4. Drug-Drug Interactions
Patient profiles will be assessed to identify those drug regimens, which may result in clinically significant drug-drug interactions. Major drug-drug interactions considered clinically significant for sickle cell disease products are summarized in Table 3. Only those drug-drug interactions classified as clinical significance level 1/contraindicated or those considered life threatening which have not yet been classified will be reviewed.
| Target Drug | Interacting Drug | Interaction | Recommendation | Clinical Significance Level |
|---|---|---|---|---|
| hydroxyurea (Droxia, Siklos) | clozapine | unknown if concurrent use of other drugs known to cause neutropenia increases the risk of clozapine-induced neutropenia | consider increased absolute neutrophil count (ANC) monitoring and consult the treating hematologist/ oncologist | major |
| hydroxyurea (Droxia, Siklos) | febuxostat | coadministration may result in increased uric acid precursors that could result in xanthine nephropathy and calculi | avoid concurrent use | major |
| hydroxyurea (Droxia, Siklos) | filgastrim/pegfilgrastim | filgasstrim induces proliferation of neutrophil-progenitor cells, and antineoplastic agents exert toxic effects against rapidly growing cells | filgastrim is contraindicated for use during 24 hours before or after cytotoxic chemotherapy pegfilgrastim should not be given 14 days before or 24 hours after cytotoxic chemotherapy | contraindicated within 24 hours before or after cytotoxic chemotherapy contraindicated 14 days before or 24 hours after cytotoxic chemotherapy |
| Hydroxyurea (Droxia, Siklos) | live Vaccines (Bacillus Calmette-Guerin (BCG), Chikungunya, MMR*, Varicella, Zoster, Smallpox, Typhoid, Yellow fever, Rotavirus+) | May increase risk of infection by live vaccine | Avoid use until at least 3 months after discontinuation of immunosuppressive drugs unless benefits clearly outweigh potential risks | contraindicated |
| Hydroxyurea (Droxia, Siklos) | Stavudine | May increase risk of severe peripheral neuropathy, fatal pancreatitis, and hepatotoxicity | Avoid concurrent use | major |
| Hydroxyurea (Droxia, Siklos) | Didanosine | May result in fatal pancreatitis and hepatotoxicity | Avoid concurrent use | major |
| Voxelotor (Oxbryta) | Strong or moderate CYP3A4 inducers (e.g. phenytoin, nafcillin, carbamazepine) | May reduce voxelotor plasma concentration and result in reduced efficacy | Avoid concurrent use or increase voxelotor dosage to 2000-2500 mg daily | major |
| Voxelotor (Oxbryta) | Strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, itraconazole) | May increase voxelotor plasma concentration and result in increased toxicity | Avoid concurrent use, replace with alternative drug, or Decrease voxelotor dosage to 1000 mg daily | major |
| voxelotor (Oxbryta) | CYP 3A4 substrates (e.g. eliglustat, flibanserin, lomitapide, lonafarnib) | may result in increased concentration of sensitive CYP3A4 substrates | avoid concurrent use | contraindicated |
Legend:
- *MMR-Measles, mumps, rubella
- +Rotavirus vaccination is indicated up to 24 months of age; because hydroxyurea (Siklos) is indicated for use in pediatric patients 2 years and older, there is a small chance that a patient might be considered for both treatments; this combination should be avoided.