aliskiren

(redirected from Aliskiren fumarate)
Also found in: Wikipedia.

aliskiren

Tekturna

Pharmacologic class: Direct renin inhibitor

Pregnancy risk category C (first trimester), D (second and third trimesters)

Pregnancy risk category C (first trimester), D (second and third trimesters)

FDA Box Warning

• Drugs that act directly on the reninangiotensin system can cause injury and death to a developing fetus.

• Discontinue drug as soon as possible when pregnancy is detected.

Action

Decreases plasma renin activity and inhibits conversion of angiotensinogen to angiotensin

Availability

Tablets: 150 mg, 300 mg

Indications and dosages

Hypertension (alone or in combination with other antihypertensives)

Adults: Initially, 150 mg P.O. once daily; may increase to 300 mg if blood pressure isn't adequately controlled

Contraindications

• Concurrent use of angiotensin receptor blockers (ARBs) or ACE inhibitors in patients with diabetes

Precautions

Use cautiously in:
• patients with severe renal dysfunction, nephrotic syndrome, renovascular hypertension, or history of dialysis
• angioedema (laryngeal edema)
• concurrent use of ACE inhibitors or ARBs in patients with renal impairment (GFR less than 60 ml/minute; avoid use)
• concurrent use of NSAIDs including selective COX-2 inhibitors, potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other drugs that increase potassium levels
• females of childbearing age
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

• Give consistently with or without food, but not with high-fat foods.

Adverse reactions

CNS: headache, fatigue

CV: dizziness, hypotension

EENT: nasopharyngitis

GI: diarrhea, gastroesophageal reflux

Musculoskeletal: back pain

Respiratory: upper respiratory tract infection, cough

Skin: rash

Other: edema, angioedema

Interactions

Drug-drug.ACE inhibitors, ARBs: increased risk of renal impairment, hypotension, and hyperkalemia

Cyclosporine, itraconazole: significantly increased aliskiren level

NSAIDs (including selective COX-2 inhibitors): increased risk of deterioration of renal function, including possible acute renal failure, and increased aliskiren antihypertensive effect

Drug-diagnostic tests.BUN, creatine kinase, potassium, serum creatinine, serum uric acid: increased values

Hematocrit, hemoglobin: decreased values

Drug-food.High-fat meals: decreased drug absorption

Patient monitoring

• Stay alert for signs and symptoms of renal dysfunction, especially in patients receiving NSAIDs.

Monitor patient for signs and symptoms of angioedema; discontinue drug if signs and symptoms are present.

Patient teaching

• Instruct patient to take drug consistently with or without food, but not with high-fat foods.
• Instruct patient not to stop drug suddenly because doing so could result in uncontrolled high blood pressure.
• Advise female to tell prescriber if she's pregnant or breastfeeding before taking drug.
• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs, tests, and foods mentioned above.

aliskiren

(a-lis-ki-ren) ,

Rasilez

(trade name),

Tekturna

(trade name)

Classification

Therapeutic: antihypertensives
Pharmacologic: renin inhibitors
Pregnancy Category: D

Indications

Treatment of hypertension (alone or with other agents).

Action

Inhibition of renin results in decreased formation of angiotensin II, a powerful vasoconstrictor.

Therapeutic effects

Decreased BP.

Pharmacokinetics

Absorption: Poorly absorbed (bioavailability 2.5%).
Distribution: Unknown.
Metabolism and Excretion: 2% excreted unchanged in urine, remainder is probably metabolized (CYP3A4 enzyme system).
Half-life: 24 hr.

Time/action profile (antihypertensive effect)

ROUTEONSETPEAKDURATION
POunknown2 wk24 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Concurrent use with cyclosporine or itraconazole;Concurrent use with ACE inhibitors or ARBs in patients with diabetes or moderate-to-severe renal impairment (CCr <60 mL/min); Obstetric: May cause fetal injury or death—if pregnancy occurs, discontinue immediately; Lactation: Discontinue drug or use formula.
Use Cautiously in: Salt or volume depletion (correct before use);Severe renal impairment; Pediatric: Safety and efficacy not established.

