Caffeine - a Central Nervous System Stimulant

Caffeine acts as a central nervous system stimulant by sensitizing the respiratory center in the brain to carbon dioxide and increasing the contraction of the diaphragmatic muscles. It is used to treat the following conditions:

  • For the treatment of idiopathic apnea of prematurity

  • It is used as an OTC drug for mental alertness and wakefulness in individuals experience fatigue

  • Uses of Caffeine (off label) in Adults include:

    • For seizure induction during electroconvulsive therapy.
    • Headache caused by a postdural hematoma 
    • For the purpose of reversing unfavourable effects caused by dipyridamole or regadenoson, such as angina and hypotension, during nuclear cardiac stress testing.  

Caffeine Dose in Adults


It is not recommended to use caffeine-citrate in place of caffeine-sodium-benzoate.

Off label use for treating Augmentation of seizure induction during ECT:

  • 500 - 1,000 mg intravenous caffeine and sodium benzoate.
  • A maximum of 2,000 mg of caffeine plus sodium benzoate may be taken at one time.

Off-label use for treating Postdural puncture headache:

  • Following a one-hour infusion of 1,000 mL of 0.9% saline with 500 mg of intravenous caffeine and sodium benzoate  (equal to 250 mg of caffeine base),  1,000 mL of 0.9% saline was then administered over a two-hour period.
  • If the symptoms continue after four hours, a second dose of caffeine may be administered.
  • 300 mg of caffeine base) taken orally all at once.

Off-label use during nuclear cardiac stress testing as a substitute medication for the treatment of adverse effects caused by regadenoson or dipyridamole, such as angina and hypotension:

  • Caffeine citrate:
    • 60 mg diluted in 25 mL of 5% Dextrose Water Intravenous over 3 - 5 minutes.

Use as a stimulant (OTC labeling):

  • 100 - 200 mg orally every 3 - 4 hours as needed

Caffeine Dose in Childrens


The terms caffeine-citrate and caffeine-sodium-benzoate formulation should not be used interchangeably.

Caffeine use as a stimulant (OTC labeling):

  • Caffeine:
    • Children older than 12 years and Adolescents:
      • 100 - 200 mg orally every 3 - 4 hours as needed

Pregnancy Risk Factor: C

  • The serum levels of the foetus and mother are equal after caffeine passes the placental barrier.
  • Caffeine intake is not linked to fetal harm. However, pregnant women should avoid caffeine.
  • Caffeine administration during pregnancy has been linked to spontaneous abortions and growth retardation.
  • When given higher doses of medication during pregnancy, symptoms such as irritability and jitteriness in the neonate have been reported.
  • According to ACOG, the current guidelines recommend that pregnant women reduce their caffeine intake to 200mg/day.

Caffeine use during breastfeeding:

  • Breastmilk contains caffeine and its metabolites.
  • The serum concentrations determine the concentration of breastmilk.
  • The iron content of breastmilk may be decreased by taking in caffeine.
  • Breastfeeding may be done in moderate amounts (less than 300 mg/day).

Caffeine Dose in Renal Disease:

Use with caution in patients with Renal disease. Adjustment in the dose has not been recommended.

Caffeine Dose in Liver Disease:

Use with caution in patients with liver disease. Adjustment in the dose has not been recommended. 

Common Side Effects Of Caffeine Include:

  • Cardiovascular:
    • Chest pain
    • Ventricular arrhythmia
    • Flushing
    • Supraventricular tachycardia
    • Sinus tachycardia
    • Palpitations
    • Vasodilatation
    • Angina pectoris
  • Central nervous system:
    • Psychosis
    • Delirium
    • Insomnia
    • Headache
    • Irritability
    • Dizziness
    • Hallucination
    • Restlessness
    • Agitation
  • Dermatologic:
    • Urticaria
  • Gastrointestinal:
    • Gastritis
    • Esophageal motility disorder
  • Genitourinary:
    • Diuresis
  • Neuromuscular & skeletal:
    • Fasciculations
  • Ophthalmic:
    • Miosis
    • Increased intraocular pressure

Contraindication to Caffeine Include:

  • Allergy reactions to caffeine or any other component of the formulation
  • Avoid using sodium benzoate in children.

Warnings and Precautions

  • Anxiety
    • The drug should not be used by patients suffering from anxiety, agitation, or shaking.
  • Cardiovascular disease
    • Patients with heart problems or those who are at a high risk for symptomatic arrhythmias shouldn't use it.
  • Gastrointestinal Disease:
    • Patients with a history of gastroesophageal reflux disease or peptic ulcer disease should not consume coffee.
  • Hepatic impairment
    • Patients with liver disease should be cautious.
  • Renal impairment
    • Patients with kidney disease should be cautious.
  • Seizure disorder:
    • Patients who have a history of seizure disorder or patients with epilepsy should be cautious about using it as it lowers the seizure threshold.

