Pitasor 2

Light pink, round, biconvex film coated tablet and plain on both sides.
Each film coated tablet contains: Pitavastatin calcium 2 mg.

Pharmacology: Pharmacodynamics: Pitavastatin inhibits 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase by competition with its substrate so that it inhibits hepatic cholesterol synthesis. The total plasma cholesterol decreases when the expression of low-density lipoprotein (LDL) receptors followed by the uptake of LDL from blood to liver is accelerated. Additionally, the levels of very low density decrease from the sustained inhibition of cholesterol synthesis in the liver.
Pharmacokinetics: Tmax, oral: 1 hour.
Bioavailability: 51%.
Effect of food: decreases Cmax by 43% but has no significant effect on AUC.
Distribution: Vd: 148 L.
Protein binding: albumin and alpha 1-acid glycoprotein: 99%.
Metabolism: Liver: extensive glucuronide conjugation by UGT1A3 and UGT2B7 and minimally by CYP2C9 and CYP2C8.
Lactone (major metabolite): inactive.
Excretion: Bile: extensive, fecal: 79%, renal: 15%.
Elimination half life: 11 to 12 hours.

Dyslipidemias or mixed dyslipidemia.
Familial hypercholesterolemia.

Daily dose may be administered at any time of the day, with or without food.
The recommended initial adult dosage is 2 mg once daily. The usual maintenance dosage is 1-4 mg once daily.
The maximum dosage of pitavastatin is 4 mg once daily.
Assess lipid levels 4 weeks after dose initiation or titration.
Safety and efficacy not established in pediatric patients. Avoid using in pediatric patients.
Renal impairment: Moderate renal impairment (GFR 30 to 59 mL/min/1.73 m²: initial: 1 mg orally daily. Maximum dose is 2 mg daily.
Severe renal impairment (GFR 15 to 29 mL/min/1.73 m², not receiving dialysis): initial: 1 mg orally daily. Maximum dose is 2 mg daily.
ESRD receiving hemodialysis: initial: 1 mg orally daily. Maximum dose is 2 mg daily.

Management of mild to moderate toxicity: Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with vomiting or diarrhea.
Management of severe toxicity: Treatment is symptomatic and supportive.
Consider activated charcoal only after very large ingestions or if coingestants with significant toxicity are involved.

Known hypersensitivity to pitavastatin or any ingredient in the formulation.
Breastfeeding.
Concomitant use of cyclosporine.
Active liver disease, including unexplained, persistent elevation in serum aminotransferase (transaminase) concentrations.
Pregnancy or pregnancy potential.

Based on the notification of the Ministry of Public Health: Do not use the drug in pregnant and breast-feeding women.
Do not use the drug in patients with liver disease.
If there is myalgia at calf, back or whole body, stop the drug and consult physician.
Liver function tests should be performed before taking the drug and 6 and 12 weeks after taking the drug. For patients who routinely use the drug, liver function tests should be performed every 6 months or as recommended by a physician. If the transaminase level is greater than three times of upper normal limit, stop taking the drug and consult physician.
Use with caution with digoxin, warfarin because the level of these drugs in blood may be high and become dangerous.
The risk of myopathy or rhabdomyolysis will be increased when the drug is administered with other following drugs, e.g. azole antifungals such as ketoconazole, itraconazole; macrolides such as erythromycin, clarithromycin; HIV protease inhibitors such as indinavir, ritonavir, nelfinavir, saquinavir; verapamil; diltiazem; gemfibrozil; nicotinic acid; cyclosporine; amiodarone.
The risk of rhabdomyolysis will be increased under the following conditions, e.g., use at high dose, the elderly; patients with hepatic or renal insufficiency; alcoholism; patients with hypothyroidism.
Use with caution with colchicine especially in the elderly or patients with renal insufficiency because there is a risk of myopathy or rhabdomyolysis.
The use of this drug may increase the risk of increasing blood sugar level.

