Accupril

Name: Accupril

Side effects

Dizziness, lightheadedness, or tiredness may occur as your body adjusts to the medication. Dry cough, nausea, or vomiting may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if any of these unlikely but serious side effects occur: fainting, symptoms of a high potassium blood level (such as muscle weakness, slow/irregular heartbeat), signs of infection (such as fever, chills, persistent sore throat), change in the amount of urine.This drug may rarely cause serious (possibly fatal) liver problems. Tell your doctor right away if you notice any of the following rare but serious side effects: yellowing eyes/skin, dark urine, severe stomach/abdominal pain, persistent nausea/vomiting.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Overdose

If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe dizziness, fainting.

What is quinapril?

Quinapril is an ACE inhibitor. ACE stands for angiotensin converting enzyme.

Quinapril is used to treat high blood pressure (hypertension) and heart failure.

Quinapril may also be used for purposes not listed in this medication guide.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Accupril Dosage and Administration

General

BP Monitoring and Treatment Goals

  • Carefully monitor BP during initial titration or subsequent upward adjustment in dosage.500 501

  • When available, use evidence-based dosing information (i.e., dosages shown in randomized controlled trials to reduce complications of hypertension) to determine target dosages; target dosages usually can be achieved within 2–4 weeks but may take up to several months.501

  • If adequate BP response not achieved with a single antihypertensive agent, add a second drug with demonstrated benefit; if goal BP still not achieved with optimal dosages of 2 antihypertensive agents, add a third drug.501 May maximize dosage of the first drug before adding a second drug, or add a second drug before maximizing dosage of the initial drug.501

  • Consider initiating antihypertensive therapy with a combination of drugs if patient's BP exceeds goal BP by >20/10 mm Hg.500 501 503 504

  • Goal is to achieve and maintain optimal control of BP; individualize specific target BP based on consideration of multiple factors, including patient age and comorbidities, and currently available evidence from clinical studies.500 501 (See Hypertension under Uses.)

Administration

Oral Administration

Administer orally once or twice daily.1 47

Manufacturer makes no specific recommendation regarding administration of quinapril with meals;1 47 administer quinapril/hydrochlorothiazide fixed combinations without regard to meals.47 (See Food under Pharmacokinetics.)

Dosage

Available as quinapril hydrochloride; dosage expressed in terms of quinapril.1 47

May minimize risk of hypotension in patients currently receiving diuretic therapy by discontinuing the diuretic, reducing diuretic dosage, or cautiously increasing salt intake prior to initiating quinapril; if diuretic therapy cannot be discontinued, initiate quinapril at a reduced dosage.600 (See Hypotension under Cautions and see the individual dosage sections in Dosage and Administration.)

Pediatric Patients

Hypertension† Oral

Some experts recommend an initial dosage of 5–10 mg once daily.62 Increase dosage as necessary to a maximum dosage of 80 mg once daily.62

Adults

Hypertension Quinapril Therapy Oral

Initially, 10 or 20 mg once daily in patients not receiving a diuretic.2 3 28 600 Adjust dosage at ≥2-week intervals to achieve BP control.1

In patients currently receiving diuretic therapy, discontinue diuretic, if possible, 2–3 days before initiating quinapril.600 May resume diuretic therapy if BP not controlled adequately with quinapril alone.600 If diuretic cannot be discontinued, initiate quinapril at a dose of 5 mg under close medical supervision for several hours until BP has stabilized.600

Usual maintenance dosage: 20–80 mg daily, given in 1 dose or 2 divided doses.28 600

If effectiveness diminishes toward end of dosing interval in patients treated once daily, consider increasing dosage or administering drug in 2 divided doses.1 28

If intolerable adverse effects occur, consider dosage reduction; if adverse effects worsen or fail to resolve, may need to discontinue and switch to another antihypertensive drug class.501

Quinapril/Hydrochlorothiazide Fixed-combination Therapy Oral

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy.47

If BP is not adequately controlled by monotherapy with quinapril or hydrochlorothiazide, can switch to the fixed-combination preparation containing quinapril 10 mg and hydrochlorothiazide 12.5 mg or, alternatively, quinapril 20 mg and hydrochlorothiazide 12.5 mg.47 Adjust dosage of either or both drugs according to patient’s response.47

