Kacperski J, Hershey AD. Newly Approved Agents for the Treatment and
Prevention of Pediatric Migraine. CNS Drugs. 2016 Sep;30(9):837-44.
Treatment of pediatric migraine remains an unmet medical need. There continues to be a paucity of pediatric randomized controlled trials for the treatment of migraine, both in the acute and preventive settings. Pediatric studies are often complicated by high placebo-response rates and much of our current practice is based on adult trials. This lack of significant pediatric studies results in a wide variation in migraine management both amongst clinicians and between institutions, and evidence-based treatments are not always administered. In this article, we aim to briefly review newly approved abortive and preventive agents for migraine in the pediatric age group. Over-the-counter anti-inflammatory medications, including ibuprofen, naproxen sodium, aspirin, and acetaminophen are reasonable first-line options for abortive therapy. In addition, studies have shown triptans, or migraine-specific agents, to be safe and effective in children and adolescents and several formulations have been approved for the pediatric population, including rizatriptan, almotriptan, zolmitriptan nasal spray, and naproxen sodium/sumatriptan in combination.
Winner P, Farkas V, Štillová H, Woodruff B, Liss C, Lillieborg S, Raines S;
TEENZ Study Group. Efficacy and tolerability of zolmitriptan nasal spray for the
treatment of acute migraine in adolescents: Results of a randomized,
double-blind, multi-center, parallel-group study (TEENZ). Headache. 2016
The primary objective of the TEENZ Study (NCT01211145) was to assess the efficacy of zolmitriptan nasal spray in the acute treatment of adolescent migraine patients (ages 12 to 17 years), as measured by the primary outcome variable of pain-free status at 2 hours post-treatment.
This randomized, double-blind, placebo-controlled, four-arm parallel group study compared zolmitriptan nasal spray with placebo in the treatment of a single episode of adolescent migraine. Patients completed a 30-day run-in period to treat a single migraine attack with single-blind placebo nasal spray. Eligible patients, who had not responded to placebo, were randomized to one of three zolmitriptan nasal spray doses (5, 2.5, or 0.5 mg) or placebo in a ratio of 5:3:3:5 according to a computer-generated randomization scheme. Patients completed diaries for 24 hours after treatment, recording headache pain scores, adverse events (AEs), and medications taken.
In an interim futility analysis, zolmitriptan nasal spray doses of 0.5 and 2.5 mg were declared futile relative to placebo and further randomization to these treatment arms was discontinued. Of 1653 patients enrolled into the study, 855 patients failed to meet study eligibility criteria and were considered screen failures. The most common reason for screen failure was response to placebo challenge (325 patients [38.0%]). Of the 798 patients who were randomized to treatment, 721 (90.4%) completed the study period. Of these, 657 (82.3%) treated a migraine within the study period and contributed data for analysis. Zolmitriptan nasal spray 5 mg was significantly more effective than placebo in achieving pain-free status at 2 hours after treatment (P < .001), with 30% of patients achieving pain-free status at 2 hours vs 17% of placebo-treated patients (OR 2.18; 95% CI 1.40, 3.39). Zolmitriptan nasal spray 5 mg was also more effective than placebo in achieving pain-free status at 3 and 4 hours post-treatment (45 vs 24%, and 56 vs 39%; both P < .001). Zolmitriptan nasal spray 5 mg was also more effective than placebo in achieving headache response at 2, 3, and 4 hours after treatment (51 vs 39%, 61 vs 48%, and 69 vs 57%, respectively; all P ≤ .011). Zolmitriptan nasal spray was well-tolerated at all doses. Dysgeusia was the most frequently reported AE, with greater frequencies reported in active treatment groups versus placebo. No serious AEs or AEs leading to discontinuation were reported. Most AEs were mild or moderate in severity, and consistent with the known profile of zolmitriptan in adult and adolescent populations.
Zolmitriptan nasal spray was well-tolerated in the acute treatment of adolescent (ages 12 to 17 years) migraine. Zolmitriptan 5 mg nasal spray demonstrated superior efficacy compared with placebo for the primary efficacy endpoint of pain-free status 2 hours after treatment and the efficacy of the 5 mg dose was supported by the majority of secondary efficacy endpoints.
Courtesy of: http://www.medscape.com/viewarticle/866905
Gutman D, Hellriegel E, Aycardi E, Bigal ME, Kunta J, Chitra R, Kansagra S,
Kidron OS, Knebel H, Linder S, Ma Y, Pierce M, Winner PK, Spiegelstein O. A Phase
I, Open-Label, Single-Dose Safety, Pharmacokinetic, and Tolerability Study of the
Sumatriptan Iontophoretic Transdermal System in Adolescent Migraine Patients.
Headache. 2016 Sep;56(8):1300-9.
To evaluate the safety, tolerability, and pharmacokinetics of sumatriptan delivered by the iontophoretic transdermal system (TDS) in adolescent patients.
Since nausea can be a prominent and early symptom of migraine, nonoral treatment options are often required. Sumatriptan iontophoretic TDS is approved for the acute treatment of migraine in adults. The present study evaluates the pharmacokinetics of sumatriptan administered via the iontophoretic TDS in adolescents, contrasting the findings with historical data from adults.
Patients aged 12-17 years (inclusive) with acute migraine were treated with sumatriptan iontophoretic TDS for 4 hours. Blood samples for pharmacokinetic profiling of sumatriptan were obtained prior to dosing and at predetermined time points covering the 12 hours postonset of treatment. Key pharmacokinetic endpoints included Cmax (peak plasma drug concentration), tmax (time to Cmax ), AUC0-∞ (area under the plasma concentration-time curve from time 0 to infinity), and t½ (terminal elimination half-life). Safety was evaluated by monitoring of adverse events in addition to laboratory and clinical assessments.
The sample consisted of 37 patients, and 36 were included in the PK evaluable population. Cmax , tmax , AUC0-∞ , and t½ values were all similar between male and female patients and between younger (12-14 years) and older (15-17 years) adolescents. When compared with historical adult data, adolescent patients demonstrated similar systemic exposures to those observed in adults (mean Cmax 20.20 (±6.43) ng/mL in adolescents vs 21.89 (±6.15) ng/mL in adults; mean AUC0-∞ 98.1 (±28.1) ng·h/mL in adolescents vs 109.7 (±26.1) ng·h/mL in adults). All adverse events were mild or moderate, with application-site paresthesia being the most common (32%). No clinically relevant changes in laboratory values, vital signs, or electrocardiogram findings were observed.
The iontophoretic TDS produced mean systemic exposures to sumatriptan in younger and older adolescents, in line with what was seen in adult subjects. It was generally well tolerated.