ZAN-EXTRA

What it is

ZAN-EXTRA is a combination of lercanidipine hydrochloride and enalapril maleate in film-coated tablets for oral use. Two strengths are available: ZAN-EXTRA 10/10 containing 10 mg of lercanidipine hydrochloride and 10 mg of enalapril maleate, and ZAN-EXTRA 10/20 containing 10 mg of lercanidipine hydrochloride and 20 mg of enalapril maleate. ZAN-EXTRA combines a calcium channel blocker (lercanidipine) and an angiotensin converting enzyme inhibitor (enalapril).

Approved indications

— Treatment of hypertension.

Dosing overview

The recommended dosage for ZAN-EXTRA tablets is one tablet once daily taken orally at least 15 minutes before meals. The 10/10 strength tablets may be administered to patients whose blood pressure is not adequately controlled on lercanidipine 10 mg alone. The 10/20 strength tablets may be administered to patients whose blood pressure is not adequately controlled on enalapril 20 mg alone. Treatment should not be initiated with these fixed dose combinations.

Key safety warnings

Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with enalapril and may occur at any time during treatment. In such cases, ZAN-EXTRA should be promptly discontinued and the patient carefully observed until the swelling disappears. Even where swelling of only the tongue is involved without respiratory distress, patients may require prolonged observation since treatment with antihistamines and corticosteroids may not be sufficient. Very rarely, fatalities have been reported due to angioedema associated with laryngeal oedema or tongue oedema. Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. Where there is involvement of the tongue, glottis or larynx likely to cause airway obstruction, appropriate therapy including subcutaneous adrenaline solution 1:1000 (0.3 mL to 0.5 mL) and/or measures to ensure a patent airway should be promptly administered. Symptomatic hypotension was rarely seen in uncomplicated hypertensive patients. In hypertensive patients receiving enalapril, symptomatic hypotension is more likely to occur if the patient has been volume-depleted by diuretic therapy, dietary salt restriction, dialysis, diarrhoea or vomiting. In patients with heart failure with or without associated renal insufficiency, symptomatic hypotension has been observed and may be associated with oliguria and/or progressive azotaemia, and rarely with acute renal failure and/or death. This is most likely to occur in those patients with more severe degrees of heart failure, as reflected by the use of high doses of loop diuretics, hyponatraemia or functional renal impairment. Because of the potential fall in blood pressure in these patients, therapy should be started under very close medical supervision. A persistent, non-productive, ticklish cough has been reported in some patients undergoing treatment with enalapril and other ACE inhibiting drugs. The cough is often worse when lying down and is commoner in women, who account for about two thirds of reported cases. Elevated serum potassium (greater than 5.7 mmol/L) was observed in approximately one percent of hypertensive patients in clinical trials. In most cases these were isolated values which resolved despite continued therapy. Hyperkalaemia was a cause of discontinuation of therapy in 0.28% of hypertensive patients. Risk factors for the development of hyperkalaemia may include renal insufficiency, diabetes mellitus and the concomitant use of potassium supplements and/or potassium-containing salt substitutes.

Contraindications

Hypersensitivity to lercanidipine or enalapril, to any dihydropyridine calcium antagonist or ACE inhibitor, or to any of the excipients. ZAN-EXTRA is contraindicated in pregnancy, lactation, and in women of child-bearing potential unless effective contraception is used. Severe renal impairment (GFR less than 30 mL/min), including patients undergoing dialysis, and severe hepatic impairment. Co-administration is contraindicated with ciclosporin, strong CYP3A4 inhibitors, grapefruit or grapefruit juice, aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR less than 60 mL/min), and sacubitril/valsartan. History of angioedema, whether hereditary or idiopathic, or associated with previous ACE inhibitor therapy. Left ventricular outflow track obstruction, untreated congestive cardiac failure, and unstable angina pectoris or recent (within one month) myocardial infarction.

PBS listing

No PBS listing information is provided in the source documents.

Regulatory history

ZAN-EXTRA 10/10 and ZAN-EXTRA 10/20 were first listed on the ARTG on 14 February 2008.