Usage
- Medical Conditions: Pitavastatin is prescribed to lower high levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C) in adults with primary hyperlipidemia or mixed dyslipidemia as an adjunct to diet. It is also used to treat heterozygous familial hypercholesterolemia (HeFH) in children 8 years of age and older. It may help prevent cardiovascular events like heart attacks and strokes.
- Pharmacological Classification: HMG-CoA reductase inhibitor (statin), Lipid-lowering agent.
- Mechanism of Action: Pitavastatin inhibits HMG-CoA reductase, an enzyme crucial in cholesterol biosynthesis in the liver. This inhibition reduces cholesterol production, forcing the liver to remove LDL-C from the bloodstream, ultimately lowering cholesterol levels.
Alternate Names
- International/Regional Variations: None explicitly stated.
- Brand Names: Livalo, Zypitamag.
How It Works
- Pharmacodynamics: Pitavastatin lowers “bad” cholesterol (LDL-C) and triglycerides, while increasing “good” cholesterol (HDL-C). This helps reduce the risk of atherosclerosis and cardiovascular disease.
- Pharmacokinetics:
- Absorption: Well-absorbed orally. Food does not significantly affect absorption.
- Metabolism: Primarily metabolized in the liver, involving CYP2C9 and CYP3A4 enzymes to a lesser extent.
- Elimination: Mainly excreted in bile and feces, with minimal renal excretion.
- Mode of Action: Pitavastatin competitively inhibits HMG-CoA reductase.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Competitive inhibition of HMG-CoA reductase.
- Elimination Pathways: Primarily hepatic excretion through bile and feces.
Dosage
Standard Dosage
Adults:
- Initial: 2 mg orally once daily.
- Maintenance: May increase to a maximum of 4 mg orally once daily, adjusted after 4 weeks based on lipid levels and patient response.
Children (8 years and older with HeFH):
- Initial: 2 mg orally once daily.
- Maintenance: May increase to a maximum of 4 mg orally once daily, adjusted based on lipid levels and patient response.
- Children younger than 8 years: Safety and efficacy not established.
Special Cases:
- Elderly Patients: Start with a lower dose (1 mg) and adjust cautiously due to increased risk of myopathy.
- Patients with Renal Impairment:
- Moderate to severe (CrCl 15-59 mL/min/1.73 m²): Initial 1 mg orally once daily, maximum 2 mg once daily.
- End-stage renal disease (ESRD) requiring hemodialysis: Same as moderate to severe renal impairment.
- Patients with Hepatic Dysfunction: Contraindicated in active liver disease or decompensated cirrhosis. Use with caution in mild hepatic impairment.
- Patients with Comorbid Conditions: Consider individual patient characteristics (e.g., diabetes, hypothyroidism) and adjust dose accordingly.
Clinical Use Cases
Pitavastatin’s use is focused on long-term lipid management and isn’t typically adjusted for short-term procedures like intubation, surgery, or mechanical ventilation. It is also not indicated for emergency situations like cardiac arrest. Its use in the ICU setting would be consistent with chronic management for hyperlipidemia if deemed necessary by the treating physician.
Dosage Adjustments
- Drug Interactions:
- Erythromycin: Do not exceed 1 mg pitavastatin daily.
- Rifampin: Do not exceed 2 mg pitavastatin daily.
- Cyclosporine: Contraindicated.
- Other factors: Renal/hepatic dysfunction, age, concomitant medications (e.g., fibrates, niacin), and genetic polymorphisms (SLCO1B1) may necessitate dose adjustments.
Side Effects
Common Side Effects:
- Back pain, muscle aches (myalgia), pain in limbs, constipation, diarrhea.
Rare but Serious Side Effects:
- Myopathy (muscle weakness/tenderness), rhabdomyolysis (muscle breakdown), hepatotoxicity (liver damage), allergic reactions (rash, hives, angioedema), increased blood sugar.
Long-Term Effects:
- Development of myopathy, rhabdomyolysis, or hepatotoxicity with prolonged use. Increased risk of diabetes.