Advanced age (greater than 65 years); increased risk of myopathy.
Heavy alcohol use.
Preexisting amyotrophic lateral sclerosis (ALS); rate of ALS functional decline may increase with statin therapy.
Avoid concomitant use of gemfibrozil.
Conditions predisposing to renal failure secondary to rhabdomyolysis/myoglobinuria (eg, sepsis, hypotension, dehydration, major surgery, trauma, severe metabolic, endocrine and electrolyte disorder or uncontrolled seizures); temporary discontinuation may be required.
Markedly elevated creatinine kinase levels may occur; discontinuation may be warranted.
Increased HbA1c and serum glucose levels have been reported.
Higher doses are associated with increased risk of severe myopathy/ rhabdomyolysis.
Inadequately treated hypothyroidism may increase risk of myopathy.
Immune-mediated necrotizing myopathy, an autoimmune myopathy, has been reported; discontinue therapy immediately if myopathy is diagnosed or suspected.
Liver failure, some cases fatal, has been reported; interrupt treatment if serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs.
Myopathy and rhabdomyolysis, with acute renal failure secondary to myoglobinuria, have been reported; discontinue if diagnosed or suspected.
Moderate to severe renal impairment (GFR 15 to 59 mL/min/1.73 m²) or end-stage renal disease in patients receiving hemodialysis may increase risk of myopathy; dose adjustments recommended.
Serum transaminase level increases have been reported; monitoring recommended; interruption of therapy may be necessary.

Pregnancy category X.
This drug is contraindicated in pregnant women and nursing women.

Gastrointestinal: Constipation, diarrhea.
Musculoskeletal: Backache, myalgia, pain in limb, disorder of muscle, rhabdomyolysis.

Pitavastatin is a substrate of organic anion transport polypeptide (OATP) 1B1 (OATP2). Drugs that inhibit OATP1B1 (e.g., cyclosporine, erythromycin, rifampin) can increase bioavailability of pitavastatin.
Cyclosporine substantially increases pitavastatin exposure; such effects were considered clinically important. Concomitant use of pitavastatin with cyclosporine is contraindicated.
Concomitant use of pitavastatin and digoxin decreased pitavastatin peak plasma concentration, increased pitavastatin area under the curve (AUC) and decreased digoxin peak plasma concentration and AUC.
Concomitant use of pitavastatin and extended-release diltiazem hydrochloride increased pitavastatin peak plasma concentration and AUC and decreased diltiazem peak plasma concentration and AUC.
Erythromycin substantially increases pitavastatin exposure; such effects were considered clinically important. If used concomitantly with erythromycin, dosage of pitavastatin should not exceed 1 mg once daily.
Concomitant use of statins and gemfibrozil increases the risk of myopathy or rhabdomyolysis. Concomitant use of pitavastatin and gemfibrozil should be avoided. Caution is advised when pitavastatin is used concomitantly with other fibric acid derivatives (e.g., fenofibrate).
Concomitant use of pitavastatin and grapefruit juice decreased pitavastatin peak plasma concentration and increased pitavastatin AUC.
Concomitant use of pitavastatin and HIV protease inhibitors such as atazanavir, ritonavir-boosted darunavir, and lopinavir/ritonavir may disturb peak plasma concentration and AUC of pitavastatin and HIV protease inhibitors. Dosage adjustment are not necessary when pitavastatin is used concomitantly with HIV protease inhibitors.
Concomitant use of pitavastatin and itraconazole decreased pitavastatin peak plasma concentration and AUC.
Concomitant use of pitavastatin and antilipemic dosages (1 g daily or higher) of niacin increased the risk of myopathy. If used concomitantly with antilipemic dosage of niacin, caution is advised, and reduction in pitavastatin dosage should be considered.
Rifampin substantially increases pitavastatin exposure. If used concomitantly with rifampin, dosage of pitavastatin should not exceed 2 mg once daily.
Pitavastatin had no clinically important pharmacokinetic interaction with warfarin. In addition, pitavastatin had no clinically important effect on prothrombin time (PT) and international normalized ratio (INR) in patients receiving long-term warfarin therapy.
However, PT and INR should be monitored when pitavastatin is initiated in patients receiving warfarin.

Store below 30°C.

Dyslipidaemic Agents

C10AA08 - pitavastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.

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