Dosing & Uses
Dosage Forms & Strengths
tablet
- 150mg/5mg
- 150mg/10mg
- 300mg/5mg
- 300mg/10mg
Hypertension
May switch to aliskiren/amlodipine if patient inadequately controlled with aliskiren alone or amlodipine alone (or another dihydropyridine calcium channel blocker); may use as replacement therapy for patients currently maintained on aliskiren and amlodipine
Initial: 150 mg/5 mg PO qDay
If blood pressure remains uncontrolled after 2-4 weeks, may titrate upward as needed, not to exceed 300 mg/10 mg daily
Renal Impairment
<30 mL/min: Dose adjustment not necessary; use caution (monitor for hyperkalemia or renal dysfunction)
>30 mL/min: Dose adjustment not necessary
Hepatic Impairment
Use caution; consider lower initial dose; titrate slowly
Administration
High fat meals decrease bioavailability substantially
Safety and efficacy not established
In the short-term controlled clinical trials, 17% of patients treated were ≥65 yr; no overall differences in safety or effectiveness were observed between these subjects and younger subjects
Aliskiren AUC and Cmax increased by 57% and 28% respectively; no significant effect on clinical efficacy or safety
Amlodipine AUC increased by 40-60% in elderly patients ≥ 65 years and older; consider starting with lowest available dose of amlodipine (5 mg)
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (9)
- azilsartan
azilsartan decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ARBs in patients with diabetes; avoid coadministration with ARBs if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ARBS with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- benazepril
benazepril decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ACE-inhibitors in patients with diabetes; avoid coadministration with ACE-inhibitors if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ACE-inhibitors with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- candesartan
candesartan decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ARBs in patients with diabetes; avoid coadministration with ARBs if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ARBS with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- captopril
captopril decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ACE-inhibitors in patients with diabetes; avoid coadministration with ACE-inhibitors if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ACE-inhibitors with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- dantrolene
dantrolene, amlodipine. Either increases toxicity of the other by Mechanism: pharmacodynamic synergism. Contraindicated. Rare incidence of cardiovascular collapse and marked hyperkalemia observed when coadministered; may be higher risk with nondihydropyridine calcium channel blockers.
- enalapril
enalapril, aliskiren. Either increases toxicity of the other by Mechanism: pharmacodynamic synergism. Contraindicated. Aliskiren use contraindicated with ACEIs in patients with diabetes; avoid coadministration with ACEIs if GFR <60 mL/min; dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.
enalapril decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ACE-inhibitors in patients with diabetes; avoid coadministration with ACE-inhibitors if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ACE-inhibitors with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically. - eprosartan
eprosartan decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ARBs in patients with diabetes; avoid coadministration with ARBs if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ARBS with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- fezolinetant
amlodipine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors
- fosinopril
fosinopril decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ACE-inhibitors in patients with diabetes; avoid coadministration with ACE-inhibitors if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ACE-inhibitors with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
Serious - Use Alternative (25)
- abametapir
abametapir will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.
- apalutamide
apalutamide will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
- azilsartan
aliskiren, azilsartan. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Coadministration associated with increased risk of non-fatal stroke, renal complications, hyperkalemia, and hypotension.
- captopril
aliskiren, captopril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Aliskiren use contraindicated with ACEIs in patients with diabetes. Avoid coadministration with ACEIs if CrCl<60mL/min.
- chloramphenicol
chloramphenicol will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- chloroquine
chloroquine will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- conivaptan
conivaptan will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Calcium channel blockers with depressant effects on the sinus and AV nodes could potentiate dronedarone's effects on conduction. Give a low dose of calcium channel blockers initially and increase only ECG is reviewed and tolerated.
- cyclosporine
cyclosporine will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concurrent use. Coadministration of 200 mg and 600 mg cyclosporine, with 75 mg aliskiren resulted in an approximately 2.5-fold increase in Cmax and 5-fold increase in AUC of aliskiren
cyclosporine will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid concurrent use. Coadministration of 200 mg and 600 mg cyclosporine, with 75 mg aliskiren resulted in an approximately 2.5-fold increase in Cmax and 5-fold increase in AUC of aliskiren - diltiazem
diltiazem will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Concomitant use with amlodipine and diltiazem reported an a 60% increase in amlodipine AUC. Monitor increased effects and toxicities (eg, bradycardia, sinus arrest, decreased cardiac output) if amiodarone is concomitantly used with nondihydropyridine calcium channel blocker (ie, diltiazem).
