Pitavastatin Calcium

FDA Drug Information • Also known as: Livalo, Pitavastatin, Pitavastatin Calcium

Brand Names: Livalo, Pitavastatin, Pitavastatin Calcium
Dosage Form: GRANULE
Product Type: BULK INGREDIENT

Description

11 DESCRIPTION Pitavastatin tablets for oral use are HMG-CoA reductase inhibitors. The chemical name for pitavastatin calcium is monocalcium bis [(3 R ,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolinyl]-3,5-dihydroxy-6-heptenoate]. The structural formula is: The molecular formula for pitavastatin calcium is C 50 H 46 CaF 2 N 2 O 8 and the molecular weight is 880.98. Pitavastatin calcium is a white to pale yellow crystalline powder. It is slightly soluble in methanol. Pitavastatin calcium is slightly hygroscopic and slightly unstable in light. Each film-coated tablet of pitavastatin contains 1 mg, 2 mg, or 4 mg of pitavastatin, which is equivalent to 1.045 mg, 2.09 mg, or 4.18 mg, respectively, of pitavastatin calcium and the following inactive ingredients: colloidal anhydrous silica, hypromellose, lactose monohydrate, low substituted hydroxypropyl cellulose, magnesium stearate, sodium carbonate anhydrous, titanium dioxide and triethyl citrate. pitvastatintabletsstructure.

What Is Pitavastatin Calcium Used For?

1 INDICATIONS AND USAGE Pitavastatin tablets are indicated as an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C) in:

Adults with primary hyperlipidemia.

Adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH). Pitavastatin tablets are a HMG-CoA reductase inhibitor (statin) indicated as an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C) in: ( 1 )

Adults with primary hyperlipidemia.

Adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH).

Dosage and Administration

2 DOSAGE AND ADMINISTRATION

Take orally once daily with or without food at the same time each day. ( 2.1 )

For patients requiring a high-intensity statin or are unable to achieve their LDL-C goal receiving pitavastatin tablets 4 mg daily, prescribe alternative LDL-C- lowering treatment. ( 2.1 )

Assess LDL-C when clinically appropriate, as early as 4 weeks after initiation of pitavastatin tablets and adjust the dosage if necessary. ( 2.1 )

Recommended dosage is 2 mg to 4 mg once daily. Maximum recommended dosage is 4 mg once daily. ( 2.2 )

Recommended starting dosage for patients with moderate and severe renal impairment and end-stage renal disease on hemodialysis is 1 mg once daily. Maximum recommended dosage is 2 mg once daily. ( 2.3 )

See full prescribing information for pitavastatin tablets dosage modifications due to drug interactions. ( 2.4 ) 2.1 Important Dosage and Administration Information

Take pitavastatin tablets orally once daily with or without food at the same time each day.

For patients that require a high-intensity statin or are unable to achieve their LDL-C goal receiving pitavastatin tablets 4 mg daily, prescribe alternative LDL-C-lowering treatment.

Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating pitavastatin tablets, and adjust the dosage if necessary. 2.2 Recommended Dosage for Adults and Pediatric Patients Aged 8 Years and Older

The recommended dosage range of pitavastatin tablets are 2 mg to 4 mg daily.

The maximum recommended dosage is pitavastatin tablets 4 mg once daily. 2.3 Recommended Dosage in Patients with Renal Impairment

The recommended starting dosage for patients with moderate and severe renal impairment (estimated glomerular filtration rate 30 to 59 mL/minute/1.73 m 2 and 15 to 29 mL/minute/1.73 m 2 , respectively) and patients with end-stage renal disease receiving hemodialysis is pitavastatin tablets 1 mg once daily. The maximum recommended dose for these patients is pitavastatin tablets 2 mg once daily [see Use in Specific Populations (8.5) ] .

There are no dosage adjustment recommendations for patients with mild renal impairment. 2.4 Dosage Modifications Due to Drug Interactions

In patients taking erythromycin, do not exceed pitavastatin tablets 1 mg once daily [see Drug Interactions (7) ].

In patients taking rifampin, do not exceed pitavastatin tablets 2 mg once daily [see Drug Interactions (7) ].

Side Effects (Adverse Reactions)

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

Myopathy and Rhabdomyolysis [see Warnings and Precautions (5.1) ]

Immune-Mediated Necrotizing Myopathy [see Warning and Precautions (5.2) ]

Hepatic Dysfunction [see Warning and Precautions (5.3) ]

Increases in HbA1c and Fasting Serum Glucose Levels [see Warning and Precautions (5.4) ] . The most frequent adverse reactions (rate ≥ 2%) were myalgia, constipation, diarrhea, back pain, and pain in extremity. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Annora Pharma Limited at 1-866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 In 10 controlled clinical studies and 4 subsequent open-label extension studies, 3,291 adult patients with primary hyperlipidemia 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 52% were females. Approximately 93% of the patients were White, 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 Adults with Primary Hyperlipidemia in Studies up to 12 Weeks Adverse Reactions Placebo (n=208) % Pitavastatin 1 mg (n=309) % Pitavastatin 2 mg (n=951) % Pitavastatin 4 mg (n=1540) % Myalgia 1.4 1.9 2.8 3.1 Constipation 1.9 3.6 1.5 2.2 Diarrhea 1.9 2.6 1.5 1.9 Back pain 2.9 3.9 1.8 1.4 Pain in extremity 1.9 2.3 0.6 0.9 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. Adverse Reactions in Pediatric Patients Aged 8 Years and Older with HeFH In...

