FOSINOPRIL SODIUM Tablet Ref.[8410] Active ingredients: Fosinopril

Posology

Fosinopril sodium should be administered orally in a single daily dose. As with all other medicinal products taken once daily, it should be taken at approximately the same time each day. The absorption of fosinopril sodium is not affected by food. The usual initial 10 mg dose has not been studied in patients with severe heart failure NYHA IV and in patients over 75 years treated for heart failure (see section 4.4). The maintenance dose should be individualised according to patient profile and blood pressure response (see section 4.4). Hypertension Fosinopril sodium may be used as a monotherapy or in combination with other classes of antihypertensive medicinal products (see sections 4.3, 4.4, 4.5 and 5.1).

Hypertensive patients not being treated with diuretics

Starting dose The initial recommended dose is 10 mg once a day. Patients with a strongly activated renin-angiotensin-aldosterone system (in particular, renovascular hypertension, salt and/or volume depletion, cardiac decompensation, or severe hypertension) may experience an excessive blood pressure fall following the initial dose. The initiation of treatment should take place under medical supervision.

Maintenance dose

The usual daily dose is 10 mg to a maximum of 40 mg administered in a single dose. In general if the desired therapeutic effect cannot be achieved in a period of 3 to 4 weeks on a certain dose level, the dose can be further increased.

Hypertensive patients being treated with concomitant diuretic therapy

Symptomatic hypotension may occur following initiation of therapy with fosinopril sodium. This is more likely in patients who are being treated currently with diuretics, especially in patients with heart failure, elderly patients (over 75 years) and patients with renal dysfunction. Caution is recommended therefore, since these patients may be volume and/or salt depleted. If possible, the diuretic should be discontinued 2 to 3 days before beginning therapy with fosinopril sodium. In hypertensive patients in whom the diuretic cannot be discontinued, therapy with fosinopril sodium should be initiated with a 10 mg dose. Renal function and serum potassium should be monitored. The subsequent dosage of fosinopril sodium should be adjusted according to blood pressure response. If required, diuretic therapy may be resumed (see sections 4.4 and 4.5). When treatment is initiated in a patient already taking diuretics, it is recommended that the treatment with fosinopril sodium is started under medical supervision for several hours and until blood pressure is stabilised.

Special populations

Heart Failure

The recommended initial dose is 10mg once daily, initiated under close medical supervision. If the initial dose is well tolerated patients should then be titrated to a dose of up to 40mg once daily. The appearance of hypotension after the initial dose should not preclude careful dose titration of Fosinopril Sodium 10mg Tablets, following effective management of the hypotension. Fosinopril Sodium 10mg Tablets should be used in addition to diuretics and digitalis where appropriate.

Heart Failure – High Risk Patients

It is recommended that treatment is initiated in hospital for patients with severe cardiac failure (NYHA IV) and those at particular risk of first dose hypotension, i.e. patients on multiple or high dose diuretics (e.g. >80mg furosemide), patients with hypovolaemia, hyponatraemia (serum sodium <130 meq/l), pre-existing hypotension (systolic blood pressure <90 mmHg), patients with unstable cardiac failure and those on high-dose vasodilator therapy. Renal function and serum potassium should be monitored (see section 4.4).

Paediatric population

Use in this age group is not recommended. There is limited clinical trial experience of the use of fosinopril in hypertensive children aged 6 years and above (see section 5.1, 5.2 and 4.8). The optimum dosage has not been determined in children of any age. An appropriate dose strength is not available for children weighing less than 50kg.

Elderly

No dosage reduction is necessary in patients with clinically normal renal and hepatic function as no significant differences in the pharmacokinetic parameters or antihypertensive effect of fosinoprilat have been found compared with younger subjects.

Impaired hepatic function

Treatment should be initiated at a dose of 10mg. Although the rate of hydrolysis may be slowed, the extent of hydrolysis is not appreciably reduced in patients with hepatic impairment. In this group of patients, there is evidence of reduced hepatic clearance of fosinoprilat with compensatory increase in renal excretion.

Renal impairment

Treatment should be initiated at a dose of 10mg, however caution is advised especially with a GFR of less than 10 ml/min. Depending on the response, the dose should then be titrated to achieve the desired therapeutic effect.

Absorption, bioavailability, protein binding, biotransformation and metabolism are not appreciably altered by reduced renal function. In patients with impaired renal function, the total body clearance of fosinoprilat is approximately 50% slower than that in patients with normal renal function. However, since hepatobiliary elimination compensates at least partially for diminished renal elimination, the body clearance of fosinoprilat is not appreciably different over a wide range of renal insufficiency (creatinine clearances ranging from <10 to 80 ml/min/1.73m², i.e. including end-stage renal failure).

Neither haemodialysis nor peritoneal dialysis is effective in clearing fosinoprilat. Peritoneal clearance is insignificant, ranging from 0.07 to 0.23ml per minute. Similarly haemodialysis for four hours clears only approximately 1.5% of the administered dose. This corresponds to 7% and 2% respectively, of urea clearance. Hence no dose adjustment is necessary to correct for drug loss during these procedures.

NB Fosinopril is NOT licensed for use in acute myocardial infarction.

Method of administration

For oral administration.

Symptoms

The symptoms of overdosage may include severe hypotension, circulatory shock, electrolyte disturbance, renal failure, hyperventilation tachycardia, palpitations, bradycardia, dizziness, anxiety and cough. The recommended treatment of overdose is intravenous infusion of normal saline solution.

After ingestion of an overdose the patient should be kept under very close supervision preferably in an intensive care unit. Serum electrolytes and creatinine should be monitored frequently. Therapeutic measures depend on the nature and severity of the symptoms. Measures to prevent absorption such as gastric lavage, administration of adsorbents and sodium sulfate within 30 minutes after intake and hasten elimination should be applied if ingestion is recent. If severe hypotension occurs the patient should be placed in the shock position and salt and volume supplementation should be given rapidly. Treatment with angiotensin II (if available) may be considered. Bradycardia or extensive vagal reactions should be treated by administering atropine. The use of high-flux polyacrylonitrile dialysis membrane should be avoided. Serum electrolytes and creatinine should be monitored frequently. The use of a pacemaker may be considered.

Management

Treatment overview:

• ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
• HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid, place in Trendelenburg position. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or noradrenaline (norepinephrine) (0.1 to 0.2 mcg/kg/min), titrate to desired response.
• ** Angiotensin infusion at doses ranging from 8.5 to 18 mcg/minute has been successful in reversing hypotension in patients who did not respond to volume and pressor infusions.
• ** Naloxone has also been effective in some patients with hypotension.
• ANGIOEDEMA: Administer antihistamines and corticosteroids. Monitor airway carefully and administer oxygen.

18 months.

Do not store above 25°C.

Aluminium-aluminium blisters: Each carton will contain either 7, 10, 14, 20, 21, 28, 30, 50, 56, 60, 84, 90, 98, 100* tablets.

* Not all pack sizes may be marketed.

No special requirements.