hye-drox-ee-yoor-EE-a

Therapeutic Classification: antineoplastics

Pharmacologic Classification: antimetabolites

Droxia, Siklos, and Xromi:

• • Reduction in frequency of painful crises in sickle cell anemia and decreased need for transfusions in patients with a history of recurrent moderate to severe crises.

Hydrea:

• • Head and neck carcinoma.
  • Resistant chronic myelogenous leukemia.

• Interferes with DNA synthesis (cell-cycle S-phase-specific).
• May alter characteristics of RBCs.

• Decreased frequency of painful crises and decreased need for transfusions in sickle cell anemia.
• Death of rapidly replicating cells, particularly malignant ones.

Absorption: Well absorbed following oral administration.

Distribution: Crosses the blood-brain barrier; concentrates in RBCs and leukocytes.

Metabolism/Excretion: 50% excreted unchanged by the kidneys; 50% metabolized by the liver and eliminated as respiratory CO.

Half-life: 3–4 hr.

(effects on blood counts)

Contraindicated in:

• Hypersensitivity to any component (some products contain tartrazine [FDC yellow dye #5])
• Severe bone marrow depression
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Renal impairment (close monitoring of hematologic parameters recommended; dosage ↓ may be necessary)
• Interferon therapy (may ↑ risk of vasculitic ulcerations and gangrene)
• Active infection
• Previously received radiation or chemotherapy (↑ risk of bone marrow suppression)
• Previously received radiation (↑ risk of postradiation erythema)
• Obese patients or patients with edema (dose should be determined using ideal body weight)
• Women of reproductive potential and men with female partners of reproductive potential
• Pedi: Safety and effectiveness not established in children <6 mo (Xromi), <2 yr (Siklos), or <18 yr (Droxia or Hydrea)
• Geri: Older adults may be more sensitive to effects; lower doses may be required.

Derm: alopecia, cutaneous vasculitis, exacerbation of postradiation erythema, erythema, pruritus, rash.

GU: ↓fertility (males).

Hemat: leukopenia, anemia, hemolytic anemia, macrocytosis, thrombocytopenia.

Metab: hyperuricemia.

Resp: INTERSTITIAL LUNG DISEASE.
Misc: chills, fever, malaise, (INCLUDING LEUKEMIA AND SKIN CANCER)SECONDARY MALIGNANCY .

Drug-Drug:

• Additive bone marrow depression with agents that depress bone marrow, including radiation therapy.
• May ↓ antibody response to and ↑ risk of adverse reactions to live-virus vaccines.

Head and Neck Cancer or Resistant Chronic Myelogenous Leukemia

• PO (Adults): 15 mg/kg/day as a single dose.

Sickle Cell Anemia

• PO (Adults): Droxia: 15 mg/kg once daily; may ↑ by 5 mg/kg/day every 12 wk (max = 35 mg/kg/day). Siklos: 15 mg/kg once daily; may ↑ by 5 mg/kg/day every 8 wk (max = 35 mg/kg/day).
• PO (Children 2 yr): Siklos: 20 mg/kg once daily (based on ideal or actual body weight, whichever is less); may ↑ by 5 mg/kg/day every 8 wk (or if a painful crisis occurs) (max = 35 mg/kg/day).
• PO (Children 6 mo–<2 yr): Xromi: 15 mg/kg (rounded to nearest 10 mg) once daily (based on actual body weight); may ↑ by 5 mg/kg/day every 8–12 wk (max = 35 mg/kg/day).

(Generic available)

• Capsules: 200 mg; 300 mg ; 400 mg; 500 mg;
• Film-coated tablets: 100 mg; 1000 mg;
• Oral solution (Xromi) (strawberry flavor): 100 mg/mL;

• Assess for signs of infection (fever, sore throat, cough, hoarseness, pain in lower back or side, difficult or painful urination). If these symptoms occur, notify health care professional immediately.
• Anemia may occur. Monitor for ↑ fatigue, dyspnea, and orthostatic hypotension.
• Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis). Avoid IM injections and taking rectal temperatures. Hold pressure on all venipuncture sites for at least 10 min.
• Monitor intake and output, appetite, and nutritional intake. Adjust diet as tolerated to maintain nutritional status.
• Monitor for signs and symptoms of cutaneous vasculitis (vasculitic ulcerations, gangrene) during therapy. If signs occur treat vasculitis and discontinue hydroxyurea.
• Monitor for signs and symptoms of pulmonary toxicity (pyrexia, cough, dyspnea, or other respiratory symptoms) frequently; investigate and treat promptly. Discontinue hydroxyurea and manage with corticosteroids.