Drug Interactions

7 DRUG INTERACTIONS Table 2 includes a list of drugs that increase the risk of myopathy and rhabdomyolysis when administered concomitantly with pitavastatin and instructions for preventing or managing drug interactions [see Warnings and Precautions (5.1) , Clinical Pharmacology (12.3) ]. Table 2: Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Pitavastatin Cyclosporine Clinical Impact: Cyclosporine significantly increases pitavastatin exposure and increases the risk of myopathy and rhabdomyolysis . Intervention: Concomitant use of cyclosporine with pitavastatin is contraindicated [see Contraindications (4) ]. Gemfibrozil Clinical Impact: Gemfibrozil may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of gemfibrozil with statins, including pitavastatin. Intervention: Avoid concomitant use of gemfibrozil with pitavastatin. Erythromycin Clinical Impact: Erythromycin significantly increases pitavastatin exposure and increases the risk of myopathy and rhabdomyolysis . Intervention: In patients taking erythromycin, do not exceed pitavastatin 1 mg once daily [see Dosage and Administration (2.4) ]. Rifampin Clinical Impact: Rifampin significantly increases peak pitavastatin exposure and increases the risk of myopathy and rhabdomyolysis . Intervention: In patients taking rifampin, do not exceed pitavastatin 2 mg once daily [see Dosage and Administration (2.4) ]. Fibrates Clinical Impact: Fibrates may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of fibrates with statins, including pitavastatin. Intervention: Consider if the benefit of using fibrates concomitantly with pitavastatin outweighs the increased risk of myopathy and rhabdomyolysis. Niacin Clinical Impact: The risk of myopathy and rhabdomyolysis may be increased with concomitant use of lipid-modifying doses (≥1 g/day) of niacin with pitavastatin. Intervention: Consider if the benefit of using lipid-modifying doses (≥1 g/day) of niacin concomitantly with pitavastatin outweighs the increased risk of myopathy and rhabdomyolysis. Colchicine Clinical Impact: Cases of myopathy and rhabdomyolysis have been reported with concomitant use of colchicine with statins, including pitavastatin. Intervention: Consider the risk/benefit of concomitant use of colchicine with pitavastatin. See full prescribing information for details regarding concomitant use of pitavastatin with other drugs that increase the risk of myopathy and rhabdomyolysis. ( 2.4 , 7 )

Contraindications

4 CONTRAINDICATIONS Pitavastatin tablets are contraindicated in the following conditions:

Concomitant use of cyclosporine [see Drug Interactions (7) ] .

Acute liver failure or decompensated cirrhosis [see Warnings and Precautions (5.3) ].

Hypersensitivity to pitavastatin or any excipents in pitavastatin. Hypersensitivity reactions including angioedema, rash, pruritus, and urticaria have been reported with pitavastatin [see Adverse Reactions (6) ] .

Cyclosporine ( 4 , 7 )

Active liver failure or decompensated cirrhosis ( 4 , 5.3 )

Hypersensitivity to pitavastatin or any excipients in pitavastatin ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Discontinue pitavastatin when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Pitavastatin decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, pitavastatin may cause fetal harm when administered to pregnant patients based on the mechanism of action [see Clinical Pharmacology (12.1) ]. In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. Available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. Published data from prospective and retrospective observational cohort studies with statin use in pregnant women are insufficient to determine if there is a drug associated risk of miscarriage (see Data). In animal reproduction studies, no embryo-fetal toxicity or congenital malformations were observed in pregnant rats and rabbits orally administered pitavastatin during the period of organogenesis at doses which were 22 and 4 times, respectively, the human exposure at the maximum recommended human dosage (MRHD) of 4 mg, based on AUC [see Data]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data A Medicaid cohort linkage study of 1152 statin-exposed pregnant women compared to...

8.4 Pediatric Use The safety and effectiveness of pitavastatin as an adjunctive therapy to diet to reduce elevated LDL-C in pediatric patients aged 8 years and older with HeFH have been established. Use of pitavastatin for this indication is supported by a 12-week, double-blind, placebo- controlled trial in 82 pediatric patients 8 to 16 years of age with HeFH [see Clinical Studies (14) ] and a 52-week open-label trial in 85 pediatric patients with HeFH. The safety and effectiveness of pitavastatin have not been established in pediatric patients younger than 8 years of age with HeFH or in pediatric patients with other types of hyperlipidemia (other than HeFH).

Overdosage

10 OVERDOSAGE No specific treatment for pitavastatin overdose is known. Contact Poison Control (1-800-222-1222) for latest recommendations. Hemodialysis is unlikely to be of benefit due to high protein binding ratio of pitavastatin.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Pitavastatin tablets 1 mg are white to off-white, round, bevel edged biconvex film coated tablets debossed with ‘H1’ on one side and ‘P’ on other side. They are supplied as follows: Bottles of 90 tablets NDC 31722-875-90 Pitavastatin tablets 2 mg are white to off-white, round, bevel edged biconvex film coated tablets debossed with ‘H2’ on one side and ‘P’ on other side. They are supplied as follows: Bottles of 90 tablets NDC 31722-876-90 Pitavastatin tablets 4 mg are white to off-white, round, biconvex film coated tablets debossed with ‘H4’ on one side and ‘P’ on other side. They are supplied as follows: Bottles of 90 tablets NDC 31722-877-90 Storage Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.