- enzalutamide
enzalutamide will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- erdafitinib
erdafitinib will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.
- fexinidazole
fexinidazole will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
- idelalisib
idelalisib will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates
- itraconazole
itraconazole will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Consider an alternative with no or minimal potential to inhibit CYP3A4. If concomitant use of strong CYP3A4 inhibitors is unavoidable, closely monitor for respiratory depression and sedation, and consider decreasing alfentanil dose necessary.
- ivosidenib
ivosidenib will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
- lasmiditan
lasmiditan increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- lofexidine
lofexidine, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.
- lonafarnib
amlodipine will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.
lonafarnib will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling. - nifedipine
nifedipine will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Aliskiren product labeling recommends avoiding concomitant use with CYP3A4 and P-gp inhibitors.
- potassium phosphates, IV
aliskiren and potassium phosphates, IV both increase serum potassium. Avoid or Use Alternate Drug.
- simvastatin
amlodipine increases levels of simvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: Benefits of combination therapy should be carefully weighed against the potential risks of combination. Potential for increased risk of myopathy/rhabdomyolysis. Limit simvastatin dose to no more than 20 mg/day when used concurrently.
- sotorasib
sotorasib will decrease the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.
- tepotinib
tepotinib will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.
- voxelotor
voxelotor will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.
Monitor Closely (183)
- acebutolol
acebutolol and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.
- aldesleukin
aldesleukin increases effects of amlodipine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.
- alfuzosin
alfuzosin and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.
- amifostine
amifostine, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.
amifostine, aliskiren. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine. - asenapine
asenapine and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.
- aspirin
aspirin will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- aspirin rectal
aspirin rectal will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- atenolol
atenolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.
- atogepant
amlodipine will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- atorvastatin
atorvastatin will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
atorvastatin increases levels of aliskiren by unspecified interaction mechanism. Use Caution/Monitor. - avanafil
avanafil increases effects of amlodipine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.
avanafil increases effects of aliskiren by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension. - avapritinib
amlodipine will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- berotralstat
berotralstat will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.
- axitinib
amlodipine increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- belzutifan
belzutifan will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.
- betaxolol
betaxolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.
- bisoprolol
bisoprolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.
- bosentan
bosentan will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for decreased effects of amlodipine (CYP3A4 substrate) if bosentan is initiated/dose increased. Also, monitor toxicities of amlodipine if bosentan is discontinued/dose decreased.
- bosutinib
bosutinib increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- bretylium
amlodipine, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.
- butabarbital
butabarbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- butalbital
butalbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- calcium acetate
calcium acetate decreases effects of amlodipine by pharmacodynamic antagonism. Use Caution/Monitor.
- calcium carbonate
calcium carbonate decreases effects of amlodipine by pharmacodynamic antagonism. Use Caution/Monitor.
- calcium chloride
calcium chloride decreases effects of amlodipine by pharmacodynamic antagonism. Use Caution/Monitor.
- calcium citrate
calcium citrate decreases effects of amlodipine by pharmacodynamic antagonism. Use Caution/Monitor.
- calcium gluconate
calcium gluconate decreases effects of amlodipine by pharmacodynamic antagonism. Use Caution/Monitor.
- canagliflozin
aliskiren and canagliflozin both increase serum potassium. Use Caution/Monitor.
- carbamazepine
carbamazepine will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
- carbidopa
carbidopa increases effects of amlodipine by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
- carvedilol
carvedilol and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.
- celecoxib
celecoxib will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- celiprolol
celiprolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.
- cenobamate
cenobamate will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
- ceritinib
ceritinib will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- choline magnesium trisalicylate
choline magnesium trisalicylate will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- clarithromycin
clarithromycin will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased effect of calcium channel blockers may lead to hypotension, edema, decreased HR, and acute kidney injury due to reduced renal blood flow
- clevidipine
amlodipine and clevidipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.
