lowed by a double-blind,placebo-controlled, Comparative Phase. The mean age of patients enrolled in theComparative Phase (N=201) was 33 years, 51% were female, and 95% were White.
Table 2 lists the adverse reactions occurring in 2% or more of the NAYZILAM-treatedpatients and at a rate greater than the placebo-treated patients in the Comparative Phase ofStudy 1.
Table 2: Adverse Reactionsa that Occurred in ≥2% of Patients (Any NAYZILAM) andGreater than Placebo in the Comparative Phase of Study 1
Body System/Adverse
Reaction Placebo
NAYZILAMb
NAYZILAM
5 mg
Placebo +
NAYZILAM
5 mg
NAYZILAM
5 mg + 5 mg
Any NAYZILAM
Treatment Group
N = 26
%
N = 91
%
N = 41
%
N = 43
%
N = 175
%
Nervous System
Somnolence 4 10 10 9 10
Headache 0 7 0 2 4
Dysarthria 0 2 2 2 2
Application Site
Nasal Discomfort 8 5 7 16 9
Throat Irritation 0 2 2 7 3
Rhinorrhea 0 3 0 5 3
Product Taste
Abnormal 0 4 0 0 2
Eye Disorders
Lacrimation Increased 0 1 2 2 2
a Adverse reactions that occurred within 2 days after NAYZILAM administration are included
b Patients in Study 1 were permitted to take a second, open-label dose of NAYZILAM 5 mg between 10 minutesand 6 hours following the initial blinded dose of NAYZILAM 5 mg or placebo if they experience seizurerecurrence or an incomplete resolution of the episode.
The Placebo + NAYZILAM 5 mg and NAYZILAM 5mg + 5 mg columns represent patients who received a second dose of NAYZILAM 5 mg and received a blindedinitial dose of placebo or NAYZILAM 5 mg, respectively.
For patients who experienced a decrease in peripheral oxygen saturation in the Test DosePhase of Study 1, the decreases were generally transitory. Two patients (one with a historyof sleep apnea and one with intercurrent seizure) with decreases in peripheral oxygensaturation in the Test Dose Phase required therapeutic supplemental oxygen.
7 DRUG INTERACTIONS
Table 3: Clinically Significant Drug Interactions With NAYZILAM
7.1 CYP3A4 Inhibitors
Clinical Impact: Concomitant use of CYP3A4 inhibitors may result in prolongedsedation because of a decrease in plasma clearance ofmidazolam.
Intervention: Avoid co-administration of NAYZILAM with moderate orstrong CYP3A4 inhibitors. NAYZILAM should be used withcaution when co-administered with mild CYP3A4 inhibitors.
Examples: Moderate CYP3A4 inhibitors: erythromycin, diltiazem,verapamil
Strong CYP3A4 inhibitors: ketoconazole, itraconazole,clarithromycin
7.2 Opioids
Clinical Impact: The concomitant use of benzodiazepines and opioids increasesthe risk of respiratory depression because of actions at differentreceptor sites in the CNS that control respiration.
Benzodiazepines interact at GABAA sites and opioids interactprimarily at mu receptors. When benzodiazepines and opioidsare combined, the potential for benzodiazepines to significantlyworsen opioid-related respiratory depression exists.
Intervention: Reserve concomitant prescribing of these drugs for use inpatients for whom alternative treatment options are inadequate.
Limit dosages and durations to the minimum required [seeWarnings and Precautions (5.1)].
Examples: Morphine, hydrocodone, oxymorphone, codeine, fentanyl
7.3 Other Central Nervous System (CNS) DepressantsClinical Impact: Concomitant use of barbiturates, alcohol, or other CNSdepressants may increase the risk of hypoventilation, airwayobstruction, desaturation, or apnea and may contribute toprofound and/or prolonged drug effec |
