Usage
Cerivastatin was prescribed for the treatment of primary hypercholesterolemia, including type IIa and IIb. It belongs to the pharmacological class of HMG-CoA reductase inhibitors, commonly known as statins. Cerivastatin worked by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis. This inhibition led to a decrease in hepatic cholesterol production, which in turn increased the number of LDL receptors on liver cells, promoting the removal of LDL cholesterol from the bloodstream.
Alternate Names
Cerivastatin’s most recognized brand name was Baycol. However, this drug was withdrawn from the market in 2001 due to safety concerns.
How It Works
Pharmacodynamics: Cerivastatin primarily reduced LDL cholesterol levels. It also showed modest reductions in triglycerides and a slight increase in HDL cholesterol. The main cholesterol-lowering effect was attributed to the parent drug itself.
Pharmacokinetics:
- Absorption: Cerivastatin was rapidly and almost completely absorbed following oral administration, with peak plasma concentrations reached within 2-3 hours. Food or time of administration did not significantly impact absorption.
- Metabolism: Cerivastatin was extensively metabolized in the liver by the cytochrome P450 (CYP) enzyme system, particularly CYP2C8 and CYP3A4. The metabolites M1 and M23 were the primary forms excreted.
- Elimination: The parent drug, cerivastatin, was not found in urine or feces. Metabolites were excreted through both renal and hepatic pathways. Elimination half-life was approximately 2-3 hours, reaching steady-state plasma concentrations within a few days.
Mode of Action: Cerivastatin competitively inhibited HMG-CoA reductase, the rate-limiting enzyme in the mevalonate pathway, which is essential for cholesterol synthesis. This inhibition reduced intracellular cholesterol levels, leading to increased LDL receptor expression on hepatocytes and enhanced clearance of LDL cholesterol from circulation.
Dosage
Cerivastatin is no longer available on the market and therefore dosage information is not relevant. It was withdrawn from the market in 2001 due to safety concerns, particularly an increased risk of rhabdomyolysis.
Side Effects
Common Side Effects
Common side effects included:
- Gastrointestinal issues (gas, bloating, nausea, stomach upset, heartburn, indigestion, abdominal pain, constipation, diarrhea)
- Dizziness and headache
- Rash, sore throat, runny or stuffy nose
- Joint pain and muscle aches
- Flu-like symptoms and weakness
Rare but Serious Side Effects
The most serious side effect was rhabdomyolysis, a potentially fatal breakdown of skeletal muscle. Symptoms included muscle aches, pain, weakness, fever, dark urine, and decreased urine output. Acute renal failure could result from rhabdomyolysis. Other serious side effects included myopathy and myositis (muscle inflammation).
Contraindications
Cerivastatin was contraindicated in patients with:
- Active liver disease or unexplained persistent elevations in liver enzymes
- Hypersensitivity to the drug
- Pregnancy and breastfeeding
Drug Interactions
Cerivastatin had interactions with multiple drugs. Co-administration with gemfibrozil, other fibrates, cyclosporine, erythromycin, azole antifungals (itraconazole, ketoconazole, fluconazole), or niacin increased the risk of rhabdomyolysis. Other interactions included increased cerivastatin levels with itraconazole and cholestyramine reducing cerivastatin bioavailability.
Pregnancy and Breastfeeding
Cerivastatin was classified as Pregnancy Category X and was contraindicated during pregnancy due to the risk of fetal harm, including skeletal malformations. It was also contraindicated during breastfeeding because it was excreted into human milk and posed a risk of serious adverse reactions in nursing infants.
Drug Profile Summary
Cerivastatin is no longer available on the market due to an increased risk of severe side effects, specifically rhabdomyolysis.
Popular Combinations
Cerivastatin is no longer available on the market and hence not used in any combinations.
Precautions
Cerivastatin is no longer available on the market.
FAQs (Frequently Asked Questions)
Q1: What was the mechanism of action of Cerivastatin?
A: Cerivastatin inhibited HMG-CoA reductase, reducing cholesterol biosynthesis in the liver.
Q2: Why was Cerivastatin withdrawn from the market?
A: It was withdrawn due to an unacceptably high risk of rhabdomyolysis, particularly when combined with certain other medications.
Q3: What were the most serious side effects associated with Cerivastatin?
A: Rhabdomyolysis and associated renal failure were the most serious side effects.
Q4: What were the common side effects of Cerivastatin?
A: Common side effects included gastrointestinal issues, headache, dizziness, and muscle aches.
Q5: Could Cerivastatin be used during pregnancy or breastfeeding?
A: No, it was contraindicated in both pregnancy and breastfeeding.
Q6: What drugs interacted with Cerivastatin?
A: Gemfibrozil, fibrates, cyclosporine, erythromycin, azole antifungals, and niacin were among the drugs that interacted significantly with cerivastatin.
Q7: What was the usual dosage range for Cerivastatin?
A: The dosage range was typically between 0.2 mg and 0.8 mg per day.
Q8: What was the brand name of Cerivastatin?
A: The brand name was Baycol.
Q9: What type of drug was Cerivastatin?
A: Cerivastatin was a statin, an HMG-CoA reductase inhibitor.
