Atorvin

ATORVIN 10: White, elliptical, biconvex film coated tablet with engraved 10 on one side and plain on the other.
Each film-coated tablet contains Atorvastatin calcium eq. to Atorvastatin 10 mg.
ATORVIN 20: White, elliptical, biconvex film coated tablet with engraved 20 on one side and plain on the other.
Each film-coated tablet contains Atorvastatin calcium eq. to Atorvastatin 20 mg.
ATORVIN 40: White, elliptical, biconvex film coated tablet with engraved 40 on one side and plain on the other.
Each film-coated tablet contains Atorvastatin calcium eq. to Atorvastatin 40 mg.

Pharmacology: Pharmacodynamics: Atorvastatin inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis (reduces the production of mevalonic acid from HMG-CoA); this then results in a compensatory increase in the expression of LDL receptors on hepatocyte membranes and a stimulate LDL catabolism.
Pharmacokinetics: Onset of action: Initial change 3-5 days, maximal reduction in plasma cholesterol and triglyceride 2-4 weeks.
Absorption: Rapidly absorbed; extensive first-pass metabolism in GI mucosa and liver.
Distribution: V_d~381 L.
Protein binding: ≥98%.
Metabolism: Hepatic via CYP34; forms active Ortho- and parahydroxylated derivatives and inactive beta-oxidation product.
Bioavailability: ~14% (parent drug) and ~30% (parent drug and equipotent metabolites).
Half-life elimination: Parent drug ~14 hours and metabolites 20-30 hours.
Time to peak, serum: 1-2 hours.
Excretion: Bile, urine (<2% as unchanged drug).

Atorvastatin is indicated as an adjunct to diet for the treatment of patients with elevated total cholesterol (total-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo B), and triglycerides (TG) and to increase high density lipoprotein cholesterol (HDL-C) in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial hypercholesterolemia), combined (mixed) hyperlipidemia (Fredrickson types IIa and IIb), elevated serum TG levels (Fredrickson type IV), and for patients with dysbetalipoproteinemia (Fredrickson types III) who do not respond adequately to diet.
Atorvastatin is also indicated for the reduction of total-C and LDL-C in patients with homozygous familial hypercholesterolemia.
Prevention of cardiovascular complication: In patients without clinically evident cardiovascular disease (CVD), and with or without dyslipidemia, but with multiple risk factors for coronary heart disease (CHD) such as smoking, hypertension, diabetes, low HDL-C, or a family history of early CHD, atorvastatin is indicated to: Reduce the risk of fatal CHD and non-fatal myocardial infarction (MI); Reduce the risk of stroke; Reduce the risk of revascularization procedures and angina pectoris.
In patients with clinically evident CHD, atorvastatin is indicated to: Reduce the risk of non-fatal MI; Reduce the risk of fatal and non-fatal stroke; Reduce the risk for revascularization procedures; Reduce the risk of hospitalization for congestive heart failure (CHF); Reduce the risk of angina.
Chronic kidney disease (CKD): In patients with diabetes with moderately decreased estimated glomerular filtration rate (eGFR), atorvastatin is indicated to reduce the risk for CVD.
In patients with clinically evident CHD and CKD not requiring dialysis, atorvastatin is indicated to reduce the risk of major cardiovascular events including stroke.
In patients with clinically evident CHD and/or diabetes with microalbuminuria, atorvastatin is indicated to reduce the rate of GFR decline and progression of CKD.
Pediatric patients (10-17 years of age): Atorvastatin is indicated as an adjunct to diet to reduce total-C, LDL-C, and apo B levels in boys and post-menarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia if, after an adequate trial of diet therapy, the following findings are present: LDL-C remains ≥190 mg/dl or LDL-C remains ≥160 mg/dl and there is a positive family history of premature CVD or two or more other CVD risk factors are present in the pediatric patient.

