Siklos hydroxyurea 100 mg Tablet, Film Coated, 60-count
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Antimetabolite class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Hydroxyurea (Hydrea) is used alone or with other medications or radiation therapy to treat a certain type of chronic myelogenous leukemia (CML; a type of cancer of the white blood cells) and certain types of head and neck cancer (including cancer of the mouth, cheek, tongue, throat, tonsils, and sinuses). Hydroxyurea (Droxia, Siklos) is used to reduce the frequency of painful crises and reduce the need for blood transfusions in adults and children 2 years of age and older with sickle cell anemia (an inherited blood disorder in which the red blood cells are abnormally shaped [shaped like a sick...
Read the full MedlinePlus article ↗- It's actually both, depending on the specific product. Droxia, Siklos, and Xromi are each approved to reduce the painful crises and blood transfusion needs in sickle cell anemia. H...
- What exactly is hydroxyurea used for — is it a cancer drug or a sickle cell drug?
- Very regularly — typically every two weeks while your dose is being adjusted. Hydroxyurea can lower your white blood cell and platelet counts, so monitoring is built into the treat...
- How often will I need blood tests while I'm on this medication?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Hydroxyurea — tap one for details:
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
Where does this data come from?
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII 905HNO1SIH
A synthetic polymer made from methacrylate compounds that forms a film coating on tablets or capsules. It helps control how quickly the medicine dissolves and releases its active ingredient in the digestive system.
-
UNII ND2M416302
Isopropyl alcohol is a clear liquid solvent derived from petroleum. In medicines, it dissolves active ingredients and other components, helps the product flow smoothly, and aids in sterilization during manufacturing.
-
UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
-
UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
-
UNII 7CV7WJK4UI
Sodium stearyl fumarate is a synthetic compound made from stearyl alcohol and fumaric acid. It acts as a lubricant and glidant in tablets and capsules, helping ingredients flow smoothly during manufacturing and preventing sticking.
5 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $6.230 | $373.79 / 60 tablets |
| Medicaid paysCMS SDUD · 12 mo | $6.08 | $364.99 / 60 tablets |
| Medicare drug plans payPart D · Q2 2026 | $6.52 | $391.16 / 60 tablets |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Siklos 100 mgthis 71770-0105-60 | Medunik | 60 tablets | $6.230 | — | Availability likely | — |
Where does this data come from?
⏳ Availability & generic status
The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.
Where does this data come from?
🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 71770-0105-60 You're viewing this | 1 BOTTLE in 1 CARTON (71770-105-60) / 60 TABLET, FILM COATED in 1 BOTTLE | 2020-10-15 | Active |
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: MYELOSUPPRESSION and MALIGNANCIES WARNING: MYELOSUPPRESSION and MALIGNANCIES See full prescribing information for complete boxed warning . Myelosuppression : SIKLOS may cause severe myelosuppression. Do not give if bone marrow function is markedly depressed.
Monitor blood counts at baseline and throughout treatment. Interrupt treatment and reduce dose as necessary. ( 5.1 ) Malignancies : Hydroxyurea is carcinogenic.
Advise sun protection and monitor patients for malignancies. ( 5.2 ) Myelosuppression: SIKLOS may cause severe myelosuppression. Monitor blood counts at baseline and throughout treatment.
Interrupt treatment and reduce dose as necessary [see Warnings and Precautions (5.1) ] . Malignancies: Hydroxyurea is carcinogenic. Advise sun protection and monitor patients for malignancies [see Warnings and Precautions (5.2) ] .
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE SIKLOS ® is 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.
( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Initial dose: 15 mg/kg in adults and 20 mg/kg in children once daily. Monitor blood counts every two weeks. ( 2.1 ) The dose may be increased by 5 mg/kg/day every 8 weeks, or sooner if a severe painful crisis occurs, until a maximum tolerated dose or 35 mg/kg/day is reached if blood counts are in an acceptable range.
( 2.1 ) Discontinue SIKLOS until hematologic recovery if blood counts are considered toxic. Resume treatment after reducing the dose by 5 mg/kg/day from the dose associated with hematological toxicity. ( 2.1 ) Renal impairment: Reduce the dose of SIKLOS by 50% in patients with creatinine clearance less than 60 mL/min.
