(am LOW di peen & a TORE va sta tin)
For use when treatment with both amlodipine and atorvastatin is appropriate:
Amlodipine: Treatment of hypertension; treatment of chronic stable angina, vasospastic (Prinzmetals) angina (confirmed or suspected); prevention of hospitalization or to decrease coronary revascularization procedure due to angina with documented CAD (limited to patients without heart failure or ejection fraction <40%)
Atorvastatin: Treatment of dyslipidemias or primary prevention of cardiovascular disease (atherosclerotic) as detailed here:
Primary prevention of cardiovascular disease (high-risk for CVD): To reduce the risk of MI or stroke in patients without evidence of coronary heart disease who have multiple CVD risk factors or type 2 diabetes; also reduces the risk for angina or revascularization procedures in patients with multiple CVD risk factors without evidence of coronary heart disease
Secondary prevention of cardiovascular disease: To reduce the risk of MI, stroke, revascularization procedures, angina, and hospitalization for heart failure
Primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) according to the American College of Cardiology/American Heart Association: To reduce the risk of ASCVD in patients with clinical ASCVD (eg, coronary heart disease, stroke/TIA, or peripheral arterial disease presumed to be of atherosclerotic origin); in patients without clinical ASCVD if LDL-C is 190 mg/dL or greater; in patients without clinical ASCVD who have type 1 or type 2 diabetes and are between 40 and 75 years of age; in patients with an estimated 10-year ASCVD risk 7.5% or greater and who are between 40 and 75 years of age (Stone, 2013). Specific recommendations from the Kidney Disease: Improving Global Outcomes (KDIGO) organization have also been released for patients with chronic kidney disease (KDIGO [Tonelli, 2013]).
Treatment of dyslipidemias: To reduce elevations in total cholesterol, LDL-C, apolipoprotein B, and triglycerides in patients with elevations of one or more components, and/or to increase low HDL-C as present in heterozygous familial/nonfamilial hypercholesterolemia and mixed dyslipidemia (Fredrickson type IIa and IIb hyperlipidemias); treatment of primary dysbetalipoproteinemia (Fredrickson type III), elevated serum TG levels (Fredrickson type IV), and homozygous familial hypercholesterolemia
Treatment of heterozygous familial hypercholesterolemia (HeFH) in adolescent patients (10 to 17 years of age, females >1 year postmenarche) having LDL-C ≥190 mg/dL or LDL-C ≥160 mg/dL with positive family history of premature cardiovascular disease (CVD) or with two or more CVD risk factors.
Hypersensitivity to amlodipine, atorvastatin, or any component of the formulation; active liver disease; unexplained persistent elevations of serum transaminases; pregnancy (or those who may become pregnant); breast-feeding
Note: Telaprevir Canadian product monograph contraindicates use with atorvastatin.
Note: Dose is individualized; combination product may be used as initial therapy or substituted for individual components in patients currently maintained on both agents separately or in patients not adequately controlled with monotherapy (using one of the agents or an agent within same pharmacologic class).
Hypertension, angina, and hyperlipidemia: Oral:
Initial therapy: Amlodipine 5 mg and atorvastatin 10-20 mg once daily; dose may be titrated after 1-2 weeks (amlodipine component) and after 2-4 weeks (atorvastatin component) to a maximum daily dose: Amlodipine 10 mg; atorvastatin 80 mg
Add-on therapy/replacement therapy: Amlodipine 5-10 mg and atorvastatin 10-80 mg once daily; dose may be titrated after 1-2 weeks (amlodipine component) and after 2-4 weeks (atorvastatin component) to a maximum daily dose: Amlodipine 10 mg; atorvastatin 80 mg
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)
Refer to adult dosing. Consider starting amlodipine at the lower end of dosing range due to increased incidence of hepatic, renal, or cardiac impairment. Elderly patients also show decreased clearance of amlodipine.
Note: Dose is individualized; combination product may be used as initial therapy or substituted for individual components in patients currently maintained on both agents separately or in patients not adequately controlled with monotherapy (using one of the agents or an agent within same pharmacologic class).
