Lipitor 10mg. 20mg. 40mg. 80mg Tablet

Hypercholesterolaemia

LIPITOR is indicated:

• As an adjunct to diet for reduction of elevated total-cholesterol (total-C), LDL-cholesterol (LDL-C), apolipoprotein B and triglycerides (TG) levels and to moderately increase HDL-cholesterol (HDL-C) in patients with primary hypercholesterolaemia (heterozygous familial and non-familial hypercholesterolaemia) and combined/mixed dyslipidaemia.
• To reduce total-C and LDL-C in adult patients with homozygous familial hypercholesterolaemia as an adjunct to other lipid-lowering treatments (e.g. LDL apheresis) or if such treatments are unavailable.

Paediatric patients (10 u2013 17 years of age)

LIPITOR is indicated as an adjunct to diet to reduce total-C, LDL-C, and apolipoprotein B levels in boys and postmenarchal girls, > 10 to 17 years of age, with heterozygous familial hypercholesterolaemia if after an adequate trial of diet therapy, the following findings are present:

• LDL- C remains u2265 4,98 mmol/L (190 mg/dL) or
• LDL- C remains u2265 4,04 mmol/L (160 mg/dL) and:
• There is a positive family history of premature cardiovascular disease, or
• Two or more other cardiovascular disease risk factors are present in the paediatric patient.

Reduction of cardiovascular complications

In patients without clinically evident cardiovascular disease, and with or without dyslipidaemia, but with multiple risk factors for coronary heart disease such as smoking, hypertension, diabetes, low HDL-C, or a family history of early coronary heart disease, LIPITOR is indicated to:

• Reduce the risk of ischaemic cardiovascular and cerebrovascular diseases.

Secondary reduction

Reduction of cardiovascular events in patients with clinically evident coronary heart disease and increased cholesterol levels. Therapy with lipid-lowering medicines should be a component of multiple-risk-factor intervention in individuals at increased risk of atherosclerotic vascular disease due to hypercholesterolaemia. Lipid-altering medicines should be used in addition to a diet restricted in saturated fat and cholesterol only when the response to diet and other non-pharmacological measures has been inadequate. Prior to initiating therapy with LIPITOR, secondary causes for hypercholesterolaemia (e.g. poorly controlled diabetes mellitus, hypothyroidism, nephrotic syndrome, dysproteinaemia, obstructive liver disease, other medicine therapy, and alcoholism) should be excluded, and a lipid profile performed to measure total-C, LDL-C, HDL-C, and TG.

The patient should be placed on a standard cholesterol-lowering diet before receiving LIPITOR and should continue on this diet during treatment with LIPITOR.

Posology

The usual starting dose is 10 mg once a day and should be individualised according to the baseline LDL-C levels, the goal of therapy, and patient response. Adjustment of dosage should only be made after an interval of 4 weeks or more. The maximum recommended daily dose is 80 mg once a day.

Primary hypercholesterolaemia and combined (mixed) hyperlipidaemia

The majority of patients are controlled with 10 mg LIPITOR once a day. A therapeutic response is evident within 2 weeks, and the maximum therapeutic response is usually achieved within 4 weeks. The response is maintained during chronic therapy.

Heterozygous familial hypercholesterolaemia

Patients should be started with LIPITOR 10 mg daily. Doses should be individualised and adjusted every 4 weeks to 40 mg daily. Thereafter, either the dose may be increased to a maximum of 80 mg daily or a bile acid sequestrant may be combined with 40 mg LIPITOR once daily.

Homozygous familial hypercholesterolaemia

In a compassionate-use, uncontrolled study of patients with homozygous familial hypercholesterolaemia, most patients responded to a dose of 80 mg of LIPITOR, with a greater than 15 % reduction in LDL-C (18 % u2013 45 %). The dose of LIPITOR is 10 to 80 mg daily (see section 5.1). LIPITOR should be used as an adjunct to other lipid-lowering treatments (e.g. LDL apheresis) in these patients.

