Siklos: Uses, Dosage & Side Effects
An oral ribonucleotide reductase inhibitor and fetal hemoglobin inducer used to prevent painful vaso-occlusive crises and acute chest syndrome in children and adults with sickle cell disease
Siklos (hydroxycarbamide, also known internationally as hydroxyurea) is an oral disease-modifying therapy used for the long-term prevention of recurrent painful vaso-occlusive crises and acute chest syndrome in adults, adolescents, and children over 2 years of age with sickle cell disease. Siklos works primarily by stimulating the production of fetal hemoglobin (HbF), which counteracts the polymerization of abnormal sickle hemoglobin (HbS) inside red blood cells and prevents them from assuming the rigid crescent shape that blocks blood vessels and damages organs. Decades of clinical evidence show that consistent treatment with hydroxycarbamide reduces hospitalizations, transfusion requirements, and mortality in sickle cell disease. Siklos is supplied as a scored 100 mg film-coated tablet that allows precise weight-based dosing, particularly in children.
Quick Facts: Siklos
Key Takeaways
- Siklos (hydroxycarbamide) is the cornerstone oral disease-modifying medication for sickle cell disease in patients aged 2 years and older, approved to prevent recurrent pain crises and acute chest syndrome.
- Its main mechanism is induction of fetal hemoglobin (HbF), which disrupts the polymerization of sickle hemoglobin (HbS) and reduces red blood cell sickling; additional benefits include lower white blood cell counts, reduced vascular adhesion, and improved nitric oxide availability.
- Treatment requires regular monitoring with complete blood counts, liver and kidney function tests, and clinical review because myelosuppression (neutropenia, thrombocytopenia, anemia) is the most common dose-limiting toxicity.
- Siklos is teratogenic and genotoxic: both women and men of reproductive potential must use effective contraception during treatment and for at least 6 months after the last dose, and pregnancy should be excluded before initiation.
- Long-term adherence is essential — clinical benefits develop gradually over months and accumulate over years, with studies demonstrating reductions in mortality, stroke risk, and organ damage in both children and adults.
What Is Siklos and What Is It Used For?
Siklos contains the active substance hydroxycarbamide, which is known in many countries by its alternative international name hydroxyurea. Although hydroxycarbamide was originally developed as a cytotoxic chemotherapy agent more than half a century ago, its most significant role in modern medicine is as a disease-modifying therapy for sickle cell disease. Siklos is formulated specifically for this indication: the 100 mg scored tablet allows the precise, weight-based dosing that pediatric and adult hematology require, and the film coating and size are designed for easier administration to children.
Sickle cell disease (SCD) is a group of inherited red blood cell disorders caused by a mutation in the HBB gene that codes for the beta chain of adult hemoglobin. The mutation produces an abnormal form of hemoglobin called sickle hemoglobin (HbS). When HbS loses oxygen, it polymerizes into long rigid fibers that distort the normally flexible disc-shaped red blood cell into a characteristic crescent or "sickle" shape. Sickled red cells are inflexible, have a shortened lifespan (approximately 10–20 days versus 120 days for healthy red cells), and tend to become trapped in small blood vessels. The resulting microvascular obstruction causes the hallmark features of sickle cell disease: recurrent episodes of severe pain (vaso-occlusive crises), tissue and organ damage, acute chest syndrome, stroke, and chronic hemolytic anemia.
Siklos is indicated for the prevention of recurrent painful vaso-occlusive crises including acute chest syndrome in adults, adolescents, and children over 2 years of age who have symptomatic sickle cell disease. By reducing the frequency and severity of crises, Siklos lowers hospitalization rates, reduces the need for blood transfusions, preserves organ function over time, and improves quality of life. Robust clinical trial data and decades of real-world use have shown that consistent treatment with hydroxycarbamide is also associated with reduced mortality in both children and adults with sickle cell disease.
