Updates from FDA
APhA Staff
New Drugs
ALPELISIB
(Vijoice—Novartis Pharmaceuticals Corporation)
Drug class: Kinase inhibitor.
Indication: Vijoice has received an accelerated approval for the treatment of severe presentations of PIK3CA-related overgrowth spectrum (PROS). It is approved for use in adults and pediatric patients who are aged at least 2 years. Due to the accelerated approval, continued approval requires continuous demonstration of clinical benefits.
Recommended dosage and administration: Patients aged 2 to 18 years old should take 50 mg alpelisib by mouth once daily with food. Patients who are 18 years and older should take 250 mg alpelisib by mouth once daily with food. Vijoice is supplied as 50 mg, 125 mg, and 250 mg oral tablets.
Common adverse effects: Diarrhea, stomatitis, hyperglycemia.
Warnings and precautions: Vijoice is not approved for any use related to oncology and has been associated with numerous severe adverse reactions including severe hypersensitivity, severe cutaneous adverse reactions, severe hyperglycemia, severe pneumonitis, and severe diarrhea.
If any patient shows any of the previously mentioned symptoms, regardless of setting, Vijoice should be discontinued. Vijoice also increases risk for embryo-fetal toxicity; people with the potential to get pregnant should be counseled appropriately.
New Dosage Form
DEXMEDETOMIDINE
(Igalmi—BioXcel Therapeutics, Inc.)
Drug class: Alpha-2 adrenergic receptor agonist.
Indication: Igalmi is indicated for short-term treatment of agitation related to schizophrenia or bipolar I or II. Use beyond 24 hours (1 day) has not been proven to be safe or effective.
Recommended dosage and administration: Igalmi is supplied as a sublingual film and is available in two different strengths: 120 mcg and 180 mcg. The sublingual film may be administered either buccally or sublingually; the film should not be chewed or swallowed. Additionally, both strengths of the film may be cut in half to provide either a 60 mcg or a 90 mcg dose of dexmedetomidine.
As with most medications that are administered sublingually, patients should not eat or drink for at least 15 minutes after administration. Similarly, when administered buccally, eating and drinking should be avoided for at least 60 minutes after administration.
Dosing is based on several factors, including the level of severity of agitation (mild/moderate or severe), if the patient has hepatic impairment, and age (dosing decreases if patient is greater than or equal to 65 years).
See full prescribing information for a detailed dosing chart. Up to two additional doses may be given if the initial dose does not eliminate the agitation. Vital signs must be assessed prior to giving any additional doses due to risk of hypotension; see recommendations for when to hold additional doses based on blood pressure or heart rate.
Common adverse effects: Somnolence/sleepiness, paresthesia (tingling or prickling sensation), mouth numbness, dizziness, dry mouth, hypotension, orthostatic hypotension.
Warnings and precautions: Increased risk of hypotension, orthostatic hypotension, and bradycardia; avoid use in patients with any of these symptoms or patients with advanced heart block, severe ventricular dysfunction, or patients who have a history of fainting. Increased risk of QT prolongation.
Increased risk of somnolence or sleepiness; patients should wait at least 8 hours after Igalmi administration before operating a vehicle.
New Patient Population
CEFTOLOZANE/TAZOBACTAM
(Zerbaxa—Cubist Pharmaceuticals, LLC)
Drug class: Ceftolozane is a cephalosporin antibacterial and tazobactam is a beta-lactamase inhibitor.
Indication: Zerbaxa was previously only approved for use in patients over 18 years. As of April 21, 2022, it received approval for use in pediatric patients for two of the three previously approved indications.
It is approved for use in complicated intra-abdominal infections (cIAI) when used in combination with metronidazole and for complicated urinary tract infections (cUTI) in both adult and pediatric patients. The use for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) is still only approved for patients who are 18 years and older.
Recommended dosage and administration: Dosage and duration of treatment is dependent on the age of the patient, the indicated use for the medication, and kidney function. When looking at kidney function in adults for this medication, the dosing chart utilizes creatinine clearance (CrCl).
However, when looking at kidney function in pediatric patients for this medication, the dosing chart looks at estimated glomerular filtration rate (eGFR). Dosing for pediatric patients with an eGFR greater than 50 mL/min/1.73 m2 for both approved indications is 30 mg/kg and should not exceed 1.5 g in a dose.
