Caxeta Warnings

Diarrhoea: Capecitabine can induce diarrhea, which can sometimes be severe. Patients with severe diarrhea should be carefully monitored and, if they become dehydrated, should be given fluid and electrolyte replacement. Standard anti-diarrhea treatments (e.g. loperamide) should be initiated, as medically appropriate, as early as possible. Dose reduction should be applied as necessary (see RECOMMENDED DOSE under Dosage & Administration).
Dehydration: Dehydration should be prevented or corrected at the onset. Patients with anorexia, asthenia, nausea, vomiting or diarrhea may rapidly become dehydrated.
Dehydration may cause acute renal failure, especially in patients with pre-existing compromised renal function or when capecitabine is given concomitantly with known nephrotoxic agents. Fatal outcome of renal failure has been reported in these situations (see ADVERSE REACTIONS).
If Grade 2 (or higher) dehydration occurs, capecitabine treatment should be immediately interrupted and the dehydration corrected. Treatment should not be restarted until the patient is rehydrated and any precipitating causes have been corrected or controlled. Dose modifications should be applied for the precipitating ADRs as necessary (see RECOMMENDED DOSE under Dosage & Administration).
Dihydropyrimidine dehydrogenase (DPD) deficiency: Rarely, unexpected, severe toxicity (e.g. stomatitis, diarrhea, mucosal inflammation, neutropenia and neurotoxicity) associated with 5-FU has been attributed to a deficiency of DPD activity, an enzyme involved in fluorouracil degradation.
Patients with certain homozygous or certain compound heterozygous mutations in the DPYD gene locus that cause complete or near complete absence of DPD activity, are at the highest risk for severe, life-threatening, or fatal adverse reactions caused by fluorouracil. These patients should not be treated with capecitabine. No dose has been proven safe for patients with complete absence of DPD activity (see CONTRAINDICATIONS).
Patients with certain heterozygous DPYD variants (e.g. DPYD*2A variant) that may cause partial DPD deficiency have been reported to have increased risk of severe toxicity when treated with capecitabine. For patients with partial DPD deficiency where the benefits of capecitabine are considered to outweigh the risks (taking into account the suitability of an alternative non-fluoropyrimidine chemotherapeutic regimen), these patients must be treated with extreme caution, initially with a substantial dose reduction and frequent subsequent monitoring and dose adjustment according to toxicity.
Testing for DPD deficiency should be considered based on the local availability and current guidelines.
In patients with unrecognised DPD deficiency treated with capecitabine, as well as patients who test negative for specific DPYD variations, life threatening toxicities manifesting as acute overdose may occur. In the event of grade 2-4 acute toxicity, treatment must be discontinued immediately. Permanent discontinuation should be considered based on clinical assessment of the onset, duration and severity of the observed toxicities (see OVERDOSE AND TREATMENT under Overdosage).