• Hypertension (as monotherapy or in combination with other antihypertensives).

Captopril, enalapril, fosinopril, lisinopril, quinapril, ramipril, trandolapril:

• Management of HF.

Captopril, lisinopril, ramipril, trandolapril:

• Reduction of risk of death or development of HF following MI.

Enalapril:

• Slowed progression of left ventricular dysfunction into overt HF.

Ramipril:

• Reduction of the risk of MI, stroke, and death from cardiovascular disease in patients at risk (>55 yr old with a history of CAD, stroke, peripheral vascular disease, or diabetes with another cardiovascular risk factor).

Captopril:

• ↓progression of diabetic nephropathy.

Perindopril:

• Reduction of risk of death from cardiovascular causes or nonfatal MI in patients with stable CAD.

Contraindicated in:

• Hypersensitivity
• History of angioedema with previous use of ACE inhibitors (also in absence of previous use of ACE inhibitors for benazepril)
• Concurrent use with aliskiren in patients with diabetes or moderate-to-severe renal impairment (CCr <60 mL/min)
• Concurrent use with sacubitril/valsartan; must be a 36–hr wash-out period after switching to/from sacubitril/valsartan
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Renal impairment, hepatic impairment, hypovolemia, hyponatremia, concurrent diuretic therapy
• Black patients with hypertension (monotherapy less effective, may require additional therapy; ↑ risk of angioedema)
• Women of reproductive potential
• Surgery/anesthesia (hypotension may be exaggerated)
• Pedi: Safety and effectiveness not established in children <18 yr (moexipril, perindopril, quinapril ramipril, trandolapril) or <6 yr (benazepril, fosinopril, lisinopril)
• Geri: Initial dose ↓ recommended for most agents due to age-related ↓ in renal function.

Exercise Extreme Caution in:

• Family history of angioedema.

CV: hypotension, chest pain, edema, tachycardia.

Derm: flushing, pruritus, rashes.

Endo: hyperuricemia.

F and E: hyperkalemia.

GI: taste disturbances, abdominal pain, anorexia, constipation, diarrhea, nausea, vomiting.

GU: erectile dysfunction, proteinuria, renal dysfunction, renal failure.

Hemat: AGRANULOCYTOSIS, neutropenia (captopril only).

MS: back pain, muscle cramps, myalgia.

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

Resp: cough, dyspnea.
Misc: ANGIOEDEMA, fever.

Drug-Drug:

• Concurrent use with sacubitril↑ risk of angioedema; concurrent use contraindicated; do not administer within 36 hr of switching to/from sacubitril/valsartan.
• Excessive hypotension may occur with concurrent use of diuretics and other antihypertensives.
• ↑risk of hyperkalemia with concurrent use of potassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes.
• ↑risk of hyperkalemia, renal dysfunction, hypotension, and syncope with concurrent use of angiotensin II receptor blockers or aliskiren; avoid concurrent use with aliskiren in patients with diabetes or CCr <60 mL/min; avoid concurrent use with angiotensin II receptor blockers.
• NSAIDs and selective COX-2 inhibitors may blunt the antihypertensive effect and ↑ the risk of renal dysfunction.
• Absorption of fosinopril may be ↓ by antacids (separate administration by 1–2 hr).
• ↑levels and may ↑ risk of lithium toxicity.
• Quinapril may ↓ absorption of tetracycline, doxycycline, and fluoroquinolones (because of magnesium in tablets).
• ↑risk of angioedema with temsirolimus, sirolimus, or everolimus.

Drug-Food:

• Food significantly ↓ absorption of captopril and moexipril (administer drugs 1 hr before meals).

Benazepril

(Generic available)

• Tablets: 5 mg; 10 mg; 20 mg; 40 mg;
• In combination with: amlodipine (Lotrel) and hydrochlorothiazide (Lotensin HCT). See Appendix [not included in this PDA edition].

Captopril

(Generic available)

• Tablets: 12.5 mg; 25 mg; 50 mg; 100 mg;
• In combination with: hydrochlorothiazide (Capozide). See Appendix [not included in this PDA edition].

Enalapril

(Generic available)

• Tablets: 2.5 mg; 5 mg; 10 mg; 20 mg;
• Oral solution (mixed berry flavor): 1 mg/mL;
• In combination with: hydrochlorothiazide (Vaseretic). See Appendix [not included in this PDA edition].

Enalaprilat

(Generic available)

• Solution for injection: 1.25 mg/mL;

Fosinopril

(Generic available)

• Tablets: 10 mg; 20 mg; 40 mg;
• In combination with: hydrochlorothiazide. See Appendix [not included in this PDA edition].

