Caffeine Citrate: Package Insert and Label Information (Page 2 of 2)

OVERDOSAGE

Following overdose, serum caffeine levels have ranged from approximately 24 mg/L (a postmarketing spontaneous case report in which an infant exhibited irritability, poor feeding, and insomnia) to 350 mg/L. Serious toxicity has been associated with serum levels greater than 50 mg/L (see PRECAUTIONS, Laboratory Tests and DOSAGE AND ADMINISTRATION). Signs and symptoms reported in the literature after caffeine overdose in preterm infants include fever, tachypnea, jitteriness, insomnia, fine tremor of the extremities, hypertonia, opisthotonos, tonic-clonic movements, nonpurposeful jaw and lip movements, vomiting, hyperglycemia, elevated blood urea nitrogen, and elevated total leukocyte concentration. Seizures have also been reported in cases of overdose. One case of caffeine overdose complicated by development of intraventricular hemorrhage and long-term neurological sequelae has been reported. Another case of caffeine citrate overdose (from New Zealand) of an estimated 600 mg caffeine citrate (approximately 322 mg/kg) administered over 40 minutes was complicated by tachycardia, ST depression, respiratory distress, heart failure, gastric distention, acidosis, and a severe extravasation burn with tissue necrosis at the peripheral intravenous injection site. No deaths associated with caffeine overdose have been reported in preterm infants. Treatment of caffeine overdose is primarily symptomatic and supportive. Caffeine levels have been shown to decrease after exchange transfusions. Convulsions may be treated with intravenous administration of diazepam or a barbiturate such as pentobarbital sodium.

DOSAGE AND ADMINISTRATION

Prior to initiation of caffeine citrate injection USP, 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 caffeine citrate injection, USP follow.

* Using a syringe infusion pump ** Beginning 24 hours after the loading dose
	Dose of Caffeine Citrate Injection, USP Volumme	Dose of Caffeine Citrate Injection, USP mg/kg	Route	Frequency
Loading Dose	1 mL/kg	20mg/kg	Intravenous* (over 30 minutes)	One time
Maintenance Dose	0.25 mL/kg	5 mg/kg	Intravenous* (Over 10 minutes) of Orally	Every 24 hours**

NOTE THAT THE DOSE OF CAFFEINE BASE IS ONE-HALF THE DOSE WHEN EXPRESSED AS CAFFEINE CITRATE (e.g., 20 mg of caffeine citrate is equivalent to 10 mg of caffeine base).

Serum concentrations of caffeine may need to be monitored periodically throughout treatment to avoid toxicity. Serious toxicity has been associated with serum levels greater than 50 mg/L.

Caffeine citrate injection, USP should be inspected visually for particulate matter and discoloration prior to administration. Vials containing discolored solution or visible particulate matter should be discarded.

Drug Compatibility

To test for drug compatibility with common intravenous solutions or medications, 20 mL of caffeine citrate injection, USP were combined with 20 mL of a solution or medication, with the exception of an Intralipid^® admixture, which was combined as 80 mL/80 mL. The physical appearance of the combined solutions was evaluated for precipitation. The admixtures were mixed for 10 minutes and then assayed for caffeine. The admixtures were then continually mixed for 24 hours, with further sampling for caffeine assays at 2, 4, 8, and 24 hours.
Based on this testing, caffeine citrate injection USP, 60 mg/3 mL is chemically stable for 24 hours at room temperature when combined with the following test products.
• Dextrose Injection, USP 5%
• 50% Dextrose Injection USP
• Intralipid^® 20% IV Fat Emulsion
• Aminosyn^® 8.5% Crystalline Amino Acid Solution
• Dopamine HCI Injection, USP 40 mg/mL diluted to 0.6 mg/mL with Dextrose Injection, USP 5%
• Calcium Gluconate Injection, USP 10% (0.465 mEq/Ca⁺² /mL)
• Heparin Sodium Injection, USP 1000 units/mL diluted to 1 unit/mL with Dextrose Injection, USP 5%
• Fentanyl Citrate Injection, USP 50 mcg/mL diluted to 10 mcg/mL with Dextrose Injection, USP 5%

HOW SUPPLIED

Caffeine citrate injection, USP is available as a clear, colorless, sterile, non-pyrogenic, preservative-free, aqueous solution in 5 mL colorless glass vial. The vials are sealed with a 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).

Caffeine citrate injection, USP is supplied as:

3 mL Single-Dose Vial,
individually packaged in a carton. NDC 55150-187-03

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

The vial stopper is not made with natural rubber latex.

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

Intralipid^® is a registered trademark of Fresenius Kabi AB.

Aminosyn^® is a registered trademark of Hospira, Inc.

To report SUSPECTED ADVERSE REACTIONS, contact AuroMedics Pharma LLC at 1-866-850-2876 or www.auromedics.com or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

For Product Inquiry call 1-866-850-2876.

Distributed by:
AuroMedics Pharma LLC
279 Princeton-Hightstown Rd.
E. Windsor, NJ 08520
Manufactured by:
Eugia Pharma Specialities Limited
Hyderabad — 500032
India
Revised: November 2021

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL — 60 mg per 3 mL — Container Label

Rx only NDC 55150-187-03
Caffeine
Citrate
Injection USP
60 mg per 3 mL
(20 mg / mL)
For Intravenous Use Only

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL — 60 mg per 3 mL — Container-Carton (1 Vial)

Rx only NDC 55150-187-03
Caffeine
Citrate
Injection USP
60 mg per 3 mL
(20 mg / mL)
For Intravenous Use Only
For single-dose only;
discard unused portion.
3 mL Single-Dose Vial
AUROMEDICS

CAFFEINE CITRATE caffeine citrate injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:55150-187 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CAFFEINE CITRATE (CAFFEINE) CAFFEINE CITRATE 20 mg in 1 mL

Inactive Ingredients Ingredient Name Strength CITRIC ACID MONOHYDRATE 5 mg in 1 mL TRISODIUM CITRATE DIHYDRATE 8.3 mg in 1 mL WATER

Packaging # Item Code Package Description Multilevel Packaging 1 NDC:55150-187-03 1 VIAL, SINGLE-DOSE in 1 CARTON contains a VIAL, SINGLE-DOSE 1 3 mL in 1 VIAL, SINGLE-DOSE This package is contained within the CARTON (55150-187-03)

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA205013 09/22/2015

Labeler — AuroMedics Pharma LLC (968961354)

Establishment
Name	Address	ID/FEI	Operations
Eugia Pharma Specialities Limited		650498244	ANALYSIS (55150-187), MANUFACTURE (55150-187)

Revised: 11/2021 AuroMedics Pharma LLC