Updates from FDA
New drugs
ECULIZUMAB-AEEB
(Bkemv—Amgen)
Drug class: Bkemv is a complement inhibitor that is biosimilar to Soliris (eculizumab).
Indication: Bkemv is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis and atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy. It is not indicated for the treatment of patients with Shiga toxin E. coli–related hemolytic uremic syndrome.
Recommended dosage and administration: Patients should be vaccinated against meningococcal infection according to current ACIP guidelines at least 2 weeks prior to initiation of Bkemv. For patients 18 years and older, the recommended dosage is 600 mg weekly for the first 4 weeks, followed by 900 mg for the fifth dose 1 week later, then 900 mg every 2 weeks thereafter. For treatment of aHUS in patients 18 years and older, the recommended dosage is 900 mg weekly for the first 4 weeks, followed by 1,200 mg for the fifth dose 1 week later, then 1,200 mg every 2 weeks thereafter. For patients less than 18 years old, dosing recommendations are based on body weight. Bkemv is administered as an I.V. infusion.
Common adverse effects: The most frequently reported adverse reactions are headache, nasopharyngitis, back pain, nausea, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, anemia, cough, peripheral edema, UTIs, and pyrexia.
Boxed warning: Eculizumab products increase the risk of serious and life-threatening infections caused by Neisseria meningitidis. Complete or update meningococcal vaccination at least 2 weeks prior to the first dose of Bkemv, unless the risks of delaying Bkemv outweigh the risk of developing a serious infection. Use the most current ACIP recommendations for meningococcal vaccination in patients receiving a complement inhibitor. Patients receiving eculizumab products are at increased risk for invasive disease caused by Neisseria meningitidis, even if they develop antibodies following vaccination. Monitor patients for symptoms of meningococcal infections and evaluate immediately if infection is suspected. Bkemv is only available through a restricted program called REMS.
Other warnings and precautions: Bkemv is contraindicated for initiation in patients with unresolved Neisseria meningitidis infection. Use caution when administering Bkemv to patients with any systemic infection. Monitor patients during infusion, interrupt for reactions, and institute appropriate supportive measures.
IMETELSTAT
(Rytelo—Geron Corporation)
Drug class: Rytelo is an oligonucleotide telomerase inhibitor.
Indication: Rytelo is indicated for the treatment of adult patients with low to intermediate risk myelodysplastic syn-dromes with transfusion-dependent anemia requiring 4 or more red blood cell units over 8 weeks who have not responded to, have lost response to, or are ineligible for erythropoiesis-stimulating agents.
Recommended dosage and administration: The recommended dosage of Rytelo is 7.1 mg/kg administered as an I.V. infusion over 2 hours every 4 weeks. Premedicate for potential infusion–related reactions prior to administration.
Common adverse effects: The most common adverse reactions include decreased platelets, decreased white blood cells, decreased neutrophils, increased AST, increased alkaline phosphatase, increased ALT, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infection, and headache.
Warnings and precautions: Grade 3 or Grade 4 thrombocytopenia or Grade 3 or Grade 4 neutropenia may occur during treatment with Rytelo. Obtain complete blood cell counts prior to initiation of Rytelo, weekly for the first 2 cycles, and prior to each cycle thereafter to monitor. Delay or dose reduce as needed based on results. If infusion-related reactions occur, interrupt, decrease the rate of infusion, or permanently discontinue Rytelo based on the severity of the reaction. Rytelo can cause embryo-fetal harm. Advise patients of reproductive potential of the possible risk to a fetus and to use effective contraception. Advise patients not to breastfeed.
New dosage forms
CLONIDINE HYDROCHLORIDE EXTENDED-RELEASE ORAL SUSPENSION
(Onyda XR—Tris Pharma)
Drug class: Clonidine is a centrally acting alpha-2 adrenergic agonist.
Indication: Onyda XR is indicated for the treatment of ADHD as monotherapy or as adjunctive therapy to CNS stimulant medications in pediatric patients 6 years and older.
Recommended dosage and administration: The starting dosage of Onyda XR is 0.1 mg orally once daily at bedtime with or without food. The dose may be increased in increments of 0.1 mg per day at weekly intervals. The maximum recommended dose is 0.4 mg once daily at bedtime. Due to differing pharmacokinetic profiles, Onyda XR should not be substituted for other clonidine products on a mg per mg basis. When discontinuing therapy, taper the dose in increments of 0.1 mg or less every 3 to 7 days to avoid rebound hypertension.
Common adverse effects: The most common adverse reactions in patients taking Onyda XR are somnolence, fatigue, irritability, nightmare, insomnia, constipation, dry mouth, decreased appetite, and dizziness.
