Lovastatin; Uses, Dosage, Side Effects, Drug Interactions

Lovastatin is a statin drug, used for lowering cholesterol? in those with hypercholesterolemia to reduce the risk of cardiovascular disease. Lovastatin is a naturally occurring compound found in low concentrations in food such as oyster mushrooms, red yeast rice. Lovastatin differs structurally from mevastatin by a single methyl group at the 6’ position. Lovastatin is a prodrug that is activated by in vivo hydrolysis of the lactone ring. It, along with mevastatin, has served as one of the lead compounds for the development of the synthetic compounds used today.

Mechanism of Action of Lovastatin

Lovastatin is structurally similar to the HMG, a substituent of the endogenous substrate of HMG-CoA reductase. Lovastatin is a prodrug that is activated in vivo via hydrolysis of the lactone ring to form the β-hydroxyacid. The hydrolyzed lactone ring mimics the tetrahedral intermediate produced by the reductase allowing the agent to bind to HMG-CoA reductase with 20,000 times greater affinity than its natural substrate. The bicyclic portion of lovastatin binds to the coenzyme A portion of the active site. Lovastatin lowers hepatic cholesterol? synthesis by competitively inhibiting HMG-CoA reductase, the enzyme that catalyzes the rate-limiting step in the cholesterol biosynthesis pathway via the mevalonic acid pathway. Decreased hepatic cholesterol levels cause increased uptake of low-density lipoprotein (LDL) cholesterol and reduce cholesterol levels in the circulation. At therapeutic doses, lovastatin decreases serum LDL cholesterol by 29-32%, increases high-density lipoprotein (HDL) cholesterol by 4.6-7.3%, and decrease triglyceride levels by 2-12%. HDL cholesterol is thought to confer protective effects against CV disease, whereas high LDL and triglyceride levels are associated with higher risk of disease.

or

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), atorvastatin, cerivastatin, fluvastatin, pravastatin, lovastatin, and simvastatin, reduce atherogenesis and cardiovascular morbidity. Besides, there is growing evidence that statins have immunomodulatory activities. Statins downregulate the expression of adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), monocyte chemotactic protein-1 (MAC-1) and lymphocyte? function-associated antigen-1 (LFA-1), on leucocytes and endothelial cells and, through binding to LFA-1, interfere with ICAM-1-LFA-1 interaction, which is crucial for activation of lymphocytes by antigen-presenting cells, ingress of leucocytes into the infection?, or irritation, often causing pain?, swelling?, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation? sites and immunologic cytotoxicity. Statins inhibit the inducible expression of major histocompatibility complex class II in several cell types including macrophages and downregulate the expression of T-helper-1 (Th1) chemokine receptors on T cells, leading further to inhibition of activation of lymphocytes and their infiltration into the inflammation sites. Statins block the induction of inducible nitric oxide synthase and the expression of several proinflammatory cytokines such as tumor necrosis factor-alpha and interferon-gamma in macrophages and possess antioxidant effects. These agents inhibit the proliferation of immunocytes and the activation of natural killer cells.

Indications of Lovastatin

• Hyperlipoproteinemia Type IIa, Elevated LDL
• High cholesterol?
• High cholesterol?, familial heterozygous
• Hyperlipoproteinemia
• Hyperlipoproteinemia Type IIb, Elevated LDL VLDL
• Coronary heart disease
• Dyslipidemias
• Heterozygous familial hypercholesterolemia
• High blood cholesterol? level
• Primary prevention of coronary artery disease
• Primary prevention myocardial infarction?
• Primary prevention unstable angina
• For management as an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels in patients with primary hypercholesterolemia and mixed dyslipidemia. For primary prevention of coronary heart disease and to slow progression of coronary atherosclerosis in patients with coronary heart disease.

Contraindications of Lovastatin

• Uncontrolled epilepsy
• Hemorrhage in the brain
• Severely low blood pressure
• Liver problems
• Rhabdomyolysis
• Recent operation
• Loss of memory
• High blood sugar
• Abnormal liver function tests
• Trauma
• Pregnancy
• A mother who is producing milk and breastfeeding
• Muscle pain? or tenderness? with increase creatine kinase
• Metabolic syndrome X
• Muscle damage due to auotimmunity
• Pregnancy, breast feeding, and liver disease

Dosage? of Lovastatin

Strengths: 10 mg; 20 mg; 40 mg; 60 mg

Hyperlipidemia

Immediate-release formulation

• Initial dose: 20 mg orally once a day with the evening meal.
• Maintenance dose: 10 to 80 mg orally once a day or in 1 or 2 divided doses.

Extended-release formulation

• Initial dose: 20, 40, or 60 mg orally once a day at bedtime. Patients requiring smaller reductions in cholesterol? may start with 10 mg orally at bedtime.
• Maintenance dose: 10 to 60 mg orally given once a day at bedtime.

Pediatric Hypercholesterolemia

Immediate-release

• 10 to 17 years: 10 mg orally once a day

Maintenance

• 10 to 17 years: 10 to 40 mg orally once a day

Side Effects of Lovastatin

The most common

• Nausea and vomiting
• Severe stomach ache
• epigastric pain,
• diarrhoea,
• anorexia,
• flatulence,
• headache,
• dizziness,
• cold symptoms such as runny nose, sneezing, and coughing
• heartburn
• joint pain

 Common

• Nausea and vomiting
• Severe stomach ache
• Severe diarrhea
• Mouth sores
• Vaginal thrush
• Skin rash
• Headache

Rare

• muscle pain, tenderness, or weakness
• lack of energy
• weakness
• fever
• dark colored urine
• jaundice?: yellowing of the skin or eyes
• pain in the upper right part of the stomach
• nausea
• unusual bleeding or bruising
• loss of appetite
• flu-like symptoms
• rash
• hives
• itching
• difficulty breathing or swallowing

Drug Interactions of Lovastatin

Lovastatin may interact with following drugs, supplements & may change the efficacy of drugs

• antacids (e.g., aluminum hydroxide, calcium carbonate, magnesium hydroxide)
• aripiprazole
• “azole” antifungal medications (e.g., itraconazole, ketoconazole)
• birth control pills
• calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
• cancer medications (e.g., daunorubicin, doxorubicin, etoposide, methotrexate, mitotane, paclitaxel, temsirolimus, vinblastine, vincristine)
• carbamazepine
• carvedilol
• cetirizine
• ciprofloxacin
• cyclosporine
• desipramine
• dexamethasone
• estrogens (e.g., conjugated estrogen, estradiol, ethinyl estradiol)
• “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
• haloperidol
• loperamide
• macrolide antibiotics (e.g., azithromycin, erythromycin, clarithromycin)
• metronidazole
• midazolam
• ondansetron
• phenobarbital
• phenytoin
• prazosin
• propranolol
• proton pump inhibitors (PPIs; e.g., lansoprazole, omeprazole, pantoprazole)
• ranitidine
• sertraline
• sildenafil

Pregnancy & Lactation of Lovastatin

FDA Pregnancy Category X

Pregnancy

This medication should not be used during pregnancy. If you become pregnant while taking this medication, stop taking it immediately and call your doctor.

Lactation

It is not known if lovastatin passes into breast milk. If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding.

References