The second opioid overdose reversal agent for over-the-counter (OTC) sale, RiVive (naloxone – Harm Reduction Therapeutics) nasal spray, 3mg/0.1mL, received approval from the U.S. Food and Drug Administration (FDA) on July 28, 2023. RiVive provides temporary reversal of opioid overdoses in emergency settings. By blocking opioid receptors, it displaces the opioid drug and decreases the negative effects of a drug overdose. One dose (one spray) should be given as soon as an overdose is observed or suspected, based on the patient’s breathing difficulty and/or unconsciousness. Emergency medical help should be requested immediately after the first spray. If needed, one additional spray can be given every two to three minutes until professional assistance arrives. With its partner, Catalent, the manufacturer expects to deliver 200,000 doses of RiVive to first responders, state governments, and other agencies free of charge. Although exact pricing for commercial sales has not been revealed, Harm Reduction Therapeutics, a nonprofit organization, states that its price will cover only the expense of making it; no profit will be realized from selling RiVive. Funding partners are being recruited to finance manufacturing and increase production. Packaged in boxes containing two single-dose devices, its release to the U.S. market is planned for early in 2024. Narcan® (naloxone – Emergent BioSolutions) 4mg/0.1mL nasal spray was granted FDA approval for OTC sale in March 2023, but it is not yet available at retail or online. However, in the U.S., naloxone nasal spray, 4mg, can be dispensed at pharmacies without a prescription or it can be prescribed for a caregiver of an at-risk patient, depending on state regulations. Another intranasal product, Amphastar Pharmaceuticals’ Naloxone Nasal Spray, 4mg, is prescription-only, as is a higher strength formulation, Kloxxado® (naloxone nasal spray, 8mg). Neither presently has generic equivalents. Other dosage forms of naloxone remain prescription only, as well. Check here for RiVive’s packaging.
Expanded Indication for Jemperli
GSK’s programmed death receptor-1 (PD-1)-blocker, Jemperli (dostarlimab-gxly) injection, gained new approval from the FDA on July 31, 2023. It already was FDA approved to treat adults who have advanced endometrial cancer that tests positive for deficient mismatch repair (dMMR), that previously has been treated with platinum-containing chemotherapy (chemo) and that is not treatable with surgery or radiation. Now, that indication is extended to frontline therapy, along with chemotherapy (chemo) that includes carboplatin and paclitaxel, to treat primary advanced or recurrent dMMR or microsatellite instability-high (MSI-H) endometrial cancer. Given as 30-minute-long intravenous (IV) infusions, recommended dosing for Jemperli is 500mg once every three weeks, together with chemo, for six cycles. Then, Jemperli is used alone at 1,000mg once every six weeks. In the RUBY clinical study, the Jemperli regimen reduced the chances of cancer worsening by 72% and death by 36% compared to chemo plus a placebo infusion. Keytruda® (pembrolizumab – Merck) is FDA-approved to treat dMMR-positive tumors that originate in multiple tissues, including the endometrium. Jemperli also has Accelerated Approval as second-or-later line therapy for dMMR-positive solid tumors that have no other treatment options. Here is its updated prescribing information.
Lonsurf Indication Extended
The FDA broadened the use of Lonsurf ® (trifluridine/tipiracil – Taiho Oncology) tablets for treating colorectal cancer (CRC) on Aug. 2, 2023. It now is approved for use with the vascular endothelial growth factor (VEGF) inhibitor, bevacizumab, which is available as Avastin® and biosimilars. Lonsurf contains a nucleoside metabolic inhibitor that interrupts DNA production and impedes cell multiplication, and a thymidine phosphorylase inhibitor that limits the breakdown of trifluridine. It now can be used together with bevacizumab to treat adults who have metastatic CRC that already has been treated with chemo that includes fluoropyrimidine, oxaliplatin, and irinotecan; and with a VEGF biological therapy. If the cancer is a renin-angiotensin system (RAS) wild-type, the patient must have been treated with an epidermal growth factor receptor (EGFR) blocker, as well. In the clinical trial that lead to the new indication, overall survival (OS) for patients using Lonsurf and bevacizumab averaged 10.8 months versus 7.5 months for those taking Lonsurf alone. It is taken with food twice a day on days one through five and eight through 12 on 28-day cycles. Its recommended dosing is 35mg/m2/dose with an upper limit of 80mg of trifluridine per dose. Two strengths, trifluridine 15mg/tipiracil 6.14mg and trifluridine 20mg /tipiracil 8.19mg, are available. Lonsurf also is indicated as monotherapy for previously treated metastatic CRC and for metastatic adenocarcinomas of the stomach or gastroesophageal junction for adults who have had two or more specific courses of therapy. Revised prescribing information for Lonsurf is here.