Adverse Reactions/Side Effects

Respiratory

  • cough

Cardiovascular

  • hypotension

Gastrointestinal

  • abdominal pain
  • diarrhea (↑ in females and elderly)
  • dyspepsia
  • reflux

Miscellaneous

  • angioedema (life-threatening)

Interactions

Drug-Drug interaction

↑ risk of hyperkalemia, renal impairment, and hypotension with concurrent use of ACE inhibitors or angiotensin II receptor blockers in patients with diabetes or moderate-to-severe renal impairment (CCr <60 mL/min); concurrent use contraindicated.Blood levels are ↑ by atorvastatin, itraconazole, ketoconazole, verapamil, and cyclosporine ; avoid concurrent use with cyclosporine or itraconazole.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 blockerspotassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes.NSAIDs and selective COX-2 inhibitors may blunt the antihypertensive effect and ↑ the risk of renal dysfunction.High fat meals significantly ↓ absorption.

Route/Dosage

Oral (Adults) 150 mg/day initially; may be ↑ to 300 mg/day.

Availability

Tablets: 150 mg, 300 mg
In combination with: hydrochlorothiazide (Tekturna HCT), amlodipine (Tekamlo), and amlodipine/hydrochlorothiazide (Amturnide); see combination drugs.

Nursing implications

Nursing 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 frequency of prescription refills to determine adherence.
  • Lab Test Considerations: May cause minor ↑ in BUN, serum creatinine, potassium, uric acid, and creatine kinase.
    • May cause small ↓ in hemoglobin and hematocrit.

Potential Nursing Diagnoses

Noncompliance (Patient/Family Teaching)

Implementation

  • Correct volume or sodium depletion prior to initiating therapy.
  • Oral: Administer at the same time each day without regard to meals.

Patient/Family Teaching

  • Instruct patient to take aliskiren 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.
  • May cause dizziness. Caution patient to lie down and notify health care professional. Also, avoid driving and other activities requiring alertness until response to aliskiren 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.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Advise female patients to notify health care professional if pregnancy is planned or suspected or if breast feeding. If pregnancy is detected, discontinue aliskiren as soon as possible.

Evaluation/Desired Outcomes

  • Decrease in BP without appearance of side effects. Antihypertensive effect is 90% attained by 2 wk.

aliskiren/amlodipine

(a-lis-ki-ren/am-loe-di-peen) ,

Tekamlo

(trade name)

Classification

Therapeutic: antihypertensives
Pharmacologic: renin inhibitors
Pregnancy Category: D

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 effects

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

Contraindications/Precautions

Contraindicated in: Severe renal impairment; Obstetric: Pregnancy (can cause fetal/neonatal morbidity and death).
Use Cautiously in: Severe hepatic impairment (titrate carefully); Obstetric: Women with child-bearing potential.

Adverse Reactions/Side Effects

Aliskiren

Respiratory

  • cough

Gastrointestinal

  • abdominal pain
  • diarrhea (↑ in females and elderly)
  • dyspepsia
  • reflux

Miscellaneous

  • angioedema (life-threatening)

Amlodipine

Central nervous system

  • headache (most frequent)
  • dizziness
  • fatigue

Cardiovascular

  • peripheral edema (most frequent)
  • angina
  • bradycardia
  • hypotension
  • palpitations

Gastrointestinal

  • gingival hyperplasia
  • nausea

Dermatologic

  • flushing

Interactions

Drug-Drug interaction

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.Aliskiren—.High fat meals significantly ↓ absorption.Amlodipine—.Grapefruit juice ↑ serum levels and effect.

Route/Dosage

Oral (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

Nursing implications

Nursing 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 Nursing Diagnoses

Noncompliance (Patient/Family Teaching)

Implementation

  • If BP remains uncontrolled after 2–4 wks, titrate to maximum dose of aliskiren 300 mg/amlopidine 10 mg once daily.
  • Oral: 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.

aliskiren

an antihypertensive.
indications This drug is used to treat hypertension, alone or in combination with other antihypertensives.
contraindications Second and third trimester pregnancy and known hypersensitivity to this drug prohibit its use.
adverse effects Adverse effects of this drug include orthostatic hypotension, hypotension, headache, dizziness, renal stones, increased uric acid, rash, and hyperkalemia. Life-threatening side effects include angioedema.

aliskiren

A non-peptide, orally-active RENIN inhibitor still (October 2006) in the clinical trial stage. Renin inhibition may be expected to be even more effective than ACE inhibitor drugs.