Updates from FDA
APhA Staff
New drugs
ELAMIPRETIDE HYDROCHLORIDE
(Forzenity—Stealth BioTherapeutics)
Drug class: Forzenity is a mitochondrial cardiolipin binder.
Indication: Forzenity is indicated to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg. This indication is approved under accelerated approval based on an improvement in knee extensor muscle strength, an intermediate clinical endpoint. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Recommended dosage and administration: For patients weighing 30 kg and greater, the recommended dosage is 40 mg S.C. once daily. Reduce the dose in adults with severe renal impairment.
Common adverse effects: The most common adverse effects are injection site reactions.
Warnings and precautions: Forzenity is contraindicated in serious hypersensitivity to any of the ingredients. Do not use in neonates as benzyl alcohol toxicity may occur.
IMLUNESTRANT
(Inluriyo—Eli Lilly Co)
Drug class: Inluriyo is an estrogen receptor antagonist.
Indication: Inluriyo is indicated for the treatment of adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.
Recommended dosage and administration: Select patients for treatment based on the presence of ESR1 mutations. The recommended dosage is 400 mg orally once daily, on an empty stomach. Reduce the dose in patients with moderate or severe hepatic impairment. Dosage modifications may be required.
Common adverse effects: The most common adverse effects are decreased hemoglobin, musculoskeletal pain, decreased calcium, decreased neutrophils, increased AST, fatigue, diarrhea, increased ALT, increased triglycerides, nausea, decreased platelets, constipation, increased cholesterol, and abdominal pain.
Warnings and precautions: Inluriyo can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. Advise patients not to breastfeed during treatment. Avoid concomitant use with strong CYP3A inhibitors, and if concomitant use cannot be avoided, decrease the Inluriyo dosage. Avoid concomitant use with strong CYP3A inducers, and if concomitant use cannot be avoided, increase the Inluriyo dosage.
PALTUSOTINE
(Palsonify—Crinetics Pharmaceuticals)
Drug class: Palsonify is a somatostatin receptor agonist.
Indication: Palsonify is indicated for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option.
Recommended dosage and administration: Take orally once daily with water on an empty stomach, at least 6 hours after a meal and at least 1 hour before the next meal. The recommended initial dosage is 40 mg once daily. During initiation, Palsonify may be temporarily reduced to 20 mg once daily if needed, based on tolerability. Once adverse reactions have resolved, resume Palsonify 40 mg once daily.
Common adverse effects: The most common adverse effects are diarrhea, abdominal pain, nausea, decreased appetite, sinus bradycardia, hyperglycemia, palpitations, and gastroenteritis.
Warnings and precautions: Cholelithiasis and its complications may occur. If complications occur, discontinue Palsonify and treat appropriately. Monitor glucose and adjust antidiabetic treatment as needed. Bradycardia or conduction abnormalities may occur. Dosage adjustments of concomitantly used drugs with bradycardia effects may be necessary.
Hypothyroidism may occur. Assess thyroid function periodically. New onset steatorrhea, stool discoloration, loose stools, abdominal bloating, and weight loss may occur. If new occurrence or worsening of these symptoms are reported, evaluate for potential pancreatic exocrine insufficiency.
Monitor vitamin B12 levels during treatment if indicated. PPIs, strong CYP3A4 inducers, and moderate CYP3A4 inducers may decrease Palsonify exposure and may require a Palsonify dosage increase. Palsonify may decrease cyclosporine exposure and may require a cyclosporine dosage adjustment.
New dosage forms
CLOTRIMAZOLE OTIC SOLUTION
(Clotic—Laboratorios Salvat)
Drug class: Clotic is an azole antifungal.
Indication: Clotic is indicated for the treatment of fungal otitis externa (otomycosis) due to Aspergillus species and Candida species in patients 18 years and older. Clotic has only been studied in patients with intact tympanic membranes. The use of Clotic is not recommended for the treatment of otomycosis in patients with perforated tympanic membranes.
Recommended dosage and administration: Clotic is for otic use only. Instill the contents of one single-dose Clotic vial into the affected ear canal twice daily, morning and evening, preferably 12 hours apart for 14 consecutive days.
Common adverse effects: The most common adverse effects are headache, application site pain, tinnitus, tympanic membrane perforation, and paresthesia.
Warnings and precautions: Forzenity is contraindicated in patients with known hypersensitivity to clotrimazole.
LAMOTRIGINE ORAL SUSPENSION
(Subvenite—OWP Pharmaceuticals)
Drug class: Subvenite is a triazine anticonvulsant.