Ervebo Receives Pediatric Indication
Ervebo® (Ebola Zaire vaccine, live – Merck) suspension, was FDA-approved on July 27, 2023, for use in children as young as one year old. It originally was approved late in 2019 to prevent Ebola virus disease resulting from the Zaire strain of Ebola for adults. Transmitted from infected animals that may include fruit bats, Ebolaviruses transfer easily from person to person. Although Ebola is extremely rare in the United States, it is common in other parts of the world, particularly in Africa. Typical symptoms include achiness, fatigue, fever, and unusual bruising or bleeding. If not treated, it can be fatal. For individuals of any age, the dose is 1mL administered as one intramuscular (IM) injection. Injections should be given in a facility that is staffed and equipped to manage rare anaphylactic reactions after inoculation. Other side effects may include decreased appetite, headaches, muscle pain, and injection-site pain; in addition to symptoms similar to those of Ebola infection. However, the vaccine contains only one gene from Zaire Ebola, not the entire virus, so it cannot cause an infection. Because Ervebo is ineffective for other strains of Ebola and for the similar Marburg virus, vaccinated individuals should continue to take precautions against infection. Look here for current prescribing information.
FDA Approval for Onglyza Generics
Several generic companies were approved by the FDA on July 31, 2023, for saxagliptin tablets 2.5mg and 5mg, the first generics for Onglyza® (AstraZeneca). The dipeptidyl peptidase-4 (DPP-4) inhibitor is taken once a day to treat adults who have type 2 diabetes. It can be used alone or taken with other antidiabetes drugs. Claiming shared 180-day exclusivity, Aurobindo introduced its saxagliptin tablets to the U.S. market as soon as it received FDA approval for them. No other company has announced the launch of its generic, yet; and combinations, such as Kombiglyze® XR (saxagliptin/metformin) extended-release tablets continue to be brand-only. For the 12-month period that ended on June 30, 2023, IQVIA estimated annual sales of Onglyza at $101 million.
Generic Approved for Indocin Suppositories
The FDA has approved Zydus Lifesciences’ generic to Indocin® (indomethacin) rectal suppositories, 50mg. The topical non-steroidal anti-inflammatory drug (NSAID) is indicated to treat adults who have moderate-to-severe inflammatory conditions that include acute gouty arthritis, ankylosing spondylitis, bursitis, osteoarthritis, rheumatoid arthritis, and tendinitis. Doses up to 150mg per day should be divided into three or four insertions. Zydus has 180-day exclusivity under the FDA’s Competitive Generic Therapy (CGT) process, which expedites approvals for drugs that have no or very limited alternatives. All prescription-strength NSAIDs have boxed warnings about possibly life-threatening blood clots and gastrointestinal (GI) side effects that may be associated with using them. Launch date and pricing plans are not available for the generic. From May 1, 2022, through April 30, 2023, U.S. sales of Indocin suppositories amounted to about $95 million, according to IQVIA.
On July 31, 2023, Lupin voluntarily recalled two lots of Tydemy™ (drospirenone/ethinyl estradiol/levomefolate calcium) to the consumer level due to out-of-specification test results that could potentially reduce the potency of the medication. Tydemy is an oral contraceptive indicated for the prevention of pregnancy and for raising folate levels in women who choose to use oral contraception for this purpose. Affected lots could be less potent and less effective resulting in an unexpected pregnancy. The FDA notice is here.