FDA Approves Dextroamphetamine Patches

On March 22, 2022, the U.S. Food and Drug Administration (FDA) approved Noven Pharmaceuticals’ Xelstrym™ (dextroamphetamine) transdermal system, C-II, the first transdermal dosage form for dextroamphetamine. It is approved to treat attention deficit hyperactivity disorder (ADHD) for patients who are at least six years old. One patch is applied to varying places on the patient’s chest, hip, side, upper arm or upper back daily about two hours before the full effect is needed, and then removed after nine hours. Launch is planned for the second half of 2022 in boxes of 30 individually wrapped patches of 4.5mg, 9mg, 13.5mg or 18mg strengths per nine hour use period. The recommended initial doses are 4.5mg/9hrs for patients between six years and 17 years old, and 9mg/9hrs for older patients. For either age group, the maximum daily dose is 18mg/9hr. Because Xelstrym is a central nervous system (CNS) stimulant, it carries a boxed warning about its risks for abuse and dependency. It cannot be interchanged for equal strengths of other amphetamines. Used patches should be folded with the sticky sides together, placed into sealed containers and taken to a local drug-take-back site.

New Keytruda Indication

Merck received an additional approval for Keytruda® (pembrolizumab) injection on March 21, 2022. The FDA approved it as monotherapy to treat patients who have advanced endometrial carcinoma that is proven by an FDA-certified diagnostic test to be microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). The cancer must have gotten worse despite previous systemic therapy and it must not be treatable with surgery or radiation. In the open-label clinical trial that led to the approval, responses lasted at least 24 months for 44% of the 41 patients who responded fully or partially to treatment with Keytruda. The recommended dose is 200mg once every three weeks or 400mg once every six weeks for up to two years or until the cancer progresses or the patient cannot stand the drug’s side effects. Some patients have had severe immune-related adverse reactions that can involve nearly any organ system. It can harm developing fetuses, so Keytruda should not be used during pregnancy. Administered as a 30-minute intravenous (IV) infusion, Keytruda is used alone or in combination with one of several other oncology drugs. Along with Lenvima® (lenvatinib), it is indicated for certain endometrial carcinoma that is neither MDI-H nor dMMR. Its multiple other indications include treatment for Merkel cell carcinoma, multiple myeloma, non-Hodgkin lymphoma and some esophageal, head and neck, kidney, lung and stomach cancers.

Revision for Cabenuva Dosing

When it was first approved by the FDA in January 2021, Cabenuva (co-packaged cabotegravir extended-release injection and rilpivirine extended-release injection – ViiV Healthcare) required lead-in therapy with oral treatment for one month before the first injection. One tablet each of Vocabria (cabotegravir) and Edurant® (rilpivirine) were taken daily to assure that patients did not have severe reactions to the medications. The oral phase-in period now is not required, but it can be used if desired. In the long-term results from an ongoing clinical study, the effectiveness and safety of Cabenuva were comparable whether or not the patient used its corresponding oral therapy, first. Dosing for Cabenuva is separate injections of cabotegravir and rilpivirine given by a health professional as intramuscular (IM) shots at the same time once a month. It is indicated as an alternative to oral therapy for adult patients who have HIV-1 with no previous treatment failures and viral loads less than 50 copies of HIV-1 RNA/mL due to a current stable anti-HIV-1 regimen. Adverse effects from Cabenuva generally are mild-to-moderate and temporary. They include dizziness, fatigue, fever, headache, nausea, rash and irritation at the injection site.

Nonprescription Nasonex Now Approved

Nasonex® 24HR Allergy (mometasone) was FDA approved for over-the-counter (OTC) sale on March 17, 2022. The corticosteroid nasal spray relieves congested, itchy, runny noses and sneezing due to allergic rhinitis for adults, teens and children as young as two years old. For children up to 11 years of age, the daily dose is one 50mcg spray per nostril; older patients use two sprays per nostril once a day. Perrigo hopes to introduce bottles containing 30, 60 or 120 sprays to retail sites later in 2022. Price is not yet known.

