Atorvastatin Calcium - Uses, Mechanism of Action, Side Effects, and Precautions

Overview:

Atorvastatin reduces cholesterol and fatty substances in the blood of kids and teenagers 10 to 17 years of age with familial heterozygous hypercholesterolemia. It is an inherited disorder in which cholesterol cannot be released from the body naturally. It stops the production of cholesterol in the body to reduce the cholesterol that may build up on the arterial walls and obstruct blood flow.

Accumulating cholesterol and fats along the arterial walls is an atherosclerosis method that reduces blood flow and, thus, the oxygen supply to the heart, brain, and other body parts. Reducing the blood level of cholesterol and fats with Atorvastatin has been established to control heart disease, angina, strokes, and heart attacks. Atorvastatin was approved by the Food and Drug Administration (FDA) in the year 2001

Indications and Usage:

Treatment with lipid-altering contents should be only one part of multiple risk element intervention in people at greatly improved hazard for atherosclerotic vascular disease due to hypercholesterolemia. Medication is suggested as an adjunct to a diet plan when the reaction to a diet is limited in saturated fat and cholesterol and additional nonpharmacologic steps alone have been ineffective. In cases with congenital heart disease (CHD) or multiple risk factors for CHD, Atorvastatin can be initiated along with diet.

Prevention of Cardiovascular Disease in Adults - In grown-up cases without clinically obvious coronary heart disease but with numerous hazard elements for coronary heart disease like age, smoking, hypertension, reduced level of HDL-C, or familial history of early coronary heart disease.

Atorvastatin is suggested to -

• Decrease the hazard of myocardial infarction.

• Decrease the hazard of stroke.

• Decrease the hazard for revascularization processes and angina.

In grown-up cases with Type 2 diabetes and without clinically obvious coronary heart disease but with multiple hazard elements for coronary heart disease like Retinopathy, albuminuria, smoking, or hypertension, Atorvastatin is suggested to -

• Decrease the hazard of myocardial infarction.

• Decrease the hazard of stroke.

In grown-up cases with clinically evident Coronary heart disease, Atorvastatin is suggested to -

• Decrease the hazard of non-fatal myocardial infarction.

• Decrease the hazard of fatal and non-fatal stroke.

• Decrease the hazard for revascularization processes.

• Decrease the hazard of hospitalization for CHF.

• Decrease the hazard of angina.

Hyperlipidemia - Atorvastatin is given in cases:

• As an adjunct to diet to decrease raised total cholesterol, LDL (low-density lipoprotein)cholesterol, apo B, and Triglycerides levels and to improve HDL cholesterol in grown-up cases with primary hypercholesterolemia and mixed dyslipidemia.

• As an adjunct to diet for the therapy of grown-up patients with raised serum triglyceride levels. For the therapy of grown-up cases with primary dysbetalipoproteinemia who do not react sufficiently to diet.

• To decrease total cholesterol and LDL cholesterol in cases with homozygous familial hypercholesterolemia as an adjunct to additional lipid-lowering therapies or if such therapies are unavailable.

• As an adjunct to diet to decrease total cholesterol, LDL cholesterol, and apo B (apolipoprotein B) levels in pediatric cases, ten years to 17 years of age, with heterozygous familial hypercholesterolemia. If following a satisfactory test of diet treatment, the subsequent findings are present -

  • - LDL-C remains greater than or equal to 190 mg/dL.

  • - LDL-C remains greater than or equal to 160 mg/dL.

There is a positive familial record of premature cardiovascular disease or more additional other CVD hazard factors present in pediatric cases.

Limitations of Use:

Atorvastatin has not been analyzed in circumstances where the main lipoprotein abnormality is the elevation of chylomicrons.

Dosage and Administration:

Hyperlipidemia and Mixed Dyslipidemia - The suggested initial dosage of Atorvastatin is 10 mg or 20 mg one time daily. Cases that demand a big decrease in LDL that is more than 45 percent may be initiated at 40 mg one time every day. The dosage range of Atorvastatin is 10 mg to 80 mg, once daily.