The mechanism of action of hydroxycarbamide in sickle cell disease is multifactorial. Its best-characterized effect is the induction of fetal hemoglobin (HbF). HbF is the dominant hemoglobin of fetal and early infant life and is gradually replaced by adult hemoglobin (HbA or, in SCD, HbS) after birth. HbF does not participate in sickle polymer formation; when present in sufficient amounts within a red cell, it physically interferes with the polymerization of HbS and prevents sickling. Siklos stimulates the production of HbF through epigenetic and cellular mechanisms that reactivate fetal globin gene expression, typically raising HbF levels from 1–5% of total hemoglobin at baseline to 10–25% or higher during sustained therapy.
Beyond its effects on fetal hemoglobin, Siklos provides several additional benefits in sickle cell disease. It lowers the absolute white blood cell count, particularly neutrophils, thereby reducing the chronic inflammation and abnormal adhesion of leukocytes to blood vessel walls that contribute to vaso-occlusion. It decreases the expression of adhesion molecules on red cells and endothelium, improves red cell hydration, and increases the local generation of nitric oxide, which promotes vasodilation. Together, these effects translate into fewer and less severe pain crises, less acute chest syndrome, and better long-term organ preservation.
Siklos is a disease-modifying therapy, not a cure. It reduces the frequency and severity of complications but does not correct the underlying genetic mutation. Curative treatments for sickle cell disease currently include allogeneic hematopoietic stem cell transplantation and, more recently, autologous gene therapy products, but these options are complex, costly, and not accessible to all patients worldwide. For most people living with sickle cell disease, hydroxycarbamide remains the foundational pharmacologic therapy. The World Health Organization has included hydroxyurea on its Model List of Essential Medicines, and current guidelines from the American Society of Hematology (ASH), the National Heart, Lung, and Blood Institute (NHLBI), and the British Society for Haematology recommend offering hydroxycarbamide to all children with sickle cell anemia (HbSS or HbSβ0-thalassemia) starting as early as 9 months of age, regardless of symptoms.
Siklos is intended for continuous, long-term use. Clinical benefits develop gradually over weeks to months, and regular follow-up with a specialist hematologist is essential. Stopping treatment abruptly or missing doses can lead to a return of painful crises and other complications, sometimes within weeks.
What Should You Know Before Taking Siklos?
Contraindications
Siklos must not be used in the following situations. Your doctor will perform a complete medical history and baseline laboratory workup before starting treatment to exclude these contraindications.
- Hypersensitivity: Do not use Siklos if you are allergic to hydroxycarbamide or any of the other ingredients in the tablet (listed in the "What Does Siklos Contain" section below).
- Severe hepatic impairment: Siklos is not recommended in patients with severe liver dysfunction (Child-Pugh Class C), as this may prolong drug exposure and increase toxicity.
- Severe renal impairment: Siklos should not be used when creatinine clearance is below 30 mL/min, since the kidneys are a major route of elimination.
- Severe bone marrow depression: Treatment must not be initiated or continued if the neutrophil count is below 2.0 × 109/L, the platelet count is below 80 × 109/L, or the hemoglobin is below 4.5 g/dL (or as otherwise defined by your hematologist based on baseline values).
- Pregnancy and breastfeeding: Siklos is teratogenic and genotoxic and must not be used during pregnancy or lactation unless there is no safer alternative and the potential benefit clearly outweighs the serious risk to the fetus or infant.
Warnings and Precautions
Hydroxycarbamide is genotoxic and a presumed human carcinogen. Long-term treatment of myeloproliferative disorders has been associated with rare cases of secondary leukemia and skin cancer. Although the risk in patients treated for sickle cell disease appears to be very low, it cannot be completely excluded. Protect your skin from the sun, attend regular skin checks, and report any unusual lumps, skin lesions, persistent fever, or unexplained bleeding to your doctor.
Before and during treatment with Siklos, discuss the following points carefully with your doctor:
- Myelosuppression (bone marrow suppression): The most common and predictable side effect of Siklos is a dose-dependent reduction in white blood cells (neutropenia), platelets (thrombocytopenia), and red blood cells (anemia). Regular complete blood counts (CBC) are required: typically every 2 weeks while the dose is being titrated, and every 4 to 8 weeks once a stable dose is reached. Treatment must be paused if counts fall below safety thresholds.
