Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

tablet

  • 150mg/5mg
  • 150mg/10mg
  • 300mg/5mg
  • 300mg/10mg
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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)

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Interactions

Interaction Checker

and aliskiren/amlodipine

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            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
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            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%)
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            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.

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            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%)
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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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