Updates from FDA
APhA staff
New drugs
CRINECERFONT
(Crenessity—Neurocrine Bioscience)
Drug class: Crenessity is a corticotropin-releasing factor type 1 receptor antagonist.
Indication: Crenessity is indicated as adjunctive treatment to glucocorticoid replacement to control androgens in adults and pediatric patients 4 years and older with classic congenital adrenal hyperplasia.
Recommended dosage and administration: The recommended dosage for adults is 100 mg orally, twice daily with a meal in the morning and evening. The recommended dosage for pediatric patients, aged 4 years and older, is weight-based. Patients should continue glucocorticoid replacement therapy for adrenal insufficiency associated with congenital adrenal hyperplasia.
Common adverse effects: The most common adverse reactions are fatigue, headache, dizziness, arthralgia, back pain, decreased appetite, myalgia, abdominal pain, nasal congestion, and epistaxis.
Warnings and precautions: Crenessity is contraindicated in patients with a hypersensitivity to crinecerfont or any excipients of Crenessity. Hypersensitivity reactions include throat tightness, angioedema, and generalized rash. If clinically significant hypersensitivity occurs, initiate appropriate therapy and discontinue treatment with Crenessity. There is a risk of acute adrenal insufficiency or adrenal crisis with inadequate concomitant glucocorticoid therapy. Continue glucocorticoids upon initiation and during treatment. Do not reduce the glucocorticoid dose below the dose required for cortisol replacement. Any adjustment of daily glucocorticoid dosage after initiation of Crenessity should be performed under the supervision of a health care provider. Use glucocorticoid stress doses in cases of increased cortisol need such as acute intercurrent illness, serious trauma, or surgical procedures. If Crenessity is taken concomitantly with strong CYP3A4 inducers, increase the Crenessity morning and evening doses twofold. If Crenessity is taken concomitantly with moderate CYP3A4 inducers, increase the Crenessity evening dose twofold.
ENSARTINIB
(Ensacove—Xcovery)
Drug class: Ensacove is a kinase inhibitor.
Indication: Ensacove is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not previously received an ALK-inhibitor.
Recommended dosage and administration: Prior to initiating Ensacove, evaluate liver function tests and fasting blood glucose. The recommended dosage is 225 mg orally once daily with or without food until disease progression or unacceptable toxicity.
Common adverse effects: The most common adverse reactions are rash, musculoskeletal pain, constipation, pruritus, cough, nausea, edema, vomiting, fatigue, pyrexia, increased uric acid, decreased lymphocytes, increased alanine aminotransferase, decreased phosphate, increased gamma glutamyl transferase, increased magnesium, increased amylase, decreased sodium, increased glucose, decreased hemoglobin, increased bilirubin, decreased potassium, and increased creatine phosphokinase.
Warnings and precautions: Use of Ensacove is contraindicated in patients with a history of hypersensitivity reaction to Ensacove, FD&C Yellow No. 5 (tartrazine), or to any of its components. Monitor patients for new or worsening symptoms indicative of interstitial lung disease/pneumonitis. Permanently discontinue Ensacove in patients with interstitial lung disease/pneumonitis. Monitor liver function during treatment. If hepatotoxicity occurs, withhold, reduce the dose, or permanently discontinue Ensacove based on severity. Monitor for dermatologic adverse reactions. Withhold, reduce the dose, or permanently discontinue Ensacove based on severity. Monitor heart rate and serum glucose periodically during treatment with Ensacove. If bradycardia or hyperglycemia occurs, withhold, reduce the dose, or permanently discontinue treatment based on severity of the condition. Advise patients to report visual disturbances during treatment. Increased creatine phosphokinase may occur so monitor creatine phosphokinase periodically during treatment. Monitor uric acid levels as hyperuricemia may occur. Ensacove may cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. Avoid concomitant use with moderate or strong CYP3A inhibitors, moderate or strong CYP3A inducers, and P-glycoprotein inhibitors. Avoid use of Ensacove in patients with severe hepatic impairment. Advise patients not to breastfeed during treatment.
OLEZARSEN
(Tryngolza—Ionis Pharmaceuticals)
Drug class: Tryngolza is an APOC-III-directed antisense oligonucleotide.
Indication: Tryngolza is indicated as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome.
Recommended dosage and administration: The recommended dosage of Tryngolza is 80 mg administered subcutaneously once monthly. Administer Tryngolza into the abdomen or front of the thigh. The back of the upper arm can also be used as an injection site if a health care provider or caregiver administers the injection.
Common adverse effects: The most common adverse reactions are injection site reactions, decreased platelet count, and arthralgia.
Warnings and precautions: Tryngolza is contraindicated in history of hypersensitivity reactions to olezarsen or any of the excipients in Tryngolza. Advise patients of the signs and symptoms of hypersensitivity reactions and instruct patients to promptly seek medical attention and discontinue use of Tryngolza if hypersensitivity reactions occur.
