Updates from FDA
New drugs
SELADELPAR
(Livdelzi—Ascendis Pharma)
Drug class: Livdelzi is a peroxisome proliferator-activated receptor-Δ agonist.
Indication: Livdelzi is indicated for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. This indication is approved under accelerated approval based on a reduction of alkaline phosphatase. Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Recommended dosage and administration: The recommended dosage of Livdelzi is 10 mg orally once daily with or without food.
Common adverse effects: The most common adverse reactions are headache, abdominal pain, nausea, abdominal distension, and dizziness.
Warnings and precautions: Use of Livdelzi is not recommended in patients who have or develop decompensated cirrhosis. Consider the risk of fracture in patients treated with Livdelzi and monitor bone health according to current standards of care. Obtain baseline and laboratory liver assessments prior to starting Livdelzi and monitor during treatment.
Interrupt or discontinue Livdelzi if the liver tests worsen.
Avoid use in patients with complete biliary obstruction. If biliary obstruction is suspected, interrupt Livdelzi and treat as clinically indicated. Monitor patients with cirrhosis for evidence of decompensation. Consider discontinuation if the patient progresses to moderate or severe hepatic impairment. Avoid concomitant use with OAT3 inhibitors and strong CYP2C9 inhibitors. If taken concomitantly with rifampin, monitor biochemical response when rifampin is initiated. Monitor closely for adverse effects if Livdelzi is taken concomitantly with dual moderate CYP2C9 and moderate to strong CYP3A4 inhibitors or BCRP inhibitors. Additionally, monitor frequently for adverse effects in CYP2C9 poor metabolizers using moderate to strong CYP3A4 inhibitors. Administer bile acid sequestrants at least 4 hours before or 4 hours after taking a bile acid sequestrant, or at as great an interval as possible.
ARIMOCLOMOL
(Miplyffa—Zevra Therapeutics)
Drug class: Miplyffa is a pyridinium derivative.
Indication: Miplyffa is indicated for use in combination with miglustat for the treatment of neurological manifestations of Niemann-Pick disease type C in adult and pediatric patients 2 years and older.
Recommended dosage and administration: The recommended Miplyffa oral dosage, in combination with miglustat, is based on actual body weight. For patients with an actual body weight of 8 kg to 15 kg, the recommended dose is 47 mg 3 times a day. For patients with an actual body weight of greater than 15 kg to 30 kg, the recommended dose is 62 mg 3 times a day. For patients with an actual body weight of greater than 30 kg to 55 kg, the recommended dose is 93 mg 3 times a day. For patients with an actual body weight of greater than 55 kg, the recommended dose is 124 mg 3 times a day. Miplyffa can be administered with or without food. Dose adjustments may be needed in patients with an eGFR between 15 mL/minute and 50 mL/minute.
Common adverse effects: The most common adverse reactions are upper respiratory tract infection, diarrhea, and decreased weight.
Warnings and precautions: Discontinue Miplyffa in patients who develop urticaria and angioedema. Miplyffa may cause fetal harm. Advise patients of reproductive potential of the potential risk to the fetus and consider pregnancy planning and prevention. Mean increases in serum creatinine of 10–20% have been reported. Use alternative measures that are not based on creatinine to assess renal function. If Miplyffa is taken concomitantly with substrates of OCT2, monitor for adverse reactions and reduce the dosage of the OCT2 substrate. Based on animal findings, Miplyffa may impair fertility.
LEVACETYLLEUCINE
(Aqneursa—IntraBio)
Drug class: Aqneursa is a modified form of leucine.
Indication: Aqneursa is indicated for the treatment of neurological manifestations of Niemann-Pick disease type C in adults and pediatric patients weighing greater than or equal to 15 kg.
Recommended dosage and administration: For patients of reproductive potential, verify that the patient is not pregnant prior to initiating treatment. For patients weighing 15 kg to less than 25 kg, the recommended dosage is 1 g in the morning and 1 g in the evening. For patients weighing 25 kg to less than 35 kg, the recommended dosage is 1 g in the morning, 1 g in the afternoon, and 1 g in the evening. For patients weighing 35 kg or more, the recommended dosage is 2 g in the morning, 1 g in the afternoon, and 1 g in the evening. Aqneursa is an oral suspension that is packaged as 1 g of levacetylleucine in a unit-dose packet.
Common adverse effects: The most common adverse reactions are abdominal pain, dysphagia, upper respiratory tract infections, and vomiting.
Warnings and precautions: Aqneursa may cause fetal harm. Advise patients of reproductive potential to use effective contraception during treatment and for 7 days after the last dose. Avoid concomitant use with N-acetyl-DL-leucine or N-acetyl-D-leucine. Monitor for adverse reactions if Aqneursa is used with P-glycoprotein transporter substrates.