Caffeine: Drug Interaction

Risk Factor C (Monitor therapy)

Abiraterone Acetate

May elevate CYP1A2 substrates' serum concentration (High risk with Inhibitors).


Amifampridine may have a stronger neuroexcitatory and/or seizure-potentiating  impact when combined with substances with seizure threshold lowering potential.


Could make sympathomimetics' hypertensive effects stronger.  The tachycardic impact of sympathomimetics may be increased by atoMOXetine.


The absorption of bromperidol may be decreased by caffeine and products containing caffeine.


Agents With Seizure Threshold Lowering Potential may have an enhanced neuroexcitatory and/or  seizure-potentiating impact.

Cannabinoid-Containing Products

Perhaps makes sympathomimetics' tachycardic effect stronger. Cannabidiol is an exception.

Ciprofloxacin (Systemic)

May raise the level of caffeine in the blood.


CYP1A2 Inhibitors (Weak) may raise the level of CloZAPine in the serum.

CYP1A2 Inhibitors (Moderate)

Management: Separate drug interaction monographs go into further detail about the medications  indicated as exceptions to this book.


May slow down CYP1A2 substrate metabolism (High risk with Inhibitors).


May elevate CYP1A2 substrates' serum concentration (High risk with Inhibitors).


Caffeine and products containing caffeine may intensify Formoterol's negative or hazardous effects.  Formoterol's ability to cause hypokalemia may be enhanced by caffeine  and products containing caffeine.


Could make sympathomimetics more arrhythmogenic.  Guanethidine might make sympathomimetic drugs more hypertensive.


The negative/toxic effects of indacaterol may be increased by caffeine and products containing caffeine.  The hypokalemic impact of indacaterol may be enhanced by caffeine and products containing caffeine.


The serum content of lithium may be decreased by caffeine and products containing caffeine.


May raise the level of caffeine and products containing caffeine in the blood.

Obeticholic Acid

May elevate CYP1A2 substrates' serum concentration (High risk with Inhibitors).


Olodaterol's negative/toxic effects may be exacerbated by caffeine and products containing caffeine.  Olodaterol's ability to cause hypokalemia may be enhanced by caffeine and products containing caffeine.

Peginterferon Alfa-2b

May elevate CYP1A2 substrates' serum concentration (High risk with Inhibitors).

Pipemidic Acid

May raise the level of caffeine and products containing caffeine in the blood.


Sympathomimetics may intensify Solriamfetol's hypertensive effects.


Solriamfetol's ability to cause hypertension may be enhanced by CNS stimulants.


Could intensify the hazardous or harmful effects of other sympathomimetics.


Could make sympathomimetics' hypertensive effects stronger.  The tachycardic impact of sympathomimetics may be increased by tedizolid.


May lower the serum level of caffeine and products containing caffeine.

Tobacco (Smoked)

May lower the serum level of caffeine and products containing caffeine.

Risk Factor D (Consider therapy modification)


The therapeutic effects of adenosine may be diminished by caffeine and products containing caffeine.  Management: If the patient is taking caffeine, watch for adenosine's diminished action.  When feasible, stop drinking caffeine before adenosine is to be used for a scheduled diagnostic procedure.

Cocaine (Topical)

Could make sympathomimetics' hypertensive effects stronger. Management: Whenever possible, look at  alternatives  to using this combo. When used concurrently, keep a close eye out for noticeably elevated  blood pressure or  heart rate as well as any signs of myocardial ischemia.

CYP1A2 Inhibitors (Strong)

May slow down CYP1A2 substrate metabolism (High risk with Inhibitors).


The negative/toxic effects of iohexol may be amplified by substances with the potential to  lower seizure thresholds. More specifically, there may be a higher chance of seizures.  Treatment: Stop using medications 48 hours before using intrathecal iohexol that  could lower the seizure threshold. To restart using such agents, give the treatment at least 24 hours.  Prophylactic anticonvulsants may be used in nonelective surgeries.


The negative/toxic effect of Iomeprol may be increased by substances with the potential to  lower seizure thresholds. More specifically, there may be a higher chance of seizures.  Treatment: Stop using medications 48 hours before using intrathecal iomeprol if they  could lower the seizure threshold. To restart using such agents, give the treatment at least 24 hours.  Prophylactic anticonvulsants may be used in nonelective surgeries.


The negative/toxic effects of iopamidol may be increased by substances with the potential  to lower seizure thresholds. More specifically, there may be a higher chance of seizures.  Treatment: 48 hours before using intrathecal iopamidol, stop using any medications that  could lower the seizure threshold. To restart using such agents, give the treatment at least 24 hours.  Prophylactic anticonvulsants may be used in nonelective surgeries.


