FDA Approved Drugs: December 2020

Recall Nostrum Laboratories Metformin Extended Release

Nostrum Laboratories recalled four lots of metformin extended-release tablets, 500mg and 750mg on Nov. 2, 2020. Tablets in the recalled lots tested above the limits allowed by the FDA for a potential carcinogen, N-nitrosodimethylamine (NDMA). Patients are advised not to stop taking affected tablets, but to consult with their prescribers for a different prescription, if necessary. More information is in the FDA notices here and here.

New Brilinta Indication

On Nov. 5, 2020, the FDA approved Brilinta^® (ticagrelor – AstraZeneca) tablets to lessen the risk of a stroke forpatients who have had an acute ischemic stroke classed at five or below on the National Institutes of Health (NIH) Stroke Scale or who have had a high-risk transient ischemic attack (TIA). For the new indication, the recommended dose is 180mg of Brilinta on the first day, and then 90mg taken twice daily for up to one month. It is used along with a 300mg or 325mg aspirin on day one, followed by 75mg to 100mg of aspirin daily. In the decisive clinical trial, the risk of a stroke or death was 17% lower for patients taking both Brilinta and aspirin than it was for patients taking only aspirin. However, more patients in the Brilinta/aspirin group experienced severe bleeding episodes (28 vs seven in the aspirin group); and no significant differences in the rates of disability were seen between the two participant groups. Brilinta actually carries a boxed warning that it poses an increased risk of bleeding. Its label also cautions that doses of aspirin exceeding 100mg/day should not be taken at the same time as Brilinta because higher doses diminish the drug’s effectiveness. The antiplatelet agent already had an indication to decrease the chance of a first heart attack or a stroke for patients who have coronary artery disease (CAD) and who are at high risk for an adverse cardiovascular (CV) event. It also is FDA approved to reduce the risk of additional CV events for patients who have had a heart attack or who have acute coronary syndrome (ACS).Check here for its complete revised prescribing information.

First Vascepa Generic Launched

Hikma Pharmaceuticals USA announced on Nov. 5, 2020, that it has released icosapent ethyl 1 gram capsules, a generic for Amarin’s Vascepa^®, in the United States. It is used along with diet changes to decrease triglyceride (TG) levels for patients who have severely high TG. It has an additional indication with the highest tolerable doses of a statin drug to decrease the risk of adverse CV events for patients who have high TG levels along with known CV disease or type 2 diabetes and two or more CV disease risk factors. Recommended dosing is 4gm daily – taken as two capsules (2gm each) with food two times a day. Initially, supplies of icosapent ethyl capsules will be limited as Hikma ramps up production capacity. According to Amarin’s 2019 financial reports, sales of Vascepa totaled over $400 million for the year.

FDA Approves Sesquient

The FDA approved Sesquient^™ (fosphenytoin for injection - Sedor Pharmaceuticals) on Nov. 5, 2020. It is indicated for the treatment of adults who are experiencing status epilepticus, which is a serious generalized tonic-clonic seizure that lasts five minutes or longer or recurs within five minutes. Also approved to prevent and treat seizures that may be associated with neurosurgery, it can be used temporarily to replace oral doses of phenytoin tablets for patients at least two years old when oral treatment isn’t possible. A new formulation of fosphenytoin, it is the first injectable that can be stored at room temperature, making it faster to dilute for quick injection. Dosing by intravenous (IV) infusion differs according to the condition being treated and the age of the patient. A boxed warning cautions that infusing Sesquient too fast may radically lower blood pressure and/or cause heart rhythm changes. Cardiac monitoring is required for all patients while and after receiving it. For its full prescribing information, look here.

Recall Paroex by Sunstar Americas

Following a previous recall of the branded product, Paroex^® by Sunstar Americas, Lohxa recalled its alcohol-free chlorhexidine oral rinse, 0.12% to the consumer level on Nov 9, 2020. Both products are manufactured in the same facility by Sunstar. Some of Lohxa’s product, which is distributed to hospitals in single-dose cups, may be contaminated with bacteria that could cause infections in the mouth. Patients who have immunocompromising conditions may have a risk of systemic infections that could be fatal. For more information about the recall, the FDA notice is here.

