Atriance
Atriance Uses, Dosage, Side Effects, Food Interaction and all others data.
Atriance is an antineoplastic agent that is typically employed to treat acute T-cell lymphoblastic leukemia. Atriance is a purine nucleoside analog converted to its corresponding arabinosylguanine nucleotide triphosphate (araGTP), resulting in inhibition of DNA synthesis and cytotoxicity.
Atriance is a prodrug of the cytotoxic deoxyguanosine analogue 9-ß-D-arabinofuranosylguanine (ara-G). Atriance is demethylated by adenosine deaminase (ADA) to ara-G. Ara-G is then transported into cells, where it undergoes three phosphorylation steps, resulting in the formation of ara-G triphosphate (ara-GTP). In the first phosphorylation step, ara-G is converted to ara-G monophosphate (ara-GMP). Ara-GMP is then monophosphorylated by deoxyguanosine kinase and deoxycytidine kinase to ara-G diphosphate, and then subsequently to the active ara-G triphosphate (ara-GTP). Ara-GTP is the one that exerts the pharmacological effect. Pre-clinical studies have demonstrated that targeted T-cells possess marked sensitivity to the agent.
| Trade Name | Atriance |
| Availability | Prescription only |
| Generic | Nelarabine |
| Nelarabine Other Names | Nelarabina, Nelarabine, Nelzarabine |
| Related Drugs | prednisone, methotrexate, dexamethasone, doxorubicin, Revlimid, imatinib, Gleevec, Imbruvica, mercaptopurine, Sprycel |
| Type | infusion |
| Formula | C11H15N5O5 |
| Weight | Average: 297.2673 Monoisotopic: 297.107318615 |
| Protein binding | Nelarabine and ara-G are not substantially bound to human plasma proteins (<25%) in vitro, and binding is independent of nelarabine or ara-G concentrations up to 600 mM. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | Novartis Pharmaceuticals Uk Ltd, Glaxo Group Ltd |
| Available Country | United Kingdom, France, Italy, Netherlands, Portugal, Spain, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Atriance is a purine nucleoside analog and antineoplastic agent used for the treatment of with acute T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma with inadequate clinical response to prior chemotherapeutic treatments.
For the treatment of pediatric and adult patients with acute T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens.
Atriance is also used to associated treatment for these conditions: Lymphoblastic lymphoma (Precursor T-lymphoblastic lymphoma/leukemia) refractory, Refractory Acute Lymphoblastic Leukemia
How Atriance works
Once nelarabine is metabolized into ara-GTP, the metabolite accumulates in leukemic blasts and incorporates into DNA to exert its S phase-specific cytotoxic effects, leading to the induction of fragmentation and apoptosis. Ara-GTP competes with endogenous deoxyGTP (dGTP) for incorporation into DNA. Once ara-GTP is incorporated at the 3' end of DNA, further DNA elongation is inhibited, which signals apoptosis and leads to cellular destruction. Additional cytotoxic activities may exist, but these are not fully understood.
Toxicity
A single IV dose of 4,800 mg/m^2 was lethal in monkeys, and was associated with CNS signs including reduced/shallow respiration, reduced reflexes, and flaccid muscle tone. It is anticipated that overdosage would result in severe neurotoxicity (possibly including paralysis, coma), myelosuppression, and potentially death.
Food Interaction
No interactions found.Atriance Drug Interaction
Unknown: charcoal, charcoal, citalopram, citalopram, clotrimazole, clotrimazole, sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprim, ubiquinone, ubiquinone, prochlorperazine, prochlorperazine, copper gluconate, copper gluconate, metoprolol, metoprolol, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin
Atriance Disease Interaction
Major: neurotoxicity, vaccinationModerate: bone marrow depression, liver dysfunction, renal impairment, tumor lysis syndrome
Half Life
Atriance and ara-G are rapidly eliminated from plasma with a half-life of approximately 30 minutes and 3 hours.
Clearance
- 197 +/- 189 L/h/m2 [Adult patients with refractory leukemia or lymphoma receiving doses of 199 to 2,900 mg/m2]
- 259 +/- 409 L/h/m2 [Pediatric patients with refractory leukemia or lymphoma receiving doses of 104 to 2,900 mg/m2]
Elimination Route
Excretion: Atriance and ara-G are partially eliminated by the kidneys.
Innovators Monograph
You find simplified version here Atriance
