Cafcit

Caffeine citrate should not be given to a child who has ever had an allergic reaction to this medicine.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Avoid giving the child food or drinks that contain caffeine, such as cola or chocolate milk.

Avoid giving the child food or drinks that contain caffeine, such as cola or chocolate milk.

• If your child has an allergy to Cafcit (caffeine oral solution) or any part of this medicine.
• If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If your child is taking theophylline.

This is not a list of all drugs or health problems that interact with Cafcit.

Tell the doctor and pharmacist about all of your child's drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this medicine with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.

Cafcit (caffeine citrate) is indicated for the short-term treatment of apnea of prematurity in infants between 28 and <33 weeks gestational age.

General

Apnea of prematurity is a diagnosis of exclusion. Other causes of apnea (e.g., central nervous system disorders, primary lung disease, anemia, sepsis, metabolic disturbances, cardiovascular abnormalities, or obstructive apnea) should be ruled out or properly treated prior to initiation of Cafcit (caffeine citrate).

Caffeine is a central nervous system stimulant and in cases of caffeine overdose, seizures have been reported. Cafcit should be used with caution in infants with seizure disorders.

The duration of treatment of apnea of prematurity in the placebo-controlled trial was limited to 10 to 12 days. The safety and efficacy of Cafcit for longer periods of treatment have not been established. Safety and efficacy of Cafcit for use in the prophylactic treatment of sudden infant death syndrome (SIDS) or prior to extubation in mechanically ventilated infants have also not been established.

Cardiovascular

Although no cases of cardiac toxicity were reported in the placebo-controlled trial, caffeine has been shown to increase heart rate, left ventricular output, and stroke volume in published studies. Therefore, Cafcit should be used with caution in infants with cardiovascular disease.

Renal and Hepatic Systems

Cafcit should be administered with caution in infants with impaired renal or hepatic function. Serum concentrations of caffeine should be monitored and dose administration of Cafcit should be adjusted to avoid toxicity in this population. (See CLINICAL PHARMACOLOGY, Elimination and Special Populations.)

Laboratory Tests

Prior to initiation of Cafcit (caffeine citrate), 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.

In the placebo-controlled clinical trial, caffeine levels ranged from 8 to 40 mg/L. A therapeutic plasma concentration range of caffeine could not be determined from the placebo-controlled clinical trial. Serious toxicity has been reported in the literature when serum caffeine levels exceed 50 mg/L. Serum concentrations of caffeine may need to be monitored periodically throughout treatment to avoid toxicity.

In clinical studies reported in the literature, cases of hypoglycemia and hyperglycemia have been observed. Therefore, serum glucose may need to be periodically monitored in infants receiving Cafcit.

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 four 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 2-year study in Sprague-Dawley rats, caffeine (as caffeine base) administered in drinking water was not carcinogenic in male rats at doses up to 102 mg/kg or in female rats at doses up to 170 mg/kg (approximately 2 and 4 times, respectively, the maximum recommended intravenous loading dose for infants on a mg/m2 basis). In an 18-month study in C57BL/6 mice, no evidence of tumorigenicity was seen at dietary doses up to 55 mg/kg (less than the maximum recommended intravenous loading dose for infants on a mg/m2 basis).

Caffeine (as caffeine base) increased the sister chromatid exchange (SCE) SCE/cell metaphase (exposure time dependent) in an in vivo mouse metaphase analysis. Caffeine also potentiated the genotoxicity of known mutagens and enhanced the micronuclei formation (5-fold) in folate-deficient mice. However, caffeine did not increase chromosomal aberrations in in vitro Chinese hamster ovary cell (CHO) and human lymphocyte assays and was not mutagenic in an in vitro CHO/hypoxanthine guanine phosphoribosyltransferase (HGPRT) gene mutation assay, except at cytotoxic concentrations. In addition, caffeine was not clastogenic in an in vivo mouse micronucleus assay.

Caffeine (as caffeine base) administered to male rats at 50 mg/kg/day subcutaneously (approximately equal to the maximum recommended intravenous loading dose for infants on a mg/m2 basis) for 4 days prior to mating with untreated females, caused decreased male reproductive performance in addition to causing embryotoxicity. In addition, long-term exposure to high oral doses of caffeine (3 g over 7 weeks) was toxic to rat testes as manifested by spermatogenic cell degeneration.

