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Drug Details

VASCACE Tablets (hypertension)

• Drug Class Description
  ACE inhibitors.
• Generic Name
  Cilazapril - hypertension
• Presentation
  One film coated tablet 0.5mg contains: Cilazapril, anhydrous 0.5mg, in the form of the monohydrate (cilazapril 0.522mg). One film coated tablet 1.0mg contains; Cilazapril, anhydrous 1.0mg, in the form of the monohydrate (cilazapril 1.044mg). One film coated tablet 2.5mg contains: Cilazapril, anhydrous 2.5mg, in the form of the monohydrate (cilazapril 2.61mg). One film coated tablet 5.0mg contains: Cilazapril, anhydrous 5mg, in the form of the monohydrate (cilazapril 5.22mg).
• Description
  Tablets
• Indications
  Vascace is indicated in treatment of all grades of essential hypertension. Vascace is also indicated in the treatment of chronic heart failure, usually as an adjunctive therapy with digitalis and/or diuretics.
• Adult Dosage
  

  Vascace should be administered once-daily. As food intake has no clinically significant influence on absorption, Vascace can be administered before or after a meal. The dose should always be taken at about the same time of day.

  Special Dosage Instructions:

  Essential hypertension

  The recommended initial dosage is 1mg once a day. Dosage should be adjusted individually in accordance with the blood pressure response until control is achieved. Most patients can be maintained on between 2.5 and 5.0mg/day. If the blood pressure is not adequately controlled with 5mg Vascace once daily, a low dose of a non-potassium-sparing diuretic may be administered concomitantly to enhance the anti-hypertensive effect.

  Hypertensive patients receiving diuretics

  The diuretic should be discontinued two to three days before beginning therapy with Vascace to reduce the likelihood of symptomatic hypotension. It may be resumed later if required. The recommended starting dose in these patients is 0.5mg once daily.

  Chronic heart failure

  Vascace can be used as adjunctive therapy with digitalis and/or diuretics in patients with chronic heart failure. Therapy with Vascace should be initiated with a recommended starting dose of 0.5mg once daily under close medical supervision. The dose should be increased to the lowest maintenance dose of 1mg daily according to tolerability and clinical status. Further titration within the usual maintenance dose of 1mg to 2.5mg daily should be carried out based on patients response, clinical status and tolerability. The usual maximum dose is 5mg once daily.

  Results from clinical trials showed that clearance of cilazaprilat in patients with chronic heart failure is correlated with creatinine clearance. Thus in patients with chronic heart failure and impaired renal function special dosage recommendation as given under "Impaired Renal Function" should be followed.

  Impaired renal function

  Reduced dosages may be required for patients with renal impairment, depending on their creatinine clearance

  The following dose schedules are recommended

  Creatinine clearance	Initial dose of Vascace	Maximal dose of Vascace
  > 40ml/min	1mg once daily	5mg once daily
  10 - 40ml/min	0.5mg once daily	2.5mg once daily
  < 10ml/min	Not recommended	Not recommended

  In patients requiring haemodialysis, Vascace should be administered on days when dialysis is not performed and the dosage should be adjusted according to blood pressure response.

  Impaired hepatic function

  In the unlikely event that a patient with liver cirrhosis should require treatment with cilazapril, it should be initiated with caution, at a dose of 0.5 mg or less once daily, because significant hypotension may occur 

  Vascace is contraindicated in patients with ascites

• Child Dosage
  

  Safety and efficacy in children have not been established therefore there is no recommendation for administration of cilazapril to children.

• Elderly Dosage
  

  In the treatment of hypertension, Vascace should be initiated with between 0.5mg and 1mg once daily. Thereafter, the maintenance dose must be adapted to individual response.

  In the treatment of chronic heart failure, Vascace should be initiated with a dose of 0.5mg daily. The maintenance dose of 1mg to 2.5mg must be adapted to individual tolerability, response and clinical status.

  In elderly patients with chronic heart failure on high diuretic dosage the recommended starting dose of Vascace 0.5mg must be strictly followed.

• Contra Indications
  

  Vascace is contraindicated in patients who are hypersensitive to cilazapril, other ACE-inhibitors or any of the product excipients, in patients with ascites and in the second and third trimesters of pregnancy.