( 2.2 , 8.6 , 12.3 )
2.1Recommended Dosing The recommended SIKLOS dosing is described in Table 1. Table 1: Dosing Recommendation Based on Blood Count Dosing Regimen Dose Dose Modification Criteria Monitoring Parameters Initial Recommended Dosing Adults: 15 mg/kg Pediatrics: 20 mg/kg once daily based on patient's actual or ideal weight, whichever is less. Monitor the patient's blood count every 2 weeks [see Warnings and Precautions (5.1) ] .
Dosing Adjustment Based on Blood Counts in an acceptable range Increase dose 5 mg/kg/day every 8 weeks or if a painful crisis occurs. Give until mild myelosuppression (absolute neutrophil count 2,000/uL to 4,000/uL) is achieved, up to a maximum of 35 mg/kg/day. Increase dosing only if blood counts are in an acceptable range.
Increase dosing if a painful crisis occurs. Do not increase if myelosuppression occurs. Blood Counts Acceptable Range: - neutrophils greater than or equal to 2,000 cells/mm 3 - platelets greater than or equal to 80,000/mm 3 - hemoglobin greater than 5.3 g/dL - reticulocytes greater than or equal to 80,000/mm 3 if the hemoglobin concentration less than 9 g/dL Dosing Adjustment Based on Blood Counts in a toxic range Discontinue treatment.
If blood counts are considered toxic, discontinue SIKLOS until hematologic recovery. Blood Counts Toxic Range: - neutrophils less than 2,000 cells/mm 3 younger patients with lower baseline counts may safely tolerate absolute neutrophil counts down to 1,250/mm 3 . - platelets less than 80,000/mm 3 - hemoglobin less than 4.5 g/dL - reticulocytes less than 80,000/mm 3 if the hemoglobin concentration less than 9 g/dL Dosing After Hematologic Recovery Reduce dose by 5 mg/kg/day. Reduce the dose from the dose associated with hematologic toxicity.
May titrate up or down every 8 weeks in 5 mg/kg/day increments. The patient should be at a stable dose with no hematologic toxicity for 24 weeks. Discontinue the treatment permanently if a patient develops hematologic toxicity twice.
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).
Therefore, the two strengths can be used to deliver doses of 1,000 mg, 750 mg, 500 mg, 250 mg, 100 mg, 50 mg and combinations thereof. Calculate the rounded doses to the nearest 50 mg or 100 mg strength based on clinical judgment. Patients must be able to follow directions regarding drug administration and their monitoring and care.
Fetal hemoglobin (HbF) levels may be used to evaluate the efficacy of SIKLOS in clinical use. Obtain HbF levels every three to four months. Monitor for an increase in HbF of at least two-fold over the baseline value.
Administration: 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 [see References (15) ].
2.2Dose Modifications for Renal Impairment Reduce the dose of SIKLOS by 50% in patients with creatinine clearance of less than 60 mL/min or with end-stage renal disease (ESRD) [see Use in Specific Populatio…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Tablets: functionally scored 100 mg and functionally triple-scored 1,000 mg tablet ( 3 ) Tablets: 100 mg tablets: off-white, capsule-shaped, film-coated, functionally scored tablet with scoring on both sides which can be divided into two equal parts, each part is debossed with "H" on one side. 1,000 mg tablets: off-white, capsule-shaped, film-coated, functionally triple-scored tablet with scoring on both sides which can be divided into four equal parts, each part is debossed with "T" on one side.
⛔ Contraindications ▾
4 CONTRAINDICATIONS SIKLOS is contraindicated in: Patients who have demonstrated a previous hypersensitivity to hydroxyurea or any other component of its formulation [see Adverse Reactions (6) ]. Patients who have demonstrated a previous hypersensitivity to hydroxyurea or any other component of its formulation. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Embryo-Fetal toxicity: Can cause fetal harm. Advise of potential risk to a fetus and use of effective contraception. ( 5.3 , 8.1 , 8.3 ) Cutaneous vasculitic toxicities (incl. leg ulcers): Institute treatment and discontinue SIKLOS and/or reduce dose if this occurs.
( 5.4 ) Risks with concomitant use of antiretroviral drugs: Pancreatitis, hepatotoxicity, and neuropathy have occurred. Monitor for signs and symptoms patients with HIV infection using antiretroviral drugs; discontinue SIKLOS, and implement treatment. ( 5.5 ) Concomitant use with live virus vaccine: increased risk of severe infections.
