Usage
Atorvastatin + Bempedoic acid is prescribed to lower low-density lipoprotein cholesterol (LDL-C) levels in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), or established atherosclerotic cardiovascular disease (ASCVD) who require additional LDL-C lowering. Bempedoic acid is specifically indicated for patients who cannot achieve target LDL-C levels with statins alone or who are statin-intolerant.
It falls under the pharmacological classification of lipid-lowering agents. More specifically, Atorvastatin is an HMG-CoA reductase inhibitor (statin), while Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor.
Atorvastatin inhibits HMG-CoA reductase, an enzyme crucial for cholesterol synthesis in the liver. This leads to increased hepatic LDL receptor expression and enhanced LDL clearance from the bloodstream. Bempedoic acid inhibits ACL, another enzyme in the cholesterol synthesis pathway, further reducing cholesterol production. The combination of these two distinct mechanisms results in synergistic LDL-C lowering.
Alternate Names
There are no widely recognized alternate names for this specific drug combination.
Brand Names: Nexletol (bempedoic acid) and Lipitor (atorvastatin) are common brand names, but they are not available as a fixed-dose combination.
How It Works
Pharmacodynamics: Atorvastatin primarily acts in the liver to reduce cholesterol synthesis. Bempedoic acid also targets cholesterol synthesis in the liver but through a distinct mechanism.
Pharmacokinetics:
- Absorption: Both drugs are orally administered and absorbed from the gastrointestinal tract.
- Metabolism: Atorvastatin is extensively metabolized by CYP3A4. Bempedoic acid is primarily metabolized via glucuronidation in the liver and is not a CYP enzyme substrate.
- Elimination: Both drugs are mainly eliminated through the biliary route, and a minor part through renal excretion.
Mode of Action: Atorvastatin competitively inhibits HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol synthesis. This inhibition leads to a compensatory increase in LDL receptors on hepatocytes, resulting in enhanced removal of LDL-C from circulation. Bempedoic acid inhibits ACL, an enzyme upstream of HMG-CoA reductase in the cholesterol synthesis pathway. This inhibition leads to decreased cholesterol production. The combination of these mechanisms results in a synergistic reduction in LDL-C levels.
Receptor Binding/Enzyme Inhibition: Atorvastatin targets HMG-CoA reductase. Bempedoic acid targets ACL.
Elimination Pathways: Both drugs are primarily eliminated via biliary excretion and to a lesser extent via renal excretion.
Dosage
The drugs are administered separately. There is no fixed-dose combination currently available.
Standard Dosage
Adults:
- Atorvastatin: Dosages range from 10 mg to 80 mg once daily, depending on the patient’s LDL-C goal and response.
- Bempedoic acid: 180 mg orally once daily.
Children: Bempedoic acid is not approved for use in children. Atorvastatin can be used in children, but dosage depends on the specific condition and should be determined by a pediatrician.
Special Cases:
- Elderly Patients: No dosage adjustment is typically necessary for bempedoic acid. Atorvastatin dosage should be initiated at the lower end of the range and titrated as needed.
- Patients with Renal Impairment: No dosage adjustment is necessary for mild or moderate renal impairment for either drug. For severe renal impairment, bempedoic acid use should be cautious, while atorvastatin may require dosage adjustment.
- Patients with Hepatic Dysfunction: No dosage adjustment is necessary for mild or moderate hepatic impairment for either drug. Bempedoic acid has not been studied in severe hepatic impairment. Atorvastatin should be used with caution in patients with active liver disease.
- Patients with Comorbid Conditions: Close monitoring is required for patients with diabetes, cardiovascular disease, or other conditions.
Clinical Use Cases The combination of atorvastatin and bempedoic acid is not specifically indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. These drugs are used for long-term management of hyperlipidemia and cardiovascular risk reduction.
Dosage Adjustments Dosage adjustments may be necessary based on individual patient characteristics, such as renal or hepatic impairment, concomitant medications, and response to therapy.
Side Effects
Common Side Effects
- Atorvastatin: Muscle pain, tenderness, or weakness (myalgia), headache, stomach pain, heartburn, nausea.
- Bempedoic acid: Upper respiratory tract infections, back pain, muscle spasms, pain in extremities, anemia, gout.
Rare but Serious Side Effects
- Atorvastatin: Rhabdomyolysis (severe muscle breakdown), liver damage, allergic reactions.
- Bempedoic acid: Tendon rupture, severe hypersensitivity reactions.
Long-Term Effects
- Atorvastatin: Potential for liver enzyme elevations, muscle damage with long-term use.
