s on the cardio-respiratory and central nervous system. If concurrent use is indicated, cardiac rhythm and blood pressure must be carefully monitored.
4.6 Pregnancy and lactation
Caffeine in animal studies, at high doses, was shown to be embryotoxic and teratogenic. These effects are not relevant with regard to short term administration in the preterm infant population (see section 5.3).
Caffeine is excreted into breast milk and readily crosses the placenta into the foetal circulation (see section 5.2).
Breast-feeding mothers of neonates treated with caffeine citrate should not ingest caffeine-containing foods, beverages or medicinal products containing caffeine.
In neonates born to mothers who consumed large quantities of caffeine prior to delivery, baseline plasma caffeine concentrations should be measured prior to initiation of treatment with caffeine citrate (see section 4.4).
4.7 Effects on ability to drive and use machines
Not relevant.
4.8 Undesirable effects
The known pharmacology and toxicology of caffeine and other methylxanthines predict the likely adverse reactions to caffeine citrate. Effects described include central nervous system (CNS) stimulation such as irritability, restlessness and jitteriness, and cardiac effects such as tachycardia, hypertension and increased stroke volume. These effects are dose related and may necessitate measurement of plasma levels and dose reduction.
The adverse reactions described in the short- and long-term published literature that can be associated with caffeine citrate are listed below by System Organ Class and Preferred Term (MedDRA).
Frequency is defined as: very common (≥ 1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).
|
System Organ Class
|
Adverse Reaction
|
Frequency
|
|
Infections and infestations
|
Sepsis
|
Not known
|
|
Immune system disorders
|
Hypersensitivity reaction
|
Rare
|
|
Metabolism and nutrition disorders
|
Hypoglycaemia, hyperglycaemia, failure to thrive, feeding intolerance
|
Not known
|
|
Nervous system disorders
|
Irritability, jitteriness, restlessness, brain injury*, convulsion*
|
Not known
|
|
Ear and labyrinth disorders
|
Deafness*
|
Not known
|
|
Cardiac disorders
|
Tachycardia, also associated with increased left ventricular output and increased stroke volume
|
Not known
|
|
Gastrointestinal disorders
|
Regurgitation, increased gastric aspirate, necrotising enterocolitis**
|
Not known
|
|
General disorders and administration site conditions
|
Infusion site phlebitis, infusion site inflammation
|
Common
|
|