- cobicistat
cobicistat will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- crizotinib
crizotinib increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
crizotinib increases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A. - cyclosporine
cyclosporine will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
amlodipine increases levels of cyclosporine by unspecified interaction mechanism. Modify Therapy/Monitor Closely. A prospective study in renal transplant recipients averaged a 40% increase in cyclosporine trough levels. - diclofenac
diclofenac will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- dabrafenib
dabrafenib will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
- darunavir
darunavir will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- deferasirox
deferasirox will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dichlorphenamide
dichlorphenamide and amlodipine both decrease serum potassium. Use Caution/Monitor.
- diflunisal
diflunisal will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- diltiazem
amlodipine and diltiazem both increase anti-hypertensive channel blocking. Use Caution/Monitor.
- doxazosin
doxazosin and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.
- dronedarone
dronedarone will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Calcium channel blockers with depressant effects on the sinus and AV nodes could potentiate dronedarone's effects on conduction. Give a low dose of calcium channel blockers initially and increase only ECG is reviewed and tolerated.
- efavirenz
efavirenz will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- elagolix
elagolix will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.
elagolix will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - eliglustat
eliglustat increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.
- encorafenib
encorafenib, amlodipine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
- erythromycin base
erythromycin base will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
erythromycin base will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
erythromycin ethylsuccinate will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
erythromycin lactobionate will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - erythromycin stearate
erythromycin stearate will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
erythromycin stearate will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- etodolac
etodolac will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- esmolol
esmolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.
- fedratinib
fedratinib will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
- felodipine
amlodipine and felodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.
- fenoprofen
fenoprofen will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- finerenone
amlodipine will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.
- flibanserin
amlodipine will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.
- fluconazole
fluconazole will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- flurbiprofen
flurbiprofen will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- fosamprenavir
fosamprenavir will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fosphenytoin
fosphenytoin will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fostamatinib
fostamatinib will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of P-gp substrates. Monitor for toxicities of the P-gp substrate drug that may require dosage reduction when given concurrently with fostamatinib.
- furosemide
aliskiren decreases levels of furosemide by unspecified interaction mechanism. Use Caution/Monitor.
- glecaprevir/pibrentasvir
glecaprevir/pibrentasvir will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.
- griseofulvin
griseofulvin will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ibuprofen
ibuprofen will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- ibuprofen IV
ibuprofen IV will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- ibuprofen/famotidine
ibuprofen/famotidine will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- iloperidone
iloperidone and amlodipine both increase additive vasodilation. Use Caution/Monitor. Calcium channel blockers with iloperidone may potentiate the hypotensive effects.
- indomethacin
indomethacin will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- irbesartan
irbesartan decreases levels of aliskiren by unspecified interaction mechanism. Use Caution/Monitor.
- isavuconazonium sulfate
amlodipine will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- isradipine
amlodipine and isradipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.
- istradefylline
istradefylline will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.
istradefylline will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates. - itraconazole
itraconazole will increase the level or effect of amlodipine by Other (see comment). Modify Therapy/Monitor Closely. CCBs elicit negative inotropic effects which may be additive to those of itraconazole; additionally, itraconazole can inhibit the metabolism of calcium channel blockers. Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.
- ivacaftor
ivacaftor increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.
- ketoconazole
ketoconazole will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
ketoconazole will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
ketoconazole will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - ketoprofen
ketoprofen will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- labetalol
labetalol and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.
- ketorolac
ketorolac will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- ketorolac intranasal
ketorolac intranasal will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- lemborexant
amlodipine will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.
- lenacapavir
lenacapavir will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- lesinurad
lesinurad decreases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- letermovir
letermovir increases levels of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
letermovir increases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - levodopa
levodopa increases effects of amlodipine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
- levoketoconazole
levoketoconazole will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
levoketoconazole will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - levoketoconazole
levoketoconazole will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lomitapide
lomitapide increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing dose when used concomitantly with lomitapide.
amlodipine increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day. - lopinavir
lopinavir will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lurasidone
lurasidone increases effects of aliskiren by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.
- lorlatinib
lorlatinib will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lurasidone
lurasidone increases effects of amlodipine by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.
- magnesium supplement
magnesium supplement, amlodipine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Calcium channel blockers may increase toxic effects of magnesium; magnesium may increase hypotensive effects of calcium channel blockers.
- maraviroc
maraviroc, aliskiren. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.
maraviroc, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension. - meclofenamate
meclofenamate will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- mefloquine
mefloquine increases levels of amlodipine by decreasing metabolism. Use Caution/Monitor. Risk of arrhythmia.