Reduction of cardiovascular complications

The dosage range is 10 to 80 mg once daily.

Special populations

Dosage in patients with renal insufficiency

Renal disease has no influence on the plasma concentrations or on the lipid effects of LIPITOR; thus, no adjustment of dose is required (see section 4.4).

Dosage in patients with hepatic dysfunction

In patients with moderate to severe hepatic dysfunction, the therapeutic response to LIPITOR is unaffected but serum levels of the medicine are greatly increased. In patients with chronic alcoholic liver disease, plasma concentrations of LIPITOR are markedly increased. C max and AUC are each 4-fold greater in patients with mild (Child-Pugh class A) liver disease. C max and AUC are approximately 16-fold and 11-fold increased, respectively, in patients with moderate (Child-Pugh class B) liver disease. Therefore, caution with dosage should be exercised in patients who consume substantial quantities of alcohol and/or have a history of liver disease (see sections 4.3 and 4.4).

Elderly

Efficacy and safety in patients older than 70 years of age using recommended doses are similar to those seen in the general population.

Paediatric population

Paediatric use should only be carried out by medical practitioners experienced in the treatment of paediatric hyperlipidaemia and patients should be re-evaluated on a regular basis to assess progress. No clinically significant effect on growth and sexual maturation was observed in a 3-year study based on the assessment of overall maturation and development, assessment of Tanner Stage, and measurement of height and weight.

Heterozygous familial hypercholesterolaemia in paediatric patients (> 10 u2013 17 years of age)

Experience in paediatrics is limited to a small number of patients (age 10 u2013 17 years) with severe dyslipidaemias, such as familial hypercholesterolaemia. Patients should be started with LIPITOR 10 mg daily; the maximum recommended dose is 20 mg/day.

There are limited safety and efficacy data available in children with Heterozygous Familial Hypercholesterolemia between 6 to 10 years of age derived from open-label studies. LIPITOR is not indicated in the treatment of patients below the age of 10 years.

Method of administration

For oral use. Each daily dose of LIPITOR is given all at once and may be given at any time of day with or without food.

• Hypersensitivity to atorvastatin or to any of the excipients of LIPITOR (listed in section 6.1).
• Active liver disease or unexplained persistent elevations of serum transaminases exceeding three times the upper limit of normal (see section 4.4).
• Patients treated with the hepatitis C antivirals glecaprevir/pibrentasvir.
• Concomitant use with rifampicin, diltiazem and grapefruit juice (see section 4.5).
• Patients with moderate (Child-Pugh class B) and severe (Child-Pugh class C) liver impairment.
• Pregnancy and lactation and women of childbearing potential not using adequate contraceptive measures (see section 4.6).

Liver effects

Persistent elevations (> 3 times the upper limit of normal (ULN) which occurred on 2 or more occasions) in serum transaminases occurred in 0,7 % of patients who received LIPITOR in clinical trials. The incidence of these abnormalities was 0,2 %, 0,2 %, 0,6 % and 2,3 % for 10, 20, 40 and 80 mg, respectively. Liver function tests should be performed before the initiation of treatment with LIPITOR and repeated as clinically indicated. Patients who develop increased serum transaminase levels should be monitored until the abnormality(ies) resolve. Should an increase in serum transaminases of greater than 3 times the ULN persist, withdrawal of LIPITOR is recommended (see section 4.3). If serious liver injury with clinical symptoms and/or hyperbilirubinaemia or jaundice occurs during treatment with LIPITOR, promptly interrupt therapy. If an alternate aetiology is not found, do not restart LIPITOR.

LIPITOR should be used with caution in patients who consume substantial quantities of alcohol and/or have a history of liver disease. Active liver disease or unexplained persistent serum transaminase elevations are contraindications to the use of LIPITOR (see section 4.3).