Atorvastatin can be taken as a single dose at any period of the day and taken with or without food. The initial dosage and maintenance dosage of Atorvastatin should be individualized based on patient factors such as the goal of treatment and reaction. After initiation and titration of Atorvastatin, lipid levels should be examined within two to four weeks, and the dose should be changed.

Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10 Years to 17 Years of Age) - The suggested initial dosage of Atorvastatin is 10 mg daily; the standard dosage range is 10 mg to 20 mg orally one time daily. Dosage should be individualized based on the suggested objective of treatment. Alterations should be created at intervals of four weeks or more.

Homozygous Familial Hypercholesterolemia - The dosage of Atorvastatin in cases with homozygous familial hypercholesterolemia is 10 mg to 80 mg daily. Atorvastatin should be utilized as an adjunct to additional lipid-lowering therapies in these cases or if such therapies are unavailable.

Concomitant Lipid-Lowering Therapy - Atorvastatin may be utilized with bile acid resins. The mixture of HMG-CoA reductase inhibitors and fibrates should be cautiously utilized.

Dosage in Patients With Renal Impairment - Renal disorder does not impact the plasma concentrations nor LDL reduction of Atorvastatin. Thus, dose adjustment in cases with renal dysfunction is not required.

Dosage in Patients Taking Cyclosporine, Clarithromycin, Itraconazole, or Certain Protease Inhibitors - In cases of having Cyclosporine or the HIV (human immunodeficiency virus) protease inhibitor Tipranavir and Ritonavir or the hepatitis C virus protease inhibitor Glecaprevir with Pibrentasvir, treatment with Atorvastatin should be bypassed. In cases with HIV accepting Lopinavir with Ritonavir utilize the most inferior dosage required of Atorvastatin.

In cases accepting Clarithromycin, Itraconazole, Elbasvir with Grazoprevir, or in cases with HIV having a mixture of Saquinavir with Ritonavir, Darunavir with Ritonavir, Fosamprenavir, or Fosamprenavir with Ritonavir, treatment with Atorvastatin should be restricted to 20 mg, and relevant clinical examination is suggested to confirm that the reduced dosage required of Atorvastatin is utilized.

Patients having the HIV protease inhibitor nelfinavir treatment with Atorvastatin should be restricted to 40 mg. When co-prescribing Atorvastatin with additional protease inhibitors, relevant clinical examination is suggested to confirm that the reduced dosage required of Atorvastatin is utilized.

Dosage Forms and Strengths:

Atorvastatin tablets are white-colored, elliptical in shape, film-coated, and obtainable in four strengths. Atorvastatin is available in 10 mg, 20 mg, 40 mg, and 80 mg.

Contraindications:

• Active Liver Disorder may incorporate an undefined constant increase in hepatic transaminase levels.

• Hypersensitivity - It can occur in any ingredient of this medicine.

• Pregnancy.

• Lactation.

Warnings and Precautions:

• Skeletal Muscle - Periodic cases of rhabdomyolysis with acute renal failure due to myoglobinuria have been noted with atorvastatin and with additional medicines in this class. Patients deserve more close monitoring for skeletal muscle outcomes. Atvastatin treatment should be transiently withheld or paused in any case with an acute, serious situation or hazard characteristic predisposing to the evolution of renal failure.

• Cyclosporine, Tipranavir with Ritonavir, Glecaprevir with Pibrentasvir - Atorvastatin should be avoided.

• Clarithromycin, Itraconazole, Saquinavir with Ritonavir, Darunavir with Ritonavir, Fosamprenavir, Fosamprenavir with Ritonavir, Elbasvir with Grazoprevir - Atorvastatin should not be taken more than 20 mg every day.

• Nelfinavir - Atorvastatin should not be taken more than 40 mg daily.

• Lopinavir with Ritonavir, Simeprevir, Fibric acid derivatives, Erythromycin, Azole antifungals, Lipid-modifying dosage of Niacin, Colchicine - Utilized with caution, and most reduced dosage required.

• Atorvastatin treatment should be transiently withheld or stopped in any case with an acute, serious disease representative of myopathy or having a hazard characteristic predisposing to the evolution of renal failure due to rhabdomyolysis.