Sutab FDA Approved

The Braintree Laboratories division of Sebela Pharmaceuticals received FDA approval for Sutab^® (sodium sulfate/magnesium sulfate/potassium chloride) tablets on Nov. 10, 2020. Sutab is an oral osmotic laxative indicated for use by adults to cleanse the bowels before a colonoscopy. It is a new option to the currently available bowel preparation products, including GoLYTELY^® (polyethylene glycol 3350/electrolytes oral solution), which typically require patients to drink one gallon (128 ounces) of solution at a rate of eight ounces every 10 minutes. Although Sutab does not need as much liquid taken so fast, it still must be taken with a good amount of water. On the day before the colonoscopy is scheduled, the patient should not have any solid foods, milk or alcohol after a light breakfast. Only clear liquids, such as black coffee or tea, clear soda, gelatin or fruit juices without any bits of fruit in them, should be consumed. The first dose of Sutab is taken in the evening. Directions are to fill the 16-ounce container that comes with each Sutab prescription with water and to drink the entire amount as the first 12 tablets are swallowed over 15 to 30 minutes. Another full container of water should follow the first dose after about 60 minutes and a third about 30 minutes after the second. The next day, at least four hours after the first dose and five to eight hours before the procedure, the second dose should be taken in the same way as the first. A Medication Guide gives the patient clear instructions on doses and timing. Sutab is expected to be launched on Jan. 1, 2021, in cartons that include two bottles of 12 tablets each and one container that holds 16 ounces of water. Here is prescribing information for Sutab.

New Indication for Keytruda

To be used along with chemotherapy (chemo), Keytruda^® (pembrolizumab - Merck) is now FDA approved to treat triple negative breast cancer (TNBC) that has metastasized or that cannot be removed by surgery. Keytruda is a human programmed death receptor-1 (PD-1)-blocking antibody that helps the body’s immune system attack cancer cells. The new indication was granted on Nov. 13, 2020 for patients whose TNBC tests positive for PD-1. TNBC is a difficult-to-treat cancer that accounts for about 15% to 20% of the estimated 270,000 cases of breast cancer diagnosed annually in the U.S. In clinical trials, the risk of dying or cancer worsening was reduced by 35% for patients receiving Keytruda along with a chemo regimen that included either paclitaxel, Abraxane^® (paclitaxel, protein bound) or the combination of carboplatin and gemcitabine than for patients who got only chemo. Keytruda also has a number of previous indications for various other types of cancer, including some that are classified by particular genetic mutations, rather than by organ system. For most of its indications, including for TNBC, Keytruda is administered as a 30-minute IV infusion at 200mg once every three weeks or 400mg once every six weeks. Because the TNBC indication was given under the FDA’s Accelerated Approval program, safety and effectiveness will need to be confirmed in further studies before full approval is given. Revised, complete prescribing information may be found here.

Vimpat’s Indications Extended

Vimpat^® (lacosamide - UCB) was approved by the FDA on Nov. 16, 2020, for use as an add-on to treat patients who are at least four years old and who have primary generalized tonic-clonic seizures. It initially was FDA approved as combination therapy with other drugs to treat adults who have partial-onset seizures due to epilepsy. Later, the C-V controlled substance got additional approvals, including as a single agent and as treatment for children as young as four years old who have partial-onset seizures. Although its exact mechanisms are not completely understood, Vimpat works differently from other antiepileptic medications. By reducing sodium channel over-activity it is believed to calm nerve cells and contribute to the control of seizures. Designed to be used twice a day, doses vary according to the condition being treated and the age of the patient. Vimpat is available as oral tablets and an oral solution as well as an injectable form for short-term use when oral dosing is not possible. Look here for full prescribing information.

Fixed-Dose Use Expanded for Imfinzi

On Nov. 18, 2020, AstraZeneca received FDA approval for a set Imfinzi^® (durvalumab) dose of 1,500mg for two indications that previously only had dosing that depends on the patient’s weight. Now, patients who weigh 30kg (66 pounds) or more and whose advanced urothelial carcinoma or stage III non-small cell lung cancer (NSCLC) progresses despite prior drug therapy, can be treated with either regimen. Earlier in 2020, it received an indication, along with chemo, at the fixed 1,500mg dose administered once every three weeks to treat adults who have extensive-stage small cell lung cancer (ES-SCLC). For its other two indications, Imfinzi is given as one-hour IV infusions once every two weeks when based on weight or once every four weeks at the 1,500mg dose. Patients weighing less than 30kg still will receive 10mg/kg once every two weeks to treat urothelial carcinoma or NSCLC; and 20mg/kg once every three weeks for ES-SCLC. Here is updated prescribing information.