- Infections: Low neutrophil counts may increase your susceptibility to infections. Fever (≥38.5°C or 101.3°F), chills, sore throat, or signs of a new infection must be reported urgently. Patients with sickle cell disease are already at increased risk of encapsulated bacterial infections (including Streptococcus pneumoniae) due to functional asplenia, so up-to-date vaccinations and antibiotic prophylaxis in children remain essential.
- Leg ulcers: Hydroxycarbamide can delay healing or cause new painful leg ulcers, typically located around the ankles. Existing leg ulcers in sickle cell disease may worsen. If this occurs, your doctor may reduce the dose or temporarily stop treatment.
- Skin changes: Hyperpigmentation, skin atrophy, melanonychia (dark longitudinal streaks in the nails), rash, and increased sensitivity to ultraviolet radiation are well recognized. Use broad-spectrum sunscreen, cover exposed skin, and attend regular dermatologic review.
- Hepatotoxicity: Hydroxycarbamide may cause mild to moderate elevations of liver enzymes. Severe hepatotoxicity is uncommon but has been reported. Liver function tests are monitored at baseline and periodically during treatment.
- Renal toxicity: Uric acid levels may rise due to increased cell turnover, occasionally precipitating gout or nephrolithiasis. Adequate hydration is essential, and patients with pre-existing kidney disease require dose adjustment and close monitoring.
- Pulmonary toxicity: Rare cases of interstitial lung disease, pulmonary fibrosis, and pneumonitis have been reported. Report any new or worsening cough, shortness of breath, or fever that is not obviously infectious.
- Concurrent use with antiretroviral therapy: Patients with HIV receiving stavudine or didanosine should not be treated with hydroxycarbamide because of an increased risk of pancreatitis, hepatotoxicity, and peripheral neuropathy.
- Macrocytosis: Siklos causes a marked increase in mean corpuscular volume (MCV) in almost all treated patients. This is an expected pharmacodynamic effect and a useful marker of adherence; it is not harmful and does not need to be corrected with vitamin therapy unless folate or vitamin B12 deficiency coexists.
- Radiation exposure: Hydroxycarbamide can potentiate the effects of previous or concurrent radiotherapy, including delayed recall reactions in previously irradiated skin. Inform your doctor of any prior radiation treatment.
- Fertility: Hydroxycarbamide can impair spermatogenesis and may cause reversible or, occasionally, persistent reductions in sperm count, motility, and morphology. Effects on female fertility are less well characterized but cannot be excluded. Men planning a family should discuss sperm cryopreservation with their specialist before starting therapy.
Your doctor will arrange baseline and ongoing tests to monitor safety. These typically include complete blood count with reticulocyte count, liver function tests (ALT, AST, bilirubin), renal function (creatinine, urea), uric acid, and urinalysis. Adjustments to the dose or treatment interruption may be required based on these results.
Other Medications
Hydroxycarbamide can interact with several medications and vaccines. Tell your doctor and pharmacist about every prescription medicine, over-the-counter product, herbal supplement, and recreational substance you use. Particular caution is needed with other cytotoxic drugs, antiretroviral therapy, live vaccines, uricosuric agents, and medicines that affect bone marrow function (see the dedicated interactions section below).
Pregnancy and Breastfeeding
Siklos must not be used during pregnancy unless there is no safer alternative and the maternal benefit clearly outweighs the fetal risk. Hydroxycarbamide has been shown to be teratogenic and embryotoxic in multiple animal species, and clinical data, while limited, suggest a potential for adverse pregnancy outcomes including spontaneous abortion and congenital malformations. Women of reproductive potential must have a negative pregnancy test before starting Siklos, use highly effective contraception during treatment, and continue contraception for at least 6 months after the last dose. If pregnancy is planned, Siklos should be discontinued at least 3 to 6 months in advance, with careful transition to alternative sickle cell disease management (such as transfusion therapy) under specialist supervision.
