A 2012 report described three case reports evaluating the safety and efficacy of acetazolamide in individuals with sulfonamide antibiotic allergies and neurologic channelopathies. The described cases included a 61-year-old man with late-onset episodic ataxia, an 83-year-old woman with genetically confirmed Andersen-Tawil syndrome type 1, and a 21-year-old woman with episodic ataxia type 2 associated with a CACNA1A genetic mutation. All three patients presented with a history of severe hypersensitivity reactions to sulfonamide antibiotics, manifesting as skin rashes, facial swelling, and generalized hives. Due to these documented allergies, they were initially denied treatment with acetazolamide, a carbonic anhydrase inhibitor frequently used in managing episodic ataxia and periodic paralysis. Following a comprehensive review of the pharmacologic literature, which indicated that cross-reactivity between sulfonamide antibiotics and nonantibiotic sulfonamides was negligible, acetazolamide was prescribed to these patients under close observation. [1]
The 2012 report outlines the outcomes following acetazolamide administration, emphasizing its clinical benefits and tolerability. The 61-year-old male patient experienced significant improvements in gait and coordination at a dosage of 250 mg twice daily, with paresthesias being the only reported side effect. The 83-year-old female patient, treated with the same dosage, showed no adverse reactions and was able to complete an 18-week course without complications. The 21-year-old female patient demonstrated complete resolution of headaches, vertigo, and ataxia with a daily dosage of 125 mg, again with no hypersensitivity reactions noted. These findings are further supported by chemical and immunologic analyses, suggesting that the structural and metabolic characteristics of acetazolamide differ significantly from sulfonamide antibiotics, reducing the likelihood of cross-reactivity. The report concludes that acetazolamide can be safely administered to individuals with sulfonamide antibiotic allergies, providing effective symptomatic relief in neurologic channelopathies. [1]
A 2010 review investigated the role of acetazolamide in individuals with a history of sulfonamide allergies, focusing on its safety profile and the mechanisms of hypersensitivity reactions. The review explored distinct chemical differences between sulfonamide antibiotics and nonantibiotics, noting that only the antibiotic subgroup contains the arylamine moiety associated with hypersensitivity. Evidence from observational studies was critical in examining cross-reactivity within and between these subgroups. While earlier data suggested potential cross-reactivity, the review highlighted findings from studies that demonstrated a lack of immunologic cross-reactivity between the two groups. Additionally, it was emphasized that a patient's general predisposition to drug hypersensitivity could increase reported allergic reactions to unrelated medications, further complicating clinical interpretations. [2]
The review detailed the wide spectrum of allergic manifestations linked to sulfonamides, from mild cutaneous reactions to life-threatening conditions such as Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN). While data revealed SJS/TEN to be strongly associated with sulfonamide antibiotics, no significant link was found with nonantibiotic sulfonamides like acetazolamide. The authors proposed a systematic approach to evaluate acetazolamide's safety in individuals with sulfonamide allergies, considering the severity and type of prior reactions. For patients with minor hypersensitivity to antibiotic sulfonamides, a test dose under medical observation could be employed to assess tolerance. By reevaluating prior contraindications in light of newer evidence, the review concluded that acetazolamide may be safely used in most cases, provided careful patient evaluation and monitoring are implemented. [2]
A retrospective case series published in 2004 investigated whether acetazolamide or furosemide induces allergic cross-reactions in patients with self-reported sulfa allergies. This analysis encompassed a 31-year period (1972-2003) at the University of Iowa Hospitals and Clinics and included all patients diagnosed with idiopathic or secondary intracranial hypertension who reported a sulfa allergy and received treatment with acetazolamide, furosemide, or both. The review was conducted on 363 patient charts, with 329 cases excluded for reasons such as the absence of self-reported sulfa allergy or lack of treatment with the studied medications, resulting in the inclusion of 34 eligible patients. Follow-up ranged from seven weeks to 21 years (median: 2.5 years). The adverse events related to medication were categorized as predictable side effects (e.g., paresthesias, fatigue) or unpredictable adverse reactions (e.g., urticaria, Stevens-Johnson syndrome). Additionally, a literature search spanning 1966-2003 was performed to assess the pharmacological basis for cross-reactivity between sulfonamide antimicrobials and non-antimicrobial sulfonamides. [3]
Among 27 patients treated with acetazolamide, 37% reported no allergic cross-reactions, while 7% (two patients) experienced urticaria, neither of which was life-threatening. Predictable side effects such as paresthesias (66.7%) and gastrointestinal symptoms (53.4%) were the most commonly reported adverse events, while no cases of severe sulfa-related hypersensitivity reactions (e.g., Stevens-Johnson syndrome or anaphylaxis) were documented. Of the 21 patients treated with furosemide, either alone or alongside acetazolamide, no unpredictable reactions or sulfa cross-reactions were observed. The analysis highlighted distinctions in chemical structure between sulfonamide antibiotics and non-antimicrobial sulfonamides, emphasizing the absence of arylamine groups in acetazolamide and furosemide, which are implicated in hypersensitivity reactions. The findings concurred with prior pharmacological evidence suggesting that the risk of cross-reactivity between these sulfonamide-containing agents and antimicrobial sulfonamides is exceedingly low, supporting their consideration in patients with intracranial hypertension when clinically warranted. [3]
An expert commentary from the American Academy of Allergy Asthma & Immunology (AAAAI) states that the risk of reaction to acetazolamide in a patient with sulfonamide allergy is low. However, acetazolamide is listed as possibly cross-reacting with sulfonamide in the package insert. The expert recommends discussing with the patient that although the risk is low, a reaction without challenge cannot be excluded. It is recommended that a clinic drug challenge (simple administration under observation; not a graded challenge) may be feasible for determining if the patient can tolerate the medication. [4]