Caffeine


Generic Medicine Info
Indications and Dosage
Intravenous
Short-term treatment of neonatal apnoea of prematurity
Child: Neonates As caffeine citrate: Loading dose: 20 mg/kg (10 mg/kg caffeine) via infusion over 30 minutes. If there is no adequate response within 4 hours, a 2nd loading dose may be given. If there is continued inadequate response, measure caffeine blood levels before giving further doses. Maintenance: 5-10 mg/kg (2.5-5 mg/kg caffeine) daily via infusion over 10 minutes, starting 24 hours after the loading dose(s).

Oral
Short-term treatment of neonatal apnoea of prematurity
Child: Neonates As caffeine citrate oral solution: Loading dose: 20 mg/kg (10 mg/kg caffeine). If there is no adequate response within 4 hours, a 2nd loading dose may be given. If there is continued inadequate response, measure caffeine blood levels before giving further doses. Maintenance: 5-10 mg/kg (2.5-5 mg/kg caffeine) daily, starting 24 hours after the loading dose(s). Dosage adjustments and further monitoring may be required according to clinical judgement in at-risk situations (refer to detailed product guideline).

Oral
Mild stimulant of the central nervous system
Adult: As tab: Usual dose: 50-100 mg, or up to 200 mg. Doses must not be taken more often than 3 or 4 hourly. Dosage recommendations may vary among countries and individual products (refer to detailed product guideline).
Child: As tab: Dosage recommendations may vary among countries and individual products (refer to detailed product guideline).
Renal Impairment
Short-term treatment of neonatal apnoea of prematurity:
Reduced maintenance daily dose may be necessary and must be guided by blood caffeine measurements.
Hepatic Impairment
Short-term treatment of neonatal apnoea of prematurity:
Dose adjustments and monitoring of plasma levels may be required.
Administration
May be taken with or without food.
Contraindications
Symptomatic or history of cardiac arrhythmia, anxiety disorders. Concomitant use with other xanthines (e.g. theophylline).
Special Precautions
Patient with existing or history of seizure disorders, other known CV diseases, history of peptic ulcer and/or GERD, hypertension, agitation, tremor. Patient recovering from chronic alcoholism and is taking disulfiram. Caffeine-naive and -sensitive individual. Renal and hepatic impairment. Neonates and children. Pregnancy and lactation.
Adverse Reactions
Significant: Increased left ventricular output, and stroke volume, tachycardia, hyper- or hypoglycaemia, diuresis, electrolyte loss, withdrawal symptoms (e.g. tiredness, decreased alertness), increased metabolism.
Cardiac disorders: Arrhythmia.
Gastrointestinal disorders: Gastrointestinal disturbances.
Nervous system disorders: Convulsion, tremor, headache.
Psychiatric disorders: Insomnia, nervousness, irritability, anxiety.
Respiratory, thoracic and mediastinal disorders: Elevated respiration.
Potentially Fatal: Necrotising enterocolitis.
IM/IV/Parenteral/PO: C
Monitoring Parameters
When used for apnoea of prematurity: Rule out or properly treat other causes of apnoea (e.g. CNS disorders, primary lung disease, anaemia, sepsis, metabolic disturbances, CV abnormalities, obstructive apnoea) before initiating treatment; monitor caffeine plasma concentrations periodically during treatment (in case of incomplete clinical response or signs of toxicity); heart rate, number and severity of apnoea spells (as necessary); serum glucose periodically (in infants receiving caffeine citrate). Obtain baseline caffeine plasma concentrations before initiating treatment in neonates born to mothers who consumed large quantities of caffeine before delivery, or in neonates previously treated with theophylline. Monitor for development of necrotising enterocolitis.
Overdosage
Symptoms: Seizure, jitteriness, tachypnoea, tachycardia, opisthotonos, rigidity, tonic-clonic movements, hypokalaemia, fine tremor of extremities, gastric irritation, restlessness, gastrointestinal haemorrhage, involuntary jaw and lip movements, increased WBC count, compromised circulation, vomiting, fever, agitation, hypertonia, gastric residues, hyperexcitability, distended abdomen, metabolic acidosis, hyperglycaemia, increased urea levels, pallor, dilated pupils, insomnia, headache, rapid speech, diuresis, tinnitus, and elevated respiration. Management: Supportive and symptomatic treatment. Monitor blood levels of caffeine and electrolyte (e.g. plasma K). Correct hypokalaemia and hyperglycaemia. Consider exchange transfusion for severe cases. Administer IV anticonvulsants (e.g. diazepam, phenobarbital) to treat convulsion. May administer activated charcoal (adult: 50 g; children: 10-15 g) or perform gastric lavage (in adults) within 1 hour of ingestion; correct electrolyte imbalances if needed. Monitor pulse, cardiac rhythm, and blood pressure. Administer amiodarone or disopyramide for ventricular arrhythmias occurring in patient having convulsions. May give β-blocker for persistent hypertension.
Drug Interactions
Decreased elimination or clearance with cimetidine, ketoconazole, pipemidic acid or methoxsalen. Increased elimination or clearance with phenobarbital, phenytoin or disulfiram. May decrease the vasodilating effect of adenosine and dipyridamole. May enhance the tachycardic effect of phenylpropanolamine. May antagonise the effect of tranquilisers, sedatives and β-blockers (e.g. atenolol, metoprolol, propranolol). Inhibits the metabolism of clozapine. Significant CV effects. with ephedrine. Concomitant use with lithium carbonate may result in small to moderate increase in serum lithium levels. May increase stimulant effects with MAOIs.
Potentially Fatal: Interconversion between caffeine and other xanthines (e.g. theophylline) may occur in preterm neonates.
Food Interaction
May increase caffeine levels when given concomitantly with other caffeine-containing foods or beverages which may cause nervousness, irritability, sleeplessness or rapid heartbeat.
Action
Description: Caffeine is a methylxanthine that inhibits the phosphodiesterase enzyme and has antagonistic activity on central adenosine receptors. It is a CNS stimulant, especially in the higher centres, and can result in a wakefulness condition and enhanced mental activity. Although its exact mechanism in apnoea of prematurity is unknown, it is believed to have several effects including stimulation of the respiratory centre, reducing threshold to hypercapnia and diaphragmatic fatigue; increasing minute ventilation, skeletal muscle tone, metabolic rate and oxygen consumption.
Pharmacokinetics:
Absorption: Rapidly and completely absorbed from the gastrointestinal tract. Time to peak plasma concentration: 30 minutes to 2 hours (neonates).
Distribution: Widely distributed throughout the body; readily passes into the CNS and saliva (caffeine citrate). Crosses the placenta; enters breast milk (small amounts). Volume of distribution: 0.8-0.9 L/kg (neonates); 0.6 L/kg (adults). Plasma protein binding: Approx 36%.
Metabolism: Almost completely metabolised in the liver via oxidation, demethylation, and acetylation by CYP1A2.
Excretion: Via urine (adults: approx 1% as unchanged drug; neonates: 86% as unchanged drug). Elimination half-life: Approx 3-7 hours (adults); approx 3-4 days (neonates).
Chemical Structure

