EXFORGE

What it is

Exforge HCT is a film-coated tablet containing amlodipine besilate, valsartan, and hydrochlorothiazide. Five strengths are available: 5/160/12.5 mg, 5/160/25 mg, 10/160/12.5 mg, 10/160/25 mg and 10/320/25 mg. Exforge HCT tablets are non-divisible and cannot be divided into equal doses.

Approved indications

— Treatment of hypertension as substitution therapy in patients whose blood pressure is already adequately controlled on the triple combination of amlodipine, valsartan and hydrochlorothiazide taken either as three single component formulations or as dual-component formulation with a single-component formulation, all components at the same dose level.

Dosing overview

Treatment should not be initiated with these fixed-dose combinations. Exforge HCT is only indicated as substitution therapy in patients whose blood pressure is already adequately controlled on the triple combination. If blood pressure is not controlled on one of the three possible dual combination therapies, then any third monotherapy must be first added as an individual therapy until dose titration is complete and blood pressure control established before the triple fixed-dose combination may be introduced. The recommended dose is one tablet per day. Exforge HCT can be taken with or without food. It is recommended to take Exforge HCT with some water.

Key safety warnings

Excessive hypotension, including orthostatic hypotension, was seen in 1.7 per cent of patients treated with the maximum dose of Exforge HCT (10/320/25 mg) in a controlled trial. In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients receiving high doses of diuretics, symptomatic hypotension may occur in patients receiving angiotensin receptor blockers. This condition should be corrected prior to administration of Exforge HCT, or the treatment should start under close medical supervision. Angioedema, including swelling of the larynx and glottis, causing airway obstruction and/or swelling of the face, lips, pharynx, and/or tongue has been reported in patients treated with valsartan. Exforge HCT should be immediately discontinued in patients who develop angioedema, and Exforge HCT should not be re-administered. An increased risk of non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma) with increasing cumulative dose of hydrochlorothiazide exposure has been observed. The risk for non-melanoma skin cancer appears to increase with long-term use. Patients taking hydrochlorothiazide should be informed of the risk of non-melanoma skin cancer and advised to regularly check their skin for any new lesions and promptly report any suspicious skin lesions. Limited exposure to sunlight and UV rays and, in case of exposure, adequate protection should be advised to patients in order to minimise the risk of skin cancer. Very rare severe cases of acute respiratory toxicity, including acute respiratory distress syndrome (ARDS), have been reported after taking hydrochlorothiazide. Pulmonary oedema typically develops within minutes to hours after hydrochlorothiazide intake. At the onset, symptoms include dyspnoea, fever, pulmonary deterioration and hypotension.

Contraindications

Exforge HCT is contraindicated in hypersensitivity to the active substances, dihydropyridine derivatives, other sulfonamide-derived drugs, or to any of the excipients; severe hepatic impairment; biliary cirrhosis and cholestasis; severe renal impairment (glomerular filtration rate less than 30 mL/min/1.73 m²), anuria and patients undergoing dialysis; refractory hypokalaemia, hyponatremia, hypercalcaemia and symptomatic hyperuricaemia; pregnancy; and concomitant use with aliskiren in patients with Type 2 diabetes mellitus.

Regulatory history

Exforge 5/80 and Exforge 5/160 and 10/160 were first registered on the ARTG on 5 February 2008. Exforge HCT 5/160/12.5, Exforge HCT 5/160/25, Exforge HCT 10/160/25, Exforge HCT 10/320/25 and Exforge HCT 10/160/12.5 were first registered on the ARTG on 9 April 2010. The TGA approved Exforge HCT on 1 April 2010 as a substitution therapy for the treatment of hypertension in patients whose blood pressure is already adequately controlled on the triple combination of amlodipine, valsartan, and hydrochlorothiazide, and is not indicated for initial therapy.