Hypertension and hyperlipidemia: 10-17 years (females >1 year postmenarche): Oral:
Initial therapy: Amlodipine 2.5 mg and atorvastatin 10 mg once daily; dose may be titrated after 1-2 weeks (amlodipine component) and after 2-4 weeks (atorvastatin component) to a maximum daily dose: Amlodipine 5 mg; atorvastatin 20 mg
Add-on therapy/replacement therapy: Amlodipine 2.5-5 mg and atorvastatin 10-20 mg once daily; dose may be titrated after 1-2 weeks (amlodipine component) and after 2-4 weeks (atorvastatin component) to a maximum daily dose: Amlodipine 5 mg; atorvastatin 20 mg
Dosage adjustment for atorvastatin with concomitant medications: Refer to adult dosing.
No dosage adjustment is necessary.
Contraindicated in patients with active liver disease.
May be administered without regard to meals.
May take with food if desired; may take without regard to time of day. Before initiation of therapy with atorvastatin, patients should be placed on a standard cholesterol-lowering diet for 3 to 6 months and the diet should be continued during drug therapy.
Red yeast rice contains variable amounts of several compounds that are structurally similar to HMG-CoA reductase inhibitors, primarily monacolin K (or mevinolin) which is structurally identical to lovastatin; concurrent use of red yeast rice with HMG-CoA reductase inhibitors may increase the incidence of adverse and toxic effects (Lapi, 2008; Smith, 2003).
Store at 25 � �C (77 � �F); excursions permitted to 15 � �C to 30 � �C (59 � �F to 86 � �F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Caduet:
2.5/10: Amlodipine 2.5 mg and atorvastatin 10 mg
2.5/20: Amlodipine 2.5 mg and atorvastatin 20 mg
2.5/40: Amlodipine 2.5 mg and atorvastatin 40 mg
5/10: Amlodipine 5 mg and atorvastatin 10 mg
5/20: Amlodipine 5 mg and atorvastatin 20 mg
5/40: Amlodipine 5 mg and atorvastatin 40 mg
5/80: Amlodipine 5 mg and atorvastatin 80 mg
10/10: Amlodipine 10 mg and atorvastatin 10 mg
10/20: Amlodipine 10 mg and atorvastatin 20 mg
10/40: Amlodipine 10 mg and atorvastatin 40 mg
10/80: Amlodipine 10 mg and atorvastatin 80 mg
Generic:
2.5/10: Amlodipine 2.5 mg and atorvastatin 10 mg
2.5/20: Amlodipine 2.5 mg and atorvastatin 20 mg
2.5/40: Amlodipine 2.5 mg and atorvastatin 40 mg
5/10: Amlodipine 5 mg and atorvastatin 10 mg
5/20: Amlodipine 5 mg and atorvastatin 20 mg
5/40: Amlodipine 5 mg and atorvastatin 40 mg
5/80: Amlodipine 5 mg and atorvastatin 80 mg
10/10: Amlodipine 10 mg and atorvastatin 10 mg
10/20: Amlodipine 10 mg and atorvastatin 20 mg
10/40: Amlodipine 10 mg and atorvastatin 40 mg
10/80: Amlodipine 10 mg and atorvastatin 80 mg
Acipimox: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Monitor therapy
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Aliskiren: AtorvaSTATin may increase the serum concentration of Aliskiren. Monitor therapy
Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
Amiodarone: May decrease the metabolism of HMG-CoA Reductase Inhibitors. Management: Dose of HMG-CoA reductase inhibitor may need to be reduced (limit simvastatin adult maximum dose to 20 mg/day, limit lovastatin adult maximum dose to 40 mg/day). Consider therapy modification
Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Antacids: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy
Antihepaciviral Combination Products: May increase the serum concentration of AmLODIPine. Management: Reduce amlodipine dose by at least 50% and monitor for increased amlodipine effects (eg, hypotension) if an antihepaciviral combination product is initiated. Consider therapy modification
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
Asunaprevir: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy
Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy
Azithromycin (Systemic): May enhance the myopathic (rhabdomyolysis) effect of AtorvaSTATin. Monitor therapy
Barbiturates: May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Bexarotene (Systemic): May decrease the serum concentration of AtorvaSTATin. Monitor therapy
Bezafibrate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Bezafibrate may increase the serum concentration of HMG-CoA Reductase Inhibitors. More specifically, bezafibrate may increase the serum concentration of fluvastatin Management: Monitor patients closely for myopathy with concomitant use of bezafibrate and HMG-CoA reductase inhibitors. Concomitant use is contraindicated in patients predisposed to myopathy and alternative therapy should be considered. Consider therapy modification
Bile Acid Sequestrants: May decrease the serum concentration of AtorvaSTATin. Monitor therapy
Boceprevir: May increase the serum concentration of AtorvaSTATin. Management: Limit the atorvastatin maximum adult dose to 40 mg daily in patients receiving boceprevir. Monitor clinical response to ensure that the lowest necessary atorvastatin dose is used. Consider therapy modification
