Droxia Drug Information
Generic name: HYDROXYUREA
Antimetabolite [EPC]
Uses of Droxia
is indicated 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. DROXIA is an antimetabolite indicated 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.
Dosage & Administration of Droxia
| 15 mg/kg/day as a single dose once daily based on the patient's actual or ideal weight, whichever is less. | |
| In an acceptable range | Increase dose 5 mg/kg/day every 12 weeks Maximal dose: 35 mg/kg/day |
| Between acceptable and toxic range | Do not increase dose. |
| Reduce dose by 2.5 mg/kg/day. | |
Side Effects of Droxia
Clinical Trial Experience
In 299 patients treated for sickle cell anemia in the Multicenter Study of Hydroxyurea in Sickle Cell Anemia, the most common adverse reactions were hematologic, with neutropenia, and low reticulocyte and platelet levels necessitating temporary cessation in almost all patients. Hematologic recovery usually occurred in two weeks. Other adverse reactions include hair loss, macrocytosis, bleeding, and melanonychia.
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of hydroxyurea in the treatment of neoplastic diseases. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency. Reproductive System and Breast disorders : azoospermia, and oligospermia Gastrointestinal disorders : stomatitis, nausea, vomiting, diarrhea, and constipation Metabolism and Nutrition disorders : anorexia Skin and subcutaneous tissue disorders: maculopapular rash, skin ulceration, cutaneous lupus erythematosus, dermatomyositis-like skin changes, peripheral and facial erythema, hyperpigmentation, nail hyperpigmentation, atrophy of skin and nails, scaling, violet papules, and alopecia Renal and urinary disorders: dysuria, elevations in serum uric acid, blood urea nitrogen (BUN), and creatinine levels Nervous system disorders: headache, dizziness, drowsiness, disorientation, hallucinations, and convulsions General disorders: fever, chills, malaise, edema, and asthenia Hepatobiliary disorders: elevation of hepatic enzymes, cholestasis, and hepatitis Respiratory disorders: diffuse pulmonary infiltrates, dyspnea, and pulmonary fibrosis, interstitial lung disease, pneumonitis, alveolitis, allergic alveolitis and cough Immune disorders: systemic lupus erythematosus Hypersensitivity: Drug-induced fever (pyrexia) (>39°C, >102°F) requiring hospitalization has been reported concurrently with gastrointestinal, pulmonary, musculoskeletal, hepatobiliary, dermatological or cardiovascular manifestations.
Onset typically occurred within 6 weeks of initiation and resolved upon discontinuation of hydroxyurea. Upon re-administration fever re-occurred typically within 24 hours. Blood and lymphatic system disorders: hemolytic anemia
Warnings & Cautions for Droxia
Myelosuppression Hydroxyurea causes severe myelosuppression. Treatment with
DROXIA 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 interrupted.
Hemolytic Anemia Cases of hemolytic anemia in patients treated with hydroxyurea for
myeloproliferative diseases have been reported . Patients who develop acute jaundice or hematuria in the presence of persistent or worsening of anemia should have laboratory tests evaluated for hemolysis (e.g., measurement of serum lactate dehydrogenase, haptoglobin, reticulocyte, unconjugated bilirubin levels, urinalysis, and direct and indirect antiglobulin tests). In the setting of confirmed diagnosis of hemolytic anemia and in the absence of other causes, discontinue DROXIA.
Malignancies Hydroxyurea is a human carcinogen.
In patients receiving long-term hydroxyurea for myeloproliferative disorders, secondary leukemia has been reported. Secondary leukemia has also been reported in patients treated with long-term hydroxyurea for sickle cell disease. Leukemia has also been reported in patients with sickle cell disease and no prior history of treatment with hydroxyurea.
All patients using DROXIA should be followed up on a long-term basis with regular blood counts to detect development of leukemia. 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.
Embryo-Fetal Toxicity
Based on the mechanism of action and findings in animals, DROXIA can cause fetal harm when 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 . 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 .
Vasculitic Toxicities 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 discontinue DROXIA.
Live Vaccinations
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 .
Macrocytosis
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 B 12 or folic acid deficiency. This may mask the diagnosis of pernicious anemia.
Prophylactic administration of folic acid is recommended.
Pulmonary Toxicity Interstitial lung disease including pulmonary fibrosis, lung infiltration, pneumonitis, and
alveolitis/allergic alveolitis (including fatal cases) have been reported in patients treated for myeloproliferative neoplasm. Safety and effectiveness have not been established for the use of DROXIA in the treatment of myeloproliferative neoplasms and the use is not approved by the FDA. Monitor patients developing pyrexia, cough, dyspnea, or other respiratory symptoms frequently, investigate and treat promptly. Discontinue DROXIA and manage with corticosteroids. . 5.10 Laboratory Test Interference Interference with Uric Acid, Urea, or Lactic Acid Assays is possible, rendering falsely elevated results of these in patients treated with hydroxyurea . Hydroxyurea may falsely elevate sensor glucose results from certain continuous glucose monitoring (CGM) systems and may lead to hypoglycemia if sensor glucose results are relied upon to dose insulin.
If a patient using a CGM is to be prescribed hydroxyurea, consult with the CGM prescriber about alternative glucose monitoring methods .