Zokinvy Approved to Treat Progeria

Eiger BioPharmaceuticals received approval from the FDA on Nov. 20, 2020, for Zokinvy^™ (lonafarnib) capsules. It is the first drug approved to treat children at least one year old and who have a body surface area (BSA) of at least 0.39m², for the very rare terminal condition, Hutchinson-Gilford progeria syndrome, which commonly is known as progeria. It also is indicated to treat some progeroid laminopathies (mutations in the lamin A or another gene) that are similar to, but different from progeria. Ultra-rare hereditary conditions, progeria and its associated laminopathies cause defective proteins that accumulate in the body to destabilize cell nuclei and greatly accelerate the aging process for fewer than 400 patients worldwide. Zokinvy inhibits farnesyltransferase, an enzyme involved in producing defective lamin A. It is taken twice daily with a starting dose of 115mg/m² rounded off to the nearest 25mg. After four months of treatment, doses increase to 150mg/m², also rounded to increments of 25mg. Cost and launch plans are not yet available. Check here for its complete prescribing information.

Oxlumo Approved to Treat Primary Hyperoxaluria

On Nov. 23, 2020, the FDA approved Oxlumo^™ (lumasiran – Alnylam Pharmaceuticals) injection. A small interfering ribonucleic acid (siRNA), it is the first drug to be approved for treating primary hyperoxaluria (PH) – specifically, type 1 (PH1), the most common form of the disorder. A group of rare inherited metabolic conditions that affect only a few thousand Americans, PH is caused by too much oxalate in the body. Oxalate accumulation damages the kidneys, leading to end-stage renal disease (ESDR) and kidney failure. Other problems, such as anemia, delayed growth, eye problems and heart disease can develop as oxalate crystals deposit in various parts of the body. By interrupting activity of the hydroxyacid oxidase 1 (HAO1) gene, Oxlumo decreases the amounts of an enzyme needed for oxalate production. Administered by subcutaneous (SC) injection, it is dosed by weight with the first three doses on a monthly schedule, then changed to once every three months. Although the wholesale acquisition cost (WAC) for Oxlumo is $490,000, Alnylam is working with payers to establish pricing agreements based on the drug’s actual value. For Oxlumo’s complete prescribing information, look here.

New Indication and Dosage Form for Xofluza

Xofluza^™ (baloxavir), Genentech’s one-dose influenza (flu) treatment, was granted a new indication on Nov. 23, 2020. Now, it is approved to prevent flu for individuals who are at least 12 years old and who have had contact with a flu patient. At the same time, the FDA also approved a new Xofluza formulation – granules for oral suspension – for patients who cannot swallow tablets. It did not, however, extend the use of the drug to children younger than 12 years old. Working differently from other flu drugs, Xofluza interferes with the ability of influenza virus to reproduce by inhibiting influenza cap-dependent endonuclease, an enzyme that is involved in viral replication. Initially, it was FDA approved in 2018 as oral tablets for the treatment of acute, uncomplicated flu for patients 12 years of age and older who have been symptomatic for no more than 48 hours. The following year, its approval expanded to include patients in the same age groups who have underlying conditions, such as asthma, diabetes and heart disease, which make them more likely to experience complications from having the flu. Recommended dosing is 40mg (two 20mg tablets or one bottle of suspension) for those who weigh between 40kg (about 88 pounds) and 80kg (about 175 pounds). Patients weighing 80kg or more should receive a single dose of 80mg (two 40mg tablets or two bottles of suspension). Xofluza is not approved for patients weighing less than 40kg. Taking it should be separated by several hours from eating or drinking dairy foods, using antacids and taking mineral supplements. No antiviral, including Xofluza, replaces the need for an annual flu vaccination, which remains the best way to help protect against getting the flu. Access revised prescribing information for Xofluza here.

