DULOXETINE SANDOZ

What it is

Duloxetine is a medicine available as capsules containing enteric-coated pellets of duloxetine hydrochloride equivalent to 30 mg or 60 mg of duloxetine that are designed to prevent degradation of the drug in the acidic environment of the stomach.

Approved indications

— Major depressive disorder (MDD). — 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 it is generally recommended that the dose 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/or the emergence of suicidal ideation and behaviours whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. 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. Patients and caregivers should be alerted about the need to monitor for any worsening of their condition and/or the emergence of suicidal ideation/behaviour or thoughts of harming themselves and to seek medical advice immediately if these symptoms present. Duloxetine should ordinarily not be prescribed to patients with evidence of acute or chronic liver disease as it is possible that duloxetine may aggravate pre-existing liver disease. Duloxetine increases the risk of elevation of serum transaminase levels. Liver transaminases elevations resulted in the discontinuation of 0.3% of duloxetine-treated patients, with a median time to detection of the transaminase elevation of about two months. Isolated cases of liver failure, including fatal cases, have been reported, with a majority of these cases in patients with past or current risk factors for liver injury, including alcohol abuse, hepatitis or exposure to drugs with known adverse effects on the liver. Because it is possible that duloxetine and alcohol may interact to cause liver injury or that duloxetine may aggravate pre-existing liver disease, duloxetine should ordinarily not be prescribed to patients with substantial alcohol use or evidence of chronic liver disease. SSRIs and SNRIs, including duloxetine, may increase the risk of bleeding events, including gastrointestinal bleeding. Therefore, caution is advised in patients taking duloxetine concomitantly with anticoagulants and/or medicinal products known to affect platelet function (e.g. NSAIDs, aspirin) and in patients with known bleeding tendencies. 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. In patients with known hypertension and/or other cardiac disease, blood pressure monitoring is recommended as appropriate. Duloxetine should be used with caution in patients whose conditions could be compromised by an increased heart rate or by an increase in blood pressure. Orthostatic hypotension and syncope have been reported with therapeutic doses of duloxetine. Syncope and hypotension tend to occur within the first week of therapy but can occur at any time during duloxetine treatment, particularly after dose increases.

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 (RIMA), 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. Cases of serious reactions, such as potentially life threatening serotonin syndrome have been reported in patients receiving an SNRI in combination with MAOIs and RIMA, and in patients who have recently discontinued an SNRI and have been started on a MAOI. 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

No source document provides PBS listing information for this medicine.

Regulatory history

Duloxetine was first approved on 13 June 2013. The brand DULOXETINE AN (duloxetine hydrochloride 30 mg and 60 mg enteric capsules) was first listed on the ARTG on 1 July 2013.