INHIBACE Tablet Ref.[27888] Active ingredients: Cilazapril

Dosing Considerations

Dosage of INHIBACE (cilazapril) must be individualized.

Initiation of therapy requires consideration of recent antihypertensive drug treatment, the extent of blood pressure elevation, salt restriction, and other pertinent clinical factors. The dosage of other antihypertensive agents being used with INHIBACE may need to be adjusted.

The dose should always be taken at about the same time each day.

Recommended Dose and Dosage Adjustment

Hypertension

Monotherapy:

The recommended initial dose of INHIBACE is 2.5 mg once daily. Dosage should be adjusted according to blood pressure response, generally, at intervals of at least two weeks. The usual dose range for INHIBACE is 2.5 to 5 mg once daily. Minimal additional blood pressure lowering effects were achieved with a dose of 10 mg once daily. A dose of 10 mg should not be exceeded.

In most patients, the antihypertensive effect of INHIBACE is maintained with a once a day dosing regimen. In some patients treated once daily, the antihypertensive effect may diminish toward the end of the dosing interval. This can be evaluated by measuring blood pressure just prior to dosing to determine whether satisfactory control is being maintained for 24 hours. If it is not, either twice daily administration with the same total daily dose, or an increase in dose should be considered. If blood pressure is not adequately controlled with INHIBACE alone a non-potassium-sparing diuretic may be administered concomitantly. After the addition of a diuretic, it may be possible to reduce the dose of INHIBACE.

Patients with a strongly activated renin-angiotensin-aldosterone system (in particular, salt and/or volume depletion, cardiac decompensation or severe hypertension) may experience an excessive drop in blood pressure following the initial dose. A lower starting dose of 0.5 mg once daily is recommended in such patients and the initiation of treatment should take place under medical supervision.

Concomitant Diuretic Therapy:

In patients receiving diuretics, INHIBACE therapy should be initiated with caution, since they are usually volume depleted and more likely to experience hypotension following ACE inhibition. Whenever possible, all diuretics should be discontinued two to three days prior to the administration of INHIBACE to reduce the likelihood of hypotension (see WARNINGS AND PRECAUTIONS). If this is not possible because of the patient’s condition, INHIBACE should be started at 0.5 mg once daily and the blood pressure closely monitored after the first dose until stabilized. Thereafter, the dose should be adjusted according to individual response.

Dosage in Elderly Patients (Over 65 Years)

INHIBACE treatment should be initiated with 1.25 mg (half of a 2.5 mg tablet) once daily or less, depending on the patient’s volume status and general condition. Thereafter, the dose of INHIBACE must be adjusted according to individual tolerability, response, and clinical status.

Dosage Adjustment in Renal Impairment

(see WARNINGS AND PRECAUTIONS, Immune, Anaphylactoid Reactions during Membrane Exposure)

See Table 2 for the dose schedules recommended in patients with hypertension.

Table 2. Recommended Dosage Schedule for Patients with Hypertension and Renal Impairment:

Dosage Adjustment in Hepatic Impairment

In patients with liver cirrhosis (but without ascites) who require therapy for hypertension, cilazapril should be dosed with great caution not exceeding 0.5 mg/day accompanied by a careful monitoring of the blood pressure, because severe hypotension may occur. In patients with ascites, cilazapril administration is not recommended (see WARNINGS AND PRECAUTIONS).

Congestive Heart Failure

INHIBACE can be used as adjunctive therapy with digitalis and/or diuretics in patients with congestive heart failure. Therapy should be initiated under close medical supervision. Blood pressure and renal function should be monitored both before and during treatment with INHIBACE because severe hypotension and more rarely, renal failure have been reported (see WARNINGS and PRECAUTIONS).

Initiation of therapy requires consideration of recent diuretic therapy and the possibility of severe salt/volume depletion. If possible, the dose of diuretic should be reduced before beginning treatment, to reduce the likelihood of hypotension. Serum potassium should also be monitored (see WARNINGS AND PRECAUTIONS, DRUG INTERACTIONS, Drug-Drug Interactions).

Therapy with INHIBACE should be initiated with a recommended starting dose of 0.5 mg once daily under close medical supervision. In elderly patients with congestive heart failure on high diuretic dosage the recommended starting dose of INHIBACE 0.5 mg must be strictly followed (see WARNINGS AND PRECAUTIONS).

The dose should be increased to the lowest maintenance dose of 1 mg daily, usually within a 5-day period, according to tolerability and clinical status. Further titration within the usual maintenance dose of 1 mg to 2.5 mg daily should be carried out based on patient’s response, clinical status and tolerability.

The usual maximum dose is 2.5 mg once daily. A few patients have been titrated to 5 mg once daily with some additional benefits being achieved. However only limited data is available in congestive heart failure patients treated with 5 mg once daily.

Dosage Adjustment in Patients with Congestive Heart Failure and Renal Impairment or Hyponatremia

Reduced dosage may be required for patients with congestive heart failure and renal impairment or hyponatremia depending on the creatinine clearance. See Table 3 below.

Table 3. Recommended Dosage Schedule for Patients with Congestive Heart Failure and Renal Impairment or Hyponatremia:

Creatinine Clearance Initial Dose of INHIBACE Maximal Dose of INHIBACE >40 mL/min 0.5 mg once daily 2.5 mg once daily 10-40 mL/min 0.25 – 0.5 mg once daily 2.5 mg once daily <10 mL/min Not recommended.

Limited data are available with regard to overdosage in humans. Symptoms associated with overdosage of ACE inhibitors may include hypotension, which may be severe, circulatory shock, electrolyte disturbances including hyperkalemia and hyponatremia, renal impairment with metabolic acidosis, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety and cough.

The recommended treatment of overdosage is intravenous infusion of sodium chloride 9 mg/ml (0.9%) solution. If hypotension occurs, the patient should be placed in the shock position. If available, treatment with angiotensin II infusion and/or intravenous catecholamines may also be considered. Specific therapy with angiotensinamide may be considered if conventional therapy is ineffective.

Pacemaker therapy is indicated for therapy-resistant bradycardia. Vital signs, serum electrolytes and creatinine concentrations should be monitored continuously.

Hemodialysis removes cilazapril and cilazaprilat from the general circulation to a limited extent.

For management of a suspected drug overdose, contact your regional Poison Control Centre.

Store 15-30°C. Keep container tightly closed.