Lisinopril

(Generic available)

• Tablets: 2.5 mg; 5 mg; 10 mg; 20 mg; 30 mg; 40 mg;
• Oral solution: 1 mg/mL;
• In combination with: hydrochlorothiazide (Prinzide, Zestoretic). See Appendix [not included in this PDA edition].

Moexipril

(Generic available)

• Tablets: 7.5 mg; 15 mg;
• In combination with: hydrochlorothiazide (Uniretic).

Perindopril

(Generic available)

• Tablets: 2 mg; 4 mg; 8 mg;
• In combination with: amlodipine (Prestalia). See Appendix [not included in this PDA edition].

Quinapril

(Generic available)

• Tablets: 5 mg; 10 mg; 20 mg; 40 mg;
• In combination with: hydrochlorothiazide (Accuretic). See Appendix [not included in this PDA edition].

Ramipril

(Generic available)

• Capsules: 1.25 mg; 2.5 mg; 5 mg; 10 mg; 15 mg;

Trandolapril

(Generic available)

• Tablets: 0.5 mg; 1 mg; 2 mg; 4 mg;
• In combination with: verapamil. See Appendix [not included in this PDA edition].

Benazepril

• PO (Adults): 10 mg once daily, ↑ gradually to maintenance dose of 20–40 mg/day in 1–2 divided doses (begin with 5 mg/day in patients receiving diuretics).
• PO (Children 6 yr): 0.2 mg/kg once daily; may be titrated up to 0.6 mg/kg/day (or 40 mg/day).

Captopril

• PO (Adults): Hypertension — 12.5–25 mg 2–3 times daily, may be ↑ at 1–2 wk intervals up to 150 mg 3 times daily (begin with 6.25–12.5 mg 2–3 times daily in patients receiving diuretics) (maximum dose = 450 mg/day); HF — 25 mg 3 times daily (6.25–12.5 mg 3 times daily in patients who have been vigorously diuresed); titrated up to target dose of 50 mg 3 times daily; Post-MI — 6.25-mg test dose, followed by 12.5 mg 3 times daily, may be ↑ up to 50 mg 3 times daily; Diabetic nephropathy — 25 mg 3 times daily.
• PO (Children): HF — 0.3 mg/kg–0.5 mg/kg/dose 3 times daily, titrate up to a maximum of 6 mg/kg/day in 2–4 divided doses; Older Children — 6.25–12.5 mg/dose every 12–24 hr, titrate up to a maximum of 6 mg/kg/day in 2–4 divided doses.
• PO (Infants): HF — 0.15–0.3 mg/kg/dose, titrate up to a maximum of 6 mg/kg/day in 1–4 divided doses.
• PO (Neonates): HF — 0.05–0.1 mg/kg/dose every 8–24 hr, may ↑ as needed up to 0.5 mg/kg every 6–24 hr; Premature neonates — 0.01 mg/kg/dose every 8–12 hr.

Enalapril/Enalaprilat

• PO (Adults): Hypertension — 2.5–5 mg once daily, ↑ as required up to 40 mg/day in 1–2 divided doses (initiate therapy at 2.5 mg once daily in patients receiving diuretics); HF — 2.5 mg 1–2 times daily, titrated up to target dose of 10 mg twice daily; begin with 2.5 mg once daily in patients with hyponatremia (serum sodium <130 mEq/L); Asymptomatic left ventricular dysfunction — 2.5 mg twice daily, titrated up to a target dose of 10 mg twice daily.
• PO (Children >1 mo): Hypertension — 0.08 mg/kg once daily; may be slowly titrated up to a maximum of 0.58 mg/kg/day.
• IV (Adults): Hypertension — 0.625–1.25 mg (0.625 mg if receiving diuretics) every 6 hr; can be titrated up to 5 mg every 6 hr.
• IV (Children >1 mo): Hypertension — 5–10 mcg/kg/dose given every 8–24 hr.

Fosinopril

• PO (Adults): Hypertension — 10 mg once daily, may be ↑ as required up to 80 mg/day. HF — 10 mg once daily (5 mg once daily in patients who have been vigorously diuresed), may be ↑ over several wk up to 40 mg/day.
• PO (Children 6 yr and >50 kg): Hypertension — 5–10 mg once daily.