( 5.6 ) Hemolytic Anemia: Monitor blood counts throughout treatment. If hemolysis persists, discontinue SIKLOS. ( 5.9 )
5.1Myelosuppression 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 recommended initial dose of 15 mg/kg/day in adults or 20 mg/kg/day in children, have experienced severe or life-threatening myelosuppression. Due to the change in body weight requiring 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 [see Dosage and Administration (2.1) ] .
5.2Malignancies 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.
5.3Embryo-Fetal Toxicity Based on the mechanism of action and findings in animals, SIKLOS can cause fetal harm when administered to a pregnant woman. Hydroxyurea was embryotoxic and teratogenic in rats and rabbits at doses 0.8 times and 0.3 times, respectively, the maximum recommended human daily dose on a mg/m2 basis. Advise pregnant women of the potential risk to a fetus [see Use in Specific Populations (8.1) ] .
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 [see Use in Specific Populations (8.1 , 8.3) ] .
5.4Vasculitic 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. Due to potentially severe clinical outcomes for the cutaneous vasculitic ulcers reported in patients with myeloproliferative disease (a condition for which SIKLOS is not approved), 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).
5.5 Risks with Concomitant Use of Antiretrovi…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Myelosuppression [see Warnings and Precautions (5.1) ] Malignancies [see Warnings and Precautions (5.2) ] Vasculitic toxicities (including Leg Ulcers) [see Warnings and Precautions (5.4) ] Risks with concomitant use of antiretroviral drugs [see Warnings and Precautions (5.5) ] Risk with concomitant use of live virus vaccine [see Warnings and Precautions (5.6) ] Macrocytosis [see Warnings and Precautions (5.7) ] Hemolytic Anemia [see Warnings and Precautions (5.9) ] Most common adverse reactions to SIKLOS (incidence > 10%) include infections and neutropenia in children and infections and headache and dry skin in adults.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact the marketer Medunik at 1 844-884-5520 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical 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 and 1077 adults 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 and 32% of the 1077 adults with sickle cell disease in ESCORT-HU. The most frequent serious adverse reactions were infections (18%), and blood and lymphatic system disorders (9%) in children, including 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%). Among adults, the most frequent serious adverse reactions were infections (12.9%), respiratory, thoracic and mediastinal disorders (5.8%), blood and lymphatic disorders (4.8%), nervous system disorders (3.6%), and general disorders and administration site disorders (3.1%). Table 2: Most frequent (greater than or equal to 2%) adverse reactions reported in pediatric patients enrolled in ESCORT-HU Global Safety Set (N=405) Total Severity Mild Moderate Severe n % n % n % n % n: number of patients with an adverse reaction 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
2.5Viral 40 10 23 6 14 3.5 3
0.7Parvovirus B19 15 4 7 1.7 5 1.2 2
0.5 Blood and lymphatic system disorders 85 21 51 13 59 15 14
3.5Neutropenia 51 13 26 6 31 8 4 1 Thrombocytopenia 30 7 16 4 15 3.7 2
0.5Anemia 17 4.2 4 1 8 2 7
1.7Gastrointestinal disorders 53 13 29 7 30 7 4 1 Other Gastrointestinal Disorders 30 7 13 3.2 15 3.7 2
0.5Constipation 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 disorders 44 11 24 6 21 5 1
0.2Deficiency of vitamin D 25 6 19 4.7 7 1.7 1
0.2Other Metabolic and nutrition disorders 8 2 3 0.7 4 1 1
0.2Weight 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
0.5Skin and subcutaneous tissue disorders 38 9 29 7 14 3.5 1
0.2Skin reactions 15 4 8 2 7 1.7 1
0.2Other 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
0.2Other Not SCD-related reactions 23 6 16 4 3 0.7 1
0.2 Respiratory tho…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS
7.1Increased Toxicity with Concomitant Use of Antiretroviral Drugs Pancreatitis Pancreatitis (including fatal cases) have occurred in patients with HIV infection during therapy with hydroxyurea and didanosine, with or without stavudine. Hydroxyurea is not indicated for the treatment of HIV infection; however, if patients with HIV infection are treated with hydroxyurea, and in particular, in combination with didanosine and/or stavudine, monitor closely for signs and symptoms of pancreatitis. Permanently discontinue therapy with hydroxyurea in patients who develop signs and symptoms of pancreatitis.
