Side Effects of Monopril (fosinopril)

Monopril (fosinopril) is an angiotensin converting enzyme (ACE) inhibitor used to treat high blood pressure (hypertension) and heart failure and to prevent kidney failure due to high blood pressure and diabetes. 

ACE is an enzyme in blood which controls the formation of angiotensin II, a chemical that circulates in blood and causes constriction of arteries and veins. Constriction of arteries and veins elevates blood pressure. 

ACE inhibitors inhibit ACE and block the formation of angiotensin II. By blocking the formation of angiotensin II, Monopril relaxes the arteries and veins and lowers blood pressure. By reducing blood pressure, Monopril also reduces the work that the heart must do to pump blood through the arteries and veins. This improves the output of blood from the heart especially when the heart is failing.

Common side effects of Monopril include

• headache,
• cough,
• dizziness,
• diarrhea,
• fatigue,
• nausea,
• vomiting,
• increased potassium levels,
• sexual dysfunction, and
• abnormal liver tests. 

Serious side effects of Monopril include

• impaired kidney function,
• liver failure,
• low white blood cell counts (neutropenia), and
• angioedema (swelling of lips and throat that can obstruct breathing).

Drug interactions of Monopril include potassium supplements, potassium-containing salt substitutes, or potassium-conserving diuretics such as amiloride, spironolactone, and triamterene, because it can lead to dangerously high blood levels of potassium (hyperkalemia) since Monopril has a tendency to reduce the excretion of potassium.

• Monopril should not be taken at the same time as aluminum or magnesium-based antacids, such as simethicone or Maalox since these antacids bind Monopril and decrease the amount of Monopril absorbed from the intestine.
• Monopril can cause an increase in the amount of lithium in the body in patients taking lithium, sometimes causing lithium-associated side effects.
• Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, indomethacin, and naproxen may reduce the effects of ACE inhibitors on blood pressure.
• Combining Monopril or other ACE inhibitors with nonsteroidal anti-inflammatory drugs (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.
• These effects usually are reversible. Nitritoid reactions (symptoms include facial flushing, nausea, vomiting, and hypotension) may occur when injectable gold sodium aurothiomalate, used in the treatment of rheumatoid arthritis, is combined with ACE inhibitors, including Monopril.

ACE inhibitors, including Monopril, can be harmful to the fetus and should not be taken by pregnant women. Monopril is secreted in breast milk and is not recommended for breastfeeding mothers.

Fosinopril is generally well tolerated. The most common side effects are:

• headache,
• cough,
• dizziness,
• diarrhea,
• fatigue,
• nausea,
• vomiting, and
• increase in potassium levels.

Sexual dysfunction and abnormal liver tests also occur. Impairment of kidney function has been reported with ACE inhibitors, especially in patients with severe heart failure or kidney disease.

Other important and serious side effects, although rare, include:

• liver failure,
• low white blood cell counts (neutropenia) and
• angioedema (swelling of lips and throat that can obstruct breathing).

Monopril (fosinopril sodium) has been evaluated for safety in more than 2100 individuals in hypertension and heart failure trials, including approximately 530 patients treated for a year or more. Generally adverse events were mild and transient, and their frequency was not prominently related to dose within the recommended daily dosage range.

Hypertension

In placebo-controlled clinical trials (688 Monopril (fosinopril sodium) -treated patients), the usual duration of therapy was 2 to 3 months. Discontinuations due to any clinical or laboratory adverse event were 4.1% and 1.1% in Monopril (fosinopril sodium) -treated and placebo-treated patients, respectively.

The most frequent reasons (0.4 to 0.9%) were

• headache,
• elevated transaminases,
• fatigue,
• cough,
• diarrhea, and
• nausea and vomiting.

During clinical trials with any Monopril (fosinopril sodium) regimen, the incidence of adverse events in the elderly ( ≥ 65 years old) was similar to that seen in younger patients.

Clinical adverse events probably or possibly related or of uncertain relationship to therapy, occurring in at least 1% of patients treated with Monopril (fosinopril sodium) alone and at least as frequent on Monopril (fosinopril sodium) as on placebo in placebo-controlled clinical trials are shown in the table below.

Clinical Adverse Events in Placebo-Controlled Trails (Hypertension)

The following events were also seen at > 1% on Monopril (fosinopril sodium) but occurred in the placebo group at a greater rate:

• headache,
• diarrhea,
• fatigue, and
• sexual dysfunction.

