L03AX14 - Histamine Dihydrochloride |
Propably not porphyrinogenic |
PNP |
Rationale
Histamine dihydrochloride has no pharmacodynamic or pharmacokinetic properties of relevance in acute porphyria. The effect of co-administered Il-2 is induction of cellular immunity against leukemic cells and liberation of pro-inflammatory cytokines, which damp the production of drug-metabolizing Cyp enzymes via negative modulation of nuclear transcription factors. Gastrointestinal side effects and anorexia interfering with caloric intake, and stress resulting from pain and insomnia are potentially porphyrogenic effects and are to be counteracted.
Therapeutic characteristics
Histamine dihydrochloride is co-administered with interleukin 2 (IL-2, aldesleukin) in acute myeloid leukaemia (AML) in first remission. Histamine hydrochloride is given subcutaneously. Interleukin-2 is a cytokine normally produced by activated T-lymphocytes. It activates cellular immunity as well as the proinflammatory cytokines IFN gamma, IL-1 and TNFs. The liberated proinflammatory cytokines modulate the expression of the nuclear transcription factors PXR, CAR, HNF-4 and NF-kB, in a way to damp clinically significant the expression of hepatic drug-metabolizing Cyp enzymes.
Common adverse reactions that may be confused with an acute porphyric attack are nausea, vomiting, upper abdominal pain, constipation, tachycardia, insomnia, depression, arthalgia, myalgia, dorsal pain and paraesthesia.
Metabolism and pharmacokinetics
Histamine is rapidly metabolized in liver, kidneys and other tissues by methylation and oxidation catalyzed by histamine-N-metyltransferase and diamine oxidase, respectively.
References
- Scientific articles
- Morgan ET, Goralski KB, et al. Regulation of drug-metabolizing enzymes and transporters in infection, inflammation, and cancer. Drug Metab Dispos. 2008 Feb;36(2):205-16. PMID 18218849. #4606
- Drug reference publications
- Sweetman SC, editor. Martindale: The complete drug reference. Histamine hydrochloride. Pharmaceutical Press 2009. #2247
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Ceplene. #2246
Similar drugs
© NAPOS 2024