Caffeine

Psychostimulant, xanthine derivative

ATC code: N06BC01

Brand names: NoDoz, Vivarin

Updated 24 Sep 2026 · Methodology

Indications

Fatigue and low energy (supplement marketing)

Adjunct

Caffeine tablets – Durvitan in Spain – are sold as a remedy for tiredness, and the AEMPS ficha técnica frames the indication exactly so: symptomatic and occasional relief of transient states of asthenia. The word «occasional» carries the weight. Caffeine removes the feeling of sleepiness by blocking adenosine receptors, but it does not treat sleep debt and does not cancel the need for sleep: once the effect ends, tiredness returns together with the accumulated adenosine. In its 2015 safety assessment gives the reference points for adults: single doses up to 200 mg and up to 400 mg a day from all sources do not raise concerns in healthy adults, while in pregnancy the limit is lower, 200 mg a day. The ficha técnica warns about accumulation: coffee, tea, energy drinks and a tablet add up, and the signs of overdose are anxiety, tremor, palpitations and insomnia.

Sources

ICD-10: R53 · ICD-11: MG22

Mild to moderate pain in adults

Adjunct

Caffeine does not relieve pain by itself but strengthens an analgesic – that is what the Spanish combinations Cafiaspirina and Actron Compuesto rest on. The Cochrane review by Derry and colleagues (2014) pooled 20 studies in 7238 participants: adding 100 mg of caffeine or more to paracetamol or ibuprofen increased the share of patients with good pain relief by roughly 5 to 10 percent compared with the analgesic alone. The gain is small but real, and for some people it turns «almost helped» into «helped». Two caveats. First, caffeine from a tablet adds to coffee and energy drinks, and the daily limit from the 2015 assessment – 400 mg for adults, 200 mg in pregnancy – is easy to exceed without noticing. Second, combination analgesics taken often produce medication overuse headache.

Sources

ICD-10: R52 · ICD-11: MG31

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Weight loss

Not recommended

Caffeine is the base of almost every «fat burner»: the promises are a faster metabolism, fat oxidation and endurance at training. The European regulator has tested those claims. In 2011 assessed health claims for caffeine and judged the link with increased fat oxidation unproven. A short-term rise in energy expenditure after a caffeine dose is indeed described, but it does not affect weight: it cannot create a calorie deficit, and tolerance to the stimulant effect develops. The AEMPS ficha técnica knows one indication for caffeine – occasional asthenia – and says nothing about weight loss. The price of the attempt shows up in the contraindications: severe cardiovascular disease, uncontrolled hypertension, anxiety states, epilepsy, peptic ulcer. If a caffeine «fat burner» was offered for weight loss, consider seeking a second opinion.

Sources

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

Caffeine blocks adenosine receptors of the A1, A2A and A2B subtypes. Adenosine builds up in the brain across waking hours and, binding to those receptors, triggers sleepiness; caffeine takes their place and the fatigue signal does not get through. A second effect runs through the A1 receptors – a mild excitatory action on the nervous system. The AEMPS ficha técnica adds practical detail: caffeine is metabolized in the liver, so the dose is adjusted in hepatic impairment, and in people with diabetes the drug can raise blood glucose. The last dose is not taken within 6 hours of bedtime, otherwise insomnia is guaranteed. For adults the ficha allows 300 mg per intake and no more than 1000 mg a day; the product is not intended for children under 12.

Safety

Contraindications

Hypersensitivity to caffeine
Severe cardiovascular disease
Uncontrolled arterial hypertension
Insomnia and anxiety states
Psychiatric disorders with nervous excitation, and epilepsy
Peptic ulcer of the stomach and duodenum
Severe hepatic impairment
Children under 12 years

Serious adverse effects

Cardiac arrhythmias
Seizures at high doses and in people with epilepsy
Anxiety and neurotic states at high doses
Withdrawal syndrome on abrupt stopping: headache, irritability, drowsiness

Common adverse effects

Insomnia, agitation, restlessness
Nausea, vomiting, stomach pain, diarrhea
Headache
Palpitations, tachycardia, extrasystoles
Tinnitus
Frequent urination

Pregnancy: can you take Caffeine?

The safety of caffeine in pregnancy has not been established. High doses are linked with a higher risk of preterm birth and low birth weight, so the ficha técnica asks not to exceed 300 mg a day, while the 2015 EFSA assessment sets 200 mg a day from all sources as the limit in pregnancy. Caffeine crosses the placenta and reaches fetal tissue concentrations close to those in the mother.

Breastfeeding: can you take Caffeine?