Skeletal muscle effects

Myalgia has been reported in patients treated with LIPITOR (see section 4.8). Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values greater than 10 times the upper limit of normal, should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CPK. Patients should be advised to report promptly any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. LIPITOR therapy should be discontinued if markedly elevated CPK levels occur, or myopathy is diagnosed or suspected.

The risk of myopathy during treatment with LIPITOR is increased with concurrent administration of immunosuppressive medicines, including ciclosporin, fibric acid derivatives, nicotinic acid, azole antifungals, erythromycin, clarithromycin, colchicine, letermovir, the hepatitis C protease inhibitors telaprevir, boceprevir, glecaprevir/pibrentasvir, elbasvir/grazoprevir, ledipasvir/sofosbuvir and simeprevir and combinations of HIV protease inhibitors, including saquinavir plus ritonavir, lopinavir plus ritonavir, tipranavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, and fosamprenavir plus ritonavir and cytochrome P450/transporter inhibitors. Medical practitioners considering combined therapy with these medicines should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs and symptoms of muscle pain, tenderness, or weakness, particularly during the initial months of therapy and during any periods of upward dosage titration of either medicine. When patients are receiving medicines that increase the plasma concentration of LIPITOR, a lower dose of LIPITOR is recommended (see section 4.5).

The risk of myopathy and/or rhabdomyolysis may be increased by concomitant administration of HMG- CoA reductase inhibitors (e.g. atorvastatin) and daptomycin (see section 4.5). Consideration should be given to temporarily suspend LIPITOR in patients taking daptomycin unless the benefits of concomitant administration outweigh the risk. If co-administration cannot be avoided, CK levels should be measured 2 u2013 3 times per week and patients should be closely monitored for any signs or symptoms that might represent myopathy.

Muscle-related adverse events have been reported with concomitant administration of LIPITOR and fusidic acid. In patients where the use of systemic fusidic acid is considered essential, LIPITOR treatment should be discontinued throughout the duration of fusidic acid treatment (see section 4.5). The patient should be advised to seek medical advice immediately if they experience any symptoms of muscle weakness, pain or tenderness. LIPITOR therapy may be re-introduced seven days after the last dose of fusidic acid. In exceptional circumstances, where prolonged systemic fusidic acid is needed e.g. for the treatment of severe infections, the need for co-administration of LIPITOR and fusidic acid should only be considered on a case-by-case basis and under close medical supervision.

Rhabdomyolysis with or without renal impairment has been reported with the use of LIPITOR. A history of renal impairment may be a risk factor for the development of rhabdomyolysis. Such patients merit closer monitoring for skeletal muscle effects. LIPITOR therapy should be withdrawn in any patient with an acute, serious condition suggestive of a myopathy or having a risk factor predisposing to the development of renal failure secondary to rhabdomyolysis (e.g. severe acute infection, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders, and uncontrolled seizures).

There have been very rare reports of an immune mediated necrotizing myopathy (IMNM) during or after treatment with some statins. IMNM is clinically characterised by persistent proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment, positive anti-HMG CoA reductase antibody and improvement with immunosuppressive agents.

Protease inhibitors

Co-administration of LIPITOR and protease inhibitors was associated with increased plasma concentrations of LIPITOR.

Haemorrhagic stroke

In a post-hoc analysis of a clinical study, patients without coronary heart disease (CHD) who had a stroke or transient ischaemic attack (TIA) within the preceding 6 months who were initiated on LIPITOR 80 mg revealed a higher incidence of haemorrhagic stroke compared to placebo. Patients with haemorrhagic stroke on entry appeared to be at increased risk for recurrent haemorrhagic stroke.

Interstitial lung disease

Exceptional cases of interstitial lung disease have been reported with some statins, especially with long term therapy. Presenting features can include dyspnoea, non-productive cough and deterioration in general health (fatigue, weight loss and fever). If it is suspected a patient has developed interstitial lung disease, statin therapy should be discontinued.

Endocrine function

Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including LIPITOR.

