CAPECITABINE-DRLA

What it is

Capecitabine-DRLA is supplied as biconvex oblong film-coated tablets for oral administration, available in 150 mg and 500 mg strengths.

Approved indications

— Adjuvant treatment of patients with Dukes' stage C and high-risk stage B colon cancer, either as monotherapy or in combination with oxaliplatin. — Treatment of patients with advanced or metastatic colorectal cancer. — First-line treatment of patients with advanced oesophagogastric cancer in combination with a platinum-based regimen. — Treatment of patients with locally advanced or metastatic breast cancer after failure of taxanes and an anthracycline containing chemotherapy regimen unless therapy with these and other standard agents are clinically contraindicated. — Treatment of patients with locally advanced or metastatic breast cancer after failure of prior anthracycline containing chemotherapy, in combination with docetaxel.

Dosing overview

For monotherapy in colon, colorectal and breast cancer, the recommended starting dose is 1250 mg/m² administered twice daily for 2 weeks followed by a 7 day rest period, given as 3 week cycles. In combination with docetaxel for breast cancer, the recommended starting dose is 1250 mg/m² administered twice daily for 2 weeks followed by a 7 day rest period, combined with docetaxel 75 mg/m² as a 1 hour intravenous infusion every 3 weeks. In combination with oxaliplatin with or without bevacizumab for colorectal cancer, the recommended starting dose is 1000 mg/m² twice daily for 2 weeks followed by a 7 day rest period. For adjuvant colon cancer in combination with oxaliplatin, the recommended starting dose is 1000 mg/m² twice daily for 2 weeks followed by a 7 day rest period. For oesophagogastric cancer in triplet combination with epirubicin and cisplatin or oxaliplatin, the recommended starting dose is 625 mg/m² twice daily as a continuous regimen. Capecitabine tablets should be swallowed with water within 30 minutes after the end of a meal. For metastatic disease, capecitabine is intended for long-term administration unless clinically inappropriate. In the adjuvant setting, treatment duration is recommended for 24 weeks.

Key safety warnings

Capecitabine can induce diarrhoea, which can sometimes be severe. In patients receiving capecitabine monotherapy, the median time to first occurrence of Grade 2 to 4 diarrhoea was 31 days, and median duration of Grade 3 or 4 diarrhoea was 4.5 days. Patients with severe diarrhoea should be carefully monitored and, if they become dehydrated, should be given fluid and electrolyte replacement. Capecitabine can induce hand-foot syndrome, a cutaneous toxicity. Persistent or severe hand-foot syndrome (Grade 2 and above) can lead to loss of fingerprints. For patients receiving capecitabine monotherapy in the metastatic setting, the median time to onset was 79 days (range from 11 to 360 days), with a severity range of Grades 1 to 3. The spectrum of cardiotoxicity observed with capecitabine is similar to that of other fluorinated pyrimidines. This includes myocardial infarction, angina, dysrhythmias, cardiac arrest, cardiac failure and electrocardiograph changes. These adverse reactions may be more common in patients with a prior history of coronary artery disease. Rarely, unexpected, severe toxicity such as stomatitis, diarrhoea, neutropenia and neurotoxicity associated with fluorouracil has been attributed to a deficiency of dihydropyrimidine dehydrogenase (DPD) activity. DPD-deficiency related toxicity usually occurs during the first cycle of treatment or after dose increase. Fatal outcome has been reported in some cases. Capecitabine can induce severe skin reactions such as Stevens-Johnson syndrome and Toxic Epidermal Necrosis. Capecitabine should be permanently discontinued in patients who experience a severe skin reaction possibly attributable to capecitabine treatment.

Contraindications

Capecitabine-DRLA tablets are contraindicated in patients who have a known hypersensitivity to capecitabine or to any of the excipients contained in the tablets; a history of severe and unexpected reactions to fluoropyrimidine therapy or with known hypersensitivity to fluorouracil; severe renal impairment (creatinine clearance below 30 mL/min); known dihydropyrimidine dehydrogenase (DPD) deficiency; or treatment with sorivudine or its chemically related analogues, such as brivudine.

Regulatory history

Capecitabine-DRLA 150 mg tablets were first registered on the Australian Register of Therapeutic Goods (ARTG 200935) on 24 June 2013, and Capecitabine-DRLA 500 mg tablets were first registered (ARTG 200933) on 24 June 2013.