Hepatotoxicity Hepatotoxicity and hepatic failure resulting in death have been reported during postmarketing surveillance in patients with HIV infection treated with hydroxyurea and other antiretroviral drugs. Fatal hepatic events were reported most often in patients treated with the combination of hydroxyurea, didanosine, and stavudine. Avoid this combination.
Peripheral Neuropathy Peripheral neuropathy, which was severe in some cases, has been reported in patients with HIV infection receiving hydroxyurea in combination with antiretroviral drugs, including didanosine, with or without stavudine.
7.2Concomitant Use of Live Virus Vaccine Concomitant use of SIKLOS with a live virus vaccine may potentiate the replication of the vaccine virus and/or may increase the adverse reactions of the vaccine virus, because normal defense mechanisms may be suppressed by SIKLOS therapy. Vaccination with a live vaccine in a patient taking SIKLOS may result in severe infections. Generally, the patient's antibody response to vaccines may be decreased.
Treatment with SIKLOS and concomitant immunization with live virus vaccines should only be performed if benefits clearly outweigh potential risks. Consider consultation with a specialist.
7.3Test Interference Interference with Uric Acid, Urea, or Lactic Acid Assays Studies have shown that there is an analytical interference of SIKLOS with the enzymes (urease, uricase, and lactate dehydrogenase) used in the determination of urea, uric acid, and lactic acid, rendering falsely elevated results of these in patients treated with SIKLOS. Interference with Continuous Glucose Monitoring Systems Hydroxyurea may falsely elevate sensor glucose results from certain continuous glucose monitoring (CGM) systems and may lead to hypoglycemia if sensor glucose results are relied upon to dose insulin.
If a patient using a CGM is to be prescribed hydroxyurea, consult with the CGM prescriber about alternative glucose monitoring methods.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation: Advise women to stop breastfeeding while taking SIKLOS. ( 8.2 )
8.1Pregnancy Risk Summary SIKLOS can cause fetal harm based on findings from animal studies and the drug's mechanism of action [see Clinical Pharmacology (12.1) ] . There are no studies with the use of SIKLOS in pregnant women, and limited available data on SIKLOS use during pregnancy are insufficient to inform drug-associated risks. Drugs which affect DNA synthesis, such as hydroxyurea, may be potential mutagenic agents.
In animal reproduction studies, administration of hydroxyurea to pregnant rats and rabbits during organogenesis produced embryotoxic and teratogenic effects at doses 0.8 times and 0.3 times, respectively, the maximum recommended human daily dose on a mg/m 2 basis. In rats and rabbits, fetal malformations were observed with partially ossified cranial bones, absence of eye sockets, hydrocephaly, bipartite sternebrae, and missing lumbar vertebrae. Embryotoxicity was characterized by decreased fetal viability, reduced live litter sizes, and developmental delays (see Data ) .
Advise pregnant women of the potential risk to a fetus (see Clinical Considerations ). Background risk of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively. Clinical Considerations Fetal/Neonatal adverse reactions Although the data on a limited number of exposed pregnancies indicate no adverse effects on pregnancy or on the health of the fetus/newborn, patients on SIKLOS should be made aware of the potential risks to the fetus. Based on the limited amount of available information, in case of an exposure to SIKLOS of pregnant female patients or pregnant partners of male patients, treated by SIKLOS, a careful follow-up with adequate clinical, biological and ultrasonographic examinations should be considered.
Data Human Data According to a retrospective analysis of a cohort of 123 adult patients treated with hydroxyurea, twenty-three pregnancies have been reported from 15 women treated with hydroxyurea and partners of 3 men not using barrier contraception treated with hydroxyurea. Most (61%) had no adverse developmental outcomes. In the other cases with known evolution, pregnancy had been interrupted either voluntarily or upon medical advice.
In retrospective cohorts of 352 children and adolescents with sickle cell disease older than 2 years treated with hydroxyurea for a period of up to 12 years, 3 pregnancies under hydroxyurea were reported with no adverse developmental outcomes. From post-marketing data of SIKLOS, 3 pregnancies have been reported while the father was treated with SIKLOS and 16 pregnancies have been reported in 15 females treated with SIKLOS. Among the 13 cases with known evolution, 5 pregnancies had no adverse developmental outcomes, 4 led to premature birth, and 4 were early terminated.
