Quviviq Approved for Insomnia

The U.S. Food and Drug Administration (FDA) approved Quviviq™ (daridorexant – Idorsia) on Jan. 7, 2022. It is used to treat adults who have insomnia. In the dual orexin receptor antagonist class of drugs, it interferes with neuropeptides that stimulate wakefulness. According to the American Academy of Sleep Medicine, approximately 30% of adults in the U.S. (roughly 62 million people) have occasional insomnia, and about one-third of them have a chronic form of the condition. Defined as trouble falling asleep, frequent awakening during the night and/or early wake-up times on at least three nights a week for at least three months, chronic insomnia is associated with high absenteeism and an increased risk for other conditions, such as depression. To treat insomnia, one tablet, either 25mg or 50mg, of Quviviq will be taken approximately one-half hour before bedtime when the patient has at least seven hours for uninterrupted sleep. Idorsia plans an extensive educational campaign about insomnia leading up to the launch of Quviviq after the U.S. Drug Enforcement Agency (DEA) assigns it to a controlled substance schedule, which typically takes about three months. Two other dual orexin receptor antagonists, Belsomra® (suvorexant – Merck) and Dayvigo® (lemborexant – Eisai), both scheduled as C-IV controlled substances, already have been approved by the FDA, and others are in clinical trials.

MedWatch Updates

LuSys COVID-19 Tests

The FDA issued a safety communication on Jan. 11, 2022, for the nonprescription LuSys COVID-19 tests. Consumers are being asked not to use either the LuSys Laboratories COVID-19 Antigen Test, which uses a nasal or throat swab, or the LuSys Laboratories COVID-19 IgG/IgM Antibody Test, which needs a blood sample. Also labeled as EagleDx, Luscient Diagnostics or Vivera Pharmaceuticals; the tests have not been FDA approved for the U.S. market. The FDA has determined that they are likely to be inaccurate – sometimes missing true COVID-19 infections and sometimes incorrectly indicating a person has COVID-19. Anyone who suspects a result from a LuSys COVID-19 test was wrong should ask a healthcare provider if a new test should be done. More information is in this FDA notice.

Dissolvable Buprenorphine

On Jan. 12, 2022, the FDA issued a caution about increased risks of cavities and other dental problems from using forms of buprenorphine that dissolve under the tongue or on the inside of the cheek. Some patients have had serious infections or other dental issues that have resulted in the need for root canals, dental surgery or tooth extractions. Although problems typically appeared an average of two years after beginning therapy, some patients experienced trouble in as little as two weeks. Indicated to relieve pain and as part of a combination of therapies to treat opioid use disorder, buprenorphine may be used alone or in films or tablets that also contain naloxone. It should not be stopped without the advice of a health professional. The FDA is advising patients who use one of the dissolving dosage forms to work with their dentists on ways to decrease the risk. Additionally, once the film or tablet is completely dissolved, the patient should swish a large sip of water carefully around the mouth and then swallow the water. Patients should not brush their teeth for at least one hour. Look here for additional information.

Recorlev Approved for Treating Cushing’s Syndrome

On Dec. 30, 2021, the U.S. Food and Drug Administration (FDA) approved Xeris Biopharma’s Recorlev® (levoketoconazole) tablets. It inhibits the production of cortisol to treat adults who have Cushing’s syndrome. Known as the “stress hormone”, cortisol suppresses nonessential body functions during emergencies. Too much of it can raise blood pressure, blood sugar and cholesterol. For patients who have the rare disease, Cushing’s syndrome, continual excessively high cortisol levels can lead to blood clots, depression, diabetes, heart attacks, infections and strokes. An isomer of ketoconazole, Recorlev reduces excess cortisol by blocking enzymes that are crucial to cortisol production. Starting at 150mg twice a day, doses can be raised by 150mg/day once every three to four weeks as needed to a maximum of no more than 1,200mg divided into two equal doses daily. Recorlev carries a boxed warning that patients need electrocardiograms (ECGs) before and periodically during treatment with it, because it may cause heart rhythm disturbances. Taking ketoconazole may be associated with rare cases of liver damage, so liver enzyme tests also should be performed regularly while patients are taking Recorlev. Xeris, the company that recently acquired Strongbridge Biopharma, the developer of Recorlev, intends to release the drug in the first quarter of 2022, but cost estimates are not yet available.