Diabetes mellitus

Some evidence suggests that statins as a class raise blood glucose and in some patients at high risk of future diabetes, may produce a level of hyperglycaemia where formal diabetes care is appropriate. This risk, however, is outweighed by the reduction in vascular risk with statins and therefore should not be a reason for stopping statin treatment. Patients at risk (fasting glucose 5,6 to 6,9 mmol/L, BMI > 30kg/m2, raised triglycerides, hypertension) should be monitored both clinically and biochemically according to national guidelines.

Myasthenia gravis

In few cases, statins have been reported to induce de novo or aggravate pre-existing myasthenia gravis or ocular myasthenia (see section 4.8). LIPITOR should be discontinued in case of aggravation of symptoms. Recurrences when the same or a different statin was (re-) administered have been reported.

Excipients

LIPITOR contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

The risk of myopathy during treatment with LIPITOR is increased with concurrent administration of immunosuppressive medicines, including ciclosporin, fibric acid derivatives, niacin (nicotinic acid) or cytochrome P450 3A4/transporter inhibitors (macrolide antibiotics e.g. erythromycin, and azole antifungals e.g. clotrimazole), colchicine, telaprevir, boceprevir or the combination of tipranavir/ritonavir (see section 4.4 u2013 Skeletal muscle effects). CYP3A4 is the primary hepatic isozyme known to be involved in the biotransformation of atorvastatin. Medical practitioners considering combined therapy with LIPITOR and any of the abovementioned medicines should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs and symptoms of muscle pain, tenderness, or weakness, particularly during the initial months of therapy and during any periods of upward dosage titration of either medicine. Therefore, lower starting and maintenance doses of LIPITOR should also be considered when taken concomitantly with the aforementioned medicines.

Inhibitors of cytochrome P450 3A4

LIPITOR is metabolised by cytochrome P450 3A4. Concomitant administration of LIPITOR with inhibitors of cytochrome P450 3A4 can lead to increases in plasma concentrations of LIPITOR. The extent of interaction and potentiation of effects depends on the variability of effect on cytochrome P450 3A4 (see section 4.4).

Ticagrelor

Co-administration of LIPITOR and ticagrelor increased atorvastatin acid C max by 23 % and AUC by 36 %. Similar increases in AUC and C max were observed for all atorvastatin acid metabolites. These increases are not considered clinically significant.

Erythromycin/clarithromycin

Co-administration of LIPITOR and erythromycin or clarithromycin, known inhibitors of cytochrome P450 3A4, was associated with higher plasma concentrations of LIPITOR (see section 4.4 u2013 Skeletal muscle effects).

Protease inhibitors

Plasma concentrations of LIPITOR increased with concomitant administration of LIPITOR with several combinations of HIV protease inhibitors, as well as with the hepatitis C protease inhibitor telaprevir, compared to that of LIPITOR alone. Therefore, in patients taking the HIV protease inhibitor tipranavir plus ritonavir, or the hepatitis C protease inhibitor telaprevir, concomitant use of LIPITOR should be avoided. Concomitant administration of LIPITOR 10 mg single dose with tipranavir 500 mg twice daily plus ritonavir 200 mg twice daily for seven days, resulted in a 9,4-fold increase in atorvastatin AUC and 8,6-fold increase in atorvastatin C max. LIPITOR did not result in a change in pharmacokinetics of tipranavir plus ritonavir. Concomitant administration of LIPITOR 20 mg single dose with telaprevir 750 mg every eight hours, for 10 days, resulted in a 7,9-fold increase in atorvastatin AUC and 10,6-fold increase in atorvastatin C max.