May be taken at any time of the day with or without food.
Adult & Geriatric: Primary prevention: Dose should be individualized according to baseline LDL-cholesterol and patient response; adjustment should be made at intervals of 2 to 4 weeks (4 weeks in pediatric).
Hypercholesterolemia (heterozygous familial, nonfamilial and mixed hyperlipidemia (Fredrickson type IIa and IIb): initial 10-20 mg once daily; patients requiring >45% reduction in LDL-C may be started at 40 mg once daily; range 10-80 mg once daily.
Homozygous familial hypercholesterolemia: 10-80 mg once daily.
ACC/AHA blood cholesterol guideline recommendations: adult >21 years: Primary prevention: LDL-C ≥190 mg/dL: high intensity therapy 80 mg once daily; if unstable to tolerate, may reduce dose to 40 mg once daily.
Type 1 or 2 diabetes, age 40-75 years: moderate intensity therapy: 10-20 mg once daily.
Type 1 or 2 diabetes, age 40-75 years and an estimated 10-year ASCVD risk ≥7.5%: high intensity statin therapy 80 mg once daily.
Age 40-75 years and an estimated 10-year ASCVD risk ≥7.5%: moderate to high intensity statin therapy 10-80 mg once daily.
Secondary prevention: Patient has ASCVD (e.g. Coronary heart disease, stroke/TIA or peripheral arterial disease) and: Age ≤75 years: high intensity therapy 80 mg once daily; if unable to tolerate, may reduce dose to 40 mg once daily.
Age >75 years or not a candidate for high intensity statin therapy: moderate intensity therapy 10-20 once daily.
Pediatric: 10-17 years (females postmenarche) for HeFH: Initial 10 mg once daily (max dose 20 mg once daily).
Dosage adjustment for atorvastatin with concomitant medications: Boceprevir, nelfinavir: use lowest effective atorvastatin dose (not to exceed 40 mg daily).
Clarithromycin, itraconazole, fosamprenavir, ritonavir (plus darunavir, fosamprenavir or saquinavir): use lowest effective atorvastatin dose (not to exceed 20 mg daily).
Lomitapide: consider atorvastatin dose reduction.
Renal impairment: No dosage adjustment necessary.
Hepatic impairment: Contraindicated in active liver disease or in patients with unexplained persistent elevations of serum transaminases.

Mild to moderate toxicity: Overdose effects are anticipated to be an extension of adverse effects observed following therapeutic doses.
Treatment is symptomatic and supportive. Correct any significant fluid and/or electrolyte abnormalities in patients with vomiting or diarrhea.
Severe toxicity is not expected, unless a coingestant is present.
Treatment is symptomatic and supportive.

Hypersensitivity to atorvastatin or any component of the formulation.
Active liver disease.
Unexplained persistent elevation of serum transaminases.
Pregnancy or women who may become pregnant.
Breast-feeding.

Based on the notification of the Ministry of Public Health: Do not use the drug in pregnant and breast-feeding women.
Do not use the drug in patients with liver disease.
If there is myalgia at calf, back or whole body, stop taking drug and consult physician.
Liver function tests should be performed before taking drug 6 and 12 weeks after taking drug. For patients who routinely use the drug, liver function tests should be performed every 6 months or as recommended by a physician. If the transaminase level is greater than three times of upper normal limit, stop taking drug and consult physician.
Use with caution with digoxin, warfarin because the level of these drugs in blood may be high and become dangerous.
The risk of myopathy of rhabdomyolysis will increase when administer the drug with other following drugs, e.g., azole antifungal such as ketoconazole, itraconazole, macrolides such as erythromycin, clarithromycin; HIV protease inhibitors such as indinavir, ritonavir, nelfinavir, saquinavir; verapamil, diltiazem, gemfibrozil, nicotinic acid, cyclosporine, amiodarone.
The risk of rhabdomyolysis will increase under the following conditions, e.g., use at high dose, the elderly; patients with hepatic or renal insufficiency, alcoholism, patients with hypothyroidism.
Caution should be exercised when taking this drug with colchicine especially in the elderly or patients with renal insufficiency because there is a risk of myopathy or rhabdomyolysis.
The use of this drug may increase the risk of increasing in blood sugar level.

Secondary caused of hyperlipidemia should be ruled out prior to therapy that has not been studied when the primary lipid abnormality is chylomicron elevation (Fredrickson types I and V).
Liver enzyme tests should be obtained at baseline and as clinically indicated and if signs/symptoms of liver injury occur. Patients should be monitored closely. Use with caution in patients who consume large amounts of ethanol or have a history of liver disease. Use is contraindicated in patients with active liver disease or unexplained persistent elevations of serum transaminase.
Use long-term high dose atorvastatin (80 mg/day) with caution in patients with prior stroke or TIA may be at increased risk for hemorrhagic stroke.
Rhabdomyolysis with acute renal failure secondary to myoglobinuria and/or myopathy has occurred. Risk is dose related and is increased with concurrent use of lipid lowering agent which may cause rhabdomyolysis (fibric acid derivatives or niacin at dose ≥1 g/day) or strong CYP3A4 inhibitors (eg. clarithromycin, itraconazole, and protease inhibitor), cyclosporine. Ensure patient is on the lowest effective atorvastatin dose.
Do not use with cyclosporine, gemfibrozil, tipranavir plus ritonavir and glecaprevir/pibrentasvir.
Discontinue in any patient in which CPK levels are markedly elevated (≥10 times ULN) or if myopathy is suspected/diagnosis.
Discontinue for elective major surgery experiencing and acute or serious condition predisposing to renal failure (eg. sepsis, hypotension, trauma, uncontrolled seizures).
Based on current research, HMG-CoA reductase inhibitor should be continued in perioperative period.
Use in the Elderly: Use with caution in patients with advanced age (65 years and older), these patients are predisposed to myopathy.

