Stefamlor 5/10

Rx

Indications

• Stefamlor 5/10 is indicated for the prevention of cardiovascular events in hypertensive patients with 3 associated cardiovascular risk factors, with normal to moderately elevated cholesterol without established coronary artery disease, and in whom, according to current recommendations, the concomitant use of amlodipine and a low dose of atorvastatin is suitable.
• Stefamlor 5/10 should be used when the response to the regimen and other non-pharmacological measures is inadequate.

Dosage

• The usual starting dose is 5 mg/10 mg once a day.
• If tighter blood pressure control is required, a dose of 10 mg/10 mg once daily may be administered (using other suitable preparation).
• No dose adjustment is necessary in patients with impaired renal function and in elderly patients.
• In combination with ciclosporin, the dose of atorvastatin should not exceed 10 mg.
• Use with caution and use with the lowest atorvastatin dose necessary.
• Do not exceed 20 mg atorvastatin daily if co-administering with darunavir combined with ritonavir, fosamprenavir, fosamprenavir combined with ritonavir, saquinavir combined with ritonavir.
• Do not exceed 20 mg atorvastatin daily if co-administering with nelfinavir.
• The risk of muscle injury increases when certain other medications are taken with statins: Gemfibrozil, blood cholesterol-lowering agents of other fibrates, high doses of niacin (> 1 g/day), colchicine.
• Co-administration of HIV and hepatitis C virus (HCV) protease inhibitors and cholesterol-lowering statin drugs can increase the risk of muscle injury. The most serious form of myopathy, called rhabdomyolysis, can damage the kidneys and lead to kidney failure, which can be fatal.

Usage

• Administered orally.
• The tablets can be taken at any time of the day, with or without food.
• Stefamlor 5/10 can be used alone or in combination with other antihypertensive drugs, but it must not be used in combination with other calcium channel blockers or another statin.

• Hypersensitivity to dihydropyridines, to the active substances amlodipine and atorvastatin or to any of the excipients.
• With active liver disease or a persistent and unexplained increase in serum transaminases exceeding 3 times the upper limit of normal.
• Pregnant women, breastfeeding or of childbearing potential and not using reliable contraception.
• In combination with itraconazole, ketoconazole, telithromycin.
• Patients with severe hypotension.
• Patients having shock (including cardiogenic shock).
• Patients having an obstruction of the efferent passage of the left ventricle (e.g. severe aortic stenosis).
• Patients with haemodynamically unstable heart failure after acute myocardial infarction.
• Patients treated with hepatitis C antivirals glecaprevir/pibrentasvir.
• Co-administering with tipranavir + ritonavir, telaprevir.
• Patients with hepatic insufficiency.
• Pediatric population.

Common

• Edema.
• Drowsiness, dizziness, headache (especially at the start of treatment).
• Visual disturbances (including diplopia).
• Palpitations.
• Flushing.
• Dyspnea.
• Nausea, upper and lower abdominal pain, dyspepsia, changes in intestinal transit (including diarrhea and constipation).
• Swelling of the joints (including swelling of the ankles), muscle cramps, muscle spasms.
• Tired, asthenia.