Lisinopril

• PO (Adults): Hypertension — 10 mg once daily, can be ↑ up to 20–40 mg/day (initiate therapy at 5 mg/day in patients receiving diuretics); HF — 5 mg once daily; may be titrated every 2 wk up to 40 mg/day; begin with 2.5 mg once daily in patients with hyponatremia (serum sodium <130 mEq/L); Post-MI — 5 mg once daily for 2 days, then 10 mg daily.
• PO (Children 6 yr): Hypertension — 0.07 mg/kg once daily (up to 5 mg/day), may be titrated every 1–2 wk up to 0.6 mg/kg/day (or 40 mg/day).

Moexipril

• PO (Adults): 7.5 mg once daily, may be ↑ up to 30 mg/day in 1–2 divided doses (begin with 3.75 mg/day in patients receiving diuretics).

Perindopril

• PO (Adults): Hypertension — 4 mg once daily, may be slowly titrated up to 16 mg/day in 1–2 divided doses (should not exceed 8 mg/day in elderly patients) (begin with 2–4 mg/day in 1–2 divided doses in patients receiving diuretics); Stable CAD — 4 mg once daily for 2 wk, may be ↑, if tolerated, to 8 mg once daily; for elderly patients, begin with 2 mg once daily for 1 wk (may be ↑, if tolerated, to 4 mg once daily for 1 wk, then, ↑ as tolerated to 8 mg once daily).

Quinapril

• PO (Adults): Hypertension — 10–20 mg once daily initially, may be titrated every 2 wk up to 80 mg/day in 1–2 divided doses (initiate therapy at 5 mg/day in patients receiving diuretics); HF — 5 mg twice daily initially, may be titrated at weekly intervals up to 20 mg twice daily.

Ramipril

• PO (Adults): Hypertension — 2.5 mg once daily, may be ↑ slowly up to 20 mg/day in 1–2 divided doses (initiate therapy at 1.25 mg/day in patients receiving diuretics). HF post-MI — 1.25–2.5 mg twice daily initially, may be ↑ slowly up to 5 mg twice daily. Reduction in risk of MI, stroke, and death from cardiovascular causes — 2.5 mg once daily for 1 wk, then 5 mg once daily for 3 wk, then ↑ as tolerated to 10 mg once daily (can also be given in 2 divided doses).

Trandolapril

• PO (Adults): Hypertension — 1 mg once daily (2 mg once daily in black patients); HF post-MI — Initiate therapy at 1 mg once daily, titrate up to 4 mg once daily if possible.

benazepril: Lotensin

captopril: Capoten

Enalapril/Enalaprilat: Epaned, Vasotec

fosinopril: Monopril

lisinopril: Prinivil

moexipril: Univasc

perindopril: Aceon

quinapril: Accupril

ramipril: Altace

• 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 levels and ↓ aldosterone levels. Net result is systemic vasodilation.

• Lowering of BP in hypertensive patients.
• Improved symptoms in patients with HF (selected agents only).
• ↓development of overt heart failure (enalapril only).
• Improved survival and ↓ development of overt HF after MI (selected agents only).
• ↓risk of death from cardiovascular causes or MI in patients with stable CAD (perindopril only).
• ↓risk of MI, stroke or death from cardiovascular causes in high-risk patients (ramipril only).
• ↓progression of diabetic nephropathy (captopril only).

Therapeutic Classification: antihypertensives

Pharmacologic Classification: ace inhibitors

Absorption: Benazepril — 37% absorbed after oral administration. Captopril — 60–75% absorbed after oral administration (↓ by food). Enalapril — 55–75% absorbed after oral administration. Enalaprilat — IV administration results in complete bioavailability. Fosinopril — 36% absorbed after oral administration. Lisinopril — 25% absorbed after oral administration (much variability). Moexipril — 13% bioavailability as moexiprilat after oral administration (↓ by food). Perindopril — 25% bioavailability as perindoprilat after oral administration. Quinapril — 60% absorbed after oral administration (high-fat meal may ↓ absorption). Ramipril — 50–60% absorbed after oral administration. Trandolapril — 70% bioavailability as trandolapril at after oral administration.

Distribution: All ACE inhibitors cross the placenta. Benazepril, captopril, enalapril, fosinopril, quinapril, and trandolapril — Enter breast milk. Lisinopril — Minimal penetration of CNS. Ramipril — Probably does not enter breast milk. Trandolapril — Enters breast milk.

Protein Binding: Benazepril — 95%, Fosinopril — 99.4%, Moexipril — 90%, Quinapril — 97%.

