In our article on Bijuva, the oral fixed-dose combination of estradiol and progesterone (Med Lett Drugs Ther 2019; 61:99), Table 1 should have included single-ingredient oral formulations of estradiol and progesterone (see below). They will be added to the table as it appears online, along with medroxyprogesterone (Provera, and generics), another single-ingredient progestin available for use in women with an intact uterus who take systemic estrogen for menopausal symptoms. Taking generic estradiol and progesterone separately may be less convenient than taking Bijuva, but they cost less and allow for more dosing flexibility.

In our article in issue 1564 on Plenvu for colonoscopy preparation (Med Lett Drugs Ther 2019; 61:11), the comparator drug in the DAYB trial was not Prepopik, but rather Citrafleet, a similar sodium picosulfate-based preparation that is not available in the US. Also, we said that Plenvu can be taken as a single- or split-dose regimen; we should have said that it can be taken as two doses in a single day or split over two days.

The FDA has approved use of dinutuximab (Unituxin [yoo ni tux' in] – United Therapeutics) in combination with interleukin-2 (IL-2), granulocyte-macrophage colony-stimulating factor (GM-CSF), and isotretinoin for treatment of children with high-risk neuroblastoma who previously responded to first-line therapies. Dinutuximab is a monoclonal antibody that binds to GD2, a glycolipid that is overexpressed on the surface of neuroblastoma cells.1

Dinutuximab received a priority review and orphan drug designation. Approval was based on the results of an open-label trial in 226 patients with high-risk neuroblastoma that had at least a partial response to induction chemotherapy, autologous stem cell transplantation, and radiation. Patients were randomized to receive a combination of dinutuximab, GM-CSF, IL-2, and isotretinoin, or isotretinoin alone. At 2 years, the event-free survival rate, the primary endpoint, was 66% with the dinutuximab regimen and 46% with isotretinoin alone (p<0.01). The overall survival rate was 86% with the dinutuximab regimen compared to 75% with isotretinoin alone (p<0.02).2 The recommended dose of dinutuximab is 17.5 mg/m² daily infused IV over 10-20 hours for 4 consecutive days for up to 5 cycles. Dinutuximab can cause life-threatening infusion reactions, severe pain requiring treatment with IV opioids, peripheral neuropathy, capillary leak syndrome, visual disturbances, hemolytic-uremic syndrome, and other serious adverse effects. The cost for one 17.5 mg single-use vial is $7,500.3

1. S Dhillon. Dinutuximab: first global approach. Drugs 2015; 75: 923.
2. AL Yu et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med 2010; 363:1324.
3. Approximate WAC. WAC = wholesaler acquisition cost, or manufacturer's published price to wholesalers; WAC represents published catalogue or list prices and may not represent an actual transactional price. Source: AnalySource® Monthly. March 5, 2016. Reprinted with permission by First Databank, Inc. All rights reserved. ©2016. www.fdbhealth.com/policies/drug-pricing-policy.

Download complete U.S. English article

The FDA has approved ensitrelvir (Xocova – Shionogi), a SARS-CoV-2 main protease inhibitor, for postexposure prophylaxis of COVID-19 in patients ≥12 years old who had contact with an infected individual. Ensitrelvir is the first oral antiviral drug to be approved in the US for this indication. The parenteral monoclonal antibody combinations bamlanivimab and etesevimab and casirivimab and imdevimab (REGEN-COV) are no longer authorized for postexposure prophylaxis of COVID-19 in the US.

The FDA has approved the pyrimidine analog uridine triacetate (Xuriden [zur' uh den] – Wellstat Therapeutics) for treatment of hereditary orotic aciduria, a rare autosomal recessive disorder (estimated birth prevalence: <1:1,000,000) in infants and children caused by a deficiency in uridine 5'-monophosphate (UMP) synthase. This deficiency prevents synthesis of uridine nucleotides and causes developmental delays, failure to gain weight, hematologic abnormalities, and excessive urinary excretion of orotic acid, which can lead to urinary obstruction.1 Xuriden is the first drug to be approved in the US for this indication. Uridine triacetate is also available as Vistogard for treatment of fluorouracil (5-FU) or capecitabine (Xeloda, and generics) overdose or severe or life-threatening toxicity.

In an unpublished, single-arm, 6-week trial with a 6-month extension (summarized in the package insert), 4 patients 3-19 years old with hereditary orotic aciduria were treated with uridine triacetate 60 mg/kg once daily for 6 weeks, followed by 60-120 mg/kg once daily for 6 months. After 6 months of treatment, hematologic parameters (neutrophil count, WBC count, or mean corpuscular volume) either improved or remained stable and orotic acid levels remained stable in all 4 patients. Weight growth either improved or remained stable and height growth remained stable in 3 patients measured after 6 months of treatment. No adverse effects were reported.

Xuriden is available as oral granules in 2-gram single-use packets. The recommended starting dosage is 60 mg/kg once daily. The dose can be increased to 120 mg/kg (max 8 grams) once daily if urine orotic acid levels increase or remain above normal, or for worsening disease. The granules should be mixed in applesauce, pudding, yogurt, milk, or infant formula and swallowed immediately, without chewing. Once the packet is opened, any unused granules should be discarded. The cost for 30 2-gram packets of Xuriden is $22,500.2

1. S Balasubramaniam et al. Inborn errors of pyrimidine metabolism: clinical update and therapy. J Inherit Metab Dis 2014: 37:687.
2. Approximate WAC = wholesaler acquisition cost, or manufacturer's published price to wholesalers; WAC represents published catalogue or list prices and may not represent an actual transactional price. Source: AnalySource® Monthly. March 5, 2016. Reprinted with permission by First Databank, Inc. All rights reserved. ©2016. www.fdbhealth.com/policies/drug-pricing-policy.

Download complete U.S. English article

The FDA has required new warnings in the labels of gabapentin (Neurontin, and others) and pregabalin (Lyrica, Lyrica CR, and generics) about the risk of life-threatening or fatal respiratory depression in patients with respiratory risk factors. Respiratory risk factors include chronic obstructive pulmonary disease (COPD) and concurrent use of opioids or other CNS depressants. Elderly patients are also at increased risk.

The FDA has approved Trijardy XR (Boehringer Ingelheim/Lilly), a fixed-dose combination of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin, the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin, and extended-release metformin, for oral treatment of type 2 diabetes in adults. Empagliflozin and linagliptin have been available in a fixed-dose combination as Glyxambi since 2015, and both have been available in 2-drug combinations with extended-release metformin for years (see Table 1).

In Table 3 on page 116 (Med Lett Drugs Ther 2017; 59:113), the price provided for Prevpac was for a 14-day supply, rather than for a 10-day supply as stated in footnote 1. The footnote has been corrected and the price of the generic formulation of Prevpac has been added.

The FDA has approved onasemnogene abeparvovec-xioi (Zolgensma – Avexis), an adeno-associated virus vector-based gene therapy, for one-time IV treatment of children <2 years old who have spinal muscular atrophy (SMA) and bi-allelic mutations in the survival motor neuron 1 (SMN1) gene. It is the first gene therapy and the second drug to be approved in the US for SMA; nusinersen (Spinraza) was approved in 2016.

The FDA has approved bremelanotide (Vyleesi – Amag), a melanocortin receptor agonist, for subcutaneous treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD). Bremelanotide is not approved for use in men or postmenopausal women. It is the second drug to be approved in the US for this indication; flibanserin (Addyi), which was approved in 2015, was the first.