7%). 1%). 3% of patients. 6% of patients who received voxelotor in the pivotal study. 1%). 4). Tabulated list of adverse reactions Table 1 lists adverse drug reactions that occurred in patients treated with voxelotor 1500 mg during a 72-week, randomized, double-blind, placebo-controlled pivotal Phase 3 study (n=88), as well as adverse reactions from postmarketing experience.
Adverse reactions reported with voxelotor are listed by system organ class and preferred term. Within each system organ class, adverse reactions are listed under frequency categories. Frequencies are defined as very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from available clinical study data).
Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Table 1:
Adverse reactions System organ class Adverse reactionsa Frequency category Immune system disorders Drug hypersensitivity Uncommon Nervous system disorders Headache Very common Gastrointestinal disorders Diarrhoea Abdominal painb Nausea Very common Rashc Very common Pruritus Common Skin and subcutaneous tissue disorders Drug reaction with eosinophilia and systemic symptoms (DRESS) Angioedemad Not known a.
Adverse reactions were NCI Grades 1 or 2 except for Grade 3 diarrhoea (n=1), nausea (n=1), rash (n=1), rash generalized (n=3) and hypersensitivity (n=1). b. Abdominal pain includes abdominal pain, abdominal pain upper, and abdominal pain lower.
c. Rash includes rash, urticaria, rash generalized, rash macular, rash maculo-papular, rash pruritic, and rash papular. d. Angioedema includes swelling of eyelid, face oedema, lip swelling, and periorbital swelling. Description of selected adverse reactions Gastrointestinal (GI) disorders In the pivotal Phase 3 study, the most commonly reported GI adverse reactions were diarrhoea, abdominal pain and nausea with diarrhoea and nausea showing a dose-dependent effect.
The majority of reported GI events were Grade 1 or 2 and were manageable without the need for dose interruption, reduction or treatment discontinuation and resolved with continued use. 5% of patients. 0% of patients in the voxelotor 1500 mg, and placebo groups, respectively.
1%) report of Grade 3 diarrhoea. 1%) patient in the voxelotor 1500 mg group. 1%) experienced drug hypersensitivity on Study Day 40. Observed symptoms included generalized morbilliform rash, urticaria, mild shortness of breath, mild facial swelling, pyrexia, headache, and diarrhoea.
Elevated eosinophils were noted. Symptoms abated after voxelotor was withheld, and recurrence was observed after reintroduction of voxelotor. Event resolved with antihistamine and oral corticosteroids. 0% of patients in the voxelotor 1500 mg and placebo groups, respectively.
The majority of rash events were similar in appearance (consistent with typical maculopapular drug eruptions) and distribution, were not associated with extradermal symptoms, and were clinically manageable with or without treatment including oral antihistamines or topical corticosteroids.
Exposure-response analysis did not reveal a statistically significant dose- or exposure-response relationship. Paediatric population The safety profile observed in paediatric patients 12 to < 18 years of age treated with voxelotor in the clinical studies was similar to that seen in adult patients.
Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.