cilazapril

ACE inhibitors block the conversion of angiotensin I to the vasoconstrictor angiotensin II. ACE inhibitors also prevent the degradation of bradykinin and other vasodilatory prostaglandins. ACE inhibitors also ↑ plasma renin concentrations and ↓ aldosterone concentrations. Net result is systemic vasodilation.

Therapeutic effects:

Lowering of BP in hypertensive patients.
Improved symptoms in patients with HF.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following oral administration; rapidly converted to active metabolite, cilazaprilat (57% bioavailability for cilazaprilat).

Distribution: Unknown.

Metabolism/Excretion: Cilazaprilat is eliminated unchanged by the kidneys (91%).

Half-Life: Early elimination phase: 0.9 hr; terminal elimination phase (enzyme-bound cilazaprilat): 36–49 hr.

Time/Action Profile ⬆ ⬇

(effects on hemodynamics)

ROUTE	ONSET	PEAK	DURATION
PO (hypertension)	within 1 hr	3–7 hr	12–24 hr
PO (HF)	1–2 hr	2–4 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
History of angioedema with previous use of ACE inhibitors;
Concurrent use with aliskiren in patients with diabetes or moderate to severe renal impairment (CCr <60 mL/min);
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Renal impairment, hepatic impairment, hypovolemia, hyponatremia, or concurrent diuretic therapy;
Black patients with hypertension (monotherapy less effective and may require additional therapy; ↑ risk of angioedema);
Surgery/anesthesia (hypotension may be exaggerated);
Rep: Women of reproductive potential;
Geri: Initial dose ↓ recommended in older adults due to age-related ↓ in renal function;
Pedi: Safety and effectiveness not established in children.

Exercise Extreme Caution in:

Family history of angioedema.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, chest pain, edema, tachycardia

Derm: flushing, pruritus, rash

F and E: hyperkalemia

GI: abdominal pain, anorexia, constipation, diarrhea, nausea, vomiting

GU: erectile dysfunction, proteinuria, renal impairment

Hemat: AGRANULOCYTOSIS

Metab: hyperuricemia

MS: back pain, myalgia

Neuro: dysgeusia, dizziness, drowsiness, fatigue, headache, insomnia, vertigo, weakness

Resp: cough, dyspnea

Misc: ANGIOEDEMA, fever

Interactions ⬆ ⬇

Drug-drug:

Excessive hypotension may occur with diuretics, other antihypertensives, or alcohol.
↑risk of hyperkalemia with potassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes.
↑risk of hyperkalemia, renal impairment, hypotension, and syncope with angiotensin II receptor antagonists or aliskiren; avoid concurrent use with aliskiren in patients with diabetes or CCr <60 mL/min.
NSAIDs and selective COX-2 inhibitors may blunt the antihypertensive effect and ↑ the risk of renal impairment.
May ↑ levels and risk of toxicity of lithium.

Route/Dosage ⬆ ⬇

Hypertension

PO (Adults ≤65 yr): As monotherapy: 2.5 mg once daily initially; may ↑ every 2 wk by 2.5 mg/day; usual dose 2.5–5 mg once daily; max = 10 mg/day. Twice-daily administration may be necessary in some patients; With diuretics: 0.5 mg once daily initially; titrate carefully.
PO (Adults >65 yr): As monotherapy: 1.25 mg once daily initially; titrate carefully.

Renal Impairment

PO (Adults ): CCr >40 mL/min: 1 mg once daily initially; titrate carefully (max dose = 5 mg/day); CCr 10–40 mL/min: 0.5 mg once daily initially; titrate carefully (max dose = 2.5 mg/day); CCr <10 mL/min: 0.25–0.5 mg once or twice weekly according to BP response.

Hepatic Impairment

PO (Adults ): 0.5 mg once daily or less.

Heart Failure

PO (Adults ): 0.5 mg/day with careful monitoring; after 5 days, dose may ↑ to 1 mg/day; dose may then be carefully titrated as needed/tolerated up to 2.5 mg/day; rarely patients may require 5 mg/day.

Renal Impairment

PO (Adults ): CCr >40 mL/min: 0.5 mg once daily (max dose = 2.5 mg/day); CCr 10–40 mL/min: 0.25–0.5 mg once daily (max dose = 2.5 mg/day); CCr <10 mL/min: 0.25–0.5 mg once or twice weekly according to BP response.

Availability ⬆ ⬇

Tablets: 1 mg; 2.5 mg; 5 mg
In combination with: hydrochlorothiazide (Inhibace Plus)

Assessment ⬆ ⬇

Assess for signs/symptoms of angioedema (dyspnea, facial swelling, stridor). Implement emergent supportive measures as needed.
Hypertension: Monitor BP and HR frequently during initial dose adjustment and periodically during therapy.
Heart Failure: Monitor daily weight and assess frequently for fluid overload (dyspnea, rales/crackles, weight gain, jugular venous distention).

Lab Test Considerations:

Monitor BUN, serum creatinine, and electrolytes periodically during therapy.
- Monitor CBC periodically. May cause agranulocytosis.
- May ↑ AST, ALT, alkaline phosphatase, bilirubin, uric acid, and glucose.

Implementation ⬆ ⬇

PO: Administer with or without food.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Advise to take as directed. Take missed dose as soon as remembered. If not until the following day, skip missed dose. Do not double doses.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Advise patient to change positions slowly to minimize hypotension. Use of alcohol, standing for long periods, exercising, and hot weather may ↑ risk of orthostatic hypotension.
May cause dizziness. Advise patient to avoid driving and other activities requiring alertness until response to medication is known.
Educate patient on proper technique for monitoring BP. Advise patient to check BP and weight weekly and record and report results to health care provider.
Provide patient with additional interventions for hypertension control (weight ↓, low-sodium diet, smoking cessation, exercise regimen, stress management, moderation of alcohol consumption). Medication controls but does not cure hypertension.
Advise patient that cilazapril may cause a dry, hacking nonproductive cough that usually occurs within the 1st few months of treatment and generally resolves within 1–4 wk after discontinuation. Advise to notify health care provider is cough becomes bothersome.
Rep: Advise women of reproductive potential to use contraception and to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Discontinue medication immediately if pregnancy is confirmed.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