Usage
- Ezetimibe + Pitavastatin is prescribed for the reduction of elevated 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 patients with primary hypercholesterolemia (including heterozygous familial hypercholesterolemia) and mixed dyslipidemia, when response to diet and other non-pharmacological measures is inadequate. It is also used to lower cholesterol in patients with homozygous familial hypercholesterolemia and to reduce high blood levels of plant-based sterols in people with homozygous sitosterolemia.
- Pharmacological Classification: Antihyperlipidemic agent, HMG-CoA reductase inhibitor (statin), cholesterol absorption inhibitor.
- Mechanism of Action: Ezetimibe inhibits the intestinal absorption of cholesterol. Pitavastatin inhibits HMG-CoA reductase, an enzyme crucial for cholesterol synthesis in the liver, thereby reducing LDL-C production.
Alternate Names
No widely used alternate names for the combination product exist. Brand names may vary regionally (Livazo, Lipvas, Ezetimibe/Pitavastatin).
How It Works
- Pharmacodynamics: Ezetimibe selectively inhibits the Niemann-Pick C1-Like 1 (NPC1L1) protein, responsible for intestinal cholesterol absorption, without affecting the absorption of fat-soluble vitamins or triglycerides. Pitavastatin competitively inhibits HMG-CoA reductase, reducing hepatic cholesterol synthesis and increasing LDL receptor expression, which enhances LDL clearance from the bloodstream.
- Pharmacokinetics: Ezetimibe is extensively metabolized in the small intestine and liver via glucuronidation. Pitavastatin is primarily metabolized by glucuronidation with minimal CYP involvement. Both drugs are excreted in feces and urine.
- Mode of Action: Ezetimibe acts on the brush border of the small intestine to block cholesterol absorption. Pitavastatin acts within hepatocytes to inhibit HMG-CoA reductase.
- Receptor Binding/Enzyme Inhibition: Ezetimibe targets the NPC1L1 transporter. Pitavastatin inhibits HMG-CoA reductase.
- Elimination Pathways: Both drugs are eliminated through hepatic metabolism and excretion in bile and urine.
Dosage
Standard Dosage
Adults:
- Initial dose: Ezetimibe 10 mg + Pitavastatin 2 mg once daily.
- Titration: Pitavastatin may be increased to 4mg daily based on LDL-C goals and patient response. Administer at the same time each day, preferably in the evening.
Children:
- Limited safety and efficacy data are available for children under 10 years of age. Pitavastatin might be considered in children aged eight years and older with HeFH, starting with 2 mg once daily.
Special Cases:
- Elderly Patients: No specific dose adjustment is typically needed, but initiate with caution due to potential for increased sensitivity.
- Patients with Renal Impairment: Moderate to severe impairment: initiate Pitavastatin at 1 mg once daily, not exceeding 2mg.
- Patients with Hepatic Dysfunction: Active liver disease or unexplained persistent elevations in liver transaminases contraindicate Ezetimibe + Pitavastatin. Mild impairment requires caution. Moderate to severe impairment is contraindicated.
- Patients with Comorbid Conditions: Patients with diabetes or at risk of developing diabetes should be monitored closely.
Clinical Use Cases
Ezetimibe + Pitavastatin is primarily indicated for long-term management of hyperlipidemia and doesn’t have specific dosage recommendations for acute clinical scenarios like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Adjustments may be necessary based on individual patient characteristics, including renal or hepatic dysfunction, concomitant medications, and response to therapy. Regular monitoring of liver enzymes and lipid profile is essential.
Side Effects
Common Side Effects
Headache, diarrhea, joint pain, muscle pain or tenderness (myalgia), weakness, pain in extremities.
Rare but Serious Side Effects
Myopathy, rhabdomyolysis, liver damage, allergic reactions.
Long-Term Effects
Potential for chronic complications with long-term statin use needs ongoing assessment, with regular monitoring of liver enzymes, muscle function, and lipid profiles.