- mefenamic acid
mefenamic acid will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- meloxicam
meloxicam will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- metformin
amlodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.
- methylphenidate
methylphenidate will decrease the level or effect of amlodipine by pharmacodynamic antagonism. Use Caution/Monitor. Methylphenidate may diminish antihypertensive effects. Monitor BP.
- midazolam intranasal
amlodipine will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.
- mifepristone
mifepristone will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- mitotane
mitotane decreases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.
- moxisylyte
moxisylyte and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.
- nabumetone
nabumetone will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- nadolol
nadolol and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.
- naproxen
naproxen will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- nebivolol
nebivolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.
- nefazodone
nefazodone will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
nefazodone will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. - nevirapine
nevirapine will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nitroglycerin rectal
nitroglycerin rectal, aliskiren. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Observe for possible additive hypotensive effects during concomitant use. .
- nicardipine
amlodipine and nicardipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.
- nifedipine
amlodipine and nifedipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.
- nilotinib
nilotinib will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nirmatrelvir
nirmatrelvir will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce amlodipine dose by 50% during coadministration and for 3 more days after the last nirmatrelvir/ritonavir dose.
- nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce amlodipine dose by 50% during coadministration and for 3 more days after the last nirmatrelvir/ritonavir dose.
- nisoldipine
amlodipine and nisoldipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.
- nitroglycerin rectal
nitroglycerin rectal, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Marked orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used concomitantly. Observe for possible additive hypotensive effects during concomitant use. .
- nitroglycerin sublingual
amlodipine, nitroglycerin sublingual. Either increases toxicity of the other by additive vasodilation. Modify Therapy/Monitor Closely. Marked orthostatic hypotension reported with concomitant use.
- nitroprusside sodium
amlodipine increases effects of nitroprusside sodium by pharmacodynamic synergism. Use Caution/Monitor.
- ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease dose of calcium channel blocker; dose of amlodipine should be decreased by at least 50%; clinical monitoring of patients is recommended for edema and/or signs and symptoms of hypotension. if such events occur, consider further dose reduction of calcium channel blocker or switching to alternative to calcium channel blocker
ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of amlodipine by altering metabolism. Modify Therapy/Monitor Closely. Decrease dose of calcium channel blocker; dose of amlodipine should be decreased by at least 50%; clinical monitoring of patients is recommended for edema and/or signs and symptoms of hypotension. if such events occur, consider further dose reduction of calcium channel blocker or switching to alternative to calcium channel blocker - oxaprozin
oxaprozin will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- penbutolol
penbutolol and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.
- pentobarbital
pentobarbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- phenobarbital
phenobarbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- phenoxybenzamine
phenoxybenzamine and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.
- phentolamine
phentolamine and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.
- phenytoin
amlodipine will increase the level or effect of phenytoin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
- pindolol
pindolol and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.
- piroxicam
piroxicam will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- ponatinib
ponatinib increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- posaconazole
posaconazole will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- potassium citrate/citric acid
aliskiren and potassium citrate/citric acid both increase serum potassium. Use Caution/Monitor.
- prazosin
prazosin and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.
- primidone
primidone will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- propranolol
propranolol and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.
- quinidine
quinidine will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ribociclib
ribociclib will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rifabutin
rifabutin will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rifampin
rifampin will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rifapentine
rifapentine will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ritonavir
ritonavir will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rucaparib
rucaparib will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- salsalate
salsalate will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- saquinavir
saquinavir increases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .
- sarecycline
sarecycline will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.
- silodosin
silodosin and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.
- sodium sulfate/?magnesium sulfate/potassium chloride
amlodipine, sodium sulfate/?magnesium sulfate/potassium chloride. Either increases effects of the other by unknown mechanism. Use Caution/Monitor. Monitor for hypotension or muscle weakness in patients receiving calcium channel blockers with elevated serum magnesium concentrations.
- sodium sulfate/potassium sulfate/magnesium sulfate
amlodipine, sodium sulfate/potassium sulfate/magnesium sulfate. Either increases effects of the other by unknown mechanism. Use Caution/Monitor. Monitor for hypotension or muscle weakness in patients receiving calcium channel blockers with elevated serum magnesium concentrations.
- sotalol
sotalol and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.
