SIKLOS- hydroxyurea tablet, film coated

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

hydroxyurea (UNII: X6Q56QN5QC) (hydroxyurea - UNII:X6Q56QN5QC)

Available from:

Medunik

INN (International Name):

hydroxyurea

Composition:

hydroxyurea 100 mg

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

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 contraindicated in: 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/m2 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/m2 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/m2 basis) in rats and at 30 mg/kg/day (about 0.3 times the maximum recommended human daily dose on a mg/m2 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/m2 basis) to rats caused growth retardation and impaired learning ability. Risk Summary It is not known whether SIKLOS is excreted in human milk, the effects of SIKLOS on the breastfed child, or the effects of SIKLOS on milk production. 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. Pregnancy Testing SIKLOS can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Verify the pregnancy status of females of reproductive potential prior to initiating SIKLOS therapy. Contraception Females Advise females of reproductive potential to use effective contraception during and after treatment with SIKLOS for at least 6 months after therapy. Advise females to immediately report pregnancy. Males SIKLOS may damage spermatozoa and testicular tissue, resulting in possible genetic abnormalities. Males with female sexual partners of reproductive potential should use effective contraception during and after treatment with SIKLOS for at least 6 months after therapy [see Nonclinical Toxicology (13.1)] . Infertility Males Based on findings in animals and humans, male fertility may be compromised by treatment with SIKLOS. Azoospermia or oligospermia, sometimes reversible, has been observed in men. Before the start of therapy, inform male patients about the possibility of sperm conservation [see Adverse Reactions (6) and Nonclinical Toxicology (13.1)] . 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. The exposure to SIKLOS is higher in patients with creatinine clearance of less than 60 mL/min. Reduce dosage and closely monitor the hematologic parameters when SIKLOS is to be administered to these patients [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)] . Monitor hematologic parameters more frequently in patients with hepatic impairment receiving SIKLOS. SIKLOS (See – k – los) (hydroxyurea) tablets Read this Instructions for Use before you start taking SIKLOS and each time you get a refill. There may be new information. This Instructions for Use does not take the place of talking to your healthcare provider about your medical condition or treatment. You and your healthcare provider should talk about SIKLOS when you start taking it and at regular checkups. Important Information: - Wash your hands with soap and water before and after handling SIKLOS tablets or bottles containing SIKLOS. - Wear disposable gloves when handling SIKLOS tablets or bottles containing SIKLOS. - Take SIKLOS 1 time a day at the same time each day. - Powder spilled from a broken tablet should be wiped up right away with a damp disposable paper towel and thrown away in a closed container, such as a plastic bag to avoid harm to other people. The spill area should then be cleaned using a detergent solution followed by clean water. - When the tablet is broken, avoid touching the broken surfaces. - If contact with crushed tablets happens on the skin, wash the skin area right away and thoroughly with soap and water. - If contact with crushed tablets happens in the eyes, flush the eyes thoroughly with water or isotonic eyewash used for that purpose for at least 15 minutes. SIKLOS is supplied in 2 different strengths: SIKLOS 100 mg tablet has one separation line (score line) and can be broken at this score line to provide smaller doses. Each 100 mg tablet can be divided into 2 equal parts (each part is 50 mg). SIKLOS 1,000 mg tablet has three separation lines (score lines) and can be broken at these score lines to provide smaller doses. Each 1,000 mg tablet can be divided into 4 equal parts (each part is 250 mg). SIKLOS tablet breaking instructions You will need the following supplies to break a SIKLOS tablet: - SIKLOS tablets - A damp disposable paper towel - A tablet cutter - Disposable gloves - 1/2 of a tablet for a dose of 50 mg of SIKLOS:   1/2 of a tablet for a dose of 50 mg of SIKLOS:   - a whole tablet for a dose of 100 mg of SIKLOS (no breaking needed) :   a whole tablet for a dose of 100 mg of SIKLOS (no breaking needed) :   - 1/4 of a tablet for a dose of 250 mg of SIKLOS:   1/4 of a tablet for a dose of 250 mg of SIKLOS:   - 1/2 of a tablet for a dose of 500 mg of SIKLOS:   1/2 of a tablet for a dose of 500 mg of SIKLOS:   - 3/4 of a tablet for a dose of 750 mg of SIKLOS:   3/4 of a tablet for a dose of 750 mg of SIKLOS:   - a whole tablet for a dose of 1,000 mg of SIKLOS (no breaking needed) :   a whole tablet for a dose of 1,000 mg of SIKLOS (no breaking needed) :   For people who cannot swallow SIKLOS tablets You will need the following supplies to prepare and take your dose by dissolving the tablet: - Your bottle of SIKLOS tablets Note: If you need to break your tablets, use the SIKLOS Tablet Breaking Instructions above to get your prescribed dose before you begin the steps below. - Note: If you need to break your tablets, use the SIKLOS Tablet Breaking Instructions above to get your prescribed dose before you begin the steps below. - A teaspoon - Water to dissolve tablets Storing your SIKLOS tablets: - Store SIKLOS at room temperature between 68°F to 77°F (20°C to 25°C). - Keep the SIKLOS bottle tightly closed. Keep SIKLOS and all medicines out of the reach of children. This Instructions for Use has been approved by the U.S. Food and Drug Administration. Revised 11/2023

Product summary:

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: 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. 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.

Authorization status:

New Drug Application

Patient Information leaflet

Medunik
----------
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 y

Summary of Product characteristics

SIKLOS- HYDROXYUREA TABLET, FILM COATED
MEDUNIK
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
SIKLOS SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR SIKLOS.
SIKLOS (HYDROXYUREA) TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 1967
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)
RECENT MAJOR CHANGES
Warnings and Precautions, Test Interference (5.8)
11/2023
Drug interactions, Test Interference (7.3)
11/2023
INDICATIONS AND USAGE
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
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)
DOSAGE FORMS AND STRENGTHS
Tablets: functionally scored 100 mg and functionally triple-scored
1,000 mg tablet (3)
CONTRAINDICATIONS
Patients who have demonstrated a previous hypersensitivity t