Men treated with hydroxycarbamide should also use effective contraception during treatment and for at least 6 months after the last dose, as the drug may be present in seminal fluid and may affect sperm DNA. Cryopreservation of sperm before starting therapy is recommended for men who wish to father children.
Hydroxycarbamide is excreted in human breast milk, and due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is contraindicated during treatment with Siklos. If a patient must receive Siklos during the postpartum period, breastfeeding should be discontinued.
Use in Elderly Patients
Elderly patients may be more sensitive to the hematological effects of Siklos, particularly if they have reduced renal function. The same dosing principles apply, but baseline assessment of kidney function is especially important, and more cautious dose titration with closer monitoring is recommended.
Driving and Operating Machinery
Siklos may cause dizziness, drowsiness, or headache in some patients. If you experience these symptoms, avoid driving or operating machinery until they have resolved. Underlying sickle cell disease itself can also affect cognitive function, particularly after a crisis or during severe anemia, so decisions about driving should be individualized.
Important Information About Ingredients
Siklos tablets contain lactose as an inactive ingredient. If your doctor has told you that you have an intolerance to some sugars, contact them before taking this medicine. The tablets also contain very small amounts of sodium (less than 1 mmol per tablet) and can be considered essentially "sodium-free".
How Does Siklos Interact with Other Drugs?
Hydroxycarbamide is not primarily metabolized by cytochrome P450 enzymes, so classic CYP-based interactions are limited. However, several clinically important interactions are driven by additive pharmacological effects on the bone marrow, liver, kidneys, and immune system. Always inform your treating hematologist and pharmacist about every medication, supplement, and vaccine before starting or changing therapy.
Major Interactions
| Interacting Drug or Class | Effect | Clinical Significance |
|---|---|---|
| Didanosine ± stavudine (antiretrovirals) | Greatly increased risk of pancreatitis (sometimes fatal), severe hepatotoxicity, and peripheral neuropathy | Combination contraindicated. If HIV treatment is required, use a different antiretroviral regimen. |
| Live attenuated vaccines (e.g., MMR, varicella, yellow fever, BCG, oral polio, oral typhoid, rotavirus) | Risk of vaccine-strain infection due to hydroxycarbamide-induced immunosuppression | Avoid during treatment. Inactivated vaccines (pneumococcal, influenza, hepatitis B) are safe and strongly recommended in SCD. |
| Other cytotoxic agents or radiotherapy | Additive myelosuppression and mucosal toxicity; potential for recall reactions in previously irradiated skin | Use only under oncology/hematology supervision with close blood count monitoring and dose adjustments. |
| Interferon alfa | Increased risk of vasculitic leg ulcers and bone marrow suppression | Avoid combination if possible; monitor closely for skin and hematological toxicity. |
| Clozapine | Additive risk of severe neutropenia and agranulocytosis | Combination generally avoided; if unavoidable, enhanced hematologic monitoring is mandatory. |
Minor and Monitor-Required Interactions
| Interacting Drug or Class | Effect | Clinical Significance |
|---|---|---|
| Uricosuric agents (probenecid, sulfinpyrazone) | Reduced efficacy because hydroxycarbamide increases serum uric acid | Consider xanthine oxidase inhibitors (allopurinol, febuxostat) instead for gout prophylaxis. |
| Allopurinol or febuxostat | Effective for hydroxycarbamide-induced hyperuricemia and gout; no harmful interaction | Preferred agents for uric acid control during Siklos therapy. |
| Laboratory assays (urease, uricase, lactate dehydrogenase) | Hydroxycarbamide may interfere with enzymatic laboratory determinations of urea, uric acid, and lactic acid, giving falsely elevated results | Inform laboratory staff of Siklos therapy; use alternative analytical methods where possible. |
| Azathioprine, 6-mercaptopurine, methotrexate | Additive bone marrow suppression | Combinations are generally avoided; if unavoidable, intensive blood count monitoring is required. |
| Alcohol | May increase hepatotoxicity and worsen dehydration — a known trigger for sickle cell crises | Minimize alcohol intake; avoid binge drinking. |
In addition to these interactions, certain commonly used supportive therapies in sickle cell disease — such as penicillin prophylaxis in children, folic acid supplementation, iron chelation in chronically transfused patients, and non-steroidal anti-inflammatory drugs (NSAIDs) for pain — can generally be continued alongside Siklos, but should be reviewed and monitored by your hematologist.
