A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Cafcit Side Effects, and Drug Interactions - Caffeine Citrate
Cafcit Side Effects, and Drug Interactions - Caffeine Citrate
SIDE EFFECTS
Overall, the reported number
of adverse events in the double-blind period of the controlled trial
was similar for the CAFCIT® (caffeine citrate) and placebo
groups. The following table
shows adverse events that occurred in the double-blind period
of the controlled trial and that were more frequent in CAFCIT®
treated patients than placebo.
ADVERSE EVENTS THAT
OCCURRED MORE FREQUENTLY IN CAFCIT® TREATED PATIENTS THAN
PLACEBO DURING DOUBLE-BLIND THERAPY
|
Adverse Event (AE)
|
CAFCIT®
N= 46
|
Placebo
N= 39
|
|
n (%)
|
n (%)
|
|
BODY AS
A WHOLE
|
|
Accidental Injury
|
1 (2.2)
|
0 (0.0)
|
|
Feeding Intolerance
|
4 (8.7)
|
2 (5.1)
|
|
Sepsis
|
2 (4.3)
|
0 (0.0)
|
|
CARDIOVASCULAR SYSTEM
|
|
Hemorrhage
|
1 (2.2)
|
0 (0.0)
|
|
DIGESTIVE SYSTEM
|
|
Necrotizing enterocolitis
|
2 (4.3)
|
1 (2.6)
|
|
Gastritis
|
1 (2.2)
|
0 (0.0)
|
|
Gastrointestinal Hemorrhage
|
1 (2.2)
|
0 (0.0)
|
|
HEMIC AND LYMPHATIC SYSTEM
|
|
Disseminated Intravascular Coagulation
|
1 (2.2)
|
0 (0.0)
|
|
METABOLIC AND NUTRITIVE DISORDERS
|
|
Acidosis
|
1 (2.2)
|
0 (0.0)
|
|
Healing Abnormal
|
1 (2.2)
|
0 (0.0)
|
|
NERVOUS SYSTEM
|
|
Cerebral Hemorrhage
|
1 (2.2)
|
0 (0.0)
|
|
RESPIRATORY SYSTEM
|
|
Dyspnea
|
1 (2.2)
|
0 (0.0)
|
|
Lung Edema
|
1 (2.2)
|
0 (0.0)
|
|
SKIN AND APPENDAGES
|
|
Dry Skin
|
1 (2.2)
|
0 (0.0)
|
|
Rash
|
4 (8.7)
|
3 (7.7)
|
|
Skin Breakdown
|
1 (2.2)
|
0 (0.0)
|
|
SPECIAL SENSES
|
|
Retinopathy of Prematurity
|
1 (2.2)
|
0 (0.0)
|
|
UROGENITAL SYSTEM
|
|
Kidney Failure
|
1 (2.2)
|
0 (0.0)
|
In addition to the
cases above, three cases of necrotizing enterocolitis were diagnosed
in patients receiving CAFCIT® (caffeine citrate) during the
open-label phase of the
study.
Three of the infants who developed necrotizing enterocolitis
during the trial died. All had been exposed to caffeine. Two were
randomized to caffeine, and one placebo
patient was “rescued”
with open-label caffeine for uncontrolled apnea.
Adverse events described in the published literature include: central
nervous system stimulation
(i.e., irritability, restlessness, jitteriness), cardiovascular
effects (i.e., tachycardia,
increased left ventricular
output, and increased stroke
volume), gastrointestinal
effects (i.e., increased gastric aspirate, gastrointestinal
intolerance), alterations in serum
glucose (hypoglycemia and hyperglycemia) and renal
effects (increased urine
flow rate, increased creatinine
clearance, and increased
sodium and calcium excretion).
Published long-term follow-up
studies have not shown caffeine to adversely affect
neurological development
or growth parameters.
DRUG INTERACTIONS
Cytochrome P450 1A2 (CYP1A2) is known to
be the major enzyme involved
in the metabolism
of caffeine. Therefore, caffeine has the potential
to interact with drugs that are substrates for CYP1A2,
inhibit CYP1A2, or induce CYP1A2.
Few data exist on drug
interactions with caffeine
in preterm neonates.
Based on adult data, lower
doses of caffeine may
be needed following coadministration of drugs which are reported
to decrease caffeine
elimination (e.g.,
cimetidine and ketoconazole) and higher caffeine
doses may be needed following coadministration of drugs that increase
caffeine elimination
(e.g., phenobarbital
and phenytoin).
Caffeine administered concurrently with ketoprofen reduced the
urine volume in 4 healthy
volunteers. The clinical
significance of this interaction in preterm
neonates is not known.
Interconversion between caffeine
and theophylline
has been reported in preterm
neonates. The concurrent use of these drugs is not recommended.
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