Oral Chronic stable angina, Hyperlipidaemia, Hypertension, Prinzmetal's angina, Prophylaxis of cardiovascular events in high-risk patients
Adult: Available preparations:
Amlodipine 2.5 mg and atorvastatin 10 mg tab
Amlodipine 2.5 mg and atorvastatin 20 mg tab
Amlodipine 2.5 mg and atorvastatin 40 mg tab
Amlodipine 5 mg and atorvastatin 10 mg tab
Amlodipine 5 mg and atorvastatin 20 mg tab
Amlodipine 5 mg and atorvastatin 40 mg tab
Amlodipine 5 mg and atorvastatin 80 mg tab
Amlodipine 10 mg and atorvastatin 10 mg tab
Amlodipine 10 mg and atorvastatin 20 mg tab
Amlodipine 10 mg and atorvastatin 40 mg tab
Amlodipine 10 mg and atorvastatin 80 mg tab
In patients whom treatment with both amlodipine and atorvastatin is considered appropriate as initial therapy or may be used to substitute individual titrated components; or to provide additional therapy for patients currently receiving 1 of its components. Dosages must be individualised based on effectiveness and tolerance for each individual component, and according to goals consistent with current treatment guidelines. Dosage range: 5 mg/10 mg to 10 mg/80 mg (Max) once daily; may be adjusted accordingly or titrated after 1-2 weeks (amlodipine) and after 2-4 weeks (atorvastatin). Elderly: May initiate amlodipine component at 2.5 mg once daily.
Special Patient Group
Patients receiving clarithromycin, itraconazole, elbasvir/grazoprevir, or HIV protease inhibitors (e.g. saquinavir/ritonavir, darunavir/ritonavir, fosamprenavir or fosamprenavir/ritonavir): Use the lowest necessary atorvastatin doses. Max: 20 mg atorvastatin daily.
Patients receiving nelfinavir or boceprevir: Max: 40 mg atorvastatin daily.
May initiate amlodipine component at 2.5 mg once daily.
May be taken with or without food.
Active liver disease or unexplained persistent elevated hepatic transaminases. Pregnancy and lactation.
Patient with severe aortic stenosis or obstructive coronary artery disease, hypertrophic cardiomyopathy with outflow tract obstruction; inadequately treated hypothyroidism, recent stroke, transient ischaemic attack, history of liver disease or renal impairment. Patient who consumes large quantities of alcoholic beverages. Withhold treatment in patient with risk factors predisposing to development of renal failure secondary to rhabdomyolysis (e.g. trauma, major surgery, severe acute infection, hypotension, uncontrolled seizures; severe metabolic, endocrine, and electrolyte disorders). Renal and hepatic impairment. Elderly. Concomitant use with fusidic acid or letermovir co-administered with ciclosporin is not recommended.
Significant: Worsening angina, acute MI; increased HbA1c and fasting serum glucose levels; increased serum transaminases, hyperbilirubinaemia, jaundice, hypotension, syncope, myopathy, rhabdomyolysis, peripheral oedema. Rarely, rhabdomyolysis with acute renal failure secondary to myoglobinuria, immune-mediated necrotising myopathy. Blood and lymphatic system disorders: Leucopenia, thrombocytopenia. Cardiac disorders: Palpitation. Ear and labyrinth disorders: Tinnitus. Eye disorders: Conjunctivitis, diplopia, eye pain, blurred vision. Gastrointestinal disorders: Nausea, dyspepsia, diarrhoea, constipation, flatulence, abdominal pain, pancreatitis. General disorders and administration site conditions: Fatigue, asthenia, malaise. Immune system disorders: Anaphylaxis, myositis, oedema. Metabolism and nutrition disorders: Hyperglycaemia. Musculoskeletal and connective tissue disorders: Muscle cramps or spasms, arthralgia, pain in extremity, musculoskeletal pain, myalgia, tendon rupture. Nervous system disorders: Headache, dizziness, somnolence, peripheral neuropathy, extrapyramidal disorder. Psychiatric disorders: Insomnia, anxiety, depression. Renal and urinary disorders: Micturition disorder, nocturia, UTI. Reproductive system and breast disorders: Gynaecomastia. Respiratory, thoracic and mediastinal disorders: Nasopharyngitis, dyspnoea, pharyngolaryngeal pain, epistaxis, interstitial lung disease. Skin and subcutaneous tissue disorders: Rash, pruritus, urticaria, bullous rashes (including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme). Vascular disorders: Flushing. Potentially Fatal: Rarely, hepatic failure.
