Atorvastatin – Uses, Side Effects, and Composition

Background

Atorvastatin (Lipitor®), is a lipid-lowering drug included in the statin class of medications. By inhibiting the endogenous production of cholesterol in the liver, statins lower abnormal cholesterol and lipid levels, and ultimately reduce the risk of cardiovascular disease. More specifically, statin medications competitively inhibit the enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) Reductase, which catalyzes the conversion of HMG-CoA to mevalonic acid. This conversion is a critical metabolic reaction involved in the production of several compounds involved in lipid metabolism and transport, including cholesterol, low-density lipoprotein (LDL) (sometimes referred to as “bad cholesterol”), and very-low-density lipoprotein (VLDL). Prescribing statins is considered standard practice for patients following any cardiovascular event, and for people who are at moderate to high risk of developing cardiovascular disease. The evidence supporting statin use, coupled with minimal side effects and long-term benefits, has resulted in wide use of this medication in North America.

Properties and Characteristics of Atorvastatin

Drug class	Statins
Brand Names	Atorvaliq, Caduet, Lipitor, Lypqozet
Synonyms	Atorvastatin, atorvastatina, atorvastatine, atorvastatinum
Molecular Formula	C33H35FN2O5
Molecular Weight	558.6 g/mol
IUPAC Name	(3R,5R)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid
Structural formula of main components
Pure active ingredient	Atorvastatin calcium trihydrate
Appearance	Solid
Melting point	176°C
Solubility	Practically insoluble
Excretion	Mainly eliminated in the bile without enterohepatic recirculation
Storage	Keep container tightly closed in a dry and well-ventilated place. Light sensitive
Available Forms	Tablet, Capsule, Suspension, Powder
Prescription	Prescription is required

What is Lipitor (Atorvastatin) used for?

• Hyperlipidemia
• Hyperlipoproteinemia Type IIa (Elevated LDL)
• Hyperlipoproteinemia Type IIb (Elevated LDL + VLDL)
• Hyperlipoproteinemia Type III (Elevated beta-VLDL + IDL)
• Hyperlipoproteinemia Type IV (Elevated VLDL)
• Homozygous Familial Hypercholesterolemia
• Hypertriglyceridemia
• Prevention of Cardiovascular Disease
• Heterozygous Familial Hypercholesterolemia

What side effects can Atorvastatin cause?

Atorvastatin may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• Diarrhea
• Heartburn
• Gas
• Joint pain
• Forgetfulness or memory loss
• Confusion

Some side effects can be serious. The following symptoms are uncommon, but if you experience any of them, call your doctor or get emergency medical help immediately:

• Muscle pain, tenderness, or weakness
• Lack of energy
• Fever
• Chest pain
• Nausea
• Extreme tiredness
• Weakness
• Unusual bleeding or bruising
• Loss of appetite
• Pain in the upper right part of the stomach
• Flu-like symptoms
• Dark colored urine
• Yellowing of the skin or eyes
• Rash
• Hives
• Itching
• Difficulty breathing or swallowing
• Swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• Hoarseness

Atorvastatin may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

Mechanism of action

Atorvastatin is a statin medication and a competitive inhibitor of the enzyme HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis. It acts primarily in the liver, where decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low-density lipoprotein (LDL) receptors, which increases hepatic uptake of LDL. Atorvastatin also reduces Very-Low-Density Lipoprotein-Cholesterol (VLDL-C), serum triglycerides (TG) and Intermediate Density Lipoproteins (IDL), as well as the number of apolipoprotein B (apo B) containing particles, but increases High-Density Lipoprotein Cholesterol (HDL-C).

In vitro and in vivo animal studies also demonstrate that atorvastatin exerts vasculoprotective effects independent of its lipid-lowering properties, also known as the pleiotropic effects of statins. These effects include improvement in endothelial function, enhanced stability of atherosclerotic plaques, reduced oxidative stress and inflammation, and inhibition of the thrombogenic response. Statins were also found to bind allosterically to β2 integrin function-associated antigen-1 (LFA-1), which plays an essential role in leukocyte trafficking and T cell activation.

Atorvastatin may interact with other medications

Atorvastatin oral tablet can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Examples of drugs that can cause interactions with atorvastatin are listed below.

