TCW-AMLODIPINE

What it is

TCW-AMLODIPINE is a film-coated tablet containing amlodipine, valsartan and hydrochlorothiazide, available in five strengths: 5/160/12.5 mg, 5/160/25 mg, 10/160/12.5 mg, 10/160/25 mg and 10/320/25 mg.

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 as three single component formulations or as dual-component formulation with a single-component formulation, all components at the same dose level.

Dosing overview

The recommended dose is one tablet per day, which can be taken with or without food. Treatment should not be initiated with these fixed-dose combinations; if blood pressure is not controlled on one of the three possible dual combination therapies, then any third monotherapy must first be added as an individual therapy until dose titration is complete and blood pressure control established before the triple fixed-dose combination may be introduced. There can be no direct dose-titration within the product range, and if a patient's blood pressure is uncontrolled at one of the lower dosages, dose titration must be carried out with the separately administered components.

Key safety warnings

Excessive hypotension, including orthostatic hypotension, was reported in some patients treated with the maximum dose. 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; this condition should be corrected prior to administration 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. TCW-AMLODIPINE should be immediately discontinued in patients who develop angioedema, and should not be re-administered. Hydrochlorothiazide has been associated with choroidal effusion with visual field defect, acute transient myopia and acute angle-closure glaucoma, with symptoms typically occurring within hours to weeks of drug initiation. Untreated acute-angle closure glaucoma can lead to permanent vision loss; the primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. An increased risk of non-melanoma skin cancer with increasing cumulative dose of hydrochlorothiazide exposure has been observed. Patients taking hydrochlorothiazide should be informed of this risk and advised to regularly check their skin for any new lesions and promptly report any suspicious skin lesions. Very rare severe cases of acute respiratory distress syndrome have been reported after taking hydrochlorothiazide, with pulmonary oedema typically developing within minutes to hours. If diagnosis of acute respiratory distress syndrome is suspected, TCW-AMLODIPINE should be withdrawn and appropriate treatment given.

Contraindications

TCW-AMLODIPINE 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 (GFR less than 30 ml/min/1.73 m²), anuria and patients undergoing dialysis; refractory hypokalaemia, hyponatraemia, hypercalcaemia and symptomatic hyperuricaemia; pregnancy; and concomitant use with aliskiren in patients with Type 2 diabetes mellitus.

Regulatory history

TCW-AMLODIPINE was first registered on the Australian Register of Therapeutic Goods on 13 April 2017, with two registered variants: amlodipine besylate 5 mg (ARTG 264392) and amlodipine besylate 10 mg (ARTG 264393) tablet blister packs, sponsored by Ipca Pharma.