Updates from FDA
New drugs
UBROGEPANT
(Ubrelvy—Allergan)
Drug class: Oral calcitonin gene-related peptide receptor antagonist
Indication: First drug in its class for acute treatment of migraine with or without aura in adults; not indicated for preventive treatment of migraine.
Recommended dosage: 50 mg or 100 mg taken orally, as needed. A second dose may be administered at least 2 hours after the initial dose. The maximum dose in a 24-hour period is 200 mg. For severe hepatic or severe renal impairment, the recommended dose is 50 mg; if needed, a second 50- mg dose may be taken at least 2 hours after the initial dose.
Adverse effects: Nausea, tiredness, dry mouth
Contraindications: Concomitant use of strong CYP3A4 inhibitors
GOLODIRSEN
(Vyondys 53—Sarepta Therapeutic)
Drug class: Antisense oligonucleotide
Indication: Treatment of patients with Duchenne muscular dystrophy who have a confirmed mutation of the dystrophin gene that is amenable to exon 53 skipping
Recommended dosage: 30 mg per kg administered as an I.V. infusion over 35 to 60 minutes once weekly. Measurement of glomerular filtration rate and dilution required prior to initiation.
Adverse effects: Headache, fever, cough, vomiting, abdominal pain, cold symptoms (nasopharyngitis), nausea
Warnings and precautions: Hypersensitivity reactions, including rash, fever, itching, hives, skin irritation, and skin peeling. Renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides; patients’ renal function should be monitored.
FAM-TRASTUZUMAB
DERUXTECAN-NXKI
(Enhertu—Daiichi Sankyo)
Drug class: HER2-directed antibody and topoisomerase inhibitor conjugate
Indication: Treatment of adults with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting
Recommended dosage: 5.4 mg/kg administered via I.V. infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity
Adverse effects: Nausea, fatigue, vomiting, hair loss, constipation, decreased appetite, anemia, decreased neutrophil count, diarrhea, leukopenia, cough, decreased platelet count; increased risk of left ventricular dysfunction (as seen with other HER2-directed therapies for breast cancer)
Boxed warning: Risk of interstitial lung disease, pneumonitis, and embryo-fetal toxicity. Contraindicated in pregnancy; may cause harm to a developing fetus or newborn baby or cause delivery complications. Females of reproductive age and males with a female partner of reproductive potential should use effective contraception during treatment.
ENFORTUMAB VEDOTIN-EJFV
(Padcev—Astellas Pharma)
Drug class: Nectin-4-directed antibody and microtubule inhibitor conjugate
Indication: Treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy
Recommended dosage: 1.25 mg/kg (up to a maximum dose of 125 mg) given as an I.V. infusion over 30 minutes on days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity
Adverse effects: Fatigue, peripheral neuropathy, decreased appetite, rash, hair loss, nausea, altered taste, diarrhea, dry eye, itching, dry skin
Warnings and precautions: Hyperglycemia, whether or not patient has diabetes (monitor blood glucose levels closely); new or worsening peripheral neuropathy (interrupt, reduce, or discontinue the dose if needed); eye disorders, including dry eyes and vision changes (consider prophylactic artificial tears for dry eyes and referral to an ophthalmologist for any new eye-related symptoms); delayed extravasation site reactions with pain, blisters, and peeling of skin. Patients of reproductive age should use effective contraception during treatment and for a period of time thereafter. Contraindicated in pregnancy; may cause harm to a developing fetus or newborn baby or cause delivery complications.
AVAPRITINIB
(Ayvakit—Blueprint Medicines Corp.)
Drug class: Kinase inhibitor
Indication: Treatment of adults with unresectable or metastatic GI stromal tumor—a type of tumor that occurs most commonly in the stomach or small intestine—harboring a platelet-derived growth factor receptor alpha exon 18 mutation
Adverse effects: Edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash, dizziness
Warnings and precautions: Risk of intracranial hemorrhage (reduce dose or discontinue drug); central nervous system effects, including cognitive impairment; dizziness; sleep, mood, and speech disorders; and hallucinations (depending on severity, withhold drug and resume at the same or reduced dose upon improvement, or permanently discontinue). May harm a developing fetus or newborn baby. Females of reproductive potential and males with female partners of reproductive potential should use effective contraception during treatment and for 6 weeks after the final dose.