Animal Data Hydroxyurea has been demonstrated to be a potent teratogen in a wide variety of animal models, including mice, hamsters, cats, miniature swine, dogs, and monkeys at doses within 1-fold of the human dose given on a mg/m 2 basis. Hydroxyurea is embryotoxic and causes fetal malformations (partially ossified cranial bones, absence of eye sockets, hydrocephaly, bipartite sternebrae, missing lumbar vertebrae) at 180 mg/kg/day (about 0.8 times the maximum recommended human daily dose on a mg/m 2 basis) in rats and at 30 mg/kg/day (about 0.3 times the maximum recommended human daily dose on a mg/m 2 basis) in rabbits.
Embryotoxicity was characterized by decreased fetal viability, reduced live litter sizes, and developmental delays. Hydroxyurea crosses the placenta. Single doses of ≥375 mg/kg (about 1.7 times the maximum recommended human daily dose o…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary SIKLOS can cause fetal harm based on findings from animal studies and the drug's mechanism of action [see Clinical Pharmacology (12.1) ] . There are no studies with the use of SIKLOS in pregnant women, and limited available data on SIKLOS use during pregnancy are insufficient to inform drug-associated risks. Drugs which affect DNA synthesis, such as hydroxyurea, may be potential mutagenic agents.
In animal reproduction studies, administration of hydroxyurea to pregnant rats and rabbits during organogenesis produced embryotoxic and teratogenic effects at doses 0.8 times and 0.3 times, respectively, the maximum recommended human daily dose on a mg/m 2 basis. In rats and rabbits, fetal malformations were observed with partially ossified cranial bones, absence of eye sockets, hydrocephaly, bipartite sternebrae, and missing lumbar vertebrae. Embryotoxicity was characterized by decreased fetal viability, reduced live litter sizes, and developmental delays (see Data ) .
Advise pregnant women of the potential risk to a fetus (see Clinical Considerations ). Background risk of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively. Clinical Considerations Fetal/Neonatal adverse reactions Although the data on a limited number of exposed pregnancies indicate no adverse effects on pregnancy or on the health of the fetus/newborn, patients on SIKLOS should be made aware of the potential risks to the fetus. Based on the limited amount of available information, in case of an exposure to SIKLOS of pregnant female patients or pregnant partners of male patients, treated by SIKLOS, a careful follow-up with adequate clinical, biological and ultrasonographic examinations should be considered.
Data Human Data According to a retrospective analysis of a cohort of 123 adult patients treated with hydroxyurea, twenty-three pregnancies have been reported from 15 women treated with hydroxyurea and partners of 3 men not using barrier contraception treated with hydroxyurea. Most (61%) had no adverse developmental outcomes. In the other cases with known evolution, pregnancy had been interrupted either voluntarily or upon medical advice.
In retrospective cohorts of 352 children and adolescents with sickle cell disease older than 2 years treated with hydroxyurea for a period of up to 12 years, 3 pregnancies under hydroxyurea were reported with no adverse developmental outcomes. From post-marketing data of SIKLOS, 3 pregnancies have been reported while the father was treated with SIKLOS and 16 pregnancies have been reported in 15 females treated with SIKLOS. Among the 13 cases with known evolution, 5 pregnancies had no adverse developmental outcomes, 4 led to premature birth, and 4 were early terminated.
Animal Data Hydroxyurea has been demonstrated to be a potent teratogen in a wide variety of animal models, including mice, hamsters, cats, miniature swine, dogs, and monkeys at doses within 1-fold of the human dose given on a mg/m 2 basis. Hydroxyurea is embryotoxic and causes fetal malformations (partially ossified cranial bones, absence of eye sockets, hydrocephaly, bipartite sternebrae, missing lumbar vertebrae) at 180 mg/kg/day (about 0.8 times the maximum recommended human daily dose on a mg/m 2 basis) in rats and at 30 mg/kg/day (about 0.3 times the maximum recommended human daily dose on a mg/m 2 basis) in rabbits.
