The first and only hydroxyurea-based treatment for BOTH adult and pediatric patients with sickle cell anemia

  • Unique hydroxyurea pediatric indication
  • Body-weight adjusted dosing
  • Dissolvable in water for oral administration
All individuals depicted throughout
website are not actual patients.

What is
Siklos®?

Siklos® is the first and only FDA-approved hydroxyurea-based treatment 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

Impact of
Sickle Cell Disease

Children with sickle cell disease (SCD) are at increased risk of infection and recurrent painful episodes during childhood. These may lead to multi-organ damage, associated with poor prognosis and early mortality.2

Therefore, as recommended by the National Institutes of Health (NIH), it is important to start disease-modifying therapy with hydroxyurea as early as possible.3

Additionally, it is important to continue Hydroxyurea treatment into adulthood in order to reduce the frequency and severity of complications of Sickle Cell Disease.3

Consider Siklos for your appropriate patients!

Why
Siklos®?

  • Siklos® is the first and only hydroxyurea-based sickle cell disease treatment indicated for both adult and pediatric patients..
  • Siklos® has two strengths to help optimize dosing: 100 mg scored tablets and 1,000 mg triple-scored tablets.
  • Siklos® tablets are small* and breakable allowing for dosing adjustments in 50 mg increments.
  • Siklos® has been found to be safe and effective in adults and children aged 2 and older with sickle cell disease with recurrent moderate to severe painful crisis. See Clinical Data.
  • Siklos® tablets may be dissolved in water for those who have trouble swallowing them whole. Please see Instructions for Use.
  • Siklos® can accompany growing patients along their treatment journeys into adulthood.

* can be broken into smaller parts

Prescribing
Siklos®

As the patient grows, Siklos® allows for flexible dosing based on body weight, blood count, and clinical response. Therefore, patient growth and blood counts must be closely monitored throughout treatment and dosage adjusted accordingly.

Learn more about prescribing Siklos®

Siklos® is available in 100 mg scored (2 x 50 mg) tablets and in 1,000 mg triple-scored (4 x 250 mg) tablets to allow dose adjustments in increments as small as 50 mg, based on patient body weight, blood count, and clinical response.

When both strengths of Siklos® (100 mg and 1,000 mg) are prescribed simultaneously, make sure that the patient and/or the parents or caregivers understand the dosing in order to avoid confusion.

Please see Full Prescribing Information, including Boxed Warning regarding myelosuppression and malignancies.

Mechanism
of Action

“Hydroxyurea has many characteristics of an ideal drug for sickle cell anemia (SCA) and provides therapeutic benefit through multiple mechanisms of action”.4

Fetal hemoglobin (HbF) appears to minimize clinical severity of sickle cell disease and low levels of HbF are associated with a higher risk of vaso-occlusive complications, organ damage and early death.5

That is where hydroxyurea comes in. As explained by Dr. Barbara P. Yawn and colleagues6, “Increasing the concentration of fetal hemoglobin is the primary effect of hydroxyurea and provides the greatest benefit to persons with SCD, but other mechanisms of action and benefits exist. For example, hydroxyurea lowers the number of circulating leukocytes and reticulocytes and decreases their expression of adhesion molecules, thus reducing vascular occlusion.

Hydroxyurea also increases red blood cell size and improves cellular deformability, which increases blood flow and reduces vaso-occlusion. In addition, nitric oxide released directly from hydroxyurea metabolism may contribute to local vasodilation.7 Hydroxyurea therapy substantially reduces the frequency of painful episodes and ACS events and the need for erythrocyte transfusions and hospitalizations.8 Long-term hydroxyurea administration results in a reduction in mortality."9-10

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.1

The mechanisms by which Siklos® produces its beneficial effects in patients with sickle cell anemia are uncertain. Known pharmacologic effects of Siklos® that may contribute to its beneficial effects include increasing hemoglobin F levels in red blood cells, decreasing neutrophils, increasing the water content of red blood cells, increasing deformability of sickled cells, and altering the adhesion of red blood cells to endothelium.