  Vascace is also contraindicated in patients with a history of angioedema after treatment with other ACE-inhibitors.

• Special Precautions
  

  Vascace should be used with caution in patients with aortic stenosis, hypertrophic cardiomyopathy or outflow obstruction.

  In elderly patients with chronic heart failure on high diuretic dosage the recommended starting dose of Vascace 0.5mg must be strictly followed.

  Hypersensitivity/angioneurotic oedema

  Angioneurotic oedema has been reported in patients being treated with ACE-inhibitors.

  Haemodyalysis/anaphylaxis

  Although the mechanism involved has not been definitely established, there is clinical evidence that haemodialysis with polyacrylonitrile methallyl sulphate high-flux membranes (e.g. AN69), haemofiltration or LDL-apheresis, if performed in patients being treated with ACE-inhibitors, including cilazapril, can lead to the provocation of anaphylaxis/anaphylactoid reactions including life-threatening shock. The above-mentioned procedures must therefore be avoided in such patients.

  Symptomatic hypotension

  Occasionally, symptomatic hypotension has been reported with ACE-inhibitor therapy, particularly in patients with sodium or volume depletion in connection with conditions such as vomiting, diarrhoea, pre-treatment with diuretics, low sodium diet or after dialysis. In patients with angina pectoris or cerebrovascular disease, treatment with ACE-inhibitors should be started under close medical supervision, as excessive hypotension could result in myocardial infarction or cerebrovascular accident.

  Patients with chronic heart failure, especially those taking high doses of loop diuretics, may experience a pronounced blood pressure decrease in response to ACE-inhibitors. This should be treated by having the patient rest in the supine position and may require infusion of normal saline or volume expanders. After volume repletion, Vascace therapy may be continued. However, if symptoms persist, the dosage should be reduced or the drug discontinued.

  Renal impairment

  Reduced dosages may be required for patients with renal impairment, depending on their creatinine clearance. Treatment with ACE-inhibitors may produce increases in blood urea nitrogen and/or serum creatinine. Although these alterations are usually reversible upon discontinuation of Vascace and/or diuretic therapy, cases of severe renal dysfunction and, rarely, acute renal failure have been reported.

  In this patient population, renal function should be monitored during the first weeks of therapy.

  Hepatic impairment

  In patients with severe liver function impairment, hypotension may occur.

  Hepatic failure

  Rarely, ACE-inhibitors have been associated with hepatotoxicity including cholestatic and hepatocellular hepatitis. More severe reactions such as fulminant hepatic necrosis have also been reported. Patients receiving ACE-inhibitors who develop jaundice or elevations of hepatic enzymes should discontinue the ACE-inhibitor and receive appropriate medical follow-up.

  Serum potassium

  Concomitant administration of potassium-sparing diuretics, potassium supplements or potassium containing salt substitutes may lead to increases in serum potassium, particularly in patients with renal impairment. Therefore, if concomitant use for such agents is indicated, their dosage should be reduced when Vascace is initiated and serum potassium and renal function should be monitored carefully.

  Surgery anaesthesia

  The use of ACE-inhibitors in combination with anaesthetic drugs in surgery that also have blood-pressure-lowering effects, can produce arterial hypotension. If this occurs, volume expansion by means of intravenous infusion or - if resistant to these measures - angiotensin II infusion is indicated.

  Neutropenia

  Neutropenia and agranulocytosis have been rarely reported with ACE-inhibitors. Periodic monitoring of white blood cell counts should be considered in patients with collagen vascular disease and renal disease such as systemic lupus erythematosus and scleroderma, or in patients receiving immunosuppressive therapy, especially when they also have impaired renal function.

  Pregnancy

  ACE-inhibitors should not be initiated during pregnancy. 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.

  Owing to the presence of lactose monohydrate, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

• Interactions
  

  There was no increase in plasma digoxin concentrations when Vascace was administered concomitantly with digoxin. No clinically significant drug interactions were observed when Vascace was administered concomitantly with nitrates, oral antidiabetics, H2-receptor blockers and coumarin anticoagulants. No significant pharmacokinetic drug interactions between Vascace and furosemide or thiazides were noted. An additive effect may be observed when Vascace is administered in combination with other blood-pressure-lowering agents.

  Potassium-sparing diuretics, potassium supplements or potassium containing salt substitutes administered together with Vascace can lead to increases in serum potassium, particularly in patients with renal impairment.