Embryotoxicity was characterized by decreased fetal viability, reduced live litter sizes, and developmental delays. Hydroxyurea crosses the placenta. Single doses of ≥375 mg/kg (about 1.7 times the maximum recommended human daily dose on a mg/m 2 basis) to rats caused growth retardation and impaired learning ability.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of SIKLOS have been established in pediatric patients aged 2-18 years with sickle cell anemia with recurrent moderate to severe painful crises. Use of SIKLOS in these age groups is supported by evidence from a non-interventional cohort study, the European Sickle Cell Disease prospective Cohort study, ESCORT-HU, in which 405 pediatric patients ages 2 to <18 were enrolled. Among the 405 pediatric patients treated with SIKLOS, 274 were children (2-11) and 108 were adolescents (12-16) [see Clinical Studies (14) ] .
Continuous follow-up of the growth of treated children is recommended. Pediatric patients aged 2-16 years had a higher risk of neutropenia than patients more than 16 years old. The safety and effectiveness of SIKLOS have not been established in pediatric patients less than 2 years of age.
🆘 Overdosage ▾
10 OVERDOSAGE 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 times and 8.57 times of the maximum recommended dose of 35 mg/kg b.w./day).
Monitor blood counts weekly until recovery. Treatment of overdose consists of gastric lavage, followed by symptomatic treatment and control of bone marrow function.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The precise mechanism by which hydroxyurea produces its cytotoxic and cytoreductive effects is not known. However, various studies support the hypothesis that hydroxyurea causes an immediate inhibition of DNA synthesis by acting as a ribonucleotide reductase inhibitor, without interfering with the synthesis of ribonucleic acid or of protein. The mechanisms by which SIKLOS produces its beneficial effects in patients with sickle cell Anemia (SCA) are uncertain.
Known pharmacologic effects of SIKLOS that may contribute to its beneficial effects include increasing hemoglobin F levels in red blood cells (RBCs), decreasing neutrophils, increasing the water content of RBCs, increasing deformability of sickled cells, and altering the adhesion of RBCs to endothelium.
12.2Pharmacodynamics The correlation between hydroxyurea concentrations, reduction of crisis rate, and increase in HbF, is not known.
12.3Pharmacokinetics Mean peak plasma concentrations and AUCs increase more than proportionally with increase of dose. There is no drug accumulation upon once daily dosing of hydroxyurea. Absorption Following oral administration, hydroxyurea reaches peak plasma concentrations in 1 to 4 hours.
The oral bioavailability of hydroxyurea was reported to be 85 -100%. Effect of Food There are no data on the effect of food on the absorption of hydroxyurea. Distribution Hydroxyurea distributes throughout the body with a volume of distribution approximating total body water.
Hydroxyurea concentrates in leukocytes and erythrocytes. Elimination Half-life of hydroxyurea is about 2-4 hours. Metabolism Up to 60% of an oral dose undergoes conversion through saturable hepatic metabolism and a minor pathway of degradation by urease found in intestinal bacteria.
Excretion The percentage of the dose excreted in urine was approximately 40% in pediatric patients with sickle cell anemia. Specific Populations Patients with Renal Impairment The effect of renal impairment on the pharmacokinetics of hydroxyurea was assessed in adult patients with sickle cell anemia and renal impairment. Patients with normal renal function (creatinine clearance [CrCl] >80 mL/min), mild (CrCl 50-80 mL/min), moderate (CrCl =30-<50 mL/min), or severe (<30 mL/min) renal impairment received a single oral dose of 15 mg/kg hydroxyurea.
Creatinine clearance values were obtained using 24-hour urine collections. Patients with ESRD received two doses of 15 mg/kg separated by 7 days; the first was given following a 4-hour hemodialysis session, the second prior to hemodialysis. The exposure to hydroxyurea (mean AUC) in patients with CrCl <60 mL/min and those with ESRD was 64% higher than in patients with normal renal function (CrCl >60 mL/min).
Reduce the dose of SIKLOS when it is administered to patients with creatinine clearance of <60 mL/min or with ESRD following hemodialysis [see Dosage and Administration (2.2) and Use in Specific Populations (8.6) ]. Patients with Hepatic impairment There are no data that support specific guidance for dose adjustment in patients with hepatic impairment. Pediatric Patients The pharmacokinetics of hydroxyurea is similar between children (4 to 17 years) and adults.
🧬 Mechanism of Action ▾
12.1Mechanism of Action The precise mechanism by which hydroxyurea produces its cytotoxic and cytoreductive effects is not known. However, various studies support the hypothesis that hydroxyurea causes an immediate inhibition of DNA synthesis by acting as a ribonucleotide reductase inhibitor, without interfering with the synthesis of ribonucleic acid or of protein. The mechanisms by which SIKLOS produces its beneficial effects in patients with sickle cell Anemia (SCA) are uncertain.
