DEPRETA

What it is

DEPRETA contains duloxetine (present as the hydrochloride) and comes in two strengths with enteric coated pellets equivalent to 30 mg or 60 mg of duloxetine. The 30 mg strength is an opaque blue/white hard gelatin capsule marked '157' on the body and 'A' on the cap with green ink, while the 60 mg strength is an opaque blue/opaque green hard gelatin capsule marked '158' on the body and 'A' on the cap with white ink. Duloxetine is a selective serotonin and noradrenaline reuptake inhibitor, and weakly inhibits dopamine uptake with no significant affinity for histaminergic, dopaminergic, cholinergic and adrenergic receptors.

Approved indications

DEPRETA is indicated for the treatment of: — Major depressive disorder (MDD) — Diabetic peripheral neuropathic pain (DPNP) — Generalised anxiety disorder (GAD)

Dosing overview

For patients in whom initial tolerability may be a concern, such as treatment-naïve patients or those with a history of adverse events with other medications, use of a lower starting dose such as 30 mg once daily for one week before increasing the dose to 60 mg once daily should be considered. A lower dose of 30 mg once daily should be used in patients with end stage renal disease (creatinine clearance < 30 mL/min). When discontinuing duloxetine after more than one week of therapy, the dose should generally be tapered to minimise the risk of discontinuation symptoms, with the dose reduced by half or administered on alternate days during a period of not less than two weeks.

Key safety warnings

The risk of suicide attempt is inherent in depression and may persist until significant remission occurs. Patients with depression may experience worsening of their depressive symptoms and emergence of suicidal ideation and behaviours whether or not they are taking antidepressant medications. 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. Duloxetine should ordinarily not be prescribed to patients with evidence of acute or chronic liver disease. Duloxetine increases the risk of elevation of serum transaminase levels, with elevations of alanine transaminase to more than three times the upper limit of normal occurring in 1.1% of duloxetine-treated patients and 0.2% of placebo treated patients. Postmarketing reports have described cases of hepatitis with abdominal pain, hepatomegaly and elevation of transaminase levels to more than twenty times the upper limit of normal with or without jaundice, cases of cholestatic jaundice with minimal elevation of transaminase levels, and isolated cases of liver failure, including fatal cases. Duloxetine is associated with an increase in blood pressure in some patients, with treatment associated with small increases in systolic blood pressure averaging 2 mm Hg and small increases in diastolic blood pressure averaging 0.5 mm Hg compared to placebo. Large, potentially clinically significant, elevations in blood pressure do not appear to be more common with duloxetine than with placebo. SSRIs and SNRIs, including duloxetine, may increase the risk of bleeding events, including gastrointestinal bleeding. Caution is advised in patients taking duloxetine concomitantly with anticoagulants and medicinal products known to affect platelet function such as NSAIDs and aspirin.

Contraindications

Duloxetine is contraindicated in patients with known hypersensitivity to duloxetine or to any of the excipients in the formulation. Duloxetine should not be used in combination with monoamine oxidase inhibitors (MAOI) or the reversible MAOI moclobemide, or within 14 days of discontinuing treatment with a MAOI. At least 5 days should be allowed after stopping duloxetine before starting a MAOI. Duloxetine is also contraindicated with potent CYP1A2 inhibitors. Duloxetine is contraindicated in patients with liver disease resulting in hepatic impairment.

Regulatory history

DEPRETA 60 mg and DEPRETA 30 mg were first listed on the Australian Register of Therapeutic Goods on 1 July 2013.