SIKLOS is an antimetabolite indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in adult and pediatric patients 2 years of age and older, with sickle cell anemia with recurrent moderate to severe painful crises.
See Full Prescribing Information for complete Boxed Warning
SIKLOS is contraindicated in patients who have demonstrated a previous hypersensitivity to hydroxyurea or any other component of its formulation.
SIKLOS dosing is based on patient’s actual or ideal weight, whichever is less. Specific parameters (blood counts) must be monitored every 2 weeks throughout treatment with SIKLOS and dosing must be adjusted accordingly.
Dosing recommendation based on blood count:
SIKLOS is available in 100 mg and 1,000 mg tablets. The 100 mg tablets have 1 score line and can be split into 2 parts (each 50 mg). The 1,000 mg tablets have 3 score lines and can be split into 4 parts (each 250 mg).
The tablets should be taken once daily, at the same time each day, with a glass of water.
For patients who are not able to swallow the tablets, these can be dispersed immediately before use in a small quantity of water in a teaspoon.
SIKLOS is a cytotoxic drug. Follow applicable special handling and disposal procedures.
Myelosuppression
Hydroxyurea causes severe myelosuppression. Do not initiate treatment with hydroxyurea in patients if bone marrow function is markedly depressed. Bone marrow suppression may occur, and leukopenia is generally its first and most common manifestation. Thrombocytopenia and anemia occur less often and are seldom seen without a preceding leukopenia.
Some patients, treated at the initial dose in adults or in children, have experienced severe or life-threatening myelosuppression. During body weight change modification of daily dose, pediatric patients have an increased risk of myelosuppression at the time of dose adjustment.
Evaluate hematologic status prior to and every two weeks during treatment with SIKLOS. Provide supportive care and modify dose or discontinue SIKLOS as needed. Recovery from myelosuppression is usually observed within 15 days when therapy is interrupted. Resume therapy after interruption at a lower dose.
Malignancies
Hydroxyurea is a human carcinogen. In patients receiving long-term hydroxyurea for myeloproliferative disorders (a condition for which SIKLOS is not approved), secondary leukemia has been reported. Leukemia secondary to long-term hydroxyurea has also been reported in patients with sickle cell disease. Leukemia has also been reported in patients with sickle cell disease and no prior history of treatment with hydroxyurea.
Skin cancer has also been reported in patients receiving long-term hydroxyurea. Advise protection from sun exposure and monitor for the development of secondary malignancies.
Embryo-Fetal Toxicity
Based on the mechanism of action and findings in animals, SIKLOS can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception during and after treatment with SIKLOS for at least 6 months after therapy. Advise males of reproductive potential to use effective contraception during and after treatment with SIKLOS for at least 6 months after therapy.
Vasculitic Toxicities (including Leg Ulcers)
Cutaneous vasculitic toxicities, including vasculitic ulcerations and gangrene, have occurred in patients with myeloproliferative disorders during therapy with hydroxyurea. These vasculitic toxicities were reported most often in patients with a history of, or currently receiving, interferon therapy. Treatment with SIKLOS should be discontinued and/or its dose reduced if cutaneous vasculitic ulcerations develop. Rarely, ulcers are caused by leukocytoclastic vasculitis.
Avoid use of SIKLOS in patients with wounds on the legs (leg ulcers).
Risks with Concomitant Use of Antiretroviral Drugs
Pancreatitis, hepatotoxicity, and peripheral neuropathy have occurred when hydroxyurea was administered concomitantly with antiretroviral drugs. Monitor for signs and symptoms in patients with HIV infection using antiretroviral drugs. Discontinue SIKLOS and implement treatment.
Risks with Concomitant Use of Live Virus Vaccine
Avoid use of live virus vaccine in patients taking SIKLOS as it may potentiate the replication of the vaccine virus and/or may increase the adverse reactions of the vaccine virus and result in severe infection. Patient’s antibody response to vaccines may be decreased. Consider consultation with a specialist.
Macrocytosis
SIKLOS may cause macrocytosis, which is self-limiting, and is often seen early in the course of treatment. The morphologic change resembles pernicious anemia but is not related to vitamin B12 or folic acid deficiency. This may mask the diagnosis of pernicious anemia. Prophylactic administration of folic acid is recommended.
Test Interference
Interference with Uric Acid, Urea, or Lactic Acid Assays is possible, rendering falsely elevated results of these in patients treated with hydroxyurea.
Hemolytic Anemia
Cases of hemolytic anemia in patients treated with hydroxyurea for myeloproliferative disease have been reported. Monitor blood counts throughout treatment. If hemolysis persists, discontinue SIKLOS.
The most common adverse reactions to SIKLOS (incidence >10%) include infections and neutropenia in children and infections and headache and dry skin in adults.
Other adverse reactions include skin and subcutaneous disorders (skin depigmentation/melanonychia, skin rash, alopecia), gastrointestinal disorders, vitamin D deficiency and headache.
Acute mucocutaneous toxicity has been reported in patients receiving hydroxyurea at doses several times above the therapeutic dose. Soreness, violet erythema, oedema on palms and soles followed by scaling of hand and feet, severe generalized hyperpigmentation of the skin and stomatitis have been observed. In patients with sickle cell anemia, neutropenia was reported in isolated cases of hydroxyurea overdose (1.43 – 8.57 times the maximum recommended dose). Treat overdose with gastric lavage, symptom treatment and control of bone marrow function. Monitor blood counts weekly until recovery.
To report suspected adverse reactions, contact Medunik USA at 1-844-884-5520 or medicalinfo@medunikusa.com.
Please read the Full Prescribing Information, including Boxed Warning at hcp.SIKLOSusa.com.
SIKLOS is an antimetabolite indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in adult and pediatric patients 2 years of age and older, with sickle cell anemia with recurrent moderate to severe painful crises.
SIKLOS is an antimetabolite indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in adult and pediatric patients 2 years of age and older, with sickle cell anemia with recurrent moderate to severe painful crises.