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Bosutinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib. Avoid combination
Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy
Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Monitor therapy
CarBAMazepine: May increase the metabolism of Calcium Channel Blockers (Dihydropyridine). Management: Consider calcium channel blocker (CCB) dose adjustments or alternative therapy in patients receiving concomitant carbamazepine. Nimodipine Canadian labeling contraindicates concurrent use with carbamazepine. Consider therapy modification
Cimetidine: AtorvaSTATin may enhance the adverse/toxic effect of Cimetidine. Specifically, there is a theoretical potential for enhanced effects on reducing endogenous steroid activity. Monitor therapy
Ciprofibrate: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Management: Avoid the use of HMG-CoA reductase inhibitors and ciprofibrate if possible. If concomitant therapy is considered, benefits should be carefully weighed against the risks, and patients should be monitored closely for signs/symptoms of muscle toxicity. Consider therapy modification
Clarithromycin: May increase the serum concentration of AtorvaSTATin. Management: Limit atorvastatin to a maximum dose of 20 mg/day (for adults) when used with clarithromycin. If this combination is used, monitor patients more closely for evidence of atorvastatin toxicity. Consider therapy modification
Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Monitor therapy
Cobicistat: May increase the serum concentration of AtorvaSTATin. Management: Initiate atorvastatin at the lowest recommended dose and titrate slowly as needed while monitoring closely for evidence of atorvastatin toxicity. Consider therapy modification
Colchicine: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CycloSPORINE (Systemic): May increase the serum concentration of AtorvaSTATin. Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification
Cyproterone: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Avoid use of statins metabolized by CYP3A4 (eg, simvastatin) and consider avoiding fluvastatin as well in patients receiving high dose cyproterone (300 mg/day). Consider use of pravastatin, rosuvastatin, or pitavastatin if statin therapy is needed. Consider therapy modification
Dabigatran Etexilate: AtorvaSTATin may decrease the serum concentration of Dabigatran Etexilate. Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Daclatasvir: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy
Danazol: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Concurrent use of simvastatin with danazol is contraindicated. Initiate lovastatin at an adult maximum dose of 10 mg/day, and do not exceed 20 mg/day, when danazol is given concomitantly. Fluvastatin, pravastatin and rosuvastatin may pose lower risk. Consider therapy modification
Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Monitor therapy
DAPTOmycin: HMG-CoA Reductase Inhibitors may enhance the adverse/toxic effect of DAPTOmycin. Specifically, the risk of skeletal muscle toxicity may be increased. Management: Consider temporarily stopping HMG-CoA reductase inhibitor therapy prior to daptomycin. If used together, regular (i.e., at least weekly) monitoring of CPK concentrations is recommended. Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Digoxin: AtorvaSTATin may increase the serum concentration of Digoxin. Monitor therapy
DiltiaZEM: AtorvaSTATin may increase the serum concentration of DiltiaZEM. DiltiaZEM may increase the serum concentration of AtorvaSTATin. Management: Consider using lower atorvastatin doses when used together with diltiazem. Consider therapy modification
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Dronedarone: May increase the serum concentration of AtorvaSTATin. Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification
Efavirenz: May decrease the serum concentration of AtorvaSTATin. Monitor therapy
Elbasvir: May increase the serum concentration of AtorvaSTATin. Management: Limit the dose of atorvastatin to a maximum of 20 mg/day when used together with elbasvir and grazoprevir. Monitor closely for evidence of statin-related toxicities such as myalgia or myopathy. Consider therapy modification
Eltrombopag: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Monitor therapy
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Etravirine: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. This applies to atorvastatin, lovastatin and simvastatin. Conversely, levels of fluvastatin may be increased. Management: Dose adjustment of the HMG-CoA reductase inhibitor may be warranted. No interaction is expected with rosuvastatin, pravastatin, or pitavastatin. Monitor therapy
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification
Fenofibrate and Derivatives: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy
Fluconazole: May increase the serum concentration of AtorvaSTATin. Monitor therapy
