Cold Medications Safe With Lithium
In our latest question and answer, the pharmacist discusses safe cold medications, and which to avoid, with lithium.

Question
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?

Answered by Dr. Brian Staiger, PharmD
Medical Content Reviewed By HelloPharmacist
Staff
Last updated May 20, 2025
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."
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
NSAIDs
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.
Caffeine
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
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
Tylenol (acetaminophen) is considered a safe analgesic to take with lithium. There are no known drug interactions.
Mucinex
Mucinex (guaifenesin) is a commonly used expectorant that has few drug interactions. It is considered safe to take with lithium.
Sudafed
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.
References
- 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
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Dr. Brian Staiger, PharmD
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