APO-DULOXETINE

What it is

APO-DULOXETINE is an enteric-coated capsule formulation containing duloxetine hydrochloride, available in 30 mg and 60 mg strengths. Duloxetine is a selective serotonin and noradrenaline reuptake inhibitor that weakly inhibits dopamine uptake.

Approved indications APO-DULOXETINE is indicated for the treatment of:

— Major depressive disorder — Diabetic peripheral neuropathic pain — Generalised anxiety disorder

Dosing overview

For patients in whom initial tolerability may be a concern, a lower starting dose of 30 mg once daily for one week before increasing to 60 mg once daily should be considered. When discontinuing duloxetine after more than one week of therapy, the dose should be tapered by reducing it by half or administering on alternate days over a period of not less than two weeks to minimise the risk of discontinuation symptoms.

Key safety warnings

The risk of suicide is inherent in depression and may persist until significant remission occurs. Patients with depression may experience worsening of depressive symptoms and/or emergence of suicidal ideation and behaviours whether or not they are taking antidepressants, 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 treatment or at the time of dose changes. Duloxetine should ordinarily not be prescribed to patients with evidence of acute or chronic liver disease, as it may aggravate pre-existing liver disease and increases the risk of elevation of serum transaminase levels. Liver transaminase elevations resulted in discontinuation of 0.3% of duloxetine-treated patients, with the median time to detection approximately two months. Postmarketing reports have described cases of hepatitis with significantly elevated transaminase levels, cholestatic jaundice, and isolated cases of liver failure, including fatal cases. SSRIs and SNRIs, including duloxetine, may increase the risk of bleeding events, including gastrointestinal bleeding. Caution is advised in patients taking duloxetine with anticoagulants and/or medicinal products known to affect platelet function such as NSAIDs and aspirin, and in patients with known bleeding tendencies. Duloxetine is associated with an increase in blood pressure in some patients. In placebo-controlled clinical trials, treatment was 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. Withdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt. In clinical trials, adverse events following abrupt discontinuation occurred in approximately 45% of duloxetine-treated patients and 23% of placebo patients. The most commonly reported symptoms have included dizziness, nausea, headache, paraesthesia, fatigue, vomiting, irritability, nightmares, insomnia, diarrhoea, anxiety, hyperhidrosis, vertigo, somnolence and myalgia.

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 reversible MAOI (RIMA) such as 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, as serious reactions including potentially life-threatening serotonin syndrome have been reported. Duloxetine is contraindicated in patients with liver disease resulting in hepatic impairment. Duloxetine should not be used in combination with potent CYP1A2 inhibitors.

PBS listing

APO-DULOXETINE 60 mg capsule is listed on the PBS with 2 items, restriction type is restricted, and ex-manufacturer price is A$4.00. The 30 mg capsule is listed with 1 PBS item, restriction type is restricted, and ex-manufacturer price is A$3.86.

Regulatory history

APO-DULOXETINE was first registered on the ARTG on 30 November 2012 in both 30 mg and 60 mg strengths as enteric capsules in bottle form. In September 2024, blister pack formulations of both 30 mg and 60 mg strengths were registered on the ARTG.