SIKLOS SIDE EFFECTS
- Generic Name: hydroxyurea tablets, for oral use
- Brand Name: Siklos
- Drug Class: Antineoplastics, Antimetabolite
SIDE EFFECTS
The following clinically significant adverse reactions are described elsewhere in the labeling:
- Myelosuppression
- Malignancies
- Embryo-fetal toxicity
- Vasculitic toxicities (including Leg Ulcers)
- Risks with concomitant use of antiretroviral drugs
- Risk with concomitant use of live virus vaccine
- Macrocytosis
Clinical Trial 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 SIKLOS has been assessed in 405 pediatric patients with sickle cell disease from 2-18 years of age in the European Sickle Cell Disease prospective Cohort study ESCORT-HU.
The most frequently reported adverse reactions in ESCORT-HU were infections and myelosuppression, with mild to moderate neutropenia as the most common manifestation.
Other adverse reactions include skin and subcutaneous disorders (skin depigmentation/melanonychia, skin rash, alopecia), gastrointestinal disorders, vitamin D deficiency and headache.
At least one serious adverse reaction was reported in 33% of the 405 pediatric patients with sickle cell disease in ESCORT-HU. The most frequent serious adverse reactions were infections (18%), and blood and lymphatic system disorders (9%). This included serious neutropenia (3.2%), thrombocytopenia (3%) and anemia (3%). Other reported serious adverse reactions were gastrointestinal disorders (3.2 %), fever (2.5 %) and nervous system disorders (4%), including headache (2.7%).
Table 1: Most frequent (greater than or equal to 2%) adverse reactions reported in pediatric patients enrolled in ESCORT-HU
| Global Safety Set (N=405) | Total | Intensity | ||||||
| Mild | Moderate | Severe | ||||||
| n | % | n | % | n | % | n | % | |
| At least one adverse reaction | 261 | 64 | ||||||
| Infections | 161 | 40 | 120 | 30 | 88 | 22 | 18 | 4.4 |
| Other Infections | 92 | 23 | 66 | 16 | 32 | 8 | 3 | 0.7 |
| Bacterial | 65 | 16 | 24 | 6 | 37 | 9 | 10 | 2.5 |
| Viral | 40 | 10 | 23 | 6 | 14 | 3.5 | 3 | 0.7 |
| Parvovirus B19 | 15 | 4 | 7 | 1.7 | 5 | 1.2 | 2 | 0.5 |
| Blood and lymphatic system disorders | 85 | 21 | 51 | 13 | 59 | 15 | 14 | 3.5 |
| Neutropenia | 51 | 13 | 26 | 6 | 31 | 8 | 4 | 1 |
| Thrombocytopenia | 30 | 7 | 16 | 4 | 15 | 3.7 | 2 | 0.5 |
| Anemia | 17 | 4.2 | 4 | 1 | 8 | 2 | 7 | 1.7 |
| Gastrointestinal disorders | 53 | 13 | 29 | 7 | 30 | 7 | 4 | 1 |
| Other Gastrointestinal Disorders | 30 | 7 | 13 | 3.2 | 15 | 3.7 | 2 | 0.5 |
| Constipation | 10 | 2.5 | 5 | 1.2 | 5 | 1.2 | 0 | 0 |
| Nausea | 10 | 2.5 | 4 | 1 | 4 | 1 | 2 | 0.5 |
| Metabolic and nutrition dis orders | 44 | 11 | 24 | 6 | 21 | 5 | 1 | 0.2 |
| Deficiency of vitamin D | 25 | 6 | 19 | 4.7 | 7 | 1.7 | 1 | 0.2 |
| Other Metabolic and nutrition disorders | 8 | 2 | 3 | 0.7 | 4 | 1 | 1 | 0.2 |
| Weight gain | 8 | 2 | 1 | 0.2 | 7 | 1.7 | 0 | 0 |
| Nervous system disorders | 45 | 11 | 19 | 4.7 | 19 | 4.7 | 8 | 2 |
| Headache | 30 | 7 | 15 | 3.7 | 7 | 1.7 | 4 | 1 |
| Other Nervous system disorders | 11 | 2.7 | 2 | 0.5 | 4 | 1 | 4 | 1 |
| General disorders | 41 | 10 | 22 | 5 | 17 | 4.2 | 4 | 1 |
| Fever | 31 | 8 | 20 | 4.9 | 12 | 3 | 2 | 0.5 |
| Skin and subcutaneous tissue disorders | 38 | 9 | 29 | 7 | 14 | 3.5 | 1 | 0.2 |
| Skin reactions | 15 | 4 | 8 | 2 | 7 | 1.7 | 1 | 0.2 |
| Other Skin and subcutaneous tissue disorders | 13 | 3.2 | 8 | 2 | 5 | 1.2 | 0 | 0 |
| Other Not SCD-related reactions | 23 | 6 | 16 | 4 | 3 | 0.7 | 1 | 0.2 |
| Other Not SCD-related reactions | 23 | 6 | 16 | 4 | 3 | 0.7 | 1 | 0.2 |
| Respiratory thoracic and mediastinal disorders | 11 | 3 | 6 | 1.5 | 3 | 0.7 | 2 | 0.5 |
| Renal and urinary disorders | 8 | 2 | 2 | 0.5 | 4 | 1 | 0 | 0 |
| n: number of patients with an adverse reaction | ||||||||
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of SIKLOS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Infections and infestations: Parvovirus B19 infection
- Blood and lymphatic system disorders: bone marrow depression including neutropenia (<2.0 × 109/l), reticulocytopenia (<80 × 109/l), macrocytosis, thrombocytopenia (<80 × 109/l), anemia (hemoglobin <4.5g/dl)
- Nervous system disorders: headache, dizziness
- Gastrointestinal disorders: nausea, gastrointestinal disturbances, vomiting, gastrointestinal ulcer, severe hypomagnesemia
- Hepatobiliary disorders: elevation of hepatic enzymes
- Skin and subcutaneous tissue disorders: skin reactions (oral, ungula and cutaneous pigmentation), oral mucositis, rash, melanonychia, alopecia, leg ulcers, cutaneous dryness
- Reproductive system and breast disorders: oligospermia, azoospermia, amenorrhea
- General disorders: fever
- Investigations: weight gain
SRC: NLM .