The most common adverse reactions reported with Zanosar are gastrointestinal and renal disorders. The former are not life threatening but can be disturbing for the patient and may result in treatment discontinuation if very severe; the latter are indolent but potentially serious.
The frequency and intensity of nausea and vomiting has decreased over time, due to the utilization of efficacious antiemetic drugs. Renal toxicity can be avoided or reduced with careful assessment of renal function before and during treatment, patient hydration during streptozocin administration, and dose adjustment in case of renal function impairment.
Streptozocin has the potential to cause hyperglycaemia due to its mechanism of action; however, glucose intolerance or diabetes have been rarely reported in clinical practice. Myelotoxicity is usually mild and transient. Hepatic toxicity has been described, but not reported as a major issue during treatment.
Tabulated list of adverse reactions (from published data and post-marketing experience): Adverse reactions are listed below by MedDRA system organ class and frequency using the following convention: very common (≥1/10), common (≥ 1/100 to < 1/10), uncommon (≥1/1,000 to < 1/100) and not known (cannot be estimated from the available data).
MedDRA system organ class Very common adverse reactions Common adverse reactions Frequency not known Blood and lymphatic system disorders Decreased haematocrit, leukocytes and platelet counts Metabolism and nutrition disorders glucose intolerance Nervous system disorders Confusion, lethargy, depression Gastrointestinaldisorders Severe nausea and vomiting, Diarrhoea Nephrogenic diabetes insipidus Hepatobiliary disorders Elevated liver enzymes (SGOT and LDH) Hepatotoxicity Hypoalbuminemia Renal and urinary disorders Renal toxicity – proteinuria, proximal tubular injury, phosphaturia, acute renal failure Urinary disorders General disorders and administration site conditions Fever, Injection site reactions Gastrointestinal disorders: Patients treated with Zanosar have experienced nausea and vomiting.
In the earliest studies, up to 80-90% of patients reported nausea and vomiting, while in the most recent ones, this percentage ranges from 23 to 37%. In the earliest studies, severe nausea and vomiting was reported in 20 to 41% of patients.
6% of patients. Severe nausea and vomiting occasionally required discontinuation of drug therapy. Some patients experienced diarrhoea.
Renal and urinary disorders:
Literature data suggest that renal and urinary disorders are frequent. Renal toxicity is dose-related and cumulative in most cases and may be severe or fatal. However, an accurate incidence cannot be provided in the absence of recent prospective studies, using comprehensive toxicity reporting.
4).
Hepatobiliary disorders:
Serum aminotransferase elevations can occur in up to two-thirds of patients treated with streptozocin, but the abnormalities are generally mild, transient and not associated with symptoms or jaundice. 4).
Blood and lymphatic system disorders:
Acute haematological toxicity is rare, consisting most often of mild decreases in haematocrit values, leukocytes and platelets counts. However, fatal haematological toxicity with substantial reductions in leukocyte and platelet count has been observed.
Haematological toxicity may increase the sensitivity to infections. Rare cases of late haematological toxicity (myelodysplatic syndrome or acute myeloid leukemia) have been reported in patients previously treated by a streptozocin-based chemotherapy, who received subsequent peptide receptor radionuclide therapy.
1): Mild to moderate glucose intolerance has been noted in patients treated with Zanosar. These have generally been reversible. Due to the mechanism of action of streptozocin, diabetes cannot be excluded.
General disorders and administration site conditions:
Severe tissue necrosis has been described following extravasation. Burning sensation, extending from injection site to the arm has been reported in some patients following bolus administration. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.