Zypitamag (pitavastatin)

Zypitamag (pitavastatin) tablets are an HMG-CoA reductase inhibitor indicated for patients with primary hyperlipidemia or mixed dyslipidemia 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).

Zypitamag (pitavastatin) is an inhibitor of HMG-CoA reductase. It is a synthetic lipid-lowering agent for oral administration.

Limitations Of Use

The effect of Zypitamag on cardiovascular morbidity and mortality has not been determined.

Common side effects of Zypitamag include:

• muscle pain,
• back pain,
• diarrhea,
• constipation,
• pain in extremities,
• joint pain,
• headache,
• influenza, and
• runny or stuffy nose.

The following serious adverse reactions are discussed in other sections of the labeling:

• Myopathy and Rhabdomyolysis
• Immune-Mediated Necrotizing Myopathy
• Hepatic Dysfunction
• Increases in HbA1c and Fasting Serum Glucose Levels

Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of one drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Adverse Reactions In Adults With Primary Hyperlipidemia And Mixed Dyslipidemia

In 10 controlled clinical studies and 4 subsequent open-label extension studies, 3,291 adult patients with primary hyperlipidemia or mixed dyslipidemia were administered pitavastatin 1 mg to 4 mg daily. The mean continuous exposure of pitavastatin (1 mg to 4 mg) was 36.7 weeks (median 51.1 weeks).

The mean age of the patients was 60.9 years (range; 18 years - 89 years) and the gender distribution was 48% males and 52% females. Approximately 93% of the patients were Caucasian, 7% were Asian/Indian, 0.2% were African American and 0.3% were Hispanic and other.

In controlled clinical studies and their open-label extensions, 3.9% (1 mg), 3.3% (2 mg), and 3.7% (4 mg) of pitavastatin-treated patients were discontinued due to adverse reactions.

The most common adverse reactions that led to treatment discontinuation were:

• elevated creatine phosphokinase (0.6% on 4 mg) and
• myalgia (0.5% on 4 mg).

Adverse reactions reported in ≥ 2% of patients in controlled clinical studies and at a rate greater than or equal to placebo are shown in Table 1. These studies had treatment duration of up to 12 weeks.

Table 1: Adverse Reactions (≥ 2% and ≥ placebo) in Adult Patients with Primary Hyperlipidemia and Mixed Dyslipidemia in Studies up to 12 Weeks

Other adverse reactions reported from clinical studies were

• arthralgia,
• headache,
• influenza, and
•  nasopharyngitis.

Hypersensitivity reactions including

• rash,
• pruritus, and
• urticaria have been reported with pitavastatin.

The following laboratory abnormalities have been reported:

• elevated creatine phosphokinase,
• transaminases,
• alkaline phosphatase,
• bilirubin, and
• glucose.

Adverse Reactions In Adult HIV-Infected Patients With Dyslipidemia

• In a double-blind, randomized, controlled, 52-week trial, 252 HIV-infected patients with dyslipidemia were treated with either pitavastatin 4 mg once daily (n=126) or another statin (n=126).
• All patients were taking antiretroviral therapy (excluding darunavir) and had HIV-1 RNA less than 200 copies/mL and CD4 count greater than 200 cell/μL for at least 3 months prior to randomization.
• The safety profile of pitavastatin was generally consistent with that observed in the clinical trials described above. One patient (0.8%) treated with pitavastatin had a peak creatine phosphokinase value exceeding 10 times the upper limit of normal (ULN), which resolved spontaneously.
• Four patients (3%) treated with pitavastatin had at least one ALT value exceeding 3 times but less than 5 times the ULN, none of which led to drug discontinuation.
• Virologic failure was reported for four patients (3%) treated with pitavastatin, defined as a confirmed measurement of HIV-1 RNA exceeding 200 copies/mL that was also more than a 2-fold increase from baseline.

Pediatric use information is approved for Kowa Co Ltd's LIVALO (pitavastatin) tablets. However, due to Kowa Co Ltd's marketing exclusivity rights, this drug product is not labeled with that information.