Side Effects of Accupril (quinapril)

Accupril (quinapril) is an angiotensin converting enzyme (ACE) inhibitor used to treat high blood pressure (hypertension) and heart failure and for preventing kidney failure due to high blood pressure and diabetes.

ACE is important because it produces angiotensin II, which contracts the muscles of the arteries in the heart and the rest of the body, narrowing the arteries and thereby elevating blood pressure.

In the kidney, the narrowing caused by angiotensin II decreases blood flow and increases the arterial filtration pressure in the kidney. ACE inhibitors such as Accupril lower blood pressure by inhibiting the formation of angiotensin II, thereby relaxing the arterial muscles and enlarging the arteries. This increases the flow of blood and oxygen to the heart so that it can pump blood more efficiently.

The enlargement of the arteries elsewhere in the body also makes it easier for the heart to pump blood. This is particularly beneficial when there is heart failure. In the kidneys ACE inhibitors increase blood flow and reduce the filtration pressure in the kidneys.

Common side effects of Accupril include

• cough,
• abdominal pain,
• constipation,
• diarrhea,
• rash,
• dizziness,
• fatigue,
• headache,
• loss of taste,
• loss of appetite,
• nausea,
• vomiting,
• fainting, and
• numbness or tingling in the hands or feet.

Serious side effects of Accupril include

• kidney failure and
• increased levels of potassium in the blood.

The most serious but very rare side effects of Accupril are

• liver failure and
• swelling of lips and throat (angioedema).

Drug interactions of Accupril include potassium supplements, salt substitutes, or diuretics that increase potassium in the blood, which may lead to excessive potassium levels in the body.

Patients receiving diuretics or are dehydrated or have low blood sodium may experience excessive reduction in blood pressure when Accupril is started.

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the effects of ACE inhibitors.

Combining Accupril or other ACE inhibitors with NSAIDs in patients who are elderly, volume-depleted (including those on diuretic therapy), or with poor kidney function may result in reduced kidney function, including kidney failure.

There have been reports of increased lithium levels when lithium is used in combination with ACE inhibitors.

Nitritoid reactions may occur when injectable gold (sodium aurothiomalate) is combined with ACE inhibitors, including Accupril. Symptoms include

• facial flushing,
• nausea,
• vomiting and
• hypotension

Accupril should not be combined with aliskiren because the combination increases the blockade of angiotensin, leading to low blood pressure, increased blood potassium, and possible kidney damage.

Angiotensin converting enzyme inhibitors, including Accupril, are very harmful to a fetus and should not be used during pregnancy. Accupril is secreted into breast milk. Because of the risk of harm to the infant, Accupril should be used with caution during breastfeeding.

Quinapril is generally well tolerated, and side effects are usually mild and transient. A dry, persistent cough has been reported with the use of quinapril and other ACE inhibitors. Coughing resolves after discontinuing the medication.

Other side effects include:

• abdominal pain,
• constipation,
• diarrhea,
• rash,
• dizziness,
• fatigue,
• headache,
• loss of taste,
• loss of appetite,
• nausea, vomiting,
• fainting, and
• numbness or tingling in the hands or feet.

Quinapril and other ACE inhibitors may also cause kidney failure and increased levels of potassium in the blood. The most serious but very rare side effects are liver failure and angioedema (swelling of lips and throat).

Hypertension

Accupril has been evaluated for safety in 4960 subjects and patients. Of these, 3203 patients, including 655 elderly patients, participated in controlled clinical trials. Accupril has been evaluated for long-term safety in over 1400 patients treated for 1 year or more.

Adverse experiences were usually mild and transient.

In placebo-controlled trials, discontinuation of therapy because of adverse events was required in 4.7% of patients with hypertension.

Adverse experiences probably or possibly related to therapy or of unknown relationship to therapy occurring in 1% or more of the 1563 patients in placebo-controlled hypertension trials who were treated with Accupril are shown below.

Adverse Events in Placebo-Controlled Trials

Heart Failure

Accupril has been evaluated for safety in 1222 Accupril treated patients. Of these, 632 patients participated in controlled clinical trials. In placebo-controlled trials, discontinuation of therapy because of adverse events was required in 6.8% of patients with congestive heart failure.

Adverse experiences probably or possibly related or of unknown relationship to therapy occurring in 1% or more of the 585 patients in placebo-controlled congestive heart failure trials who were treated with Accupril are shown below.

Hypertension And/Or Heart Failure

Clinical adverse experiences probably, possibly, or definitely related, or of uncertain relationship to therapy occurring in 0.5% to 1.0% (except as noted) of the patients with CHF or hypertension treated with Accupril (with or without concomitant diuretic) in controlled or uncontrolled trials (N=4847) and less frequent, clinically significant events seen in clinical trials or post-marketing experience (the rarer events are in italics) include (listed by body system):

General: back pain, malaise, viral infections, anaphylactoid reaction

Cardiovascular: palpitation, vasodilation, tachycardia, heart failure, hyperkalemia, myocardial infarction, cerebrovascular accident, hypertensive crisis, angina pectoris, orthostatic hypotension, cardiac rhythm disturbances, cardiogenic shock

Hematology: hemolytic anemia

Gastrointestinal: flatulence, dry mouth or throat, constipation, gastrointestinal hemorrhage, pancreatitis, abnormal liver function tests, dyspepsia

Metabolism and Nutrition Disorders: hyponatremia

Nervous/Psychiatric: somnolence, vertigo, syncope, nervousness, depression, insomnia, paresthesia

Integumentary: alopecia, increased sweating, pemphigus, pruritus, exfoliative dermatitis, photosensitivity reaction, dermatopolymyositis

Urogenital: urinary tract infection, impotence, acute renal failure, worsening renal failure

Respiratory: eosinophilic pneumonitis

Other: amblyopia, edema, arthralgia, pharyngitis, agranulocytosis, hepatitis, thrombocytopenia

Angioedema

Angioedema has been reported in patients receiving Accupril (0.1%). Angioedema associated with laryngeal edema may be fatal. If angioedema of the face, extremities, lips, tongue, glottis, and/or larynx occurs, treatment with Accupril should be discontinued and appropriate therapy instituted immediately.

Clinical Laboratory Test Findings

Hematology

Hyperkalemia

Creatinine and Blood Urea Nitrogen

Increases (>1.25 times the upper limit of normal) in serum creatinine and blood urea nitrogen were observed in 2% and 2%, respectively, of all patients treated with Accupril alone.

Increases are more likely to occur in patients receiving concomitant diuretic therapy than in those on Accupril alone. These increases often remit on continued therapy.

In controlled studies of heart failure, increases in blood urea nitrogen and serum creatinine were observed in 11% and 8%, respectively, of patients treated with Accupril; most often these patients were receiving diuretics with or without digitalis.

Concomitant Diuretic Therapy

As with other ACE inhibitors, patients on diuretics, especially those on recently instituted diuretic therapy, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with Accupril.

The possibility of hypotensive effects with Accupril may be minimized by either discontinuing the diuretic or cautiously increasing salt intake prior to initiation of treatment with Accupril. If it is not possible to discontinue the diuretic, the starting dose of quinapril should be reduced.

Agents Increasing Serum Potassium

Coadministration of Accupril with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients.

Tetracycline and other drugs that interact with magnesium: Simultaneous administration of tetracycline with Accupril reduced the absorption of tetracycline by approximately 28% to 37%, possibly due to the high magnesium content in Accupril tablets. This interaction should be considered if coprescribing Accupril and tetracycline or other drugs that interact with magnesium.

Lithium

Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving concomitant lithium and ACE inhibitor therapy. These drugs should be coadministered with caution and frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, it may increase the risk of lithium toxicity.

Gold

Nitritoid reactions (symptoms include facial flushing, nausea, vomiting, and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy.

Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors)

In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including quinapril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving quinapril and NSAID therapy.

The antihypertensive effect of ACE inhibitors, including quinapril may be attenuated by NSAIDs.

Agents That Inhibit mTOR

Patients taking concomitant mTOR inhibitor (e.g. temsirolimus) therapy may be at increased risk for angioedema.

Other Agents

Drug interaction studies of Accupril with other agents showed:

• Multiple dose therapy with propranolol or cimetidine has no effect on the pharmacokinetics of single doses of Accupril.
• The anticoagulant effect of a single dose of warfarin (measured by prothrombin time) was not significantly changed by quinapril coadministration twice-daily.
• Accupril treatment did not affect the pharmacokinetics of digoxin.
• No pharmacokinetic interaction was observed when single doses of Accupril and hydrochlorothiazide were administered concomitantly.
• Co-administration of multiple 10 mg doses of atorvastatin with 80 mg of Accupril resulted in no significant change in the steady-state pharmacokinetic parameters of atorvastatin.