In patients taking the HIV protease inhibitor lopinavir plus ritonavir, caution should be used when prescribing LIPITOR and the lowest dose necessary (not exceeding 10 mg) of LIPITOR should be used. Concomitant administration of LIPITOR 20 mg with lopinavir plus ritonavir (400 mg + 100 mg twice daily) resulted in a 5,9-fold increase in atorvastatin AUC. In patients taking the HIV protease inhibitors saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, or fosamprenavir plus ritonavir, the dose of LIPITOR should not exceed 20 mg and should be used with caution. Concomitant administration of LIPITOR 40 mg once a day for 4 days with saquinavir 400 mg twice daily plus ritonavir 400 mg twice daily for 15 days resulted in a 3,9-fold increase in atorvastatin AUC and 4,3-fold increase in atorvastatin C max. The dose of saquinavir plus ritonavir in this study is not the clinically used dose. The increase in atorvastatin exposure when used clinically is likely to be higher than what was observed in this study. Therefore, caution should be applied and the lowest dose necessary should be used. Concomitant administration of LIPITOR 10 mg once a day for 4 days with darunavir 300 mg twice daily plus ritonavir 100 mg twice daily for 9 days resulted in a 3,4-fold increase in atorvastatin AUC and 2,3-fold increase in atorvastatin C max. Concomitant administration of LIPITOR 10 mg once a day for 4 days with fosamprenavir 1 400 mg twice a day for 14 days resulted in a 2,3-fold increase in atorvastatin AUC and 4,0-fold increase in atorvastatin C max. LIPITOR resulted in a 1,27-fold decrease in fosamprenavir. Concomitant administration of LIPITOR 10 mg once a day for 4 days with fosamprenavir 700 mg twice a day plus ritonavir 100 mg twice a day for 14 days resulted in a 2,5-fold increase in atorvastatin AUC and 2,8-fold increase in atorvastatin C max. LIPITOR did not result in a change in pharmacokinetics of fosamprenavir 700 mg plus ritonavir.

In patients taking nelfinavir, the dose of LIPITOR should not exceed 40 mg daily. Concomitant administration of LIPITOR 10 mg once a day for 28 days with nelfinavir 1 250 mg twice a day for 14 days resulted in a 74 % increase in atorvastatin AUC and 2,2-fold increase in atorvastatin C max. Concomitant administration of LIPITOR 40 mg single dose with boceprevir 800 mg three times a day for 7 days resulted in a 2,3-fold increase in atorvastatin AUC and 2,66-fold increase in atorvastatin C max (see section 4.4 u2013 Skeletal muscle effects).

Diltiazem hydrochloride

Co-administration of LIPITOR with diltiazem was associated with an increase in AUC of 51 % of LIPITOR (see section 4.3).

Cimetidine

LIPITOR plasma concentrations and LDL-C reduction were not altered by co-administration of cimetidine.

Itraconazole

Co-administration of LIPITOR 40 mg, single dose and itraconazole 200 mg, once daily, was associated with a 3,3-fold increase in AUC and a 20 % increase in C max.

Grapefruit juice

Contains one or more components that inhibit CYP3A4 and can increase plasma concentrations of LIPITOR by 2,5 to 3,3-fold and the combination should be avoided (see section 4.3).

Transporter inhibitors

Atorvastatin and atorvastatin metabolites are substrates of the organic anion-transporting polypeptide 1B1 (OATP1B1) transporter (see section 5.2 u2013 Elimination). Inhibitors of the OATP1B1 (e.g. ciclosporin) can increase the bioavailability of atorvastatin.

Ciclosporin

Concomitant administration of LIPITOR 10 mg and ciclosporin 5,2 mg/kg/day resulted in an 8,7-fold increase in exposure to atorvastatin. Do not exceed 10 mg LIPITOR daily.

Glecaprevir/pibrentasvir

Glecaprevir and pibrentasvir are inhibitors of OATP1B1, OATP1B3, MDR1 and BCRP, thus they increase exposure to LIPITOR. Do not exceed 10 mg LIPITOR daily.

Elbasvir/grazoprevir

Elbasvir and grazoprevir are inhibitors of OATP1B1, OATP1B3, MDR1 and BCRP, thus they increase exposure to LIPITOR. Use with caution and lowest dose necessary.

