NORDIP

What it is

NORDIP contains amlodipine, valsartan and hydrochlorothiazide and is available as film-coated tablets 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. NORDIP 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 (as substitution therapy only).

Dosing overview

NORDIP is indicated only as substitution therapy for patients whose blood pressure is already adequately controlled on the triple combination of amlodipine, valsartan and hydrochlorothiazide, and treatment should not be initiated with this fixed-dose combination. The recommended dose is one tablet per day. If blood pressure is not controlled on one of the three possible dual combination therapies, any third monotherapy must be first 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 NORDIP product range; if blood pressure is uncontrolled at one of the lower dosages, dose titration must be carried out with separately administered components.

Key safety warnings

Angioedema, including swelling of the larynx and glottis causing airway obstruction and swelling of the face, lips, pharynx and tongue has been reported in patients treated with valsartan. NORDIP should be immediately discontinued in patients who develop angioedema and 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 choroidal effusion with visual field defect, acute transient myopia and acute angle-closure glaucoma, with symptoms including acute onset of decreased visual acuity or ocular pain typically occurring within hours to weeks of drug initiation. Untreated acute-angle closure glaucoma can lead to permanent vision loss. 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, with the risk appearing 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. Possible preventive measures such as limited exposure to sunlight and ultraviolet rays and adequate protection should be advised to minimise the risk of skin cancer. Very rare severe cases of acute respiratory toxicity, including acute respiratory distress syndrome have been reported after taking hydrochlorothiazide. Pulmonary oedema typically develops within minutes to hours after hydrochlorothiazide intake, with symptoms including dyspnoea, fever, pulmonary deterioration and hypotension. If diagnosis of acute respiratory distress syndrome is suspected, NORDIP should be withdrawn and appropriate treatment given.

Contraindications

NORDIP is contraindicated in: hypersensitivity to the active substances, dihydropyridine derivatives, other sulfonamide-derived drugs or 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

NORDIP amlodipine 5 mg and 10 mg tablets were first registered on the Australian Register of Therapeutic Goods on 30 November 2007.