Usage
This combination medication is prescribed to lower high cholesterol and triglyceride levels in the blood when lifestyle modifications (diet and exercise) are insufficient. It is specifically indicated for patients with mixed dyslipidemia or hyperlipidemia, conditions characterized by elevated levels of cholesterol and triglycerides. It’s crucial to note that this particular combination is not approved by the FDA and is primarily available in certain regions like India.
Pharmacological Classification: Lipid-lowering agent (combination drug) and Vitamin (Folic acid component).
Mechanism of Action: This fixed-dose combination (FDC) works synergistically through its components:
- Atorvastatin: Inhibits HMG-CoA reductase, an enzyme essential for cholesterol synthesis in the liver, leading to a reduction in LDL cholesterol.
- Fenofibrate: Activates PPAR-α, modulating lipid metabolism, leading to lower triglycerides and elevated HDL cholesterol levels.
- Folic Acid: Reduces homocysteine levels, a factor potentially contributing to elevated cholesterol.
Alternate Names
- AFF Tablet
- Atorvastatin/Fenofibrate/Folic Acid Fixed-Dose Combination (FDC)
- Inovas-F (Atorvastatin + Fenofibrate)
- Orvas-FT (Atorvastatin + Fenofibrate)
How It Works
Pharmacodynamics: Atorvastatin lowers LDL cholesterol by inhibiting HMG-CoA reductase. Fenofibrate lowers triglycerides and raises HDL cholesterol by activating PPAR-α. Folic acid reduces homocysteine levels.
Pharmacokinetics:
- Atorvastatin: Well-absorbed orally, metabolized by CYP3A4, excreted in bile.
- Fenofibrate: Well-absorbed orally, extensively metabolized, primarily excreted in urine.
- Folic Acid: Absorbed in the small intestine, converted to active forms, eliminated renally and in bile.
Mode of Action: Atorvastatin acts through competitive inhibition of HMG-CoA reductase, while Fenofibrate acts as a PPAR-α agonist. Folic acid, a B vitamin, plays a role in various metabolic processes, including homocysteine metabolism.
Receptor Binding/Enzyme Inhibition: Atorvastatin inhibits HMG-CoA reductase. Fenofibrate activates PPAR-α receptors.
Elimination Pathways: Atorvastatin is primarily eliminated through hepatic metabolism and biliary excretion. Fenofibrate is eliminated predominantly through urine. Folic Acid is eliminated through both renal and biliary routes.
Dosage
Standard Dosage
Adults:
The common starting dose is one tablet of Atorvastatin 10 mg/Fenofibrate 160 mg/Folic Acid 5 mg taken orally once daily with the evening meal. The dosage may be adjusted according to individual response and lipid levels, with the maximum dose of Atorvastatin generally not exceeding 80mg per day, and the maximum dose of Fenofibrate being 200mg per day.
Children: This combination is not recommended for children and adolescents under 18 years of age due to lack of established safety and efficacy data.
Special Cases:
- Elderly Patients: Start with a lower Atorvastatin dose (e.g., 10 mg daily) and titrate cautiously, monitoring renal function.
- Patients with Renal Impairment: Reduce Fenofibrate dose for creatinine clearance <50 mL/min. No dose reduction is needed for moderate renal impairment (creatinine clearance 50-90 mL/min), however monitor closely.
- Patients with Hepatic Dysfunction: Use with caution. Closely monitor liver function tests (LFTs) and adjust dosage accordingly. Contraindicated in active liver disease.
- Patients with Comorbid Conditions: Careful monitoring of blood glucose in diabetic patients is needed. Caution is advised in patients with pre-existing gallbladder disease.
Clinical Use Cases
The provided sources do not specify dosages for specific medical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. The primary use of this combination is for chronic management of dyslipidemia.
Dosage Adjustments
Dose adjustments are determined by the patient’s response to therapy and tolerability. Regular monitoring of lipid panels and liver function is crucial, and renal function should be assessed, especially in the elderly and those with known renal impairment.
Side Effects
Common Side Effects:
- Headache
- Nausea
- Constipation
- Flatulence
- Indigestion
- Diarrhea
- Abdominal pain
- Muscle pain
Rare but Serious Side Effects:
- Myopathy/Rhabdomyolysis (muscle damage/breakdown)
- Hepatotoxicity (liver damage)
- Allergic reactions (including angioedema)
- Pancreatitis
- Hyperglycemia
Long-Term Effects:
- Increased risk of gallstones (with Fenofibrate)
- Potential for increased risk of new-onset diabetes (with Atorvastatin), although the overall cardiovascular benefits generally outweigh this risk.
Adverse Drug Reactions (ADR):
Any signs of myopathy/rhabdomyolysis (muscle pain, tenderness, weakness), hepatotoxicity (jaundice, dark urine), or allergic reactions (rash, swelling) necessitate immediate discontinuation and medical evaluation.
