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Acetaminophen with Codeine

Drug Information

This drug combines two primary active ingredients: acetaminophen and 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.

Common brand names:

Aceta-codeine, Capital with codeine, Tylenol-codeine

Summary of Interactions with Vitamins, Herbs, & Foods

Types of interactions: Beneficial Adverse Check

Replenish Depleted Nutrients

  • none

Reduce Side Effects

  • N-Acetyl Cysteine

    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.

  • Fiber

    Constipation is a common side effect of codeine. Increasing fluid and fiber intake can ease constipation.3

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • High-Fiber

    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.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Milk Thistle

    Silymarin is a collection of complex flavonoids found in milk thistle (Silybum marianum) that has been shown to elevate liver glutathione levels in rats.8 Acetaminophen can cause liver damage, which is believed to involve glutathione depletion.9 In one study involving rats, silymarin protected against acetaminophen-induced glutathione depletion.10 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.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

Support Medicine

  • none

Reduces Effectiveness

  • Cruciferous Vegetables

    Food, especially foods high in pectin (including jellies), carbohydrates, and many types of cruciferous vegetables (broccoli, Brussels sprouts, cabbage, and others) can interfere with acetaminophen absorption.14 It is unclear how much effect this interaction has on acetaminophen activity.

  • 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.15

  • High-Pectin

    Food, especially foods high in pectin (including jellies), carbohydrates, and many types of cruciferous vegetables (broccoli, Brussels sprouts, cabbage, and others) can interfere with acetaminophen absorption.19 It is unclear how much effect this interaction has on acetaminophen activity.

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
  • Teas and Herbs with Tannin

    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.25 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).

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

Potential Negative Interaction

  • N-Acetyl Cysteine

    Hospitals use oral and intravenous NAC to treat liver damage induced by acetaminophen overdose poisoning.27 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.28 However, acetaminophen toxicity is a potential medical emergency, and should only be managed by qualified healthcare professionals.

Explanation Required 

  • Schisandra

    Gomisin A is a constituent found in the Chinese herb schisandra (Schisandra chinensis). 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 depletion29 (unlike milk thistle, as reported above). Studies have not yet confirmed this action in humans.

  • Vitamin C

    Taking 3 grams vitamin C with acetaminophen has been shown to prolong the amount of time acetaminophen stays in the body.31 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. However, increasing the time acetaminophen is in the body might also theoretically increase its toxicity. Consult with a doctor before taking vitamin C along with acetaminophen.32

    The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
The Drug-Nutrient Interactions table may not include every possible interaction. Taking medicines with meals, on an empty stomach, or with alcohol may influence their effects. For details, refer to the manufacturers’ package information as these are not covered in this table. If you take medications, always discuss the potential risks and benefits of adding a new supplement with your doctor or pharmacist.

References

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. Tylenol with Codeine (Codeine and acetaminophen) tablet [package insert]. Ortho-McNeil Pharmaceutical, Inc. Rarition, New Jersey http://www.losepain.com/pdf/tylenol.pdf Accessed September 12, 2011

4. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 2.

5. 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.

6. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 2.

7. 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.

8. 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.

9. Threlkeld DS, ed. Central Nervous System Drugs, Acetaminophen. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Mar 1997, 247–f.

10. 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.

11. 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.

12. Threlkeld DS, ed. Central Nervous System Drugs, Acetaminophen. In Facts and Comparisons Drug Information. St. Louis, MO: Facts and Comparisons, Mar 1997, 247–f.

13. 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.

14. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 2.

15. 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.

16. 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.

17. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 2.

18. 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.

19. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 2.

20. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 2.

21. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 2.

22. 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.

23. Holt GA. Food & Drug Interactions. Chicago: Precept Press, 1998, 2.

24. 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.

25. Brinker F. Interactions of pharmaceutical and botanical medicines. J Naturopathic Med 1997;7(2):14–20.

26. Brinker F. Interactions of pharmaceutical and botanical medicines. J Naturopathic Med 1997;7(2):14–20.

27. Vale JA, Proudfoot AT. Paracetamol (acetaminophen) poisoning. Lancet 1995;346:547–52.

28. Perry HE, Shannon MW. J Pediatr 1998;132:149–52.

29. 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.

30. 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.

31. Houston JB, Levy G. Drug biotransformation interactions in man. VI: Acetaminophen and ascorbic acid. J Pharm Sci 1976;65:1218–21.

32. FDA Information on Acetaminophen, Jan 13, 2011. http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm165107.htm

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