Medications for Sickle Cell Disease

Editor’s note: As of September 2024, Oxbryta^® (voxelotor) has been voluntarily withdrawn from the market by the manufacturer due to safety concerns. Pfizer, the manufacturer of Oxbryta, has also ceased distribution and discontinued all active clinical trials and expanded access programs for Oxbryta. Patients and caregivers should contact their healthcare provider about stopping Oxbryta and starting another approved medication for the treatment of sickle cell disease.

Several medicines have been approved by the US Food and Drug Administration (FDA) to treat sickle cell disease (SCD). Hydroxyurea was the only medicine available until 2017, and it is still the most commonly used and studied treatment for sickle cell disease. Other medicines for SCD include:^1,2

• Endari™ (L-glutamine)
• Adakveo^® (crizanlizumab-tmca)

Like hydroxyurea, Endari and Adakveo reduce the frequency of pain crises. These medicines can be used alone or with hydroxyurea. Another common treatment is folic acid, either in foods or as a supplement. Many doctors recommend daily folic acid supplements to treat anemia.^1,2

Hydroxyurea

Hydroxyurea has been used to treat SCD since the 1980s. The FDA approved it to treat adults with SCD in 1998 and to treat children with SCD in 2017. It is also used to treat some forms of cancer. However, doctors use a lower dose to treat SCD.¹

Hydroxyurea helps reduce sickling of red blood cells, mostly by increasing your fetal hemoglobin levels. Fetal hemoglobin protects newborns from the effects of sickle hemoglobin. As people age, the amount of fetal hemoglobin decreases and complications begin. Increasing fetal hemoglobin levels reduces clumping of sickle hemoglobin and helps keep your red blood cells round and flexible.^2,3

Hydroxyurea reduces many problems caused by SCD. For example, people with SCD who take hydroxyurea have fewer:^2-4

• Pain crises
• Acute chest syndrome episodes
• Blood transfusions
• Hospital stays

Access and cost limit hydroxyurea use for many people, especially in lower-resource areas.

Like other drugs, hydroxyurea has risks. There have been reports of skin complications during long-term therapy. Some of these complications are serious. Though rare, hydroxyurea has been linked to cases of skin cancer with long-term use.^1,4-8

Other serious complications of hydroxyurea include bone marrow suppression. This is when fewer blood cells are made in the bone marrow. Bone marrow is the spongy middle part of the long bones in the body and is where most of the body’s blood cells are made. Bone marrow suppression is common in drugs that treat cancer, like hydroxyurea. This may include:^1,4-8

• Anemia – decreased oxygen-carrying red blood cells
• Neutropenia – decreased white blood cells that help fight infection
• Thrombocytopenia – decreased platelets that help stop bleeding
• Pancytopenia – a general decrease in all of these types of blood cells

Hydroxyurea can harm an unborn baby. If you or your partner can become pregnant, you should use birth control during treatment and for some time after the last dose of hydroxyurea. You should also not breastfeed during treatment with hydroxyurea and for some time after the last dose. Talk to your doctor about your options for birth control and breastfeeding while taking hydroxyurea.^1,4-8

Endari

Endari was the first treatment approved for children with SCD and the first new treatment for adults in nearly 20 years. Endari was approved in 2017 to treat SCD in people 5 years of age and older.⁹

Endari contains an amino acid called glutamine. When glutamine circulates in the blood, it gets taken up by sickle cells and produces antioxidants. Antioxidants help neutralize toxic chemicals that cause red blood cells to become rigid and sickle-shaped. This helps sickle cells regain flexibility and flow better through blood vessels.^9,10

Endari reduces the number of pain crises. People who take Endari also have fewer and shorter hospital stays. The twice-daily powder form may be more challenging than the once-daily hydroxyurea tablets. However, it is a non-chemotherapeutic option with minimal side effects.^9,10

Adakveo

The FDA approved Adakveo in 2019 to treat SCD in people 16 years of age and older. Adakveo contains an antibody (a protein designed to bind to a specific molecule in the body). Adakveo binds to P-selectin, which is a protein on cells that line blood vessel walls. P-selectin sticks sickle cells to blood vessel walls. P-selectin can also be found on platelets, and it can also cause platelets, white blood cells, and red blood cells to stick together.^4,11

Adakveo blocks P-selectin to prevent sickle cells from sticking to blood vessel walls. This helps maintain normal blood flow and reduce pain. It reduces the frequency of acute episodes and the length of hospital stays.¹¹

Adakveo is given by infusion into the bloodstream. Possible side effects include joint pain, diarrhea, and itching. Ongoing clinical trials are evaluating the success of Adakveo to treat children and specific complications.¹¹

Folic acid

Folate is a vitamin that bone marrow needs to make new red blood cells. Folate deficiency can lead to anemia. Our bodies do not make folate, so we must get it from food. Many foods have folate, including vegetables, fruit, and nuts.¹²

Folic acid can be used as a dietary supplement because it is converted into folate by the body. People with SCD often have low levels of folate because of the high turnover of red blood cells. Folic acid supplements can increase hemoglobin levels and red blood cell count.¹²

There is not much evidence that folic acid reduces symptoms or treats SCD. Many doctors still recommend taking daily supplements because it may prevent worsening anemia from folate deficiency. Talk to your doctor about folic acid and other vitamins, and ask what types of foods to include in your diet.^12-14

Other things to know

All drugs have side effects. Side effects can vary depending on the specific drug you are taking. Talk to your doctor about what to expect when taking a prescription drug for SCD. You also should call your doctor if you have any changes that concern you when taking one of these drugs.

Before beginning treatment for SCD, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs.