Fosinopril

Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors.

Concomitant use of certain anaesthetic medicinal products, tricyclic antidepressants and antipsychotics with ACE inhibitors may result in further reduction of blood pressure.

Alcohol enhances the hypotensive effect of fosinopril sodium.

Antacids (ie, aluminum hydroxide, magnesium hydroxide, and simethicone) may impair absorption of fosinopril. Administration of Fosinopril and antacids should be separated by at least 2 hours.

Epidemiological studies have suggested that concomitant administration of ACE inhibitors and antidiabetic medicinal products (insulins, oral hypoglycaemic agents) may cause an increased blood glucose lowering effect with risk of hypoglycaemia. This phenomenon appeared to be more likely to occur during the first weeks of combined treatment and in patients with renal impairment.

Although serum potassium usually remains within normal limits, hyperkalaemia may occur in some patients treated with fosinopril sodium. Potassium sparing diuretics (e.g. spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium. Care should also be taken when fosinopril sodium is co-administered with other agents that increase serum potassium, such as trimethoprim and cotrimoxazole (trimethoprim/sulfamethoxazole) as trimethoprim is known to act as a potassium-sparing diuretic like amiloride. Therefore, the combination of fosinopril sodium with the above-mentioned drugs is not recommended. If concomitant use is indicated, they should be used with caution and with frequent monitoring of serum potassium. Risk factors for the development of hyperkalaemia include renal insufficiency, diabetes mellitus, and concomitant use of potassium-sparing diuretics (e.g., spironolactone, triamterene or amiloride), potassium supplements, potassium-containing salt substitutes or other medicinal products associated with increases in serum potassium (e.g. heparin). The use of the abovementioned products, particularly in patients with impaired renal function, may lead to a significant increase in serum potassium.

If fosinopril sodium is given with a potassium-losing diuretic, diuretic-induced hypokalaemia may be ameliorated.

Combination with other anti-hypertensive agents such as beta blockers, methyldopa, calcium antagonists, and diuretics may increase the anti-hypertensive effect. Concomitant use with glyceryl trinitrate and other nitrates, or other vasodilators, may further reduce blood pressure.

Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosteronesystem (RAAS) through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent.

Patients on diuretics and especially those in whom diuretic therapy was recently instituted, as well as those on severe dietary salt restrictions or dialysis, may occasionally experience a precipitous reduction of blood pressure usually within the first hour after receiving the initial dose of fosinopril sodium.

Concomitant use of fosinopril with immunosuppressants (e.g. azathioprine) may increase the risk of leucopenia developing.

The combination of fosinopril sodium with immunosuppressant medicinal products and/or medicinal products that can cause leucopenia should be avoided.

Non-steroidal anti-inflammatory drugs and more than 3g/day aspirin may interfere with the antihypertensive effect. However, the concomitant use of fosinopril and NSAIDs (including aspirin) is not associated with an increase in clinically significant adverse reactions. As with any ACE inhibitor, in some patients with compromised renal function the co-administration of fosinopril and NSAIDs may result in a further deterioration of renal function.

Hyperkalaemia may occur during concomitant use of ACE inhibitors with ciclosporin. Monitoring of serum potassium is recommended.

Hyperkalaemia may occur during concomitant use of ACE inhibitors with heparin. Monitoring of serum potassium is recommended.

It has been reported that indomethacin may reduce the antihypertensive effect of other ACE inhibitors, especially in cases of low renin hypertension. Other nonsteroidal anti-inflammatory agents (eg, aspirin) may have a similar effect.

Increased serum lithium levels and risk of lithium toxicity have been reported in patients receiving ACE inhibitors concomitantly with lithium. Fosinopril sodium and lithium should be coadministered with caution, and frequent monitoring of serum lithium levels is recommended.

Concomitant use of ACE inhibitors with racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin may lead to an increased risk for angioedema.

Patients taking concomitant co-trimoxazole (trimethoprim/sulfamethoxazole) may be at increased risk for hyperkalaemia.

Therapy with fosinopril sodium should be interrupted for a few days before carrying out tests for parathyroid function.

Elevations in serum potassium have been observed in some patients treated with ACE inhibitors, including fosinopril. ACE inhibitors can cause hyperkalemia because they inhibit the release of aldosterone. The effect is usually not significant in patients with normal renal function. However, in patients with impaired renal function and/or in patients taking potassium supplements (including salt substitutes), potassium-sparing diuretics, trimethoprim or co-trimoxazole also known as trimethoprim/sulfamethoxazole and especially aldosterone antagonists or angiotensin-receptor blockers, hyperkalemia can occur. Potassium-sparing diuretics and angiotensin-receptor blockers should be used with caution in patients receiving ACE inhibitors, and serum potassium and renal function should be monitored.

