according to patient characteristics, such as goal of therapy and response.

After initiation or upon titration of Zypitamag, lipid levels should be analyzed after 4 weeks and the dosage adjusted accordingly.

Dosage in Patients with Renal Impairment

Patients with moderate and severe renal impairment (glomerular filtration rate 30 mL/min/1.73 m2 to 59 mL/min/1.73 m2 and 15 mL/min/1.73 m2 to 29 mL/min/1.73 m2 not receiving hemodialysis, respectively) as well as end-stage renal disease receiving hemodialysis should receive a starting dose of Zypitamag 1 mg once daily and a maximum dose of Zypitamag 2 mg once daily.

Use with Erythromycin

In patients taking erythromycin, a dose of Zypitamag 1 mg once daily should not be exceeded [see Drug Interactions (7.2)].

Use with Rifampin

In patients taking rifampin, a dose of Zypitamag 2 mg once daily should not be exceeded [see Drug Interactions (7.3)].

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.

Zypitamag should be prescribed with caution in patients with predisposing factors for myopathy. These factors include advanced age (≥ 65 years), renal impairment, and inadequately treated hypothyroidism. The risk of myopathy may also be increased with concurrent administration of fibrates or lipid-modifying doses of niacin. Zypitamag should be administered with caution in patients with impaired renal function, in elderly patients, or when used concomitantly with fibrates or lipid-modifying doses of niacin [see Drug Interactions (7.6), Use in Specific Populations (8.5, 8.6) and Clinical Pharmacology (12.3)].

Cases of myopathy, including rhabdomyolysis, have been reported with HMG-CoA reductase inhibitors coadministered with colchicine, and caution should be exercised when prescribing Zypitamag with colchicine [see Drug Interactions (7.7)].

There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. 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 therapy should be discontinued if markedly elevated creatine kinase (CK) levels occur or myopathy is diagnosed or suspected. Zypitamag therapy 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). All patients should be advised to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing Zypitamag.

Liver Enzyme Abnormalities

Increases in serum transaminases (aspartate aminotransferase [AST]/serum glutamic-oxaloacetic transaminase, or alanine aminotransferase [ALT]/serum glutamic-pyruvic transaminase) have been reported with HMG-CoA reductase inhibitors, including pitavastatin. In most cases, the elevations were transient and resolved or improved on continued therapy or after a brief interruption in therapy.

In placebo-controlled Phase 2 studies, ALT > 3 times the upper limit of normal was not observed in the placebo, pitavastatin 1 mg, or pitavastatin 2 mg groups. One out of 202 patients (0.5%) administered pitavastatin 4 mg had ALT > 3 times the upper limit of normal.

It is recommended that liver enzyme tests be performed before the initiation of Zypitamag and if signs or symptoms of liver injury occur.

There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including pitavastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with Zypitamag, promptly interrupt therapy. If an alternate etiology is not found do not restart Zypitamag.

As with other HMG-CoA reductase inhibitors, Zypitamag should be used with caution in patients who consume substantial quantities of alcohol. Active liver disease, which may include unexplained persistent transaminase elevations, is a contraindication to the use of Zypitamag [see Contraindications (4)].

Endocrine Function

Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including pitavastatin.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 92 week carcinogenicity study in mice given pitavastatin, at the maximum tolerated dose of 75 mg/kg/day with systemic maximum exposures (AUC) 26 times the clinical maximum exposure at 4 mg/day, there was an absence of drug-related tumors.

In a 92 week carcinogenicity study in rats given pitavastatin at 1 mg/kg/day, 5 mg/kg/day, 25 mg/kg/day by oral gavage there was a significant increase in the incidence of thyroid follicular cell tumors at 25 mg/kg/day, which represents 295 times human systemic exposures based on AUC at the 4 mg/day maximum human dose.

In a 26 week transgenic mouse (Tg rasH2) carcinogenicity study where animals were given pitavastatin at 30 mg/kg/day, 75 mg/kg/day, and 150 mg/kg/day by oral gavage, no clinically significant tumors were observed.

Pitavastatin was not mutagenic in the Ames test with Salmonella typhimurium and Escherichia coli with and without metabolic activation, the micronucleus test following a single administration in mice and multiple administrations in rats, the unscheduled DNA synthesis test in rats, and a Comet assay in mice. In the chromosomal aberration test, clastogenicity was observed at the highest doses tested which also elicited high levels of cytotoxicity.

Pitavastatin had no adverse effects on male and female rat fertility at oral doses of 10 mg/kg/day and 30 mg/kg/day, respectively, at systemic exposures 56 and 354 times clinical exposure at 4 mg/day based on AUC.

Pitavastatin treatment in rabbits resulted in mortality in males and females given 1 mg/kg/day (30 times clinical systemic exposure at 4 mg/day based on AUC) and higher during a fertility study. Although the cause of death was not determined, rabbits had gross signs of renal toxicity (kidneys whitened) indicative of possible ischemia. Lower doses (15 times human systemic exposure) did not show significant toxicity in adult males and females. However, decreased implantations, increased resorptions, and decreased viability of fetuses were observed.

Animal Toxicology and/or Pharmacology

Central Nervous System Toxicity

CNS vascular lesions, characterized by perivascular hemorrhages, edema, and mononuclear cell infiltration of perivascular spaces, have been observed in dogs treated with several other members of this drug class. A chemically similar drug in this class produced dose-dependent optic nerve degeneration (Wallerian degeneration of retinogeniculate fibers) in dogs, at a dose that produced plasma drug levels about 30 times higher than the mean drug level in humans taking the highest recommended dose. Wallerian degeneration has not been observed with pitavastatin. Cataracts and lens opacities were seen in dogs treated for 52 weeks at a dose level of 1 mg/kg/day (9 times clinical exposure at the maximum human dose of 4 mg/day based on AUC comparisons).

NDC 25208-200-09

Zypitamag (Pitavastatin) Tablets, 1 mg

90 Tablets

Rx only

NDC 25208-201-09

Zypitamag (Pitavastatin) Tablets, 2 mg

90 Tablets

Rx only

NDC 25208-202-09

Zypitamag (Pitavastatin) Tablets, 4 mg

90 Tablets

Rx only

Zypitamag is an HMG CoA reductase inhibitor, or "statin." This medicine reduces levels of "bad" cholesterol (low-density lipoprotein, or LDL) and triglycerides in the blood, while increasing levels of "good" cholesterol (high-density lipoprotein, or HDL).

Zypitamag is used to treat high cholesterol in adults. Lowering your cholesterol may help prevent heart disease and hardening of the arteries, conditions that can lead to heart attack, stroke, and vascular disease.

Zypitamag may also be used for purposes not listed in this medication guide.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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