Livalo Information
Livalo () Indications And 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.
Doses of Livalo () 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 Livalo () .
The effect of Livalo () on cardiovascular morbidity and mortality has not been determined.
Livalo () has not been studied in Fredrickson Type I, III, and V dyslipidemias.
Livalo () Dosage And Administration
The dose range for Livalo () is 1 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 Livalo () should be individualized according to patient characteristics, such as goal of therapy and response.
After initiation or upon titration of Livalo () , lipid levels should be analyzed after 4 weeks and the dosage adjusted accordingly.
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Livalo () Dosage Forms And Strengths
1 mg: Round white film-coated tablet. Debossed “KC” on one side and “1” on the other side of the tablet.2 mg: Round white film-coated tablet. Debossed “KC” on one side and “2” on the other side of the tablet.4 mg: Round white film-coated tablet. Debossed “KC” on one side and “4” on the other side of the tablet.
Livalo () Contraindications
The use of Livalo () is contraindicated in the following conditions:
Livalo () Warnings And Precautions
Cases of myopathy and rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with HMG-CoA reductase inhibitors, including Livalo () .
Livalo () 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. Livalo () 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
Livalo () therapy should be discontinued if markedly elevated creatine kinase (CK) levels occur or myopathy is diagnosed or suspected. Livalo () 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.
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 Livalo () . 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, Livalo () 1 mg, or Livalo () 2 mg groups. One out of 202 patients (0.5%) administered Livalo () 4 mg had ALT >3 times the upper limit of normal.
It is recommended that liver enzyme tests be performed before and at 12 weeks following both the initiation of therapy and any elevation of dose and periodically (e.g., semiannually) thereafter.
Patients who develop increased transaminase levels should be monitored until the abnormalities have resolved. Should an increase in ALT or AST of >3 times upper limit of normal persist, reduction of dose or withdrawal of Livalo () is recommended.
As with other HMG-CoA reductase inhibitors, Livalo () 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 Livalo ()
Livalo () Adverse Reactions
The following serious adverse reactions are discussed in greater detail in other sections of the label:
Of 4,798 patients enrolled in 10 controlled clinical studies and 4 subsequent open-label extension studies, 3,291 patients 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.
Livalo () Overdosage
There is no known specific treatment in the event of overdose of pitavastatin. In the event of overdose, the patient should be treated symptomatically and supportive measures instituted as required. Hemodialysis is unlikely to be of benefit due to high protein binding ratio of pitavastatin.
Livalo () Description
Livalo () (pitavastatin) is an inhibitor of HMG-CoA reductase. It is a synthetic lipid-lowering agent for oral administration.
The chemical name for pitavastatin is (+)monocalcium {(3R, 5S, 6)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3,5-dihydroxy-6-heptenoate}. The structural formula is:
The empirical formula for pitavastatin is CHCaFNO and the molecular weight is 880.98. Pitavastatin is odorless and occurs as white to pale-yellow powder. It is freely soluble in pyridine, chloroform, dilute hydrochloric acid, and tetrahydrofuran, soluble in ethylene glycol, sparingly soluble in octanol, slightly soluble in methanol, very slightly soluble in water or ethanol, and practically insoluble in acetonitrile or diethyl ether. Pitavastatin is hygroscopic and slightly unstable in light.
Each film-coated tablet of Livalo () contains 1.045 mg, 2.09 mg, or 4.18 mg of pitavastatin calcium, which is equivalent to 1 mg, 2 mg, or 4 mg, respectively of free base and the following inactive ingredients: lactose monohydrate, low substituted hydroxypropylcellulose, hypromellose, magnesium aluminometasilicate, magnesium stearate, and film coating containing the following inactive ingredients: hypromellose, titanium dioxide, triethyl citrate, and colloidal anhydrous silica.
Livalo () Nonclinical Toxicology
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, 5, 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, 75, and 150 mg/kg/day by oral gavage, no clinically significant tumors were observed.
Pitavastatin was not mutagenic in the Ames test with and 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 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.
Livalo () Clinical Studies
Livalo () How Supplied/storage And Handling
Livalo () tablets for oral administration are provided as white, film-coated tablets that contain 1 mg, 2 mg, or 4 mg of pitavastatin. Each tablet has “KC” debossed on one side and a code number specific to the tablet strength on the other.
Livalo () (pitavastatin) Tablets are supplied as;
Livalo () Patient Counseling Information
The patient should be informed of the following:
It is recommended that liver enzymes be checked before and at 12 weeks following both the initiation of therapy and any elevation of dose, and periodically (e.g., semiannually) thereafter.
Livalo () is a trademark of the Kowa group of companies. © Kowa Pharmaceuticals America, Inc. (2009)
Manufactured under license from: Kowa Company, Limited Tokyo 103-8433 JapanProduct of Japan Manufactured into tablets by: Patheon, Inc. Cincinnati, OH 45237 USAMarketed by: Kowa Pharmaceuticals America, Inc. Montgomery, AL 36117 USAand Lilly USA, LLC. Indianapolis, IN 46285 USA To request additional information or if you have questions concerning Livalo () please phone Kowa Pharmaceuticals America, Inc. at 877-8-Livalo () (877-854-8256) or fax your inquiry to 800-689-0244
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