What Is the Correct Dosage of Siklos?
The correct dose of Siklos must be determined individually by a physician with experience in the treatment of sickle cell disease. Dosing is based on actual body weight (measured in kilograms), laboratory results, and clinical response. The scored 100 mg tablet allows precise dose adjustment in small increments, which is particularly important in children and in patients whose weight changes during treatment.
Adults and Adolescents
Standard Dosing Schedule (Aged 12 Years and Older)
Starting dose: 15 mg/kg body weight taken orally once daily.
Titration: Provided blood counts remain acceptable, the dose may be increased in steps of 5 mg/kg/day every 8 to 12 weeks.
Maximum tolerated dose: Generally 30–35 mg/kg/day; some patients may tolerate and benefit from higher doses up to 35 mg/kg/day under close specialist supervision.
The goal of titration is to reach the maximum tolerated dose that does not cause significant bone marrow suppression, because efficacy is dose-related. Absolute neutrophil count, hemoglobin, and platelet count should be checked before each dose increase.
Children Aged 2 Years and Older
Pediatric Dosing
Starting dose: 15 mg/kg body weight taken orally once daily.
Titration: Dose may be increased by 5 mg/kg every 8 to 12 weeks if tolerated, guided by complete blood count, reticulocyte count, and clinical response.
Maximum: Up to 35 mg/kg/day as tolerated.
The 100 mg scored tablet allows flexible dosing. For young children unable to swallow tablets, the tablet can be dispersed in a small amount of water just before administration; consult the product leaflet for specific instructions.
Siklos is not licensed for children younger than 2 years of age. In this age group, off-label use of hydroxycarbamide is common in many countries, guided by the landmark BABY HUG trial and international recommendations to start treatment as early as 9 months of age; however, this must always be supervised by a pediatric hematologist experienced in sickle cell disease.
Renal Impairment
Kidney Function Adjustments
Hydroxycarbamide is largely cleared by the kidneys. In patients with reduced renal function, dose adjustment is essential:
- Creatinine clearance ≥ 60 mL/min: No dose adjustment required.
- Creatinine clearance 30–59 mL/min: Reduce the starting dose by approximately 50%, with careful monitoring.
- Creatinine clearance < 30 mL/min: Siklos is contraindicated.
Hepatic Impairment
Liver Function Adjustments
Although no formal pharmacokinetic studies have been performed in patients with liver dysfunction, caution is warranted:
- Mild to moderate impairment (Child-Pugh A–B): No standard dose reduction, but close monitoring of liver enzymes and blood counts is recommended.
- Severe impairment (Child-Pugh C): Siklos is not recommended.
Elderly Patients
Considerations in Older Adults
Hydroxycarbamide dosing in elderly patients should begin at the lower end of the range and be adjusted cautiously, taking into account the greater likelihood of reduced hepatic, renal, and cardiac function, and concomitant medications. Baseline creatinine clearance should be calculated (not estimated from serum creatinine alone) before treatment initiation.
How to Take Siklos
Siklos is taken by mouth once a day, at the same time each day, preferably before a meal with a glass of water. The tablet is scored and can be divided to deliver half a dose of 50 mg when needed. For patients who cannot swallow tablets, Siklos tablets can be dispersed in a small quantity of water (approximately a teaspoon) and taken immediately. Hands should be washed thoroughly after handling the tablets or the dispersion, and dust generated from broken tablets should not be inhaled.
Healthcare workers and caregivers handling Siklos should take standard cytotoxic-drug handling precautions: wear disposable gloves when manipulating the tablets, avoid creating dust, and wash hands before and after handling. Pregnant caregivers should avoid contact with the tablets if possible.
