L01BB04 - Cladribine |
Propably not porphyrinogenic |
PNP |
Rationale
Insignificant hepatic exposure. Little is known about the metabolism of cladribine, but as there is no data supporting CYP-affinity or capacity for CYP-induction or inhibition, probably non-CYP metabolism. However, side effects such as nausea, vomiting and loss of appetite may be potentially porphyrinogenic through reduction in caloric intake.
Chemical description
Cladribine is a chlorinated purine nucleoside analogue (chemical name: 2-chloro-2-deoxy-adenosine).
Therapeutic characteristics
Cladribine is used to treat active hairy cell leukemia, and is being tested for use in multiple sclerosis. Administered as an infusion. Common adverse reactions of cladribine that can be confused with an acute porphyric attack are nausea, vomiting, obstipation or diarrhoes, abdominal pain, tachycardia and myalgia. Side effects such as nausea and vomiting may be potentially porphyrinogenic through reduction in caloric intake.
Hepatic exposure
Insignificant hepatic exposure. The recommended intravenous dose of cladribine is a single course of 0,1 mg/kg daily for 7 days by continuous infusion. Piro et al (1988) found that 0.05 to 0.2 mg/kg/daily via continuous infusion for 7 days resulted in daily drug levels of less than 10 nanomoles/liter during therapy, well below the 1 micromolar limit.
Metabolism and pharmakokinetics
Plasma concentration of cladribine declines multiexponentially with time; terminal half life 3-20 h. Steady state plasma concentration is about 5.7 ng/ml. Accumulates in cells deficient in deoxynucleotidas (lymphocytes, monocytes) and undergoes consecutive phosphorlylations to the active triphosphate nucleotid (CdATP). Limited information on metabolism and elimination. No observations of interactions with CYP-metabolized drugs. Not listed by Rendic as having CYP-affinity or capable of CYP-induction or inhibition.
IPNet drug reports
No.
References
- Scientific articles
- Rendic, S. Summery of information on human CYP enzymes: human P450 metabolism. Drug metabolism reviews 2002; 34(1&2), 83-448. #1025
- Piro LD, Carrera CJ, et al. 2-Chlorodeoxyadenosine: an effective new agent for the treatment of chronic lymphocytic leukemia. Blood 1988; 72(3):1069-73. PMID 2901280. #4569
- Drug reference publications
- McEvoy GK, editor. Cladribine. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (02.12.09). #3323
- Sweetman SC, editor. Martindale: The complete drug reference. Cladribine. Pharmaceutical Press 2009. #3326
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Leustatin. #3324
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