Information on level of drugs into breastmilk
Wendy Jones in Breastfeeding and Medication, 2013
Mizolastine has a weak potential to prolong QT intervals and should not be used in patients with significant cardiac or hepatic disease, with hypokalaemia or other electrolyte imbalance, or with known or suspected QT prolongation. It is a non-sedating anti-histamine with a long duration of action. It is licensed for use over the age of 12 years but there is no data on transfer into breastmilk. The BNF states that significant amounts of some anti-histamines are present in breastmilk – although not known to be harmful, manufacturers advise avoiding use in mothers who are breastfeeding. Avoid if possible especially if the baby has concurrent cardiac problems. No data on levels transferring so use of other non-sedating antihistamines preferable. Use loratadine unless choice is essential. Chlorpheniramine
Pharmacokinetic-Pharmacodynamic Correlations of Antihistamines
Hartmut Derendorf, Günther Hochhaus in Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
Chlorpheniramine was investigated in 11 children with severe perennial allergic rhinitis56 and in 8 healthy elderly female subjects57 after a single oral dose of 0.12 mg/kg. In children, the symptom and sign scores were significantly suppressed from 1 to 30 h after intake. During that time period the serum concentration decreased from 21.1 to 2.3 ng/ml. The greatest wheal and flare diameter was significantly inhibited from 6 to 24 h after intake, during which period the serum concentration fell from 10.0 to 4.1 ng/ml. Furthermore, the serum chlorpheniramine concentrations at each observation time were inversely correlated with the symptom and sign scores (r = 0.75). In elderly female subjects, peak serum concentrations were reached within 3 h after intake, whereas the histamine-induced wheal was maximally suppressed by 36 to 37% after 5 to 6 h. The flare inhibition was maximal (43 to 46%) at 2 to 6 h after intake. A significant inhibition of the wheal and flare area started in the first hour and lasted 10 to 12 h.
Substrates of Human CYP2D6
Shufeng Zhou in Cytochrome P450 2D6, 2018
Chlorpheniramine, a propylamine H1 receptor antagonist available as an over-the-counter drug, is indicated for use in the common cold and for symptomatic treatment of allergies. Chlorpheniramine has a chiral carbon and is usually given as a racemic mixture, and it demonstrates stereoselectivity in its disposition (Yasuda et al. 2002) and pharmacological response (Tran et al. 1978). The S-enantiomer is approximately 100 times more potent than the R-enantiomer with regard to the antihistamine activity (Tran et al. 1978). The metabolism of chlorpheniramine has been extensively studies in animals (Cashman et al. 1992a; Kammerer and Lampe 1987; Nomura et al. 1997; Peets et al. 1972), and it has been found that chlorpheniramine undergoes extensive N-demethylation. Rat CYP2B1 and 2C11 are involved in its N-demethylation (Nomura et al. 1997). Chlorpheniramine can also be converted to its N-oxide by FMO from hog liver (Cashman et al. 1992a). In humans, chlorpheniramine is N-demethylated by CYP2D6 (Figure 3.74). For S-chlorpheniramine, administration of quinidine, an inhibitor of CYP2D6, results in an increase in Cmax, a reduction in oral clearance, and a prolongation of elimination half-life. Administration of quinidine decreased the oral clearance of R-chlorpheniramine. Stereoselective elimination of chlorpheniramine occurs in humans, with the most pharmacologically active S-enantiomer cleared more slowly than the R-enantiomer. In addition, a difference in receptor occupancy is observed between individuals who are CYP2D6 PMs or EMs (Yasuda et al. 1995).
Pediatric drug safety signal detection of non-chemotherapy drug-induced neutropenia and agranulocytosis using electronic healthcare records
Published in Expert Opinion on Drug Safety, 2019
Ran Wei, Lu-Lu Jia, Yun-Cui Yu, Xiao-Lu Nie, Zi-Yang Song, Duan-Fang Fan, Yue-Feng Xie, Xiao-Xia Peng, Zhi-Gang Zhao, Xiao-Ling Wang
The associations of chlorpheniramine with neutropenia and agranulocytosis can be considered as potential new signals in children. Chlorpheniramine is a first-generation antihistamine used to relieve histamine-mediated symptoms in a variety of allergies and cold conditions. To the best of our knowledge, these associations had not been mentioned in the SPCs, and the association of chlorpheniramine with agranulocytosis has been previously reported only in two adults [18,19]. Despite being marketed for years, little is known about its safety in the pediatric population because it has not been investigated adequately in children. Although there is no evidence of such association in children, a recent study using spontaneous reports retrieved from VigiBase demonstrated that dexchlorpheniramine is more likely to induce agranulocytosis in children (0−16 years old) than any other drugs [20].
Association of H1-antihistamines with torsade de pointes: a pharmacovigilance study of the food and drug administration adverse event reporting system
Published in Expert Opinion on Drug Safety, 2021
Zahid Ali, Mohammad Ismail, Fahadullah Khan, Hira Sajid
There also exist mixed reports in the literature regarding the association of loratadine with QTIP and TdP, one study reported the possibility that loratadine when dosed higher than the therapeutic one can cause 40% blockade of potassium channel thus causing QTIP and subsequent TdP [31]. One study reported the association of loratadine with TdP mainly due to drug-interactions (especially with amiodarone) and enzyme inhibitors [29]. In our study loratadine was associated with the highest number of QTIP cases, cardiac reactions, electrolyte abnormalities, drug–drug interactions, and overdose cases among new signals (Table 5). Literature also supports the association of chlorpheniramine with QTIP and TdP [32]. Chlorpheniramine can increase the duration of action potential and induce QT prolongation by blocking the hERG channel as evident from studies [33,34]. One study concluded that chlorpheniramine can induce cardiac toxicity when used in higher doses [10].
An international Delphi study on the burden of allergic rhinoconjunctivitis and urticaria and the role of bilastine among current treatment options
Published in Expert Review of Clinical Immunology, 2023
MK Church, GW Canonica, P Kuna, M Maurer, R Mösges, Z Novak, NG Papadopoulos, P Rodriguez del Rio
The fact that some, albeit few experts were undecided on this statement may reflect that most clinicians, who manage allergic rhinitis and urticaria, do not assess sleep stages in their patients and therefore cannot be certain that impairing effects of first-generation antihistamines are due to specific effects on sleep. On the other hand, there is still a widespread belief that sleep is aided by adding a sedating first-generation H1-antihistamine, as hydroxyzine, at night, although this is not supported by available data [47]. Moreover, with a terminal half-life of 20–25 h [48], hydroxyzine has hangover effects into the next day, with a negative impact on overall performance [47]. Similarly, the first-generation antihistamine chlorpheniramine has shown to cause a significant worsening of next day cognitive functioning and psychomotor performance, whereas a single nocturnal dose of fexofenadine has advantages over chlorpheniramine, demonstrating to be free of disruption of nighttime sleep and detrimental effects on cognitive performance the next day [49]. Further information on the effects of antihistamines on sleep and sensory-motor performance may be a good target for further analysis.
Related Knowledge Centers
- Allergic Rhinitis
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- Antihistamine
- Oral Administration
- H1 Antagonist
- Generic Drug
- Over-The-Counter Drug