Atorvastatin

Atorvastatin is a medication that belongs to the class of statins, which is used to lower blood cholesterol levels. It is an inhibitor of the enzyme hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase), which plays a key role in the process of cholesterol formation in the body.

Atorvastatin helps to lower the level of "bad" (LDL) cholesterol and triglycerides in the blood, and increase the level of "good" (HDL) cholesterol. This helps reduce the risk of cardiovascular diseases such as myocardial infarction, stroke and angina pectoris.

The drug is usually taken daily in a dose that depends on the severity of hypercholesterolemia and other cardiovascular risk factors. The dosage may be adjusted by a physician depending on the individual needs of the patient.

Indications Atorvastatin

1. Hypercholesterolemia: The drug is used to reduce the level of total and LDL ("bad") cholesterol in the blood in patients with elevated cholesterol.
2. Hypertriglyceridemia: Atorvastatin may be used to lower blood triglyceride levels.
3. Prevention of cardiovascular complications: The medicine is used to reduce the risk of cardiovascular events, such as myocardial infarction and stroke, in patients at high or moderate risk.
4. Angina: Atorvastatin may be used to treat angina pectoris, chest pain caused by inadequate blood supply to the heart muscle.
5. Prevention of recurrent myocardial infarction: In patients who have had a myocardial infarction, atorvastatin may be prescribed to prevent recurrent cardiovascular complications.

Release form

Oral tablets

• Conventional tablets: Atorvastatin is usually available in the form of oral tablets.
• Dosage: Atorvastatin tablets are available in various dosages including 10 mg, 20 mg, 40 mg, and 80 mg.
• Specifications: Tablets may be either film-coated or uncoated. The film coating helps protect the active ingredient from degradation in the gastrointestinal tract and provides more stable absorption.

Pharmacodynamics

1. HMG-CoA reductase inhibition:

   • Atorvastatin inhibits HMG-CoA reductase activity, resulting in decreased cholesterol production in the liver.
   • This mechanism results in decreased levels of total cholesterol, low-density lipoprotein (LDL, or "bad" cholesterol), and triglycerides in the blood.

2. Increase in high-density lipoprotein (HDL) levels:

   • Atorvastatin may also increase high-density lipoprotein (HDL, or "good" cholesterol) levels, which is considered favorable for cardiovascular health.

3. Anti-inflammatory properties:

   • In addition to its primary cholesterol-lowering action, atorvastatin also has anti-inflammatory properties.
   • This may be particularly useful in the treatment and prevention of cardiovascular disease, as inflammation plays a key role in its development.

4. Prevention of cardiovascular disease:

   • Atorvastatin is used to prevent cardiovascular diseases such as coronary heart disease, myocardial infarction and stroke, especially in patients with elevated cholesterol and other cardiovascular risk factors.

Pharmacokinetics

1. Absorption: Atorvastatin is absorbed from the gastrointestinal tract after oral administration. Its absorption is improved when taken with food, but this does not lead to clinically significant changes in the efficacy of the drug.
2. Metabolism: About 70% of atorvastatin is metabolized in the liver by oxidation through the cytochrome P450 enzymatic system, mainly involving CYP3A4 isoenzyme. The main metabolite is the ortho- and para-hydroxylated derivative of atorvastatin, which also has inhibitory properties to hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase), as well as atorvastatin itself.
3. Excretion: Metabolites of atorvastatin are excreted in the feces and to a lesser extent in the urine. Unexcreted atorvastatin is not detectable in the urine.
4. Half-life: The half-life of atorvastatin is about 14 hours for atorvastatin and about 20-30 hours for its active metabolite.

Dosing and administration

Method of application

Atorvastatin is taken orally, usually once a day. The drug can be taken at any time of the day, but it is preferable to take it at the same time each day to maintain a stable level of the drug in the blood. Atorvastatin can be taken with food or on an empty stomach. However, some studies suggest that taking it in the evening may be more effective, given the circadian rhythms of cholesterol synthesis in the body.

Dosage

Atorvastatin dosage may vary depending on the patient's blood cholesterol levels, the presence of comorbidities, and response to treatment. General recommendations are presented below:

• Initial dose: The usual starting dose is 10 mg or 20 mg once daily. Patients at high cardiovascular risk may start at a dose of 40 mg once daily.
• Maintenance dose: The dosage may be adjusted by your doctor depending on the LDL cholesterol level achieved and your overall risk level. The dose may be increased up to a maximum of 80 mg per day.
• Elderly patients: For elderly patients, it is generally recommended to start with a lower dose due to possible increased sensitivity to the drug's action and a greater likelihood of side effects.
• Patients with renal impairment: Dose adjustment may be required in patients with renal impairment, especially if renal function is significantly reduced.

Special Instructions

• Before starting atorvastatin and during treatment, it is recommended to perform tests to monitor blood lipid levels.
• Atorvastatin may interact with other medications, so it is important to notify your doctor of all medications you are taking.
• It is important to eat a diet low in cholesterol and fats and maintain an active lifestyle for best results from treatment.