Antibiotics

Taking atorvastatin with certain antibiotics increases your risk for muscle problems. Examples of these drugs include:

• Clarithromycin
• Erythromycin

Fungal drugs

Taking atorvastatin with certain drugs used to treat fungal infections may cause it to build up in your body. This raises your risk for muscle breakdown. If you need to take these drugs together, your doctor may decrease your dosage of atorvastatin. Examples of these drugs include:

• Itraconazole
• Ketoconazole

Cholesterol-lowering drugs

Taking atorvastatin with other cholesterol-lowering drugs raises your risk for muscle problems. Your doctor may change your dosage of these medications or have you avoid taking them together. Examples of these drugs include:

• Gemfibrozil
• Medications that contain fibrate
• Niacin

Rifampin

Taking rifampin with atorvastatin may lower the amount of atorvastatin in your body. This means that the atorvastatin may not work as well.

HIV drugs

Taking atorvastatin with certain drugs used to treat HIV may cause atorvastatin to build up in your body. This raises your risk for muscle breakdown. If you need to take these drugs together, your doctor may decrease your dosage of atorvastatin. Examples of these drugs include protease inhibitors such as:

• Darunavir
• Fosamprenavir
• Lopinavir
• Ritonavir
• Saquinavir
• Tipranavir
• Digoxin

Taking digoxin with atorvastatin can increase the amount of digoxin in your blood to dangerous levels. If you need to take these drugs together, your doctor will monitor these levels and adjust your medication doses if needed.

Oral birth control pills

Taking atorvastatin with oral birth control pills may increase the levels of oral contraceptive hormones in your blood.

Colchicine

Taking colchicine with atorvastatin raises your risk for muscle breakdown.

Cyclosporine

Taking cyclosporine with atorvastatin raises your risk for muscle breakdown. Your doctor should avoid this combination.

What is the dosage for atorvastatin?

• Lipitor is prescribed once daily.
• The usual starting dose for adults is 10-20 mg per day, and the maximum dose is 80 mg per day. Adults who need more than a 45% reduction in LDL cholesterol may be started at 40 mg daily.
• Pediatric patients should receive 10 mg once daily up to a maximum dose of 20 mg daily.
• Lipitor may be taken with or without food and at any time of day.

What should be done in case of overdose?

Don’t take more atorvastatin oral tablets than your doctor prescribes. Using more than this can lead to serious side effects.

If you accidentally took a double dose of atorvastatin, you may experience side effects. Call your doctor if you have any of the serious side effects listed below.

Symptoms of overdose

Symptoms of atorvastatin overdose may include:

• Muscle pain, tenderness, or weakness
• Diarrhea
• Nausea
• Confusion
• Yellowing of the whites of your eyes or your skin
• Dark colored urine

Precautions

Before taking atorvastatin, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of:

• Liver disease
• Kidney disease
• Alcohol use

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Limit alcoholic beverages. Daily use of alcohol may increase your risk for liver problems, especially when combined with atorvastatin. Ask your doctor or pharmacist for more information.

Older adults may be more sensitive to the side effects of this drug, especially muscle problems.

Pregnancy, breastfeeding and fertility while taking atorvastatin

Pregnancy

Atorvastatin is not recommended during pregnancy. If you become pregnant while taking atorvastatin, stop taking the medicine and tell your doctor.

Talk to your doctor if you are trying to get pregnant. Whether you continue to take atorvastatin or not depends on your reason for taking it. It may be possible to switch to an alternative medicine that is better during pregnancy. Sometimes it may be better to keep taking atorvastatin until you have a positive pregnancy test and then stop.

Breastfeeding

It might be OK to take atorvastatin while breastfeeding, but you might also be advised to stop taking your medicine until you are no longer breastfeeding. Your doctor or pharmacist will help you decide.

It’s not yet known how much atorvastatin passes into breast milk, but it’s likely to be a very small amount. It is unlikely to cause any side effects in your baby, or affect their cholesterol.

If you notice that your baby is not feeding as well as usual, or not putting on weight as you would expect, or if you have any other concerns about your baby, talk to your health visitor, midwife or doctor as soon as possible.

Fertility

There’s no clear evidence to suggest that taking atorvastatin will reduce fertility in either men or women.

However, speak to a pharmacist or your doctor before taking it if you’re trying to get pregnant.