Warnings and precautions: Onyda XR is contraindicated in patients with a history of hypersensitivity reaction to clonidine. Hypotension and bradycardia may occur so dosage should be titrated slowly and patients at risk for hypotension, heart block, bradycardia, syncope, cardiovascular disease, vascular disease, cerebrovascular disease, or chronic renal failure should be monitored frequently. Measure heart rate and blood pressure prior to initiation of therapy, following dose increases, and periodically while on therapy. Avoid concomitant use of drugs with additive effects unless clinically indicated. Advise patients to avoid becoming dehydrated or overheated. Somnolence and sedation have been observed in some patients. Consider the potential for additive sedative effects with CNS depressant drugs. Caution patients against operating heavy equipment or driving until they know how they respond to the medication. The use of Onyda XR may worsen sinus node dysfunction and atrioventricular block, especially in patients taking other sympatholytic drugs. Titrate slowly and monitor vital signs frequently. Concomitant use with tricyclic antidepressants may reduce the hypotensive effect of clonidine. Avoid use of Onyda XR with agents known to affect sinus node function or AV nodal conduction due to the potential for additive effects such as bradycardia and AV block. Use caution when antihypertensive drugs are co-administered with Onyda XR. The dosage of Onyda XR must be adjusted in patients with renal impairment and these patients should be carefully monitored.
New formulations
MYCOPHENOLATE MOFETIL ORAL SUSPENSION
(Myhibbin—Azurity)
Drug class: Myhibbin is an antimetabolite immunosuppressant.
Indication: Myhibbin is indicated for the prophylaxis of organ rejection in adult and pediatric recipients 3 months and older of allogeneic kidney, heart or liver transplants, in combination with other immunosuppressants.
Recommended dosage and administration: Myhibbin is packaged as an oral suspension of mycophenolate mofetil 200 mg/mL. The recommended dosage for kidney transplant in adults is 1 g orally twice daily. For heart and liver transplant in adult patients, the recommended dosage is 1.5 g orally twice daily. In pediatric patients, the dosing is based on body surface area. Dosing should also be modified for renal impairment or neutropenia.
Common adverse effects: The most common adverse reactions in patients using Myhibbin include diarrhea, leukopenia, infection, vomiting, and opportunistic infections.
Warnings and precautions: Myhibbin is contraindicated in patients with a history of hypersensitivity to mycophenolate mofetil, mycophenolic acid, polysorbate 80 or any component of the drug product. Blood dyscrasias may occur so patients should be monitored with blood tests. Treatment interruption or dose reduction should be considered if a blood dyscrasia does occur. Monitor patients for GI complications such as bleeding, ulceration and perforations, paying special attention to those with underlying GI disorders. Avoid the use of Myhibbin in patients with hypoxanthine-guanine phosphoribosyl-transferase deficiency. Monitor patients for acute inflammatory syndrome. Avoid live attenuated vaccines during therapy. Avoid blood donation during therapy and for 6 weeks after therapy is completed. Avoid semen donation during therapy and for 90 days after therapy is completed. Myhibbin may affect ability to drive or operate machinery. Some drugs such as antacids with magnesium or aluminum hydroxide, proton pump inhibitors, drugs that interfere with enterohepatic recirculation, telmisartan, and calcium-free phosphate binders may interfere with systemic exposure and reduce Myhibbin efficacy. The effectiveness of oral contraceptives may be reduced during therapy with Myhibbin. Use of additional barrier contraceptive methods is recommended. Sexually active male patients and/or their female partners are recommended to use effective contraception during treatment of the male patient and for at least 90 days after cessation of treatment. ■
FDA approves the first mRNA vaccine against RSV
In May of 2024, FDA approved Moderna’s mRESVIA for use in adults aged 60 years and over for active immunization against severe lower respiratory tract disease caused by respiratory syncytial virus (RSV-LRTD). mRESVIA is administered intramuscularly as a single dose. The most commonly reported adverse reactions in clinical trials were injection-site pain, fatigue, headache, myalgia, arthralgia, axillary swelling or tenderness, and chills.
mRESVIA is an RSV vaccine that consists of an mRNA sequence encoding a stabilized prefusion F glycoprotein. This glycoprotein is expressed on the surface of the virus and helps the virus to enter host cells. The prefusion conformation of the F protein is a significant target of potent neutralizing antibodies and is highly conserved across both RSV-A and RSV-B subtypes.
A randomized, placebo-controlled, observer-blind, case-driven clinical study was performed to evaluate the safety and efficacy of mRESVIA to prevent RSV-LTRD in individuals aged 60 years and older with or without underlying medical conditions after receiving a single dose. The primary efficacy endpoints were the prevention of a first episode of RSV-LRTD with at least 2 or 3 signs/symptoms starting 14 days after vaccination. The vaccine efficacy based on hazard ratio was 78.7% for RSV-LRTD with 2 or more signs/symptoms and 80.9% for RSV-LRTD with 3 or more signs/symptoms. ■