Rosuvastatin

BRAND NAMES

Crestor: It reduces cholesterol levels for an inherited type of high cholesterol known as heterozygous familial hypercholesterolaemia. Crestor is available as an oral tablet. It comes in four strengths of tablets: 5 mg, 10 mg, 20 mg, and 40 mg.

Ezallor sprinkle: It is available in the form of capsules with the strengths 5 mg, 10 mg, 20 mg, and 40 mg.

Roszet: It is the combination of Ezetimibe and Rosuvastatin with the available strengths 10 mg/5 mg, 10 mg/10 mg, 10 mg/20 mg, 10 mg/40 mg.

MECHANISM OF ACTION

The mechanism of action of rosuvastatin is the inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase. This enzyme slows the production of mevalonic acid from HMG-CoA, which is the rate-limiting step in the synthesis of cholesterol. Moreover, this promotes low-density lipoprotein catabolism and increases the quantity of low-density lipoprotein receptors on hepatocyte membranes. Inhibitors of HMG-CoA reductase also lower high-sensitivity C-reactive protein (CRP) levels. In addition, they have pleiotropic properties such as reduced inflammation at the location of a coronary plaque, improved endothelial function, and inhibition of platelet aggregation.

PHARMACOKINETICS

Absorption

Rosuvastatin's absolute oral bioavailability was found to be at 20%, with absorption predicted to reach 50%, indicating a considerable first-pass effect after oral dosing. Another study in healthy adults found that the maximum plasma concentration (Cmax) of rosuvastatin was 6.06ng/mL, which was reached at a median of 5 hours after oral administration. Cmax and AUC increased roughly equally with dose. Food and overnight vs. morning treatment had no effect on rosuvastatin's AUC. Many statins have been shown to interact with hepatic uptake transporters, resulting in elevated concentrations near their site of action in the liver.

Distribution

Rosuvastatin is initially extracted in the liver, which is where cholesterol is synthesized and LDL-C is cleared. Rosuvastatin has a mean distribution volume of approximately 134 liters at steady state.

Metabolism

Rosuvastatin is not substantially metabolized, as evidenced by the minimal quantity of radiolabeled dosage recovered as a metabolite (10%). Cytochrome P450 (CYP) 2C9 is principally responsible for the production of rosuvastatin's primary metabolite, N-desmethyl rosuvastatin, which has roughly 20-50% of the pharmacological activity of its parent molecule in vitro. However, this metabolic pathway is not considered clinically significant because there were no visible effects on rosuvastatin pharmacokinetics when rosuvastatin was coadministered with fluconazole, a powerful CYP2C9 inhibitor.

Elimination

Rosuvastatin is not substantially metabolized; roughly 10% of a radiolabeled dosage is recovered as a metabolite. Rosuvastatin and its metabolites are mostly eliminated in feces after oral treatment (90%). Following an intravenous dosage, roughly 28% of total body clearance occurred via the renal route and 72% through the hepatic route. Rosuvastatin has an elimination half-life of approximately 19 hours and does not increase with higher doses.

PHARMACODYNAMICS

An artificial, enantiomerically pure anti-lipemic drug is rosuvastatin. It is used to raise HDL-C levels while lowering TG, LDL-C, total cholesterol, and non-HDL-C plasma levels. Elevated blood levels of TG, low HDL-C, and high LDL-C are associated with a higher risk of cardiovascular disease and atherosclerosis. Greater ratios are linked to an increased risk of coronary artery disease. The total cholesterol to HDL-C ratio is a potent predictor of the condition. There's evidence linking lower risk of cardiovascular disease to higher HDL-C levels. Rosuvastatin raises HDL-C and lowers TG and LDL-C levels to reduce the risk of cardiovascular illness and death.

DOSAGE AND ADMINISTRATION

Rosuvastatin is given as a pill or tablet. The capsule can be administered orally or by a nasogastric tube. The oral approach can be used with or without meals, at any time of day, and must be eaten entirely. The capsule shouldn't be crushed or chewed. When opening the capsule, pour the contents into one teaspoon of applesauce and swallow rapidly without chewing.

To administer through a nasogastric tube, open the capsule and empty it into a 60 ml catheter-tipped syringe. The recommended procedure is to add 40 mL of water, reinsert the plunger, and shake the syringe for 15 seconds. Then, attach the syringe to at least a 16 French nasogastric tube and flush it with 20 mL of water. The mixture must be used immediately after preparation.

CONTRAINDICATIONS

• Like with many medications, the patient must stop taking the medication if they are allergic to rosuvastatin or any other ingredient in the formulation. Additional warnings are included below.
• pregnancy (category X pregnancy) 
• Reports of congenital abnormalities exist. 
• nursing while having an active liver illness 
• Unexpected and continuous increases in serum transaminases

DRUG INTERACTIONS

• Rosuvastatin's myopathic action may be enhanced by the following medications: acipimox, bezafibrate, ciprofibrate, colchicine, daptomycin, fenofibrate, fusidic acid, gemfibrozil, niacin, niacinamide, raltegravir, red yeast rice, and rupatadine.
• Antacids, apalutamide, elagolix, and eslicarbazepine can all lower rosuvastatin serum levels.
• This list of drugs can improve the serum concentrations of rosuvastatin: asunaprevir, clopidogrel, cobicistat, cyclosporine, daclatasvir, dasabuvir, dronedarone, elbasvir, eltrombopag, eluxadoline, fostamatinib, glecaprevir, pibrentasvir, grazoprevir, itraconazole, ledipasvir, letermovir, ombitasvir, paritaprevir, ritonavir, osimertinib, protease inhibitors, simeprevir, teriflunomide, velpatasvir, voxilaprevir.

SIDE EFFECTS 

Some common side effects of rosuvastatin include

• Headache
• nausea
• weakness
• Creatinine kinase levels exceeding ten times the upper limit of normal 
• Severe myopathy 
• Rhabdomyolysis occurs when AST or ALT levels exceed three times the upper limit of normal. 
• Renal failure
• constipation
• interstitial cystitis

TOXICITY

Myalgia is the most commonly reported harmful side effect of rosuvastatin. If the patient experiences mild to moderate muscle discomfort, the medicine should be discontinued to rule out other causes of myalgia. If the underlying cause is resolved, the patient can resume the original or lower dose of rosuvastatin; however, if symptoms reappear for the second time, rosuvastatin should be discontinued permanently. Switching to a new statin drug with a lower dose may alleviate muscle pain.

It is known that if severe muscle complaints or weariness arise, the provider should withdraw the medicine and order a creatinine phosphokinase level, blood creatinine, and urinalysis to assess for myoglobinuria.