Known pharmacologic effects of SIKLOS that may contribute to its beneficial effects include increasing hemoglobin F levels in red blood cells (RBCs), decreasing neutrophils, increasing the water content of RBCs, increasing deformability of sickled cells, and altering the adhesion of RBCs to endothelium.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied SIKLOS (hydroxyurea) film-coated tablet is supplied in high density polyethylene (HDPE) bottle with polypropylene child-resistant cap with a desiccant unit containing 30 (SIKLOS 1,000 mg) or 60 (SIKLOS 100 mg) film coated tablets. Each bottle containing SIKLOS 100 mg tablets or SIKLOS 1000 mg tablets is supplied in a carton. SIKLOS is supplied in the following strengths: 100 mg off-white, capsule-shaped, film-coated, functionally scored tablet with scoring on both sides which can be divided into two equal parts, each part is debossed with "H" on one side.
1,000 mg off-white, capsule-shaped, film-coated, functionally triple-scored tablet with scoring on both sides which can be divided into four equal parts, each part is debossed with "T" on one side. Bottles of 30 Bottles of 60 100 mg N/A NDC 71770-105-60 1,000 mg NDC 71770-120-30 N/A
16.2Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Keep tightly closed. Broken tablets must be stored in the bottle and must be used within three months.
16.3Handling and Disposal SIKLOS is a cytotoxic drug. Follow applicable special handling and disposal procedures [see References (15) ] . To decrease the risk of contact, advise caregivers to wear disposable gloves when handling SIKLOS or bottles containing SIKLOS.
Wash hands with soap and water before and after contact with the bottle or tablets when handling SIKLOS. Avoid exposure to crushed tablets. If contact with crushed tablets occurs on the skin, wash affected area immediately and thoroughly with soap and water.
If contact with crushed tablets occurs on the eye(s), the affected area should be flushed thoroughly with water or isotonic eyewash designated for that purpose for at least 15 minutes. Powder spilled from the broken tablet should be wiped up with a damp disposable towel which must be thrown away in a closed container such as a plastic bag to avoid ingestion of powder by other people. The spill areas should then be cleaned using a detergent solution followed by clean water.
📦 Storage and Handling ▾
16.2Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Keep tightly closed. Broken tablets must be stored in the bottle and must be used within three months.
16.3Handling and Disposal SIKLOS is a cytotoxic drug. Follow applicable special handling and disposal procedures [see References (15) ] . To decrease the risk of contact, advise caregivers to wear disposable gloves when handling SIKLOS or bottles containing SIKLOS.
Wash hands with soap and water before and after contact with the bottle or tablets when handling SIKLOS. Avoid exposure to crushed tablets. If contact with crushed tablets occurs on the skin, wash affected area immediately and thoroughly with soap and water.
If contact with crushed tablets occurs on the eye(s), the affected area should be flushed thoroughly with water or isotonic eyewash designated for that purpose for at least 15 minutes. Powder spilled from the broken tablet should be wiped up with a damp disposable towel which must be thrown away in a closed container such as a plastic bag to avoid ingestion of powder by other people. The spill areas should then be cleaned using a detergent solution followed by clean water.
📋 Description ▾
11 DESCRIPTION SIKLOS (hydroxyurea) is an antimetabolite that is available for oral use as functionally scored 100 mg film-coated tablet and functionally triple-scored 1,000 mg film-coated tablet containing 100 and 1,000 mg of hydroxyurea, respectively. Inactive ingredients include silicified microcrystalline cellulose, sodium stearyl fumarate, and film-coating agent amino methacrylate copolymer. Hydroxyurea is a white crystalline powder.
It has a molecular weight of 76.05. Its structural formula is: Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient or caregiver to read the FDA-approved patient labeling (Instructions for Use and Medication Guide). There is a risk of myelosuppression. Emphasize the importance of monitoring blood counts every two weeks throughout the duration of therapy to patients taking SIKLOS [see Warnings and Precautions (5.1) ] .
Advise patients to report signs and symptoms of infection or bleeding immediately. Advise patients that there is a risk of cutaneous vasculitic toxicities and secondary malignancies including leukemia. Advise use of sun protection [see Warnings and Precautions (5.1) ] .