Contraindications
- Hypersensitivity to any component
- Active liver disease or unexplained persistent elevations in LFTs
- Gallbladder disease
- Severe renal impairment (creatinine clearance <30 mL/min for Atorvastatin, <50 mL/min for Fenofibrate)
- Pregnancy and breastfeeding
Drug Interactions
- Fibrates (gemfibrozil): Increased risk of myopathy
- Certain antibiotics (clarithromycin, erythromycin): Increased statin levels
- Oral contraceptives: Increased risk of contraceptive-related side effects
- Anticoagulants (warfarin): Potentiation of anticoagulant effect
- Immunosuppressants (cyclosporine): Increased statin levels
- Grapefruit juice: Inhibits statin metabolism
- Alcohol: Increased risk of liver damage
Pregnancy and Breastfeeding
This medication is contraindicated during pregnancy and breastfeeding due to potential fetal risks. Atorvastatin is classified as Pregnancy Category X. It is advisable to avoid fenofibrate and folic acid during pregnancy unless benefits significantly outweigh risks. It is unknown whether these drugs are excreted in breast milk. Safe alternatives should be considered during these periods.
Drug Profile Summary
- Mechanism of Action: Atorvastatin: HMG-CoA reductase inhibitor; Fenofibrate: PPAR-α activator; Folic acid: Reduces homocysteine.
- Side Effects: Myopathy, hepatotoxicity, allergic reactions, GI disturbances.
- Contraindications: Active liver disease, gallbladder disease, severe renal impairment, pregnancy, breastfeeding.
- Drug Interactions: Fibrates, certain antibiotics, oral contraceptives, anticoagulants, grapefruit juice.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: One tablet daily, adjusted as needed. Not recommended for children.
- Monitoring Parameters: Lipid panel, LFTs, renal function, blood glucose (in diabetics).
Popular Combinations
While this FDC contains Atorvastatin, Fenofibrate, and Folic Acid, other combinations, such as statin monotherapy or statin with ezetimibe, are available for managing lipid disorders. Treatment choice depends on the patient’s specific lipid profile and cardiovascular risk.
Precautions
- General Precautions: Pre-screening for allergies, metabolic disorders, organ dysfunction.
- Pregnant Women: Contraindicated due to potential fetal risks.
- Breastfeeding Mothers: Contraindicated due to potential neonatal exposure through breast milk.
- Children & Elderly: Not recommended for children under 18. Use with caution in elderly patients and closely monitor renal function.
- Lifestyle Considerations: Avoid alcohol; limit or avoid grapefruit juice.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Atorvastatin + Fenofibrate + Folic Acid?
A: The common starting dose for adults is one tablet of Atorvastatin 10 mg/Fenofibrate 160 mg/Folic Acid 5 mg once daily, taken with the evening meal. Dosage can be adjusted based on the patient’s response and lipid levels, under careful medical supervision. Not recommended for children under 18.
Q2: What are the common side effects?
A: Common side effects include headache, nausea, constipation, flatulence, indigestion, diarrhea, abdominal pain, and muscle pain.
A: Serious side effects include myopathy/rhabdomyolysis (muscle damage), hepatotoxicity (liver damage), allergic reactions, and pancreatitis. Seek immediate medical attention if these occur.
Q4: Can this combination be used during pregnancy or breastfeeding?
A: No, this combination is contraindicated during pregnancy and breastfeeding due to potential risks to the fetus or neonate.
Q5: Are there any drug interactions I should be aware of?
A: Yes, this combination can interact with several medications, including fibrates, certain antibiotics (clarithromycin, erythromycin), oral contraceptives, anticoagulants (warfarin), immunosuppressants (cyclosporine), and grapefruit juice. Inform your doctor about all medications you are taking.
Q6: What should I do if I miss a dose?
A: If you miss a dose, take it as soon as you remember. However, if it is close to the time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not double the dose to catch up.
Q7: What are the long-term effects of taking this medication?
A: Long-term use may slightly increase the risk of gallstones and potentially new-onset diabetes. However, the cardiovascular benefits generally outweigh these risks. Regular monitoring is essential.
Q8: Can I consume alcohol while taking this medication?
A: Alcohol consumption should be avoided as it can increase the risk of liver damage and raise triglyceride levels, counteracting the medication’s effects.
Q9: What are the monitoring parameters for patients taking this medication?
A: Regular monitoring of lipid panel, liver function tests (LFTs), renal function, and blood glucose (especially in diabetics) is recommended.
Q10: What is the role of Folic Acid in this combination?
A: Folic acid helps reduce homocysteine levels, which can contribute to cardiovascular risk. While the benefits are debated, it’s included as a supplementary cardioprotective measure.
