Rosuvastatin

Usage

• Rosuvastatin is prescribed to lower “bad” cholesterol (LDL, triglycerides) and raise “good” cholesterol (HDL) in the blood. It is also used to slow the progression of atherosclerosis (hardening of the arteries) and reduce the risk of cardiovascular events such as heart attack and stroke in high-risk individuals. It is effective in treating primary hypercholesterolemia (including heterozygous familial hypercholesterolemia), mixed dyslipidemia (Fredrickson Type IIa and IIb), isolated hypertriglyceridemia (Fredrickson Type IV), and homozygous familial hypercholesterolemia.
• Pharmacological Classification: HMG-CoA reductase inhibitor (statin).
• Mechanism of Action: Rosuvastatin inhibits HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. This leads to increased expression of LDL receptors in the liver, enhancing the uptake and clearance of LDL cholesterol from the bloodstream. It also reduces the synthesis of very-low-density lipoproteins (VLDL), which contribute to triglyceride levels.

Alternate Names

• International Nonproprietary Name (INN): Rosuvastatin Calcium
• Brand Names: Crestor, Ezallor Sprinkle

How It Works

• Pharmacodynamics: Rosuvastatin lowers LDL cholesterol, total cholesterol, triglycerides, ApoB, non-HDL-C, VLDL-C, VLDL-TG, and the LDL-C/HDL-C, total C/HDL-C, nonHDL-C/HDL-C, ApoB/ApoA-I ratios. It increases HDL-C and ApoA-I. The lipid-lowering effect contributes to the reduction of cardiovascular risk.
• Pharmacokinetics:
  • Absorption: Rosuvastatin reaches peak plasma concentrations 3 to 5 hours after oral administration. Absorption is not significantly affected by food.
  • Metabolism: Minimally metabolized by the cytochrome P450 (CYP) system, primarily CYP2C9. This reduces the potential for drug-drug interactions compared to other statins.
  • Elimination: Primarily excreted unchanged in bile and feces (approximately 90%), with a small portion (approximately 10%) eliminated renally.
• Mode of Action: Rosuvastatin competitively binds to and inhibits HMG-CoA reductase in the liver. This inhibition blocks the conversion of HMG-CoA to mevalonate, a key precursor in cholesterol synthesis.
• Receptor Binding/Enzyme Inhibition: Competitive inhibition of HMG-CoA reductase. OATP1B1 plays a role in hepatic uptake.
• Elimination Pathways: Hepatic (biliary and fecal) excretion is the primary route, with minor renal excretion.

Dosage

Standard Dosage

Adults:

• Initial: 5-10 mg orally once daily. For severe hypercholesterolemia or high cardiovascular risk, an initial dose of 20 mg can be considered. For homozygous familial hypercholesterolemia, the initial dose is 20 mg once daily.
• Maintenance: 5-40 mg orally once daily. The maximum dose is 40 mg and should be reserved for patients at high risk who do not achieve their cholesterol goals on lower doses.
• Administration: Oral, with or without food, at any time of day.

Children:

• Heterozygous Familial Hypercholesterolemia:
  • 8-9 years: 5-10 mg orally once daily.
  • 10-17 years: 5-20 mg orally once daily.
• Homozygous Familial Hypercholesterolemia:
  • 7-17 years: 20 mg orally once daily.
• Safety Considerations: Safety and efficacy in children younger than 7 years with homozygous familial hypercholesterolemia or younger than 8 years with heterozygous familial hypercholesterolemia have not been established.

Special Cases:

• Elderly Patients (≥70 years): Initial dose of 5 mg is recommended. Close monitoring for adverse effects, especially myopathy, is essential.
• Patients with Renal Impairment: Mild to moderate impairment: no dose adjustment necessary. Severe impairment (creatinine clearance <30 mL/min): do not exceed 10 mg daily.
• Patients with Hepatic Dysfunction: Mild to moderate impairment: usual dose range applies. Active liver disease or decompensated cirrhosis: contraindicated.
• Patients with Comorbid Conditions: Caution is advised in patients with diabetes, hypothyroidism, or other conditions affecting lipid metabolism. Dose adjustments may be necessary. Asian patients: Start with 5 mg due to increased plasma concentrations.

Clinical Use Cases

Rosuvastatin is not typically used in acute clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its role is in long-term management of hyperlipidemia and cardiovascular risk reduction.

Dosage Adjustments

• Dosage should be individualized based on the patient’s response and lipid goals. Titration should occur at intervals of 2-4 weeks.
• Consider lower starting doses and careful monitoring in patients with renal or hepatic impairment, Asian ancestry, or predisposing factors for myopathy.
• Adjust dosage when co-administered with interacting medications (e.g., cyclosporine, gemfibrozil).

Side Effects

Common Side Effects:

• Headache, myalgia, arthralgia, nausea, constipation, asthenia, abdominal pain, dizziness.

