ar disease or family history of QT prolongation, and in concomitant use with other medicinal products known to prolong the QT interval. The potential risk of QTc prolongation due to interaction with medicinal products known to prolong QTc interval is unknown.
Seizures/convulsions
Loxapine should be used with caution in patients with a history of convulsive disorders since it lowers the convulsive threshold. Seizures have been reported in patients receiving oral loxapine at antipsychotic dose levels, and may occur in epileptic patients even with maintenance of routine anticonvulsant drug therapy (see section 4.5).
Anticholinergic activity
Because of anticholinergic action, ADASUVE should be used cautiously in patients with glaucoma or a tendency to urinary retention, particularly with concomitant administration of anticholinergic-type antiparkinson medicinal products.
Intoxication or physical disease (delirium)
The safety and efficacy of ADASUVE has not been eva luated in patients with agitation due to intoxication or physical disease (delirium). ADASUVE should be used with caution in patients who are intoxicated or delirious (see section 4.5).
4.5 Interaction with other medicinal products and other forms of interaction
Concomitant administration of benzodiazepines or other hypnosedatives or respiratory depressants may be associated with excessive sedation and respiratory depression or respiratory failure. If benzodiazepine therapy is deemed necessary in addition to loxapine, patients should be monitored for excessive sedation and for orthostatic hypotension.
A study of inhaled loxapine and intramuscular lorazepam 1 mg in combination found no significant effects on respiratory rate, pulse oximetry, blood pressure, or heart rate compared with either drug administered alone. Higher doses of lorazepam have not been studied. The effects of the combination on sedation appeared to be additive.
Potential for ADASUVE to affect other medicinal products
Loxapine is not expected to cause clinically important pharmacokinetic interactions with medicinal products that are either metabolised by cytochrome P450 (CYP450) isozymes or glucuronidated by human uridine 5'-diphosphoglucuronosyl transferases (UGTs) .
Caution is advised if loxapine is combined with other medicinal products known to lower the seizure threshold, e.g. phenothiazines or butyrophenones, clozapine, tricyclics or selective serotonine reuptake inhibitors (SSRIs), tramadol, mefloquine (see section 4.4).
In vitro studies indicated that loxapine was not a substrate for P-glycoprotein (P-gp), but does inhibit P-gp. At therapeutic concentrations, however, it is not expected to inhibit P-gp-mediated transport of other medicinal products in a clinically significant manner.
Given the primary CNS effects of loxapine, ADASUVE should be used with caution in combination with alcohol or other centrally acting medicinal products, e.g., anxiolytics, most antipsychotics, hypnotics, opiates, etc. The use of loxapine in patients with alcohol or medicinal product intoxication (either with prescribed or illicit medicinal products) has not been eva luated. Loxapine may cause severe respiratory depression if combined with other CNS-depressants (see section 4.4).
Potential for other medicinal products to affect ADASUVE
Loxapine is a substrate for flavin-containing mono-oxygenases (FMOs), and for several CYP450 isozymes (see secti |
