AMLOZIC

What it is

AMLOZIC is a fixed-dose combination 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. AMLOZIC tablets are non-divisible and cannot be divided into equal doses.

Approved indications

— Treatment of hypertension 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

AMLOZIC is indicated only as substitution therapy and treatment should not be initiated with this fixed-dose combination. AMLOZIC is only indicated as substitution therapy for 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, any third monotherapy must first be added as an individual therapy until dose titration is complete and blood pressure control is established before the triple fixed-dose combination may be introduced. There can be no direct dose-titration within the AMLOZIC product range. If a patient's blood pressure is uncontrolled at one of the lower dosages of the combination, dose titration must be carried out with the separately administered components. The recommended dose is one tablet per day.

Key safety warnings

Excessive hypotension, including orthostatic hypotension, was seen in 1.7% of patients treated with the maximum dose of AMLOZIC (10/320/25 mg). Rarely, patients, particularly those with severe obstructive coronary artery disease, have developed documented increased frequency, duration and/or severity of angina and/or acute myocardial infarction on starting calcium channel blocker therapy or at the time of dosage increase. 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. AMLOZIC should be immediately discontinued in patients who develop angioedema, and AMLOZIC should not be re-administered. Thiazide diuretics, including hydrochlorothiazide, have been reported to exacerbate or activate systemic lupus erythematosus. Hydrochlorothiazide, a sulfonamide, has been associated with an idiosyncratic reaction resulting in choroidal effusion with visual field defect, acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. An increased risk of non-melanoma skin cancer [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] with increasing cumulative dose of hydrochlorothiazide exposure has been observed in two epidemiological studies. The risk for non-melanoma skin cancer appears to increase with long-term use. 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

AMLOZIC 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<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.