September 27 2022


Simultaneous use of barbiturates or primidone can induce enzymatically the elimination of caffeine and can antagonize the hypnotic effect of barbiturates or anticonvulsant.

Hydantoins also have an enzyme-inducing effect, enhancing the removal of caffeine.


Simultaneous administration of caffeine and ketoprofen reduced urinary volume. This effect appears to have no clinical significance.


Mexiletine significantly reduces the elimination of caffeine (up to 50%), and may increase the toxic effects of this substance. Can be applied here the additive effects of central stimulants, exacerbated by the reduction of caffeine metabolism. Avoid concomitant use.


Co-administration of caffeine with lithium may increase urinary excretion and clearance of this, with a possible decrease in the effect of lithium. Lithium levels should be monitored in the blood.

Although caffeine alone can result in large amounts of arrhythmias and hypertension, its association with MAO inhibitors, even in moderate amounts, can cause tachycardia and hypertension. Avoid concomitant use.


Coadministration of caffeine with narcotic analgesics can partially reduce respiratory depression induced by these.


The effects of adenosine may be offset in part by the caffeine, so that higher doses are required to balance adenosine decreased effect produced by caffeine. It is advisable to stop taking the latter containing beverages.


The combined use of these agents can produce inhibition of effects of both substances. This also includes those used locally to reduce intraocular pressure.


Some observations suggest that coadministration of clozapine with doses of 400-1000 mg/day of caffeine can increase by almost 20% the AUC of clozapine and reduce up to 14% removal of this substance. This seems to support the idea that in some patients the elevation of blood clozapine may be relevant.

Central nervous system stimulants     

Cocaine may diminish the antihypertensive effect of postganglionic blockers guanethidine and guanadrel. So, patients using cocaine should be monitored if received any of these antihypertensive medicines. Furthermore, these drugs can enhance sympathetic stimulation induced by cocaine, thus increasing the risk of hypertension and arrhythmias.


There have been reports of severe hypertensive reactions following the combined use of both substances. A study of healthy volunteers highlights a significant increase in concentration of caffeine after administration of 75 mg of phenylpropanolamine and 400 mg of caffeine, as well as a rise of blood pressure and adverse effects. Avoid coadministration.

Metabolic inhibitors of caffeine     

The antiH2 cimetidine may inhibit the hepatic metabolism of numerous substrates, interacting through CYP450. In the case of caffeine may cause a delay in the removal of this and subsequent increase of its plasma levels.

Similarly, the concomitant intake of caffeine and ciprofloxacin, enoxacin or norfloxacin can increase the plasma concentration of caffeine and delay its elimination.

Pipemidic acid and to a lesser degree the quinolones inhibit the demethylation of caffeine.

Other substances also reduce caffeine clearance and elevate their serum level including oral contraceptives, macrolide antibiotics (TAO, erythromycin) and disulfiram. In the latter case, patients in treatment for alcoholic addiction should be counseled to avoid drinking beverages or ingest other substances containing caffeine, which can complicate the core symptoms of alcohol withdrawal signs of nervous excitement by raising the rate of caffeine.

Calcium supplements     

The administration of calcium salts together with large amounts of caffeine can inhibit calcium absorption in the intestine.


As is known, the tobacco is an inducer of hepatic metabolism and therefore concurrent use with caffeine increases its metabolism and decreases the levels of this substance.


Caffeine removal competes with other similar substances, such as theophylline, so concurrent use reduces the rate of removal of both, increasing the risk sum of pharmacodynamic and toxic effects. Avoid concomitant use.

additional Information     

Caffeine during pregnancy

Date of update of this page: November 10, 2008.


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