Letermovir

Concomitant administration of LIPITOR 20 mg and letermovir 480 mg daily resulted in an increase in exposure to LIPITOR (ratio of AUC: 3,29). Do not exceed 20 mg LIPITOR daily. Use of LIPITOR is not recommended in patients taking letermovir co-administered with ciclosporin.

Inducers of cytochrome P450 3A4

Concomitant administration of LIPITOR with inducers of cytochrome P450 3A4 (e.g. efavirenz, rifampicin, St. Johnu2019s Wort) can lead to variable reductions in plasma concentrations of LIPITOR. Due to the dual interaction mechanism of rifampicin, (cytochrome P450 3A induction and inhibition of hepatocyte uptake transporter OATP1B1), simultaneous co-administration of LIPITOR with rifampicin is recommended, as delayed administration of LIPITOR after administration of rifampicin has been associated with a significant reduction in LIPITOR plasma concentrations. The effect of rifampicin on atorvastatin concentrations in hepatocytes is, however, unknown and if concomitant administration cannot be avoided, patients should be carefully monitored for efficacy.

Antacids

Co-administration of an oral antacid suspension containing magnesium and aluminium hydroxides decreased plasma concentrations of LIPITOR approximately 35 %; however, LDL-C reduction was not altered.

Antipyrine

Because LIPITOR does not affect the pharmacokinetics of antipyrine, interactions with other medicines metabolised via the same cytochrome isozymes are not expected.

Colestipol

Plasma concentrations of LIPITOR decreased approximately 25 % when colestipol and LIPITOR were co-administered. However, LDL-C reduction was greater when LIPITOR and colestipol were co-administered than when either medicine was given alone.

Cholestyramine

No data is available.

Digoxin

Co-administration of multiple doses of LIPITOR and digoxin increased steady-state plasma digoxin concentrations by approximately 20 %. Patients taking digoxin should be monitored appropriately.

Azithromycin

Co-administration of LIPITOR (10 mg once daily) and azithromycin (500 mg once daily) did not alter the plasma concentrations of LIPITOR.

Oral contraceptives

Co-administration of LIPITOR and an oral contraceptive increased AUC values of norethindrone and ethinyl estradiol approximately 30 % and 20 %, respectively. These increases should be considered when selecting an oral contraceptive for a woman taking LIPITOR.

Warfarin

LIPITOR had no clinically significant effect on prothrombin/INR time when administered to patients receiving combined LIPITOR and warfarin therapy for two weeks. Nevertheless, patients receiving LIPITOR should be closely monitored when LIPITOR is combined with warfarin therapy.

Colchicine

Although interaction studies with LIPITOR and colchicine have not been conducted, cases of myopathy have been reported with LIPITOR co-administered with colchicine, and caution should be exercised when prescribing LIPITOR with colchicine.

Daptomycin

Cases of myopathy and/or rhabdomyolysis have been reported with HMG-CoA reductase inhibitors (e.g. atorvastatin) co-administered with daptomycin. If co-administration cannot be avoided, appropriate clinical monitoring is recommended (see section 4.4).

Amlodipine

LIPITOR pharmacokinetics were not altered by the co-administration of LIPITOR 80 mg and amlodipine 10 mg at steady state.

Fusidic acid

Although interaction studies with LIPITOR and fusidic acid have not been conducted, severe muscle problems such as rhabdomyolysis have been reported in post-marketing experience with this combination. The mechanism of this interaction is unknown. If treatment with systemic fusidic acid is necessary, treatment with LIPITOR should be discontinued throughout the duration of the fusidic acid treatment (see section 4.4). LIPITOR therapy may be re-introduced seven days after the last dose of fusidic acid.

Other concomitant therapy

In clinical studies, LIPITOR was used concomitantly with antihypertensive medicines and estrogen replacement therapy without evidence of clinically significant adverse interactions. Interaction studies with specific medicines have not been conducted.

LIPITOR is contraindicated in pregnancy, in mothers breastfeeding their infants and in women of childbearing potential not using adequate contraceptive measures (see section 4.3).