Could make sympathomimetics' hypertensive effects stronger.  Reduce the first doses of sympathomimetic drugs and closely monitor individuals on  linezolid for an augmented pressor response. There are currently no suggestions for  specific dose adjustments.


Regadenoson's vasodilatory effects may be diminished by caffeine and products containing caffeine.  Management: For at least 12 hours before to the administration of regadenoson, refrain from using  products that include caffeine or other methylxanthine, such as theophylline.


The concentration of TiZANidine in the serum may rise in response to CYP1A2 Inhibitors (Weak).  Management: Whenever you can, stay away from these pairings.  If combination use is necessary, commence tizanidine at an adult dose of 2 mg and increase  in 2 to 4 mg increments dependent on patient response.  Watch out for tizanidine side effects, such as increased effects.


May increase the serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Management: Whenever possible, look into alternatives to such combinations, especially if the  CYP1A2 substrate has a relatively limited therapeutic index.  Drugs marked as exclusions from this document are covered in separate monographs on drug interactions.

Risk Factor X (Avoid combination)


Could make CNS stimulants more stimulating.


Doxofylline's harmful or hazardous effects may be increased by caffeine and products containing caffeine.


May raise the level of caffeine and products containing caffeine in the blood.

Monitoring parameters:

Keep an eye on your blood pressure and heart rate.  Keep an eye out for seizures, agitation, and neuroexcitability.

How to Administer Caffeine?

  • It can be given without taking a meal.
  • It is possible to administer the injectable medication (caffeine citrate) orally.

Parenteral administration of caffeine:

  • Caffeine citrate:
    • During cardiac stress testing, it is utilised as a parenteral drug to reverse dipyridamole- or regadenoson-induced adverse effects.
    • It should be injected for 3 to 5 minutes after being diluted in 25 mL of 5% Dextrose Water.
  • Caffeine and sodium benzoate:
    • Use a 0.22-micron in-line filter before administering, and administer gently.
  • Postdural puncture headaches:
    • 1,000 mL of normal saline should be administered during a two-hour period after a one-hour infusion of a diluted solution.

Mechanism of action of Caffeine:

  • It inhibits the enzyme phosphodiesterase, which increases 3'5' cyclicAMP levels.
  • Also acts as a central nervous stimulant.
  • It stimulates the brain by increasing carbon dioxide sensitivity.
  • It stimulates the central inspiratory drive and also increases the contraction of diaphragmatic muscle.
  • It is used to prevent apnea because it inhibits adenosine.

It is not bound to plasma proteins in any significant way (17% for children, 36% for adults It is metabolized in the livervia CYP1A2 demethylation Half-life elimination for neonates is 72-96 hours, and for children is more than 9 months.

After oral intake, the time it takes to reach maximum serum concentration isIt can be taken in 30 minutes to 2 hours, and it is more common in pregnant women, smokers and people with liver disease. It is mostly excreted via urine. 

International Brands of Caffeine:

  • Cafcit; Keep Alert
  • No Doz Maximum Strength
  • Stay Awake Maximum Strength
  • Vivarin
  • Cafcit
  • Cafnea
  • Coffeinum Natrium Benzoicum
  • Kofex
  • NeoCaf
  • Peyona

Brands in Pakistan (Caffeine is used in combination in the follwoing formulations)

Syrup 5 Mg/5ml

Vikonon Forte Popular Chemical Works (Pvt) Ltd.

Syrup 25 mg/5ml

Mb-Forte Multinational Buisness Link
Mb-Tone Forte Multinational Buisness Link

Syrup 5 mg/15ml

Summervita Helicon Pharmaceutek Pakistan (Pvt) Ltd.

Syrup 1.25 mg/5ml

Tonum Pliva Pakistan (Pvt) Limited

Oral Soln 10 mg/ml

Vasoloid Zafa Pharmaceutical Laboratories (Pvt) Ltd.

Caffeine [Elixir 30 Mg/5ml]

Ferroglobin Specific Research Laboratories

10 Mg Tablets

Iodopyrin Ideal Pharmaceutical Industries
Trigesic Wilshire Laboratories (Pvt) Ltd.

15 Mg Tablets

Febricod C Xenon Pharmaceuticals (Pvt) Ltd.
Vigrol Forte Popular Chemical Works (Pvt) Ltd.

25 Mg Tablets

Amsidal English Pharmaceuticals Industries
Amtalidin English Pharmaceuticals Industries
Baridon Davis Pharmaceutical Laboratories
Optalidon Novartis Pharma (Pak) Ltd
Romtolido Regent Laboratories Ltd.

