Updates from FDA
New drugs
CEFTOBIPROLE MEDOCARIL SODIUM
(Zevtera—Basilea Pharmaceutica)
Drug class: Zevtera is a cephalosporin antibiotic.
Indication: Zevtera is indicated for the treatment of adult patients with Staphylococcus aureus bacteremia (SAB), including those with right-sided infective endocarditis; adult patients with acute bacterial skin and skin structure infections (ABSSSI); and adult and pediatric patients with community-acquired bacterial pneumonia (CABP). Zevtera should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.
Recommended dosage and administration: In adults being treated for SAB, the recommended dose is 667 mg every 6 hours on days 1 to 8 and every 8 hours from day 9 until the end of treatment, which can be up to 42 days. In adults being treated for ABSSSI or CABP, the recommended dose is 667 mg every 8 hours for 5 to 14 days. In adults, each prepared I.V. infusion solution of Zevtera should be administered over 2 hours at a concentration of 2.67 mg/mL. In pediatric patients ≥3 months and <12 years old, the recommended dose for CABP is 20 mg/kg (up to 667 mg/dose) every 8 hours. In pediatric patients 12 years to <18 years old, the recommended dose for CABP is 13.3 mg/kg (up to 667 mg/dose) every 8 hours. The duration of treatment for pediatric patients is 7 to 14 days. In patients 12 years to <18 years old, each prepared I.V. infusion solution of Zevtera should be administered over a 2-hour period at a concentration of 2.67 mg/mL. In patients aged 3 months to <12 years old, each prepared I.V. infusion solution of Zevtera should be administered over 2 hours at a concentration of 5.33 mg/mL. The initial dosage should be increased in adult patients with a creatinine clearance >150 mL/min. The dosage should be reduced in adult and pediatric patients with a creatine clearance of <50 mL/min.
Common adverse effects: The most common adverse reactions are anemia, nausea, hypokalemia, vomiting, increased bilirubin and hepatic enzymes, diarrhea, increased blood creatinine, hypertension, leukopenia, pyrexia, headache, injection site reaction, rash, dysgeusia, insomnia, abdominal pain, dizziness, and phlebitis.
Warnings and precautions: Zevtera is contraindicated in patients with a known history of severe hypersensitivity to Zevtera, or to other members of the cephalosporin class. The safety and effectiveness of Zevtera for the treatment of ventilator-associated bacterial pneumonia has not been established, so use for this indication is not approved. If a hypersensitivity reaction occurs, discontinue Zevtera and institute appropriate treatment. Seizures and other adverse central nervous system reactions have been associated with use. Clostridioides difficile–associated diarrhea has been reported with use. Zevtera may increase the plasma concentrations of OATP1B1 and OATP1B3 substrates, so concomitant administration is not recommended.
TOVORAFENIB
(Ojemda—Day One Biopharmaceuticals)
Drug class: Ojemda is a kinsase inhibitor.
Indication: Ojemda is indicated for the treatment of patients 6 months and older with relapsed or refractory pediatric low-grade glioma harboring a BRAF fusion or rearrangement or BRAF V600 mutation.
Recommended dosage and administration: Prior to initiation of treatment with Ojemda, the presence of BRAF fusion or rearrangement or BRAF V600 mutation should be confirmed. The recommended dosage is based on body surface area. Administer Ojemda orally, once weekly, with or without food. Tablets should be swallowed whole with water.
Common adverse effects: The most common adverse reactions are rash; hair color changes; fatigue; viral infection; vomiting; headache; hemorrhage; pyrexia; dry skin; constipation; nausea; dermatitis acneiform; upper respiratory tract infection; decreased phosphate, hemoglobin, albumin, lymphocytes, leukocytes, potassium, and sodium; and increased creatinine phosphokinase, alanine aminotransferase, and aspartate aminotransferase.
Warnings and precautions: Major hemorrhagic events can occur during treatment with Ojemda; withhold, resume at reduced dose, or permanently discontinue based on severity. Advise patients to monitor new or worsening skin reactions. Advise patients to limit direct exposure to ultraviolet light and to use precautionary measures during treatment. If skin reactions occur, withhold, reduce the dose, or permanently discontinue based on severity.
Ojemda can cause hepatotoxicity; monitor liver function tests prior to administration and during treatment and withhold, reduce the dose, or permanently discontinue based on severity. Reduction in growth velocity has been reported. Routinely monitor growth in pediatric patients. Ojemda can cause fetal harm, so advise patients of the potential risk to a fetus and to use effective nonhormonal contraception. Increased tumor growth may occur with Ojemda. Avoid coadministration with moderate and strong CYP2C8 inhibitors and inducers. Avoid coadministration with hormonal contraceptives and CYP3A substrates where minimal concentration changes can cause reduced efficacy. Advise patients not to breastfeed during treatment and that Ojemda may impair fertility in males and females.