What to Do If You Miss a Dose
Missed Dose Guidance
If you miss a dose, take it as soon as you remember on the same day. If it is nearly time for your next scheduled dose, skip the missed dose and take the next dose as usual. Do not take a double dose to make up for a missed one. If you miss several doses, contact your doctor for advice rather than trying to catch up yourself.
Overdose
Acute overdose with hydroxycarbamide may cause severe mucocutaneous reactions such as tender erythematous dusky skin, oral and mucosal ulcers, nail changes, and severe myelosuppression. Gastrointestinal symptoms including nausea, vomiting, and diarrhea may also occur. If overdose is suspected, contact your nearest emergency department or poison control center immediately. Treatment is supportive: stop hydroxycarbamide, provide intensive blood count monitoring, transfuse blood products if required, and treat any superinfection. There is no specific antidote.
What Are the Side Effects of Siklos?
Like all medicines, Siklos can cause side effects, although not everyone gets them. The safety profile of hydroxycarbamide has been characterized over decades of use in both sickle cell disease and hematological malignancies. In sickle cell disease populations, serious adverse events are uncommon and most side effects are dose-dependent and reversible on dose reduction or temporary treatment interruption.
Some laboratory changes observed during Siklos therapy are not truly side effects but rather expected pharmacodynamic markers. The most notable is a rise in the mean corpuscular volume (MCV) of red cells, often to 100–120 fL, which accompanies the induction of fetal hemoglobin and confirms medication adherence. A modest reduction in white blood cell and platelet counts is also intended, and the presence of a mild rise in HbF is a marker of therapeutic effect rather than a complication.
Very Common
May affect more than 1 in 10 people
- Bone marrow suppression: neutropenia (low white blood cells), thrombocytopenia (low platelets), reticulocytopenia, or anemia
- Macrocytosis (enlarged red blood cells) — expected and generally harmless
- Abnormal liver enzyme levels (ALT, AST)
- Headache
- Dizziness
- Nausea
- Skin rash
- Skin hyperpigmentation (darkening)
- Melanonychia (dark streaks or pigmentation of the nails)
- Loss or thinning of hair (mild)
- Reduction in sperm count and quality in men
Common
May affect up to 1 in 10 people
- Mouth ulcers or stomatitis
- Diarrhea or constipation
- Vomiting
- Dry skin, skin atrophy, or itching
- Leg ulcers, usually around the ankles
- Fever
- Elevated uric acid (may precipitate gout)
- Amenorrhea or menstrual irregularities
- Fatigue or general malaise
- Elevated creatinine or urea
Uncommon
May affect up to 1 in 100 people
- Severe bacterial or viral infections including sepsis
- Peripheral neuropathy or paresthesia
- Gastrointestinal bleeding
- Hepatitis or cholestasis
- Photosensitivity reactions
- Dermatomyositis-like skin changes
- Pneumonitis or interstitial lung disease
- Dactylitis
Rare
May affect up to 1 in 1,000 people
- Acute pancreatitis (especially with concomitant didanosine or stavudine)
- Severe hepatotoxicity (rarely fatal with antiretroviral combinations)
- Secondary malignancies: skin cancer (non-melanoma) and, very rarely, acute myeloid leukemia or myelodysplastic syndrome with long-term use
- Tumor lysis syndrome (rarely reported in sickle cell disease)
- Allergic reactions (urticaria, angioedema)
Not Known
Frequency cannot be estimated from available data
- Azoospermia or oligospermia (may be reversible)
- Cutaneous vasculitic ulcerations
- Squamous cell carcinoma of the skin (with long-term, high-dose exposure)
- Radiation recall reactions in previously irradiated skin
- Fever of unknown origin directly attributed to hydroxycarbamide
Most adverse effects of Siklos are identified early through routine laboratory monitoring and respond promptly to dose adjustment. Regular complete blood counts, liver and kidney function tests, clinical review, and skin examination allow your hematology team to preserve the substantial benefits of therapy while minimizing risk.
If you experience any side effects, including those not listed here, tell your doctor or nurse. You can also report suspected side effects to your national pharmacovigilance authority (for example, the EMA in Europe, the FDA MedWatch program in the United States, or the MHRA Yellow Card Scheme in the United Kingdom). Reporting helps to continuously monitor the benefit-risk profile of Siklos.
