Hydrea - Hydroxyurea capsule

HYDREA is indicated for the treatment of:

• Resistant chronic myeloid leukemia
• Locally advanced squamous cell carcinomas of the head and neck (excluding the lip) in combination with chemoradiation.

HYDREA is indicated for the treatment of:

• •Resistant chronic myeloid leukemia.
• •Locally advanced squamous cell carcinomas of the head and neck (excluding the lip) in combination with chemoradiation.

• Individualize treatment based on tumor type, disease state, response to treatment, patient risk factors, and current clinical practice standards.

  2.1 Dosing Information

  HYDREA is used alone or in conjunction with other antitumor agents or radiation therapy to treat neoplastic diseases. Individualize treatment based on tumor type, disease state, response to treatment, patient risk factors, and current clinical practice standards.

  Base all dosage on the patient's actual or ideal weight, whichever is less.

  HYDREA is a cytotoxic drug. Follow applicable special handling and disposal procedures

  [see References (15)].

  Swallow HYDREA capsules whole. Do NOT open, break, or chew capsules because HYDREA is a cytotoxic drug.

  Prophylactic administration of folic acid is recommended

  [see Warnings and Precautions (5.8)]

  .

  Monitor blood counts at least once a week during HYDREA therapy. Severe anemia must be corrected before initiating therapy with HYDREA.

• Renal impairment: Reduce the dose of HYDREA by 50% in patients with creatinine clearance less than 60 mL/min.

  2.3 Dose Modifications for Renal Impairment

  Reduce the dose of HYDREA by 50% in patients with measured creatinine clearance of less than 60 mL/min or with end-stage renal disease (ESRD) [

  see Use in Specific Populations and Clinical Pharmacology

  ].

  Creatinine Clearance (mL/min)	Recommended HYDREA Initial Dose (mg/kg once daily)
  ≥60	15
  <60 or ESRD*	7.5

  * On dialysis days, administer HYDREA to patients following hemodialysis.

  Close monitoring of hematologic parameters is advised in these patients.
  ,
  8.6 Renal Impairment

  The exposure to hydroxyurea is higher in patients with creatinine clearance of less than 60 mL/min or in patients with end-stage renal disease (ESRD). Reduce dosage and closely monitor the hematologic parameters when HYDREA is to be administered to these patients

  [see Dosage and Administration (2.3)and Clinical Pharmacology (12.3)]

  .
  ,
  12.3 Pharmacokinetics

  Absorption

  Following oral administration of HYDREA, hydroxyurea reaches peak plasma concentrations in 1 to 4 hours. Mean peak plasma concentrations and AUCs increase more than proportionally with increase of dose.

  There are no data on the effect of food on the absorption of hydroxyurea.

  Distribution

  Hydroxyurea distributes throughout the body with a volume of distribution approximating total body water.

  Hydroxyurea concentrates in leukocytes and erythrocytes.

  Metabolism

  Up to 60% of an oral dose undergoes conversion through saturable hepatic metabolism and a minor pathway of degradation by urease found in intestinal bacteria.

  Excretion

  In patients with sickle cell anemia, the mean cumulative urinary recovery of hydroxyurea was about 40% of the administered dose.

  Specific Populations

  Renal Impairment

  The effect of renal impairment on the pharmacokinetics of hydroxyurea was assessed in adult patients with sickle cell disease and renal impairment. Patients with normal renal function (creatinine clearance [CrCl] >80 mL/min), mild (CrCl 50‑80 mL/min), moderate (CrCl = 30-<50 mL/min), or severe (<30 mL/min) renal impairment received a single oral dose of 15 mg/kg hydroxyurea. Patients with ESRD received two doses of 15 mg/kg separated by 7 days; the first was given following a 4-hour hemodialysis session, the second prior to hemodialysis. The exposure to hydroxyurea (mean AUC) in patients with CrCl <60 mL/min and those with ESRD was 64% higher than in patients with normal renal function (CrCl >60 mL/min). Reduce the dose of HYDREA when it is administered to patients with creatinine clearance of <60 mL/min or with ESRD following hemodialysis

  [see

  Dosage and Administration (2.3)

  and Use in Specific Populations (8.6)]

  .

Capsules: 500 mg opaque green cap and opaque pink body imprinted with "HYDREA" and "500".

• Lactation: Advise women not to breastfeed.
  8.2 Lactation

  Risk Summary

  Hydroxyurea is excreted in human milk. Because of the potential for serious adverse reactions in a breastfed infant from hydroxyurea, including carcinogenicity, discontinue breastfeeding during treatment with HYDREA.
• Geriatric Use: Care should be taken in dose selection and may require a lower dose regimen and monitoring of renal function.
  8.5 Geriatric Use

  Elderly patients may be more sensitive to the effects of hydroxyurea and may require a lower dose regimen. Hydroxyurea is excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function

  [see Dosage and Administration (2.3)]

  .