Two drugs, voxelotor (Oxbryta) and crizanlizumab-tmca (Adakveo), have been approved by the Food and Drug Administration (FDA) for the treatment of sickle cell disease.
Voxelotor, approved in patients 12 years of age and older, was granted accelerated approval, which allows the FDA to approve drugs before clinical trials have been completed in instances when the drugs are likely to provide a clinical benefit over current therapy. Further clinical trials are required by the FDA to prove the clinical benefit.
Sickle cell disease alters the shape of the hemoglobin molecule, which causes red blood cells to have a curved (or sickled) shape. Sickle cells are not as flexible as normal red blood cells and stick to vessel walls, blocking blood flow and limiting oxygen delivery to the tissues, which cause severe pain. Sickle cells also break apart more easily, leading to anemia. Voxelotor prevents red blood cells from forming the sickle shape.
In a randomized, double-blind, placebo-controlled, multicenter clinical trial of 274 patients with sickle cell disease, 51.2% of patients who received voxelotor 1,500 mg had an increased hemoglobin response of more than 1 g/dL from baseline compared with 6.5% of those who received placebo.
The most common adverse effects of voxelotor (in more than 10% of patients) are diarrhea, headache, abdominal pain, nausea, fatigue, rash, and fever. Hypersensitivity reactions are possible (in less than 1% of patients). Adverse effects in clinical trials were similar for pediatric and adult patients.
Nurses should check to see if any coprescribed drugs are strong cytochrome P-450 (CYP) 3A4 inhibitors or strong or moderate CYP3A4 inducers. CYP3A4 inhibitors will increase circulating levels of voxelotor, necessitating a smaller voxelotor dose, and CYP3A4 inducers will decrease circulating levels of voxelotor, necessitating a larger voxelotor dose. Fluconazole, a moderate CYP3A4 inhibitor, should be avoided as it increases voxelotor's circulation between 40% and 116%. Administration of voxelotor with CYP3A4-sensitive substrates will significantly increase the substrates' circulating levels; coadministration with sensitive substrates that have a narrow therapeutic index should be avoided. Voxelotor should be taken daily with or without food, the tablets swallowed whole. Patients should be told to seek emergency medical help if they experience rash, hives, shortness of breath, or facial swelling.
To read the complete prescribing information for voxelotor, go to http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/213137s000lbl.pdf.
Crizanlizumab-tmca, a selectin blocker, reduces the frequency of vasoocclusive crisis from obstructed blood flow. Selectin contributes to red blood cells sticking together.
Approval for crizanlizumab-tmca was based on results of a randomized clinical trial of 198 patients with sickle cell disease and a history of vasoocclusive crisis. Patients receiving crizanlizumab-tmca had fewer health care visits a year for vasoocclusive crisis than patients who received placebo (a median annual rate of 1.63 versus 2.98 visits).
The most common adverse effects of crizanlizumab-tmca (in more than 10% of patients) are back pain, nausea, fever, and arthralgia. Serious adverse effects include infusion-related reactions and interference with automated platelet counts (the reported count may be much lower than actual platelet levels).
Crizanlizumab-tmca is administered as an IV infusion over a 30-minute period at week 0, week 2, and then every four weeks. The dose is weight based. Nurses should be aware that crizanlizumab-tmca must be administered as soon after dilution as possible; once the vials are at room temperature, the drug should be completely infused within 4.5 hours after piercing the first vial. If the drug is refrigerated, it must be infused within 24 hours of piercing the vials, including the time needed for the drug to return to room temperature. Patients should be monitored for up to 24 hours after infusion for signs and symptoms of infusion-related reactions, including fever, chills, nausea, vomiting, fatigue, dizziness, pruritus, urticaria, sweating, shortness of breath, or wheezing.
To read complete prescribing information for crizanlizumab-tmca, see http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761128s000lbl.pdf.