Other clinical events probably or possibly related, or of uncertain relationship to therapy occurring in 0.2 to 1.0% of patients (except as noted) treated with Monopril (fosinopril sodium) in controlled or uncontrolled clinical trials (N=1479) and less frequent, clinically significant events include (listed by body system):

• General: Chest pain, edema, weakness, excessive sweating.
• Cardiovascular: Angina/myocardial infarction, cerebrovascular accident, hypertensive crisis, rhythm disturbances, palpitations, hypotension, syncope, flushing, claudication.
• Orthostatic: hypotension occurred in 1.4% of patients treated with fosinopril monotherapy. Hypotension or orthostatic hypotension was a cause for discontinuation of therapy in 0.1% of patients.
• Dermatologic: Urticaria, rash, photosensitivity, pruritus.
• Endocrine/Metabolic: Gout, decreased libido.
• Gastrointestinal: Pancreatitis, hepatitis, dysphagia, abdominal distention, abdominal pain, flatulence, constipation, heartburn, appetite/weight change, dry mouth.
• Hematologic: Lymphadenopathy.
• Immunologic: Angioedema.
• Musculoskeletal: Arthralgia, musculoskeletal pain, myalgia/muscle cramp.
• Nervous/Psychiatric: Memory disturbance, tremor, confusion, mood change, paresthesia, sleep disturbance, drowsiness, vertigo.
• Respiratory: Bronchospasm, pharyngitis, sinusitis/rhinitis, laryngitis/hoarseness, epistaxis. A symptom-complex of cough, bronchospasm, and eosinophilia has been observed in two patients treated with fosinopril.
• Special Senses: Tinnitus, vision disturbance, taste disturbance, eye irritation.
• Urogenital: Renal insufficiency, urinary frequency.

Heart Failure

In placebo-controlled clinical trials (361 Monopril (fosinopril sodium) -treated patients), the usual duration of therapy was 3-6 months. Discontinuations due to any clinical or laboratory adverse event, except for heart failure, were 8.0% and 7.5% in Monopril (fosinopril sodium) -treated and placebo-treated patients, respectively.

The most frequent reason for discontinuation of Monopril (fosinopril sodium) was angina pectoris (1.1%). Significant hypotension after the first dose of Monopril (fosinopril sodium) occurred in 14/590 (2.4%) of patients; 5/590 (0.8%) patients discontinued due to first dose hypotension.

Clinical adverse events probably or possibly related or of uncertain relationship to therapy, occurring in at least 1% of patients treated with Monopril (fosinopril sodium) and at least as common as the placebo group, in placebo-controlled trials are shown in the table below.

Clinical Adverse Events in Placebo-Controlled Trails (Heart Failure)

The following events also occurred at a rate of 1% or more on Monopril (fosinopril sodium) (fosinopril sodium tablets) but occurred on placebo more often:

• fatigue,
• dyspnea,
• headache,
• rash,
• abdominal pain,
• muscle cramp,
• angina pectoris,
• edema, and
• insomnia.

The incidence of adverse events in the elderly ( ≥ 65 years old) was similar to that seen in younger patients.

Other clinical events probably or possibly related, or of uncertain relationship to therapy occurring in 0.4 to 1.0% of patients (except as noted) treated with Monopril (fosinopril sodium) in controlled clinical trials (N=516) and less frequent, clinically significant events include (listed by body system):

• General: Fever, influenza, weight gain, hyperhidrosis, sensation of cold, fall, pain.
• Cardiovascular: Sudden death, cardiorespiratory arrest, shock (0.2%), atrial rhythm disturbance, cardiac rhythm disturbances, non-anginal chest pain, edema lower extremity, hypertension, syncope, conduction disorder, bradycardia, tachycardia.
• Dermatologic: Pruritus.
• Endocrine/Metabolic: Gout, sexual dysfunction.
• Gastrointestinal: Hepatomegaly, abdominal distention, decreased appetite, dry mouth, constipation, flatulence.
• Immunologic: Angioedema (0.2%).
• Musculoskeletal: Muscle ache, swelling of an extremity, weakness of an extremity.
• Nervous/Psychiatric: Cerebral infarction, TIA, depression, numbness, paresthesia, vertigo, behavior change, tremor.
• Respiratory: Abnormal vocalization, rhinitis, sinus abnormality, tracheobronchitis, abnormal breathing, pleuritic chest pain.
• Special Senses: Vision disturbance, taste disturbance.
• Urogenital: Abnormal urination, kidney pain.
• Fetal/Neonatal Morbidity and Mortality: See product labeling.

