ROSUVASTATIN CALCIUM (rosuvastatin calcium)

There are 4 contraindications. Absolute contraindication.

Contraindication List
Child-pugh class B hepatic impairment
Child-pugh class C hepatic impairment
Hepatic failure
Lactation

There are 11 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Acute renal failure
Alcohol use disorder
Child-pugh class A hepatic impairment
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Disease of liver
Immune-mediated necrotizing myopathy
Intracerebral hemorrhage
Myopathy with CK elevation
Pregnancy
Rhabdomyolysis

There are 8 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Dehydration
Hematuria
Hyperglycemia
Kidney disease with likely reduction in glomerular filtration rate (GFr)
Memory impairment
Myasthenia gravis
Proteinuria
Untreated hypothyroidism

There are 23 severe adverse reactions.

More Frequent	Less Frequent
Myalgia	Diabetes mellitus Increased alanine transaminase Increased aspartate transaminase

Rare/Very Rare
Abnormal hepatic function tests Angioedema Depression DRESS syndrome Eaton-lambert syndrome Hepatic failure Hepatitis Hypersensitivity drug reaction Immune-mediated necrotizing myopathy Interstitial lung disease Jaundice Myopathy Myositis Ocular myasthenia Pancreatitis Proteinuria Rhabdomyolysis Thrombocytopenic disorder Urticaria

There are 21 less severe adverse reactions.

More Frequent	Less Frequent
Acute abdominal pain General weakness Headache disorder Nausea	Arthralgia Constipation Dizziness Increased creatine kinase level Skin rash

Rare/Very Rare
Acute cognitive impairment Gynecomastia Hematuria Hyperglycemia Insomnia Lichenoid keratosis Memory impairment Muscle weakness Nightmares Peripheral neuropathy Pruritus of skin Sleep disorder

All statins were previously contraindicated in pregnant women because the fetal risk with these drugs was thought to outweigh any possible benefit. This determination was based on several factors including safety signals from animal data. In addition, congenital anomalies including severe CNS defects and unilateral limb deficiencies were reported in a case series of pregnant women who were exposed to a lipophilic statin (rosuvastatin is a hydrophilic statin) during the first trimester.

Because statins decrease synthesis of cholesterol and possibly other products of the cholesterol biosynthetic pathway, there is also a concern that these drugs can potentially cause fetal harm. More recent data from case series and observational cohort studies have not shown evidence of an increased risk of major birth defects with statin use during pregnancy, and this was observed after controlling for potential confounders such as maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use. The overall evidence from animal studies suggests limited potential for statins to cause malformations or other adverse fetal effects.

While an increased risk of miscarriage has been reported in pregnant women exposed to statins, it is not clear whether this effect is related to the drugs or to other confounding factors. FDA conducted a comprehensive review of all available clinical and nonclinical data related to statin use in pregnant women and concluded that the totality of evidence suggests that there is limited potential for statins to cause malformations and other adverse embryofetal effects. Because statins may prevent serious or potentially fatal cardiovascular events in certain high-risk patients who are pregnant, FDA has requested that the contraindication in pregnant women be removed from the prescribing information for all statins.

While FDA still advises that most pregnant patients discontinue statins because of the possibility of fetal harm, there may be some patients (e.g., those with homozygous familial hypercholesterolemia (HoFH) or established cardiovascular disease) in whom continued therapy may be beneficial; therefore, decisions should be individualized based on the patient's risks versus benefits. Patients who become pregnant or suspect that they are pregnant while receiving a statin should notify their clinician who can advise them on the appropriate course of action.

Limited data indicate that rosuvastatin is distributed into human milk; however, the effects of the drug on breast-fed infants or milk production are not known. Because of the potential for serious adverse reactions from rosuvastatin in nursing infants, the drug is not recommended in nursing women. Women who require rosuvastatin therapy should not breast-feed their infants. Many patients can stop statin therapy temporarily until breast-feeding is complete; patients who require ongoing statin treatment should not breast-feed and should use alternatives such as infant formula.

Of the total number of patients receiving rosuvastatin in clinical studies, 31% were 65 years of age or older, and 6.8% were 75 years of age or older. Although no overall differences in efficacy or safety were observed between geriatric and younger patients, and other clinical experience has not revealed age-related differences in response, the possibility that some geriatric patients may exhibit increased sensitivity to the drug cannot be ruled out.

Advanced age (>=65 years) is a risk factor for rosuvastatin-associated myopathy and rhabdomyolysis. There are no differences in plasma concentrations of rosuvastatin between geriatric (65 years of age or older) and younger patients. Because patients older than 75 years of age may have a higher risk of adverse effects and lower adherence to therapy, the expected benefits versus adverse effects should be considered before initiating statin therapy in this population. Monitor geriatric patients for development of myopathy.