Abbreviated Prescribing Information:

Xromi® (hydroxycarbamide) 100 mg/ml oral solution

Please refer to the Summary of Product Characteristics (SmPC) before prescribing.

 

Presentation: Oral solution, each 1 ml contains 100 mg hydroxycarbamide and 0.5 mg methyl hydroxybenzoate.
Indications: For the prevention of vaso-occlusive complications of Sickle Cell Disease in patients over 2 years of age.
Dosage and Administration: The usual starting dose of hydroxycarbamide is 15 mg/kg/day and usual maintenance dose is between 20-25 mg/kg/day. The maximum dose is 35 mg/kg/day. Full blood cell count with white cell differential and reticulocyte count should be monitored once a month for the first 2 months following treatment initiation. Once a maximum tolerated dose is established, laboratory safety monitoring should include full blood cell count with white cell differential, reticulocyte count, and platelet count every 2–3 months. Elderly May be more sensitive to the myelosuppressive effects, consider reducing dose. Renal impairment If creatinine clearance (CrCl) ≤ 60 ml/min reduce the initial dose by 50%. Close monitoring of blood parameters is advised. Must not be administered to patients with severe renal impairment (CrCl < 30 ml/min). Hepatic impairment No data to support specific dose adjustments in patients with hepatic impairment. Close monitoring of blood parameters is advised. Hydroxycarbamide is contraindicated in patients with severe hepatic impairment. Children Not recommended below the age of 2 years. Administration May be taken with or after meals at any time of the day but patients should standardise the method of administration and time of day.
Contraindications: Hypersensitivity to the active substance or to any of the excipients. Patients with severe hepatic impairment (Child-Pugh classification C), severe renal impairment (CrCl < 30 ml/min), myelosuppression, breastfeeding, pregnancy, concomitant anti-retroviral medicinal products for HIV disease.
Warnings and Precautions: Bone marrow suppression The complete status of the blood, including bone marrow examination, if indicated, as well as kidney function and liver function should be determined prior to, and repeatedly during, treatment. If bone marrow function is depressed, treatment with hydroxycarbamide should not be initiated. The full blood cell count with white cell differential, reticulate count, and platelet count should be monitored regularly. Hydroxycarbamide may produce bone marrow suppression; leukopenia is generally its first and most common manifestation. Thrombocytopenia and anaemia occur less often and are seldom seen without a preceding leukopenia. Bone marrow depression is more likely in patients who have previously received radiotherapy or cytotoxic cancer chemotherapeutic medicinal products; hydroxycarbamide should be used cautiously in such patients. The recovery from myelosuppression is rapid when hydroxycarbamide therapy is interrupted. Hydroxycarbamide therapy can then be re-initiated at a lower dose. Severe anaemia must be corrected with whole blood replacement before initiating therapy with hydroxycarbamide. If, during treatment, anaemia occurs, correct without interrupting hydroxycarbamide therapy. Erythrocytic abnormalities; megaloblastic erythropoiesis, which is self-limiting, is often seen early in the course of hydroxycarbamide therapy. The morphologic change resembles pernicious anaemia, but is not related to vitamin B12 or folic acid deficiency. The macrocytosis may mask the incidental development of folic acid deficiency; regular determinations of serum folic acid are recommended. Hydroxycarbamide may also delay plasma iron clearance and reduce the rate of iron utilisation by erythrocytes but it does not appear to alter the red blood cell survival time. HIV patients Hydroxycarbamide must not be used in combination with anti-retroviral medicinal products for HIV disease and it may cause treatment failure and toxicities (in some cases fatal) in HIV patients. Secondary leukaemia and skin cancer In patients receiving long-term therapy with hydroxycarbamide for myeloproliferative disorders, such as polycythemia, secondary leukaemia has been reported. It is unknown