Hydroxyureaside effects

The following clinically significant adverse reactions are described in detail in other labeling sections: Myelosuppression Hemolytic anemia Malignancies Vasculitic toxicities Live vaccinations Macrocytosis Pulmonary toxicity Most common adverse reactions (incidence > 5%) are neutropenia and thrombocytopenia, and popular rash. To report SUSPECTED ADVERSE REACTIONS, contact Rare Disease Therapeutics, Inc. at 844-472-7389 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of XROMI was evaluated in 32 pediatric patients aged 10 months -16 years with sickle cell anemia in a single-arm, open-label, prospective, multi-center, pharmacokinetic, safety and efficacy study (HUPK study). Only adverse reactions associated with the use of XROMI in pediatric patients aged 10 months to less than 2 years are presented. The most frequently reported adverse reactions in HUPK study (<33%) were neutropenia, and thrombocytopenia. Table 3. Adverse Reactions Reported in Pediatric Patients Aged 10 Months and Older Enrolled in HUPK 10 Months–<2 Years 2 –<6 Years 6 –<18 Years Overall Body System Adverse Reactions (n=6)% (n=16)% (n=10)% (n=32)% Neutropenia 3 1 0 4 Thrombocytopenia 2 1 0 3 Diarrhea 1 0 0 1 GGT Increased 0 0 1 1 Absolute Reticulocyte Count Decreased 1 0 0 1 Alopecia 0 1 0 1 Nail Discolouration 0 0 1 1 Rash 0 0 1 1 Rash Popular 0 1 1 2

6.2 Post marketing

Experience The following adverse reactions have been identified during post-approval use of hydroxyurea. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency. Reproductive System and Breast disorders: azoospermia, and oligospermia Gastrointestinal disorders: stomatitis, nausea, vomiting, diarrhea, and constipation Metabolism and Nutrition disorders: anorexia Skin and subcutaneous tissue disorders: maculopapular rash, skin ulceration, cutaneous lupus erythematosus, dermatomyositis-like skin changes, peripheral and facial erythema, hyperpigmentation, nail hyperpigmentation, atrophy of skin and nails, scaling, violet papules, and alopecia Renal and urinary disorders: dysuria, elevations in serum uric acid, blood urea nitrogen (BUN), and creatinine levels Nervous system disorders: headache, dizziness, drowsiness, disorientation, hallucinations, and convulsions General disorders: fever, chills, malaise, edema, and asthenia Hepatobiliary disorders: elevation of hepatic enzymes, cholestasis, and hepatitis Respiratory disorders: diffuse pulmonary infiltrates, dyspnea, and pulmonary fibrosis, interstitial lung disease, pneumonitis, alveolitis, allergic alveolitis and cough Immune disorders: systemic lupus erythematosus Hypersensitivity: Drug-induced fever (pyrexia) (>39°C, >102°F) requiring hospitalization has been reported concurrently with gastrointestinal, pulmonary, musculoskeletal, hepatobiliary, dermatological or cardiovascular manifestations. Onset typically occurred within 6 weeks of initiation and resolved upon discontinuation of hydroxyurea. Upon re-administration fever reoccurred typically within 24 hours. Blood and lymphatic system disorders: hemolytic anemia