- St John's Wort
St John's Wort will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
- stiripentol
stiripentol will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.
stiripentol, amlodipine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment. - sulindac
sulindac will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- tacrolimus
amlodipine will increase the level or effect of tacrolimus by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Adjust dose when appropriate.
- tadalafil
tadalafil increases effects of amlodipine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.
tadalafil increases effects of aliskiren by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension. - tazemetostat
tazemetostat will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
amlodipine will decrease the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - tolmetin
tolmetin will decrease the level or effect of aliskiren by Other (see comment). Use Caution/Monitor. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.
- tecovirimat
tecovirimat will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
- temsirolimus
amlodipine increases toxicity of temsirolimus by Other (see comment). Use Caution/Monitor. Comment: Combination of mTOR inhibitors with calcium channel blockers increases risk of angioedema.
- terazosin
terazosin and amlodipine both increase anti-hypertensive channel blocking. Use Caution/Monitor.
- timolol
timolol and amlodipine both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.
- tinidazole
amlodipine will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tipranavir
tipranavir increases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. Tipranavir is used with ritonavir (boosted therapy) which is a potent CYP3A4 inhibitor.
- trazodone
trazodone will decrease the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- trimagnesium citrate anhydrous
trimagnesium citrate anhydrous, amlodipine. Either increases effects of the other by Other (see comment). Use Caution/Monitor. Comment: Possible additive effect of magnesium and calcium channel blockers on reduction of ionic calcium may increase risk of hypotension or muscle weakness.
- trimethoprim
trimethoprim and aliskiren both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.
- tucatinib
tucatinib will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.
- vemurafenib
vemurafenib increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- verapamil
amlodipine and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.
verapamil will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
verapamil will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - voclosporin
voclosporin and aliskiren both increase serum potassium. Use Caution/Monitor.
voclosporin, aliskiren. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity. - voriconazole
voriconazole will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
voriconazole increases levels of amlodipine by decreasing metabolism. Use Caution/Monitor. - xipamide
xipamide increases effects of amlodipine by pharmacodynamic synergism. Use Caution/Monitor.
Minor (72)
- acetazolamide
acetazolamide will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- agrimony
agrimony increases effects of amlodipine by pharmacodynamic synergism. Minor/Significance Unknown.
- amiodarone
amiodarone will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- amobarbital
amobarbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- aprepitant
aprepitant will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- armodafinil
armodafinil will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- artemether/lumefantrine
artemether/lumefantrine will decrease the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
artemether/lumefantrine will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. - atazanavir
atazanavir will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
atazanavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. - atracurium
amlodipine increases effects of atracurium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.
- clarithromycin
clarithromycin will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
clarithromycin will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown. - brimonidine
brimonidine increases effects of amlodipine by pharmacodynamic synergism. Minor/Significance Unknown.
- cisatracurium
amlodipine increases effects of cisatracurium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.
- conivaptan
conivaptan will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cornsilk
cornsilk increases effects of amlodipine by pharmacodynamic synergism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- darunavir
darunavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- dasatinib
dasatinib will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- dexamethasone
dexamethasone will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- DHEA, herbal
DHEA, herbal will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- dronedarone
dronedarone will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- erythromycin base
erythromycin base will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- erythromycin stearate
erythromycin stearate will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- etravirine
etravirine will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- fo-ti
fo-ti increases effects of amlodipine by pharmacodynamic synergism. Minor/Significance Unknown.
- forskolin
forskolin increases effects of amlodipine by pharmacodynamic synergism. Minor/Significance Unknown.
- fosamprenavir
fosamprenavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- fosaprepitant
fosaprepitant will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- grapefruit
grapefruit will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- hydrocortisone
hydrocortisone will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
hydrocortisone will decrease the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. - incobotulinumtoxinA
amlodipine increases effects of incobotulinumtoxinA by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.
- indinavir
indinavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- lapatinib
lapatinib will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- lithium
amlodipine increases toxicity of lithium by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of neurotoxicity.
- maitake
maitake increases effects of amlodipine by pharmacodynamic synergism. Minor/Significance Unknown.
- metipranolol ophthalmic
metipranolol ophthalmic increases effects of amlodipine by pharmacodynamic synergism. Minor/Significance Unknown.