Women of childbearing potential

LIPITOR should be administered to women of childbearing age only when such patients are using adequate contraception and have been informed of the potential hazards to the foetus. An interval of one month should be allowed from stopping LIPITOR treatment to conception in the event of planning a pregnancy.

Breastfeeding

LIPITOR is contraindicated while breastfeeding. It is unknown whether LIPITOR is excreted in human milk. Because of the potential for adverse reactions, women taking LIPITOR should not breastfeed their infants (see section 4.3).

LIPITOR has negligible influence on the ability to drive and use machines.

Summary of the safety profile

In placebo-controlled trials, 5,2 % of patients on LIPITOR discontinued treatment due to adverse events compared to 4,0 % of the patients on placebo.

Tabulated summary of adverse reactions

Adverse events have been categorised as follows: Very common ( uf0b3 1/10); common ( uf0b3 1/100 to < 1/10); uncommon ( uf0b3 1/1 000 to < 1/100); rare ( uf0b3 1/10 000 to < 1/1 000); very rare ( < 1/10 000).

Adverse events in placebo-controlled studies (% of patients)

The following additional adverse events have been reported in LIPITOR clinical trials:

System organ class Frequency Side effects

Infections and infestations Common Nasopharyngitis

Blood and lymphatic system disorders Uncommon Thrombocytopenia

Immune system disorders Common Allergic reactions (including anaphylaxis)

Metabolism and nutrition disorders Common Hyperglycaemia

Uncommon Hypoglycaemia, anorexia, weight gain

Psychiatric disorders Common Insomnia

Uncommon Nightmare

Nervous system disorders Common Hypoaesthesia, paraesthesia, dizziness, headache

Uncommon Peripheral neuropathy, amnesia, dysgeusia

Not known Myasthenia gravis

Eye disorders Uncommon Blurred vision

Not known Ocular myasthenia

Ear and labyrinth disorders Uncommon Tinnitus

Vascular disorders Rare Vasculitis

Respiratory, thoracic and mediastinal disorders Common Pharyngolaryngeal pain, epistaxis

Gastrointestinal disorders Common Nausea, diarrhoea, abdominal pain, dyspepsia, constipation, flatulence

Uncommon Vomiting, eructation, pancreatitis

Hepatobiliary disorders Uncommon Hepatitis

Rare Cholestasis, cholestatic jaundice

Skin and subcutaneous tissue disorders Common Pruritus, rash

Uncommon Alopecia, urticaria

Rare Angioedema, bullous rashes, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, lichenoid drug reaction

Musculoskeletal and connective tissue disorders Common Myalgia, arthralgia, pain in extremity, muscle spasms, joint swelling, back pain

Uncommon Neck pain, muscle fatigue

Rare Myopathy, myositis, rhabdomyolysis, muscle cramps

Reproductive system and breast disorders Uncommon Impotence

General disorders and administration site conditions Common Asthenia, chest pain

Uncommon Malaise, peripheral oedema, fatigue, pyrexia

Investigations Common Abnormal liver function test, increased blood creatine kinase

Uncommon White blood cells urine positive

Injury, poisoning and procedural complications Uncommon Tendon rupture

Paediatric population

Patients treated with LIPITOR had an adverse experience profile generally similar to that of patients treated with placebo, the most common adverse experiences observed in both groups, regardless of causality assessment, were infections.

Post-marketing experience

There have been post-marketing reports of cognitive impairment (e.g. memory loss, forgetfulness, amnesia, memory impairment, confusion) and immune-mediated necrotizing myopathy associated with use of LIPITOR. These side effects may be reversible upon discontinuation of treatment.

The following adverse events have been reported with some statins:

• Depression.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website.

There is no specific treatment for LIPITOR overdosage. In the event of an overdose, the patient should be treated symptomatically, and supportive measures instituted as required. Liver function tests should be performed and serum CK levels should be monitored. Due to extensive medicine binding to plasma proteins, haemodialysis is not expected to significantly enhance LIPITOR clearance.