Danyelza Approved for Neuroblastoma

On Nov. 25, 2020, the FDA approved Danyelza^® (naxitamab-gqgk – Y-mAbs Therapeutics). In combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), it is approved for the treatment of pediatric patients one year of age and older and adult patients who have relapsed or refractory high-risk neuroblastoma in the bone or bone marrow and who have demonstrated a partial response, minor response or stable disease to prior therapy. Neuroblastoma, a rare type of cancer that primarily affects children, originates in underdeveloped nerve cells called neuroblasts. In the U.S., neuroblastoma affects about 800 patients annually. Danyelza is a humanized anti-GD2 monoclonal antibody. It is administered as an IV infusion at a dose of 3mg/kg/day, with a maximum of 150mg per day, on days 1, 3 and 5 of each treatment cycle. Cycles should be given every four weeks until the patient has a complete or partial response, followed by five more cycles once every four weeks. Following cycles may switch to infusions once every eight weeks on the same days of the cycle. Approval came following two clinical studies with the primary outcomes being overall response rate (ORR) and duration of response (DOR) according to the International Neuroblastoma Response Criteria (INRC). In one study evaluating 22 patients, 36% of patients had a complete response (CR) and 9% had a partial response (PR). The DOR was a median of 6.2 months with 30% having a DOR lasting six months or more. In another study evaluating 38 patients, 26% of patients had a CR and 8% had a PR. The DOR of six months or more was seen in 23% of patients. The labeling for Danyelza has a boxed warning concerning serious infusion-related reactions and neurotoxicity, including nerve pain. Danyelza should be discontinued if the disease progresses or the patient experiences too many toxic side effects. Y-mAbs Therapeutics plans to launch the medication in the coming weeks at a price that has not been disclosed. For full prescribing information see here.

Imcivree Approved to Treat Certain Genetic Causes of Obesity

Rhythm Pharmaceuticals received approval from the FDA on Nov. 25, 2020, for its first drug, Imcivree^™(setmelanotide). It also is the first drug to treat obesity resulting from deficiencies of proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR). Very rare disorders caused by defects in specific genes, the conditions involve the brain’s melanocortin-4 (MC4) receptors, which regulate hunger and energy use. Patients who have obesity caused by POMC, PCSK1 or LEPR deficiency experience continual hunger despite eating large quantities of food. Even when following a reduced-calorie diet, patients gain weight rapidly, generally becoming severely obese in childhood. By activating MC4 receptors, Imcivree helps reduce appetite, promote the feeling of fullness and increase energy output. It is given by daily SC injections. After genetic testing confirms or suggests an appropriate deficiency, dosing for Imcivree consists of two weeks at 1mg daily for patients between six and 12 years of age and 2mg for older patients. Then, doses may be adjusted to a daily maximum of 2mg for children and 3mg for teens and adults, if weight loss is not adequate. Downward dose adjustments can be considered for patients who have side effects, such as nausea, from the injections. Imcivree should be stopped for patients who have not lost 5% or more of their body weight after 12 to 16 weeks of treatment. Rhythm plans a launch in the first quarter of next year. Imcivree’s full prescribing information may be found here.

Xolair Receives Additional FDA Approval

The FDA approved Genentech’s monoclonal antibody, Xolair^® (omalizumab), for a third indication on Nov. 30, 2020. The new approval is to treat adults who have nasal polyps that have not responded to treatment with nasally inhaled corticosteroids. By blocking immunoglobulin E (IgE) Xolair reduces inflammation. While steroid therapy continues, Xolair will be administered by a healthcare provider as an SC injection once every two weeks or once every four weeks. Doses vary based on the patient’s weight and IgE blood levels. Injections must be given in a facility staffed and equipped to manage emergencies because Xolair may cause anaphylaxis (severe allergic reactions), as described in a boxed warning on its labeling. Patients should stay under observation at the healthcare facility for enough time after each injection to be sure no reaction will occur. Originally indicated to treat patients at least six years old for persistent allergic asthma that resists inhaled corticosteroid treatment, Xolair has an additional FDA approval for patients age 12 and older who have hives due to chronic idiopathic urticaria (CIU) that has not responded adequately to antihistamines. Look here for complete prescribing information.