A case report of isoniazid adverse drug reaction in a pediatric patient with defective NAT2 gene

Abstract Rationale: Adverse drug reactions (ADRs) represent a major health problem worldwide, with high morbidity and mortality rates, ranging from 0.5% to 16.8% in hospitalized children. One of the most effective and widely used drugs for anti-tuberculosis treatment is Isoniazid (INH). INH is a pro-drug and following oxidative activation, forms an adduct with NAD+ that inhibits NADH-dependent targets of Mycobacterium tuberculosis. Although this regimen is effective in treating active tuberculosis, it is associated with many ADRs considered as the main complication during therapy Patient concerns: The patient, a 14-year-old girl, presented with nodal tuberculosis exhibiting mobile laterocervical and angle-mandibular lymphadenopathy Diagnoses: INH plasmatic concentration levels above the therapeutic range and a custom NGS gene panel including NAT2 gene allowed the identification of the NAT2∗5C/∗6B slow metabolizer haplotype Interventions: The Patient was hospitalized and initially treated with quadruple antituberculosis therapy. After treatment, she was not able to continue the anti-tuberculosis treatment owing to ADR including overwhelming vomiting, nausea, worsening of clinical conditions, and hypertransaminasemia. Outcomes: Isoniazid and Rifampicin dosage was halved and then, because of the further increase of transaminases, anti-tuberculosis therapy was suspended. Clinical conditions and hematic parameters rapidly improved after suspension of anti-tuberculosis drugs Lessons: We report a 14-year-old girl with defective NAT2 that showed ADRs during anti-tuberculosis therapy. Combined strategy of therapeutic drug monitoring and pharmacogenetic analysis should be widely adopted during the routine clinical practice in order to optimize therapy and minimize ADRs