What is Hydroxyurea Toxicity?
Hydroxyurea is a type of medication used on its own or with other cancer-fighting drugs or radiation in treating stubborn forms of leukemia, a type of blood cancer, and cancers of the head and neck. This medication can also help to increase the amount of fetal hemoglobin in the blood. Hemoglobin is the part of the red blood cell that carries oxygen. By increasing the amount of this good type of hemoglobin, it can lower the number of severe health crises and the need for blood transfusions in patients with sickle cell anemia, a condition that causes misshaped red blood cells.
Even though it’s not officially approved for these uses, doctors also sometimes use hydroxyurea to treat a variety of other health conditions. These include polycythemia vera, a slow-growing blood cancer, essential thrombocythemia, a rare condition that leads to blood clots, psoriasis, a skin condition, acute myeloid leukemia, another type of blood cancer, meningioma, a type of brain tumor, melanoma, a serious skin cancer, and ovarian cancer.
What Causes Hydroxyurea Toxicity?
Hydroxyurea is a medication that is highly potent and can be harmful in small amounts.
This drug works by blocking the making of DNA, a vital part of cell growth. However, this can cause some serious side effects, including myelosuppression, which means it can decrease the ability of your bone marrow to produce blood cells.
Additionally, stopping DNA production without impacting RNA, the molecules responsible for protein building and coding, may cause red blood cells to become large and abnormal, a condition known as megaloblastic anemia.
Risk Factors and Frequency for Hydroxyurea Toxicity
There are a few documented cases of hydroxyurea overdose. One instance involved a 2-year-old child who accidentally overdosed. This led to a mild decrease in the production of blood cells, a condition referred to as myelosuppression. Despite this, after an 8-hour observation period in the emergency room, the child was sent home. The doctors continued to monitor the child’s blood counts for two weeks as an outpatient treatment.
In another case, a woman experienced symptoms such as restlessness, sudden jerky muscle movements, rotating eyeballs, rapid heart rate, and myelosuppression after taking 60 grams of hydroxyurea.
Beyond these individual cases, a report also highlighted acute skin and mucosal toxicity in three patients with advanced acute myelogenous leukemia. These patients, who were treated with oral high doses of hydroxyurea (10 grams for 8 to 10 days), wound up developing severe stomatitis, a painful condition characterized by inflammation and soreness in the mouth.
- Of these three patients, two also developed acute skin toxicity manifested through symptoms such as discomfort, deep red skin inflammation, swelling of palms and soles, which was followed by a significant darkening of the skin color.
Signs and Symptoms of Hydroxyurea Toxicity
Hydroxyurea is a medication used commonly in the treatment of certain blood disorders. However, it comes with various side effects that can affect different parts of the body.
In the area of Hematology-Oncology, side effects include bone marrow suppression leading to symptoms such as anemia, leukopenia, and thrombocytopenia. This can be managed by temporarily stopping the medication. It may cause an increase in the size of red blood cells, which can be confused with a type of anemia. There are also risks of developing secondary leukemias and skin cancer with long-term use.
Gastrointestinal side effects include stomach upset, gastritis, mucositis, and oral ulcers. This medication can also affect the liver, sometimes causing fatal liver failure especially in patients with HIV who are on certain antiretroviral medications. It can also lead to pancreatitis in patients with HIV.
When it comes to Dermatology, long-term use of hydroxyurea can cause painful skin ulcers and other skin reactions. There’s even a possibility of gangrene in toes and fingers. If such skin effects are observed, it’s recommended to stop the medication.
In terms of Reproductive health, the drug can decrease sperm count and motility in men and is not recommended during pregnancy or breastfeeding.
Pulmonary effects of this drug include potentially severe interstitial pneumonitis, which can progress to lung fibrosis and respiratory failure if undiagnosed. Again, it’s advised to discontinue the medication if such symptoms are noted.
In Cardiology, there have been a few cases of patients having a heart attack while on treatment, although the reason for this occurrence is unclear.
The Neurological side effects are rare but may include headaches, dizziness, disorientation, hallucinations, and seizures.
Testing for Hydroxyurea Toxicity
If you’re taking hydroxyurea, which is a common medication, your doctor will want to keep an eye on your electrolytes and kidney health. This is especially important if you’re dealing with severe issues like nausea, vomiting and diarrhea.
For patients experiencing myelosuppression, which is a condition where your bone marrow doesn’t make enough blood cells, it’s crucial to watch out for signs of infection. Your doctor will also regularly check your complete blood count (or CBC, which measures the amount of different types of cells in your blood) as well as your platelet levels, which are needed for your blood to clot properly.
Treatment Options for Hydroxyurea Toxicity
If a person has taken an overdose of a particular substance, the first responders or pre-hospital staff aren’t advised to try to cleanse their stomach. However, if the overdose is recent, and the person is conscious, not throwing up, and able to breathe properly, a substance called activated charcoal may be given. This substance can help to absorb the overdosed substance and prevent it from causing harm.
If the patient is struggling to breathe, a procedure called intubation may be required. This involves inserting a tube into the windpipe (trachea) to maintain an open airway and help the patient to breathe.
The treatment for an overdose mainly involves managing the symptoms and providing necessary support. This can include hydration and medications for nausea and vomiting, including a class of medications called antiemetics.
If a person’s blood cell count has been affected (a condition called myelosuppression), specific treatments may be needed. For instance, if their immune cells (neutrophils) are low, a therapy called colony-stimulating factors can be given. If their platelets are low (platelets help the blood clot), they may need a platelet transfusion. If they are anemic (low red blood cell count), they may require a transfusion of red blood cells.
If seizures occur, these will be treated using anti-seizure (antiepileptic) medications.
If the lining of the patient’s mouth becomes inflamed (mucositis), treatment will depend on the severity of the condition. For mild cases, rinsing the mouth with a mild, unflavored solution (such as saline or baking soda in water) can help. If the inflammation is moderate and causing pain, a local anesthesia may be applied to help relieve the discomfort. In more severe cases, painkillers and oral antimicrobial mouthwashes to reduce the risk of infection may be needed.
What else can Hydroxyurea Toxicity be?
When combined with other cancer drugs, hydroxyurea could cause myelosuppression (a decrease in blood cell production) and stomach and intestinal side effects.
