I am not a doctor, but I am on zoloft, was on seroquel, but gained 50 pounds on the seroquel in 3 months. I never had any problems taking motrin for a headache. The feedback you provide will help us show you more relevant content in the future. Doctors give trusted answers on uses, effects, side-effects, and cautions: Dr. Gaffney on zoloft and tylenol: Zoloft (sertraline) interferes with the metabolism of Codeine and makes it less effective. hydrocodone can you actually get off of hydrocodone completely by tapering down, such as 8 one day, 7 the next day, etc.? i am really addicted taking as many as 11 a day. Yes, you can mix Zoloft with Excedrin. Mixing these two drugs should cause no negative interactions or negative side effects. There is no known adverse interaction between Zoloft and Acetaminophen. One is a mild pain reliever the other an antidepressant. The only thing you need to worry about is liver damage from too much Acetaminophen because Zoloft is also metabolized in the liver. However, if you were to mix Xanax and Tylenol or acetaminophen combined with another substance, such as an opioid, then it can be very dangerous. Doing this can increase your risk of experiencing respiratory depression and having an overdose. If the Zoloft works, then you won't worry about this stuff so much and you can do what you like in moderate amounts, as Nursegirl says. I'm not telling you what to eat and not eat, just giving a suggestion for now on something that won't make you worry and that will also be good for you, something positive to do for yourself. Can You Take Anything For Headache Such As Tylenol Or Motrin. my daughter has been taking Zoloft for 4 days (25 mg) and tonight is the first night she started a whole pill (50 mg) can she take.