Pregnancy Risk Factor X.
Studies in animals and pregnant women have shown evidence of fetal abnormalities.
Cholesterol biosynthesis may be important in fetal development and serum cholesterol and triglyceride increase normally during pregnancy.
Use is contraindicated in women who are or may become pregnant.
It is not known if atorvastatin is excreted into breast milk. Due to the potential for serious adverse reactions in nursing infant, use while breast-feeding is contraindicated.

Cardiovascular: Hemorrhagic stroke.
Central nervous system: Insomnia.
Endocrine and metabolic: Diabetes mellitus.
Gastrointestinal: Diarrhea, dyspepsia, nausea.
Genitourinary: Cystitis, urinary tract infection.
Hepatic: Increased serum transaminases.
Neuromuscular & skeletal: Arthralgia, limb pain, myalgia, muscle spasm, musculoskeletal pain.
Respiratory: Nasopharyngitis, pharyngolaryngeal pain.
Rare but important or life-threatening: Abdominal pain, abnormal hepatic function test, alopecia, anaphylaxis, anemia, angioedema, anorexia, cholestasis, cholestatic jaundice, cognitive dysfunction (reversible), confusion (reversible), depression, elevated glycosylated hemoglobin (HbA_1c), epistaxis, eructation, erythema multiforme, gynecomastia, hematuria, hepatic failure, hepatitis, hyperglycemia, hypoesthesia, increased creatinine phosphokinase, increased serum alkaline phosphatase, increase serum glucose, jaundice, joint swelling, muscle fatigue, myasthenia, myopathy, myositis, neck stiffness, nightmares, pancreatitis, paresthesia, peripheral edema, peripheral neuropathy, rhabdomyolysis, rupture of tendon, Stevens-Johnson syndrome, thrombocytopenia, toxic epidermal necrolysis.

Avoid concomitant use of atorvastatin with, conivaptan, cyclosporine (systemic), fusidic acid (systemic), gemfibrozil, idelalisib, pazopanib, posaconazole, red rice yeast, telaprevir, tipranavir.
Atorvastatin may increase levels/effects aliskiren, aripiprazole, cimetidine, daptomycin, digoxin, diltiazem, dofetilide, filbanserin, hydrocodone, ketoconazole (systemic), lomitapide, midazolam, nimodipine, pazopanib, pimozide, repaglinide, spironolactone, trabectedin, verapamil.
The levels/effects of atorvastatin may be increased by acipimox, amiodarone, aprepitant, asunaprevir, azithromycin (systemic), bezafibrate, boceprevir, ciprofibrate, clarithromycin, cobicistat, colchicine, conivaptan, cyclosporine (systemic), CYP3A4 inhibitors (moderate/strong), cyproterone, danazol, dasatinib, diltiazem, dronedarone, elbasvir, eltrombopag, erythromycin (systemic), fenofibrate and derivatives, fluconazole, fosaprepitant, fusidic acid (systemic), gemfibrozil, grapefruit juice, idelalisib, itraconazole, ivacaftor, ketoconazole (systemic), mifepristone, netupitant, niacin, niacinamide, ombitasvir, paritaprevir, ritonavir, dasabuvir, palbociclib, P-glycoprotein/ABCB1 inhibitors, posaconazole, protease inhibitors, quinine, raltegravir, ranolazine, red yeast rice, rupatadine, simeprevir, stiripentol, telaprevir, telithromycin, teriflunomide, tipranavir, verapamil, voriconazole.
Atorvastatin may decrease levels/effects of dabigatran etexilate, lanthanum.
The levels/effects of atorvastatin may be decreased by antacid, bexarotene (systemic), bile acid sequestrants, bosentan, CYP3A4 inducers (moderate/strong), dabrafenib, deferasirox, efavirenz, etravirine, fosphenytoin, mitotane, phenytoin, rifamycin derivatives, siltuximab, St. John's wort, tocilizumab.
Atorvastatin serum concentrations may be increased by grapefruit juice; avoid concurrent intake of large quantities of grapefruit juice (>1 quart/day).

Store at below 30°C.

Dyslipidaemic Agents

C10AA05 - atorvastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.

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