AVANZA

What it is

AVANZA is an orally disintegrating tablet containing mirtazapine, available in strengths of 15 mg, 30 mg and 45 mg. The tablets contain aspartame as an excipient with known effect.

Approved indications

— Treatment of major depression including relapse prevention

Dosing overview

Treatment should begin with 15 mg daily, and dosage generally needs to be increased to obtain an optimal clinical response, with the effective daily dose usually between 30 and 45 mg, although responses have been observed at 60 mg per day. Mirtazapine has a half-life of 20–40 hours and is suitable for once-a-day administration as a single night-time dose before going to bed. It may also be given in sub-doses equally divided over the day, once in the morning and once at night-time. The recommended dose for elderly patients is the same as that for adults, although an increase in dosing should be done under close supervision to elicit a satisfactory and safe response. Mirtazapine begins to exert its effect in general after 1–2 weeks of treatment, and treatment with an adequate dose should result in a positive response within 2–4 weeks. Mirtazapine should not be used in children and adolescents under the age of 18 years.

Key safety warnings

The risk of suicidality is inherent in depression and may persist until significant remission occurs. Patients should be closely monitored for clinical worsening and suicidality, especially at the beginning of treatment or at the time of dose changes. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or whose emergent suicidality is severe, abrupt in onset, or was not part of the patient's presenting symptoms. Patients and caregivers should be alerted about the need to monitor for worsening of condition and the emergence of suicidal ideation or behaviour. Severe cutaneous adverse reactions, including Stevens–Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, bullous dermatitis and erythema multiforme, which can be life-threatening or fatal, have been reported in association with mirtazapine treatment. If signs and symptoms suggestive of these reactions appear, mirtazapine should be withdrawn immediately. Bone marrow depression, usually presenting as granulocytopenia or agranulocytosis, has been reported during treatment with mirtazapine, with symptoms mostly appearing after 2–6 weeks of treatment. Reversible agranulocytosis has been reported as a rare occurrence in clinical studies, and very rare cases of agranulocytosis have been reported in the post-marketing period, mostly reversible but in some cases fatal. Hyponatraemia has been reported very rarely with the use of mirtazapine, and caution should be exercised in patients at risk, such as elderly patients or patients concomitantly treated with medications known to cause hyponatraemia.

Contraindications

AVANZA is contraindicated in patients with hypersensitivity to mirtazapine or to any of the excipients. AVANZA should not be used in combination with MAO inhibitors, or within 14 days of initiating or discontinuing therapy with a MAO inhibitor.

PBS listing

The 30 mg tablet strength is listed on the PBS with 2 items under restricted restrictions at an ex-manufacturer price of A$9.09.

Regulatory history

AVANZA mirtazapine 30 mg film coated tablets were first registered on the ARTG on 20 February 2001 under licence category RE, sponsored by Organon Pharma.