MAVORIXAFOR
(Xolremdi—X4 Pharmaceuticals)
Drug class: Xolremdi is a CXC chemokine receptor 4 antagonist.
Indication: Xolremdi is indicated in patients 12 years and older with WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis) to increase the number of circulating mature neutrophils and lymphocytes.
Recommended dosage and administration: The recommended dosage is 400 mg orally once daily in patients who weigh >50 kg and 300 mg orally once daily in patients who weigh ≤50 kg.
Administer Xolremdi on an empty stomach after an overnight fast and at least 30 minutes before food.
Common adverse effects: The most common adverse reactions are thrombocytopenia, pityriasis, rash, rhinitis, epistaxis, vomiting, and dizziness.
Warnings and precautions: Xolremdi is contraindicated for use with drugs that are highly dependent on CYP2D6 for clearance.
Xolremdi is expected to cause fetal harm. Advise patients of reproductive potential to use effective contraception.
QTc interval prolongation may occur, so correct any modifiable risk factors, assess QTc interval at baseline, and monitor QTc interval during treatment. Reduce Xolremdi daily dosage if it is used concomitantly with strong CYP3A4 inhibitors.
If used concomitantly with P-gp inhibitors or moderate CYP3A4 inhibitors, monitor more frequently for adverse reactions and reduce the daily Xolremdi dose if necessary. Avoid concomitant use with strong CYP3A4 inducers.
Advise patients that breastfeeding while on Xolremdi is not recommended. Xolremdi is not recommended for use in patients with severe renal impairment, end stage renal disease, or moderate to severe hepatic impairment.
PEGULICIANINE
(Lumisight—Lumicell)
Drug class: Lumisight is an optical imaging agent.
Indication: Lumisight is indicated for fluorescence imaging in adults with breast cancer as an adjunct for the intraoperative detection of cancerous tissue within the resection cavity following removal of the primary specimen during a lumpectomy.
Recommended dosage and administration: The recommended dose of Lumisight is 1 mg/kg by I.V. injection over 3 minutes administered 2 to 6 hours prior to imaging.
Common adverse effects: The most common adverse reactions are hypersensitivity and chromaturia.
Boxed warning: Serious hypersensitivity reactions, including anaphylaxis, can occur during or after administration. Before Lumisight administration, assess all patients for any history of hypersensitivity reaction to contrast media or products containing polyethylene glycol. Always have emergency resuscitation drugs, equipment, and trained personnel available. Monitor all patients for hypersensitivity reactions. If a hypersensitivity reaction is suspected, immediately discontinue the injection and initiate appropriate therapy.
Other warnings and precautions: Use of Lumisight is contraindicated in patients with a history of hypersensitivity reaction to pegulicianine. There is a risk of misdiagnosis, and absence of signal in the surgical field does not rule out the presence of cancer. Positive signal may be seen in noncancerous tissue. Interference from dyes used for sentinel lymph node mapping may occur so avoid administration of dyes before imaging the lumpectomy cavity in patients receiving Lumisight.
New indications
ILOPERIDONE
(Fanapt—Vanda Pharmaceuticals)
Drug class: Fanapt is an atypical antipsychotic.
Indication: Fanapt is indicated for treatment of schizophrenia and acute treatment of manic or mixed episodes associated with bipolar I disorder in adults.
Recommended dosage and administration: Administer Fanapt twice daily without regard to meals. Titrate the dosage to avoid orthostatic hypotension. For schizophrenia, the starting dosage is 1 mg twice daily and the recommended dosage is 6 mg to 12 mg twice daily. For bipolar mania, the starting dosage is 1 mg twice daily and the recommended dosage is 12 mg twice daily. Recommended dosing differs in CYP2D6 poor metabolizers.
Common adverse effects: The most common adverse reactions are dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, increased weight, and increased hepatic enzymes.
Boxed warning: Older adult patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Fanapt is not approved for use in patients with dementia-related psychosis.
Other warnings and precautions: Fanapt prolongs the QTc interval and may be associated with arrhythmia and sudden death. Neuroleptic malignant syndrome and tardive dyskinesia may occur. Monitor for hyperglycemia, dyslipidemia, and weight gain. Warn patients of the risk of orthostatic hypotension and syncope. Use Fanapt cautiously in patients with a history of seizures or with conditions that lower seizure threshold. Perform complete blood counts in patients with pre-existing low white blood cell count or a history of leukopenia/neutropenia. Cases of priapism have been reported. Patients taking Fanapt should use caution when operating machinery.Intraoperative floppy iris syndrome may occur. The dose of Fanapt should be reduced in patients concomitantly taking a strong CYP2D6 or CYP3A4 inhibitor. Fanapt may cause extrapyramidal or withdrawal symptoms in neonates with third-trimester exposure. Advise patients not to breastfeed during treatment. Safety and effectiveness have not been established in children and adolescents. Fanapt is not recommended for patients with severe hepatic impairment. ■