Pregnancy

Pregnancy Category C

Concern for the teratogenicity of caffeine is not relevant when administered to infants. In studies performed in adult animals, caffeine (as caffeine base) administered to pregnant mice as sustained release pellets at 50 mg/kg (less than the maximum recommended intravenous loading dose for infants on a mg/m2 basis), during the period of organogenesis, caused a low incidence of cleft palate and exencephaly in the fetuses. There are no adequate and well-controlled studies in pregnant women.

Cafcit® Injection (caffeine citrate injection, USP) is available as a clear, colorless, sterile, non-pyrogenic, preservative-free, aqueous solution in 3 mL colorless glass vials. The vials are sealed with a teflon-faced gray rubber stopper and an aluminum overseal with a white flip-off printed with “FOR INTRAVENOUS USE ONLY” in red.

The vials contain 3 mL solution at a concentration of 20 mg/mL caffeine citrate (60 mg/vial) equivalent to 10 mg/mL caffeine base (30 mg/vial).

Cafcit® Injection (caffeine citrate injection, USP) is supplied as:

   NDC 0641-6164-10, 3 mL Single Dose Vial packaged in a carton of 10

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Not made with natural rubber latex.

Preservative free. For single dose only. Discard unused portion.

To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceutical Corp. at 1-877-845-0689, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

For Product Inquiry call 1-877-845-0689.

Manufactured by:

WEST-WARD

PHARMACEUTICALS

Eatontown, NJ 07724 USA

Revised February 2015

462-708-00

More frequent side effects include: necrotizing enterocolitis. See below for a comprehensive list of adverse effects.

Applies to caffeine: compounding powder, intravenous solution, oral gum, oral liquid, oral tablet, oral tablet dispersible, oral tablet extended release

Gastrointestinal

Very common (10% or more): Constipation (up to 17.4%)
Common (1% to 10%): Necrotizing enterocolitis, gastritis, GI hemorrhage, gastroesophageal reflux, dilated bowel loops
Frequency not reported: Increased gastric aspirate, GI intolerance, vomiting, regurgitation[Ref]

General

Long-term follow-up studies have not shown caffeine (the active ingredient contained in Cafcit) to adversely affect neurological development or growth parameters.[Ref]

Cardiovascular

Common (1% to 10%): Hemorrhage, tachycardia
Uncommon (0.1% to 1%): Arrhythmia
Frequency not reported: Increased left ventricular output, increased stroke volume, hypertension[Ref]

Dermatologic

Common (1% to 10%): Rash, dry skin, skin breakdown[Ref]

Hematologic

Common (1% to 10%): Disseminated intravascular coagulation, anemia
Frequency not reported: Decreased hemoglobin[Ref]

Hepatic

Common (1% to 10%): Kidney failure[Ref]

Metabolic

Common (1% to 10%): Acidosis, hyperglycemia
Frequency not reported: Hypoglycemia, temporary reduced weight gain, decreased thyroxine[Ref]

Nervous system

Common (1% to 10%): Cerebral hemorrhage
Uncommon (0.1% to 1%): Convulsions/seizures
Frequency not reported: Irritability, restlessness, jitteriness, tremors, brain injury[Ref]

Ocular

Common (1% to 10%): Retinopathy of prematurity[Ref]

Other

Common (1% to 10%): Perinatal disorder (trace aspirates, feeding intolerances), injection site reaction, sepsis, accidental injury, abnormal healing, infusion site phlebitis and inflammation
Frequency not reported: Failure to thrive, deafness[Ref]

Respiratory

Common (1% to 10%): Dyspnea, lung edema
Frequency not reported: Tachypnea[Ref]

Hypersensitivity

Rare (less than 0.1%): Hypersensitivity reaction[Ref]

Renal

Frequency not reported: Increased urine flow rate, increased creatinine clearance, increased sodium and calcium excretion[Ref]

Some side effects of Cafcit may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.