- nefazodone
nefazodone will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- nelfinavir
nelfinavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
nelfinavir will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. - nicardipine
nicardipine will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- octacosanol
octacosanol increases effects of amlodipine by pharmacodynamic synergism. Minor/Significance Unknown.
- nilotinib
nilotinib will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- onabotulinumtoxinA
amlodipine increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.
- oxcarbazepine
oxcarbazepine will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- pancuronium
amlodipine increases effects of pancuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.
- porfimer
amlodipine decreases levels of porfimer by unspecified interaction mechanism. Minor/Significance Unknown.
- posaconazole
posaconazole will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- quinupristin/dalfopristin
quinupristin/dalfopristin will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ranolazine
ranolazine will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- rapacuronium
amlodipine increases effects of rapacuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.
- reishi
reishi increases effects of amlodipine by pharmacodynamic synergism. Minor/Significance Unknown.
- rifampin
rifampin will decrease the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- ritonavir
ritonavir will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
ritonavir will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown. - rocuronium
amlodipine increases effects of rocuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.
- rufinamide
rufinamide will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ruxolitinib
amlodipine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ruxolitinib topical
amlodipine will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- secobarbital
secobarbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- shepherd's purse
shepherd's purse, amlodipine. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.
- simvastatin
simvastatin will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- St John's Wort
St John's Wort will decrease the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- succinylcholine
amlodipine increases effects of succinylcholine by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.
- tacrolimus
tacrolimus will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- tizanidine
tizanidine increases effects of amlodipine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.
- tolvaptan
tolvaptan will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.
- treprostinil
treprostinil increases effects of amlodipine by pharmacodynamic synergism. Minor/Significance Unknown.
- vecuronium
amlodipine increases effects of vecuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.
- verteporfin
amlodipine increases levels of verteporfin by pharmacodynamic synergism. Minor/Significance Unknown.
- voriconazole
voriconazole will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
Adverse Effects
Adverse reactions reported with combination product and individual agents
>10%
Amlodipine
- Peripheral edema (2-15%)
1-10%
Peripheral edema (6.2-8.9%)
Aliskiren
- Diarrhea (2.3%)
- Cough (1.1%)
- Increased creatinine kinase (1%)
- Increased BUN (≤ 7%)
- Hyperkalemia (≤1%)
- Rash (1%)
Amlodipine
- Flushing (1-5%)
- Palpitation (1-5%)
- Dizziness (1-3%)
- Fatigue (5%)
- Somnolence (1-2%)
- Rash (1-2%)
- Pruritus (1-2%)
- Male sexual dysfunction (1-2%)
- Nausea (3%)
- Dyspepsia (1-2%)
- Abdominal pain (1-2%)
- Muscle cramps (1-2%)
- Dyspnea (1-2%)
- Weakness (1-2%)
<1%
Angioedema
Increased BUN
Increased creatinine
Hyperkalemia
Hypotension
Aliskiren
- Gastroesophageal reflux
- Periorbital edema
- Toxic epiderma necrolysis
- Increased uric acid
- Severe hypotension
- Stevens Johnson syndrome
Amlodipine
- Abnormal vision
- Arthralgia
- Chest pain
- Abnormal dreams
- Increased apetite
- Acute interstitial nephritis
- Alopecia
- Conjunctivitis
- Cough
- Depression
- Dysphagia
- Flatulence
Postmarketing Reports
Nausea/vomiting
Aliskiren
- Hyponatremia
Warnings
Black Box Warnings
Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death
Contraindications
Hypersensitivity
Pregnancy (2nd and 3rd trimesters; significant risk of fetal and neonatal morbidity/mortality; see Black Box Warnings)
Concomitant use with ACEIs or ARBs in patients with diabetes mellitus
Cautions
Symptomatic hypotension may occur after initiation of treatment in patients with marked volume depletion, patients with salt depletion, or with combined use of aliskiren and other agents acting on the renin-angiotensin– aldosterone system (RAAS); volume or salt depletion should be corrected prior to administration of therapy, or treatment should start under close medical supervision; a transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once blood pressure has stabilized
Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with aliskiren and has necessitated hospitalization and intubation; treatment with antihistamines and corticosteroids may not be sufficient to prevent respiratory involvement; prompt administration of subcutaneous epinephrine solution 1:1000 (0.3 mL to 0.5 mL) and measures to ensure a patent airway may be necessary; discontinue therapy immediately in patients who develop anaphylactic reactions or angioedema, and do not readminister
Increased angina or myocardial infarction with calcium channel blockers may occur upon dosage initiation or increased
Renal impairment: Decrease in renal function may be anticipated with susceptible individuals
Titrate slowly in patients with hepatic impairment or heart failure
Cyclosporine or itraconazole increase aliskiren levels; avoid concomitant use
Preclinical studies indicate a potential for substantial increase in exposure to aliskiren in pediatric patients
Patients whose renal function may depend in part on activity of renin-angiotensin– aldosterone system (RAAS; e.g., patients with renal artery stenosis, severe heart failure, postmyocardial infarction or volume depletion) or patients receiving ARB, ACE inhibitors or nonsteroidal anti-inflammatory drug (NSAID), including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors), therapy may be at particular risk of developing acute renal failure; monitor renal function periodically; consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function
Coadministration with ACE inhibitors or ARBs
- When aliskiren was prescribed with ACE inhibitors or angiotensin receptor blockers (ARBs) in the ALTITUDE study, an increased incidence of nonfatal stroke, renal complications, hyperkalemia, and hypotension was observed after 18-24 months
- The ALTITUDE trial included patients with hypertension plus type 2 diabetes and renal impairment who were at high risk of cardiovascular and renal events
- Coadministration of aliskiren with angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with diabetes or kidney (renal) impairment; their use is contraindicated in patients with diabetes
- Avoid coadministration of aliskiren with ARBs or ACEIs in moderate to severe renal impairment (ie, GFR <60 mL/min)
- Hyperkalemia: Increases in serum potassium >5.5 mEq/L were infrequent with aliskiren (0.9% compared to 0.6% with placebo); however, when used in combination with an ACE inhibitor in a diabetic population, increases in serum potassium were more frequent (5.5%)
Pregnancy & Lactation
Pregnancy
Hypertension in pregnancy increases maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage); hypertension increases fetal risk for intrauterine growth restriction and intrauterine death; pregnant women with hypertension should be carefully monitored and managed accordingly
Use of drugs that act on renin-angiotensin system in second and third trimesters of pregnancy can result in reduced fetal renal function leading to anuria and renal failure, oligohydramnios, fetal lung hypoplasia and skeletal deformations, including skull hypoplasia, hypotension, and death
In patients taking the combination drug during pregnancy, perform serial ultrasound examinations to assess intra-amniotic environment; fetal testing may be appropriate, based on the week of gestation; patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury; closely observe infants with histories of in utero exposure to the drug combination for hypotension, oliguria, and hyperkalemia; if oliguria or hypotension occur in neonates with a history of in utero exposure to the drug combination, support blood pressure and renal perfusion; exchange transfusions or dialysis may be required as a means of reversing hypotension and substituting for disordered renal function
Lactation
There is no information regarding the presence in human milk, the effects on the breastfed infant, or the effects on milk production; limited published studies report that amlodipine is present in human milk; however, there is insufficient information to determine effects of amlodipine on the breastfed infant; there is no available information on effects of amlodipine on milk production; because of potential for serious adverse reactions, including hypotension, hyperkalemia and renal impairment in nursing infants, advise a nursing woman that breastfeeding is not recommended during treatment
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Aliskiren: Renin inhibitor; blocks effect of increased renin levels, thereby decreasing feedback loop and reducing plasma renin activity, angiotensin I, and angiotensin II
Amlodipine: Calcium channel blocker; inhibits extracellular Ca ions across the membranes of myocardial cells and vascular smooth muscle cells, resulting in inhibition of cardiac and vascular smooth muscle contraction; this action causes dilation of the main coronary and systemic arteries
Pharmacokinetics
Aliskiren
- Onset: Within 2 weeks
- Bioavailability: 3%
- Peak Plasma Time: 1-3 hr
- Metabolism: Metabolized by CYP3A4
- Half-Life: 24 hr
- Excretion: Urine (25% as parent compound in urine)
Amlodipine
- Duration: 24 hr (antihypertensive effects)
- Vd: 21 L/kg
- Bioavailability: 64-90%
- Half-life: 30-50 hr
- Metabolism: Liver (>90%)
- Protein binding: 93-98%
- Peak plasma time: 6-12 hr
- Excretion: Urine (70%)
