Erythromycin, clarithromycin, azithromycin.
Bacteriostatic not bacteriocidal, but doesn’t necessarily mean inferior.
Broad spectrum, including things that aren’t even bacterial! eg Bordetella pertussis, syphilis.
Diarrhoea and vomiting as main side effects, not an allergy as such. True allergy is virtually unheard of! Other important issues:
An abnormal finding on ECG.
QT interval changes with heart rate, so usually calculated as corrected QT (QTc), where average QT is divided by square root of RR interval (ie 1 second, if heart rate 60).
Associated with dysrhythmia, especially torsades de pointes (polymorphic ventricular tachycardia).
Seen with:
First generation have prominent CNS effects, usually drowsiness (which an be useful, eg to help sleep in chronic itch) but can be hyperactivity, paradoxically!
Second generation have lower incidence of these side effects.
Benadryl (brand name) can be either cetirizine or acrivastine. Latter marketed as “fasted allergy capsule” – I suspect the only allergy capsule.
Tmax (plasma) lowest for Rupatadine (0.75hr), levocetirizine (0.8), cetirizine (1). Chlorphenamine is 2.8, worse than diphenhydramine (best of the sedating antihistamines at 1.7). Loratadine (1.2) and Acrivastine (1.4) not far behind; Desloratadine has a range of values from 1-3, which is unhelpful, Fexo is definitely slow at 2.6.
In terms of clinical effect on wheal (because tissue distribution different from plasma), cetirizine, acrivastine, levocetirizine equivalent (1hr), diphenhydramine, fexo, desloratadin 2 hrs, CPM 3hrs (!). Rupatadine is 2 hrs, despite the short Tmax!
No particular reason to think formulation matters. Possibly liquid might work directly in the mouth and throat, but only if you don’t swallow it immediately (gargle!?).
Some examples of capsules beating liquids for specific drugs (!?) but prob not much difference between absorption from tablet, liquid etc. Prob easier to swallow liquid if oral angioedema, but liquid bolus might actually be harder than tiny tablet…
[J Investig Allergol Clin Immunol 2006; Vol. 16, Supplement 1: 3-12]
The majority of cases reported are non immediate reactions eg maculopapular rash, urticaria. The incidence of anaphylactic reactions is extremely low.
Less than 15% of those suspected of having macrolide allergy are finally confirmed as allergic, mainly by direct provocation testing.
Cross-reactivity between the different macrolides is variable and little information is available.
Current Opinion in Allergy and Clinical Immunology 14(4), August 2014, p 278–285. DOI: 10.1097/ACI.0000000000000069
Children with pneumonia with a label of penicillin allergy were found to have:
[US Journal of Allergy & Clinical Immunology in Practice. 11(6):1899-1906.e2, 2023 Jun.]
Atanaskovic-Markovic et al found that cross-reactivity between cephalosporins and penicillins varied between 0.3 and 23.9%, being higher among penicillins and between first-generation and second-generation cephalosporins.
However, it has recently been shown that all penicillin allergic children can tolerate cefuroxime, presumably as it has a different side chain.
Cross-reactivity appears to be higher in immediate reactions, and when penicillins and cephalosporins are identical or similar in the R1 side chain, as happens with the first and second-generation cephalosporins.
Currently BNFc says to avoid cefalosporins if history of immediate penicillin hypersensitivity, but if use of cefalosporin is “essential” then can be used (but not cefalexin!).
Canadian study did oral challenges for non-blistering rashes – safe – but mostly cefprozil allergy (and linked to food allergies).
In hypothetical case of de-labelled patient, 47% of anaesthetists would not prescribe penicillin to patient anyway (n=5000)!
Primary care don’t always remove label even after de-labelling! (patient held records would help…)
Needs culture change in primary care and paeds of documenting reactions!
Make sure note is added to patient record when de-labelled. Electronic labels don’t necessarily help – not always possible to remove an allergy label from drug prescription system, depending on the system, may only allow subsequent note to be added. Free text systems do not encourage accurate description!
Alabama trial from NIHR to report on RCT of de-labelling in primary care; SPACE study in secondary care (nurse/pharmacist delivered).
Ibuprofen etc are a common cause of reactions, but mostly non immune mediated, via COX -1 inhibition. Previously called pseudo-allergy or intolerance, best called hypersensitivity, then subdivided into allergic or non-allergic. Often occurs in patients with underlying problem eg asthma, chronic urticaria, rhinosinusitis – exacerbates underlying condition. Hypersensitivity can be to a single drug, or cross-reactive, ie to unrelated drugs from different families (salicylates ie aspirin, propionic derivatives eg ibuprofen, acetic acid derivatives eg diclofenac, etc). Cross reactivity suggests a non-immune mechanism. Without history to support single drug (or family) hypersensitivity, you would have to advise the patient to avoid all NSAIDs.