New indication
ICOSAPENT ETHYL
(Vascepa—Amarin Pharma)
Drug class: Antilipemic
Indication: First FDA-approved drug to reduce cardiovascular risk in patients with elevated triglyceride levels of 150 mg per dL or higher as an add-on to maximally tolerated statin therapy. Patients must also have either established cardiovascular disease or diabetes and two or more additional risk factors for cardiovascular disease. Patients are advised to continue physical activity and maintain a healthy diet.
Recommended dosage: 4 g per day taken as either four 0.5-g capsules twice daily with food or two 1-g capsules twice daily with food
Adverse effects: Musculoskeletal pain, peripheral edema, atrial fibrillation, arthralgia
Warnings and precautions: Increased risk of atrial fibrillation or atrial flutter requiring hospitalization, bleeding events (higher among patients taking other medications that increase the risk of bleeding, such as aspirin, clopidogrel, or warfarin), potential for allergic reactions in patients with allergy to fish or shellfish
New device
INTEROPERABLE AUTOMATED GLYCEMIC CONTROLLER
(t:slim X2 Insulin Pump with Control-IQ Technology—Tandem Diabetes Care)
Indication: Adjusts insulin delivery by connecting to an alternate controller-enabled insulin pump and integrated continuous glucose monitor.This is the first controller that can be used with other diabetes devices that are also designed to be integrated into a customizable diabetes management system for automated insulin delivery.
Risks: Though the system has been assessed for reliability, incorrect and inappropriate calculation, and command, delay of insulin delivery can still occur. Other risks associated with use of the interoperable controller can include incorrect insulin delivery as a result of loss of communication between connected devices or from exploitation of cybersecurity vulnerabilities. These associated risks can lead to hypoglycemia or high hyperglycemia, including diabetic ketoacidosis.
FDA approves first vaccine to prevent Ebola
The live, attenuated vaccine, Ervebo (Merck), prevents Ebola virus disease (EVD) in people ages 18 years and older. Administered as a single-dose injection, the vaccine has been genetically engineered to contain a protein from the Zaire ebolavirus.
Ervebo’s approval was supported by a randomized cluster (ring) vaccination study of individuals aged 18 years and older that was conducted in Guinea, West Africa, during the 2014–2016 outbreak. A total of 3,537 contacts and contacts of contacts of individuals with laboratory-confirmed EVD received either “immediate” or 21-day “delayed” vaccination with Ervebo. In a comparison of cases of EVD among 2,108 individuals in the immediate vaccination arm and 1,429 individuals in the delayed vaccination arm, Ervebo was determined to be 100% effective in preventing Ebola cases, with symptom onset greater than 10 days after vaccination.
No cases of EVD with symptom onset greater than 10 days after vaccination were observed in the immediate cluster group, compared with 10 cases of EVD in the 21-day delayed cluster group.
In additional studies, antibody responses to Ervebo were assessed in 477 individuals in Liberia, approximately 500 individuals in Sierra Leone, and approximately 900 individuals in Canada, Spain, and the United States. The antibody responses among those in the study conducted in Canada, Spain, and the United States were similar to those among individuals in the studies conducted in Liberia and Sierra Leone.
Ervebo’s safety was assessed in approximately 15,000 individuals in Africa, Europe, and North America. The most commonly reported adverse effects were pain, swelling, and redness at the injection site as well as headache, fever, joint and muscle aches, and fatigue.
First generics of apixaban approved
FDA granted approval of the first generics of apixaban (Bristol-Myers’ and Pfizer’s Eliquis) to Micro Labs and Mylan.
Apixaban reduces the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. It is also indicated for prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery.
In addition, apixaban is indicated for treatment of DVT and PE and to reduce the risk of recurrent DVT and PE following initial therapy.
There is an increased risk of thrombotic events or strokes if a patient stops using apixaban too early. Epi-dural or spinal hematomas may occur in patients treated with apixaban who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Health professionals should consider these risks when scheduling patients for spinal procedures.
Patients with prosthetic heart valves should not take apixaban, nor should patients with atrial fibrillation that is caused by a heart valve problem. As with other FDA-approved anticlotting drugs, bleeding, including life-threatening and fatal bleeding, is the most serious risk with apixaban.