See full prescribing information for complete dosing charts. All doses of Zerbaxa should be administered via intravenous infusion every 8 hours. All infusions should last one hour.
Common adverse effects: In adult patients being treated for cIAI or cUTI, the most commonly reported adverse effects are nausea, diarrhea, headache, fever.
In adult patients being treated for (HABP/VABP) the most commonly reported adverse effects are increased transaminases, renal impairment/renal failure, and diarrhea.
In pediatric patients, the most commonly reported adverse effects are thrombocytosis, diarrhea, fever, leukopenia, abdominal pain, vomiting, increased aspartate aminotransferase, and anemia.
Warnings and precautions: Zerbaxa may have decreased efficacy in patients who have creatinine clearance (CrCl) of 30–50 mL/min. CrCl should be monitored on a daily basis and dose adjusted, as necessary.
Zerbaxa should be used with caution in patients who have a hypersensitivity to beta-lactam antibiotics. There is a risk of Clostridioides difficile–associated diarrhea, patients should be monitored and assessed if diarrhea occurs.
REMDESIVIR
(Veklury—Gilead Sciences, Inc.)
Drug class: SARS-CoV-2 (COVID-19) nucleotide analog RNA polymerase inhibitor.
Indication: Previously FDA-approved for use in patients 12 years and older, Veklury received approval in late April 2022 for use in patients as young as 28 days old who weigh at least 3 kg.
Veklury is indicated in patients who have tested positive COVID-19 and are either hospitalized or have mild to moderate COVID-19 and have a high risk of developing severe COVID-19.
Recommended dosage and administration: There are two different formulations of Veklury, but the only formulation that is approved for pediatric patients who weigh between 3 kg and 40 kg is Veklury for injection, which is supplied as 100 mg lyophilized powder.
Pediatric patients who weigh between 3 kg and 40 kg should receive a loading dose of 5 mg/kg on the first day of treatment. After the first day of treatment, the dose should be decreased to 2.5 mg/kg. Veklury is administered as an intravenous infusion over 30–120 minutes.
Prior to initiating Veklury therapy, kidney and liver function should be assessed as well as prothrombin time.
See full prescribing information for length of therapy recommendations as well as dosing recommendations for patients who weigh more than 40 kg.
Common adverse effects: Nausea, increase in AST and ALT liver enzymes.
Warnings and precautions: Risk of hypersensitivity and infusion-related reactions. Risk of transaminase elevations; liver enzymes should be monitored prior to and during therapy.
If ALT levels increase by more than 10 times the upper limit of normal, consider discontinuing therapy. Concomitant therapy with Veklury and chloroquine phosphate or hydroxychloroquine may reduce antiviral activity of Veklury. ■
FDA Consumer Warnings
On April 20, 2022, FDA issued a consumer warning concerning the following Artri and Ortiga products: Artri Ajo King, Artri King, Ortiga Mas Ajo Rey, and Ortiga Mas Ajo Rey Extra Forte. FDA labs found that these products might contain ingredients not listed on the packaging. The unlisted ingredients that FDA found were dexamethasone, diclofenac sodium, and methocarbamol. While FDA only found unlisted ingredients in one specific lot of each of the Artri and Ortiga products tested, they are still warning against use of other products manufactured by these companies. FDA recommends that consumers who are using one of these products work with a health care provider to work to safely discontinue these supplements. FDA is continuing their investigation of these products.
On May 4, 2022, FDA issued a consumer warning about products containing Δ-8-tetrahydrocannabinol (Δ-8 THC). FDA listed 5 things they believe consumers should know about Δ-8 THC:
- Δ-8 THC products have not been evaluated or approved by FDA for safe use and may be marketed in ways that put the public health at risk.
- FDA has received adverse event reports involving Δ-8 THC-containing products.
- Δ-8 THC has psychoactive and intoxicating effects.
- Δ-8 THC products often involve use of potentially harmful chemicals to create the concentrations of Δ-8 THC claimed in the marketplace.
- Δ-8 THC products should be kept out of the reach of children and pets.
FDA is notifying the public about the potential dangers of Δ-8 THC due to increased numbers of adverse events that have been reported by people who have consumed Δ-8 THC products, the fact that products seem to be marketed in ways that are appealing to children, and concerns of harmful chemicals and contamination that could occur during the manufacturing process.