Siklos®
News

Stay up to date on Siklos®

Sign up to receive the latest news about Siklos®.

Subscribe now

Siklos®
Savings

Want to help patients pay less for their Siklos® prescription?

Download and print savings options for your patients

Patients having difficulty affording their Siklos® prescription?

Learn more about our Patient Assistance Program

References

  1. Siklos® (hydroxyurea) tablets, for oral use [Prescribing Information]. Addmedica, December 2021.
  2. Ferster, A. et al. Hydroxyurea for treatment of severe sickle cell anemia: a pediatric clinical trial. Blood 88, 1960-1964 (1996).
  3. Yawn BP, John-Sowah, J. Management of Sickle Cell Disease: Recommendations from the 2014 Expert Panel Report. Am Fam Physician. 2015 Dec 15;92(12):1069-76.
  4. Ware, R.E. How I use hydroxyurea to treat young patients with sickle cell anemia. Blood. 2010;115](26):5300-5311.
  5. Leikin SL, Gallagher D, Kinney TR, et al. Mortality in children and adolescents with sickle cell disease: Cooperative Study of Sickle Cell Disease. Pediatrics. 1989;84(3):500-508; Platt OS, Brambilla DJ, Rosse WF, et al. Mortality in sickle cell disease: life expectancy and risk factors for early death. N Engl J Med. 1994;330(23): 1639-1644.
  6. Management of Sickle Cell Disease, Summary of the 2014 Evidence-Based Report by Expert Panel Members. Barbara P. Yawn, MD, MSc, MSPH1; George R. Buchanan, MD2; Araba N. Afenyi-Annan, MD, MPH3; et al. JAMA. 2014;312(10):1033-1048. doi:10.1001/jama.2014.10517.
  7. King SB. Nitric oxide production from hydroxyurea. Free Radic Biol Med. 2004;37(6):737-744.
  8. Charache S, Terrin ML, Moore RD, et al; Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med. 1995;332(20):1317-1322.
  9. Steinberg MH, Barton F, Castro O, et al. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment [published correction appears in JAMA. 2003;290(6):756]. JAMA. 2003;289(13):1645-1651.
  10. 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.

Indication and important safety information

INDICATION

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.

IMPORTANT SAFETY INFORMATION

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.
  • Malignancies: Hydroxyurea is carcinogenic. Advise sun protection and monitor patients for malignancies.

CONTRAINDICATIONS

SIKLOS is contraindicated in patients who have demonstrated a previous hypersensitivity to hydroxyurea or any other component of its formulation.

WARNINGS AND PRECAUTIONS

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.

Interference with Continuous Glucose Monitoring (CGM) Systems is possible, rendering falsely elevated sensor glucose results from certain 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.

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.

ADVERSE REACTIONS

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.

USE IN SPECIFIC POPULATIONS

  • Pregnancy: SIKLOS can cause fetal harm. Advise pregnant women of the potential risk to a fetus.
  • Lactation: Because of the potential for serious adverse reactions in a breastfed child from SIKLOS, including carcinogenicity, advise patients not to breastfeed during treatment with SIKLOS.
  • Females and Males of Reproductive Potential: 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 for at least 6 months after therapy. Based on findings in animals and humans, male fertility may be compromised by treatment with SIKLOS. Prior to therapy, advise male patients about the possibility of sperm conservation.
  • Pediatric Use: 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.
  • Renal Impairment: Reduce dosage and closely monitor the hematologic parameters when SIKLOS is administered to patients with renal impairment – creatinine clearance of less than 60mL/min.
  • Hepatic Impairment: Monitor hematologic parameters more frequently in patients with hepatic impairment receiving SIKLOS.

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 – 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.

Indication and important safety information

INDICATION

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.

WARNING: MYELOSUPPRESION 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.
  • Malignancies: Hydroxyurea is carcinogenic. Advise sun protection and monitor patients for malignancies.

Indication and important safety information

INDICATION

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.

WARNING: MYELOSUPPRESION 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. 
  • Malignancies: Hydroxyurea is carcinogenic. Advise sun protection and monitor patients for malignancies.