Safety and effectiveness of rapid-acting intra-muscular olanzapine for agitation associated with schizophrenia – Japan postmarketing surveillance study

Figures & data

Figure 1 Disposition of patients.

Abbreviation: TEAE, treatment-emergent adverse event.

Table 1 Patient baseline characteristics

Patient characteristics	n (%)	Mean ± SD
Age (years)	999	46.1±15.3
Age category (years)
<65	860 (86.1)	–
≥65–74	103 (10.3)	–
≥75	36 (3.6)	–
Gender
Male	485 (48.5)	–
Female	514 (51.5)	–
Duration of disease (years)	739	17.5±13.5
History of diabetes in a family member
Absent	707 (70.8)	–
Present	20 (2.0)	–
Unknown	272 (27.2)	–
Inpatient/outpatient status at the start of treatment
Inpatient	848 (84.9)	–
Outpatient	150 (15.0)	–
Unknown	1 (0.1)	–
Medical history
Present	97 (9.7)	–
Unknown	3 (0.3)	–
Complications
Present	310 (31.0)	–
Diabetes-related complicationsa
Present	65 (6.5)	–
Concomitant drug therapy
Present	914 (91.5)	–
Absent	81 (8.1)	–
Unknown	4 (0.4)	–
Psychotropic drug therapyb	908 (90.9)	–
Antipsychotics	888 (88.9)	–
Oral olanzapine	547 (54.8)	–
Other than oral olanzapine	555 (55.6)	–
Typical	214 (21.4)	–
Atypical	465 (46.5)	–
Mood-stabilizer	128 (12.8)	–
Benzodiazepine	381 (38.1)	–
Anticholinergic	145 (14.5)	–
Antidepressants	37 (3.7)	–
Others	92 (9.2)	–
Other concomitant medication	190 (19.0)	–

Notes:

a Diabetes-related complications included high HbA1c and high blood glucose.

b Indicate that some patients select multiple psychotropic drugs.

Abbreviation: SD, standard deviation.

Table 2 Administration information of rapid-acting IM olanzapine

Rapid-acting IM olanzapine	Patients (n=999), n (%)
Initial dose
2.5 mg	1 (0.1)
5.0 mg	39 (3.9)
.5 mg	1 (0.1)
10.0 mg	955 (95.6)
Unknown	3 (0.3)
Total amount of dose (category)
<5 mg	1 (0.1)
≥5–9 mg	35 (3.5)
≥10–14 mg	755 (75.6)
≥15–19 mg	1 (0.1)
≥20–24 mg	65 (6.5)
≥25 mg	139 (13.9)
Unknown	3 (0.3)
Any additional dose within 24 hoursa
Present	110 (11.0)
Injection site
Shoulder	335 (33.5)
Arm	36 (3.6)
Femoral region	8 (0.8)
Gluteal region	526 (52.7)
Otherb	19 (1.9)
Unknown	75 (7.5)

Notes:

a Only patients were counted who had timing data for injections.

b Most patients had injections at the same site. Patients who had injections at different sites were categorized as “Other”.

Abbreviation: IM, intramuscular.

Table 3 Occurrence of ADRs and TEAEs

	TEAEs	ADRs
Number of patients	999	999
Number of patients with adverse events/reactions	28	19
Number of events/reactions	36	26
% of patients with adverse events/reactions	2.8	1.9
MedDRA SOC/PT	Number (%) of patients by type of event/reaction
Metabolism and nutrition disorders	3 (0.3)	1 (0.1)
Dehydration	2 (0.2)	–
Hyperglycemia	1 (0.1)	1 (0.1)
Psychiatric disorders	1 (0.1)	–
Agitation	1 (0.1)	–
Nervous system disorders	13 (1.3)	11 (1.1)
Akathisia	4 (0.4)	3 (0.3)
Dizziness	1 (0.1)	1 (0.1)
Dyslalia	5 (0.5)	5 (0.5)
Dystonia	1 (0.1)	–
Somnolence	4 (0.4)	4 (0.4)
Tremor	1 (0.1)	1 (0.1)
Respiratory, thoracic, and mediastinal disorders	2 (0.2)	–
Epistaxis	1 (0.1)	–
Pneumonia aspiration	1 (0.1)	–
Gastrointestinal disorders	3 (0.3)	3 (0.3)
Constipation	2 (0.2)	2 (0.2)
Diarrhea	1 (0.1)	1 (0.1)
Nausea	1 (0.1)	1 (0.1)
Hepatobiliary disorders	3 (0.3)	3 (0.3)
Hepatic function abnormal	3 (0.3)	3 (0.3)
Renal and urinary disorders	2 (0.2)	1 (0.1)
Urinary incontinence	1 (0.1)	–
Renal impairment	1 (0.1)	1 (0.1)
Investigations	4 (0.4)	3 (0.3)
Blood creatine phosphokinase increase	1 (0.1)	1 (0.1)
Blood glucose abnormal	1 (0.1)	–
Blood pressure decreased	1 (0.1)	1 (0.1)
Blood urea increased	1 (0.1)	1 (0.1)
Injury, poisoning, and procedural complications	1 (0.1)	–
Fall	1 (0.1)	–

Note: Adverse events and adverse reactions were classified using the terminology of the ICH Medical Dictionary for Regulatory Activities (MedDRA/J) Version 19.1.³¹ The total number of reported PT may exceed the number of SOC, because patients might report multiple TEAEs.