Caffeine passes into breast milk. Newborns clear it slowly, and with high maternal intake the infant becomes restless and sleeps worse. A moderate amount is usually tolerated, while high doses are not recommended while breastfeeding.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Label mentions31 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

MajorDisulfiram
«El disulfiram inhibe el metabolismo de la cafeína. Por lo tanto, se debe advertir a los pacientes alcohólicos que deben evitar la utilización de cafeína para evitar la aparición de excitación…»
AEMPS, section 4.5 · Open on CIMA
Ciprofloxacin
«El uso simultáneo con antiinfecciosos de tipo quinolonas (por ejemplo: ácido oxolínico, ciprofloxacino, etc.) puede retrasar la eliminación de la cafeína y de su metabolito paraxantina.»
AEMPS, section 4.5 · Open on CIMA
Erythromycin
«La eritromicina puede disminuir el aclaramiento de la cafeína.»
AEMPS, section 4.5 · Open on CIMA
Lithium
«El uso simultáneo con litio aumenta la excreción urinaria de éste, reduciendo posiblemente su efecto terapéutico.»
AEMPS, section 4.5 · Open on CIMA
Phenytoin
«El tratamiento concomitante con el antiepiléptico fenitoína aumenta la eliminación de cafeína, pudiendo disminuir su efecto por lo que no evitaría la somnolencia producida por dimenhidrato.»
AEMPS, section 4.5 · Open on CIMA
Selegiline
«El uso simultáneo con inhibidores de la monoamino-oxidasa ( IMAO ), incluyendo furazolidona , linezolida , procarbazina y selegilina, puede producir hipertensión, taquicardia y un aumento ligero de…»
AEMPS, section 4.5 · Open on CIMA
Theophylline
«La cafeína reduce la excreción de teofilina e incrementa el potencial de dependencia de las sustancias tipo efedrina.»
AEMPS, section 4.5 · Open on CIMA

