Cold Medications Safe With Lithium

In our latest question and answer, the pharmacist discusses safe cold medications, and which to avoid, with lithium.


Can I take guaifenesin and pseudoephedrine with lithium? I have them as single ingredient tablets not containing any other medications. More specifically, 1200 mg guaifenesin and 30 mg pseudoephedrine.... if they are contraindicated, are there any cold medications I CAN take with lithium?

Asked by Black Orchid On Sep 09, 2022

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Sep 09, 2022
Last updated Jul 18, 2024

Key points

  • Lithium is a 'narrow therapeutic index drug', and small changes in dose can cause significant differences in effect and adverse reactions.
  • There are several cold medications that interact with lithium, most notably, NSAIDs (e.g. ibuprofen) and caffeine-containing products.
  • Safe cold medications include Tylenol, Mucinex and Sudafed.

Lithium is a widely utilized and effective medication for the treatment of a variety of psychiatric conditions.

These conditions include:

  • Bipolar Disorder
  • Mania

However, lithium is classified as a 'narrow therapeutic index' drug. Doses of lithium resulting in therapeutic or toxic concentrations in the blood are close. Care must be taken with initial dosing and dose titration.

Due to the risk of toxicity, close monitoring of lithium concentrations is necessary when initiating therapy and routinely for the duration of treatment. In fact, the prescribing information for lithium has a boxed warning stating the following:

"Lithium toxicity is closely related to serum lithium concentrations, and can occur at doses close to therapeutic concentrations. Facilities for prompt and accurate serum lithium determinations should be available before initiating therapy."
Lithium Prescribing Information

For some individuals, lithium can be a particularly difficult drug to avoid adverse effects on as a variety of common conditions can cause fluctuating lithium levels, which could result in toxicity. These conditions include:

  • Urinary retention
  • Hyponatremia (low sodium levels)
  • Dehydration
  • Infection

Additionally, it is important to be aware of clinically significant drug interactions that can affect lithium levels. Since you are interested in over-the-counter cold medications, these are discussed below.

Cold Medications To Avoid With Lithium


Non-steroidal anti-inflammatory drugs should generally be avoided with lithium. Over-the-counter NSAIDs include:

  • Advil (Ibuprofen)
  • Motrin (Ibuprofen)
  • Aleve (Naproxen)
  • Aspirin

NSAIDs decrease blood flow in the kidneys, which results in decreased lithium clearance and increased serum lithium concentrations. This increases the risk of side effects.

A variety of studies have shown that lithium toxicity has resulted from interactions between an NSAID and lithium. One study found that both indomethacin and piroxicam have been reported to significantly increase steady-state plasma lithium concentrations.

There is also evidence that other NSAIDs, including the selective cyclooxygenase-2 (COX-2) inhibitors (e.g. Celebrex), have the same effect.

There aren't many studies looking specifically at over-the-counter NSAIDs (like ibuprofen), but they should nonetheless be avoided.


Although not traditionally seen as a 'cold' medication, caffeine is a common ingredient in many over-the-counter analgesics, including Excedrin.

Caffeine appears to reduce serum lithium concentrations. Therefore, ingesting excess caffeine can decrease the effects of lithium.

However, and this is important to note, lithium adverse reactions have also been noted to increase simultaneously with a reduction in caffeine intake.

One study noted that in 11 coffee-drinking patients stabilized on lithium, serum lithium concentrations increased during 2 weeks when coffee was withheld and fell when coffee was resumed.

It is therefore recommended to keep your caffeine intake consistent when taking lithium.

Herbal Medications

Lithium should be avoided with many herbal medications. These include:

  • Caffeine-containing products (e.g. guarana, green tea, cola nut).
  • Those with diuretic effects (e.g. agrimony, artichoke, buchu, burdock, celery, corn silk, guaiac wood, squill and uva ursi). Changing the fluid balance in our bodies can alter lithium levels.
  • Those with serotonergic effects (e.g. 5-hydroxytryptophan, Hawaiian baby woodrose, L-tryptophan, S-adenosylmethionine, and St. John's wort). Serotonin and lithium are discussed more below.

Cold Medications To Use Caution With


Dextromethorphan, a commonly used anti-tussive, can have serotonergic effects (i.e. can increase serotonin levels). Lithium can also increase serotonin levels, but only to a mild degree.

Taking multiple drugs that have serotonergic effects can increase the risk of developing serotonin syndrome. Serotonin syndrome is characterized by the rapid development of:

  • Hyperthermia
  • High blood pressure
  • Mental status changes

Serotonin syndrome with lithium is thought to be rare but is extremely serious if it occurs.

Most reported cases of serotonin syndrome with lithium have only occurred in individuals on multiple prescription serotonergic drugs. Nevertheless, it is important to be aware of and you should discuss the use of dextromethorphan with your doctor prior to using.

Sedating Antihistamines

While there is no drug-drug interaction with lithium and sedating antihistamines (like Benadryl), they can cause additive sedation and drowsiness. Therefore, caution is advisable during concurrent use of both.

Cold Medications Safe With Lithium


Tylenol (acetaminophen) is considered a safe analgesic to take with lithium. There are no known drug interactions.


Mucinex (guaifenesin) is a commonly used expectorant that has few drug interactions. It is considered safe to take with lithium.


Sudafed (pseudoephedrine) is a nasal decongestant that has no known drug interaction with lithium. Additionally, Sudafed PE, which contains phenylephrine, is not known to interact with lithium.

Final Words

It is always a good idea to check into potential drug interactions before taking over-the-counter medication. This is especially true with a drug like lithium, which has a narrow range of safety and efficacy.

Several are considered safe (e.g. Tylenol, Mucinex, and Sudafed) but several others should be avoided (e.g. NSAIDs). Be sure to ask your doctor or local pharmacist about potential drug interactions with any over the counter product you are looking at purchasing.


  • A case of serotonin syndrome precipitated by abuse of the anticough remedy dextromethorphan in a bipolar patient treated with fluoxetine and lithium, PubMed
  • Serotonin syndrome after lithium add-on medication to paroxetine, PubMed
  • A life-threatening interaction between lithium and celecoxib, PubMed
  • Piroxicam induced lithium toxicity, PubMed
  • Caffeine withdrawal increases lithium blood levels, PubMed
  • Lithium Toxicity, PubMed
  • Lithium prescribing Information, AccessFDA
  • Dextromethorphan-induced serotonin syndrome, PubMed

About the Pharmacist

Dr. Brian Staiger, PharmD

Dr. Brian has been practicing pharmacy for over 13 years and has wide-ranging experiences in many different areas of the profession. From retail, clinical, program development, and administrative responsibilities, he's your knowledgeable and go-to source for all your pharmacy and medication-related questions! Dr. Brian Staiger also has herbalist training and educational certificates in the field of medical ethnobotany. Feel free to send him an email at [email protected]! You can also connect with Dr. Brian Staiger on LinkedIn.

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