CldAdo

Uses

CldAdo is a purine antimetabolite used for the management of relapsing forms of Multiple Sclerosis (MS), used in patients who have not responded to or who were unable to tolerate alternative MS drugs.

For the treatment of active hairy cell leukemia (leukemic reticuloendotheliosis) as defined by clinically significant anemia, neutropenia, thrombocytopenia, or disease-related symptoms. Also used as an alternative agent for the treatment of chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin's lymphoma, and cutaneous T-cell lymphoma.

CldAdo is also used to associated treatment for these conditions: Chronic Lymphocytic Leukaemia (CLL), Cutaneous T-Cell Lymphoma (CTCL), Hairy Cell Leukemia (HCL), Non-Hodgkin's Lymphoma (NHL), Active confirmed by clinical features, confirmed by imaging features relapsing multiple sclerosis (MS)

How CldAdo works

CldAdo is structurally related to fludarabine and pentostatin but has a different mechanism of action. Although the exact mechanism of action has not been fully determined, evidence shows that cladribine is phosphorylated by deoxycytidine kinase to the nucleotidecladribine triphosphate (CdATP; 2-chloro-2′-deoxyadenosine 5′-triphosphate), which accumulates and is incorporated into DNA in cells such as lymphocytes that contain high levels of deoxycytidine kinase and low levels of deoxynucleotidase, resulting in DNA strand breakage and inhibition of DNA synthesis and repair. High levels of CdATP also appear to inhibit ribonucleotide reductase, which leads to an imbalance in triphosphorylated deoxynucleotide (dNTP) pools and subsequent DNA strand breaks, inhibition of DNA synthesis and repair, nicotinamide adenine dinucleotide (NAD) and ATP depletion, and cell death. Unlike other antimetabolite drugs, cladribine has cytotoxic effects on resting as well as proliferating lymphocytes. However, it does cause cells to accumulate at the G1/S phase junction, suggesting that cytotoxicity is associated with events critical to cell entry into S phase. It also binds purine nucleoside phosphorylase (PNP), however no relationship between this binding and a mechanism of action has been established.

Toxicity

Symptoms of overdose include irreversible neurologic toxicity (paraparesis/quadriparesis), acute nephrotoxicity, and severe bone marrow suppression resulting in neutropenia, anemia and thrombocytopenia.

Food Interaction

• Avoid echinacea. Echinacea should be used with caution, if at all, in patients receiving therapeutic immunosuppressants. Monitor for reduced efficacy of the immunosuppressant during concomitant use.

[Moderate] ADJUST DOSING INTERVAL: Oral cladribine may increase the bioavailability of other drugs, which may increase the risk or severity of adverse reactions.

CldAdo tablets may contain hydroxypropyl betadex, which could form a complex with the active ingredients of other drugs, especially agents with low solubility.

The clinical relevance of this interaction remains unknown.

MANAGEMENT: Administration of oral cladribine should be separated from any other oral drug by at least 3 hours.

CldAdo Drug Interaction

Moderate: enasidenib, enasidenibUnknown: lorazepam, lorazepam, sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprim, ubiquinone, ubiquinone, copper gluconate, copper gluconate, meperidine, meperidine, glycerin, glycerin, metoprolol, metoprolol, bioflavonoids, bioflavonoids, cholecalciferol, cholecalciferol

CldAdo Disease Interaction

Major: infections, myelosuppression, neurological disordersModerate: hepatic dysfunction, renal dysfunction

Volume of Distribution

• 4.5 ± 2.8 L/kg [patients with hematologic malignancies]
• 9 L/kg

Elimination Route

Oral bioavailability is 34 to 48%.

Half Life

5.4 hours

Clearance

• 978 +/- 422 mL/h/kg

Innovators Monograph

You find simplified version here CldAdo