Updates from FDA
New drugs
COPPER CU 64 DOTATATE INJECTION
(Detectnet—RadioMedix, Curium)
Drug class: Radioactive diagnostic agent
Indication: For use with positron emission tomography (PET) for localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adult patients
Recommended dosage and administration: 148 MBq (4 mCi) administered as an I.V. bolus injection. Begin acquiring images 45 to 90 minutes after administration.
Common adverse effects: Nausea, vomiting, and flushing
Warnings and precautions: Radiation risk and risk for image misinterpretation. Advise patients to interrupt breastfeeding for 12 hours after drug administration.
Drug interactions: Somatostatin analogs competitively bind to the same somatostatin receptors as copper Cu 64 dotatate and may affect imaging.
TRAMADOL HYDROCHLORIDE, ORAL SOLUTION C-IV
(Qdolo—Athena Bioscience)
Drug class: Opioid agonist
Indication: In adults, management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate
Recommended dosage and administration: Start at 25 mg/day and titrate in 25 mg increments as separate doses every 3 days to reach 100 mg/day (25 mg four times a day). Thereafter, total daily dose may be increased by 50 mg as tolerated every 3 days to reach 200 mg/day (50 mg four times a day). After titration, 50 mg to 100 mg can be administered as needed for pain relief every 4 to 6 hours not to exceed 400 mg/day. Initiate dosing regimen for each patient individually, considering patient’s severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction and misuse. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.
Common adverse effects: Dizziness/vertigo, nausea, constipation, headache, somnolence, vomiting, and pruritus
Boxed warning: Risk of medication errors; addiction and misuse; Risk Evaluation and Mitigation Strategy (REMS); life-threatening respiratory depression; accidental ingestion; ultra-rapid metabolism of tramadol and other risk factors for life-threatening respiratory depression in children; neonatal opioid withdrawal syndrome; interactions with drugs affecting cytochrome P450 isoenzymes; and risks from concomitant use with benzodiazepines or other CNS depressants.
Other warnings and precautions: Serotonin syndrome; risk of seizure; risk of suicide; adrenal insufficiency; life-threatening respiratory depression in patients with COPD or in older, cachectic, or debilitated patients; severe hypotension; risks of use in patients with increased intracranial pressure, brain tumors, head injury, or impaired consciousness. May cause fetal harm in pregnant patients. Breastfeeding not recommended during treatment.
Drug interactions: Mixed agonist/antagonist and partial agonist opioid analgesics
Contraindications: Children younger than 12 years; postoperative management in children younger than 18 years following tonsillectomy and/or adenoidectomy; significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; known or suspected GI obstruction, including paralytic ileus; hypersensitivity to tramadol, any of its components, or opioids; concurrent use of MAOIs or use of MAOIs within the last 14 days.
New formulation
HYDROCORTISONE ORAL GRANULES
(Alkindi Sprinkle—Eton Pharmaceuticals)
Drug class: Corticosteroid
Indication: Replacement therapy in pediatric patients with adrenocortical insufficiency
Recommended dosage and administration: Individualize the dose using the lowest possible dosage. The recommended starting replacement dosage is 8 to 10 mg/m2 daily. Higher doses may be needed based on patient’s age and symptoms. Round the dose to the nearest 0.5 mg or 1 mg. More than one capsule may be needed to supply the required dose. Divide the total daily dose in 3 doses and administer 3 times daily. Older patients may have their daily dose divided by 2 and administered twice daily. Alkindi Sprinkle are oral granules contained within capsules. Do not swallow the capsule. Do not chew or crush the granules.
Common adverse effects: Fluid retention, alteration in glucose tolerance, elevation in blood pressure, behavioral and mood changes, increased appetite and weight gain
Warnings and precautions: Adrenal crisis, infections, growth retardation, Cushing’s syndrome due to use of excessive doses of corticosteroids, decrease in bone mineral density, psychiatric adverse reactions, ophthalmic adverse reactions, GI adverse reactions
Drug interactions: CYP3A4 inhibitors, CYP3A4 inducers, estrogen and estrogen-containing products, antidiabetic agents, NSAIDs
Contraindications: Hypersensitivity to hydrocortisone or to any of the ingredients in Alkindi Sprinkle
New indication, formulation
TOFACITINIB ORAL SOLUTION
(Xeljanz—P zer)
Drug class: Janus kinase (JAK) inhibitor
Indication: Treatment of active polyarticular course juvenile idiopathic arthritis (pcJIA) in patients aged 2 years and older
Recommended dosage and administration: Oral solution 5 mg twice daily or weight-based equivalent twice daily. Dosage adjustment needed in patients with moderate and severe renal impairment or moderate hepatic impairment. Do not initiate if patient has an absolute lymphocyte count less than 500 cells/mm3, an absolute neutrophil count less than 1000 cells/mm3, or hemoglobin less than 9 g/dL.
