Trastuzumab/hyaluronidase, sold under the brand name Herceptin SC among others, is a fixed-dose combination medication for the treatment of HER2-overexpressing breast cancer in adults. It is a combination of trastuzumab and hyaluronidase.The most common adverse reactions include fatigue, arthralgia, diarrhea, injection site reaction, upper respiratory tract infection, rash, myalgia, nausea, headache, edema, flushing, pyrexia, cough, and pain in extremity.Trastuzumab/hyaluronidase was approved for medical use in the European Union in August 2013. Trastuzumab/hyaluronidase was approved for medical use in the United States in February 2019. Medical uses
Trastuzumab/hyaluronidase is indicated for adjuvant treatment of adults with HER2 overexpressing node positive or node negative (ER/PR negative or with one high risk feature; and it is indicated in combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer. History
Trastuzumab/hyaluronidase (Herceptin SC) was approved for medical use in the European Union in August 2013.Trastuzumab/hyaluronidase (Herceptin Hylecta) was approved for medical use in the United States in February 2019.Approval of trastuzumab/hyaluronidase was based on two randomized trials, HannaH (NCT00950300) and SafeHER (NCT01566721). In HannaH, 596 participants with HER2-positive operable or locally advanced breast cancer, including inflammatory breast cancer, were randomized to receive 8 cycles of either trastuzumab/hyaluronidase or intravenous trastuzumab concurrently with chemotherapy, followed by surgery and continued therapy with either trastuzumab/hyaluronidase or intravenous trastuzumab, for an additional 10 cycles. HannaH demonstrated comparability between trastuzumab/hyaluronidase and intravenous trastuzumab based on co-primary endpoints of pathologic complete response and pharmacokinetics.
Fasting is a risk factor, possibly because of depletion of liver glutathione reserves. The concomitant use of the CYP2E1 inducer isoniazid increases the risk of hepatotoxicity, though whether 2E1 induction is related to the hepatotoxicity in this case is unclear. Concomitant use of other drugs that induce CYP enzymes, such as antiepileptics including carbamazepine, phenytoin, and barbiturates, have also been reported as risk factors. Pathophysiology
When taken in normal therapeutic doses, paracetamol has been shown to be safe. Following a therapeutic dose, it is mostly converted to nontoxic metabolites via Phase II metabolism by conjugation with sulfate and glucuronide, with a small portion being oxidized via the cytochrome P450 enzyme system. Cytochromes P450 2E1 and 3A4 convert approximately 5% of paracetamol to a highly reactive intermediary metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Under normal conditions, NAPQI is detoxified by conjugation with glutathione to form cysteine and mercapturic acid conjugates.In cases of paracetamol overdose, the sulfate and glucuronide pathways become saturated, and more paracetamol is shunted to the cytochrome P450 system to produce NAPQI. As a result, hepatocellular supplies of glutathione become depleted, as the demand for glutathione is higher than its regeneration. NAPQI therefore remains in its toxic form in the liver and reacts with cellular membrane molecules, resulting in widespread hepatocyte damage and death, leading to acute liver necrosis. In animal studies, the livers stores of glutathione must be depleted to less than 70% of normal levels before liver toxicity occurs. Diagnosis
A persons history of taking paracetamol is somewhat accurate for the diagnosis.