Dosing and uses of Accupril (quinapril)
Adult dosage forms and strengths
tablet
- 5mg
- 10mg
- 20mg
- 40mg
Hypertension
Initial: 10-20 mg PO qDay; may administer 5 mg in patients receiving diuretic therapy if the diuretic is continued
Maintenance: 20-80 mg PO qDay or divided q12hr
Congestive Heart Failure
Initial: 5 mg PO q12hr
Maintenance: 20-40 mg PO qDay or divided q12hr
Diabetic Nephropathy (Off-Label)
Slows rate of progression of renal disease in patients with HTN, DM, and microalbuminuria
Initial: 10-20 mg PO qDay
Maintenance: 20-80 mg PO qDay or divided q12hr
Dosage modification
Renal impairment with hypertension
- CrCl >60 mL/min: 10 mg/day
- CrCl 30-60 mL/min: 5 mg/day
- CrCl 10-30 mL/min: 2.5 mg/day
- CrCl <10 mL/min: Insufficient data
Renal impairment with CHF
- CrCl >30 mL/min: 5 mg/day
- CrCl 10-30 mL/min: 2.5 mg/day
- CrCl <10 mL/min: Insufficient data
Pediatric dosage forms and strengths
tablet
- 5mg
- 10mg
- 20mg
- 40mg
Hypertension (Off-label)
5-10 mg PO qDay initially
Geriatric dosage forms and strengths
2.5-5 mg/day initially; increase dose by increments of 2.5-5 mg at 1-2 week intervals; adjust for renal impairment
Interactions
1-10%
Dizziness (4-8%)
Headache (2-6%)
Cough (2-4%)
Hyoptension (3%)
Fatigue (3%)
Hyperkalemia (2%)
Chest pain (2%)
Nausea/vomiting (1-2%)
Rash (1%)
Hyperkalemia (2%)
Myalagia (2-5%)
Back pain (1%)
Frequency not defined
Angioedema
Acute renal failure
Alopecia
Angina
Pancreatitis
Hyperkalemia
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
History of hereditary or angioedema associated with previous ACE inhibitor treatment
Bilateral renal artery stenosis
Do not coadminister with aliskiren in patients with diabetes mellitus or with renal impairment (ie, GFR <60 mL/min/1.73 m²)
Pregnancy (2nd and 3rd trimesters): Significant risk of fetal/neonatal morbidity and mortality
Cautions
Excessive hypotension if concomitant diuretics, hypovolemia, hyponatremia
Discontinue STAT if pregnant (see Contraindications and Black box warnings)
Less effective in blacks
Renal impairment may occur
Cough may occur within the first few months
Cholestatic jaundice may occur
Use caution in severe aortic stenosis
Risk of hyperkalemia, especially with renal impairment, DM, or those taking concomitant K+-elevating drugs
Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy
25-30% decreased absorption with high-fat meaL
ACE inhibition also causes increased bradykinin levels which putatively mediates angioedema
Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with angiotensin-converting enzyme inhibitors
If laryngeal stridor or angioedema of the face, tongue, or glottis occurs discontinue therapy and institute appropriate therapy immediately
Patients receiving coadministration of ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g. temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema
Intestinal angioedema has been reported in patients treated with ACE inhibitors
Dry hacking nonproductive cough may occur within few months of treatment; consider other causes of cough prior to discontinuation
Agranulocytosis, neutropenia, or leukopenia with myeloid hypoplasia reported with other ACE inhibitor; patients with renal impairment are at high risk; monitor CBC with differential in these patients
Pregnancy and lactation
Pregnancy category: C (1st trimester); D (2nd & 3rd trimester)
Discontinue as soon as pregnancy detected; during the second and third trimesters of pregnancy, drugs that act directly on the renin-angiotensin have been associated with fetal injury that includes hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure, and death
Lactation: excreted in breast milk; use caution
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.
Pharmacology of Accupril (quinapril)
Mechanism of action
Angiotensin converting enzyme (ACE) inhibitors dilate arteries and veins by competively inhibiting the conversion of angiotensin I to angiotensin II (a potent endogenous vasoconstrictor) and by inhibiting bradykinin metabolism; these actions result in preload and afterload reductions on the heart
ACE inhibitors also promote sodium and water excretion by inhibiting angiotensin-II induced aldosterone secretion; elevation in potassium may also be observed
ACE inhibitors also elicit renoprotective effects through vasodilation of renal arterioles
ACE inhibitors reduce cardiac and vascular remodeling associated with chronic hypertension, heart failure, and myocardial infarction
Pharmacokinetics
Half-life: 0.8 hr (quinapril); 3 hr (quinaprilat)
Onset: 1 hr
Duration: 24 hr
Peak plasma time: 1 hr (quinapril); 2 hr (quinaprilat)
Bioavailability: ≥60%
Protein bound: 97%
Metabolite: quinaprilat (active)
Metabolism: Liver
Excretion: Urine (50-60% primarily as quinaprilat)
Dialyzable: Minimally
