Acetaminophen with Codeine Acetaminophen with Codeine
Also indexed as: Codeine with Acetaminophen, Tylenol with Codeine
Acetaminophen is used to reduce pain and fever. Unlike NSAIDs (nonsteroidal anti-inflammatory drugs), it lacks anti-inflammatory activity. Acetaminophen is available by itself or in nonprescription and prescription-only combination products used to relieve pain and the symptoms associated with colds and flu.
Codeine is a narcotic analgesic (pain reliever) derived from opium. It is used alone and in combination products to treat mild to moderate pain and as a cough suppressant.
Summary of Interactions with Vitamins, Herbs, and Foods
In some cases, an herb or supplement may appear in more than one category, which may seem contradictory. For clarification, read the full article for details about the summarized interactions.
 May Be Beneficial: Side effect reduction/prevention—Taking these supplements may help reduce the likelihood and/or severity of a potential side effect caused by the medication. | Milk thistle* N-acetyl cysteine |
| May Be Beneficial: Supportive interaction—Taking these supplements may support or otherwise help your medication work better. | Vitamin C* |
 Avoid: Reduced drug absorption/bioavailability—Avoid these supplements when taking this medication since the supplement may decrease the absorption and/or activity of the medication in the body. | Hibiscus Tannin-containing herbs* such as green tea, black tea, uva ursi, black walnut, red raspberry, oak, and witch hazel |
 Check: Other—Before taking any of these supplements or eating any of these foods with your medication, read this article in full for details. | Schisandra |
| Depletion or interference | None known |
| Adverse interaction | None known |
| The interactions listed in this table may apply to one or more ingredient of this medication. |
An asterisk (*) next to an item in the summary indicates that the interaction is supported only by weak, fragmentary, and/or contradictory scientific evidence.
Interactions with Dietary Supplements
N-acetyl cysteine (NAC)
Hospitals use oral and intravenous N-acetyl cysteine (NAC) to treat liver damage induced by acetaminophen overdose poisoning.1 NAC is often administered intravenously by emergency room doctors. Oral NAC appears to be effective for acetaminophen toxicity.
An uncontrolled trial compared intravenous NAC with oral NAC in children with acetaminophen poisoning and found that both methods were equally effective in reversing acetaminophen-induced liver toxicity.2 However, acetaminophen toxicity is a potential medical emergency, and should only be managed by qualified healthcare professionals.
Vitamin C
Taking 3 grams of vitamin C with acetaminophen has been shown to prolong the amount of time acetaminophen stays in the body.3 This theoretically might allow people to use less acetaminophen, thereby reducing the risk of side effects. Consult with a doctor about this potential before reducing the amount of acetaminophen.
Interactions with Herbs
Hibiscus
One small study found that hibiscus could decrease levels of acetaminophen if the drug was taken after the tea was consumed though it was not entirely clear if the decreases were clinically significant.4
Milk thistle (Silybum marianum)
Silymarin is a collection of complex flavonoids found in milk thistle that has been shown to elevate liver glutathione levels in rats.5 Acetaminophen can cause liver damage, which is believed to involve glutathione depletion.6 In one study involving rats, silymarin protected against acetaminophen-induced glutathione depletion.7 While studies to confirm this action in humans have not been conducted, some doctors recommend silymarin supplementation with 200 mg milk thistle extract, containing 70–80% silymarin, three times per day for people taking acetaminophen in large amounts for more than one year and/or with other risk factors for liver problems.
Schisandra (Schisandra chinensis)
Gomisin A is a constituent found in the Chinese herb schisandra. In a study of rats given liver-damaging amounts of acetaminophen, gomisin A appeared to protect against some liver damage but did not prevent glutathione depletion8 (unlike milk thistle, as reported above). Studies have not yet confirmed this action in humans.
Tannin-containing herbs
Tannins are a group of unrelated chemicals that give plants an astringent taste. Herbs with large amounts of tannins may interfere with the absorption of codeine and should not be taken together with codeine or codeine-containing products.9 Herbs containing high levels of tannins include green tea (Camellia sinensis), black tea, uva ursi (Arctostaphylos uva-ursi), black walnut (Juglans nigra),red raspberry (Rubus idaeus),oak (Quercus spp.), and witch hazel (Hamamelis virginiana).
Interactions with Foods and Other Compounds
Alcohol
Moderate to high amounts of acetaminophen have caused liver damage in people with alcoholism.10 To prevent problems, people taking acetaminophen should avoid alcohol.
Alcohol causes a loss of coordination, impaired judgment, decreased alertness, drowsiness, and other actions. Narcotic analgesics, including codeine, cause similar loss of control. Combining codeine and alcohol increases the risk of accidental injury. People taking codeine-containing products should avoid alcohol.
Food
Food, especially foods high in pectin (including jellies), carbohydrates, and large amounts of cruciferous vegetables (broccoli, Brussels sprouts, cabbage, and others) can interfere with acetaminophen absorption.11 However, this interference is probably not of great significance, and it is generally accepted that acetaminophen can be taken with or without food.
Codeine commonly causes gastrointestinal (GI) upset. Codeine and codeine-containing products may be taken with food to reduce or prevent GI upset.12 A common side effect of narcotic analgesics, including codeine, is constipation. Increasing dietary fiber (fruits, vegetables, beans, whole-grain foods, and others) and water intake can ease constipation.
References (To view, roll mouse over the "References" heading; to hide, click on the heading)
1. Vale JA, Proudfoot AT. Paracetamol (acetaminophen) poisoning. Lancet 1995;346:547–52.
2. Perry HE, Shannon MW. J Pediatr 1998;132:149–52.
3. Houston JB, Levy G. Drug biotransformation interactions in man. VI: Acetaminophen and ascorbic acid. J Pharm Sci 1976;65:1218–21.
4. Kolawole JA, Maduenyi A. Effect of zobo drink (Hibiscus sabdariffa water extract) on the pharmacokinetics of acetaminophen in human volunteers. Eur J Drug Metab Pharmacokinet 2004;29:25–9.
5. Valenzuela A, Aspillaga M, Vial S, Guerra R. Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat. Planta Med 1989;55:420–2.
6. Threlkeld DS, ed. Central Nervous System Drugs, Acetaminophen. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Mar 1997, 247–f.
7. Campos R, Garrido A, Guerra R, Valenzuela A. Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver. Planta Med 1989;55:417–9.
8. Yamada S, Murawaki Y, Kawasaki H. Preventive effect of gomisin A, a lignan component of schizandra fruits, on acetaminophen-induced hepatotoxicity in rats. Biochem Pharmacol 1993;46:1081–5.
9. Brinker F. Interactions of pharmaceutical and botanical medicines. J Naturopathic Med 1997;7(2):14–20.
10. Threlkeld DS, ed. Central Nervous System Drugs, Acetaminophen. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Mar 1997, 247–f.
11. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 2.
12. Threlkeld DS, ed. Central Nervous System Drugs, Narcotic Agonist Analgesics. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Feb 1990, 243d.
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The information presented in Healthnotes is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires June 2009.