Paxlovid drug interaction
A physician prescribed PAXLOVID (nirmatrelvir and ritonavir) for a 34-year-old patient with flulike symptoms who tested positive for COVID-19. On day 3 of treatment, the patient presented with signs and symptoms of fatigue and bradycardia, with a heart rate below 40 beats/minute. The physician referred the patient to the ED for further evaluation, where it was discovered that the patient had been taking ivabradine, a hyperpolarization-activated cyclic nucleotide-gated channel blocker, for premature ventricular contractions.
Ivabradine is metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme, and the ritonavir component of Paxlovid is a strong CYP3A4 inhibitor. Thus, concomitant use of Paxlovid and ivabradine is contraindicated due to the risk of ivabradine accumulation and toxicity, which could lead to bradycardia, hypotension, and heart failure. Increased plasma concentrations of ivabradine may also exacerbate bradycardia and conduction disturbances. After being monitored in the ED for 24 hours, the patient recovered, and was discharged.
Prescribers and patients must be informed about the potential for Paxlovid drug interactions. Healthcare organizations should provide alerts in their electronic health records (EHRs) and pharmacy computer systems for this and other drug-drug interactions.
Eprontia oral solution concentration conversion
A new oral solution, EPRONTIA (topiramate), was approved for the treatment of certain seizure disorders in patients 2 years and older, and for the prevention of migraines in patients 12 years and older. The concentration of this new product, 25 mg/mL, differs from commonly compounded concentrations prepared by pharmacies.
The American Society of Health-System Pharmacists (ASHP) Standardize 4 Safety (S4S) initiative recommends 20 mg/mL as the standard concentration. However, some organizations also compound 6 mg/mL for smaller children to make doses easier to measure, and the Michigan Pediatric Safety Collaboration recommends a compounded concentration of 6 mg/mL. The transition to the new commercially available topiramate concentration, 25 mg/mL, raises a concern for potential errors.
Organizations should establish a proactive plan to convert to the commercially available product, which should include identifying all patients who currently receive an extemporaneous formulation of topiramate to ensure all active patients are converted to the new concentration within a defined period. Conversion charts should be prepared and validated, and the new strength and the volume of each dose communicated to providers, patients, and families before prescription conversion. Eprontia doses should be prescribed in mg, not mL, and clinicians should clarify and discuss Eprontia doses based in mg. Pharmacy staff should be alerted to this new concentration and the potential for confusion and mix-ups. Using the teach-back method, pharmacists and nurses should also educate patients and caregivers about the new concentration, the corresponding volumetric dose, and how to measure each dose with an oral syringe.
Different concentrations of oral liquid Baclofen
FLEQSUVY (baclofen) oral suspension (25 mg/5 mL [5 mg/mL]) is a new formulation of the skeletal muscle relaxant used to treat spasticity from multiple sclerosis and may also be used for patients with spinal cord injuries and other diseases. OZOBAX is another brand of baclofen oral solution that was available before Fleqsuvy. But Ozobax comes in a different strength, 5 mg/5 mL (1 mg/mL), than Fleqsuvy, 25 mg/5 mL (5 mg/mL). The Ozobax label lists the concentration as "5 mg/5 mL," which could be confused with the 5 mg/mL strength of Fleqsuvy, although Fleqsuvy is primarily labeled 25 mg/5 mL.
Giving a patient a lower or higher dose due to a concentration error could result in inadequate treatment and withdrawal syndrome or baclofen toxicity. Both the ASHP and the Michigan Pediatric Safety Collaboration recommend a concentration of 5 mg/mL for compounded baclofen oral liquid prescriptions. When possible, organizations should standardize to a single concentration of baclofen based on the patient population served-avoid adding both Fleqsuvy and Ozobax to the organization's formulary. EHRs should be configured to list the concentration of the available product. Clinicians should be made aware of the potential for error due to the different concentrations on the market, with special attention given during the medication reconciliation process to ensure accurate doses are documented and prescribed.