Potential Adverse Effects Reported with ACE Inhibitors

• Body as a whole: Anaphylactoid reactions.
• Other medically important adverse effects reported with ACE inhibitors include:
  • Cardiac arrest;
  • eosinophilic pneumonitis;
  • neutropenia/agranulocytosis, pancytopenia, anemia (including hemolytic and aplastic), thrombocytopenia;
  • acute renal failure;
  • hepatic failure, jaundice (hepatocellular or cholestatic);
  • symptomatic hyponatremia;
  • bullous pemphigus, exfoliative dermatitis;
  • a syndrome which may include:
    • arthralgia/arthritis,
    • vasculitis,
    • serositis,
    • myalgia,
    • fever,
    • rash or other dermatologic manifestations,
    • a positive ANA,
    • leukocytosis,
    • eosinophilia, or
    • an elevated ESR.

Laboratory Test Abnormalities

• Serum Electrolytes: Hyperkalemia; hyponatremia.
• BUN/Serum Creatinine: Elevations, usually transient and minor, of BUN or serum creatinine have been observed. In placebo-controlled clinical trials, there were no significant differences in the number of patients experiencing increases in serum creatinine (outside the normal range or 1.33 times the pre-treatment value) between the fosinopril and placebo treatment groups. Rapid reduction of longstanding or markedly elevated blood pressure by any antihypertensive therapy can result in decreases in the glomerular filtration rate, and in turn, lead to increases in BUN or serum creatinine.
• Hematology: In controlled trials, a mean hemoglobin decrease of 0.1 g/dL was observed in fosinopril-treated patients. In individual patients decreases in hemoglobin or hematocrit were usually transient, small, and not associated with symptoms. No patient was discontinued from therapy due to the development of anemia.
• Other: Neutropenia, leukopenia and eosinophilia.
• Liver Function Tests: Elevations of transaminases, LDH, alkaline phosphatase, and serum bilirubin have been reported. Fosinopril therapy was discontinued because of serum transaminase elevations in 0.7% of patients. In the majority of cases, the abnormalities were either present at baseline or were associated with other etiologic factors. In those cases which were possibly related to fosinopril therapy, the elevations were generally mild and transient and resolved after discontinuation of therapy.

Pediatric Patients

• The adverse experience profile for pediatric patients is similar to that seen in adult patients with hypertension.
• The long-term effects of Monopril (fosinopril sodium) on growth and development have not been studied.

• Diuretics: Patients on diuretics, especially those with intravascular volume depletion, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with Monopril (fosinopril sodium tablets). The possibility of hypotensive effects with Monopril (fosinopril sodium) can be minimized by either discontinuing the diuretic or increasing salt intake prior to initiation of treatment with Monopril (fosinopril sodium) . If this is not possible, the starting dose should be reduced and the patient should be observed closely for several hours following an initial dose and until blood pressure has stabilized.
• Potassium supplements and potassium-sparing diuretics: Monopril (fosinopril sodium) can attenuate potassium loss caused by thiazide diuretics. Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) or potassium supplements can increase the risk of hyperkalemia. Therefore, if concomitant use of such agents is indicated, they should be given with caution, and the patient's serum potassium should be monitored frequently.
• Lithium: Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium. These drugs should be coadministered with caution, and frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, the risk of lithium toxicity may be increased.
• Antacids: In a clinical pharmacology study, coadministration of an antacid (aluminum hydroxide, magnesium hydroxide, and simethicone) with fosinopril reduced serum levels and urinary excretion of fosinoprilat as compared with fosinopril administrated alone, suggesting that antacids may impair absorption of fosinopril. Therefore, if concomitant administration of these agents is indicated, dosing should be separated by 2 hours.
• 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 including Monopril (fosinopril sodium) .
• Other: Neither Monopril (fosinopril sodium) nor its metabolites have been found to interact with food. In separate single or multiple dose pharmacokinetic interaction studies with chlorthalidone, nifedipine, propranolol, hydrochlorothiazide, cimetidine, metoclopramide, propantheline, digoxin, and warfarin, the bioavailability of fosinoprilat was not altered by coadministration of fosinopril with any one of these drugs. In a study with concomitant administration of aspirin and Monopril (fosinopril sodium) , the bioavailability of unbound fosinoprilat was not altered.
• Warfarin: In a pharmacokinetic interaction study with warfarin, bioavailability parameters, the degree of protein binding, and the anticoagulant effect (measured by prothrombin time) of warfarin were not significantly changed.

Drug/Laboratory Test Interaction

• Fosinopril may cause a false low measurement of serum digoxin levels with the Digi-Tab RIA Kit for Digoxin. Other kits, such as the Coat-A-Count RIA Kit, may be used.