• Verify negative pregnancy status before starting therapy.
  • Monitor CBC and differential in patients with malignancy prior to and at least weekly during therapy. The onset of leukopenia occurs within 10 days of beginning therapy. Recovery usually occurs within 30 days. Notify health care provider if WBC <2500 mm³ or if a precipitous drop occurs. Institute thrombocytopenia precautions if platelet count <100,000/mm³. May cause temporary ↑ in mean corpuscular volume (MCV).
  • Monitor CBC with differential and platelets in patientswith sickle cell disease every 2 wk. Dose ↑ may be given until mild myelosuppression (ANC 2000 cells/mm³ to 4000 cells/mm³) is achieved, up to a maximum of 35 mg/kg/day. Hydroxyurea should be held if neutrophils <2000 cells/mm³, platelet count <80,000 cells/mm³, Hgb <4.5 g/dL, or reticulocytes <80,000 cells/mm³ (when Hgb <9 g/dL). After hematologic recovery, ↓ dose by 5 mg/kg/day from dose causing toxicity; may titrate up or down 5 mg/kg/day every 8 wk after patient stable with no hematologic toxicity for 24 wk. If hematologic toxicity occurs twice, permanently discontinue hydroxyurea.
  • Monitor renal (BUN, serum creatinine, and uric acid) and liver function tests (AST, ALT, bilirubin, and LDH) prior to and periodically during therapy. May cause ↑ BUN, serum creatinine, and uric acid concentrations.
  • Monitor fetal hemoglobin (HbF) to determine efficacy. Obtain HbF levels every 3–4 mo. Monitor for an ↑ in HbF of at least 2-fold over baseline value.
  • May cause false ↑ in serum uric acid, urea, or lactic acid concentrations.
  • May cause false ↑ in sensor glucose results from certain continuous glucose-monitoring systems and could lead to hypoglycemia if sensor glucose results are used to dose insulin.

• CBC results in an acceptable range for sickle cell diseaseinclude neutrophils 2500 cells/mm³, platelets 95,000 cells/mm³, Hgb >5.3 g/dL and reticulocytes 95,000 cells/mm³ (if Hgb <9 g/dL). Levels are toxic if neutrophils <2000 cells/mm³, platelets <80,000 cells/mm³, Hgb <4.5 g/dL and reticulocytes <80,000 cells/mm³ (if Hgb <9 g/dL).

• Do not confuse Hydrea with Lyrica. Do not confuse hydroxyurea with hydroxychloroquine, hydroxyzine, or Ure-Na (palatable form of oral urea).
• Administer folic acid prophylactically for macrocytosis.
• PO: Administer once daily, at the same time each day, with a glass of water. May be taken with or after meals. For patients who are not able to swallow tablets, Siklos tablets can be dispersed immediately before use in a small quantity of water in a teaspoon. The 100 mg Siklos tablets have 1 score line and can be split into 2 parts (each 50 mg). The 1000 mg Siklostablets have 3 score lines and can be split into 4 parts (each 250 mg).
• DNC: Wear disposable gloves when handling capsules or tablets. Wash hands before and after administering a dose. Do not open capsule; exposure to powder may cause serious skin toxicities. If powder from capsule is spilled, wipe up immediately with damp disposable towel and discard in a closed container, such as a plastic bag. Do not break tablets. Do not shake oral solution.

• Instruct patient to take medication as directed, even if nausea, vomiting, or diarrhea is a problem. Consult health care professional if vomiting occurs shortly after dose is taken. Take missed doses as soon as remembered unless just before next dose. Do not take double doses. Consult health care professional if more than one dose is missed. Do not shake oral solution.
  • Instruct patient to notify health care professional if fever; chills; sore throat; signs of infection; loss of appetite; nausea; vomiting; diarrhea; bleeding gums; bruising; petechiae; blood in urine, stool, or emesis; shortness of breath; or cough occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor. Patients should be cautioned not to drink alcoholic beverages or to take products containing aspirin or NSAIDs.
  • Instruct patient using continuous glucose-monitoring system for their diabetes to use a traditional glucometer to monitor their glucose levels while taking hydroxyurea.
  • Inform patient that long-term use may increase the risk of developing secondary cancer.
  • Instruct patient to inspect oral mucosa for erythema and ulceration. If ulceration occurs, advise patient to use sponge brush and rinse mouth with water after eating and drinking. Consult health care professional if mouth pain interferes with eating. Stomatitis pain may require treatment with opioid analgesics.
  • Discuss possibility of drowsiness with patients receiving large doses. Advise patient to avoid driving or other activities until response to drug is known.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Advise patient to use sunscreen and protective clothing to ↓ risk of skin cancer.
  • Instruct patient not to receive any vaccinations without advice of health care professional.
  • Instruct patient as to appropriate oral syringe to use with oral syringe. The 3-mL oral syringe is for measuring doses of 3 mL or less; the 12-mL oral syringe should be used for measuring doses greater than 3 mL.
  • May cause fetal harm. Advise women of reproductive potential to use effective contraception during and for at least 6 mo after completion of therapy, even if amenorrhea occurs, and to avoid breastfeeding during therapy. Advise males with a female partner of reproductive potential to use effective contraception during and for at least 1 yr after therapy. May cause male infertility.
  • Emphasize need for lab tests and follow-up visits to monitor progress and detect side effects.
• Leukemia: Encourage fluid intake of 2000–3000 mL/day. Allopurinol and alkalinization of urine may be used to help prevent urate stone formation.

• Reduction in frequency of painful crisis of sickle cell anemia.
• Decrease in size and spread of tumors.
• Improved hematologic values in leukemia. Therapy is held if leukocytes <2500 cells/mm³ or platelets <100,000 cells/mm³ and resumed when these values begin to return to normal limits, usually within 3 days.

Droxia, Hydrea, Siklos, Xromi