• Liver Dysfunction - It is suggested that liver enzyme examinations be acquired before starting treatment with Atorvastatin and replicated as clinically suggested. There have been periodic postmarketing notifications of fatal hepatic failure and non-fatal hepatic failure in cases taking statins involving Atorvastatin.

If intense liver injury with clinical manifestations, hyperbilirubinemia, or jaundice happens during therapy with Atorvastatin, immediately interrupt therapy. If an alternate etiology is not seen, do not resume Atorvastatin. Active liver disease or non-explained continued transaminase rise are contraindications to the usage of Atorvastatin. It should be utilized cautiously in cases who take significant amounts of alcohol and have a record of liver disorder.

• Endocrine Function - Increased HbA1c and fasting serum glucose levels have been informed with HMG-CoA reductase inhibitors involving Atorvastatin. Statins impede cholesterol synthesis and may blunt adrenal steroid production and gonadal steroid creation.

• Use in Cases With Recent Stroke or TIA - Based on clinical studies, The incidence of nonfatal hemorrhagic stroke was extremely increased in the Atorvastatin group.

For Patients:

What Is Hypercholesterolemia?

Therapies for hypercholesterolemia possess medicine, a healthy diet, and exercise. It is high quantities of cholesterol in the blood. A blood test detects it, as it has no significant manifestations.

What Is Atorvastatin?

Atorvastatin is a prescription medication that reduces blood cholesterol. It reduces the LDL, which is the bad cholesterol and the triglycerides level in the blood. It can increase HDL, which is good cholesterol. Atorvastatin is for grown-ups and kids over ten years of age whose cholesterol does not reach down sufficiently with exercise and a low-fat diet. Atorvastatin can reduce the hazard of heart attack, stroke, particular kinds of heart surgery, and chest aches in cases with heart conditions or hazard factors like age, smoking habit, elevated blood pressure, reduced HDL, and familial history of heart conditions. Atorvastatin can reduce the hazard of heart attack or stroke in cases with diabetes and hazard characteristics like eye issues, kidney difficulties, smoking, or increased blood pressure. Atorvastatin begins to function in about two weeks.

What Is Cholesterol?

Cholesterol and triglycerides are the fats that are produced in the body. They are even seen in edibles. Certain cholesterol is needed for good health but excessively is not suitable. Cholesterol and triglycerides can obstruct blood vessels. It is specifically significant to reduce cholesterol in case of heart condition, smoking, diabetes or elevated blood pressure, older age, or if there is a familial history of heart disease.

Who Should Not Take Atorvastatin?

• Do not accept Atorvastatin in case of pregnancy or supposed to be pregnant, or are intending to become pregnant. Atorvastatin may hurt the unborn baby. If one gets pregnant, quit Atorvastatin and contact the doctor immediately.

• In the case of breastfeeding, Atorvastatin can pass into the breast milk and may hurt the baby.

• Patients with liver issues must not take the drug.

• Allergy to Atorvastatin or any of its components.

• Atorvastatin dosing has not been documented in kids below ten years of age.

What Should Be Considered Before Taking Atorvastatin?

Inform the doctor if there are -

• Muscle pains or disability.

• Drinking more than two glasses of alcohol every day.

• Diabetes.

• Thyroid issue.

• Kidney issues.

• Certain medications should not be used with Atorvastatin. Inform the doctor about all the current medications, including prescription and non-prescription medicines, vitamins, and herbal products.

• Atorvastatin and particular additional medications can interact, inducing severe side effects.

• Particularly inform the doctor if taking medications for the immune system, cholesterol, infections, heart condition, HIV, or AIDS (acquired immunodeficiency syndrome).

How Should Atorvastatin Be Taken?

• Havevastatin precisely as specified by the doctor. Do not alter the dose or quit Atorvastatin without informing the doctor. They may do blood examinations to review cholesterol levels during therapy with Atorvastatin. The dosage may be altered based on these results.

• Take Atorvastatin daily at any daytime period at about the exact time per day. Atorvastatin can be intaken with food or without food.

• Do not break Atorvastatin tablets before taking them.

• The doctor should initiate the patient on a low-fat diet before delivering Atorvastatin.

• Remain on this low-fat diet while taking Atorvastatin.