XANOMELINE AND TROSPIUM CHLORIDE
(Cobenfy—Bristol-Myers Squibb)
Drug class: Cobenfy is a combination of xanomeline, a muscarinic agonist, and trospium chloride, a muscarinic antagonist.
Indication: Cobenfy is indicated for the treatment of schizophrenia in adults.
Recommended dosage and administration: Assess liver enzymes and bilirubin prior to initiating treatment with Cobenfy and as clinically indicated during treatment. Assess heart rate at baseline and as clinically indicated during treatment. The recommended starting dosage of Cobenfy is 50 mg/20 mg orally twice daily for at least 2 days and then 100 mg/20 mg twice daily for at least 5 days. The dosage may be increased to 125 mg/30 mg orally twice daily based on patient tolerability and response. Take Cobenfy at least 1 hour before a meal or at least 2 hours after a meal. Do not open capsules. In older patients, the recommended starting dosage is 50 mg/20 mg orally twice daily. Consider a slower titration in this population. The maximum recommended dosage in older patients is 100 mg/20 mg twice daily.
Common adverse effects: The most common adverse reactions are nausea, dyspepsia, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia, dizziness, and gastrointestinal reflux disease.
Warnings and precautions: Cobenfy is contraindicated in urinary retention, moderate or severe hepatic impairment, gastric retention, history of hypersensitivity to Cobenfy or trospium chloride, and untreated narrow-angle glaucoma. Cobenfy can cause urinary retention. Assess liver enzymes and bilirubin prior to initiating Cobenfy and as clinically indicated. Discontinue Cobenfy in the presence of signs or symptoms of substantial liver injury.
Cobenfy may decrease GI mobility. Angioedema has been reported. Cobenfy may increase heart rate. Anticholinergic adverse reactions are expected to be greater in patients with moderate and severe renal impairment so use in this population is not recommended. Cobenfy may be associated with central nervous system effects. Advise patients not to drive or operate heavy machinery until they know how Cobenfy affects them. Use is not recommended in patients with moderate or severe renal impairment or mild hepatic impairment. If taken with drugs eliminated by active tubular secretion, CYP2D6 inhibitors, sensitive substrates of CYP3A4 or P-glycoprotein, or antimuscarinic drugs, monitor for increased frequency and severity of adverse reactions.
New dosage forms
NALMEFENE INJECTION
(Zurnai—Purdue Pharma)
Drug class: Zurnai is an opioid antagonist.
Indication: Zurnai is indicated for the emergency treatment of known or suspected opioid overdose induced by natural or synthetic opioids in adults and pediatric patients aged 12 years and older, as manifested by respiratory and/or central nervous system depression. Zurnai is intended for immediate administration as emergency therapy in settings where opioids may be present. It is not a substitute for emergency medical care.
Recommended dosage and administration: Zurnai is for I.M. and S.C. use only. Seek emergency medical care immediately after use. Administer Zurnai to the outer thigh, through clothing if necessary. Administer additional doses, using a new autoinjector for each dose, if the patient does not respond or responds and then relapses into respiratory depression. Additional doses may be given every 2 to 5 minutes until emergency medical assistance arrives. Additional supportive and resuscitative measures may be helpful while awaiting emergency medical assistance.
Common adverse effects: The most common adverse reactions are feeling hot, nausea, headache, dizziness, chills, vomiting, allodynia, palpitations, tinnitus, ear discomfort, feeling abnormal, burning sensation, and irritability.
Warnings and precautions: Zurnai is contraindicated in hypersensitivity to nalmefene hydrochloride or to any other ingredients in Zurnai. A recurrence of respiratory depression is possible; therefore, keep the patient under continued surveillance and administer repeat doses using a new autoinjector with each dose while awaiting emergency medical assistance. Reversal of respiratory depression by partial agonists or mixed agonist/antagonists such as buprenorphine and pentazocine may be incomplete. Repeat doses may be required. The use of Zurnai in patients who are opioid dependent may precipitate opioid withdrawal.
Monitor for the development of opioid withdrawal in neonates. Abrupt postoperative reversal of opioid depression may result in adverse cardiovascular effects. These events have primarily occurred in patients who had preexisting cardiovascular disorders or received other drugs that may have similar adverse cardiovascular effects. Monitor these patients closely in an appropriate health care setting after use of nalmefene hydrochloride. Attempts to overcome opioid withdrawal symptoms caused by opioid antagonists with high or repeated doses of exogenous opioids may lead to opioid intoxication and death. ■