Carbamyl Hydroxamate
Carbamyl Hydroxamate Uses, Dosage, Side Effects, Food Interaction and all others data.
Carbamyl Hydroxamate is converted to a free radical nitroxide (NO) in vivo, and transported by diffusion into cells where it quenches the tyrosyl free radical at the active site of the M2 protein subunit of ribonucleotide reductase, inactivating the enzyme. The entire replicase complex, including ribonucleotide reductase, is inactivated and DNA synthesis is selectively inhibited, producing cell death in S phase and synchronization of the fraction of cells that survive. Repair of DNA damaged by chemicals or irradiation is also inhibited by hydroxyurea, offering potential synergy between hydroxyurea and radiation or alkylating agents. Carbamyl Hydroxamate also increases the level of fetal hemoglobin, leading to a reduction in the incidence of vasoocclusive crises in sickle cell anemia. Levels of fetal hemoglobin increase in response to activation of soluble guanylyl cyclase (sGC) by hydroxyurea-derived NO.
Carbamyl Hydroxamate has dose-dependent synergistic activity with cisplatin in vitro. In vivo Carbamyl Hydroxamate showed activity in combination with cisplatin against the LX-1 and CALU-6 human lung xenografts, but minimal activity was seen with the NCI-H460 or NCI-H520 xenografts. Carbamyl Hydroxamate was synergistic with cisplatin in the Lewis lung murine xenograft. Sequential exposure to Carbamyl Hydroxamate 4 hours before cisplatin produced the greatest interaction.
| Trade Name | Carbamyl Hydroxamate |
| Availability | Prescription only |
| Generic | Hydroxyurea |
| Hydroxyurea Other Names | Carbamohydroxamic acid, Carbamohydroximic acid, Carbamoyl oxime, Carbamyl hydroxamate, Hidroxicarbamida, Hydrea, Hydroxycarbamid, Hydroxycarbamide, Hydroxycarbamidum, Hydroxyharnstoff, Hydroxyurea, N-Carbamoylhydroxylamine, N-Hydroxyurea, Oxyurea |
| Related Drugs | methotrexate, Keytruda, pembrolizumab, vitamin e, cyclophosphamide, imatinib, Gleevec, Sprycel, dostarlimab, Hydrea |
| Type | |
| Formula | CH4N2O2 |
| Weight | Average: 76.0547 Monoisotopic: 76.027277382 |
| Groups | Approved |
| Therapeutic Class | Cytotoxic Chemotherapy |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Carbamyl Hydroxamate is used for the treatment of resistant chronic myeloid leukemia, locally advanced squamous cell carcinomas of the head and neck (excluding the lip) in combination with chemoradiation.
Carbamyl Hydroxamate is also used to associated treatment for these conditions: Essential Thrombocythemia (ET), Head and Neck Carcinoma, Hypereosinophilic Syndromes, Melanomas, Meningiomas, Ovarian Cancer Metastatic, Polycythemia Vera (PV), Sickle Cell Anemia, Chronic, refractory Myeloid Leukemia, Inoperable Ovarian cancer
How Carbamyl Hydroxamate works
Carbamyl Hydroxamate is converted to a free radical nitroxide (NO) in vivo, and transported by diffusion into cells where it quenches the tyrosyl free radical at the active site of the M2 protein subunit of ribonucleotide reductase, inactivating the enzyme. The entire replicase complex, including ribonucleotide reductase, is inactivated and DNA synthesis is selectively inhibited, producing cell death in S phase and synchronization of the fraction of cells that survive. Repair of DNA damaged by chemicals or irradiation is also inhibited by hydroxyurea, offering potential synergy between hydroxyurea and radiation or alkylating agents. Carbamyl Hydroxamate also increases the level of fetal hemoglobin, leading to a reduction in the incidence of vasoocclusive crises in sickle cell anemia. Levels of fetal hemoglobin increase in response to activation of soluble guanylyl cyclase (sGC) by hydroxyurea-derived NO.
Dosage
Carbamyl Hydroxamate dosage
Malignancies Chronic myeloid leukaemia: 20-30 mg/kg/day.
Solid tumours: 80 mg/kg every third day. With radiotherapy, start treatment 7 days before initiation of radiotherapy.
Sickle-cell disease: Initial: 15 mg/kg/day. Max: 35 mg/kg/ day. Adjust based on response and blood counts.
Essential thrombocythemia: 15 mg/kg/day. Adjust based on platelet counts.
Side Effects
Gl disturbances, Nausea, Vomiting, Constipation, Diarrhea, Hyperuricemia, Renal failure, Rash, Hyperpigmentation. Pulmonary oedema, dermatological reactions, headache, dizziness. Disorientation, drowsiness, hallucinations, convulsions, alopecia.
Toxicity
Oral, mouse: LD50 = 7330 mg/kg; Oral, rat: LD50 = 5760 mg/kg Teratogenicity: Teratogenic effects have occurred in experimental animals.Carbamyl Hydroxamate use during a small number of human pregnancies has been reported. Adverse effects have not been observed in any of the exposed newborns. Reproductive Effects: Adverse reproductive effects have occurred in experimental animals. Mutagenicity: Mutagenic effects have occurred in experimental animals.Mutagenic effects have occurred in humans.
Precaution
Regular monitoring of uric acid concentrations, blood counts, renal and hepatic function is recommended. Prior irradiation therapy. Elderly. Avoid use of live vaccines.
Interaction
Impairs immune response to vaccines; possible infection with live vaccines, zidovudine, zalcitabine. May alter action of oral anticoagulants and phenytoin.
Food Interaction
- Drink plenty of fluids.
- Take with or without food.
Carbamyl Hydroxamate Drug Interaction
Unknown: aspirin, aspirin, aspirin, aspirin, apixaban, apixaban, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, furosemide, furosemide, clopidogrel, clopidogrel, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol
Carbamyl Hydroxamate Disease Interaction
Major: myelosuppression, renal dysfunctionModerate: hepatic dysfunction, seizure disordersMinor: neurologic disorders
Elimination Route
Well absorbed from the gastrointestinal tract.
Half Life
3-4 hours
Elimination Route
Renal excretion is a pathway of elimination.
Pregnancy & Breastfeeding use
Pregnancy category D. There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Lactation: Excreted in breast milk, do not nurse
Contraindication
Severe bone-marrow suppression, severe anaemia, WBC <3000/mm3 or platelet count <100,000/mm3. Pregnancy and lactation. Hypersensitivity.
Innovators Monograph
You find simplified version here Carbamyl Hydroxamate
Carbamyl Hydroxamate contains Hydroxyurea see full prescribing information from innovator Carbamyl Hydroxamate Monograph, Carbamyl Hydroxamate MSDS, Carbamyl Hydroxamate FDA label
