Esketamine
Severe
Database
Drug interaction classified as: synergy
Source: DDInter
Drug reference
Caffeine
CNS Stimulant · Stimulant
Also known as caffeine hydrate
CNS StimulantStimulant
CDSCO approvedSchedule H
EXCRETION
—
not curated
INTERACTIONS
2 major
SEVERE in our sources
PREGNANCY
—
not curated
Top interactionssee all 5 →
- EsketamineSevereDatabaseDDInter
- TizanidineSevereDatabaseDDInter
Mechanism
Caffeine primarily exerts its CNS stimulant effects by competitively inhibiting cyclic nucleotide phosphodiesterases (PDEs). This inhibition prevents the degradation of cyclic adenosine monophosphate (cAMP) to 5′-AMP, leading to increased intracellular cAMP levels. Elevated cAMP levels subsequently modulate downstream signaling pathways, resulting in enhanced neuronal activity and the characteristic CNS stimulant effects.
Indications
Adjuvant in migraine treatment (as part of combination therapy)
Dosing
- Adult
- Dose changes Changes in dose statements that appear in the print edition of BNF 80 (September 2020—March 2021): . Benzoin tincture, compound p. 313 [updated child age range]. . Betamethasone with clioquinol p. 1314 [updated child age range]. Co-fluampicil p. 582 [update to dosing information]. Ergotamine tartrate with caffeine hydrate and cyclizine hydrochloride p. 500 [addition of max. courses...
Pharmacokinetics
Half-life
approximately 5 h
Metabolism
largely by CYP1A2
Contraindications
- Excessive consumption in hypertension
- In irritable bowel syndrome (reduce intake)
Side effects
Common
Fatigue (withdrawal)Sedation (withdrawal)Headaches (withdrawal with higher doses)Nausea (withdrawal with higher doses)
Drug interactions
Tizanidine
Severe
Database
Drug interaction classified as: metabolism
Source: DDInter
Ciprofloxacin
Moderate
Database
Increased plasma concentrations of caffeine, leading to exaggerated caffeine effects (nervousness, insomnia, palpitations).
Advise patients to reduce or avoid caffeine intake during ciprofloxacin therapy.
Source: DDInter
Lithium Carbonate
Moderate
Database
Decreased serum lithium levels, potentially leading to loss of therapeutic effect. Withdrawal from caffeine can lead to increased lithium levels and toxicity.
Advise patients to maintain a consistent caffeine intake. Monitor serum lithium levels if caffeine intake changes significantly (e.g., starting or stopping caffeine consumption). Adjust lithium dose as needed.
Source: DDInter
Terbinafine
Moderate
Database
Increased caffeine levels, leading to enhanced stimulant effects (nervousness, insomnia, palpitations)
Advise patients to reduce caffeine intake. Monitor for symptoms of caffeine toxicity.
Source: DDInter
7 additional low-confidence interactions hidden — those rows lack a documented mechanism or management plan in our sources.
Related guidelines
Other CNS Stimulant drugs
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Sources: KD Tripathi 7e, Goodman & Gilman 14e, BNF·Verified: 2026-05-13 · House clinical team