Updates from FDA
APhA Staff
New drug
MARIBAVIR
(Livtencity—Takeda Pharmaceuticals USA, Inc.)
Drug class: Cytomegalovirus (CMV) pUL97 kinase inhibitor.
Indication: Livtencity is indicated for patients 12 years and older with post-transplant CMV infection or disease that is resistant to other treatment options (e.g., ganciclovir, valganciclovir, cidofovir, foscarnet). It is the first medication to receive FDA approval for treating resistant CMV infection or disease.
Recommended dosage and administration: Livtencity is supplied as 200-mg oral tablets. The recommended dose is 400 mg by mouth, twice daily, and can be administered with or without food. Recommended duration of therapy is not discussed in the prescribing information, but participants in the phase 3 clinical trial that led to FDA approval received treatment for up to 8 weeks.
Common adverse effects: Taste disturbance, nausea, vomiting, diarrhea, and fatigue (all had greater than 10% incidence in clinical trials).
Warnings and precautions: Livtencity should not be coadministered with ganciclovir or valganciclovir because it inhibits the enzyme (pUL97 kinase) that activates these 2 medications. Virologic failure and resistance are possible with Livtencity—CMV DNA levels should be checked if patient is not responding to treatment. Livtencity is a weak CYP3A4 inhibitor and inhibits P-gp (P-glycoprotein). It has a number of clinically significant drug–drug interactions. Carbamazepine, phenytoin, and phenobarbital all decrease levels of Livtencity—see prescribing information for recommended dose adjustments. St. John’s wort, rifabutin, and rifampin also decrease Livtencity levels—these 3 should not be taken concomitantly with Livtencity. Livtencity causes increased levels of digoxin, cyclosporine, everolimus, tacrolimus, and sirolimus—serum levels of these medications should be closely monitored, and dose adjustments made as necessary. Livtencity also increases rosuvastatin levels—patient should be monitored for myopathy and rhabdomyolysis.
PAFOLACIANINE
(Cytalux—On Target Laboratories, Inc.)
Drug class: Optical imaging agent.
Indication: Cytalux is indicated as a companion agent to be used during surgery to identify malignant lesions in patients with ovarian cancer.
Recommended dosage and administration: Cytalux is supplied as a single-use 3.2 mg/1.6 mL vial. The recommended dosing is 0.025 mg/kg and should be administered intravenously over 60 minutes 1 hour to 9 hours prior to surgery. Patients of child-bearing age should have a negative pregnancy test prior to administration of Cytalux. Additionally, all folate, folic acid, or folate-containing supplements must be stopped at least 48 hours prior to Cytalux infusion. Antihistamines and antinausea medications may be administered prior to infusion prophylactically for infusion reactions.
Common adverse effects: Nausea, vomiting, abdominal pain, dyspepsia, flushing, pruritis, and hypersensitivity reactions.
Warnings and precautions: Infusion reactions are possible—if infusion reaction occurs, infusion should be paused and antihistamines and/or anti-nausea medications should be administered. Interpretation errors are possible with Cytalux—both false-negatives and false-positives may occur. There is a risk of embryo-fetal toxicity with this medication, patients of child-bearing potential should have a negative pregnancy test prior to infusion. Only 5% dextrose injection should be used for preparation of infusion solution; other diluents can cause aggregation of Cytalux and may induce infusion reactions.
How does Cytalux work to help surgeons find cancerous lesions?
Ovarian cancers generally cause an increased number of folate receptors to be produced in cell membranes. Cytalux works by binding to these receptors. When a surgeon uses an approved fluorescent light, the affected area(s) light up, allowing surgeons to better identify cancerous tissue.
VOSORITIDE
(Voxzogo—Biomarin Pharmaceutical Inc.)
Drug class: C type natriuretic peptide analog.
Indication: Voxzogo is indicated to promote linear growth for pediatric patients who are 5 years and older with achondroplasia (a type of dwarfism) with open epiphyses (bones that are still growing).
Note: This medication was FDA approved via an accelerated pathway. Continued approval may be dependent on further clinical trial data.
Recommended dosage and administration: Voxzogo is supplied as 0.4 mg, 0.56 mg, or 1.2 mg lyophilized powder in a single-dose vial for reconstitution and is dosed based on the patient’s actual body weight. It is recommended that children have an adequate amount of food and at least 240 mL to 300 mL of liquid intake an hour before their dose of Voxzogo. Voxzogo is a subcutaneous injection and is dosed once daily, it should be given at approximately the same time each day. The patient’s body weight, growth, and physical development should be monitored every 3 to 6 months and daily dose should be adjusted based on body weight. Once bone growth stops, the patient should no longer receive this medication. See full prescribing information for instructions on reconstitution, administration, and exact dosing based on patient’s weight range.