Common adverse effects: Upper respiratory tract infection, nasopharyngitis, diarrhea, and headache
Boxed warning: Serious infections; mortality; malignancy; and thrombosis, including deep vein and arterial
Other warnings and precautions: Increased risk of GI perforations. Laboratory monitoring recommended due to potential changes in lymphocytes, neutrophils, hemoglobin, liver enzymes, and lipids. Avoid live vaccines during treatment. Breastfeeding during treatment not recommended.
Drug interactions: Dosage adjustments for patients taking strong CYP3A4 inhibitors or a moderate CYP3A4 inhibitor with a strong CYP2C19 inhibitor. Concurrent use with strong CYP3A4 inducers. Use in combination with biologic disease-modifying antirheumatic drugs (DMARDs) or with potent immunosuppressants such as azathioprine and cyclosporine is not recommended.
FDA OKs first treatment in nearly 14 years for a group of rare blood disorders
On September 25, FDA approved mepolizumab (Nucala—GlaxoSmithKline) for treatment of hypereosinophilic syndrome (HES), a heterogeneous group of rare disorders associated with persistent eosinophilia. The drug is indicated for adult and pediatric patients aged 12 years and older who have had HES for at least 6 months without an identifiable nonhematologic secondary cause. The new indication for mepolizumab marks the first treatment approval for HES in nearly 14 years.
“[This] approval marks the first time in over a decade that there is a new FDA-approved treatment option for patients with hypereosinophilic syndrome,” said Ann Farrell, MD, director of the Division of Nonmalignant Hematology in FDA’s Center for Drug Evaluation and Research, in a statement. “FDA is committed to helping develop safe and effective treatment options for this group of rare and debilitating blood diseases and other rare conditions.”
The recommended dosage of mepolizumab for patients with HES is 300 mg as separate 100-mg injections administered subcutaneously once every 4 weeks. Common adverse effects include headache, injection site reaction, back pain, and fatigue. Patients with a history of hypersensitivity to mepolizumab or the drug’s excipients should not take the medication.
Herpes zoster infections have occurred in patients receiving mepolizumab, so providers should consider vaccination if medically appropriate.
Mepolizumab’s approval was based on a randomized, double-blind, multicenter, placebo-controlled trial that randomly assigned 108 patients with HES to receive either mepolizumab or placebo by injection every 4 weeks. The trial found that fewer patients in the mepolizumab group (28%) experienced HES flares compared with those in the placebo group (56%).
FDA approves combination treatment for mesothelioma, first in 16 years
On October 2, FDA approved nivolumab (Opdivo) in combination with ipilimumab (Yervoy) for the first-line treatment of adults with unresectable, malignant pleural mesothelioma. The combination treatment is the first regimen the agency has approved for mesothelioma in 16 years and the second systemic therapy for mesothelioma. FDA granted this approval to Bristol-Myers Squibb.
“Today’s approval of nivolumab plus ipilimumab provides a new treatment that has demonstrated an improvement in overall survival for patients with malignant pleural mesothelioma,” said Richard Pazdur, MD, director of FDA’s Oncology Center of Excellence, and acting director of the Office of Oncologic Diseases in FDA’s Center for Drug Evaluation and Research, in a statement. “In 2004, FDA approved pemetrexed in combination with cisplatin for this indication, and now patients now have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen.”
Nivolumab is a programmed death receptor-1 (PD-1)–blocking
antibody, and ipilimumab is a human cytotoxic T-lymphocyte antigen 4 (CTLA-4)–blocking antibody. When combined, the drugs decrease tumor growth by enhancing T-cell function. The recommended dosage for the regimen is nivolumab 360 mg every 3 weeks with ipilimumab 1 mg/kg every 6 weeks administered intravenously.
Common adverse effects that patients experienced with nivolumab plus ipilimumab include fatigue, diarrhea, rash, pruritus, nausea, musculoskeletal pain, pyrexia, cough, decreased appetite, vomiting, abdominal pain, dyspnea, upper respiratory tract infection, arthralgia, headache, hypothyroidism, decreased weight, and dizziness.
Ipilimumab can cause severe and fatal immune-mediated adverse reactions including colitis, hepatitis, dermatologic adverse reactions, endocrinopathies, pneumonitis, and nephritis with renal dysfunction. In addition to these reactions, nivolumab can also cause immune-mediated skin adverse reactions and encephalitis. Monitor patients for signs and symptoms of these immune-mediated adverse reactions, which may occur any time during or after treatment.
Both ipilimumab and nivolumab can cause fetal harm. Providers should advise patients of reproductive potential to use effective contraception during treatment. Patients should also not breastfeed while taking these drugs. Before starting this drug regimen, counsel patients to tell their health care providers if they have immune system, liver, or lung or breathing problems; have had an organ transplant; or are pregnant or planning to become pregnant.