Before taking two cold medicines or painkillers at the same time, read the ingredient list, keep acetaminophen in a single product, and go to the hospital the same day if you took too much even without feeling ill

Many cold medicines contain acetaminophen. Taking 2 boxes together means a double dose, and too much harms the liver. In the United States, among people whose liver failed suddenly because of it, nearly 3 in 10 died before they could get a new liver. Leaflets in China advise at most 2 grams a day. The United States also warns against more than 3 cups of alcohol a day while taking it. If you took too much, go to the hospital right away even if you feel fine. The antidote works better the sooner it is used.

Cost

No money. A glance at the ingredient list on each box, a couple of minutes.

Benefit

Over 6 years, 22 hospitals in the United States registered 662 cases of acute liver failure in a row. Of these, 275 (42%) were caused by acetaminophen, and the median dose swallowed was 24 grams. Of these 275 people, 131 (48%) had taken too much by accident, not on purpose. Among the people who took too much by accident, 38% were taking more than a single medicine that contained this ingredient at the same time. Of these 275 people, 27% died before a liver transplant, and 8% received a transplant. In 2020 the National Medical Products Administration required over-the-counter leaflets to state that using too much causes severe liver damage, and that the suggested maximum in a day is not more than 2 grams. The leaflet must also say to avoid combining the drug with medicines that contain acetaminophen or other fever and pain drugs. US rules require the opening line of the warning on this kind of over-the-counter drug to name the liver-harm situations: going over the maximum for a day, taking it together with another medicine that contains acetaminophen, and drinking more than 3 cups of alcohol a day during treatment. The same notice also requires the leaflet for an extended-release product to state that if an adult or a child takes too much, they should be seen at once, whether they feel unwell or not. The antidote is called N-acetylcysteine. The leaflet says to use it as early as possible: within 12 hours the effect is satisfactory, and after 24 hours the effect is poorer. A multicenter study in the United States from 1976 to 1985 followed 2540 overdose patients who were given this antidote. Among patients whose blood level marked them as likely to develop liver injury, liver injury appeared in 6.1% of those who started the antidote within 10 hours, and in 26.4% of those who started it only from 10 to 24 hours. Started within 8 hours after the overdose, it protected the patient no matter how high the blood level was.

Notes

Acetaminophen is also called paracetamol. Combination cold medicines whose generic name contains the characters for acetaminophen (氨酚), such as paracetamol and pseudoephedrine (氨酚伪麻) or paracetamol, caffeine, and chlorphenamine (氨咖黄敏), contain this ingredient. If you are not sure, take every box to the pharmacist at the pharmacy. The grade is B because those US figures are a case registry with no comparison group, so they cannot show how many incidents reading the ingredient list would prevent. The benefit is rated large because of the outcome: in acute liver failure, nearly 3 in 10 die directly. The figures for using the antidote as early as possible come from a multicenter observation with no random assignment, compared only with earlier cases.

Sources · 5

1. Larson AM, Polson J, Fontana RJ, et al.; Acute Liver Failure Study Group (2005). Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology, 42(6):1364-1372. doi.org/10.1002/hep.20948
2. 国家药监局关于修订对乙酰氨基酚常释及缓释制剂说明书的公告（2020年第15号）及附件1《对乙酰氨基酚常释制剂处方药说明书修订要求》、附件2《对乙酰氨基酚常释制剂非处方药说明书修订要求》、附件3《对乙酰氨基酚缓释制剂说明书修订要求》（湖南省药品监督管理局转载）. mpa.hunan.gov.cn/mpa/xxgk/tzgg/wjtz/202003/t2…
3. 21 CFR 201.326(a)(1)(iii)(A) Liver warning. ecfr.gov/current/title-21/chapter-I/subchapte…
4. Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH (1988). Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose: analysis of the national multicenter study (1976 to 1985). New England Journal of Medicine, 319(24):1557-1562. doi.org/10.1056/NEJM198812153192401
5. MedlinePlus. Acetaminophen (In case of emergency/overdose). medlineplus.gov/druginfo/meds/a681004.html