Common adverse effects: Injection site reaction, vomiting, muscle aches, gastroenteritis, and transient decrease in blood pressure.
Warnings and precautions: Transient decreases in blood pressure have been reported—patients should have adequate food and fluid intake prior to dose to help prevent this.
Virtual reality: A new tool for patients suffering from chronic back pain?
In November 2021, FDA authorized marketing of a prescription-use virtual reality system, EaseVRx. The virtual reality system is intended to be used by patients who are at least 18 years old and have a diagnosis of chronic lower back pain. The system was created to be used as a home treatment option that incorporates both cognitive behavior therapy as well as other behavioral therapies to help manage pain control. EaseVRx is meant to be used for an 8-week period and offers patients 56 different programs that vary in length from 2 minutes to 16 minutes. The goal of the virtual reality programming is not to cure pain, but to equip patients with skills they can use to help reduce pain. Some of the behavior therapies included in the programing are deep breathing, deep relaxation, and attention shifting. Because chronic lower back pain is so hard to treat, this could be a revolutionary step toward helping people achieve better pain management.
New formulation
SIROLIMUS ALBUMINBOUND
NANOPARTICLES
(Fyarro—Aadi Bioscience, Inc.)
Drug class: mTOR inhibitor.
Indication: Fyarro is indicated for treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumors.
Recommended dosage and administration: Once reconstituted, Fyarro is a suspension that should be administered intravenously over 30 minutes. The initial dose is 100 mg/m2 and is given on days 1 and 8 of a 21-day treatment cycle. Treatment can be continued until disease progression or there is unacceptable toxicity. Recommended dose reductions based on adverse effects are as follows: first dose reduction should be 75 mg/m2, second dose reduction should be 56 mg/m2, and third dose reduction should be 45 mg/m2. Dose reductions are also recommended in patients who have mild to moderate hepatic impairment and patients who are taking other medications that are weak or moderate CYP3A4 inhibitors. See full prescribing information for an expanded list of dose adjustments.
Common adverse effects: Over 30% of participants in the clinical trial experienced stomatitis, fatigue, rash, infection, nausea, edema, diarrhea, muscle pain, decreased weight and appetite, cough, vomiting, and altered taste. At least 6% of participants in the clinical trial experienced Grade 3 to 4 lab abnormalities of decreased lymphocytes, increased glucose levels, decreased potassium, decreased phosphate, decreased hemoglobin, and increased lipase.
Warnings and precautions: Extensive list of warnings and precautions related to the most common adverse effects are listed above. See package insert for entire list of recommended patient monitoring parameters. Hypersensitivity reactions are possible during and after infusion—patients should be monitored for at least 2 hours post-infusion. Patients of child-bearing potential should be using effective contraception methods due to the risk of embryo-fetal toxicity. Fyarro may cause male infertility. Live vaccines should not be administered while patient is undergoing Fyarro therapy.
New dosage form
TOPIRAMATE
(Eprontia—Azurity Pharmaceuticals, Inc.)
Drug class: Anticonvulsant.
Indication: Eprontia is indicated as initial monotherapy and adjunct therapy for patients at least 2 years old with partial-onset or primary generalized tonic-clonic seizures. It is also indicated as an adjunct therapy for patients at least 2 years old with seizures associated with Lennox-Gastaut syndrome. Eprontia may also be used as a preventative therapy for migraines in people greater than or equal to 12 years.
Recommended dosage and administration: Eprontia is the first commercially available topiramate solution in the United States. It will be available as a 25 mg/mL solution distributed in 473 mL bottles. Once opened, the solution must be used within 30 days—any solution remaining after 30 days should be discarded. When initiating topiramate therapy, the dose must be slowly titrated to full therapeutic dose over several weeks. Dosing varies based on age and indication—see full prescribing information for complete dosing and titration charts.
Common adverse effects: Tingling sensation in limbs, anorexia, weight loss, fatigue, dizziness, nervousness, somnolence, psychomotor slowing, and abnormal vision.
Warnings and precautions: Increased risk of suicidal thoughts or ideation. Risk of fetal toxicity. Eprontia should not be discontinued without slowly tapering dose. See full prescribing information for complete list of warnings. ■