30 Mg Tablets

Actiron Cf Murfy Pharmaceuticals (Pvt) Ltd
Adalgin Adamjee Pharmaceuticals (Pvt) Ltd.
Apecirin Alfalah Pharma (Pvt) Ltd.
Ascamol Eros Pharmaceuticals
Ascamol Eros Pharmaceuticals
Aspirin Comp Nawabsons Laboratories (Pvt) Ltd.
Dancin Danas Pharmaceuticals (Pvt) Ltd
Donamol Plus Rakaposhi Pharmaceutical (Pvt) Ltd.
Empirin Comp Glaxosmithkline
Femidol Plus Pacific Pharmaceuticals Ltd.
Medigesic Forte Wilshire Laboratories (Pvt) Ltd.
Medinol Polyfine Chempharma (Pvt) Ltd.
Napadoc Atco Laboratories Limited
Nopain Schazoo Zaka
Orphagesic Medicaids Pakistan (Pvt) Ltd.
Pabfin Drug Pharm (Pvt) Ltd.
Panarin Pharmacare Laboratories (Pvt) Ltd.
Pangesic+C Safe Pharmaceutical (Pvt) Ltd.
Paracetamol Compound Unexo Labs (Pvt) Ltd.
Paxfin Star Laboratories (Pvt) Ltd.
Schazopyrin The Schazoo Laboratories Ltd.
Synadoc Syntex Pharmaceuticals
Zepyrine Xenon Pharmaceuticals (Pvt) Ltd.

50 Mg Tablets

Saridon Roche Pakistan Ltd.

60 Mg Tablets

Dolmi Genix Pharma (Pvt) Ltd
Excedrin-Xtra Aries Pharmaceuticals (Pvt) Ltd
Medigesic C Wilshire Laboratories (Pvt) Ltd.

65 Mg Tablets

Amadol Extra Harmann Pharmaceutical Laboratories (Pvt) Ltd.
Amole Plus Libra Pharmaceuticals (Pvt) Ltd
Aridol Aries Pharmaceuticals (Pvt) Ltd
Axadol Plus Medisure Laboratories Pakistan (Pvt.) Ltd.
C.C Don Extra Saydon Pharmaceutical Industries (Pvt) Ltd.
Cafipar Davis Pharmaceutical Laboratories
Calpol Plus Glaxosmithkline
Canidol Ferro Pharmaceutical Laboratories
Delmol Extra Delta Pharma (Pvt) Ltd.
Detamol Extra Webros Pharmaceuticals
Disol Alson Pharmaceuticals
Estadol Extra Hamaz Pharmaceutical (Pvt) Ltd.
Fanidol Danas Pharmaceuticals (Pvt) Ltd
Febrol Xtra Barrett Hodgson Pakistan (Pvt) Ltd.
Fedramol Plus Fedro Pharmaceutical
Fenmol Plus Polyfine Chempharma (Pvt) Ltd.
Fevamol Extra Swiss Pharmaceuticals (Pvt) Ltd.
Feveramin-D Shaheen Agencies
Nedol Extra Ambrosia Pharmaceuticals
Nopain Af Schazoo Zaka
Omnidol Olive Laboratories
Panadol Extra Glaxosmithkline
Panafin Extra Medipak Limited
Para+Plus Unexo Labs (Pvt) Ltd.
Para-Caffin Mediate Pharmaceuticals (Pvt) Ltd
Paracetamol Compound Euro Pharma International
Parad Extra Safina Pharma (Pvt) Ltd
Paragray Extra Gray`S Pharmaceuticals
Paraheim Plus Pakheim Internanational Pharma
Parari Xtra Lawari International
Paratol Extra Highnoon Laboratories Ltd.
Parol Plus Bloom Pharmaceuticals (Pvt) Ltd.
Pedrol Extra Stanley Pharmaceuticals (Pvt) Ltd.
Prymin Dee Healers Laboratories
Pyrol Extra Semos Pharmaceuticals (Pvt) Ltd.
Regodol Extra Regent Laboratories Ltd.
Residol Extra Star Laboratories (Pvt) Ltd.
Rgesic Extra Euro Pharma International
Synadoc Syntex Pharmaceuticals
Terinol Unipharma (Pvt) Ltd.
Tyladol Extra Bryon Pharmaceuticals (Pvt) Ltd.
Tylenol Extra Arsons Pharmaceuticals Industries (Pvt) Ltd
Tylol Extra Don Valley Pharmaceuticals (Pvt) Ltd.
Vidol-Extra Venus Pharma

70 Mg Tablets

Pregesic Cirin Pharmaceuticals (Pvt) Ltd.

100 Mg Tablets

Asmol Irza Pharma (Pvt) Ltd.
Cafergot Novartis Pharma (Pak) Ltd
Migril Glaxosmithkline
Tagril Tagma Pharma (Pvt) Ltd.

25 mg Capsules

Mb-Forte Multinational Buisness Lin


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