Updates from FDA
New indication
SACITUZUMAB GOVITECAN-HZIY
(Trodelvy—Gilead Sciences)
Drug class: Trop 2–directed antibody and topoisomerase inhibitor conjugate.
Indication: Treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer who have received two or more prior systemic therapies, at least one of them for metastatic disease; and treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a platinum-containing chemotherapy and either a programmed death receptor-1 or a programmed death-ligand 1 inhibitor.
Recommended dosage and administration: 10 mg/kg once weekly via I.V. infusion on days 1 and 8 of continuous 21-day treatment cycles until disease progression or unacceptable toxicity; premedication for prevention of infusion reactions and chemotherapy-induced nausea and vomiting is recommended.
Patients should be monitored during the infusion and for at least 30 minutes afterward.
Common adverse events: Nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, abdominal pain.
Boxed warning: Severe neutropenia and severe diarrhea may occur. Withhold for absolute neutrophil count below 1,500/mm3 or neutropenic fever. Monitor blood cell counts periodically during treatment.
Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay.
Monitor patients with diarrhea and give fluid and electrolytes as needed. Administer atropine, if not contraindicated, for early diarrhea of any severity.
At the onset of late diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold until resolved to less than Grade 1 and reduce subsequent doses.
Warnings and precautions: Monitor patients for hypersensitivity reactions, including severe anaphylactic reactions; nausea/vomiting; and increased risk for neutropenia following treatment initiation in individuals who are homozygous for the uridine diphosphate-glucuronosyl transferase 1A1*28 allele.
The medication can cause fetal harm.
Advise patients of potential risk to a fetus and to use effective contraception.
New formulations
POSACONAZOLE
(Noxafil Powdermix Kit—MSD Merck Co.)
Drug class: Azole antifungal.
Indication: Treatment of pediatric patients aged 2 years and older (who weigh 40 kg or less) for the prophylaxis of invasive Aspergillus and Candida infections in patients who are at high risk of developing these infections due to being severely immunocompromised.
This includes hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) or those with hematologic malignancies with prolonged neutropenia from chemotherapy.
Recommended dosage: Administer 300 mg with food and using the provided notched tip syringes only. For pediatric patients aged 2 to less than 18 years of age for prophylaxis of invasive Aspergillus and Candida infections, see full prescribing information for dosing recommendations.
Common adverse effects: Pyrexia, febrile neutropenia, vomiting, mucosal inflammation, pruritus, hypertension, hypokalemia, and stomatitis.
Warnings and precautions: Risks of breakthrough fungal infections and severe renal impairment.
Contraindicated in patients with known or suspected hereditary fructose intolerance.
CYCLOSPORINE
(Verkazia—Santen)
Drug class: Calcineurin inhibitor immunosuppressant.
Indication: Treatment of vernal keratoconjunctivitis in adult and pediatric patients.
Recommended dosage: Administer 1 drop (0.1% or 1 mg/mL) ophthalmic emulsion 4 times daily (morning, noon, afternoon, and evening) in each affected eye.
Common adverse effects: Eye pain, eye pruritis.
Warnings and precautions: Advise patients not to touch the vial tip to the eye or other surfaces to avoid potential for eye injury.
DABIGATRAN
(Pradaxa—Boehringer Ingelheim)
Drug class: Direct thrombin inhibitor.
Indication: To reduce the risk of venous thromboembolic event recurrence in pediatric patients aged 3 months to <12 years who have been treated with a parenteral anticoagulant for at least 5 days.
Recommended dosage: For pediatric patients aged 3 months to <12 years: twice daily after at least 5 days of parenteral anticoagulant.
See full prescribing information for weight-based dosages.
Contraindications: Active pathologic bleeding; history of serious hypersensitivity reaction to Pradaxa; mechanical prosthetic heart valve.
Common adverse effects: GI reactions and bleeding.