Advise females of reproductive potential of the potential risk to a fetus should they become pregnant while taking SIKLOS. Advise patients to inform their healthcare provider of a known or suspected pregnancy. Advise females and males of reproductive potential to use contraception during and after treatment with SIKLOS [see Warnings and Precautions (5.3) and Use in Specific Populations (8.1 , 8.3) ] .
Advise females to discontinue breastfeeding during treatment with SIKLOS [see Use in Specific Populations (8.2) ] . Advise male patients of potential risk to fertility [see Use in Specific Populations (8.3) ] . Advise patients with HIV infection to contact their physician for signs and symptoms of pancreatitis, hepatic events, and peripheral neuropathy [see Warnings and Precautions (5.5) ] .
Advise patients to notify their healthcare provider if they are using a continuous glucose monitoring system while taking SIKLOS [see Warnings and Precautions (5.8) ]. Advise patients of the risk of hemolytic anemia. Advise patients that they will have blood tests to evaluate for this if they develop persistent anemia not related to sickle cell anemia [see Warnings and Precautions (5.9) ] .
Because SIKLOS tablets are scored, advise patients on how to take SIKLOS properly.
💬 Medication Guide ▾
This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 11/2023 MEDICATION GUIDE SIKLOS (See – k – los) (hydroxyurea) tablets What is the most important information I should know about SIKLOS?
SIKLOS can cause serious side effects including: Low blood cell counts are common with SIKLOS, including low red blood cells, white blood cells, and platelets, and can be severe and life-threatening. If your white blood cell count becomes very low, you are at increased risk for infection. Your healthcare provider will check your blood cell counts before and every 2 weeks during treatment with SIKLOS.
Your healthcare provider may change your dose or tell you to stop taking SIKLOS if you have low blood cell counts. Tell your healthcare provider right away if you get any of the following symptoms: fever or chills body aches feeling very tired shortness of breath unusual headache bleeding or unexplained bruising Cancer. Some people have developed cancer, such as leukemia and skin cancer, after taking SIKLOS for a long time.
Your healthcare provider will check you for cancer. You should protect your skin from the sun using sunblock, hats, and sun-protective clothing. SIKLOS can harm your unborn baby.
For females taking SIKLOS who can become pregnant: You should talk with your healthcare provider about the risks of SIKLOS to your unborn baby. You should use effective birth control during treatment with SIKLOS and for at least 6 months after treatment with SIKLOS. Your healthcare provider will perform a pregnancy test before you start treatment with SIKLOS.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant. For males taking SIKLOS: SIKLOS can affect your sperm. If you have a female sexual partner who can become pregnant, you should use effective birth control during treatment with SIKLOS and for at least 6 months after treatment.
SIKLOS may cause fertility problems in males. Talk to your healthcare provider if this is a concern for you. See " What are the possible side effects of SIKLOS? " for more information about side effects.
What is SIKLOS? SIKLOS is a prescription medicine that is used to reduce the frequency of painful crises and reduce the need for blood transfusions in adults and children, 2 years of age and older, with sickle cell anemia with recurrent moderate to severe painful crises. It is not known if SIKLOS is safe and effective in children less than 2 years of age.
Do not take SIKLOS if you are allergic to hydroxyurea or any of the ingredients in SIKLOS . See the end of this Medication Guide for a list of the ingredients in SIKLOS. Before taking SIKLOS, tell your healthcare provider about all of your medical conditions, including if you: have kidney problems or are receiving hemodialysis have liver problems have human immunodeficiency virus (HIV) or take HIV medicines.
Taking SIKLOS with certain HIV medicines can cause serious reactions and may lead to death. have increased levels of uric acid in your blood (hyperuricemia) have a history of receiving interferon therapy or are currently receiving interferon therapy have leg wounds or ulcers plan to receive any vaccinations. You should not receive "live vaccines" during treatment with SIKLOS. are pregnant or plan to become pregnant. See " What is the most important information I should know about SIKLOS? " are breastfeeding or plan to breastfeed.
It is not known if SIKLOS can pass into your breast milk. Do not breastfeed during treatment with SIKLOS. are using a continuous glucose monitor (CGM) to test your blood glucose. Hydroxyurea may affect your sensor glucose results and may lead to low blood sugar (hypoglycemia).
Talk to the healthcare provider that prescribed your CGM about whether it is safe to use while you are taking SIKLOS. Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. How should I take…