Chemical Structure Image
Caffeine

Source: National Center for Biotechnology Information. PubChem Database. Caffeine, CID=2519, https://pubchem.ncbi.nlm.nih.gov/compound/Caffeine (accessed on Jan. 22, 2020)

Storage
Store between 20-25°C.
MIMS Class
Other CNS Drugs & Agents for ADHD / Other Drugs Acting on the Respiratory System
ATC Classification
N06BC01 - caffeine ; Belongs to the class of xanthine derivative agents. Used as CNS stimulant.
References
Anon. Caffeine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 30/04/2021.

Buckingham R (ed). Caffeine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 30/04/2021.

Cafcit Injection (Hikma Pharmaceuticals USA Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 30/04/2021.

Caffeine Citrate 10 mg/mL Oral Solution (Macarthys Laboratories Limited T/A Martindale Pharma). MHRA. https://products.mhra.gov.uk. Accessed 30/04/2021.

Caffeine Citrate 10 mg/mL Solution for Injection (Macarthys Laboratories Limited T/A Martindale Pharma). MHRA. https://products.mhra.gov.uk. Accessed 30/04/2021.

Caffeine Citrate Solution (Micro Labs Limited). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 04/05/2021.

Caffeine Tablet (CVS Pharmacy). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 30/04/2021.

Pro Plus Tablet (GR Lane Health Products Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 30/04/2021.

Disclaimer: This information is independently developed by MIMS based on Caffeine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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