Adverse Drug Reactions (ADR)
Severe muscle pain or weakness, dark urine, signs of liver injury (jaundice, abdominal pain), allergic reactions (rash, itching, swelling).
Contraindications
- Active liver disease, unexplained persistent elevations in liver transaminases.
- Hypersensitivity to ezetimibe or pitavastatin.
- Pregnancy and breastfeeding.
- Concomitant use of cyclosporine.
Drug Interactions
- Cyclosporine, gemfibrozil, erythromycin, rifampin, protease inhibitors (e.g., atazanavir, lopinavir/ritonavir), bile acid sequestrants, fibrates, and anticoagulants (e.g., warfarin). Close monitoring is required when co-administering these drugs.
Pregnancy and Breastfeeding
Contraindicated in pregnancy and breastfeeding due to the potential for fetal harm and unknown effects on infants.
Drug Profile Summary
- Mechanism of Action: Ezetimibe inhibits intestinal cholesterol absorption; pitavastatin inhibits hepatic cholesterol synthesis.
- Side Effects: Headache, myalgia, arthralgia, gastrointestinal upset, rare but serious myopathy/rhabdomyolysis.
- Contraindications: Active liver disease, pregnancy, breastfeeding, hypersensitivity, concomitant cyclosporine.
- Drug Interactions: Cyclosporine, gemfibrozil, erythromycin, rifampin, protease inhibitors.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: Ezetimibe 10 mg + Pitavastatin 2-4 mg once daily. Pediatric and special population dosing requires individualized assessment.
- Monitoring Parameters: Liver enzymes (ALT, AST), creatine kinase (CK), lipid profile (LDL-C, HDL-C, TC, TG).
Popular Combinations
Ezetimibe is often combined with Pitavastatin to achieve synergistic LDL-C lowering effects when statin monotherapy is insufficient.
Precautions
- Monitor liver function tests and lipid panel before initiating therapy, at 12 weeks, and periodically thereafter.
- Patients with renal or hepatic impairment require careful monitoring and potential dose adjustments.
- Counsel patients about the risk of myopathy and rhabdomyolysis and advise them to report any muscle symptoms.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ezetimibe + Pitavastatin?
A: The standard adult starting dose is Ezetimibe 10 mg + Pitavastatin 2 mg once daily, taken orally. Pitavastatin can be titrated up to 4 mg daily if needed.
Q2: How should I monitor patients on Ezetimibe + Pitavastatin?
A: Monitor liver function tests (ALT, AST) and creatine kinase (CK) at baseline, 12 weeks after initiation or dose adjustments, and periodically thereafter. Regularly assess lipid profile to monitor treatment efficacy.
Q3: Are there any specific contraindications for this combination?
A: Yes, contraindications include active liver disease, unexplained persistent elevations in liver transaminases, pregnancy, breastfeeding, hypersensitivity to either drug, and concomitant cyclosporine use.
Q4: What are the common side effects?
A: Common side effects include headache, myalgia, arthralgia, diarrhea, and other gastrointestinal symptoms.
Q5: What are the serious side effects I should watch for?
A: Rare but serious side effects include myopathy, rhabdomyolysis, and hepatotoxicity. Advise patients to promptly report any unexplained muscle pain, tenderness, or weakness.
Q6: Can this combination be used in patients with renal impairment?
A: Yes, but with careful monitoring and dose adjustments. For moderate to severe renal impairment, start Pitavastatin at 1 mg daily, not exceeding 2 mg.
Q7: Is Ezetimibe + Pitavastatin safe during pregnancy?
A: No, it’s contraindicated during pregnancy and breastfeeding due to the potential for fetal harm and unknown effects on infants.
Q8: What are the major drug interactions to be aware of?
A: Key drug interactions include cyclosporine, gemfibrozil, erythromycin, rifampin, and certain protease inhibitors. Co-administration requires close monitoring and potential dose adjustments.
Q9: How does this combination work to lower cholesterol?
A: Ezetimibe reduces intestinal cholesterol absorption, while pitavastatin decreases cholesterol production in the liver. This dual mechanism provides synergistic LDL-C lowering.
