Can You Take Olanzapine with Clonazepam?

Severity assessment

Major. Concomitant use of olanzapine and benzodiazepines like clonazepam can cause potentially fatal respiratory depression, excessive sedation, and cardiorespiratory collapse.

Mechanism (plain English)

Both clonazepam and olanzapine act on the central nervous system to slow down brain activity. Clonazepam enhances the effect of GABA, a calming brain chemical, while olanzapine blocks certain dopamine and serotonin receptors. When taken together, their sedative effects add up, which can dangerously slow down breathing, lower blood pressure, and reduce alertness.

Evidence level

Regulator-flagged. The FDA has issued specific warnings against the concomitant administration of intramuscular olanzapine and parenteral benzodiazepines due to the risk of excessive sedation and cardiorespiratory depression.

Top regulator advisories (cite verbatim or close paraphrase)

• TGA (Australia): The TGA product information for olanzapine warns that caution should be used when olanzapine is taken in combination with other centrally acting drugs and alcohol. The clonazepam product information notes that concomitant use with other CNS depressants may increase the clinical effects of clonazepam, including severe sedation and respiratory depression.
• MHRA / NICE (UK): The BNF notes that both olanzapine and clonazepam have effects on the CNS and can cause sedation, which might affect the ability to perform skilled tasks. The MHRA product information for clonazepam states that concomitant use with other CNS depressants should be avoided due to the potential for severe sedation and clinically relevant respiratory and/or cardio-vascular depression.
• FDA / CDC (US): The FDA label for olanzapine states: "Concomitant administration of intramuscular olanzapine and parenteral benzodiazepine is not recommended due to the potential for excessive sedation and cardiorespiratory depression."
• EMA (Europe): The EMA product information for olanzapine advises caution when olanzapine is taken in combination with other centrally acting medicines and alcohol.

Clinical risk factors that elevate the danger

• Older age (elderly patients are more susceptible to CNS depression)
• Pre-existing respiratory conditions (e.g., COPD, sleep apnea, asthma)
• Concomitant use of other CNS depressants, including alcohol or opioids
• Hepatic impairment (which can slow the clearance of both drugs)
• High doses or parenteral (intramuscular/intravenous) administration

What a patient should be told

• What the risk is: Taking these two medicines together can cause severe drowsiness, dangerously slow breathing, and low blood pressure.
• Do not stop suddenly: Do not stop taking either medicine suddenly without talking to your doctor, as this can cause withdrawal symptoms or a return of your condition.
• Warning signs: Seek immediate medical help if you experience extreme sleepiness, difficulty breathing, shallow breathing, or feel like you might pass out.
• Safer-alternative discussion: Talk to your prescriber or pharmacist about whether this combination is safe for you, or if the doses need to be adjusted.
• Urgent-care triggers: Go to the emergency room or call for help immediately if you or someone else notices you have unusually slow or weak breathing, or if you cannot be easily awakened.

Top 3 sources (with full citation)

1. U.S. Food and Drug Administration (FDA). (2014). ZYPREXA (olanzapine) Prescribing Information. Reference ID: 3675779. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020592s062021086s040021253s048lbl.pdf
2. Medicines and Healthcare products Regulatory Agency (MHRA). (2026). Clonazepam Roma 0.5 mg Tablets Summary of Product Characteristics (SmPC). https://www.medicines.org.uk/emc/product/101985/smpc
3. European Medicines Agency (EMA). Olanzapine Apotex Summary of Product Characteristics. https://www.ema.europa.eu/en/documents/product-information/olanzapine-apotex-epar-product-information_en.pdf

Notes for the reviewing pharmacist

The most severe warnings (including FDA boxed warnings or specific contraindications) often relate to the parenteral (IM/IV) co-administration of olanzapine and benzodiazepines due to reports of fatalities from cardiorespiratory depression. However, oral co-administration also carries significant risks of additive CNS and respiratory depression, especially in vulnerable populations (elderly, respiratory compromised). Monitor closely for over-sedation and respiratory status if the combination is unavoidable.

Source metadata

{
  "pair": "clonazepam + olanzapine",
  "severity": "Major",
  "evidence_level": "Regulator-flagged",
  "source_urls": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020592s062021086s040021253s048lbl.pdf; https://www.medicines.org.uk/emc/product/101985/smpc; https://www.ema.europa.eu/en/documents/product-information/olanzapine-apotex-epar-product-information_en.pdf"
}