How Should Siklos Be Stored?
Correct storage preserves the potency and safety of Siklos throughout its shelf life. Because hydroxycarbamide is classified as a cytotoxic substance, basic precautions are recommended not only for the patient but also for carers, family members, and household pets.
- Temperature: Store below 30°C (86°F) in the original bottle with the cap tightly closed to protect from moisture. Do not refrigerate or freeze.
- Humidity: Keep the bottle in a dry place. Avoid storing in the bathroom or kitchen cabinets exposed to steam.
- Child safety: Always store Siklos out of the sight and reach of children and pets. The bottles have child-resistant closures, but this does not replace safe storage.
- Expiry date: Do not use Siklos after the expiry date (EXP) printed on the label and outer carton. The expiry refers to the last day of that month.
- Once opened: After first opening, use the bottle within the period stated in the product information (typically 3 months, depending on the local presentation).
- Visual inspection: Do not use tablets that appear discolored, chipped, or crumbled.
Do not dispose of unused or expired Siklos via household waste or wastewater systems. Return the bottle and any remaining tablets to your pharmacy for destruction according to local regulations for cytotoxic medicines. These measures help protect the environment and prevent accidental exposure.
What Does Siklos Contain?
Active Substance
The active substance of Siklos is hydroxycarbamide. Each film-coated tablet contains 100 mg of hydroxycarbamide. Hydroxycarbamide is also known internationally as hydroxyurea and has the chemical formula CH4N2O2. It is a small, water-soluble molecule that is absorbed almost completely after oral administration.
Inactive Ingredients (Excipients)
The other ingredients of the tablet core and film coating typically include:
- Sodium stearyl fumarate
- Silicified microcrystalline cellulose
- Lactose monohydrate
- Hypromellose (film coating)
- Macrogol 400 (film coating)
- Titanium dioxide (E171, film coating)
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicine because of the lactose content. The tablets are considered essentially sodium-free.
Appearance and Pack Sizes
Siklos 100 mg is an off-white, oblong, scored, film-coated tablet with markings that facilitate division into two equal halves for precise dosing. The tablets are typically supplied in high-density polyethylene (HDPE) bottles with child-resistant closures. Pack sizes vary by country and include 60-tablet and 90-tablet bottles. Higher-strength presentations (e.g., 1000 mg tablets, where available in certain markets) may also be used under specialist direction; however, the 100 mg tablet is the standard pediatric and fine-titration strength.
Marketing Authorization Holder and Manufacturer
Siklos is marketed by Addmedica (Paris, France). Siklos received its European marketing authorization in 2007 as an orphan medicinal product for sickle cell disease and subsequently gained approval in the United States and other regions. Local manufacturers and distributors may differ; consult the package leaflet supplied with your prescription for country-specific information.
Frequently Asked Questions About Siklos
Siklos (hydroxycarbamide) is used for the prevention of recurrent painful vaso-occlusive crises, including acute chest syndrome, in adults, adolescents, and children over 2 years of age with symptomatic sickle cell disease. By increasing the production of fetal hemoglobin (HbF), Siklos reduces red blood cell sickling, lowers hospitalization rates, decreases the frequency and severity of pain crises, and reduces the need for blood transfusions. It is considered a disease-modifying therapy rather than a cure.
Siklos works through several mechanisms. Its primary action is to increase the production of fetal hemoglobin (HbF), which does not sickle and which disrupts the polymerization of abnormal sickle hemoglobin (HbS) inside red blood cells. This prevents cells from taking the rigid crescent shape that blocks small blood vessels and causes pain crises. Siklos also reduces white blood cell and platelet counts (decreasing inflammation and vascular adhesion), improves red blood cell hydration, and increases nitric oxide availability in blood vessels.
The clinical effects of Siklos develop gradually over several months. Laboratory markers such as an increase in mean corpuscular volume (MCV) and a rise in fetal hemoglobin (HbF) are typically seen within the first 1 to 3 months. Clinically meaningful reductions in the frequency of pain crises, hospitalizations, and the need for transfusions are usually established after 3 to 6 months of consistent treatment at the optimal dose. Long-term benefits, including reduced mortality, continue to accumulate over years of continuous therapy.