Patients at risk for the development of hyperkalemia include those with renal insufficiency, diabetes mellitus, hypoaldosteronism or those using concomitant potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other drugs associated with increases in serum potassium (e.g, heparin, co-trimoxazole also known as trimethoprim/sulfamethoxazole). If concomitant use of the above mentioned agents is deemed appropriate, regular monitoring of serum potassium is recommended.

Fosinopril sodium has been rarely associated with hypotension in uncomplicated hypertensive patients. As with other ACE inhibitors, symptomatic hypotension is most likely to occur in salt/volume depleted patients such as those treated vigorously with diuretics, those patients undergoing renal dialysis, dietary salt restriction, diarrhoea or vomiting, or has severe renin-dependent hypertension. Volume and/or salt depletion should be corrected before initiating therapy with fosinopril. A transient hypotensive response is not a contraindication to further doses which may be given without difficulty after replenishment of salt and/or volume.

In patients with congestive heart failure, with or without associated renal insufficiency, ACE inhibitor therapy may cause excessive hypotension, which may be associated with oliguria or azotemia and, rarely, with acute renal failure and death. In such patients, fosinopril sodium therapy should be started under close medical supervision; they should be followed closely for the first 2 weeks of treatment and whenever the dose of fosinopril or diuretic is increased.

Consideration should be given to reducing the diuretic dose in patients with normal or low blood pressure who have been treated vigorously with diuretics or who are hyponatremic.

Hypotension is not per se a reason to discontinue fosinopril. The magnitude of the decrease is greatest early in the course of treatment; this effect stabilizes within a week or two, and generally returns to pretreatment levels without a decrease in therapeutic efficacy.

The safety of an initial 10mg dose has not been studied in patients with severe heart failure NYHA IV. Similar considerations apply to patients with ischaemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident.

If hypotension occurs, the patient should be placed in the supine position and, if necessary, should receive an intravenous infusion of sodium chloride 9mg/ml (0.9%) solution.

In patients with pre-existing renal impairment proteinuria may occur in rare cases. In clinically relevant proteinuria (greater than 1 g/day) Fosinopril should only be used after a very critical benefit/risk evaluation and with regular monitoring of the clinical and laboratory chemical parameters.

Fosinopril may cause a false low measurement of serum digoxin levels with assays using the charcoal absorption method for digoxin. Other kits which use the antibody coated-tube method may be used.

Very rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice or hepatitis and progresses to fulminant necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving Fosinopril sodium Tablets who develop jaundice or marked elevations of hepatic enzymes should discontinue fosinopril and receive appropriate medical follow-up.

Neutropenia/agranulocytosis, thrombocytopenia and anaemia have been reported in patients receiving ACE inhibitors. In patients with normal renal function and no other complicating factors, neutropenia occurs rarely. Neutropenia and agranulocytosis are reversible after discontinuation of the ACE inhibitor. Fosinopril sodium should be used with extreme caution in patients with collagen vascular disease, immunosuppressant therapy, treatment with allopurinol or procainamide, or a combination of these complicating factors, especially if there is pre-existing impaired renal function. Some of these patients developed serious infections, which in a few instances did not respond to intensive antibiotic therapy. If fosinopril sodium is used in such patients, periodic monitoring of white blood cell counts is advised and patients should be instructed to report any sign of infection.

Cough has been reported with the use of ACE inhibitors. Characteristically, the cough is non-productive, persistent and resolves after discontinuation of therapy. ACE inhibitor-induced cough should be considered as part of the differential diagnosis of cough.

As with other angiotensin-converting enzyme (ACE) inhibitors, fosinopril sodium should be given with caution to patients with mitral valve stenosis and obstruction in the outflow of the left ventricle such as aortic stenosis or hypertrophic cardiomyopathy.

The use of ACE inhibitors is not recommended during the first trimester of pregnancy. The use of ACE inhibitors is contraindicated during the second and third trimester of pregnancy.

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started.

Exposure to ACE inhibitor therapy during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). Should exposure to ACE inhibitor have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Infants whose mothers have taken ACE inhibitors should be closely observed for hypotension.

Fosinoprilat, which crosses the placenta, has been removed from the neonatal circulation by peritoneal dialysis with some clinical benefit, and theoretically may be removed by exchange transfusion.

Because only very limited information is available regarding the use of fosinopril during breastfeeding, Fosinopril is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

Whilst fosinopril is not expected to directly affect performance, it can cause adverse effects such as dizziness, vertigo or hypotension which may interfere with driving or use of machines. This occurs especially at the start of treatment, when increasing the dosage, when changing over from other preparations and during concomitant use of alcohol, depending on the individual’s susceptibility. Patients should make sure they are not affected before driving or operating machinery.