Adverse Drug Reactions (ADR):
- Rhabdomyolysis with acute renal failure, severe allergic reactions, significant liver dysfunction.
Contraindications
- Hypersensitivity to pitavastatin
- Active liver disease or unexplained persistent elevations in liver enzymes
- Pregnancy and breastfeeding
- Concomitant use of cyclosporine
Drug Interactions
- CYP450 Interactions: Minor interactions with CYP2C9 and CYP3A4.
- Other Interactions:
- Strong Inhibitors of OATP1B1 Transporters (e.g., cyclosporine): Contraindicated, markedly increases pitavastatin levels.
- Moderate Inhibitors of OATP1B1 (e.g., erythromycin): Reduce dose.
- Inducers of CYP3A4 (e.g., rifampin): Reduce dose.
- Fibrates (e.g., gemfibrozil): Increased risk of myopathy.
- Niacin (high doses): Increased risk of myopathy.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: X (Contraindicated). Can cause fetal harm.
- Breastfeeding: Contraindicated. It is unknown if pitavastatin is present in human milk, but another drug in the same class is, so breastfeeding is not recommended due to potential risks to infants.
Drug Profile Summary
- Mechanism of Action: HMG-CoA reductase inhibitor, reducing cholesterol biosynthesis.
- Side Effects: Myalgia, back pain, constipation, diarrhea; rarely rhabdomyolysis, hepatotoxicity.
- Contraindications: Active liver disease, pregnancy, breastfeeding, concomitant cyclosporine use, hypersensitivity.
- Drug Interactions: Cyclosporine, erythromycin, rifampin, gemfibrozil, niacin.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: 2-4 mg daily; Children (HeFH, ≥8 years): 2-4 mg daily. Renal impairment: 1-2 mg daily.
- Monitoring Parameters: Liver function tests, creatine kinase, lipid panel, blood glucose.
Popular Combinations
- Ezetimibe: Combined use enhances LDL-C lowering.
Precautions
- General Precautions: Monitor liver function, creatine kinase (CK) levels, and blood glucose. Assess for muscle symptoms. Screen for predisposing factors for myopathy (e.g., hypothyroidism, renal impairment, advanced age).
- Specific Populations: Advise women of childbearing potential to use effective contraception. Not recommended for breastfeeding mothers. Use with caution in elderly patients and patients with renal impairment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Pitavastatin?
A: Adults: 2-4 mg once daily. Children (HeFH, 8 years and older): 2-4 mg once daily. Elderly and renal impairment: Lower starting dose (1 mg) and maximum of 2 mg daily.
Q2: What are the most serious side effects of Pitavastatin?
A: Myopathy (muscle pain/weakness), rhabdomyolysis (muscle breakdown), and hepatotoxicity.
Q3: What are the common side effects of Pitavastatin?
A: Back pain, muscle aches, constipation, diarrhea.
Q4: Can Pitavastatin be used during pregnancy or breastfeeding?
A: No, pitavastatin is contraindicated during pregnancy and breastfeeding due to potential risks to the fetus/infant.
Q5: What medications should be avoided while taking Pitavastatin?
A: Cyclosporine, gemfibrozil, and high-dose niacin should be avoided due to an increased risk of myopathy. Adjust doses with erythromycin and rifampin.
Q6: How does Pitavastatin interact with grapefruit juice?
A: No clinically significant interaction with grapefruit juice has been reported.
Q7: How should Pitavastatin be administered?
A: Orally, once daily, with or without food.
Q8: What should I monitor in patients taking Pitavastatin?
A: Monitor liver function tests, creatine kinase (CK), lipid profile, and blood glucose regularly.
Q9: What is the role of genetic testing in Pitavastatin therapy?
A: SLCO1B1 gene polymorphism testing may be considered to assess risk for myopathy, especially in patients with unexplained muscle symptoms.
Q10: When should Pitavastatin be discontinued?
A: Discontinue if signs of myopathy, rhabdomyolysis, or hepatotoxicity develop. Also discontinue upon pregnancy.
