Transmucosal Nasal Drug Delivery: Systemic Bioavailability of ...

7. Project III: Transmucosal nasal delivery of low-dose midazolam – evaluation of two preparations for procedural anxiolysis
Local irritation and adverse drug reactions
Of total 110 patients receiving study medication, 53 patients (MD n=27 [48%], UD n=26 [52%])
spontaneously reported local irritation. Intensity of local irritation was rated as mild (MD n=22
[39%], UD n=13 [24%]), moderate (MD n=5 [9%], UD n=9 [17%]), or strong (MD n=0, UD n=4
[7%]), see Figure 7-6.
Besides burning (burning in the nose MD n=14 [52%], UD n=15 [58%] and burning in the throat
area MD n=3 [11%], UD n=1 [4%]), patients sporadically reported on watery eyes and coughing.
Local irritation was reported to vanish within few minutes and never had to be treated.
No severe adverse reaction occurred and hence flumazenil never had to be administered. Other
mentioned discomfort (e.g., noise, pain in the back or hip) were related to the MRI examination or
disease of the patient.
MD
UD
moderate;
9%
strong; 0%
moderate;
17%
strong; 7%
mild; 39%
none; 52%
none; 52%
mild; 24%
Figure 7-6: Spontaneous reports on local irritation; in both groups 52% of the patients did not report
on any local irritation. The intensity of the local irritation was rated as mild (MD: 39%, UD 24%),
moderate (MD: 9%, UD: 17%), and strong (MD: 0%, UD: 7%).
Monitoring
Two months after study start, difficulties in patient recruitment in two study centers (B, C) were
detected. Patients often admitted their fear only at the beginning or even during MRI examination.
To avoid delay of day’s schedule, patients admitting their fear only during MRI examination, were
not invited to enter the study and the routine anxiolytic treatment was offered.
To call attention for the possibility of treatment options for claustrophobia and general anxiety, we
designed posters and attached them in the waiting room of Centre B and C.
Katja Suter-Zimmermann Page 91 of 188 University of Basel, 2008