dministered by intramuscular, subcutaneous, intrathecal or intraperitoneal injection
Duration of treatment
The optimal duration of treatment has not been established. In a recent large multicentre study on premature newborn infants a median treatment period of 37 days was reported.
In clinical practice, treatment is usually continued until the infant has reached a post-menstrual age of 37 weeks, by which time apnoea of prematurity usually resolves spontaneously. This limit may however be revised according to clinical judgment in individual cases depending on the response to treatment, the continuing presence of apnoeic episodes despite treatment, or other clinical considerations. It is recommended that caffeine citrate administration should be stopped when the patient has 5-7 days without a significant apnoeic attack.
If the patient has recurrent apnoea, caffeine citrate administration can be restarted with either a maintenance dose or a half loading dose, depending upon the time interval from stopping caffeine citrate to recurrence of apnoea.
Because of the slow elimination of caffeine in this patient population, there is no requirement for dose tapering on cessation of treatment.
As there is a risk for recurrence of apnoeas after cessation of caffeine citrate treatment monitoring of the patient should be continued for approximately one week.
Patient with impaired hepatic or renal function
The safety of caffeine citrate in patients with renal insufficiency has not been established. In the presence of renal impairment, there is increased potential for accumulation. A reduced daily maintenance dose of caffeine citrate is required and the dose should be guided by plasma caffeine measurements.
In very premature infants, clearance of caffeine does not depend on hepatic function. Hepatic caffeine metabolism develops progressively in the weeks following birth and for the older infants, hepatic disease may indicate a need for monitoring caffeine plasma levels and may require dose adjustments (see sections 4.4 and 5.2).
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
4.4 Special warnings and precautions for use
Apnoea of prematurity is a diagnosis of exclusion. Other causes of apnoea (e.g., central nervous system disorders, primary lung disease, anaemia, sepsis, metabolic disturbances, cardiovascular abnormalities, or obstructive apnoea) should be ruled out or properly treated prior to initiation of treatment with caffeine citrate. Failure to respond to caffeine treatment (confirmed if necessary by measurement of plasma levels) could be an indication of another cause of apnoea.
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, since caffeine readily crosses the placenta into the foetal circulation (see section 4.2 and 5.2).
Breast-feeding mothers of neonates treated with caffeine citrate should not ingest caffeine-containing foods and beverages or medicinal products containing caffeine (see section 4.6), since caffeine is excreted into breast milk (see section 5.2).
In newborns previously treated with theophylline, baseline plasma caffeine concentrations should be measured prior to initiation of treatment with caffeine citrate because preterm infants metabolise theophylline to caffeine.
Caffeine |