• In case of a missed dosage, take it immediately when recalling it. Do not have Atorvastatin if it has been more than 12 hours since the last missed dosage.

• Stay and have the next dose at standard time.

• Do not have two doses of Atorvastatin at the same time.

• In case of an Atorvastatin overdose, contact the doctor or the closest emergency room.

What Should Be Avoided While Taking Atorvastatin?

• Discuss with the doctor before beginning any unused medications. This possesses prescription and nonprescription medications, vitamins, and herbal products.

• Atorvastatin and particular additional medications can interact, inducing severe side effects.

• Do not get pregnant. In case of pregnancy, quit taking Atorvastatin immediately and contact the doctor.

What Are the Side Effects of Atorvastatin?

Atorvastatin can induce severe side effects. These occurred only in a certain number of people. The doctor can observe them. These side effects typically go away if the dosage is reduced or Atorvastatin is stopped.

These severe side effects occur,

• Muscle Problems - Atorvastatin can generate severe muscle problems that can direct to kidney issues involving kidney failure. There is an increased possibility of muscle problems if taking other medications with Atorvastatin.

• Liver Problems - The doctor should do blood examinations to evaluate the liver before beginning Atorvastatin and if there is any manifestation of liver issues while taking Atorvastatin. Contact the doctor immediately in case of the subsequent manifestation of liver issues, tiredness, appetite loss, belly pain, dark amber-stained urine, and yellowing of the skin.

Contact the doctor immediately in case,

• Muscle issues that do not relieve even after the doctor has suggested quitting taking Atorvastatin. The doctor may accomplish additional examinations to analyze the reason for muscle issues.

• Allergic responses like face swelling or throat that may induce breathing difficulty or trouble swallowing demand therapy immediately.

• Nausea and vomiting.

• Dark-colored urine.

• Fatigue.

• In clinical investigations, patients have been informed of the side effects of Atorvastatin, diarrhea, muscle pain and joint pain, and changes in some laboratory blood examinations.

• The subsequent extra side effects have been informed with Atorvastatin, like fatigue, tendon issues, memory loss, and confusion.

• Discuss with a doctor or pharmacist in case of side effects that trouble or that will not go away.

How Is Atorvastatin Stored?

• Store Atorvastatin at room temperature between 68 degrees Fahrenheit to 77 degrees Fahrenheit (20 to 25°C).

• Do not use medication that is out of date or that is no longer needed.

• Keep Atorvastatin and all medications out of the reach of kids. Be certain that if the medication is thrown away, it is out of the reach of kids.

For Doctors

Clinical Pharmacology:

Mechanism of Action

Atorvastatin is a selective, competitive inhibitor of HMG-CoA reductase, the enzyme that transforms 3-hydroxy-3­ methylglutaryl-coenzyme A to mevalonate, a prototype of sterols involving cholesterol. Atorvastatin also decreases LDL production and the LDL particles.

Pharmacodynamics

Atorvastatin, and a few metabolites, are pharmacologically active in humans. The liver is the primary location of the action and the main area of cholesterol production and LDL discharge. Instead of systemic drug concentration, the drug dosage connects more acceptably with LDL reduction.

Pharmacokinetics:

• Absorption - Atorvastatin is rapidly absorbed following oral administration; maximum plasma concentrations appear within one to two hours. The degree of absorption boosts in proportion to the Atorvastatin dose. The absolute bioavailability of Atorvastatin is about 14 percent, and the systemic availability of HMG-CoA reductase inhibitory action is around 30 percent.

• Distribution - Mean volume of distribution of Atorvastatin is around 381 liters. Atorvastatin is greater than or equal to 98 percent bound to plasma proteins. A blood or plasma ratio of around 0.25 suggests poor drug penetration into red blood cells.

• Metabolism - Atorvastatin has considerably metabolized to ortho- and para-hydroxylated products and has various beta-oxidation effects.

• Excretion - Atorvastatin and its metabolites are removed, especially in bile following hepatic and extra-hepatic metabolism; nevertheless, the drug does not arise to experience enterohepatic recirculation.

Drug Interactions:

The hazard of myopathy during therapy with statins is raised with simultaneous administration of fibric acid derivatives, lipid-modifying dosages of niacin, potent CYP 3A4 inhibitors, or cyclosporine.

