Doxepin and Sodium oxybate interaction

Doxepin and Sodium oxybate: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Sodium oxybate (Xyrem) label · effective 2025-07-01

Major

Abuse or misuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death [see Warnings and Precautions ( 5.2 )].

Boxed warningby drug classView label on DailyMed
Major

Abuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death.

Warnings and precautionsby drug classView label on DailyMed
Moderate

• CNS depression: Use caution when considering the concurrent use of Xyrem with other CNS depressants ( 5.1 ).

Warnings and precautionsby drug classView label on DailyMed
Moderate

The concurrent use of Xyrem with other CNS depressants, including but not limited to opioid analgesics, benzodiazepines, sedating antidepressants or antipsychotics, sedating anti-epileptic drugs, general anesthetics, muscle relaxants, and/or illicit CNS depressants, may increase the risk of respiratory depression, hypotension, profound sedation, syncope, and…

Warnings and precautionsby drug classView label on DailyMed
Moderate

Use of other CNS depressants may potentiate the CNS-depressant effects of Xyrem [see Warnings and Precautions ( 5.1 )] .

Drug interactionsby drug classView label on DailyMed

From the Doxepin (Silenor) label · effective 2026-04-21

Moderate

Although behaviors such as "sleep-driving" may occur with hypnotics alone at therapeutic doses, the use of alcohol and other CNS depressants with hypnotics appears to increase the risk of such behaviors, as does the use of hypnotics at doses exceeding the maximum recommended dose.

Warnings and precautionsby drug classView label on DailyMed
Moderate

When taken with SILENOR, the sedative effects of alcoholic beverages, sedating antihistamines, and other CNS depressants may be potentiated [s ee Warnings and Precautions (5.2) and Drug Interactions (7.3 , 7.4) ].

Warnings and precautionsby drug classView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.