Butalbital, aspirin, caffeine, and codeine and Cimetidine interaction

Butalbital, aspirin, caffeine, and codeine and Cimetidine: 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 Butalbital, aspirin, caffeine, and codeine (BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE) label · effective 2026-01-15

Major

The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex.

Boxed warningby drug classView label on DailyMed
Major

Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE requires careful consideration of the effects on codeine, and the active metabolite, morphine.

Boxed warningby drug classView label on DailyMed
Major

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex.

Boxed warningby drug classView label on DailyMed
Moderate

Risks of Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Cytochrome P450 3A4 Interaction The concomitant use of BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE with all cytochrome P450 3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir) or discontinuation of a cytochrome P450 3A4 inducer such as rifampin, carbamazepine,…

Warnings and precautionsby drug classView label on DailyMed

From the Cimetidine label · effective 2026-01-01

Moderate

…apparently through an effect on certain microsomal enzyme systems, has been reported to reduce the hepatic metabolism of warfarin-type anticoagulants, phenytoin, propranolol, nifedipine, chlordiazepoxide, diazepam, certain tricyclic antidepressants, lidocaine, theophylline, and metronidazole, thereby delaying elimination and increasing blood levels of these drugs.

Drug interactionsby drug classView label on DailyMed
Moderate

However, a crossover study in healthy subjects receiving either 300 mg 4 times daily or 800 mg at bedtime of cimetidine tablets concomitantly with a 300 mg twice-daily dose of theophylline extended-release tablets demonstrated less alteration in steady-state theophylline peak serum levels with the 800 mg at bedtime regimen, particularly in subjects aged 54 years…

Drug interactionsby drug classView label on DailyMed
Moderate

(Note: All patients receiving theophylline should be monitored appropriately, regardless of concomitant drug therapy.) Dosage of the drugs mentioned above and other similarly metabolized drugs, particularly those of low therapeutic ratio or in patients with renal and/or hepatic impairment, may require adjustment when starting or stopping the concomitant administration…

Drug interactionsby drug classView label on DailyMed
Minor

Interaction with phenytoin, lidocaine, and theophylline has also been reported to produce adverse clinical effects.

Drug interactionsby 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.