If BP is controlled by monotherapy with hydrochlorothiazide 25 mg daily but potassium loss is problematic, can switch to fixed-combination preparation containing quinapril 10 mg and hydrochlorothiazide 12.5 mg or, alternatively, quinapril 20 mg and hydrochlorothiazide 12.5 mg.47

If BP is controlled with quinapril 20 mg and hydrochlorothiazide 25 mg (administered separately) and if no clinically important electrolyte disturbance is observed, can switch to the fixed-combination preparation containing these corresponding doses for convenience.47

Heart Failure Oral

Initially, 5 mg twice daily.1 Monitor closely for ≥2 hours until BP has stabilized.1 To minimize risk of hypotension, reduce diuretic dosage, if possible.1

Adjust dosage at weekly intervals to reach usual dosage.1

Usual dosage: 20–40 mg daily, given in 2 equally divided doses.1

Prescribing Limits

Pediatric Patients

Hypertension† Oral

Maximum 80 mg daily.62

Special Populations

Renal Impairment

Hypertension Oral

Initially, 10 mg once daily in adults with Clcr >60 mL/minute; 5 mg once daily in those with Clcr 30–60 mL/minute; or 2.5 mg once daily in those with Clcr 10–30 mL/minute.1 Titrate at 2-week intervals until BP is controlled.1 (See Renal Impairment under Cautions.)

Quinapril/hydrochlorothiazide fixed combinations are not recommended in patients with severe renal impairment (Clcr ≤30 mL/minute or Scr >3 mg/dL).47

Heart Failure Oral

Initially (first day), 5 mg in patients with moderate renal impairment (Clcr >30 mL/minute) or 2.5 mg in patients with severe renal impairment (Clcr 10–30 mL/minute) under close medical supervision.1 If well tolerated, administer as twice-daily regimen on subsequent days.1 Titrate at weekly intervals based on clinical and hemodynamic response.1

Geriatric Patients

Hypertension

Oral: Initially, 10 mg once daily as monotherapy.1 Adjust dosage at ≥2-week intervals to achieve BP control.1

Interactions for Accupril

Drugs That Interact with Magnesium

Possible decreased absorption of drugs that interact with magnesium, possibly due to high magnesium content in quinapril-containing preparations.1 47

Specific Drugs

Drug

Interaction

Comments

Atorvastatin

Pharmacokinetic interaction unlikely1

Cimetidine

Pharmacokinetic interaction unlikely1 47

Digoxin

Pharmacokinetic interaction unlikely1 47

Diuretics

Increased hypotensive effect1 47

If possible, discontinue diuretic before initiating quinapril1 47 (See Dosage under Dosage and Administration)

Diuretics, potassium-sparing (amiloride, spironolactone, triamterene)

Enhanced hyperkalemic effect1 47

Use with caution; monitor serum potassium concentrations frequently1 47

Lithium

Increased serum lithium concentrations; possible toxicity1 47

Monitor serum lithium concentrations frequently1 47

Potassium supplements or potassium-containing salt substitutes

Enhanced hyperkalemic effect1 47

Use with caution; monitor serum potassium concentrations frequently1 47

Propranolol

Pharmacokinetic interaction unlikely1 47

Tetracycline

Decreased tetracycline absorption1 47

Warfarin

Pharmacologic interaction unlikely1 47

Accupril Pharmacokinetics

Absorption

Bioavailability

About 60% of oral dose is absorbed.1 47

Peak plasma concentrations of quinapril and quinaprilat are achieved within 1 and 2 hours, respectively.1 47

Onset

Following a single oral dose, antihypertensive effects are observed within 1 hour, with peak BP reduction at 2–4 hours.1 47

During chronic therapy, maximum antihypertensive effect is achieved after 1–2 weeks.1 47

Duration

Inhibition of >80% of ACE activity persists for about 24 hours.1 47 Inhibition of 75% of the pressor response to angiotensin I persists for about 4 hours.1 47

Food

High-fat meals result in moderate (25–30%) reductions in rate and extent of absorption of quinapril.1 47 When quinapril/hydrochlorothiazide combination is administered with high-fat meals, rate of quinapril absorption is reduced by 14%, but extent of absorption is unaffected.47