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fosphenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification
Fosphenytoin: Calcium Channel Blockers may increase the serum concentration of Fosphenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Consider therapy modification
Fusidic Acid (Systemic): May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Specifically, the risk for muscle toxicities, including rhabdomyolysis may be significantly increased. Management: Avoid concurrent use whenever possible. Use is listed as contraindicated in product characteristic summaries in several countries, although UK labeling suggests that use could be considered under exceptional circumstances and with close supervision. Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Gemfibrozil: May enhance the myopathic (rhabdomyolysis) effect of AtorvaSTATin. Gemfibrozil may increase the serum concentration of AtorvaSTATin. Avoid combination
Grapefruit Juice: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Avoid concurrent use of GFJ (especially larger amounts) with lovastatin, simvastatin, or atorvastatin. Consider using a lower statin dose or a statin that is less likely to interact when possible. Consider therapy modification
Grazoprevir: May increase the serum concentration of AtorvaSTATin. Management: Limit the dose of atorvastatin to a maximum of 20 mg/day when used together with elbasvir and grazoprevir. Monitor closely for evidence of statin-related toxicities such as myalgia or myopathy. Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
HYDROcodone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of HYDROcodone. Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Itraconazole: May increase the serum concentration of AtorvaSTATin. Management: Limit atorvastatin to a maximum adult dose of 20 mg/day in patients receiving itraconazole. Assess clinical response to ensure that the lowest necessary dose of atorvastatin is used. Consider use of fluva-, rosuva-, pitava-, or pravastatin when possible. Consider therapy modification
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Ketoconazole (Systemic): AtorvaSTATin may enhance the adverse/toxic effect of Ketoconazole (Systemic). Specifically, there is a theoretical potential for additive effects on reducing endogenous steroid concentrations. Ketoconazole (Systemic) may increase the serum concentration of AtorvaSTATin. Management: Administer ketoconazole with atorvastatin cautiously, and monitor for toxic effects of atorvastatin (e.g., myalgia, rhabdomyolysis, liver function test abnormalities). Consider use of fluva-, rosuva-, pitava-, or pravastatin when possible. Consider therapy modification
Lanthanum: HMG-CoA Reductase Inhibitors may decrease the serum concentration of Lanthanum. Management: Administer HMG-CoA reductase inhibitors at least two hours before or after lanthanum. Consider therapy modification
Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Felodipine Canadian labeling specifically recommends avoiding its use in combination with clarithromycin. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Consider therapy modification
Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy
Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Midazolam: AtorvaSTATin may increase the serum concentration of Midazolam. Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nafcillin: May increase the metabolism of Calcium Channel Blockers. Consider therapy modification
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy
Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy
Niacin: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy
Niacinamide: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May increase the serum concentration of AtorvaSTATin. Management: Monitor for increased atorvastatin toxicities (eg, myopathy) if these agents are combined. Consider using lower initial doses of atorvastatin. Canadian labeling recommends avoidance of this combination. Consider therapy modification
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
PAZOPanib: AtorvaSTATin may enhance the hepatotoxic effect of PAZOPanib. AtorvaSTATin may increase the serum concentration of PAZOPanib. Avoid combination
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
Phenytoin: Calcium Channel Blockers may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers. Management: Avoid use of nimodipine or nifedipine with phenytoin. Monitor for phenytoin toxicity and/or decreased calcium channel blocker effects with any concurrent use. Consider therapy modification
Phenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination
Posaconazole: May increase the serum concentration of AtorvaSTATin. Avoid combination
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Protease Inhibitors: May increase the serum concentration of AtorvaSTATin. Management: See full monograph for recommended dose limits. Avoid atorvastatin with tipranavir/ritonavir. Consider therapy modification
Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
QuiNIDine: Calcium Channel Blockers (Dihydropyridine) may decrease the serum concentration of QuiNIDine. Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of QuiNIDine. QuiNIDine may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy
QuiNINE: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Consider using a lower starting dose and lower maintenance/maximum doses of atorvastatin, simvastatin, or lovastatin when used together with quinine. Consider therapy modification
Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Monitor therapy
Ranolazine: May increase the serum concentration of AtorvaSTATin. Monitor therapy
Red Yeast Rice: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Avoid combination
Rifamycin Derivatives: May decrease the serum concentration of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some US and Canadian calcium channel blockers contraindicate use with rifampin, however recommendations vary. Consult appropriate labeling. Consider therapy modification
Rifamycin Derivatives: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Management: Consider use of noninteracting antilipemic agents (note: pitavastatin concentrations may increase with rifamycin treatment). Monitor for altered HMG-CoA reductase inhibitor effects. Rifabutin and fluvastatin, or possibly pravastatin, may pose lower risk. Consider therapy modification
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Avoid combination
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of AtorvaSTATin. Management: The maximum atorvastatin dose should not exceed 40 mg/day with concurrent use of simeprevir, and use of the lowest necessary atorvastatin dose is recommended. Consider therapy modification
Simvastatin: AmLODIPine may increase the serum concentration of Simvastatin. Management: Avoid the concurrent use of amlodipine with simvastatin when possible. If used together, avoid doses of simvastatin greater than 20 mg/day (for adults). Consider therapy modification
Spironolactone: AtorvaSTATin may enhance the adverse/toxic effect of Spironolactone. Specifically, there is a theoretical potential for enhanced effects on reducing endogenous steroid activity. Monitor therapy
St Johns Wort: May increase the metabolism of HMG-CoA Reductase Inhibitors. Management: Consider avoiding the concomitant administration of St Johns Wort with interacting HMG-CoA reductase inhibitors in order to avoid the potential for decreased antilipemic effects. Monitor for decreased effects during concomitant therapy. Consider therapy modification
St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy
Telaprevir: May increase the serum concentration of AtorvaSTATin. Avoid combination
Telithromycin: May increase the serum concentration of AtorvaSTATin. Management: Consider limiting atorvastatin to a max (adult) dose of 20 mg/day when used with telithromycin. Although not a specific recommendation in atorvastatin labeling, this is consistent with dosing for other strong CYP3A4 inhibitors, including clarithromycin. Consider therapy modification
Teriflunomide: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Monitor therapy
Ticagrelor: May increase the serum concentration of AtorvaSTATin. Monitor therapy
Tipranavir: May increase the serum concentration of AtorvaSTATin. Avoid combination
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination
Trabectedin: HMG-CoA Reductase Inhibitors may enhance the myopathic (rhabdomyolysis) effect of Trabectedin. Monitor therapy
Velpatasvir: May increase the serum concentration of AtorvaSTATin. Monitor therapy
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification
Verapamil: AtorvaSTATin may increase the serum concentration of Verapamil. Verapamil may increase the serum concentration of AtorvaSTATin. Management: Consider using lower atorvastatin doses when used together with verapamil. Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination
Voriconazole: May increase the serum concentration of AtorvaSTATin. Management: Monitor for toxic effects of atorvastatin (e.g., myalgia, rhabdomyolysis, liver function test abnormalities) during concomitant treatment, and reduce atorvastatin dose when possible. Consider use of fluva-, rosuva-, pitava-, or pravastatin when possible. Consider therapy modification
Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Amlodipine: Blood pressure
Atorvastatin:
2013 ACC/AHA Blood Cholesterol Guideline recommendations (Stone, 2013):
Lipid panel (total cholesterol, HDL, LDL, triglycerides): Baseline lipid panel; fasting lipid profile within 4 to 12 weeks after initiation or dose adjustment and every 3 to 12 months (as clinically indicated) thereafter. If 2 consecutive LDL levels are <40 mg/dL, consider decreasing the dose.
