What the FDA labels say about taking them together
Acetaminophen/caffeine/dihydrocodeine and codeine
Acetaminophen/caffeine/dihydrocodeine's FDA label of May 2, 2022 names codeine in its boxed warning section; codeine's label does not name acetaminophen/caffeine/dihydrocodeine itself but warns about its class (Stimulants, Opioids (opioid agonists)). The acetaminophen/caffeine/dihydrocodeine label: “This combination product is contraindicated in patients with hypersensitivity to dihydrocodeine, codeine, acetaminophen, caffeine, or any of the inactive components listed above, or any situation where opioids are …”
Check it at the source: the acetaminophen/caffeine/dihydrocodeine FDA label on DailyMed (effective May 2, 2022, Proficient Rx LP); the codeine FDA label on DailyMed (effective December 22, 2025, Hikma Pharmaceuticals USA Inc.).
What does the acetaminophen/caffeine/dihydrocodeine label say about codeine?
Acetaminophen/caffeine/dihydrocodeine label, boxed warningDeath Related to Ultra-Rapid Metabolism of Codeine to Morphine Respiratory depression and death have occurred in children who received codeine following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine due to a CYP2D6 polymorphism.
Acetaminophen/caffeine/dihydrocodeine label, contraindicationsThis combination product is contraindicated in patients with hypersensitivity to dihydrocodeine, codeine, acetaminophen, caffeine, or any of the inactive components listed above, or any situation where opioids are contraindicated including significant respiratory depression (in unmonitored settings or in the absence of resuscitative equipment), acute or severe bronchial asthma or hypercapnia, and paralytic ileus.
Acetaminophen/caffeine/dihydrocodeine label, warningsDeath Related to Ultra-Rapid Metabolism of Codeine to Morphine: Respiratory depression and death have occurred in children who received codeine in the postoperative period following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine (i.e., multiple copies of the gene for cytochrome P450 isoenzyme 2D6 or high morphine concentrations).
Source: FDA drug label (Trezix), ANDA204785 (Key Therap), as published by Proficient Rx LP, effective May 2, 2022 (SPL set 45c3c2a1-6a89-471e-b6d4-5a4cd73b987a), via openFDA; the full label on DailyMed
What does the codeine label say about acetaminophen/caffeine/dihydrocodeine?
Codeine's label does not name acetaminophen/caffeine/dihydrocodeine itself; it warns about its class (Stimulants, Opioids (opioid agonists)):
Codeine label, warnings and precautionsLife-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended.
Codeine label, boxed warningSERIOUS AND LIFE-THREATENING RISKS FROM USE OF CODEINE SULFATE TABLETS Addiction, Abuse, and Misuse Because the use of Codeine Sulfate Tablets exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions ( 5.1 ), Dosage and Administration ( 2.1 )].
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
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
| Acetaminophen/caffeine/dihydrocodeine | Codeine | |
|---|---|---|
| Labeled for | Pain | Pain |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | n/a | $0.726 per tablet 30 mg tablet |
| Shortage now | No current entry | No 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?
- Check more medicines together
- up to five at once