Antihistamines are drugs which treat allergic rhinitis and other allergies. The two largest classes of antihistamines are H 1 -antihistamines and H 2 -antihistamines. H 1 -antihistamines work by binding to histamine H 1 receptors in mast cells , smooth muscle , and endothelium in the body as well as in the tuberomammillary nucleus in the brain. Antihistamines that target the histamine H 1 -receptor are used to treat allergic reactions in the nose e.

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We'd like to understand how you use our websites in order to improve them. Register your interest. Worldwide drug shortages are a recent and growing concern which involves all drug classes, including antineoplastic [ 1 ]. Successive shortages disrupt and disorganize the activity of oncology practitioners who must find adaptive solutions [ 2 ]. Drug shortage can also impact the management of patients with cancer, with potential consequences in term of overall survival [ 3 ]. However and interestingly, successive drug shortages have refocused oncology specialists on evidence-based medicine EBM [ 4 ].

For example, folate shortage has pushed oncology practitioners to experiment a standardized low dose protocol, and first results appear to be consistent with a similar efficacy [ 5 ]. Recent successive parenteral ranitidine shortage the only parenteral antihistaminergic H2 antiH2 on the French market has concerned oncology practitioners. Parenteral ranitidine is used as a premedication of hypersensitivity reaction HSR to paclitaxel [ 6 ].

Beyond adaptive propositions and in the light of literature the clinical efficacy of antiH2 medication for prevention of paclitaxel HSR should be questioned. Clinical observations have linked this HSR with those observed with radiocontrast Media RCM , which appears to be, at least in part, histaminergic [ 7 ]. Trial investigators and the National Cancer Institute have transposed premedication for RCM for clinical trials with paclitaxel association of a corticoid, antiH1, and antiH2.

Histaminergic receptors are present ubiquitously and divided according to subtypes. While H1 receptors are preferentially involved in bronchoconstriction and edema mechanisms, H2 receptors are mostly involved in gastric acid secretion. They are also involved in bronchodilation and possibly in hypotension phenomenon. Recent in vivo data based on a gene knockout approach suggest that both H1 and H2 take part in anaphylaxis [ 8 ].

A clinical study shows in 12 healthy or mildly asthmatic subjects that minimal plasmatic histamine concentration to obtain headache or flush was significantly higher only with combination of antiH1 and antiH2 and no with antiH1 or antiH2 alone. However, antiH2 also failed to influence histamine level required to elicit tachycardia whereas antiH1 or combination did it [ 9 ]. Furthermore, a controlled clinical study demonstrated the benefit of both antiH1 and antiH2 in prevention of HSR mediated by RCM compared to corticoid or antiH1 or placebo.

However, no group received corticoid and antiH1 in the design study [ 10 ]. On the other hand, in vitro data indicate that H2 agonism appears to induce paradoxical effect like bronchodilation and inhibition of mast cell and leukocyte secretions [ 11 ]. Several in vivo studies show that antiH2 are not effective for prevention on HSR [ 9 — 12 ]. Greenberg et al. Based on this data, Boehm and Maksymiuk have proposed for the prevention of HSR induced by paclitaxel the combination of a corticoid, an antiH1 and ephedrine but they do not recommend the use of an antiH2 [ 7 ].

In clinical practice, other studies have shown that antiH2-related side effects like hypotension and bradycardia pro arrhythmogenic with coronary ischemia risk [ 14 ]. Along with this, some cases report anaphylactic reaction with antiH2, especially ranitidine [ 15 , 16 ], and a retrospective observational Japanese study reports increasing risk of hand-foot syndrome and facial erythema in breast cancer patients receiving docetaxel and antiH2 as premedication [ 17 ].

Moreover, Berger et al. Finally, a systematic review from the Cochrane database on using antiH2 for urticaria underlines the lack of data and the large risk of bias of few small size and old studies [ 20 ]. In the light of these elements, efficacy of antiH2 for prevention of HSR induced by paclitaxel still appears to be controversial.

We propose an implementation of an institutional randomized clinical trial to compare a classical prevention protocol in accordance with SPR versus a prevention protocol without antiH2. The aim of this study would be to evaluate the non-superiority of the impact of HSR or to estimate the incidence of rescue medication usage during paclitaxel infusion in patients in the study group. Observations and knowledge from this study should be useful for oncology practitioners to better protect patients from HSR induced by paclitaxel.

N Engl J Med 8 — N Engl J Med 25 — N Engl J Med 26 — J Oncol Pharm Pract 22 3 — Shank BR, Seung AH, Kinsman K, Newman MJ, Donehover RC, Burton B Effect of the leucovorin shortage: pilot study investigating cost, efficacy, and toxicity comparison of low fixed-dose versus body surface area-adjusted leucovorin dosing in patients with resectable colon or metastatic colorectal cancer.

J Oncol Pharm Pract. Accessed 26 February J Natl Cancer Inst 88 7 — Allergy 68 10 — J Allergy Clin Immunol 69 3 — Ring J, Rothenberger KH, Clauss W Prevention of anaphylactoid reactions after radiographic contrast media infusion by combined histamine H1- and H2-receptor antagonists: results of a prospective controlled trial.

Int Arch Allergy Appl Immunol 78 1 :9— Schorderet M Antihistaminiques et anti-allergiques. Geneve, pp — J Allergy Clin Immunol 68 5 — Adverse experience with cimetidine and safety of beta-adrenergic antagonists. Arch Intern Med 12 — Ann Fr Anesth Reanim 30 3 — Lancet Immunopharmacol Immunotoxicol 31 3 — Breast Cancer Res Treat 2 — Support Care Cancer 20 9 — Support Care Cancer 23 7 — Google Scholar. Download references.

Correspondence to Florian Slimano. Reprints and Permissions. Slimano, F. Is antihistaminergic H2 really useful in prevention of hypersensitivity induced by paclitaxel?. Support Care Cancer 24, — Download citation. Received : 06 June Accepted : 28 July Published : 01 August Issue Date : November Search SpringerLink Search.

Download PDF. References 1. Geneve, pp — You can also search for this author in PubMed Google Scholar. View author publications. Ethics declarations Funding None. Conflict of interest The authors declare that they have no conflict of interest.

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Is antihistaminergic H2 really useful in prevention of hypersensitivity induced by paclitaxel?

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