Metabolism/Excretion: Benazepril — Converted by the liver to benazeprilat, the active metabolite. 20% excreted by kidneys; 11–12% nonrenal (biliary elimination). Captopril — 50% metabolized by the liver to inactive compounds, 50% excreted unchanged by the kidneys. Enalapril, enalaprilat — Enalapril is converted by the liver to enalaprilat, the active metabolite; primarily eliminated by the kidneys. Fosinopril — Converted by the liver and GI mucosa to fosinoprilat, the active metabolite — 50% excreted in urine, 50% in feces. Lisinopril — 100% eliminated by the kidneys. Moexipril — Converted by liver and GI mucosa to moexiprilat, the active metabolite; 13% excreted in urine, 53% in feces. Perindopril — Converted by the liver to perindoprilat, the active metabolite; primarily excreted in urine. Quinapril — Converted by the liver, GI mucosa, and tissue to quinaprilat, the active metabolite: 96% eliminated by the kidneys. Ramipril — Converted by the liver to ramiprilat, the active metabolite; 60% excreted in urine, 40% in feces. Trandolapril — Converted by the liver to trandolaprilat, the active metabolite; 33% excreted in urine, 66% in feces.

Half-life: Benazeprilat — 10–11 hr. Captopril — 2 hr (↑ in renal impairment). Enalapril — 2 hr (↑ in renal impairment). Enalaprilat — 35–38 hr (↑ in renal impairment). Fosinoprilat — 12 hr. Lisinopril — 12 hr (↑ in renal impairment). Moexiprilat — 2–9 hr (↑ in renal impairment). Perindoprilat — 3–10 hr (↑ in renal impairment). Quinaprilat — 3 hr (↑ in renal impairment). Ramiprilat — 13–17 hr (↑ in renal impairment). Trandolaprilat — 22.5 hr (↑ in renal impairment).

Enalapril/Enalaprilat: Vasotec IV

perindopril: Coversyl

trandolapril: Mavik

(effect on BP — single dose†)

†Full effects may not be noted for several wks.

• Instruct patient to take medication as directed at the same time each day, even if feeling well. Take missed doses as soon as possible but not if almost time for next dose. Do not double doses. Warn patient not to discontinue ACE inhibitor therapy unless directed by health care professional.
  • Caution patient to avoid salt substitutes or foods containing high levels of potassium or sodium unless directed by health care professional (see Appendix M).
  • Caution patient to change positions slowly to minimize hypotension. Use of alcohol, standing for long periods, exercising, and hot weather may ↑ orthostatic hypotension.
  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, especially cough, cold, or allergy remedies.
  • May cause dizziness. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
  • Advise patient to inform health care professional of medication regimen prior to treatment or surgery.
  • Advise patient that medication may cause impairment of taste that generally resolves within 8–12 wk, even with continued therapy.
  • Instruct patient to notify health care professional immediately if rash; mouth sores; sore throat; fever; swelling of hands or feet; irregular heart beat; chest pain; dry cough; hoarseness; swelling of face, eyes, lips, or tongue; difficulty swallowing or breathing occur; or if taste impairment or skin rash persists. Persistent dry cough may occur and may not subside until medication is discontinued. Consult health care professional if cough becomes bothersome. Also notify health care professional if nausea, vomiting, or diarrhea occurs and continues.
  • Advise diabetic patients to monitor blood glucose closely, especially during first mo of therapy; may cause hypoglycemia.
  • May cause fetal harm. Advise females of reproductive potential to use effective contraception during therapy and notify health care professional if pregnancy is planned or suspected. If pregnancy is detected, discontinue medication as soon as possible. Closely observe infants with histories of in utero exposure to ACE inhibitors for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occur, 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. Advise patient to avoid breast feeding during therapy.
  • Emphasize the importance of follow-up examinations to monitor progress.
• Hypertension: Encourage patient to comply with additional interventions for hypertension (weight reduction, low sodium diet, discontinuation of smoking, moderation of alcohol consumption, regular exercise, and stress management). Medication controls but does not cure hypertension.
  • Instruct patient and family on correct technique for monitoring BP. Advise them to check BP at least weekly and to report significant changes to health care professional.

benazepril: ben-AYE-ze-pril

captopril: KAP-toe-pril

Enalapril/Enalaprilat: e-NAL-a-pril/e-NAL-a-pril-at

fosinopril: foe-SIN-oh-pril

lisinopril: lyse-IN-oh-pril

moexipril: moe-EKS-i-pril

perindopril: pe-RIN-do-pril

quinapril: KWIN-a-pril

ramipril: ra-MI-pril

trandolapril: tran-DOE-la-pril