CRESTOR Dosage & Rx Info | Uses, Side Effects

Crestor Generic Name & Formulations

Legal Class

General Description

Rosuvastatin (as calcium) 5mg, 10mg, 20mg, 40mg; tabs.

Pharmacological Class

HMG-CoA reductase inhibitor.

How Supplied

Tabs 5mg, 10mg, 20mg—90; 40mg—30

Manufacturer

AstraZeneca Pharmaceuticals

Generic Availability

YES

Mechanism of Action

Crestor, a selective and competitive inhibitor of HMG-CoA reductase, has been shown to have a high uptake into, and selectivity for, action in the liver, the target for cholesterol lowering. It produces lipid-modifying effects in 2 ways: 1) increases the number of hepatic LDL receptors on the cell-surface to enhance uptake and catabolism of LDL; and 2) inhibits hepatic synthesis of VLDL, which reduces the total number of VLDL and LDL particles.

Crestor Indications

Indications

To reduce risk of MI, stroke, or arterial revascularization procedures in adults without established CHD who are at increased risk of CVD based on age, hsCRP ≥2mg/L, and at least one additional CV risk factor. As an adjunct to diet to reduce LDL-C and slow the progression of atherosclerosis in adults. As an adjunct to diet to reduce LDL-C: in adults with primary hyperlipidemia; or in adults and children aged ≥8yrs with heterozygous familial hypercholesterolemia (HeFH). As an adjunct to other LDL-C-lowering treatments (or alone if such treatments are unavailable), to reduce LDL-C in adults and children aged ≥7yrs with homozygous familial hypercholesterolemia (HoFH). As an adjunct to diet for adults with primary dysbetalipoproteinemia or hypertriglyceridemia.

Crestor Dosage and Administration

Adult

Swallow whole. Take once daily. Dose range 5–40mg. HoFH: initially 20mg. All others: usual starting dose 10–20mg. Use max 40mg dose only if 20mg is insufficient. Asian patients: consider 5mg initially (see full labeling). Concomitant cyclosporine, darolutamide: max 5mg. Concomitant regorafenib, teriflunomide, enasidenib, capmatinib: max 10mg. Concomitant fostamatinib, febuxostat: max 20mg. Concomitant gemfibrozil (if unavoidable), atazanavir/ritonavir, lopinavir/ritonavir, simeprevir, dasabuvir/ombitasvir/paritaprevir/ritonavir, elbasvir/grazoprevir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir: initiate at 5mg; max 10mg. Concomitant tafamidis (if unavoidable): initiate at 5mg; max 20mg. Severe renal impairment (CrCl <30mL/min) not on hemodialysis: initially 5mg; max 10mg.

Children

HeFH: <8yrs: not established. 8–<10yrs: usual range 5–10mg/day; 10–17yrs: 5–20mg/day. HoFH: <7yrs: not studied. 7–17yrs: 20mg once daily.

Crestor Contraindications

Contraindications

Active liver disease or decompensated cirrhosis.

Crestor Boxed Warnings

Not Applicable

Crestor Warnings/Precautions

Warnings/Precautions

Risk for myopathy and rhabdomyolysis (esp. aged ≥65yrs, uncontrolled hypothyroidism, renal impairment, concomitant use with certain drugs, higher Crestor dose). Discontinue if elevated CK levels or myopathy occur or if myopathy is suspected; withhold if a high predisposition to development of renal failure secondary to rhabdomyolysis (eg, sepsis, shock, severe hypovolemia, major surgery, trauma, uncontrolled epilepsy, or severe metabolic, endocrine, or electrolyte disorders). Discontinue if immune-mediated necrotizing myopathy is suspected. Monitor liver function before starting therapy and as clinically indicated. Discontinue promptly if serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs. History of liver disease or heavy alcohol ingestion. Severe renal impairment. Hypothyroidism (if inadequately treated). Asian patients (see Adult dose). Elderly. Pregnancy: discontinue when recognized. Nursing mothers: not recommended.

Crestor Pharmacokinetics

Absorption

In clinical pharmacology studies in man, peak plasma concentrations of rosuvastatin were reached 3–5 hours following oral dosing. The absolute bioavailability of rosuvastatin is ~20%.

Distribution

Mean volume of distribution at steady-state of rosuvastatin is ~134 liters. Rosuvastatin is 88% bound to plasma proteins, mostly albumin.

Metabolism

Rosuvastatin is not extensively metabolized. The major metabolite is N-desmethyl rosuvastatin, which is formed principally by CYP2C9.

Elimination

Following oral administration, rosuvastatin and its metabolites are primarily excreted in the feces (90%). After an intravenous dose, ~28% of total body clearance was via the renal route, and 72% by the hepatic route. The elimination half-life of rosuvastatin is ~19 hours.

Crestor Interactions

Interactions

See Adult dose. Avoid gemfibrozil, tafamidis, sofosbuvir/velpatasvir/voxilaprevir, ledipasvir/sofosbuvir. Increased risk of myopathy and rhabdomyolysis with niacin (≥1g/day), fenofibrates, cyclosporine, darolutamide, regorafenib, teriflunomide, enasidenib, capmatinib, fostamatinib, febuxostat, atazanavir/ritonavir, lopinavir/ritonavir, simeprevir, dasabuvir/ombitasvir/paritaprevir/ritonavir, elbasvir/grazoprevir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, colchicine; use caution. Monitor INR with warfarin. Caution with drugs that decrease levels or activity of steroid hormones (eg, ketoconazole, spironolactone, cimetidine). Separate dosing of aluminum/magnesium hydroxide combination antacids (give ≥2hrs after rosuvastatin).

Crestor Adverse Reactions

Adverse Reactions

Headache, myalgia, abdominal pain, asthenia, nausea; myopathy, rhabdomyolysis with renal dysfunction, elevated liver enzymes, proteinuria and hematuria (consider dose reduction if persistent), increased HbA1c and fasting serum glucose, rare: cognitive impairment, hepatic failure.

Crestor Clinical Trials

See Literature

Crestor Note