Atorvastatin Sandoz GmbH

Adjunct to diet for reduction of elevated total cholesterol (total-C), LDL-C, Apo B & triglycerides in adults, adolescents & childn ≥10 yr w/ primary hypocholesterolaemia including familial hypercholesterolaemia (heterozygous variant) or combined hyperlipidaemia (corresponding to types IIa & IIb of Fredrickson classification) when response to diet & other nonpharmacological measures is inadequate. Reduction of total-C & LDL-C in adults w/ HoFH as adjunct to other lipid-lowering treatments (eg, LDL apheresis) or if such treatments are unavailable. Prevention of CV events in patients w/o clinical evidence of CV disease who have multiple risk factors for 1st CV event, as adjunct to correction of other risk factors. Reduction of risk for CV disease in patients w/ diabetes w/ moderately decreased estimated eGFR; major CV events including stroke in patients w/ clinically evident CHD & CKD not requiring dialysis. Reduction of rate of GFR decline & progression of CKD in patients w/ clinically evident CHD &/or diabetes w/ microalbuminuria. Adjunct to diet to reduce total-C, LDL-C & Apo B levels in boys & post-menarchal girls 10-17 yr w/ heterozygous familial hypercholesterolemia.

Individualized dose. Usual dose: Initially 10 mg once daily. Dose adjustments should be in ≥4 wk intervals. Max: 80 mg once daily. Primary hypercholesterolaemia & combined hyperlipidaemia 10 mg once daily. Heterozygous familial hypercholesterolaemia Initially 10 mg daily. Adjust dose every 4 wk to 40 mg daily. Thereafter, either dose may be increased to max of 80 mg daily or 40 mg once daily w/ bile acid sequestrant. HoFH 10-80 mg daily. Childn ≥10 yr Hypercholesterolaemia Initially 10 mg daily w/ titration up to 20 mg daily. Patient taking hepatitis C antiviral agents elbasvir/grazoprevir or letermovir Max: 20 mg daily.

May be taken with or without food.

Hypersensitivity. Active liver disease or unexplained persistent elevation of serum transaminases >3x ULN. Patients treated w/ hepatitis C antivirals glecaprevir/pibrentasvir. Women of childbearing potential not using OC. Pregnancy & lactation.

Discontinue treatment in case of symptom aggravation; if clinically significant elevation of CK levels (>5x or >10x ULN) occur, or rhabdomyolysis is diagnosed or suspected; if patient is suspected to develop ILD. Consider treatment discontinuation if muscular symptoms are severe & cause daily discomfort, even if creatine kinase (CK) levels are elevated to ≤5x ULN. Myalgia, myositis & myopathy that may progress to rhabdomyolysis, myoglobinaemia & myoglobinuria which may lead to renal failure; immune-mediated necrotising myopathy. May induce de novo or aggravate pre-existing myasthenia gravis or ocular myasthenia. Patients who consume substantial quantities of alcohol &/or have history of liver disease; w/ prior hemorrhagic stroke or lacunar infarct; pre-disposing factors for rhabdomyolysis. Perform LFTs before treatment initiation & periodically thereafter, especially in patients who develop any signs or symptoms suggestive of liver injury. Monitor patients who develop increased transaminase levels until abnormalities resolve; at risk w/ fasting glucose 5.6-6.9 mmol/L, BMI >30 kg/m², raised triglycerides, HTN. Reduce dose or w/draw treatment if increase in transaminases is >3x ULN persist. Carefully consider potential risk of hemorrhagic stroke before treatment initiation. Measure CK level before starting treatment in renal impairment, hypothyroidism, personal or familial history of hereditary muscular disorders, history of muscular toxicity w/ statin or fibrate, & liver disease &/or where substantial quantities of alcohol are consumed, elderly >70 yr, situations where increase in plasma levels may occur. Remeasure CK levels w/in 5-7 days if significantly elevated at baseline (>5x ULN). Concomitant use w/ medicinal products that may increase plasma conc eg, potent inhibitors of CYP3A4 or transport proteins (eg, ciclosporin, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole, letermovir & HIV PIs including ritonavir, lopinavir, atazanavir, indinavir, darunavir, tipranavir/ritonavir); gemfibrozil & other fibric acid derivatives, antivirals for HCV treatment (eg, boceprevir, telaprevir, elbasvir/grazoprevir, ledipasvir/sofosbuvir), erythromycin, niacin or ezetimibe. Not to be co-administered w/ systemic formulations of fusidic acid or w/in 7 days of stopping fusidic acid treatment. Not recommended in patients taking letermovir co-administered w/ ciclosporin. Not to be taken by patients w/ rare hereditary problems of galactose intolerance, Lapp lactose deficiency or glucose-galactose malabsorption. Hepatic impairment. Women of child-bearing potential should use appropriate contraceptive measures during treatment. Not to be used in women who are pregnant, trying to become pregnant or suspect they are pregnant. Suspend treatment for the duration of pregnancy or until it has been determined that the woman is not pregnant. Not to breastfeed their infants. Childn 6-10 yr; not indicated in <10 yr.

Nasopharyngitis; allergic reactions; hyperglycaemia; headache; pharyngolaryngeal pain, epistaxis; constipation, flatulence, dyspepsia, nausea, diarrhoea; myalgia, arthralgia, pain in extremity, muscle spasms, joint swelling, back pain; abnormal LFT, increased blood creatine kinase. Dermatitis bullous including erythema multiforme, SJS, TEN.

Increased plasma conc & risk of myopathy w/ CYP3A4 or transport proteins inhibitors; moderate CYP3A4 inhibitors (eg, erythromycin, diltiazem, verapamil & fluconazole). Increased risk of myopathy w/ other medicinal products that have potential to induce myopathy eg, fibric acid derivates & ezetimibe; erythromycin. Increased conc w/ potent CYP3A4 inhibitors eg, ciclosporin, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole, some antivirals used in HCV treatment (eg, elbasvir/grazoprevir) & HIV PIs including ritonavir, lopinavir, atazanavir, indinavir, darunavir. Increased exposure w/ amiodarone & verapamil. Reduced plasma conc w/ CYP450 3A inducers (eg, efavirenz, rifampin, St. John's wort). Increased systemic exposure w/ transport proteins inhibitors eg, ciclosporin & letermovir; OATP1B1/1B3, P-gp & BCRP. Increased risk of muscle-related events including rhabdomyolysis w/ fibric acid derivatives, ezetimibe & fusidic acid. Decreased plasma conc w/ colestipol. Myopathy may occur w/ colchicine. May slightly increase conc of digoxin. Increased plasma conc of norethindrone & ethinyl oestradiol. May cause small decrease in prothrombin time w/ warfarin. Not recommended in concomitant use w/ grapefruit juice.

Dyslipidaemic Agents

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

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