General Information

Cafcit Injection (caffeine citrate) is a central nervous system stimulant.

Cafcit Injection is specifically indicated for the treatment of apnea of prematurity.

Prior to initiation of Cafcit, baseline serum levels of caffeine should be measured in infants previously treated with theophylline, since preterm infants metabolize theophylline to caffeine. Likewise, baseline serum levels of caffeine should be measured in infants born to mothers who consumed caffeine prior to delivery, since caffeine readily crosses the placenta.

The recommended loading dose and maintenance doses of Cafcit follow.

Dose of Cafcit (caffeine citrate) Volume

Dose of Cafcit (caffeine citrate) mg/kg

Route

Frequency

Loading Dose

1 mL/kg

20 mg/kg

Intravenous (over 30 minutes)

One time

Maintenance Dose

0.25 mL/kg

5 mg/kg

Intravenous (over 10 minutes) or Orally

Every 24 hours

Mechanism of Action

Caffeine is structurally related to other methylxanthines, theophylline, and theobromine. It is a bronchial smooth muscle relaxant, a CNS stimulant, a cardiac muscle stimulant, and a diuretic.

Although the mechanism of action of caffeine in apnea of prematurity is not known, several mechanisms have been hypothesized. These include: (1) stimulation of the respiratory center, (2) increased minute ventilation, (3) decreased threshold to hypercapnia, (4) increased response to hypercapnia, (5) increased skeletal muscle tone, (6) decreased diaphragmatic fatigue, (7) increased metabolic rate, and (8) increased oxygen consumption.

Most of these effects have been attributed to antagonism of adenosine receptors, both A1 and A2 subtypes, by caffeine, which has been demonstrated in receptor binding assays and observed at concentrations approximating those achieved therapeutically.

Side Effects

Adverse effects associated with the use of Cafcit Injection may include, but are not limited to, the following:

Feeding Intolerance

Sepsis

Necrotizing Enterocolitis

Rash

central nervous system stimulation

cardiovascular effects

gastrointestinal effects

alterations in serum glucose

renal effects

Clinical Trial Results

One multicenter, randomized, double-blind trial compared Cafcit Injection to placebo in eighty-five (85) preterm infants (gestational age 28 to <33 weeks) with apnea of prematurity. Apnea of prematurity was defined as having at least 6 apnea episodes of greater than 20 seconds duration in a 24-hour period with no other identifiable cause of apnea. A 1 mL/kg (20 mg/kg caffeine citrate providing 10 mg/kg as caffeine base) loading dose of Cafcit Injection was administered intravenously, followed by a 0.25 mL/kg (5 mg/kg caffeine citrate providing 2.5 mg/kg of caffeine base) daily maintenance dose administered either intravenously or orally (generally through a feeding tube). The duration of treatment in this study was limited to 10 to 12 days. The protocol allowed infants to be "rescued" with open-label caffeine citrate treatment if their apnea remained uncontrolled during the double-blind phase of the trial.

The percentage of patients without apnea on day 2 of treatment (24 to 48 hours after the loading dose) was significantly greater with Cafcit Injection than placebo.

% of patients with zero apnea events on day 2 was 26.7% for the Calcit Injection arm versus 8.1% for placebo.

Apnea rate on day 2 (per 24 h) was 4.9 versus 7.2, respectively

% of patients with 50% reduction in apnea events from baseline on day 2 was 76% versus 57%, respectively