VANZACAFTOR, TEZACAFTOR, AND DEUTIVACAFTOR TABLETS
(Alyftrek—Vertex Pharmaceuticals)
Drug class: Alyftrek is a combination of deutivacaftor, a CFTR potentiator, tezacaftor, and vanzacaftor.
Indication: Alyftrek is indicated for the treatment of cystic fibrosis in patients aged 6 years and older who have at least one F508del mutation or another responsive mutation in the CFTR gene. If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to confirm the presence of at least one indicated mutation.
Recommended dosage and administration: In patients aged 6 years to less than 12 years old weighing less than 40 kg, the once daily oral dosage is three tablets of vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg. In patients aged 6 years to less than 12 years old weighing more than or equal to 40 kg and patients aged 12 years and older, the recommended once daily oral dosage is two tablets of vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg.
Common adverse effects: The most common adverse reactions are cough, nasopharyngitis, upper respiratory tract infection, headache, oropharyngeal pain, influenza, fatigue, increased ALT and AST, rash, and sinus congestion.
Boxed warning: Elevated transaminases have been observed in patients treated with Alyftrek. Cases of serious and potentially fatal drug-induced liver injury and liver failure leading to transplantation and death were reported in patients taking a drug containing the same or similar active ingredients as Alyftrek. Assess liver function tests in all patients prior to initiating Alyftrek, every month for the first 6 months, every 3 months for the next 12 months, then at least annually. Interrupt Alyftrek for significant elevation in liver function tests or signs or symptoms of liver injury. Follow patients closely with clinical and laboratory monitoring until abnormalities resolve. Resume Alyftrek if abnormalities resolve and only if the benefit is expected to outweigh the risk. Alyftrek should not be used in patients with severe hepatic impairment. Alyftrek is not recommended in patients with moderate hepatic impairment.
Other warnings and precautions: Hypersensitivity reactions, including anaphylaxis, have been reported in the postmarketing setting for drugs containing elexacaftor, tezacaftor, and/or ivacaftor. If signs or symptoms of serious hypersensitivity reactions develop during treatment, discontinue Alyftrek and initiate appropriate therapy. Consider benefits and risks before using Alyftrek in patients who discontinued or interrupted elexacaftor, tezacaftor, or ivacaftor-containing drugs due to adverse reactions. If Alyftrek is used, monitor closely for adverse reactions as clinically appropriate. Concomitant use with strong or moderate CYP3A inducers decreased vanzacaftor, tezacaftor, and deutivacaftor exposure, which may reduce Alyftrek efficacy. Therefore, concomitant use is not recommended. Concomitant use with strong or moderate CYP3A inhibitors increased vanzacaftor, tezacaftor, and deutivacaftor exposure, which may increase the risk of Alyftrek-associated adverse reactions. Reduce the Alyftrek dose with concomitant use. Avoid food or drink containing grapefruit. Noncongenital lens opacities/cataracts have been reported in patients with cystic fibrosis aged 18 years or younger and treated with drugs containing ivacaftor. Baseline and follow-up ophthalmological examinations are recommended in pediatric patients treated with Alyftrek.
New dosage forms
TIZANIDINE ORAL SOLUTION
(Ontralfy—Fidelity Biopharma Co.)
Drug class: Ontralfy is a central a-2 adrenergic agonist.
Indication: Ontralfy is indicated for the treatment of spasticity in adults.
Recommended dosage and administration: Monitoring of aminotransferase levels is recommended at baseline and 1 month after the maximum dose is achieved. The recommended starting dose is 2 mg by mouth every 6 to 8 hours, as needed, up to a maximum of three doses in 24 hours. Dosage can be increased by 2 mg to 4 mg per dose every 1 to 4 days. The maximum total daily dose is 36 mg. The pharmacokinetics of Ontralfy differ when taken with or without food. These differences could result in a change in tolerability and control of symptoms. Consistent administration with respect to food is recommended. Use a lower individual dose during titration in patients with renal or hepatic impairment. If higher doses are required, individual doses rather than dosing frequency should be increased. To discontinue Ontralfy, decrease the dose by 2 mg to 4 mg per day to minimize the risk of withdrawal adverse reactions.
Common adverse effects: The most common adverse reactions are dry mouth, somnolence, asthenia, and dizziness.
Warnings and precautions: Ontralfy is contraindicated in concomitant use with strong CYP1A2 inhibitors and patients with a hypersensitivity to tizanidine or the ingredients in Ontralfy. Monitor for signs and symptoms of hypotension, particularly in patients receiving concurrent antihypertensives. Ontralfy should not be used with other a-adrenergic agonists. Discontinue Ontralfy if liver injury occurs. Ontralfy may interfere with everyday activities. The sedative effects of Ontralfy, alcohol, and other CNS depressants are additive. Consider discontinuation of Ontralfy if hallucinations occur. Avoid concomitant use with moderate or weak CYP1A2 inhibitors as this may cause hypotension, bradycardia, or excessive drowsiness. If concomitant use is necessary and adverse reactions occur, reduce Ontralfy dosage or discontinue. Ontralfy may cause fetal harm. Use with caution in older patients because clearance is decreased fourfold. ■