Adverse Reaction to Antihistamines More Common Than We Thought

Adverse reaction to Antihistamines more common than we thought

By Dr. Asem Mohamed Qatar – Pediatric Emergency Medicine Conference 2018 DISCLOSURE

I do not have any relevant financial relationship with commercial interest to disclose. Learning Objective

Identify the adverse reactions caused by antihistamines The objective • Identify the adverse reactions caused by antihistamines • The safest way to decrease side effects on our patients Contents Over view on Hyper sensitivity 01 Classification of antihistamines 02 1ST generation Adverse reactions 03 2nd generation Adverse reactions 04 Severe side effect Cases 05 Way for safety 06 over view on Hypersensitivity What is hypersensitivity ? The immune system is reacting against the body and damage it instead of protect it This could happened because of exposure to a trigger or allergens like : • certain food, pollen, Metals & medications • (IgE), part of the body's immune system, binding to an allergen and then to a receptor on mast cells or basophils where it triggers the release of inflammatory chemicals such as histamine (H1) over view on Hypersensitivity Hypersensitivity reactions

Mild hypersensitivity reactions Severe hypersensitivity reactions The allergy commonly affect one or Anaphylaxis which is a more of these organs serious allergic reactions that has • Skin and may cause eczema or rapid in onset and may affect the vital urticaria systems like respiratory system and • Sinuses and may cause sinusitis cardiovascular system & in severe • Air ways and may cause Asthma cases it may cause death. • Also affects eyes , ears & Nose And the recommended treatment is And the treatment is : Antihistamine. Or Corticosteroids.. epinephrine 2 Classification of antihistamines Old & new generation. Old & new generations Classification of antihistamines First-generation (non-selective) Second-generation (non-sedating) Oldest They are anti histamines, Newer drugs that are much more selective for non selective but are typically peripheral H1 receptors. This selectivity anticholinergic as well. Active significantly reduces the occurrence of adverse as α-adrenergic receptors and 5- drug reactions, such as sedation, while still HT receptors providing effective relief of allergic conditions Examples : Examples: • Chlorpheniramine (Histop) • Cetirizine (Zyrtec) • Diphenhydramine (Benadryl) • Desloratadine (Arius) • Fexofenadine (telfast) • Levocetirizine (Xyzal) • Loratadine (Claritin) 3 1st generation Adverse reactions . 1st generation Adverse reactions Common side effects … Adverse drug reactions first-generation. This is due to their relative lack of selectivity for the H1- receptor and their ability to cross the blood-brain barrier. The most common adverse effect is sedation; this "side-effect" is utilized in many OTC sleeping-aid preparations. Other common adverse effects in first-generation H1-antihistamines include dizziness, blurred vision, euphoria, anxiety Infrequent adverse effects include urinary retention, palpitations, hallucination and psychosis. st Chlorpheniramine… 1 generation side effects Another clinical trial evaluated the action of upon the central nervous system had induced cognitive changes, in contrast to chlorpheniramine In another study of 24 children between 7 and 14 years old , chlorpheniramine induces significant cognitive alterations versus placebo, In addition to the effects upon the central nervous system like .. CNS depression ,Disturbed coordination, Muscular weakness Restlessness CVS Affected also ( Tachycardia, palpitation ECG changes Arrhythmias (eg, extrasystole, heart block) Hypertension, Dysuria, Urinary retention Mucosal membrane Dryness of mouth, nose, and throat Visual disturbances, Blurred vision. Watemberg NA, Roth KS, Alehan FK, Epstein CE. Central anticholinergic syndrome on therapeutic doses of cyproheptadine. Pediatrics. 1999;103:158-160 Garza MB, Osterhoudt KC, Rutstein R. Central anticholinergic 0syndrome from orphendarine in a 3-year-old. Ped Emerg Care. 02000;16:97-98 1st generation side effects Diphenhydramine Diphenhydramine and hydroxyzine, were objectively assessed for effects upon cognitive processes - P300 potential latency - and drowsiness using a visual analog scale (VAS),. The study concluded that both drugs induce objective dysfunction at central nervous system level, and drowsiness plus Sedation, Confusion, Disorientation, Blurred vision, Hallucinations, Dystonia's, Catatonic states Tachycardia, Bradycardia , Obstructive jaundice , Photosensitivity Simons FE, Fraser TG, Reggin JD, Roberts JR, Simons KJ. Adverse central nervous system effects of older antihistamines in children. Pediatr Allergy Immunol. 1996;7:22-27 4 2nd generation Adverse reactions . Not the safest 2nd generation side effects Although previous studies have suggested that new generation antihistamines have few adverse reactions in children, there are some reactions worth noting ex: • Somnolence • altered behaviour • skin eruptions • headache Moreover, there is a possible relation between convulsions and (des)loratadine. according to Tjalling W. de Vries, MD, from the Department of Pediatrics, Medical Centre Leeuwarden, The Netherlands, and Florence van Hunsel, PharmD, PhD, from The Netherlands Pharmacovigilance Centre Lareb, Den Bosch 2nd generation Adverse reactions Clinical reports The investigators analyzed Anti histamines ADRs in children reported in 1991-2014 to The Netherlands Pharmacovigilance Centre Lareb. on total 228 patients. 16% desloratadine 15% loratadine 13% ketotifen The most frequently reported ADRs were skin eruptions, headache, and somnolence. Other commonly reported ADRs were aggression, agitation, and hyperactivity.