Rexulti Receives FDA Approval for Teens

The FDA extended the indications for Rexulti® (brexpiprazole – Otsuka Pharmaceuticals/Lundbeck) tablets on Dec. 27, 2021, to include monotherapy for treating schizophrenia for patients between the ages of 13 years and 18 years. Rexulti also is approved alone to treat adults who have schizophrenia and with other drugs for adults who have major depression. For adolescents younger than 18 years old, recommended dosing begins at 0.5mg/day for the first four days, increases to 1mg/day for the next three days and then to 2mg/day. If needed, the highest recommended daily dose is 4mg. A boxed warning on its labeling reminds patients and prescribers that no atypical antipsychotic, including Rexulti, should be used to manage psychoses related to dementia in elderly patients because their chances of death are increased. Additionally, taking it may increase thinking about or attempting suicide by patients up to about 24 years of age. Younger patients should be observed for any signs of suicidal tendencies. In clinical trials, teens taking Rexulti gained an average of 3.8kg (about eight pounds), about one in ten experienced increased sleepiness and smaller percentages of patients had increases in blood sugar and/or cholesterol levels. Check here for prescribing information.

Lower-Dose Bijuva Approved

A new strength of Bijuva (estradiol/progesterone – TherapeuticsMD) capsules was approved by the FDA on Dec. 28, 2021. Because using the lowest effective dose of an estrogen is recommended to minimize the risk of side effects, it contains one-half the dose (0.5mg) of estradiol as is in the original formulation, which was FDA approved in 2018 at 1mg estradiol and 100mg of progesterone. Bijuva is indicted to relieve moderate-to-severe vasomotor symptoms, such as hot flashes, for postmenopausal women who have not had hysterectomies. One capsule is taken each evening with food. Labels on all female hormone replacement therapies (HRTs) have boxed warnings that using an estrogen/progestin combination may raise the risk of serious blood clots, breast cancer, dementia, heart attacks and strokes. Taking estrogen by itself may contribute to developing cardiovascular (CV) conditions, dementia and endometrial cancer. No type of HRT should be used for preventing CV disease or dementia. Here is revised prescribing information for Bijuva.

COVID-19 Issues Document Updated

The Emerging Therapeutics department updated the “Coronavirus Disease 2019 (COVID-19) Vaccine Update” issues document. This update adds information on boosters. The issues document is attached.

Recalls

Taro Clobetasol Ointment

On Dec. 27, Taro Pharmaceuticals recalled one lot (AC13786) of clobetasol ointment, 0.05% in 60gm tubes. Samples from the affected lot contained Ralstonia pickettii bacteria, which could cause severe systemic infections if contaminated ointment is used on damaged skin – especially for immunocompromised patients. The ointment usually is prescribed to treat dermatitis, eczema and other skin conditions that can be managed by a corticosteroid. More information is in this notice from the FDA.

Padagis Nitroglycerin Spray

Padagis, the manufacturer of Nitroglycerin Lingual Spray 400mcg/spray, recalled three lots of their 12gm bottles to the consumer level because some of the spray devices may not be assembled properly. The recall was issued on Dec. 27, 2021. Doses of the drug, used to relieve acute chest pain associated with coronary artery disease, may not be accurate. Although Padagis makes the recalled devices, they are labeled in the U.S. as a Perrigo product. Here is a press release from Padagis.

Viona Metformin

Viona Pharmaceuticals, the U.S. generics division of Cadila Healthcare, recalled all 33 lots of metformin extended-release tablets, 750mg, which were released in the U.S. on Dec. 28, 2021. The recalled product tested over allowed limits for nitrosodimethylamine (NDMA), the same probable carcinogen that previously prompted the recall of other metformin products (including one from Viona in June) and drugs from other therapy classes. Although it is at Class II (retail) level, we treated the recall as Class I (patient) level because previous recalls for elevated nitrosamines have been treated in house as Class I. The FDA’s notice is here.

Hizentra

CSL Behring withdrew one lot (P100343632, which expires on Nov. 24, 2023) of Hizentra® (immune globulin injection [human]), 20% (NDC# 44206-0455-10) on Dec. 30, 2021. As with previous immune globulin withdrawals, a higher-than-normal number of patients using product from the withdrawn lot have experienced hypersensitivity reactions – some have been serious. Immune globulins are used to treat deficiency conditions such as idiopathic thrombocytopenic purpura (ITP) and primary humoral immunodeficiency (PIDD). Here is additional Information.