Use Atorvastatin during pregnancy

Atorvastatin, like other statins, is generally not recommended for use during pregnancy because of potential risks to the developing fetus. Statins can adversely affect fetal development because cholesterol plays a key role in the development of tissues and organs.

Risks of using atorvastatin during pregnancy:

1. Teratogenicity: Animal studies have shown that statins, including atorvastatin, can cause birth defects. Although specific data on the teratogenicity of atorvastatin in humans are limited, the general risk associated with all statins is reason to avoid them during pregnancy.
2. Effect on fetal development: Statins may affect the synthesis of cholesterol, which is necessary for normal fetal development, including steroid hormone synthesis and cell membrane development.

Recommendations:

• Before pregnancy: Women planning pregnancy who are taking atorvastatin are usually advised to stop taking the drug several months before conception.
• During pregnancy: Atorvastatin should be discontinued immediately if a woman becomes aware that she is pregnant during treatment with statins. Your doctor can discuss alternative methods of cholesterol control during pregnancy that are safer for the fetus.
• Consultation with your doctor: It is always important to consult your doctor for individualized advice and to consider all risks and benefits before starting or changing treatment.

Contraindications

1. Hepatic insufficiency: It is not recommended to use atorvastatin in patients with severe hepatic dysfunction.
2. Pregnancy and lactation: Atorvastatin use is contraindicated during pregnancy and lactation due to potential effects on fetal and infant development.
3. Allergic reaction: Patients with known allergies to atorvastatin or other statins should avoid their use.
4. Myopathy: Atorvastatin may cause myopathy (muscle disorders), especially when used concomitantly with other medicines that increase this side effect.
5. Hypothyroidism: In patients with uncontrolled hypothyroidism the use of atorvastatin requires caution.
6. Alcohol dependence: Patients with alcohol dependence may have an increased risk of hepatic impairment when using atorvastatin.
7. Pediatric: The efficacy and safety of atorvastatin in children and adolescents have not been fully established.
8. Use in combination with certain medicines: Atorvastatin may interact with other medicines, including some antibiotics, antimycotics, and cholesterol-lowering drugs, which may increase or decrease its effect.

Side effects Atorvastatin

1. Muscle pain and weakness: This is one of the most common side effects of statins. Patients may experience muscle pain (myalgia) or weakness. In rare cases, this may progress to the development of muscle damage known as myopathy.
2. Increasedcreatine kinase: This is an enzyme that is released into the bloodstream when muscles are damaged. Increased creatine kinase levels may be associated with the development of myopathy.
3. Gastrointestinal Disorders: Includes nausea, vomiting, diarrhea, constipation, or abdominal pain.
4. Increased aminotransferases: These are enzymes that may indicate liver damage. Increased aminotransferases may be a sign of hepatotoxicity, although it is rare.
5. Headache: Headaches or dizziness may occur.
6. Drowsiness: Some patients may experience drowsiness or fatigue.
7. Sleep disorders: May include insomnia or strange dreams.
8. Elevated blood glucose levels: Some patients may have elevated blood sugar levels.
9. Allergic reactions: Include hives, itching, swelling of the lips, face, or throat.
10. Rare: Serious side effects such as the development of rhabdomyolysis (skeletal muscle breakdown) or liver damage may occur.

Overdose

1. Myopathy and rhabdomyolysis:

   • One of the most serious complications of overdose is myopathy (muscle weakness and pain) and rhabdomyolysis (destruction of muscle cells), which can lead to the release of myoglobin into the bloodstream and the development of kidney failure.

2. Hepatotoxicity:

   • Overdose of atorvastatin can cause liver damage, which is manifested by increased levels of liver enzymes (ALT and AST) in the blood.

3. Other unwanted effects:

   • Other possible effects of atorvastatin overdose include headache, nausea, vomiting, diarrhea, somnolence, dizziness, and other symptoms characteristic of HMG-CoA reductase inhibitors.

Interactions with other drugs

1. Cytochrome P450 3A4 (CYP3A4) inhibitors: Drugs such as ketoconazole, itraconazole, clarithromycin, erythromycin, ritonavir, and the fungal drugs graveola and pamaverol may increase the blood concentration of atorvastatin, which increases the risk of side effects such as muscle damage.
2. OATP1B1 transporter inhibitors (organic antiporter 1B1): Drugs such as cyclosporine, verapamil, rifampicin, ritonavir, and some natural products (e.g., grapefruit juice) may increase the blood concentration of atorvastatin by decreasing its clearance.
3. Fibrates: Co-administration of atorvastatin with fibrates such as gemfibrozil and fenofibrate may increase the risk of myopathy and rhabdomyolysis.
4. Aminoglycosides: The use of atorvastatin with aminoglycosides such as gentamicin or amikacin may increase the risk of myopathy and rhabdomyolysis.
5. Anticoagulants: Increased blood levels of atorvastatin may increase the risk of bleeding when used concomitantly with anticoagulants such as warfarin.
6. Antifungal drugs: Fungal inhibitors such as griseofulvin and nystatin may reduce the effectiveness of atorvastatin.