Caffeine Citrate 10mg/ml Inj. Sol. Ref.[4796] Active ingredients: Caffeine

Care should be taken to exclude other causes of apnoea before initiation of treatment.

It is advisable to monitor plasma levels of caffeine periodically. However, at the recommended doses, frequent (more than weekly) monitoring of plasma levels is not normally necessary unless there are concerns regarding lack of efficacy or possible toxicity. In premature neonates, caffeine has a prolonged half-life. If higher maintenance dosages are used, the clinician should recognise this potential for accumulation and monitor plasma caffeine levels (see also Section 5.2).

If there is inadequate clinical response to the first loading dose, a second dose may be given, but if there is continued inadequate response, the plasma levels should be confirmed before further doses are given, as the failure to respond could be an indication of another cause of apnoea. Plasma levels should not normally exceed 50micrograms/ml (optimally 10-30micrograms/ml).

There may be pre-existing caffeine in the blood of neonates

(a) whose mothers may have ingested large quantities of caffeine prior to delivery.

(b) who have previously been treated with theophylline, which is metabolised to caffeine.

There is evidence that caffeine causes tachyarrhythmias in susceptible individuals. In newborn babies this is usually a simple sinus tachycardia. If there have been any unusual rhythm disturbances on a CTG trace before the baby is born, caffeine should be administered with caution. Caffeine should be used with caution in infants suffering gastro-oesophageal reflux, as the drug may exacerbate this condition.

Caffeine may increase cardiac output and heart rate in therapeutic doses. Caffeine should be used with caution in infants with cardiac disease.

Caffeine causes a generalised increase in metabolism, which may result in higher energy and nutrition requirements during therapy.

The diuresis and electrolyte loss induced by caffeine may necessitate correction of fluid and electrolyte disturbances.

This medicinal product contains 3.04mg sodium per 1ml of the solution. To be taken into consideration by patients on a controlled sodium diet.

Opening the ampoules may introduce glass particles into this solution. It is recommended that the solution be filtered prior to use by means of a suitable filter device.

No clinically significant interactions between caffeine and other medications have been reported in premature infants. Nevertheless, certain clinical situations have a theoretical potential for interaction. If the child’s mother has been treated with phenytoin or phenobarbitone during pregnancy, the child might have enhanced hepatic enzyme induction and thus require higher doses of caffeine to compensate for increased caffeine metabolism. Plasma caffeine levels should be monitored during treatment in such situations, to ensure that adequate caffeine has been administered.

Interconversion between caffeine and other xanthines such as theophylline has been reported in premature neonates. Therefore the concurrent use of these drugs should be avoided. Baseline serum levels of caffeine should be measured in patients previously treated with theophylline.

Not applicable.

Not applicable.

Caffeine has been reported to cause a number of adverse effects in premature neonates. Effects described include 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 dose reduction and measurement of plasma levels. They are generally, although not exclusively, associated with serum caffeine concentrations ≥ 50micrograms/ml.

On the available evidence, caffeine does not appear to aggravate cerebral hypoxia or to exacerbate any resulting damage, although the possibility cannot be ruled out.

Caffeine treatment may increase gastro-oesophageal reflux, induce intestinal stasis and increase enteral secretion and gastric aspirations. Caffeine treatment may also reduce splanchnic blood flow. These factors may increase the risk of necrotising enterocolitis, although the prevention of systemic hypoxia may offset this theoretical increased risk. No significantly increased incidence of necrotising enterocolitis has been reported in clinical trials.

Caffeine may suppress erythropoietin synthesis and hence reduce haemoglobin concentration with prolonged treatment.

Other adverse effects associated with caffeine are effects on blood glucose levels such as hypoglycemia and hyperglycemia, and renal effects including increased urine flow rate, increased sodium and calcium excretion.

Available evidence does not indicate any adverse long-term effects of neonatal caffeine therapy on neurodevelopmental outcome, failure to thrive, or on the cardiovascular, gastrointestinal or endocrine systems. However, the possibility of long-term adverse effects cannot be ruled out.

A withdrawal syndrome after discontinuation of caffeine treatment has not been reported in this age group.

This medical product must not be mixed with other medicinal products except those mentioned in section 6.6.