Pharm
Olanzapine
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Olanzapine
, Zyprexa, Lybalvi
See Also
Antipsychotic Medication
Psychosis
Class
Atypical Antipsychotic
(Second
Gene
ration agent)
Neuroleptic
Thienobenzodiazepine
Mechanism
Primarily
Serotonin
Type II Antagonist (
5-HT
2 antagonist -
5-HT
2A and
5-HT
2C, as well as
5-HT
3)
Also
Dopamine
(D1-4), muscarinic (M1-5)
Anticholinergic
, adrenergic (alpha-1) and histamine (H1) antagonist
Chemical structure similar to
Clozapine
Indications
Primary Indications
Schizophrenia
Acute mania phase of
Bipolar Disorder
Agitated Delirium
(emergency department)
Other Indications
Migraine Headache
Appears to have similar efficacy to
Droperidol
(
Inapsine
) for
Migraine Headache
Hill (2008) Acad Emerg Med 15(9):806-11 +PMID:19244630 [PubMed]
Avoid use in
Psychosis in Dementia
Higher risk of CVA and overall mortality in elderly
Preparations
Olanzapine (Zyprexa)
Standard preparation, and generic ($30/month)
Olanzapine/Samidorphan (Lybalvi)
Released in 2021 at $1400/month
Samidorphan is a
Naltrexone
derivative added to reduce weight gain that typically occurs with Olanzapine
Avoid all
Opioid
s while on Samidorphan (and causes withdrawal in those on
Chronic Opioid
s)
Transition to Olanzapine without Samidorphan at least 5 days before
Opioid
management needed
Marginal efficacy for cost (other strategies to reduce weight gain are preferred)
Consider
Antipsychotic
s less associated with weight gain (e.g.
Aripiprazole
,
Ziprasidone
)
Lifestyle changes (
Exercise
and diet)
Consider
Metformin
References
(2022) Presc Lett 29(1): 6
Dosing
Adults
Start: 5 to 10 mg orally daily (may be repeated every 2 hours to total maximum of 20 mg/day)
Increase in 5 mg increments weekly as tolerated
Maximum: 20 mg/day
Elderly
Initial: 1.25 to 2.5 mg orally daily
Titrate up as tolerated (watch for
Hypotension
)
Maximum: 10 mg/day
Acute management of
Agitation
Dose: 10 mg IM every 4 hours (up to 30 mg/day)
Dosing schedule may also be increased
Dose 1 at time 0 hours: 10 mg
Dose 2 at time 2 hours: 10 mg
Dose 3 at time 6 hours: 10 mg (last dose for day)
Emerging: Intravenous dosing in
Agitation
Off label use (Only FDA approved for oral and IM delivery)
Use only in closely monitored settings (respiratory depression,
Hypotension
)
Initial Dose: 5 mg IV
Subsequent dose: 2.5 to 5 mg IV at least 10 minutes after initial dose (maximum 10 mg/day)
Large HCMC ED study in 2016 demonstrated safety of 5 mg IV doses
No serious complications including no
QT Prolongation
(although
Hypoxia
did occur)
Martel (2016) Acad Emerg Med 23(1): 29-35 +PMID:26720055 [PubMed]
Adverse Effects
See
Antipsychotic
s
Weight gain (4 kg)
Sedation
Headache
Orthostatic Hypotension
(21% with oral dosing)
Seizure
s (nearly 1% of patients)
Extrapyramidal Side Effect
s
Akathisia
(27%)
Cognitive slowing
Overall higher mortality in elderly (see
Atypical Antipsychotic
s)
Lowest risk of
QTc Prolongation
compared with other
Antipsychotic
s
Hyperglycemia
Increased risk of
Diabetes Mellitus
Koro (2002) BMJ 325:243-5 [PubMed]
Hyperlipidemia
Koro (2002) Arch Gen Psychiatry 59:1021-6 [PubMed]
Other effects
Neuroleptic
malignant sydnrome (rare, but lethal)
Increased
Liver Function Test
s
Increased
Creatine Kinase
Pancreatitis
Anticholinergic
side effects
Hyperprolactinemia
(secondary reproductive function disorders)
Drug Interactions
Increase
Antipsychotic
levels (toxicity risk): Monitor for toxicity
Ciprofloxacin
Fluvoxamine
Decrease
Antipsychotic
levels (lower efficacy)
Carbamazepine
Phenytoin
Nicotine
Rifampin
Omeprazole
Cardiorespiratory depression (includes sedation,
Bradycardia
and
Hypotension
)
Benzodiazepine
s (e.g.
Midazolam
)
Based on warning in prescribing information since 2005
Combination appears safe from studies in which Olanzapine was combined with
Benzodiazepine
s
EMA recommends separating dosing by 60 minutes
Williams (2018) Ment Health Clin 8(5): 208–213 +PMID: 30206503 [PubMed]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125121/
Safety
Pregnancy Category C
However, does cross placenta
Not recommended during
Lactation
(found in
Breast Milk
)
Monitoring
See
Antipsychotic
References
Glauser and Peters (2016) Crit Dec Emerg Med 30(4): 17-27
LoVecchio (2021) Crit Dec Emerg Med 35(9): 31
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