Included as part of the PRECAUTIONS section.
Hydroxyurea causes severe myelosuppression. Treatment
with hydroxyurea should not be initiated 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 recommended initial dose of
15 mg/kg/day, have experienced severe or life-threatening myelosuppression.
Evaluate hematologic status prior to and during treatment
with DROXIA. Provide supportive care and modify dose or discontinue DROXIA as
needed. Recovery from myelosuppression is usually rapid when therapy is
Hydroxyurea is a human carcinogen. In patients receiving
long-term hydroxyurea for myeloproliferative disorders, secondary leukemia has
been reported. 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.
Based on the mechanism of action and findings in animals,
DROXIA can cause fetal harm whenÂ administered to a pregnant woman. Hydroxyurea
was embryotoxic and teratogenic in rats and rabbits at doses 0.8 times and 0.3
times, respectively, the maximum recommended human daily dose on a mg/m² basis.
Advise pregnant women of the potential risk to a fetus [see Use in Specific
Populations]. Advise females of reproductive potential to use effective
contraception during and after treatment with DROXIA for at least 6 months
after therapy. Advise males of reproductive potential to use effective contraception
during and after treatment with DROXIA for at least 1 year after therapy [see
Use in Specific Populations].
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. If cutaneous vasculitic ulcers occur, institute treatment and
Avoid use of live vaccine in patients taking DROXIA.
Concomitant use of DROXIA with a live virus vaccine may potentiate the
replication of the virus and/or may increase the adverse reaction of the vaccine
because normal defense mechanisms may be suppressed by DROXIA. Vaccination with
live vaccines in a patient receiving DROXIA may result in severe infection.
Patient's antibody response to vaccines may be decreased. Consider consultation
with a specialist.
Risks With Concomitant Use Of Antiretroviral Drugs
Pancreatitis, hepatotoxicity, and peripheral neuropathy
have occurred when hydroxyurea was administered concomitantly with
antiretroviral drugs, including didanosine and stavudine [SEE DRUG INTERACTIONS].
DROXIA 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.
Patient Counseling Information
Advise the patient to read the FDA-approved patient
labeling (PATIENT INFORMATION).
- There is a risk of myelosuppression. Monitoring blood
counts every two weeks throughout the duration of therapy should be emphasized
to patients taking DROXIA [see WARNINGS AND PRECAUTIONS]. Advise
patients to report signs and symptoms of infection or bleeding immediately.
- Advise patients that there is a risk of cutaneous
vasculitic toxicities and secondary malignancies including leukemia and skin
cancers. Advise use of sun protection [see WARNINGS AND PRECAUTIONS].
- Advise patients to inform their healthcare provider if
they have received or are planning to receive vaccinations while taking DROXIA
as this may result in a severe infection [see WARNINGS AND PRECAUTIONS].
- Advise females of reproductive potential of the potential
risk to a fetus and 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 DROXIA [see WARNINGS AND
PRECAUTIONS and Use In Specific Populations].
- Advise females to discontinue breastfeeding during
treatment with DROXIA [see Use in Specific Populations].
- Patients with HIV infection should contact their
physician for signs and symptoms of pancreatitis, hepatic events, and
peripheral neuropathy [see WARNINGS AND PRECAUTIONS].
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Conventional long-term studies to evaluate the
carcinogenic potential of DROXIA have not been performed. However,
intraperitoneal administration of 125 to 250 mg/kg hydroxyurea (about 0.6-1.2 times
the maximum recommended human oral daily dose on a mg/m² basis) thrice weekly
for 6 months to female rats increased the incidence of mammary tumors in rats
surviving to 18 months compared to control. Hydroxyurea is mutagenic in vitro to
bacteria, fungi, protozoa, and mammalian cells. Â Hydroxyurea is clastogenic in
vitro (hamster cells, human lymphoblasts) and in vivo (SCE assay in rodents, mouse
micronucleus assay). Hydroxyurea causes the transformation of rodent embryo
cells to a tumorigenic phenotype.
Hydroxyurea administered to male rats at 60 mg/kg/day
(about 0.3 times the maximum recommended human daily dose on a mg/m² basis)
produced testicular atrophy, decreased spermatogenesis, and significantly
reduced their ability to impregnate females.
Use In Specific Populations
DROXIA can cause fetal harm based on findings from animal
studies and the drug's mechanism of action [see CLINICAL PHARMACOLOGY].
There are no data with DROXIA use in pregnant women to inform a drug-associated
risk. 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 (see Data).
Advise women of the potential risk to a fetus and to
avoid becoming pregnant while being treated with DROXIA.
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.
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/m 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.
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
Females And Males Of Reproductive Potential
Verify the pregnancy status of females of reproductive
potential prior to initiating DROXIA therapy.
DROXIA can cause fetal harm when administered to a
pregnant woman [see Use In Specific Populations]. Advise females of
reproductive potential to use effective contraception during and after treatment
with DROXIA for at least 6 months after therapy. Advise females to immediately
DROXIA 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 DROXIA for at least 1 year after therapy [see Nonclinical
Based on findings in animals and humans, male fertility
may be compromised by treatment with DROXIA. Azoospermia or oligospermia,
sometimes reversible, has been observed in men. Inform male patients about the
possibility of sperm conservation before the start of therapy [see ADVERSE
REACTIONS and Nonclinical Toxicology].
Safety and effectiveness in pediatric patients have not
Clinical studies of DROXIA did not include sufficient
numbers of subjects aged 65 and over to determine whether they respond
differently from younger subjects.
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].
The exposure to hydroxyurea is higher in patients with
creatinine clearance of less than 60 mL/min. Reduce dosage and closely monitor
the hematologic parameters when DROXIA is to be administered to these patients [see
DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].
There are no data that support specific guidance for
dosage adjustment in patients with hepatic impairment. Close monitoring of hematologic
parameters is advised in these patients.