Side Effects of Hydrea (hydroxyurea)

Hydrea (hydroxyurea) is a cancer drug used to treat several types of cancers including chronic myelogenous leukemia (CML), acute myelogenous leukemia (AML), head and neck cancer, malignant melanoma, ovarian cancer, and polycythemia vera (a disorder of the bone marrow).

The exact mechanism by which Hydrea works to treat cancer is not understood. It is thought that Hydrea causes an immediate inhibition of DNA synthesis by inhibiting an enzyme called ribonucleotide reductase. Interrupting DNA synthesis reduces the growth of cancer cells.

In addition to treating cancer, Droxia, another oral form of hydroxyurea is used in the management of sickle cell disease. The exact mechanism by which hydroxyurea works to treat sickle cell disease is not understood.

Common side effects of Hydrea include

• loss of appetite,
• nausea,
• vomiting,
• diarrhea,
• constipation,
• sores in the mouth,
• skin rash,
• swelling in the hands, feet, legs and face,
• changes in skin pigmentation,
• hair loss,
• painful urination,
• drowsiness,
• headache, and
• dizziness.

Serious side effects of Hydrea include

• bone marrow suppression (drop in white blood cell, red blood cell and platelet counts),
• disorientation,
• hallucinations,
• seizures,
• liver problems,
• shortness of breath,
• metabolic disturbances, and
• kidney problems.

Drug interactions of Hydrea include live vaccines because cancer drugs weaken the immune system. People with weakened immune systems have a decreased response to vaccines.

• Hydrea may cause a drop in platelet counts, an important type of blood cells required for forming blood clots. Use of Hydrea with anticoagulants, nonsteroidal anti-inflammatory drugs (NSAIDs), antiplatelets, and thrombolytic agents increases the risk of bleeding.
• Antineoplastic agents exert their benefits by killing rapidly growing cancer cells. Use of medications that stimulate cell growth is usually not recommended in patients who have been exposed to cytotoxic chemotherapy within 24 hours. Specifically, the manufacturer of pegfilgrastim recommends that pegfilgrastim should not be administered to patients who have been treated with cytotoxic chemotherapy within the prior 14 days. Also, chemotherapy should not be administered within 24 hours of pegfilgrastim.
• Hydrea may increase blood uric acid concentration. Hydrea should be used cautiously with uricosuric medications.
• Use of Hydrea with didanosine, with or without stavudine, has been associated with an increased incidence of side effects including pancreatitis and peripheral neuropathy (nerve problems).
• In general, Hydrea is not recommended in HIV patients as decreased CD4 counts, decreased viral suppression, and increased risk of side effects has been reported.

Hydrea may harm a fetus and should not be used during pregnancy. Hydrea is secreted in breast milk. Breastfeeding should be stopped due to the potential for serious adverse reactions in the infant.

Known side effects include:

• bone marrow suppression (drop in white blood cell, red blood cell and platelet counts),
• anorexia,
• nausea,
• vomiting,
• diarrhea,
• constipation,
• sores in the mouth,
• skin rash,
• swelling in the hands, feet, legs and face,
• changes in skin pigmentation,
• hair loss,
• painful urination,
• drowsiness,
• headache,
• dizziness,
• disorientation,
• hallucinations,
• seizures,
• liver problems,
• shortness of breath,
• metabolic disturbances, and
• kidney problems. 

The following adverse reactions are described in detail in other labeling sections:

• Myelosuppression
• Malignancies
• Embryo-fetal toxicity
• Vasculitic toxicities
• Risks with concomitant use of antiretroviral drugs
• Radiation recall
• Macrocytosis

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Hydrea. 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, tumor lysis syndrome
• Skin and subcutaneous tissue disorders: maculopapular rash, skin ulceration, dermatomyositis-like skin changes, peripheral and facial erythema, 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

Adverse reactions observed with combined hydroxyurea and irradiation therapy are similar to those reported with the use of hydroxyurea or radiation treatment alone. These effects primarily include

• bone marrow depression (anemia and leukopenia),
• gastric irritation, and
• mucositis.

Almost all patients receiving an adequate course of combined hydroxyurea and irradiation therapy will demonstrate concurrent leukopenia. Platelet depression ( < 100,000 cells/mm³) has occurred in the presence of marked leukopenia. Hydrea may potentiate some adverse reactions usually seen with irradiation alone, such as gastric distress and mucositis.

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 hydroxyurea 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.

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.