AXIT

What it is

AXIT is mirtazapine film coated tablets available in strengths of 15 mg, 30 mg or 45 mg. AXIT is an antidepressant which can be given as treatment for episodes of major depression. Mirtazapine is an antagonist of central α2-auto and hetero-adrenoceptors which causes an increase in both noradrenaline and serotonin release. The effect of released serotonin is exerted specifically via 5-HT1 (hydroxytryptamine1) type receptors, because 5-HT2 and 5-HT3 type receptors are specifically blocked by mirtazapine. Mirtazapine is accordingly a noradrenergic and specific serotonergic antidepressant.

Approved indications

— Treatment of major depression including relapse prevention.

Dosing overview

Treatment should begin with 15 mg daily. The dosage generally needs to be increased to obtain an optimal clinical response. The effective daily dose is usually between 30 and 45 mg, but responses have been observed at 60 mg per day. Mirtazapine has a half-life of 20 to 40 hours and therefore mirtazapine is suitable for once-a-day administration. It should be taken preferably as a single night-time dose before going to bed. Mirtazapine begins to exert its effect in general after 1-2 weeks of treatment. Treatment with an adequate dose should result in a positive response within 2 to 4 weeks.

Key safety warnings

The risk of suicidality (suicidal ideation and suicidal behaviours) is inherent in depression and may persist until significant remission occurs. This risk must be considered in all depressed patients. Patients with depression may experience worsening of their depressive symptoms and/or the emergence of suicidal ideation and/or behaviours whether or not they are taking antidepressant medication, and this risk may persist until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored for clinical worsening and suicidality, especially at the beginning of a course of treatment, or at the time of dose changes, either increases or decreases. Bone marrow depression, usually presenting as granulocytopenia or agranulocytosis has been reported during treatment with mirtazapine. The symptoms mostly appear after 2 to 6 weeks of treatment. However, in very rare cases agranulocytosis can be fatal. One should therefore be alert for symptoms like fever, sore throat, stomatitis or other signs of infections. If such symptoms occur the treatment should be stopped, and blood counts taken. Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), 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. The effect of mirtazapine on QTc interval was assessed in a randomised, placebo and moxifloxacin controlled clinical trial involving 54 healthy volunteers using exposure response analysis. This trial revealed that both 45 mg (therapeutic) and 75 mg (supratherapeutic) doses of mirtazapine did not affect the QTc interval to a clinically meaningful extent. During the post-marketing use of mirtazapine, cases of QT prolongation, Torsades de Pointes, ventricular tachycardia, and sudden death, have been reported. Caution should be exercised when mirtazapine is prescribed in patients with known cardiovascular disease or family history of QT prolongation, and in concomitant use with other medicinal products thought to prolong the QTc interval.

Contraindications

Contraindications include hypersensitivity to mirtazapine or to any of the excipients and monoamine oxidase (MAO) inhibitors as concomitant therapy. It is recommended that mirtazapine not be used in combination with MAO inhibitors, or within 14 days of initiating or discontinuing therapy with a MAO inhibitor. AXIT should not be used in children and adolescents under the age of 18 years.

PBS listing

The 15 mg tablet has 2 PBS items listed with a restriction type, at an ex-manufacturer price of A$2.73.

Regulatory history

AXIT 15 mg and 30 mg tablets were first listed on the Australian Register of Therapeutic Goods on 25 September 2003. AXIT 45 mg tablets were first listed on 6 December 2010.