Rare but Serious Side Effects:

• Myopathy (muscle pain, tenderness, or weakness), rhabdomyolysis (muscle breakdown), hepatotoxicity (liver damage), acute kidney injury.

Long-Term Effects:

• Increased risk of diabetes with prolonged statin use has been reported.

Adverse Drug Reactions (ADR):

• Angioedema, hypersensitivity reactions (rash, pruritus, urticaria), myopathy progressing to rhabdomyolysis.

Contraindications

• Hypersensitivity to rosuvastatin.
• Active liver disease, including acute liver failure or decompensated cirrhosis.
• Pregnancy.
• Breastfeeding.

Drug Interactions

• CYP450 Interactions: Rosuvastatin is primarily metabolized by CYP2C9, but its metabolism is minimal. Drug interactions are more likely to occur through inhibition of OATP1B1-mediated hepatic uptake.
• Clinically Significant Drug Interactions:
  • Cyclosporine: Significantly increases rosuvastatin concentrations; limit rosuvastatin dose to 5 mg daily.
  • Gemfibrozil: Increases the risk of myopathy; limit rosuvastatin dose to 10 mg daily.
  • Some protease inhibitors (e.g., ritonavir): Increase rosuvastatin levels.
  • Antacids: May decrease rosuvastatin absorption.
  • Other cholesterol-lowering agents (e.g., fibrates, niacin): Increase risk of myopathy.
• Other Interactions: Erythromycin, fusidic acid, some antiviral medicines (HIV and hepatitis), antacids (Gaviscon), anticoagulants (clopidogrel, warfarin), ciclosporin, oral contraceptives, hormone replacement therapy.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: X (Contraindicated). Rosuvastatin can cause fetal harm.
• Fetal Risks: Congenital anomalies.
• Breastfeeding: Rosuvastatin is present in breast milk. Women taking rosuvastatin should not breastfeed due to potential for serious adverse reactions in nursing infants.

Drug Profile Summary

• Mechanism of Action: HMG-CoA reductase inhibitor.
• Side Effects: Myalgia, arthralgia, headache, nausea, elevated liver enzymes, rhabdomyolysis (rare).
• Contraindications: Pregnancy, breastfeeding, active liver disease.
• Drug Interactions: Cyclosporine, gemfibrozil, protease inhibitors.
• Pregnancy & Breastfeeding: Contraindicated.
• Dosage: 5-40 mg daily (adults), individualized for children.
• Monitoring Parameters: Lipid panel (LDL-C, HDL-C, triglycerides), liver function tests (LFTs), creatine kinase (CK) if myopathy is suspected.

Popular Combinations

• Rosuvastatin is sometimes combined with ezetimibe, another cholesterol-lowering agent, for additive effects in patients not reaching their LDL-C goals on rosuvastatin alone.

Precautions

• General Precautions: Monitor LFTs and CK levels. Screen for pre-existing liver disease, renal impairment, and hypothyroidism. Assess alcohol intake.
• Specific Populations:
  • Pregnant Women: Contraindicated.
  • Breastfeeding Mothers: Contraindicated.
  • Children & Elderly: Lower initial doses recommended. Close monitoring is crucial.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Rosuvastatin?

A: The recommended starting dose for adults is typically 5-10 mg once daily, with a maximum of 40 mg. Children’s doses are based on age and condition, ranging from 5-20 mg daily. Elderly patients should start with 5 mg daily.

Q2: What are the common side effects of Rosuvastatin?

A: Common side effects include headache, muscle aches, joint pain, nausea, and constipation.

Q3: How does Rosuvastatin work?

A: Rosuvastatin inhibits HMG-CoA reductase, reducing cholesterol production in the liver and increasing LDL receptor expression, leading to lower LDL cholesterol levels.

Q4: Is Rosuvastatin safe during pregnancy or breastfeeding?

A: No, Rosuvastatin is contraindicated during pregnancy and breastfeeding due to the potential for fetal harm and disruption of infant lipid metabolism.

Q5: What are the serious side effects of Rosuvastatin?

A: Serious but rare side effects include myopathy, rhabdomyolysis, and liver damage.

Q6: What drugs interact with Rosuvastatin?

A: Drugs like cyclosporine, gemfibrozil, some protease inhibitors, antacids, and other cholesterol-lowering medications can interact with rosuvastatin.

Q7: Can I take Rosuvastatin with food?

A: Yes, rosuvastatin can be taken with or without food, at any time of day.

Q8: How long will I need to take Rosuvastatin?

A: Rosuvastatin is typically a long-term medication taken to manage high cholesterol and reduce cardiovascular risk. Your doctor will determine the duration of treatment based on your individual needs.

Q9: What should I do if I miss a dose?

A: Take the missed dose as soon as you remember, unless it is close to the time for your next dose. Do not double the dose to catch up.

Q10: Should patients take precautions when using Rosuvastatin with alcohol?

A: Yes. Patients should limit alcohol consumption while taking rosuvastatin, as it can increase the risk of liver damage.