| Summary: | Jurriaan M Peters,1 Danielle A Becker,2 Sunita N Misra,3 Enrique Carrazana,3,4 Adrian L Rabinowicz3 1Department of Neurology, Harvard Medical School and Boston Children’s Hospital, Boston, MA, USA; 2Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA; 3Neurelis, Inc, San Diego, CA, USA; 4Department of Family Medicine and Community Health, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USACorrespondence: Jurriaan M Peters, Division of Epilepsy and Clinical Neurophysiology, Boston Children’s Hospital and Harvard Medical School, 300 Longwood Ave, FE9, Boston, MA, 02115, USA, Tel +1 617-355-7970, Fax +1 617-730-4850, Email jurriaan.peters@childrens.harvard.eduAbstract: In the US, 3 rescue treatment options are approved for patients with seizure clusters (ie, acute repetitive seizures), which are intermittent increases of seizure activity. This narrative PubMed review of these 3 treatments examines newer intranasal options that are well suited for adolescent and adult patients who may desire a transition from rectal treatment. Diazepam rectal gel is indicated for patients ≥ 2 years, diazepam nasal spray for those ≥ 6 years, and midazolam nasal spray for those ≥ 12 years. Approvals for diazepam rectal gel and midazolam nasal spray were based on safety and efficacy comparisons with placebo. Approval for diazepam nasal spray was based on results from long-term safety and tolerability studies in addition to its comparable bioavailability to diazepam rectal gel, while also showing less interpatient variability. The safety profiles of diazepam rectal gel and nasal spray are similar, and the medications share safety, warning, and precaution labeling. Thus, patients ≥ 6 years could be introduced to intranasal diazepam, allowing for continuity of familiar treatment while improving access and comfort. Intranasal midazolam also has a well-characterized safety profile. A proxy for effectiveness is the number of seizure clusters that were treated with a single dose, and these differed in separate, noncomparative studies. The safety and effectiveness of diazepam nasal spray have been examined in multiple subpopulations, whereas patient/caregiver experiences with both approved intranasal formulations have been characterized. Users may prefer nasal administration because it is noninvasive and effective, and provides social advantages, comfort, ease of use, and less variability compared with rectal gel. Nasal sprays are portable and convenient for use in the community (school, work, travel), and self-administration was reported in one study, with patients as young as 11 years old self-administering diazepam nasal spray. These newer, intranasal rescue treatments for seizure clusters provide an alternative to the rectal route.Plain Language Summary: Some people with epilepsy may have seizure clusters, which are often defined as 2 or more seizures in a day that are not part of their normal seizure pattern. Rescue treatments approved in the United States are diazepam rectal gel, diazepam nasal spray, and midazolam nasal spray. These rescue drugs can help stop seizure clusters at home, school, or work. Diazepam rectal gel is for adults and children ages 2 years or older. To give a rectal dose, the caregiver must pull down the patient’s underwear. Spraying nasal treatment into the nose may be less embarrassing. Because some patients may want to switch their treatment, we looked for articles about how to use these treatments and summarized what we found. Diazepam nasal spray is for patients ages 6 years or older and midazolam nasal spray is for patients 12 years or older. Diazepam rectal gel and nasal spray use the same drug, and dosing is based on patient age and weight. Midazolam nasal spray uses a different drug, and everyone uses the same dose. Some drugs may be more likely than others to need a second dose for a seizure. Patients and caregivers (care partners) felt that diazepam nasal spray was easier to use than rectal gel. They were also more comfortable using diazepam nasal spray in public. Patients as young as 11 years have used diazepam nasal spray by themselves. In all, patients may prefer nasal treatment and now have options to change from rectal treatment of seizure clusters.Keywords: nasal spray, rectal gel, diazepam, midazolam, epilepsy, switch
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