From other drugs’ labels

ModerateCiprofloxacin
«DRUG INTERACTIONS: Caffeine/Xanthine Derivatives Use with caution Reduced clearance resulting in elevated levels and prolongation of serum half-life Ciprofloxacin inhibits the formation of…»
FDA, section 7 · Open on DailyMed
ModerateClozapine
«Precauciones que incluyen ajuste de dosis: La administración concomitante de sustancias conocidas como inhibidores de la actividad de algunos de los isoenzimas del citocromo P450 puede aumentar los…»
AEMPS, section 4.5 · Open on CIMA
ModerateClozapine
«Potential for Other Drugs to Affect Clozapine: Moderate or weak CYP1A2 inhibitors include oral contraceptives and caffeine. Monitor patients closely when clozapine is coadministered with these…»
FDA, section 7 · Open on DailyMed
ModerateLithium
«Interacciones que disminuyen los niveles de litio: acetazolamida, urea, xantinas (p.e. cafeína, teofilina), agentes alcalinizantes tales como inhibidores de la anhidrasa carbónica o productos con…»
AEMPS, section 4.5 · Open on CIMA
ModerateMethotrexate
«Bebidas que contengan cafeína o teofilina: Debe evitarse el consumo excesivo de bebidas que contengan cafeína o teofilina (café, refrescos que contienen cafeína, té negro) durante el tratamiento con…»
AEMPS, section 4.5 · Open on CIMA
ModeratePhenelzine
«CONTRAINDICATIONS: The potentiation of sympathomimetic substances and related compounds by MAO inhibitors may result in hypertensive crises (see WARNINGS ). Therefore, patients being treated with…»
FDA, section 4 · Open on DailyMed
ModerateTheophylline
«Otras formas de interacción: La teofilina actúa de forma sinérgica con otras xantinas (como cafeína y sustancias similares). Por ello, debe evitarse la ingestión en cantidades altas de bebidas con…»
AEMPS, section 4.5 · Open on CIMA
ModerateTranylcypromine
«Tyramine-Containing Foods and Beverages: Beverages All varieties of tap beer and beers that have not been pasteurized so as to allow for ongoing fermentation and excessive amounts of caffeine…»
FDA, section 7 · Open on DailyMed
Ciprofloxacin
«Otros derivados xantínicos: Con la administración concomitante de ciprofloxacino y cafeína o pentoxifilina (oxipentifilina) se ha notificado un aumento de las concentraciones séricas de los derivados…»
AEMPS, section 4.5 · Open on CIMA
Diazepam
«Interacción farmacodinámica fármaco-fármaco: Las xantinas teofilina y cafeína se oponen a los efectos sedantes y posiblemente a los efectos ansiolíticos del diazepam parcialmente a través del bloqueo…»
AEMPS, section 4.5 · Open on CIMA
Duloxetine
«Drugs Metabolized by CYP1A2: In vitro drug interaction studies demonstrate that duloxetine does not induce CYP1A2 activity. Therefore, an increase in the metabolism of CYP1A2 substrates (e.g…»
FDA, section 7 · Open on DailyMed
Eletriptan
«En ensayos clínicos con cafeína/ergotamina oral administradas 1 y 2 horas después de eletriptán, se observaron pequeños, aunque aditivos, incrementos en la presión arterial, que son predecibles…»
AEMPS, section 4.5 · Open on CIMA
Eltrombopag
«Sustratos del citocromo P450: La administración de 75 mg de eltrombopag una vez al día, durante 7 días, a 24 varones sanos, no inhibió o indujo el metabolismo de los sustratos de investigación para…»
AEMPS, section 4.5 · Open on CIMA
Fluvoxamine
«Casos de incremento de efectos adversos: Es probable que los niveles plasmáticos de cafeína aumenten con la administración concomitante de fluvoxamina. Así pues, los pacientes que tomen grandes…»
AEMPS, section 4.5 · Open on CIMA
Nicotine
«La concentración plasmática de otros productos metabolizados en parte por CYP1A2, por ejemplo; cafeína, imipramina, olanzapina, clomipramina y fluvoxamina pueden aumentar cuando se deja de fumar.»
AEMPS, section 4.5 · Open on CIMA
Pantoprazole
«Otros estudios de interacciones: Los resultados de estudios sobre un registro de interacciones demuestran que pantoprazol no afecta el metabolismo de sustancias activas metabolizadas mediante las…»
AEMPS, section 4.5 · Open on CIMA
Posaconazole
«Absence of Clinically Important Interaction with Posaconazole: Additional clinical studies demonstrated that no clinically important effects on zidovudine, lamivudine, indinavir, or caffeine were…»
FDA, section 7 · Open on DailyMed
Quinidine
«Non-Interactions of Quinidine With Other Drugs: Conversely, the pharmacokinetics of quinidine are not significantly affected by caffeine, ciprofloxacin, digoxin, diltiazem, felodipine, omeprazole…»
FDA, section 7 · Open on DailyMed
Terbinafine
«DRUG INTERACTIONS: Terbinafine is an inhibitor of CYP450 2D6 isozyme and has an effect on metabolism of desipramine. Drug interactions have also been noted with cimetidine, fluconazole, cyclosporine…»
FDA, section 7 · Open on DailyMed
Theophylline
«Drug Interactions:: caffeine, dietary ingestion nifedipine»
FDA, section 7 · Open on DailyMed
Tolterodine
«Other Drugs Metabolized by Cytochrome P450 Isoenzymes: In vivo drug-interaction data show that tolterodine immediate release does not result in clinically relevant inhibition of CYP1A2, 2D6, 2C9…»
FDA, section 7 · Open on DailyMed
Venlafaxine
«Drug Interactions: Venlafaxine did not inhibit CYP1A2 in vitro . This finding was confirmed in vivo by a clinical drug interaction study in which venlafaxine did not inhibit the metabolism of…»
FDA, section 7 · Open on DailyMed
Vortioxetine
«Sustratos del citocromo P450: Tras la administración de dosis múltiples de vortioxetina, no se observó un efecto inhibidor en sujetos sanos sobre las isoenzimas del citocromo P450 CYP2C19 (omeprazol…»
AEMPS, section 4.5 · Open on CIMA
Warfarin
«CYP450 Interactions: CYP1A2 acyclovir, allopurinol, caffeine, cimetidine, ciprofloxacin, disulfiram, enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, norfloxacin, oral contraceptives…»
FDA, section 7 · Open on DailyMed

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Frequently asked

What is Caffeine used for?

Caffeine is evaluated for the following indications with varying evidence strength: Fatigue and low energy (supplement marketing) (evidence tier C), Mild to moderate pain in adults (evidence tier C), Weight loss (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Caffeine?

Common side effects of Caffeine (≥ 1 in 100): Insomnia, agitation, restlessness, Nausea, vomiting, stomach pain, diarrhea, Headache, Palpitations, tachycardia, extrasystoles, Tinnitus, Frequent urination. See the Safety section for uncommon and serious reactions.

Is Caffeine safe during pregnancy?

Is Caffeine compatible with breastfeeding?

Who should not take Caffeine?

Caffeine is contraindicated in: Hypersensitivity to caffeine; Severe cardiovascular disease; Uncontrolled arterial hypertension; Insomnia and anxiety states; Psychiatric disorders with nervous excitation, and epilepsy. Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMA

Other drugs in this group

Choline bitartrate, Citalopram, Citicoline, Cortexin (bovine brain cortex polypeptides), Fluoxetine, Memantine, Phosphatidylserine, Trazodone