ATORVASTATIN CALCIUM (atorvastatin calcium)

There are 2 contraindications. Absolute contraindication.

Contraindication List
Hepatic failure
Lactation

There are 9 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

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

There are 5 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

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

There are 25 severe adverse reactions.

More Frequent	Less Frequent
Arthralgia	Muscle spasm Myalgia

Rare/Very Rare

Abnormal hepatic function tests Anaphylaxis Angioedema Cholestasis Erythema multiforme Hepatic failure Hepatitis Immune-mediated necrotizing myopathy Increased alanine transaminase Increased aspartate transaminase Interstitial lung disease Muscle weakness Myasthenia gravis Myopathy Myositis Neck stiffness Pancreatitis Peripheral neuropathy Rhabdomyolysis Stevens-johnson syndrome Tendon rupture Toxic epidermal necrolysis

There are 31 less severe adverse reactions.

More Frequent	Less Frequent
Diarrhea Dyspepsia Pain Pharyngitis Urinary tract infection	Dizziness Insomnia Musculoskeletal pain Nausea Skin rash

Rare/Very Rare
Acute abdominal pain Acute cognitive impairment Blurred vision Depression Dysgeusia Epistaxis Eructation Fatigue Fever Flatulence Hyperglycemia Joint stiffness Malaise Memory impairment Nightmares Ocular myasthenia Paresthesia Sterile pyuria Tinnitus Urticaria Weight gain

All statins were previously contraindicated in pregnant females 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. Increased post-implantation loss occurred in rats and rabbits at maternally toxic doses of 300- and 50- or 100 mg/kg per day, respectively; decreased fetal body weight was observed at 300- and 100 mg/kg per day, respectively.

Decreased survival at birth, postnatal day 4, weaning, and post-weaning in pups, decreased pup body weight through postnatal day 21 and 91, and pup developmental delays were observed when pregnant and lactating rats received 100- or 225 mg/kg per day (a maternally toxic dose), doses corresponding to 6- and 22-times the human exposure at the maximum recommended human dose, based on AUC. In addition, congenital anomalies including severe CNS defects and unilateral limb deficiencies were reported in a case series of pregnant females 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 females 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 of 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.

Atorvastatin is distributed into milk in rats. It is not known whether atorvastatin is distributed into human milk; however, the drug is probably distributed into human milk because a small amount of another statin is distributed into human milk. Because of the potential for serious adverse reactions from atorvastatin in nursing infants, the drug is not recommended in nursing females.

Females who require atorvastatin 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 atorvastatin in clinical studies, 40% were 65 years of age or older, and 7% were 75 years of age or older. No overall differences in efficacy or safety were observed between geriatric and younger patients. Data from a pharmacokinetic study indicate that peak plasma concentration and AUC of atorvastatin were 40 or 30% higher, respectively, in geriatric individuals (65 years of age or older) compared with younger adults.

Because advanced age (65 years and older) is a predisposing factor for myopathy, including rhabdomyolysis, atorvastatin should be used with caution in geriatric patients. The manufacturer recommends cautious dosage selection of atorvastatin in geriatric patients, recognizing the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of myopathy. Monitor geriatric patients receiving atorvastatin for the increased risk of myopathy.

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 of statin therapy should be considered before initiating statin therapy in this population. Safety and efficacy of atorvastatin in fixed combination with amlodipine (Caduet(R)) have not been established in geriatric patients.