- Bempedoic acid: Long-term effects are still being studied but may include increased risk of gout and tendon disorders.
Adverse Drug Reactions (ADR)
- Atorvastatin: Rhabdomyolysis, hepatotoxicity, angioedema.
- Bempedoic acid: Severe hypersensitivity reactions, tendon rupture, gout.
Contraindications
- Atorvastatin: Active liver disease, hypersensitivity to statins, pregnancy, breastfeeding.
- Bempedoic acid: Hypersensitivity to bempedoic acid, pregnancy, breastfeeding. Coadministration with simvastatin > 40 mg daily.
Drug Interactions
- Atorvastatin: Numerous drug interactions exist. Significant interactions can occur with CYP3A4 inhibitors and inducers (e.g., certain antifungals, antibiotics, antivirals).
- Bempedoic acid: Co-administration with simvastatin or pravastatin can increase their concentrations and risk of myopathy. Avoid concomitant use of bempedoic acid with simvastatin doses > 20 mg or pravastatin doses > 40 mg. Atorvastatin and rosuvastatin have weak interactions with bempedoic acid resulting in minor AUC elevations. No dosage adjustments are needed for these combinations.
Pregnancy and Breastfeeding
Both atorvastatin and bempedoic acid are contraindicated in pregnancy and breastfeeding due to potential risks to the fetus or infant. Effective contraception should be used during treatment.
Drug Profile Summary
- Mechanism of Action: Atorvastatin inhibits HMG-CoA reductase. Bempedoic acid inhibits ACL. Both reduce cholesterol synthesis.
- Side Effects: Muscle pain, upper respiratory tract infections, back pain, gout.
- Contraindications: Pregnancy, breastfeeding, active liver disease (atorvastatin), hypersensitivity.
- Drug Interactions: CYP3A4 inhibitors/inducers (atorvastatin), simvastatin/pravastatin (bempedoic acid).
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Atorvastatin: 10-80mg/day; Bempedoic acid: 180 mg/day.
- Monitoring Parameters: LDL-C, liver function tests, creatinine kinase (if muscle symptoms occur), uric acid.
Popular Combinations
Atorvastatin and bempedoic acid are often used together in patients with hypercholesterolemia who cannot tolerate or do not respond adequately to high-dose statins alone. Ezetimibe is another commonly added medication.
Precautions
- Monitor for muscle symptoms and liver function tests.
- Monitor uric acid levels for gout.
- Patients with renal or hepatic impairment require careful monitoring.
- Contraception counseling for women of childbearing age.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Atorvastatin + Bempedoic acid?
A: Atorvastatin is typically started at 10-20 mg once daily and titrated up to 80 mg as needed. Bempedoic acid is dosed at 180 mg once daily.
Q2: What are the primary side effects to be aware of?
A: Muscle pain (myalgia) for atorvastatin and increased uric acid levels leading to gout for bempedoic acid are common side effects.
Q3: Can this combination be used during pregnancy or breastfeeding?
A: No, both atorvastatin and bempedoic acid are contraindicated during pregnancy and breastfeeding.
Q4: Are there specific monitoring parameters for this combination?
A: Monitor LDL-C, liver enzymes, and creatinine kinase (if muscle symptoms present), and uric acid.
Q5: What should be done if a patient experiences muscle pain while on this combination?
A: Check creatinine kinase levels. If significantly elevated, discontinue both medications and evaluate for rhabdomyolysis. If levels are normal, consider reducing the atorvastatin dose or switching to a different statin.
Q6: How do Atorvastatin and Bempedoic Acid differ in their mechanisms of action?
A: Atorvastatin inhibits HMG-CoA reductase, and Bempedoic acid inhibits ACL, both acting on different parts of the cholesterol synthesis pathway.
Q7: Who are the ideal candidates for this combination therapy?
A: Patients with hypercholesterolemia not adequately controlled by statins alone, or those who are statin intolerant, may benefit from this combination.
Q8: Does Bempedoic Acid interact with all statins?
A: No, it has more significant interactions with simvastatin and pravastatin, which require dosage adjustments. Interactions with atorvastatin and rosuvastatin are weak and do not require dosage adjustments.
Q9: Can Bempedoic acid be used as a monotherapy?
A: Yes, Bempedoic acid can be used as a monotherapy in patients with primary hyperlipidemia who cannot tolerate statins or need additional LDL-C lowering.
Q10: What is the significance of elevated uric acid levels with Bempedoic acid?
A: Increased uric acid can potentially lead to gout. Regular monitoring and management strategies are essential to minimize this risk.