Hepatic transaminase levels: Baseline measurement of hepatic transaminase levels (ie, ALT); measure hepatic function if symptoms suggest hepatotoxicity (eg, unusual fatigue or weakness, loss of appetite, abdominal pain, dark-colored urine or yellowing of skin or sclera) during therapy.
CPK: CPK should not be routinely measured. Baseline CPK measurement is reasonable for some individuals (eg, family history of statin intolerance or muscle disease, clinical presentation, concomitant drug therapy that may increase risk of myopathy). May measure CPK in any patient with symptoms suggestive of myopathy (pain, tenderness, stiffness, cramping, weakness, or generalized fatigue).
Evaluate for new-onset diabetes mellitus during therapy; if diabetes develops, continue statin therapy and encourage adherence to a heart-healthy diet, physical activity, a healthy body weight, and tobacco cessation.
If patient develops a confusional state or memory impairment, may evaluate patient for nonstatin causes (eg, exposure to other drugs), systemic and neuropsychiatric causes, and the possibility of adverse effects associated with statin therapy.
Manufacturer 's labeling: Baseline liver function tests and repeat when clinically indicated thereafter. Upon initiation or titration, lipid panel should be analyzed within 2 to 4 weeks.
See individual agents.
Concerns related to adverse effects:
- Angina/MI: Increased angina and/or MI has occurred with initiation or dosage titration of dihydropyridine calcium channel blockers. Reflex tachycardia may occur resulting in angina and/or MI in patients with obstructive coronary disease especially in the absence of concurrent beta-blockade.
- Diabetes mellitus: Increases in HbA1c and fasting blood glucose have been reported with HMG-CoA reductase inhibitors; however, the benefits of statin therapy far outweigh the risk of dysglycemia.
- Hepatotoxicity: Postmarketing reports of fatal and nonfatal hepatic failure with atorvastatin are rare. If serious hepatotoxicity with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, interrupt therapy. If an alternate etiology is not identified, do not restart atorvastatin. Liver enzyme tests should be obtained at baseline and as clinically indicated; routine periodic monitoring of liver enzymes is not necessary. Ethanol may enhance the potential of adverse hepatic effects; instruct patients to avoid excessive ethanol consumption.
- Hypotension/syncope: Symptomatic hypotension with or without syncope can rarely occur with amlodipine; blood pressure must be lowered at a rate appropriate for the patients clinical condition.
- Immune-mediated necrotizing myopathy (IMNM): IMNM, an autoimmune-mediated myopathy, has been reported (rarely) with HMG-CoA reductase inhibitor therapy. IMNM presents as proximal muscle weakness with elevated CPK levels, which persists despite discontinuation of HMG-CoA reductase inhibitor therapy; additionally, muscle biopsy may show necrotizing myopathy with limited inflammation. Immunosuppressive therapy (eg, corticosteroids, azathioprine) may be used for treatment.
- Myopathy/rhabdomyolysis: Patients receiving HMG-CoA reductase inhibitors have developed rhabdomyolysis with acute renal failure and/or myopathy; patients should be monitored closely. This risk is dose-related and is increased with concurrent use of CYP3A4 inhibitors (eg, clarithromycin, protease inhibitors), fibric acid derivatives (eg, gemfibrozil), or niacin (doses ≥1 g/day) (see Drug Interactions). If concurrent use of clarithromycin or combination protease inhibitors (eg, lopinavir/ritonavir or ritonavir/saquinavir) is warranted consider dose adjustment of atorvastatin. Ensure patient is on the lowest effective atorvastatin dose in all circumstances. Discontinue in any patient in which CPK levels are markedly elevated (>10 times ULN) or if myopathy is suspected/diagnosed. Use caution in patients with renal impairment, inadequately treated hypothyroidism, and those taking other drugs associated with myopathy (eg, colchicine); these patients are predisposed to myopathy. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine.