Indication: Subvenite is indicated as adjunctive therapy in patients aged 2 years and older for epilepsy with partial-onset seizures, primary generalized tonic-clonic seizures, and generalized seizures of Lennox-Gastaut syndrome. It is also indicated as monotherapy in patients aged 16 years and older with epilepsy.
Conversion to monotherapy can occur in patients with partial-onset seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug.
Subvenite is also indicated for maintenance treatment of bipolar I disorder to delay the time to occurrence of mood episodes in patients treated for acute mood episodes with standard therapy. Treatment of acute manic or mixed episodes is not recommended. Effectiveness of Subvenite in the acute treatment of mood episodes has not been established.
Recommended dosage and administration: Dosing is based on concomitant medications, indication, and patient age. To avoid an increased risk of rash, the recommended initial dose and subsequent dose escalations should not be exceeded. Do not restart Subvenite in patients who discontinued due to rash unless the potential benefits clearly outweigh the risks. Adjustments to maintenance doses will be necessary in most patients starting or stopping estrogen-containing products, including oral contraceptives. To discontinue, taper over a period of at least 2 weeks with approximately 50% dose reduction per week.
Common adverse effects: The most common adverse effects are dizziness, headache, diplopia, ataxia, nausea, blurred vision, somnolence, rhinitis, pharyngitis, rash, vomiting, fever, accidental injury, diarrhea, abdominal pain, tremor, insomnia, back pain, fatigue, and xerostomia.
Boxed warning: Cases of life-threatening serious rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, and/or rash-related death have been caused by lamotrigine. The rate of serious rash is greater in pediatric patients than in adults.
Additional factors that may increase the risk of rash include coadministration with valproate, exceeding the recommended initial dose of Subvenite, and exceeding the recommended dose escalation for Subvenite. Benign rashes are also caused by lamotrigine; however, it is not possible to predict which rashes will prove to be serious or life-threatening. Subvenite should be discontinued at the first sign of rash, unless the rash is clearly not drug-related.
Other warnings and precautions: Subvenite is contraindicated in hypersensitivity to the drug or its ingredients. Discontinue at the first sign of rash, unless the rash is clearly not drug-related. Consider a hemophagocytic lymphohistiocytosis diagnosis and evaluate patients immediately if they develop signs and symptoms of systemic inflammation. Discontinue Subvenite if an alternative etiology is not established. If drug reaction with eosinophilia and systemic symptoms occurs, discontinue if there is no alternate etiology.
Based on in vitro findings, Subvenite could cause serious arrhythmias and/or death in patients with certain underlying cardiac disorders or arrhythmias. Any expected or observed benefit of Subvenite in an individual patient with clinically important structural or functional heart disease must be carefully weighed against the risk for serious arrhythmias and/or death for that patient. Blood dyscrasias may occur, either with or without an associated hypersensitivity syndrome. Monitor for signs of anemia, unexpected infection, or bleeding. Monitor for suicidal thoughts and behaviors. Monitor for signs of meningitis.
Medication errors due to product name confusion may occur. Strongly advise patients to visually verify the product they received is correct. Valproate increases lamotrigine concentrations more than twofold. Carbamazepine, phenytoin, phenobarbital, primidone, and rifampin decrease lamotrigine concentrations by approximately 40%. Estrogen-containing oral contraceptives decrease lamotrigine concentrations by approximately 50%. Protease inhibitors lopinavir/ritonavir and atazanavir/lopinavir decrease lamotrigine exposure by approximately 50% and 32%, respectively. Coadministration with organic cationic transporter 2 substrates with narrow therapeutic index is not recommended.
Based on animal data, use during pregnancy may cause fetal harm. Dosage adjustments are required in patients with moderate and severe liver impairment. Reduced maintenance doses may be effective for patients with significant renal impairment. ■
FDA issues new guidance to expand non-opioid options for chronic pain
On September 10, 2025, FDA issued draft guidance to accelerate non-opioid treatments that are safe and effective, as well as reduce prescription-related opioid misuse. The guidance emphasizes the importance of efficient approaches to drug development, including trial design, appropriate patient populations, and meaningful outcomes.
Regulatory considerations that are outlined in the draft guidance include:
- Establishing indications for different scopes.
- Designing clinical trials that ensure safety and efficacy are robustly evaluated.
- Evaluating the ability of non-opioid drugs to avoid, reduce, or eliminate opioid use.
- Incorporating statistical principles, patient-reported outcomes, and the use of expedited programs to support drug development in this area.
This guidance fulfills a mandate that required FDA to address challenges related to non-opioid development for pain management. ■