APO-DIMETHYL

What it is

APO-DIMETHYL contains dimethyl fumarate and is available as delayed release capsules in two strengths: 120 mg and 240 mg. The 120 mg capsules are white to off-white enteric coated mini tablets in size "1" hard gelatin capsules with a green cap and white body, while the 240 mg capsules contain enteric coated mini tablets in size "0" hard gelatin capsules with a green cap and green body.

Approved indications

— Reducing the frequency of relapses and delaying the progression of disability in patients with relapsing multiple sclerosis.

Dosing overview

The starting dose of APO-DIMETHYL is 120 mg twice a day orally, increasing after 7 days to the recommended dose of 240 mg twice a day orally. Temporary dose reduction to 120 mg twice a day may reduce flushing and gastrointestinal side effects, with the recommended dose of 240 mg twice a day resuming within 1 month. The capsule or its contents should not be crushed, divided or dissolved as the enteric coating of the microtablets prevents irritant effects on the gut. APO-DIMETHYL can be taken with or without food, although taking it with food may improve tolerability for patients experiencing gastrointestinal or flushing side effects.

Key safety warnings

While decreases in lymphocyte counts observed in patients treated with dimethyl fumarate in clinical trials were not associated with increased frequencies of infections, due to the risk of serious, possibly fatal infection, patients who develop lymphopenia as a result of treatment require close monitoring. In multiple sclerosis placebo-controlled trials, mean lymphocyte counts decreased by approximately 30% during the first year of treatment and then remained stable, with WBC counts less than 3.0 × 10⁹/L and lymphocyte counts less than 0.5 × 10⁹/L reported in 6 to 7% of subjects. Progressive multifocal leukoencephalopathy has occurred in the setting of lymphopenia in patients treated with APO-DIMETHYL, predominantly in the setting of prolonged moderate to severe lymphopenia. Cases of anaphylaxis have been reported following dimethyl fumarate administration, generally occurring after the first dose but potentially at any time during treatment, and may be serious and life-threatening. Serious cases of herpes zoster have occurred with dimethyl fumarate, including disseminated herpes zoster, herpes zoster ophthalmicus, herpes zoster meningoencephalitis and herpes zoster meningomyelitis, which may occur at any time during treatment. Serious gastrointestinal reactions, including perforation, ulceration, haemorrhage, and obstruction, some with fatal outcomes, have been reported in the post-marketing setting with the use of fumaric acid esters, including dimethyl fumarate, with the majority of these events occurring within 6 months of treatment initiation. Adverse events of proteinuria were reported at slightly higher frequencies in patients treated with dimethyl fumarate compared to those receiving placebo, although the significance of these clinical observations is not known.

Contraindications

APO-DIMETHYL is contraindicated in patients with known hypersensitivity to dimethyl fumarate or any excipients in this product.

Regulatory history

APO-DIMETHYL fumarate 120 mg and 240 mg enteric coated capsule formulations were first listed on the ARTG on 28 June 2022.