- Peripheral edema: The most common side effect of amlodipine is peripheral edema (dose dependent); occurs within 2-3 weeks of starting therapy.
Disease-related concerns:
- Aortic stenosis: Use amlodipine with extreme caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia.
- Hepatic impairment and/or ethanol use: Use atorvastatin 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 transaminases. Use amlodipine with caution in patients with hepatic impairment; may require lower starting dose; titrate slowly in patients with severe hepatic impairment.
- Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Use amlodipine with caution in patients with HCM and outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition.
- Stroke: Patients with recent stroke or TIA receiving long-term therapy with high-dose (ie, 80 mg/day) atorvastatin may be at increased risk for hemorrhagic stroke (SPARCL Investigators, 2006). A subsequent post-hoc analysis demonstrated that patients with lacunar or hemorrhagic stroke may be at higher risk of hemorrhagic stroke; however, this finding was determined to be hypothesis generating. The overall benefit of treatment with atorvastatin (ie, reduced risk of stroke and cardiovascular events) in this population seems to outweigh the increased risk of hemorrhagic stroke if one truly exists (Goldstein, 2008).
Concurrent drug therapy issues:
- High potential for interactions: Use atorvastatin with caution in patients taking strong CYP3A4 inhibitors (see Drug Interactions); consider alternative agents that avoid or lessen potential for CYP-mediated. Do not use with cyclosporine, gemfibrozil, tipranavir plus ritonavir, or telaprevir.
Special populations:
- Elderly: Use atorvastatin with caution in patients with advanced age, these patients are predisposed to myopathy.
- Surgical patients: The manufacturer recommends temporary discontinuation for elective major surgery, acute medical or surgical conditions, or in any patient experiencing an acute or serious condition predisposing to renal failure (eg, sepsis, hypotension, trauma, uncontrolled seizures). Based on current research and clinical guidelines (Fleisher, 2009), HMG-CoA reductase inhibitors should be continued in the perioperative period. Postoperative discontinuation of statin therapy is associated with an increased risk of cardiac morbidity and mortality.
Other warnings/precautions:
- Appropriate use: Secondary causes of hyperlipidemia should be ruled out prior to therapy with atorvastatin. Atorvastatin has not been studied when the primary lipid abnormality is chylomicron elevation (Fredrickson types I and V).
- Titration: Dosage titration of amlodipine should occur after 7-14 days on a given dose.
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Use of atorvastatin is contraindicated in pregnancy or women who may become pregnant. See individual agents.
Amlodipine: Inhibits calcium ion from entering the "slow channels " � or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization, producing a relaxation of coronary vascular smooth muscle and coronary vasodilation; increases myocardial oxygen delivery in patients with vasospastic angina. Amlodipine directly acts on vascular smooth muscle to produce peripheral arterial vasodilation reducing peripheral vascular resistance and blood pressure.
Atorvastatin: Inhibitor of 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 stimulation of LDL catabolism. In addition to the ability of HMG-CoA reductase inhibitors to decrease levels of high-sensitivity C-reactive protein (hsCRP), they also possess pleiotropic properties including improved endothelial function, reduced inflammation at the site of the coronary plaque, inhibition of platelet aggregation, and anticoagulant effects (de Denus, 2002; Ray, 2005).
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience diarrhea, nausea, rhinorrhea, loss of strength and energy, pharyngitis, or insomnia. Have patient report immediately to prescriber severe dizziness, passing out, shortness of breath, excessive weight gain, swelling of arms or legs, angina, tachycardia, bradycardia, arrhythmia, memory impairment, severe joint pain, muscle pain, muscle weakness, muscle rigidity, tremors, abnormal movements, urinary retention, change in amount of urine passed, signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), or signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.