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What the FDA labels say about taking them together

Codeine and hydrocodone

Codeine's FDA label of December 22, 2025 names hydrocodone in its drug interactions section; hydrocodone's label does not name codeine itself but warns about its class (Opioids (opioid agonists)). The codeine label: “MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity.”

Check it at the source: the codeine FDA label on DailyMed (effective December 22, 2025, Hikma Pharmaceuticals USA Inc.); the hydrocodone FDA label on DailyMed (effective May 29, 2026).

What does the codeine label say about hydrocodone?

Codeine label, drug interactions

Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (…). Intervention: Do not use Codeine Sulfate Tablets in patients taking MAOIs or within 14 days of stopping such treatment. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of other opioids (such as oxycodone, hydrocodone, oxymorphone, hydrocodone, or buprenorphine) …

Source: FDA drug label (Codeine sulfate), Hikma Pharmaceuticals USA Inc., effective December 22, 2025 (SPL set 010905f9-3bcb-4b50-9fe8-a3ad0010f14c), via openFDA; the full label on DailyMed

What does the hydrocodone label say about codeine?

Hydrocodone's label does not name codeine itself; it warns about its class (Opioids (opioid agonists)):

Hydrocodone label, boxed warning

Instruct patients to swallow HYSINGLA ER whole to avoid exposure to a potentially fatal dose of hydrocodone. ( 5.2 ) Accidental ingestion of HYSINGLA ER, especially by children, can result in fatal overdose of hydrocodone. ( 5.2 ) Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.

Hydrocodone label, warnings and precautions

Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended.

Source: FDA drug label (Hysingla ER), Knoa Pharma LLC, effective May 29, 2026 (SPL set b7d23ac2-e776-9f62-3290-c64c2d6eb353), via openFDA; the full label on DailyMed

These are the labels' own sentences. PlainMeds does not grade interactions; a pharmacist or prescriber can say what they mean for one person's medicines.

Both medicines on the record

1Codeine generic labelers
1Hydrocodone generic labelers
CodeineHydrocodone
Labeled forPainPain
Boxed warningYesYes
Pharmacy cost (NADAC)$0.726 per tablet 30 mg tablet$7.95 per capsule 15 mg capsule
Shortage nowNo current entryNo current entry

Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)

What next?