Special Populations

Decreased quinaprilat concentrations in patients with alcoholic cirrhosis.1 47

Distribution

Extent

Quinapril and quinaprilat do not cross the blood-brain barrier.1 47

Crosses the placenta in rats.1 47 Distributed into human milk.1 47

Plasma Protein Binding

97% for both quinapril and quinaprilat.1 47

Elimination

Metabolism

Metabolized principally to an active metabolite, quinaprilat (approximately 38% of oral dose).1 47

Elimination Route

Eliminated principally in urine (as metabolites).1 47

Not removed by hemodialysis or peritoneal dialysis.1 47

Half-life

Quinaprilat: Elimination: 2 hours; prolonged terminal phase of 25 hours.1 47

Special Populations

In patients with renal impairment, elimination half-life increases with decreasing Clcr.1 47

Decreased elimination of quinaprilat in patients ≥65 years of age.1 47

What are some other side effects of Accupril?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Dizziness.
  • Cough.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

PRINCIPAL DISPLAY PANEL - 5 mg Carton

UNIT DOSE

Pfizer

NDC 0071-0527-40

Accupril®
(Quinapril HCl Tablets)

5 mg*

For in-institution use only

100 Tablets
Rx only

PRINCIPAL DISPLAY PANEL - 20 mg Carton

UNIT DOSE

Pfizer

NDC 0071-0532-40

Accupril®
(Quinapril HCl Tablets)

20 mg*

For in-institution use only

100 Tablets
Rx only

Accupril and Pregnancy

Tell your doctor if you are pregnant or plan to become pregnant. Accupril is usually not recommended for use during pregnancy. See "FDA Warning" section.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Accupril falls into category D. It has been shown that use of Accupril in pregnant women caused some babies to be born with problems. More specifically, it has been shown that use of drugs like Accupril during the second and third trimesters of pregnancy harms the unborn baby’s kidneys and even increases the risk of death to the unborn baby. A more recent study showed that there may, in fact, also be an increased risk to the fetus if it is exposed to Accupril during the first trimester.

However, in some situations the benefit of using this medication may be greater than the risk of harm to the baby.

Other Requirements

Store at controlled room temperature between 15º–30ºC (59º–86ºF).

Keep this and all medications out of the reach of children.

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

Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan

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)

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 or a neprilysin inhibitor 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 & 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

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

What is Accupril?

Accupril (quinapril) is an ACE inhibitor. ACE stands for angiotensin converting enzyme.

Accupril is used to treat high blood pressure (hypertension) and heart failure.

Accupril may also be used for purposes not listed in this medication guide.

Quinapril Pregnancy Warnings

Animal studies have revealed no evidence of teratogenicity. There are no controlled data in human pregnancy. Use of drugs that act on the renin-angiotensin system (RAS) during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details. US FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Use is not recommended during the first trimester of pregnancy. Use is contraindicated during the second and third trimesters of pregnancy. AU TGA pregnancy category: D US FDA pregnancy category: D Comments: Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.

Quinapril Levels and Effects while Breastfeeding

Summary of Use during Lactation

Because of the low levels of quinapril in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants.

Drug Levels

Quinapril is an inactive drug that is metabolized to the active metabolite quinaprilat. Quinaprilat is poorly absorbed orally.

Maternal Levels. Six women who had been breastfeeding their infants for at least 2 weeks and were 4 to 9 months postpartum were given a single oral dose of 20 mg of quinapril. Quinapril milk levels were detectable at 4 hours after the dose, but undetectable (<5 mcg/L) in all samples by 6 hours after the dose. Quinalaprilat milk levels were undetectable (<5 mcg/L) at all time points. The authors estimated that a breastfed infant would receive about 1.6% of the maternal weight-adjusted dosage of quinapril.[1]

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

Benazepril, Captopril, Enalapril

References

1. Begg EJ, Robson RA, Gardiner SJ et al. Quinapril and its metabolite quinaprilat in human milk. J Clin Pharmacol. 2001;51:478-81. PMID: 11422007

Quinapril Identification

Substance Name

Quinapril

CAS Registry Number

85441-61-8

Drug Class

Antihypertensive Agents

Angiotensin-Converting Enzyme Inhibitors

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