aliskiren/amlodipine

General

Pronunciation:
a-lis-ki-ren/am-loe-di-peen


Trade Name(s)

  • Tekamlo

Ther. Class.
antihypertensives

Pharm. Class.
renin inhibitors
calcium channel blockers

Indications

  • Initial treatment of hypertension in patients unlikely to respond to a single agent.
  • Treatment of hypertension in patients inadequately treated with a single drug (add-on).
  • Replacement therapy in patients controlled with its individual components.

Action

  • Aliskiren– Inhibition of renin results in decreased formation of angiotensin II, a powerful vasoconstrictor.
  • Aliskiren– Inhibits the transport of calcium into myocardial and vascular smooth muscle cells, resulting in inhibition of excitation-contraction coupling and subsequent contraction.

Therapeutic Effect(s):

Lowering of BP.

Pharmacokinetics

Absorption: Absorption is significantly decreased by high fat meals;  Aliskiren– Poorly absorbed (bioavailability 2.5%);  Amlodipine– Well absorbed after oral administration (64–90%).

Distribution: Aliskiren– Unk;  Amlodipine– Probably crosses the placenta.

Protein Binding: Amlodipine– 95–98%.

Metabolism and Excretion: Aliskiren– 2% excreted unchanged in urine, remainder is probably metabolized (CYP3A4 enzyme system);  Amlodipine– Mostly metabolized by the liver.

Half-life: Aliskiren– 24 hr;  Amlodipine– 30–50 hr (↑ in geriatric patients and patients with hepatic impairment).

TIME/ACTION PROFILE (effect on BP)

ROUTEONSETPEAKDURATION
aliskiren POunknown2 wk24 hr
amlodipine POunknown6–924 hr

Contraindication/Precautions

Contraindicated in:

  • Severe renal impairment
  • OB:  Pregnancy (can cause fetal/neonatal morbidity and death).

Use Cautiously in:

  • Severe hepatic impairment (titrate carefully)
  • OB:  Women with child-bearing potential.

Adverse Reactions/Side Effects

Aliskiren

Resp: cough

GI: abdominal pain, diarrhea (↑ in females and elderly), dyspepsia, reflux

Misc: ANGIOEDEMA

Amlodipine

CNS: headache, dizziness, fatigue

CV: peripheral edema, angina, bradycardia, hypotension, palpitations

GI: gingival hyperplasia, nausea

Derm: flushing

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  •  Aliskiren–.

    Blood levels are ↓ by  irbesartan.
  • Blood levels are ↑ by  atorvastatin,  ketoconazole,  verapamil, and  cyclosporine  (concurrent use with cyclosporine not recommended).
  • May ↓ effects of  furosemide.
  • Antihypertensive effects may be ↑ by other  antihypertensives,  diuretics, and  nitrates.
  • ↑ risk of hyperkalemia with concurrent use of  ACE inhibitors,  angiotensin II receptor antagonists,  potassium supplements,  potassium-sparing diuretics, or  potassium-containing salt substitutes.
  •  Amlodipine–.

    Additive hypotension may occur when used concurrently with  fentanyl, other  antihypertensives,  nitrates, acute ingestion of  alcohol, or  quinidine.
  • Antihypertensive effects may be ↓ by concurrent use of  nonsteroidal anti-inflammatory agents.
  • May ↑ risk of neurotoxicity with  lithium.

Drug-Food:

  • Aliskiren–.

    High fat meals significantly ↓ absorption.
  • Amlodipine–.

    Grapefruit juice ↑ serum levels and effect.

Route/Dosage

PO (Adults): Add-on or initial therapy– alikiren 150 mg/amlodipine, titrate up to aliskiren 300 mg/amlodipine 10 mg;  replacement therapy– substitute for individual components.

Availability

Tablets: aliskiren 150 mg/ amlodipine 5 mg, aliskiren 150 mg/ amlodipine 10 mg, aliskiren 300 mg/ amlodipine 5 mg, aliskiren 300 mg/ amlodipine 10mg

Assessment

  • Monitor BP and pulse frequently during initial dose adjustment and periodically during therapy. Notify health care professional of significant changes. If an excessive fall in BP occurs, place patient in a supine position and administer IV 0.9% NaCl, if necessary. A transient hypotensive response does not contraindicate further therapy. Monitor ECG periodically during prolonged therapy.
  • Monitor intake and output ratios and daily weight. Assess for signs of HF (peripheral edema, rales/crackles, dyspnea, weight gain, jugular venous distention).
  • Monitor frequency of prescription refills to determine adherence.

Lab Test Considerations:

Monitor electrolytes and renal function periodically during therapy. May cause minor ↑ in BUN, serum creatinine and potassium.

  • May cause small ↓ in hemoglobin and hematocrit.

Potential Diagnoses

Implementation

  • If BP remains uncontrolled after 2–4 wks, titrate to maximum dose of aliskiren 300 mg/amlopidine 10 mg once daily.
  • PO Administer 1 tablet daily. Establish a pattern for taking medication with regard to meals and at the same time each day. High fat meals substantially decrease absorption.

Patient/Family Teaching

  • Instruct patient to take medication as directed at the same time each day, even if feeling better. Take missed doses as soon as remembered, but not if almost time for next dose. Do not double doses. Do not share medication with others, even with same condition; may be harmful. Advise patient to read the  Patient Package Insert  before starting therapy and with each Rx refill in case of changes.
  • May cause lightheadedness and dizziness, especially during first days of therapy. If syncope occurs, caution patient to lie down and notify health care professional. Also, avoid driving and other activities requiring alertness until response to medication is known.
  • Advise patient to report signs and symptoms of angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty swallowing, or breathing) to health care professional immediately.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications. Advise patient not to use potassium supplements or salt substitutes containing potassium without consulting health care professional.
  • Advise female patients to notify health care professional if pregnancy is planned or suspected or if breastfeeding. If pregnancy is detected, discontinue medication as soon as possible.
  • Advise patient to notify health care professional of side effects that are persistent or bothersome.

Evaluation/Desired Outcomes

Decrease in BP. Effect is largely attained within 1–2 wks.

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