Yes, Siklos is specifically approved for the treatment of symptomatic sickle cell disease in children aged 2 years and older, as well as adolescents and adults. The 100 mg scored tablet facilitates precise weight-based dosing. Large studies, including the BABY HUG trial, have demonstrated that hydroxycarbamide is safe and effective in children as young as 9 months, and recent WHO and American Society of Hematology (ASH) guidelines recommend offering hydroxycarbamide to all children with sickle cell anemia starting from 9 months of age, regardless of clinical severity.
Hydroxycarbamide has genotoxic potential, and long-term treatment in certain myeloproliferative disorders has been associated with secondary leukemia and skin cancer in a small number of patients. However, in patients with sickle cell disease, large long-term studies have not shown a clinically significant increase in cancer rates compared to expected population rates. The benefits of preventing life-threatening complications of sickle cell disease substantially outweigh the theoretical long-term cancer risk for most patients. Regular skin checks are recommended, and sun protection is advised.
Siklos must not be used during pregnancy unless absolutely necessary, as hydroxycarbamide is teratogenic and genotoxic in animal studies and may cause harm to the unborn child. Women of reproductive potential must use effective contraception during treatment and for at least 6 months after the last dose. Men should also use effective contraception during treatment and for at least 6 months after stopping Siklos, as the drug may affect sperm. If pregnancy is being planned, treatment is typically stopped at least 3 to 6 months in advance, with careful management of sickle cell disease by a specialist.
No. Siklos is a long-term preventive therapy. If you stop taking it, the benefits — reduced pain crises, fewer hospitalizations, and protection from organ damage — will gradually reverse within weeks to months, and your risk of complications will return to baseline. Never stop Siklos without speaking to your hematology team. If you experience side effects or have concerns, your doctor can adjust the dose or schedule rather than discontinuing treatment altogether.
References
- European Medicines Agency (EMA). Siklos (hydroxycarbamide) – Summary of Product Characteristics. Last updated 2025. Available from: EMA EPAR.
- U.S. Food and Drug Administration (FDA). Siklos (hydroxyurea) Prescribing Information. Revised 2024. Available from: FDA Drug Label.
- Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH). N Engl J Med. 1995;332(20):1317–1322. doi:10.1056/NEJM199505183322001.
- Wang WC, Ware RE, Miller ST, et al. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet. 2011;377(9778):1663–1672. doi:10.1016/S0140-6736(11)60355-3.
- Ware RE, Davis BR, Schultz WH, et al. Hydroxycarbamide versus chronic transfusion for maintenance of transcranial Doppler flow velocities in children with sickle cell anaemia (TWiTCH). Lancet. 2016;387(10019):661–670. doi:10.1016/S0140-6736(15)01041-7.
- Brandow AM, Carroll CP, Creary S, et al. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain. Blood Advances. 2020;4(12):2656–2701.
- Yawn BP, Buchanan GR, Afenyi-Annan AN, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014;312(10):1033–1048. doi:10.1001/jama.2014.10517.
- Voskaridou E, Christoulas D, Bilalis A, et al. The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: results of a 17-year, single-center trial (LaSHS). Blood. 2010;115(12):2354–2363. doi:10.1182/blood-2009-05-221333.
- Tshilolo L, Tomlinson G, Williams TN, et al. Hydroxyurea for children with sickle cell anemia in sub-Saharan Africa (REACH). N Engl J Med. 2019;380(2):121–131. doi:10.1056/NEJMoa1813598.
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List. Geneva: WHO; 2023.
- National Heart, Lung, and Blood Institute (NHLBI). Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, Updated 2023.
- British Society for Haematology. Guidelines on the use of hydroxycarbamide in children and adults with sickle cell disease. Br J Haematol. 2018;183(2):179–199.
Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians with expertise in hematology, pediatric hematology, and clinical pharmacology.
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