Monitor blood pressure, heart rate; lipid panel (e.g. total cholesterol, HDL, LDL, triglycerides) and hepatic transaminase level at baseline and periodically as clinically indicated; creatine phosphokinase (in high risk patients or when myopathy is considered).
Amlodipine: May increase systemic exposure of immunosuppressants (e.g. ciclosporin, tacrolimus). Increased exposure with CYP3A4 inhibitors (e.g. ritonavir, azole antifungals, clarithromycin). May decrease plasma concentration with CYP3A4 inducers (e.g. rifampicin).
Atorvastatin: May increase risk of myopathy or rhabdomyolysis with CYP3A4 inhibitors (e.g. HIV and HCV protease inhibitors, itraconazole, clarithromycin, erythromycin), fusidic acid, ciclosporin, fibric acid derivatives (e.g. fenofibrate), gemfibrozil, nicotinic acid, colchicine, letermovir. Concomitant use with CYP3A4 inducers (e.g. rifampicin, efavirenz, phenytoin), Al- or Mg-containing antacids, and colestipol may reduce plasma concentrations of atorvastatin. May increase serum levels of digoxin and oral contraceptives (e.g. norethindrone, ethinylestradiol).
Increased plasma concentration with grapefruit or grapefruit juice. Decreased plasma concentrations with St. John’s wort.
Atorvastatin: May increase risk of adverse hepatic effects with alcohol.
Description: Amlodipine, a dihydropyridine Ca-channel blocker, reduces peripheral vascular resistance and blood pressure by relaxing coronary vascular smooth muscle and coronary vasodilation through inhibition of Ca ion transmembrane influx into cardiac and vascular smooth muscles. It also increases myocardial oxygen delivery in patients with vasospastic angina.
Atorvastatin selectively and competitively inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyses the conversion of HMG-CoA to mevalonate. The reduction of mevalonate production results to a compensatory increase in the expression of LDL receptors and stimulation of LDL catabolism, consequently lowering LDL-cholesterol levels. Onset: Amlodipine: 24-48 hours (antihypertensive effect).
Atorvastatin: Initial effect: 3-5 days. Duration: Amlodipine: 24 hours (antihypertensive effect). Pharmacokinetics: Absorption: Amlodipine: Well absorbed from the gastrointestinal tract. Bioavailability: Approx 64-90%. Time to peak plasma concentration: 6-12 hours.
Atorvastatin: Rapidly absorbed from the gastrointestinal tract. Bioavailability: Approx 14%. Time to peak plasma concentration: 1-2 hours. Distribution: Amlodipine: Crosses placenta and enters breast milk. Volume of distribution: 21 L/kg. Plasma protein binding: Approx 98%.
Atorvastatin: Volume of distribution: Approx 381 L. Plasma protein binding: ≥98%. Metabolism: Amlodipine: Extensively metabolised in the liver to inactive metabolites.
Atorvastatin: Extensively metabolised in the liver by CYP3A4 isoenzyme to ortho- and parahydroxylated derivatives (active) and β-oxidation metabolite (inactive). Undergoes extensive first-pass metabolism in the gastrointestinal mucosa. Excretion: Amlodipine: Via urine (60% as metabolites, 10% as unchanged drug). Terminal elimination half-life: 30-50 hours.
Atorvastatin: Mainly via bile; via urine (<2% as unchanged drug). Elimination half-life: Approx 14 hours; 20-30 hours (active metabolites).
C10BX03 - atorvastatin and amlodipine ; Belongs to the class of HMG CoA reductase inhibitors, other combinations.
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