Aliskiren + Amlodipine

Hypertension

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

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 the lowest available dose of amlodipine (5 mg)

Hepatic Impairment Use caution; consider lower initial dose; titrate slowly

High fat meals decrease bioavailability substantially

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

Avoid concomitant use with ARBs or ACEI in patients with renal impairment (GFR<60 mL/min) Anaphylactic Reactions and Head and Neck Angioedema: Discontinue Aliskiren + Amlodipine and monitor until signs and symptoms resolve. Hypotension in volume- and/or salt-depleted patients or with the combined use of other agents acting on RAAS: Correct imbalances before initiating therapy with Aliskiren + Amlodipine. Increased angina or myocardial infarction with calcium channel blockers may occur upon dosage initiation or increase. Impaired renal function: Monitor serum creatinine periodically. Hyperkalemia: Monitor potassium levels periodically. Monitoring Parameters Monitor serum creatinine periodically. Monitor potassium levels periodically.

Not Classi 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

Cyclosporine: Avoid concomitant use Itraconazole: Avoid concomitant use NSAIDs use may lead to an increased risk of renal impairment and loss of antihypertensive effect If simvastatin is co-administered with amlodipine, do not exceed doses greater than 20 mg daily of simvastatin Contraindicated (6) azilsartan benazepril candesartan captopril dantrolene enalapril Serious - Use Alternative (24) apalutamide azilsartan captopril chloramphenicol chloroquine conivaptan cyclosporine diltiazem enzalutamide erdafitinib fexinidazole idelalisib itraconazole ivosidenib lasmiditan lofexidine lonafarnib nifedipine nirmatrelvir/ritonavir potassium phosphates, IV simvastatin sotorasib tepotinib voxelotor

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

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