FLUVASTATIN ER (fluvastatin sodium)

There are 3 contraindications. Absolute contraindication.

Contraindication List
Hepatic failure
Lactation
Rhabdomyolysis

There are 7 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Acute renal failure
Alcohol use disorder
Disease of liver
Immune-mediated necrotizing myopathy
Intracerebral hemorrhage
Myopathy with CK elevation
Pregnancy

There are 3 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Hyperglycemia
Memory impairment
Myasthenia gravis

There are 35 severe adverse reactions.

More Frequent	Less Frequent
Myalgia	Atrial fibrillation

Rare/Very Rare

Abnormal hepatic function tests Anaphylaxis Anemia Angioedema Bullous dermatitis Dermatomyositis Diabetes mellitus Dyspnea Eosinophilia Erythema multiforme Hemolytic anemia Hepatic failure Hepatic necrosis Hepatitis Immune-mediated necrotizing myopathy Interstitial lung disease Jaundice Lupus-like syndrome Myopathy Myositis Obstructive hyperbilirubinemia Ocular myasthenia Ophthalmoplegia Pancreatitis Polymyalgia rheumatica Polymyositis Purpura Rhabdomyolysis Stevens-johnson syndrome Thrombocytopenic disorder Toxic epidermal necrolysis Urinary tract infection Vasculitis

There are 71 less severe adverse reactions.

More Frequent	Less Frequent
Acute abdominal pain Constipation Diarrhea Dizziness Dyspepsia Headache disorder Heartburn Infection Nausea Skin rash Upper respiratory infection	Arthralgia Arthritis Back pain Eczema Fatigue Flatulence Flu-like symptoms Gastritis Palpitations Sinusitis

Rare/Very Rare

Acute cognitive impairment Alopecia Anorexia Biliary calculus Blurred vision Bronchitis Cataracts Chest pain Cholecystitis Cough Cramps Depression Disorder of thyroid gland Dry skin Dyschromia Dysesthesia Dysgeusia Dysuria Edema Erectile dysfunction Facial palsy Fever Flushing General weakness Gynecomastia Hyperglycemia Hypoesthesia Increased urinary frequency Insomnia Libido changes Lichen planus Malaise Memory impairment Muscle spasm Muscle weakness Nail disorders Nightmares Nocturia Paresthesia Peripheral neuropathy Pruritus of skin Rhinitis Skin nodules Skin photosensitivity Symptoms of anxiety Tremor Urticaria Vertigo Vomiting Xerostomia

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. Fluvastatin produced delays in skeletal development in rats at doses of 12 mg/kg daily and in rabbits at doses of 10 mg/kg daily (approximately 2 and 5 times, respectively, the human exposure after a 40-mg dose based on mg/m2 surface area).

Malaligned thoracic vertebrae wereobserved in rats at 36 mg/kg, a dose that produced maternal toxicity. Maternal mortality at or near term and postpartum, as well as fetal and neonatal lethality, were observed in female rats receiving fluvastatin 12 and 24 mg/kg daily during the third trimester of pregnancy. 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 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 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 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.

Fluvastatin is distributed into milk in animals, with a milk-to-plasma ratio of 2:1. Because of the potential for serious adverse reactions from fluvastatin in nursing infants, the drug is contraindicated in nursing women; women who require fluvastatin 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.

Fluvastatin generally is well tolerated in geriatric patients. Fluvastatin exposures were not substantially different between geriatric patients (65 years of age or older) and younger patients. However, because advanced age is a predisposing factor for myopathy, fluvastatin should be used with caution in geriatric 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. Fluvastatin plasma levels are not significantly different in patients > 65 years of age compared to patients 21-49 years of age.