Aspirin desensitization works for NSAID exacerbated respiratory disease, and NSAID induced (cross reactive) skin disease, controversial for chronic urticaria and no data for single drug skin disease or anaphylaxis. But needs maintenance dosing so only really useful for chronic conditions eg needing antiplatelet therapy.
Allergy 2013:68;1219
Under-recognized, particularly when chronic blockage (without itch/sneezing) rather than sneeze/discharge. Late phase reactions involving Eosinphil induction by T cells tends to produce chronic swelling and non-specific irritability eg cold air. Nose problems impact with everything connected eg eyes, sinuses, middle ear, lungs. Differential is wide eg CF/PCD, deviated septum, polyps.
Considered trivial, and indeed work and school attendance not much affected but quality of work much more so – proven sleep problems, tiredness, impaired cognitive function. In a study of UK 15-17yr olds , students who dropped a grade between prelims and finals were significantly more likely to have had allergic rhinitis symptoms, to have taken antihistamines, and in particular, Piriton (OR=1.7). 43% increased odds of dropping an exam grade, goes up to 71% if using a sedating antihistamine [Samantha Walker, JACI 2007: 120; 381-387]
In asthma, prevalence of rhinitis increases over time to very high levels. If significant symptoms then OR=4 for poor asthma control (equivalent to poor inhaler technique!), plus combination of acute rhinitis and URTI gives OR=20 for asthma exacerbation.
Persistent defined as more than 4/7 per week, for more than 4/52. Mod/severe defined as any impairment of sleep or activity, else “troublesome symptoms” (BSACI includes seasonal or not, where you might be considering immunotherapy).
On examination (with auroscope), blue boggy wet mucosa, ?nasal crease.
SPT is pretty good at finding causes – depends how many you screen for, of course! In a US study, 65% of patients (mixed adults/children) had a positive: house dust mite (HDM) most commonly, else trees, weeds, moulds. Aspergillus and Penicillium are indoor moulds, Alternaria is outdoors. Cat allergens are commonly found in homes without cats! Nasal challenge can be done if neg SPT/IgE (Rondon, Curr Op Allerg Clin Imm 2010).
See also hay fever.
Children/adults same, just watch for doses/side effects.
Intranasal steroids most effective. Antihistamines, both intranasal and oral, are effective. Consider also leukotriene receptor antagonist (LRTA) eg montelukast (esp if co-existing asthma). Oral decongestants and steroids are also used short term sometimes.
For intermittent symptoms or mild persistent, no preferred treatment option – intranasal antihistamine, oral antihistamine, decongestant, LTRA, or combination. Nasal saline douches eg Sterimar have some evidence for efficacy, also nasal filters (not caught on yet!).
If co-existing conjunctivitis, prob best to go straight to nasal steroid, else add oral/topical antihistamine, or topical cromone, or saline.
Oral decongestant should only be used for max 10/7, can be useful diagnostically. Similarly oral steroids, if poor response or where diagnosis still unsure.
Cromoglycate (Rynacrom) has a role in young children but prob less effective than topical steroid or anthistamine, and at 4-6x a day, certainly less convenient.
Nasal ipratroprium recommended for rhinorrhoea.
Azelastine spray (Rhinolast) has been discontinued, so only nasal antihistamine is now the combination product Dymista (with flutic, from age 12). Not as good as steroid, doesn’t seem to have much effect on congestion (prob non-type 1 mechanism). Bad taste, irritation.
Montelukast licensed for rhinitis in asthmatics where resistant to other treatments, from age 15! ARIA recommend for over 6.
Intranasal steroids superior to top/systemic antihistamine, LRTA (even combinations). They also help eye symptoms, whereas nasal antihistamines don’t. Beclometasone (from age 6yr) and budesonide have relatively high bioavailability so better to use fluticasone (from age 4, furoate or propionate) or mometasone (from age 6), esp if other steroid use eg for asthma/eczema.Technique is often an issue – most gets sprayed or sniffed into back of throat!
Nasal spray Technique – (see video) Shake, head slightly forward, aim at ceiling (better to use opposite hand?), don’t sniff. Gargle and spit if taste unpleasant. Keep with toothbrush or other marker of habitual routine.
See also immunotherapy – some evidence that immunotherapy for rhinitis reduces risk of asthma!
For competitive swimmers, note FINA doping control rules (based on the World Anti-Doping Agency regulations). Most asthma medications are on the Prohibited List including inhaled steroids and inhaled Beta2 agonists.
Therefore, elite athletes with asthma must apply for special permission to use these medications, known as the “Therapeutic Use Exemption” (TUE) program. If competing at FINA events, then you apply directly to the FINA Doping Control Review Board to have their applications considered. Lower level athletes should apply to their national anti-doping body.