Somnolence was reported in Behavioral reactions included 12 patients who received 9 reports of aggression linked to use cetirizine, levocetirizine, of ketotifen, desloratadine, cetirizine, desloratadine, astemizole, levocetirizine & cyproheptadine; and cyproheptadine, dimetindene, 5 reports of hyperactivity seen with fexofenadine, oxatomide, desloratadine, ketotifen, terfenadine, oxomemazine, or loratadine, or dementindene. dexchlorpheniramine. according to Tjalling W. de Vries, MD, from the Department of Pediatrics, Medical Centre Leeuwarden, The Netherlands, and Florence van Hunsel, PharmD, PhD, from The Netherlands Pharmacovigilance Centre Lareb, Den Bosch 6 Severe side effect Cases 5 serios cases Two Cases Severe side effect Cases

Malignant neuroleptic syndrome Atrioventricular reentry Malignant neuroleptic syndrome Atrioventricular reentry tachycardia in a 14- and death in a 4-year-old girl year-old boy after use of azithromycin for after use of alimemazine as a respiratory tract infection and fexofenadine for sedative, which was administered allergy after an 8-day latency period. at a much higher dose (2 mg/kg) than for allergy treatment (0.25 mg/kg) according to Tjalling W. de Vries, MD, from the Department of Pediatrics, Medical Centre Leeuwarden, The Netherlands, and Florence van Hunsel, PharmD, PhD, from The Netherlands Pharmacovigilance Centre Lareb, Den Bosch Convulsions Severe side effect Cases Convulsions in 3 children • an 11-year-old girl who took loratadine, as well as cromoglicic acid and salbutamol • a 2-year-old girl who had convulsions after taking loratadine, with a latency of 3 days after starting treatment • 16-year-old boy who experienced tonic-clonic seizures after administration of desloratadine for an allergy to grass pollen, with a latency of 8 days after treatment initiation

according to Tjalling W. de Vries, MD, from the Department of Pediatrics, Medical Centre Leeuwarden, The Netherlands, and Florence van Hunsel, PharmD, PhD, from The Netherlands Pharmacovigilance Centre Lareb, Den Bosch 7 Way for safety Small steps toward safety Small steps toward safety Way for safety Recommendation .. Our recommendations are to use of second-generation should be first-line therapy for the management of common allergic reactions children due to well toleration over a long period, and have fewer adverse effects on cognition.. Cetirizine has at least as quick an onset of action as chlorphenamine, and is our preferred choice of second- generation due the body of literature on safety and pharmacokinetics available on this drug.. J Investig Allergol Clin Immunol 2007; Vol. 17, Suppl. 2: 28-40 © 2007 Esmon Publicidad Thank you