Med Check: Qelbree and ADHD; Lacmital and Heart Disease; FDA and Atogepant; Azstarys and ADHD; FDA and CBD; Daridorexant and Insonnia

Qelbree Approved for ADHD in Pediatric Patients

The Food and Drug Administration (FDA) in April approved Qelbree (viloxazine extended-release capsules), a selective norepinephrine reuptake inhibitor, for the treatment of attention-deficit/hyperactivity disorder (ADHD) in pediatric patients aged 6 to 17 years. Qelbree, made by Supernus Pharmaceuticals, is not a stimulant and is not a controlled substance.

In three separate phase 3 trials involving 1,118 patients aged 6 to 17 years, youth who took Qelbree experienced a greater improvement in ADHD symptoms compared with those who took placebo, as measured by the ADHD Rating Scale and the Clinical Global Impression-Improvement score. Doses during the trial ranged from 100 mg to 400 mg. The recommended starting dose for patients 6 to 11 years old is 100 mg once daily. The recommended starting dose for patients 12 to 17 years old is 200 mg once daily. Dosages for both age groups may be titrated up to 400 mg once daily. The capsules may be broken open and sprinkled on applesauce or swallowed whole.

The prescribing information for Qelbree comes with a boxed warning that states, “In clinical trials, higher rates of suicidal thoughts and behavior were reported in pediatric patients treated with Qelbree than in patients treated with placebo. Closely monitor for worsening and emergence of suicidal thoughts and behaviors.”.

Lamictal May Increase Risk of Arrhythmias in Patients With Heart Diseas

In March the FDA issued a drug safety communication about Lamictal (lamotrigine, developed by GlaxoSmithKline) after a review of study findings revealed that the drug may increase arrhythmias in patients with heart disease. The FDA required these studies after the agency received reports of abnormal electrocardiographic findings and other problems such as chest pain, loss of consciousness, and heart attack in patients who took the drug. Lamictal is approved for use alone or with other medicines to treat seizures in patients who are at least 2 years old. It is also approved as a maintenance treatment for patients with bipolar disorder to help delay the occurrence of mood episodes such as depression, mania, or hypomania.

In the safety communication, the FDA said that health professionals should assess whether the potential benefits of lamotrigine outweigh the potential risk of arrhythmias for each patient, notably those with heart failure, valvular heart disease, congenital heart disease, conduction system disease, ventricular arrhythmias, cardiac channelopathies such as Brugada syndrome, ischemic heart disease, or multiple risk factors for coronary artery disease. The agency noted that the risk of arrhythmias may increase further if Lamictal is used in combination with other medicines that block sodium channels in the heart. “Other sodium channel blockers approved for epilepsy, bipolar disorder, and other indications should not be considered safer alternatives to lamotrigine in the absence of additional information,” the FDA wrote.

FDA to Review Atogepant for Migraine Prevention

In March the FDA accepted for review a New Drug Application (NDA) for atogepant, for the prevention of migraine, AbbVie announced. Atogepant is an oral calcitonin gene-related peptide agonist.

In a phase 3 trial, 930 adults who had four to 14 migraine days a month were randomized to one of four treatment groups evaluating 10 mg, 30 mg, and 60 mg of atogepant once daily or placebo for 12 weeks. The primary endpoint was change from baseline in mean monthly migraine days across the 12-week treatment period.

Patients treated in the 10 mg, 30 mg, and 60 mg atogepant arms experienced a decrease of 3.69, 3.86, and 4.2 migraine days, respectively, compared with patients in the placebo arm, who experienced a decrease of 2.48 migraine days.

The most common adverse events were constipation, nausea, and upper respiratory infections. The majority of these cases were mild or moderate in severity and did not lead to discontinuation.

Azstarys Approved for Treatment of ADHD

In March the FDA approved Azstarys (serdexmethylphenidate and dexmethylphenidate) capsules for the treatment of ADHD in patients at least 6 years old, manufacturer KemPharm announced. The drug consists of serdexmethylphenidate, which is KemPharm’s prodrug of d-methylphenidate, and immediate-release dexmethylphenidate. Azstarys will be available in three strengths of serdexmethylphenidate/dexmethylphenidate, 26.1 mg/5.2 mg, 39.2 mg/7.8 mg, and 52.3 mg/10.4 mg.

In a trial of 150 patients with ADHD aged 6 to 12 years, patients were randomized to receive either Azstarys (mean dose of 45.6 mg/9 mg) or placebo. Teachers assessed the patients for symptoms of ADHD using the SKAMP-C scale. Teachers assessed the patients in a classroom setting 0.5, 1, 2, 4, 8, 10, 12, and 13 hours after the patients received their dose. SKAMP-C scores improved in patients who took the drug compared with those who took placebo.

Azstarys is a Schedule II drug and should not be substituted for other methylphenidate products on a milligram-per-milligram basis. KemPharm anticipates that the drug will be available this summer.

FDA Warns Companies About Illegal Sales of CBD Products for Pain

The FDA has issued warning letters to Honest Globe Inc. and Biolyte Laboratories LLC for selling products labeled as containing cannabidiol (CBD) in ways that violate the Federal Food, Drug, and Cosmetic Act, the agency announced in March.

In a statement, the FDA noted that it has not approved any CBD-containing drug products other than one prescription drug for the treatment of seizures associated with tuberous sclerosis complex, Lennox-Gastaut syndrome, and Dravet syndrome.

“The products that are the subject of the warning letters … have not gone through the FDA drug approval process and are considered unapproved new drugs. There has been no FDA evaluation of whether these unapproved drug products are effective for the uses manufacturers claim, what an appropriate dose might be, how they could interact with FDA-approved drugs or other products, or whether they have dangerous side effects or other safety concerns,” the agency said.

NDA Submitted for Daridorexant for Insomnia

Idorsia Ltd. announced in March that the FDA has accepted for review an NDA for the company’s investigational dual orexin receptor antagonist, daridorexant, for the treatment of adult patients with insomnia.

In a phase 3 trial, 930 patients with insomnia received either 25 mg or 50 mg daridorexant or placebo once nightly for three months. Compared with patients who took placebo, those who took either dose of daridorexant fell asleep faster and experienced improved sleep maintenance as measured by polysomnography in a sleep lab and as recorded in patient diaries. Daridorexant 50 mg also significantly improved daytime functioning.

In a second phase 3 trial, 924 adults with insomnia received daridorexant (10 mg or 25 mg) or placebo once in the evening for three months. Compared with patients who took placebo, those who took 25 mg of daridorexant experienced significantly improved sleep maintenance as measured by polysomnography in a sleep lab and as recorded in patient diaries. The results were statistically significant at the end of the first month and at the end of the third month. ■