Drug Interactions with Droxia
Increased Toxicity with
Concomitant Use of Antiretroviral Drugs Pancreatitis In patients with HIV infection during therapy with hydroxyurea and didanosine, with or without stavudine, fatal and nonfatal pancreatitis have occurred. Hydroxyurea is not indicated for the treatment of HIV infection; however, if patients with HIV infection are treated with hydroxyurea, and in particular, in combination with didanosine and/or stavudine, close monitoring for signs and symptoms of pancreatitis is recommended. Permanently discontinue therapy with DROXIA in patients who develop signs and symptoms of pancreatitis.
Hepatotoxicity Hepatotoxicity and hepatic failure resulting in death have been reported during postmarketing surveillance in patients with HIV infection treated with hydroxyurea and other antiretroviral drugs. Fatal hepatic events were reported most often in patients treated with the combination of hydroxyurea, didanosine, and stavudine. Avoid this combination.
Peripheral Neuropathy Peripheral neuropathy, which was severe in some cases, has been reported in patients with HIV infection receiving hydroxyurea in combination with antiretroviral drugs, including didanosine, with or without stavudine.
Laboratory Test Interference Interference with Uric Acid, Urea, or Lactic Acid Assays
Studies have shown that there is an analytical interference of hydroxyurea with the enzymes (urease, uricase, and lactate dehydrogenase) used in the determination of urea, uric acid, and lactic acid, rendering falsely elevated results of these in patients treated with hydroxyurea. Interference with Continuous Glucose Monitoring Systems Hydroxyurea may falsely elevate sensor glucose results from certain continuous glucose monitoring (CGM) systems and may lead to hypoglycemia if sensor glucose results are relied upon to dose insulin. If a patient using a CGM is to be prescribed hydroxyurea, consult with the CGM prescriber about alternative glucose monitoring methods.
Pregnancy Safety for Droxia
Pregnancy Risk Summary DROXIA can cause fetal harm based on findings from animal studies and the drug's mechanism of action . 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/m 2 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. Data 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/m 2 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/m 2 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/m 2 basis) to rats caused growth retardation and impaired learning ability.
Pediatric Use of Droxia
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Contraindications for Droxia
is contraindicated in patients who have demonstrated a previous hypersensitivity to hydroxyurea or any other component of its formulation. In patients who have demonstrated a previous hypersensitivity to hydroxyurea or any other component of its formulation.
Overdosage Information for Droxia
Acute mucocutaneous toxicity has been reported in patients receiving hydroxyurea at dosages several times the therapeutic dose. Soreness, violet erythema, edema on palms and soles followed by scaling of hands and feet, severe generalized hyperpigmentation of the skin, and stomatitis have been observed.
Clinical Studies of Droxia
The efficacy of DROXIA in sickle cell anemia was assessed in a large clinical study (Multicenter Study of Hydroxyurea in Sickle Cell Anemia) (see Table 2 ). The study was a randomized, double-blind, placebo-controlled trial that evaluated 299 adult patients (≥18 years) with moderate to severe disease (≥3 painful crises yearly). The trial was stopped by the Data Safety Monitoring Committee, after accrual was completed but before the scheduled 24 months of follow-up was completed in all patients, based on observations of fewer painful crises among patients receiving hydroxyurea. Compared to placebo treatment, treatment with hydroxyurea resulted in a significant decrease in the yearly rate of painful crises, the yearly rate of painful crises requiring hospitalization, the incidence of chest syndrome, the number of patients transfused, and units of blood transfused. Hydroxyurea treatment significantly increased the median time to both first and second painful crises.
Although patients with 3 or more painful crises during the preceding 12 months were eligible for the study, most of the benefit in crisis reduction was seen in the patients with 6 or more painful crises during the preceding 12 months. Table 2: Results from the Multicenter Study of Hydroxyurea in Sickle Cell Anemia Event Hydroxyurea (N=152) Placebo (N=147) Percent Change Versus Placebo P-value Median yearly rate of painful crises A painful crisis was defined in the study as acute sickling-related pain that resulted in a visit to a medical facility, that lasted more than 4 hours, and that required treatment with a parenteral narcotic or NSAID. Chest syndrome, priapism, and hepatic sequestration were also included in this definition. In patients with SCA treated with hydroxyurea, fetal hemoglobin (HbF) increases 4 to 12 weeks after initiation of treatment.
In general, average HbF levels correlate with dose and plasma level with possible plateauing at higher dosages. A clear relation between reduction in crisis frequency and increased HbF or F-cell levels has not been demonstrated. The dose-related cytoreductive effects of hydroxyurea, particularly on neutrophils, was the factor most strongly correlated with reduced crisis frequency. 2.5 4.6 −46 =0.001 Median yearly rate of painful crises requiring hospitalization 1.0 2.5 −60 =0.0027 Median time to first painful crisis (months) 2.76 1.35 +104 =0.014 Median time to second painful crisis (months) 6.58 4.13 +59 =0.0024 Incidence of chest syndrome (# episodes) 56 101 −45 =0.003 Number of patients transfused 55 79 −30 =0.002 Number of units of blood transfused 423 670 −37 =0.003
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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