Frequently
Asked
Questions

about Siklos®

Common questions about Siklos®

Siklos® is an antimetabolite, indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in adults and pediatric patients, 2 years of age and older, with sickle cell anemia with recurrent moderate to severe painful crises.

Yes. Siklos® received FDA approval in December 2017.

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). Please see Clinical Trial Experience. 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.

The safety and effectiveness of Siklos has been established in the adult population with sickle cell anemia with recurrent moderate to severe painful crises. Use of Siklos is supported by evident from a non-interventional cohort study, the European Sickle Cell Disease prospective Cohort Study, ESCORT-HU, in which 1,077 adult patients were enrolled. Please see Clinical Trial Experience.

Among the adult patients, the most common adverse reactions to Siklos were infections, headache, and dry skin.

Siklos® dosing is based on patient’s actual or ideal weight, whichever is less. Specific parameters (blood counts) must be monitored throughout treatment with Siklos® and dosing must be adjusted accordingly. Complete dosing recommendations based on blood count are available in the Prescribing Information.

Siklos® 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. Important: Siklos® is a cytotoxic drug. Therefore, parents/caregivers must be instructed to follow applicable special handling and disposal procedures provided in the Instructions for Use.

Patient blood counts must be monitored throughout treatment with Siklos® so that dosing can be adjusted accordingly. Complete dosing recommendations based on blood count are available in the Full Prescribing Information.

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:

Siklos® may be prescribed in the usual manner, through retail pharmacies. There are also three convenient ways to prescribe Siklos® through the Siklos At Home® program: e-Prescribe, by fax, by phone.

Patients with commercial insurance have two options that could allow them to pay as little as $0 for their Siklos® prescription:

Option 1: If they wish to fill the prescription at a local retail pharmacy, e-prescribe or instruct them to bring the prescription to a retail pharmacy, where savings will be applied automatically through the Siklos® eVoucher program – no coupon necessary.

Option 2: If they wish to fill the prescription through a mail order pharmacy, simply prescribe Siklos® through the Siklos At Home® program by phone, fax, or ePrescribe using this Siklos At Home™ Order Form

The Siklos At Home® program offers the convenience of free home delivery (minimum purchase of $99 required), on-staff pharmacists to answer patients’ product questions, assistance with prior authorizations and monthly refill reminders.

Questions? Call 1-844-716-HOME (4663)

For patients with no commercial insurance or whose insurance does not cover Siklos®

Cash payers could pay as little as:

  • Siklos® 100 mg tablets: $99 for 60 tablets or $149 for 90 tablets
  • Siklos® 1,000 mg tablets: $16.50/tablet

Medunik USA believes that every patient with sickle cell disease has the right to access safe and effective medication. We understand that the cost of prescription medications can present a challenge. That is why we created our Patient Assistance Program. If you have patients who cannot afford their Siklos® prescription, they may be eligible to receive Siklos® at no charge through our Patient Assistance Program. Please use this Enrollment Application to apply on behalf of your patient.

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.