• Strong Inhibitors of CYP 3A4 - Atorvastatin is metabolized by cytochrome P450 3A4. Simultaneous intake of Atorvastatin with strong inhibitors of CYP 3A4 can directly boost plasma concentrations of Atorvastatin. The degree of interaction relies on the variability of the effect on CYP 3A4.

• Clarithromycin - Atorvastatin AUC has especially improved with simultaneous administration of Atorvastatin 80 mg with Clarithromycin corresponding to Atorvastatin alone.

• Combination of Protease Inhibitors - Atorvastatin AUC was improved with simultaneous drug administration with several protease inhibitors.

• Itraconazole - Atorvastatin AUC (area under the curve) was particularly raised with simultaneous administration of Atorvastatin 40 mg and itraconazole 200mg.

• Grapefruit Juice - Possesses one or more components that inhibit CYP 3A4 and can improve plasma concentrations of Atorvastatin, particularly with increased grapefruit juice consumption.

• Cyclosporine - It is a substrate of hepatic transporters. Atorvastatin-metabolites are substrates of the OATP1B1 transporter. Inhibitors of the OATP1B1 can improve the bioavailability of Atorvastatin. The co-administration with Cyclosporin is not indicated.

• Glecaprevir and Pibrentasvir - Elbasvir and Grazoprevir - Simultaneous intake of Glecaprevir and Pibrentasvir or Elbasvir and Grazoprevir may direct to raised plasma concentrations of Atorvastatin and a raised hazard of Myopathy.

• Gemfibrozil - Due to a raised hazard of myopathy or rhabdomyolysis when HMG-CoA reductase inhibitors are taken along with Gemfibrozil, simultaneous administration of Atorvastatin with Gemfibrozil should be bypassed.

• Other Fibrates - Due to the hazard of myopathy during therapy with HMG-CoA reductase inhibitors, simultaneous administration of other fibrates is improved.

• Niacin - The hazard of skeletal muscle outcomes may be improved when Atorvastatin is utilized together with Niacin; a decrease in Atorvastatin dosage should be evaluated in this setting.

• Rifampin or Other Inducers of Cytochrome P450 3A4 - Simultaneous administration of Atorvastatin with inducers of cytochrome P450 3A4 can direct to inconsistent declines in plasma concentrations of Atorvastatin.

• Digoxin - When multiple doses of Atorvastatin and Digoxin were administered togetherly, constant-state plasma Digoxin concentrations improved.

• Oral Contraceptives - Atorvastatin and an oral contraceptive administered together may increase AUC values for norethindrone and Ethinyl estradiol.

• Colchicine - Chances of myopathy involving rhabdomyolysis have been informed with Atorvastatin taken together with colchicine.

Use in Specific Populations:

• Pregnancy - Atorvastatin is not indicated for usage in pregnant women since safety has not been confirmed, and there is no obvious benefit of lipid-lowering medications during pregnancy. Because HMG-CoA reductase inhibitors reduce cholesterol production and perhaps the production of additional biologically active elements derived from cholesterol, Atorvastatin may induce fetal harm when administered to a pregnant female.

• Lactation - Atorvastatin usage is not indicated during breastfeeding. There is no known data available on the consequences of the drug on breastfed newborns or the consequences of the medication on milk production.

• Females and Males of Reproductive Potential - Atorvastatin may induce fetal harm when taken by a pregnant woman. Inform females of the reproductive possibility of using adequate contraception during therapy with Atorvastatin.

• Pediatric Use - The safeness and efficacy of Atorvastatin have been demonstrated in pediatric patients, ten years to 17 years of age, with HeFH (Heterozygous familial hypercholesterolemia) as an adjunct to maintaining a diet to decrease total cholesterol, LDL-C, and apo B levels when, following an acceptable trial of diet treatment, the following are present -

  • LDL greater than or equal to 190 mg/dL.

  • LDL greater than or equal to 160 mg/dL.

  • Positive family history.

• Hepatic Impairment - Atorvastatin is not used in cases with active liver disease, which may involve not explained constant increase in hepatic transaminase levels.