Warnings and precautions: Pradaxa use is not recommended in patients with bleeding, bioprosthetic heart valves, or increased risk of thrombosis in patients with triple-positive antiphospholipid syndrome.
DAPTOMYCIN
(Daptomycin—Hospira Inc.)
Drug class: Lipopeptide antibacterial.
Indication: Treatment of complicated skin and skin structure infections and Staphylococcus aureus bloodstream infections (bacteremia) in adult patients. Daptomycin is not indicated for the treatment of left-sided infective endocarditis due to S. aureus.
Recommended dosage: Administer to adult patients intravenously in 0.9% sodium chloride, either by injection over a 2-minute period or by infusion over a 30-minute period.
See full prescribing information for recommended dosage regimen.
Contraindication: Known hypersensitivity to daptomycin.
Common adverse effects: Diarrhea, headache, dizziness, rash, abnormal liver function tests, elevated creatine phosphokinase, urinary tract infections, hypotension, dyspnea, sepsis, bacteremia, abdominal pain, chest pain, edema, pharyngolaryngeal pain, pruritus, increased sweating, insomnia, and hypertension.
Warnings and precautions: Risks of anaphylaxis/hypersensitivity; myopathy and rhabdomyolysis; eosinophilic pneumonia; drug reaction with eosinophilia and systemic symptoms; tubulointerstitial nephritis; peripheral neuropathy; Clostridioides difficile–associated diarrhea; and persisting or relapsing S. aureus bacteremia/endocarditis.
Decreased efficacy was observed in adult patients with moderate baseline renal impairment.
Rylaze gains FDA approval as component for treatment of childhood cancer
On June 30, 2021, FDA approved asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze–Jazz Pharmaceuticals) as a component of a chemotherapy regimen to treat acute lymphoblastic leukemia and lymphoblastic lymphoma in an estimated 20% of adult and pediatric patients who are allergic to the E. coli–derived asparaginase products used most often for treatment. The only other FDA-approved drug for such patients with allergic reactions has been in short supply worldwide for years.
“Today’s approval may provide a consistently sourced alternative to a pivotal component of potentially curative therapy for children and adults with this type of leukemia,” said Gregory Reaman, MD, associate director for pediatric oncology in the FDA’s Oncology Center of Excellence.
Acute lymphoblastic leukemia, the most common type of childhood cancer, occurs in approximately 5,700 patients annually, about 50% of whom are children.
The study of Rylaze’s efficacy evaluated 102 patients who either had a hypersensitivity to E. coli–derived asparaginases or experienced silent inactivation. Results indicated the recommended dosage would provide the target level of asparaginase activity in 94% of patients.
The most common adverse effects of Rylaze include hypersensitivity reactions, pancreatic toxicity, blood clots, hemorrhage, and liver toxicity.
FDA approves promising new obesity drug
On June 4, 2021, FDA approved semaglutide (Wegovy—Novo Nordisk), a glucagon-like peptide-1 receptor agonist, and the first new drug approval to treat obesity since 2014. Clinical trials revealed that weekly injections of semaglutide helped participants lose an average of 15% to 18% of their body weight. Over the course of the 69-week research trial, patients reported losing an average of about 34 pounds before plateauing. Those results are three times what has been achieved with other drugs on the market and without raising concerns regarding potential serious adverse effects similar to those caused by fen-phen and other earlier treatments for obesity.
Wegovy acts on the brain encouraging people to eat less and store less of what they eat.
The drug is indicated as a complement to a reduced calorie diet and increased physical activity for chronic weight management in adult patients with an initial BMI of 30 kg/m2 or greater (obesity) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia).
Wegovy is considered a long-term medication to treat chronic obesity. Patients reported that once they stopped receiving weekly injections, the cravings and weight returned. The question of whether insurance companies will cover the cost remains. Semaglutide is priced at $1,000 to $1,500 per month, and insurance and Medicare coverage of obesity drugs is often excluded.