  As with other ACE-inhibitors, use of Vascace concomitantly with a non-steroidal anti-inflammatory drug (NSAID) may diminish the anti-hypertensive effect of Vascace.

  Anaphylactic reactions can occur in patients undergoing desensitisation therapy with wasp or bee venom while receiving an ACE-inhibitor. Cilazapril must therefore be interrupted before the start of desensitisation therapy. Additionally, in this situation, cilazapril must not be replaced by a beta blocker.

  Concomitant administration of ACE-inhibitors and anti-diabetic medicines (insulin, oral hypoglycaemic agents) may cause an increased blood glucose lowering effect with the risk of hypoglycaemia. This phenomenon may be more likely to occur during the first weeks of combined treatment and in patients with renal impairment.

  Lithium should generally not be given with ACE-inhibitors. ACE-inhibitors reduce the renal clearance of lithium and add a risk of lithium toxicity.

  Concomitant administration of allopurinol, cytostatic or immunosuppressive agents, systemic corticosteroids or procainamide with ACE-inhibitors may lead to an increased risk of leucopenia.

  Alcohol can enhance the hypotensive effect of ACE-inhibitors.

• Adverse Drug Reactions
  

  In most cases undesirable effects are transient, mild or moderate in degree, and do not require discontinuation of therapy. The most common adverse effects include dry cough, rash, hypotension, dizziness, fatigue, headache and nausea, dyspepsia and other gastrointestinal disturbances.

  Blood and lymphatic system disorders

  Blood disorders have been reported with ACE-inhibitors and include neutropenia and agranulocytosis (especially in patients with renal failure and those with collagen vascular disorders such as systemic lupus erythematosus and scleroderma), thrombocytopenia and anaemia.

  Cardiac disorders

  Pronounced hypotension may occur at the start of therapy with ACE-inhibitors, particularly in patients with heart failure and in sodium- or volume-depleted patients. Myocardial infarction and stroke have been reported and may relate to severe falls in blood pressure in patients with ischaemic heart disease or cerbrovascular disease. Other cardiovascular effects that have occurred include tachycardia, palpitations and chest pain.

  Hepatobiliary disorders

  Single cases of liver function disorders, such as increased liver function tests (transaminases, bilirubin, alkaline phosphatase, gamma GT) and cholestatic hepatitis with or without necrosis, have been reported.

  Immune system disorders

  ACE-inhibitors have been documented to induce cough in a substantial number of patients. Rarely dyspnoea, sinusitis, rhinitis, glossitis, bronchitis and bronchospasm have been reported.

  As with other ACE-inhibitors, angioneurotic oedema has been reported, although rarely, in patients receiving Vascace. Angioedema involving the tongue, glottis or larynx may be fatal. If involvement of the face, lips, tongue, glottis and/or larynx occurs Vascace should be discontinued, replaced by an agent belonging to another class of drugs and appropriate therapy instituted without delay. Emergency therapy should be given including, but not necessarily limited to, immediate intramuscular adrenaline (epinephrine) solution 1:1000 (0.3 to 0.5ml) or slow intravenous adrenaline 1mg/ml (observing dilution instructions) with control of ECG and blood pressure. The patient should be hospitalised and observed for at least 12 to 24 hours and should not be discharged until complete resolution of symptoms has occurred.

  Gastrointestinal disorders

  Pancreatitis has been reported rarely in patients treated with ACE-inhibitors (including Vascace); in some cases this has proved fatal.

  Skin and subcutaneous tissue disorders

  Skin rashes (including erythema multiforme and toxic epidermal necrolysis) may occur; photosensitivity, alopecia and other hypersensitivity reactions have also been reported.

  Laboratory test findings

  Clinically relevant changes in laboratory test values possibly or probably related to Vascace treatment have been observed only rarely.

  Minor, mostly reversible increases in serum creatinine/urea have been observed in patients treated with Vascace. Such changes are likely to occur in patients with renal artery stenosis or with renal impairment, but they have also occasionally been observed in patients with normal renal function, particularly in those receiving concomitant diuretics.

  Renal and urinary disorders

  Isolated cases of acute renal failure have been reported in patients with severe heart failure, renal artery stenosis or renal disorders.