• Patients with heart failure should be treated with caution.
• Liver function tests should be performed before the start of treatment and then regularly after initiation of treatment, as well as in the event of signs or symptoms suggestive of hepatic impairment. Stefamlor 5/10 should be used with caution in patients who consume large amounts of alcohol, in patients with hepatic impairment and/or a history of liver disease.
• Atorvastatin can affect skeletal muscles and lead to myalgia, myositis and myopathy. These muscle damage may rarely progress to rhabdomyolysis.
• Before starting treatment with a statin, the CK level should be checked in the following situations:
  Renal impairment.
  Hypothyroidism.
  Personal or family history of genetic muscle diseases.
  Personal history of muscle toxicity during treatment with a statin or a fibrate.
  History of liver disease and/or excessive alcohol consumption.
  In elderly patients (> 70 years), the need for these measures should be assessed, depending on the presence of other predisposing factors for rhabdomyolysis.
  Situations where increased plasma concentrations may occur, due to interactions and use in special populations including genetic polymorphisms.
  In these situations, a regular reassessment of the benefit/risk of the treatment, as well as regular clinical monitoring is recommended.
  If the initial CK level is significantly elevated (more than 5 times the ULN) treatment should not be started.
  If the CK level is significantly elevated (more than 5 times the ULN), treatment should be discontinued.
  If muscular symptoms are severe and cause daily discomfort, discontinuation of treatment should be considered, even if CK levels did not exceed 5 times the ULN.
  If symptoms resolve and CK levels return to normal, the reintroduction of Stefamlor 5/10 may be considered at the lowest dose and under close supervision.
  Treatment with Stefamlor 5/10 should be discontinued in the event of a clinically significant increase in the level of CK (> 10 times the ULN) or if rhabdomyolysis is diagnosed or suspected.
  Amlodipine has no effect on laboratory parameters.
• Combinations with other drugs
  As with other statins, the risk of rhabdomyolysis is increased when Stefamlor 5/10 is administered in combination with certain drugs which may increase the plasma concentration of atorvastatin, such as strong inhibitors of CYP3A4 or protein transporters (e.g., ciclosporin, telithromycin), clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole, letermovir and HIV protease inhibitors including ritonavir, lopinavir, atazanavir, indinavir, darunavir, tipranavir/ritonavir, etc.). The risk of myopathy may also be increased in combination with gemfibrozil and other fibrates, the antivirals used in the treatment of hepatitis C (HCV) (e.g. boceprevir, telaprevir, elbasvir/ grazoprevir, ledipasvir/sofosbuvir), erythromycin, niacin (> 1 g/day), ezetimibe or, colchicine. Therapeutic alternatives (not exhibiting these interactions) should be considered as far as possible. Co-administration of HIV and hepatitis C virus (HCV) protease inhibitors and cholesterol-lowering statin drugs can increase the risk of muscle injury. The most serious form of myopathy, called rhabdomyolysis, can damage the kidneys and lead to kidney failure, which can be fatal.
  In the event that the combination of these medicinal products with Stefamlor 5/10 is necessary, the benefit/risk of concomitant treatments should be carefully assessed and appropriate clinical monitoring is recommended.
  Stefamlor 5/10 should not be administered concomitantly with fusidic acid in systemic form, and for up to 7 days after stopping treatment with fusidic acid. In patients where the use of systemic fusidic acid is considered essential, statin therapy should be discontinued for the duration of fusidic acid therapy. Cases of rhabdomyolysis (some fatal) have been reported in patients receiving fusidic acid and a statin in combination. Patients should be advised of the need to seek immediate medical attention if they experience symptoms of muscle weakness, pain, or muscle tenderness. Statin therapy can be restarted seven days after the last dose of fusidic acid. In exceptional circumstances, when prolonged treatment with systemic fusidic acid is required, for example for the treatment of severe infections, the need for co-administration of Stefamlor 5/10 and fusidic acid should only be considered if by case and under close medical supervision.
• In patients with a history of hemorrhagic stroke or lacunar infarction, the benefit/risk balance of atorvastatin 80 mg is uncertain. Therefore, the potential risk of occurrence of haemorrhagic stroke should be carefully assessed before any initiation of treatment.
• If a patient is suspected of interstitial lung disease, statin therapy should be discontinued.
• Patients at risk (fasting blood glucose between 5.6 and 6.9 mmol/L, BMI > 30 kg/m², increased triglyceride levels, arterial hypertension) should be monitored clinically and biologically in accordance with national recommendations.
• Stefamlor 5/10 is contraindicated during pregnancy and lactation.
• No studies have been performed to determine the effect of Stefamlor 5/10 on the ability to drive or use machines. Atorvastatin in Stefamlor 5/10 has negligible influence on the ability to drive and use machines. However, based on the pharmacodynamic properties of the amlodipine component of Stefamlor 5/10, the possible occurrence of dizziness, headache, fatigue or nausea should be taken into account when driving a vehicle or operating machinery.