Abbreviations: ADR, adverse drug reaction; ICH, International Council on Harmonization of Technical Requirements for Pharmaceuticals for Human Use; MedDRA SOC/PT, Medical Dictionary for Regulatory Activities System Organ Class/Preferred Terms; TEAE, treatment-emergent adverse event.

Table 4 Safety summary by injection pattern

Number of consecutive days treated	Number of doses administered	Observational period (days)							n	Number of patients with any TEAE, n	Number of patients with ADR, n
		1	2	3	4	5	6	7
1	3	RR		R					2	0	0
	2	R		R					10	1	1
	2	RR							10	1	0
	1	R							793	22	15
2	5	R		RR	RR				1	0	0
	4	RR	RR						2	0	0
	3	RR	R						3	0	0
	3	R	RR						3	0	0
	2	R	R						44	1	0
3	6	RR	RR	RR					10	0	0
	6	R	R	R		R	R	R	1	0	0
	5	R	RR	RR					10	0	0
	5	R	R	R		R	R		3	0	0
	4	R	RR	R					3	0	0
	4	R	R	RR					2	0	0
	4	R		R	R	R			1	0	0
	3	R	R	R					81	3	3
4	4	R	R	R	R				4	0	0
	7	R	RR	RR	RR	RR			2	0	0
	5	R		R	R	R	R		1	0	0
	6	R	RR	RR	R				1	0	0
	6	RR	RR	R	R				1	0	0
5	5	R	R	R	R	R			4	0	0
	10	RR	RR	RR	RR	RR			1	0	0
6	6	R	R	R	R	R	R		1	0	0
7	7	R	R	R	R	R	R	R	2	0	0
	13	R	RR	RR	RR	RR	RR	RR	1	0	0
	14	RR	RR	RR	RR	RR	RR	RR	2	0	0
Total									999	28	19

Note: The ICH Medical Dictionary for Regulatory Activities (MedDRA/J), Version 19.1, was used to classify adverse events.³¹

Abbreviations: ADR, adverse drug reaction; ICH, International Council on Harmonization of Technical Requirements for Pharmaceuticals for Human Use; IM, intramuscular; R, rapid-acting IM olanzapine injection; RR, rapid-acting IM olanzapine injections given twice a day; TEAE, treatment-emergent adverse event.

Table 5 TEAEs by concomitant use of benzodiazepine and antipsychotic drugs

Administration	Benzodiazepine (parenteral)			Benzodiazepine (oral)			Antipsychotic drug (parenteral)			Antipsychotic drug, other than olanzapine (oral)			Olanzapine (oral)
	Yes	No	Undescribed	Yes	No	Undescribed	Yes	No	Undescribed	Yes	No	Undescribed	Yes	No
n	12	983	4	375	620	4	60	935	4	529	466	4	547	452
Number of patients with TEAEs	1	27	0	16	12	0	4	24	0	14	14	0	17	11
Number of TEAEs	1	35	0	23	13	0	4	32	0	16	20	0	25	11
Percentage of patients with TEAEs	8.3	2.7	0.0	4.3	1.9	0.0	6.7	2.6	0.0	2.6	3.0	0.0	3.1	2.4

Abbreviation: TEAE, treatment-emergent adverse event.

Figure 2 PANSS-EC subscore.

Abbreviations: IM, intramuscular; LOCF, last observation carried forward; PANSS-EC, Positive and Negative Syndrome Scale – Excited Component.

Table 6 Total PANSS-EC score

Observation time point	n	Mean	SD	Min	Max	Changes from baseline	95% CI
						Point estimates
Baseline (before initial administration)	625	23.3	6.4	5	35
2 hours after initial administration	522	16.9	7.0	5	35	−6.9	−7.5 to −6.4
2 days after last administration	438	16.0	6.6	5	35	−7.6	−8.2 to −7.1
3 days after last administration	467	14.9	6.3	5	35	−8.8	−9.4 to −8.2
LOCF	650	14.9	6.5	5	35	−8.6	−9.1 to −8.1

Abbreviations: CI, confidence interval; LOCF, last observation carried forward; Max, maximum; Min, minimum; PANSS-EC, Positive and Negative Syndrome Scale – Excited Component; SD, standard deviation.

ICHIntroductory guide MedDRA version 19.1McLean, VAMedDRA2016 Available from: https://www.meddra.org/sites/default/files/guidance/file/intguide_19_1_english.pdfAccessed November 27, 2017

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