Pluvicto™

Novartis received approval from the U.S. Food and Drug Administration (FDA) on March 23, 2022, for Pluvicto™ (lutetium Lu 177 vipivotide tetraxetan) injection. The radioligand therapy (RLT), includes a targeting agent and a radioactive isotope to treat prostate cancer that tests positive for prostate-specific membrane antigen (PSMA) and that has metastasized despite previous therapy with an androgen receptor inhibitor and chemotherapy (chemo) with a taxane drug, such as docetaxel. The recommended dose is 7.4 GBq (200 mCi) given by intravenous (IV) injection or infusion once every six weeks for up to six doses, depending on how the cancer responds and how the patient tolerates therapy. It will be available to facilities that are equipped to handle radioactive pharmaceuticals within the next few weeks. The wholesale acquisition cost (WAC) will be $42,500 per dose.

At a Glance

• Brand (Generic) Name: Pluvicto (lutetium Lu 177 vipivotide tetraxetan)
• Manufacturer: Novartis
• Date Approved: March 23, 2022
• Indication: to treat adults who have PSMA-positive, metastatic castration-resistant prostate cancer (mCRPC) and who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy
• Dosage Forms Available: single-dose vials containing 7.4 GBq (200 mCi) ± 10% of lutetium Lu 177 vipivotide tetraxetan for IV injection or infusion
• Launch Date: within weeks
• Estimated Annual Cost: $255,000 if all six doses are given
• The prostate is a small gland below the bladder and surrounding the urethra in males. It is responsible for producing parts of seminal fluid.
• The American Cancer Society estimates that about 270,000 cases of prostate cancer will be discovered in the U.S. in 2022. Most patients are age 65 and older and African-Americans are affected more than members of other ethnicities. Most cases are diagnosed at early stages, but approximately 8% of newly diagnosed cases are metastatic, with a five-year survival rate of about 30%.
• Symptoms of prostate cancer are very similar to those of benign prostatic hyperplasia (BPH), a nonmalignant enlargement of the prostate. They may include bloody urine, difficulty urinating and erectile dysfunction (ED). Prostate cancer usually is detected through a blood test that measures blood levels of prostate-specific antigen (PSA).
• Pluvicto sticks to PSMA and releases radiation from its Lu component to damage DNA in prostate cancer cells.
• The FDA also approved the diagnostic test, Locametz® (gallium Ga 68 gozetotide), which is used with positron emission tomography (PET) scans to identify prostate cancer metastases.
• In the VISION clinical trial, all patients continued on their regular treatment for prostate cancer. About one-third of the patients who also were treated with Pluvicto responded to treatment versus only around 2% of those who did not. Additionally, the risk of death decreased by 38% for those using Pluvicto. Their chances of cancer progression also declined.
• The most common adverse effects for study participants using Pluvicto were anemia, constipation, decreased appetite, dry mouth, fatigue and nausea.
• The multiple treatments available for middle and late stages of prostate cancer include surgery, radiation and cryotherapy (extreme cold). Chemo, hormone therapy, immunotherapy, targeted drugs and a vaccine are among the drugs used to treat it.
• Metastatic prostate cancer most often is treated with drugs that reduce testosterone levels in the body. Although several different pathways may be effective, the cancer eventually becomes resistant to such hormonal therapies.
• Pluvicto, which has a Breakthrough Therapy designation, was approved with the FDA’s Priority Review.

Recalls

Enalapril

On March 16, 2022, Golden State Medical Supply recalled 76 lots of 90-count bottles of enalapril tablets, an angiotensin-converting enzyme (ACE) inhibitor used to manage blood pressure and heart failure. Levels of an unidentified impurity that were well above specified upper limits were detected in samples of the recalled lots. Possible effects on patients taking the recalled tablets are not known. For more information, call Golden State Medical Supply at 800.284.8633, Option 2.

Accuretic

Pfizer recalled several lots of its ACE inhibitor and diuretic combination, Accuretic®, along with its authorized generics, quinapril/hydrochlorothiazide, on March 21, 2022. Higher than allowed levels of a potentially carcinogenic substance, N-nitro-quinapril, were found in the affected lots. No patients have reported adverse effects, but the recall is to the consumer level.

Orphenadrine

Sandoz is recalling 13 lots of orp13 lots of orphenadrine extended-release tablets to the consumer level due to unacceptably high amounts of nitroso-orphenadrine (NMOA), a potential carcinogen. The drug is a muscle relaxer used to treat musculoskeletal pain.