SIKLOS Dosage & Rx Info | Uses, Side Effects

Siklos Generic Name & Formulations

Legal Class

General Description

Hydroxyurea 100mg, 1000mg; scored tabs.

Pharmacological Class

Antimetabolite.

How Supplied

Tabs 100mg—60; 1000mg—30

Manufacturer

Medunik USA Inc.

Generic Availability

Mechanism of Action

The mechanisms by which Siklos produces its beneficial effects in patients with sickle cell anemia (SCA) are uncertain. The 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.

Siklos Indications

Indications

To reduce the frequency of painful crises and to reduce the need for blood transfusions in patients with sickle cell anemia with recurrent moderate to severe painful crises.

Siklos Dosage and Administration

Adult

Base dose on ideal or actual weight, whichever is less. If difficulty swallowing, may disperse tab in teaspoonful of water immediately before use. >18yrs: initially 15mg/kg/day as a single dose. May increase dose by 5mg/kg/day every 8 weeks or if painful crisis occurs; give until mild myelosuppression (ANC 2000–4000/uL) is achieved, up to max 35mg/kg/day; increase dose only if blood counts are in an acceptable range; do not increase if myelosuppression occurs. Discontinue until hematologic recovery if blood counts are considered toxic; see full labeling for dosage adjustments. Renal impairment (CrCl <60mL/min or ESRD): initially 7.5mg/kg/day; give dose following dialysis (monitor).

Children

<2yrs: not established. Base dose on ideal or actual weight, whichever is less. If difficulty swallowing, may disperse tab in teaspoonful of water immediately before use. ≥2–18yrs: initially 20mg/kg/day as a single dose. May increase dose by 5mg/kg/day every 8 weeks or if painful crisis occurs; give until mild myelosuppression (ANC 2000–4000/uL) is achieved, up to max 35mg/kg/day; increase dose only if blood counts are in an acceptable range; do not increase if myelosuppression occurs. Discontinue until hematologic recovery if blood counts are considered toxic; see full labeling for dosage adjustments. Renal impairment (CrCl <60mL/min or ESRD): initially 10mg/kg/day; give dose following dialysis (monitor).

Siklos Contraindications

Not Applicable

Siklos Boxed Warnings

Boxed Warning

Myelosuppression. Malignancies.

Siklos Warnings/Precautions

Warnings/Precautions

Risk of severe myelosuppression. Monitor blood counts at baseline and every 2 weeks during therapy; interrupt or reduce dose if necessary; resume at lower dose. Markedly depressed bone marrow function: do not initiate. Monitor for secondary malignancies (eg, leukemia, skin cancer). Avoid sun exposure. Macrocytosis may mask folic acid deficiency; prophylactic folic acid is recommended. Myeloproliferative disorders; reduce dose or discontinue if cutaneous vasculitic ulcerations occur. Avoid in those with leg ulcers. Evaluate for hemolysis if acute jaundice or hematuria develops in the presence of anemia. Obtain fetal hemoglobin (HbF) levels every 3–4 months; may be used to assess efficacy. Renal or hepatic impairment: monitor closely. Embryo-fetal toxicity. Pregnancy: exclude status prior to initiation. Advise females with reproductive potential and males (w. female partners) to use effective contraception during and for ≥6 months after therapy. Nursing mothers: not recommended.

Siklos Pharmacokinetics

Absorption

Peak plasma concentrations reached: 1–4 hours. Oral bioavailability: 85–100%.

Distribution

Hydroxyurea distributes throughout the body with a volume of distribution approximating total body water. Hydroxyurea concentrates in leukocytes and erythrocytes.

Metabolism

Hepatic.

Elimination

Renal (~40%). Half-life: 2–4 hours.

Siklos Interactions

Interactions

Avoid concomitant didanosine, with or without stavudine, or other antiretrovirals (may cause pancreatitis [permanently discontinue if occurs], fatal hepatotoxicity, peripheral neuropathy). Avoid live vaccines. Increased risk of vasculitic toxicities with interferon therapy. May cause falsely elevated results in urea, uric acid, and lactic acid assays. May falsely elevate sensor glucose results from certain continuous glucose monitoring (CGM) systems leading to hypoglycemia, if results are relied upon to dose insulin.

Siklos Adverse Reactions

Adverse Reactions

Infections, leukopenia, thrombocytopenia, anemia, neutropenia, skin and subcutaneous disorders, GI upset, headache, fever; secondary malignancies, vasculitic toxicities, macrocytosis, hemolytic anemia.

Siklos Clinical Trials

See Literature

Siklos Note

Notes

Wear disposable gloves when handling tabs or bottle.

Siklos Patient Counseling