whether this leukaemogenic effect is secondary to hydroxycarbamide or associated with the patient’s underlying disease. Skin cancer has been reported in patients receiving long-term hydroxycarbamide. Patients should be advised to protect skin from sun exposure. In addition patients should conduct self-inspection of the skin during the treatment and after discontinuation of the therapy with hydroxycarbamide and be screened for secondary malignancies during routine follow-up visits. Cutaneous vasculitic toxicities Cutaneous vasculitic toxicities including vasculitic ulcerations and gangrene have occurred in patients with myeloproliferative disorders during therapy with hydroxycarbamide. Due to potentially severe clinical outcomes, hydroxycarbamide should be discontinued if cutaneous vasculitic ulcerations develop. Vaccines The use of live vaccines should be avoided during treatment and for at least six months after treatment has finished and individual specialist advice sought. Leg ulcers In patients with leg ulcers, hydroxycarbamide should be used with caution. Leg ulcers are a common complication of Sickle Cell Disease, but have also been reported in patients treated with hydroxycarbamide. Carcinogenicity Hydroxycarbamide is unequivocally genotoxic in a wide range of test systems. Hydroxycarbamide is presumed to be a transspecies carcinogen. Safe handling Parents and care givers should avoid hydroxycarbamide contact with skin or mucous membrane. If the solution comes into contact with skin or mucosa, it should be washed immediately and thoroughly with soap and water. Excipients Contains methyl parahydroxybenzoate (E218) which may cause allergic reactions (possibly delayed).
Interactions: The myelosuppressive activity may be potentiated by previous or concomitant radiotherapy or cytotoxic therapy. Patients must not be treated with hydroxycarbamide and anti-retroviral medicinal products concurrently, because of the risk of fatal and non-fatal pancreatitis, hepatotoxicity, fatal hepatic failure and peripheral neuropathy. There is an increased risk of severe or fatal infections with the concomitant use of live vaccines. Treatment with hydroxycarbamide and concomitant immunisation with live virus vaccines should only be performed if benefits clearly outweigh potential risks.
Pregnancy and Lactation: Not to be used during pregnancy. Both men and women of child bearing potential should use contraceptive measures prior to, during the treatment and 3-6 months after stopping treatment. Discontinue breastfeeding during treatment.
Side Effects: Very common Bone marrow depression including neutropenia, reticulocytopenia, macrocytosis, oligospermia, azoospermia. Common Thrombocytopenia, anaemia, headache, dizziness, nausea, constipation, skin ulcer, oral, nail and skin hyperpigmentation, dry skin, alopecia. Uncommon Stomatitis, diarrhoea, vomiting, elevated liver enzymes, hepatotoxicity, rash. Unknown Leukaemia, skin cancers (in elderly patients), weight gain, vitamin D deficiency, bleeding, gastrointestinal disturbances, gastrointestinal ulcer, severe hypomagnesaemia, amenorrhea, fever. Rare Leg ulcers. Very Rare Systemic and cutaneous lupus erythematosus.
Overdose: Immediate treatment consists of gastric lavage, followed by supportive therapy for the cardiorespiratory systems if required. Monitor for vital signs, blood and urine chemistry, renal and hepatic function and full blood counts for at least 3 weeks. Longer periods of monitoring may be required. If necessary, blood should be transfused.
Pack size: 1 glass bottle containing 150 ml Xromi (hydroxycarbamide) 100 mg/ml oral solution, 1 adaptor and 2 syringes (3 ml and 10 ml).
Shelf life: 2 years. After first opening: 12 weeks.
Storage: Store in a refrigerator (2°C – 8°C).
Legal category: POM
Marketing Authorisation Number: PLGB 13581/0003
Marketing Authorisation Holder: Nova Laboratories Limited, Martin House, Gloucester Crescent, Wigston, Leicester, LE18 4YL, United Kingdom
Date of latest revision: March 2023
Job number: XroABVPI003
NHS Price: £250.00
Further information is available from: Nova Laboratories Limited, Martin House, Gloucester Crescent, Wigston, Leicester, LE18 4YL, UK.
Tel: +44 (0)116 223 0100