Caffeine Citrate Oral Solution

This medication is used for the short-term treatment of a breathing problem (apnea) in premature infants. Caffeine blocks certain proteins (adenosine receptors) which lead to improved breathing in these infants.OTHER This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.This medication is also a stimulant that may be used to keep you awake and alert.

Before taking caffeine citrate, tell your doctor or pharmacist if your infant is allergic to it; or if your infant has any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your infant's medical history, especially of: heart disease, kidney disease, liver disease, stomach problems (e.g., peptic ulcers, necrotizing enterocolitis), seizures.Caution is advised when using this drug in infants because they may be more sensitive to its effects, especially the stimulant effects (e.g., trouble sleeping, restlessness, nervousness).Older adults may be more sensitive to the side effects of this drug, especially trouble sleeping.This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.This medication passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

Both caffeine citrate injection for intravenous administration and Caffeine Citrate Oral Solution are clear, colorless, sterile, non-pyrogenic, preservative-free, aqueous solutions adjusted to pH 4.7. Each mL contains 20 mg caffeine citrate (equivalent to 10 mg of caffeine base) prepared in solution by the addition of 10 mg caffeine anhydrous, USP to 5 mg citric acid monohydrate, USP, 8.3 mg sodium citrate dihydrate, USP and Water for Injection, USP.

Caffeine, a central nervous system stimulant, is an odorless white crystalline powder or granule, with a bitter taste. It is sparingly soluble in water and ethanol at room temperature. The chemical name of caffeine is 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione. In the presence of citric acid it forms caffeine citrate salt in solution. The structural formula and molecular weight of caffeine citrate follows.

Caffeine citrate injection and Caffeine Citrate Oral Solution are indicated for the short term treatment of apnea of prematurity in infants between 28 and <33 weeks gestational age.

Prior to initiation of 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.

The recommended loading dose and maintenance doses of caffeine citrate follow.

* using a syringe infusion pump † beginning 24 hours after the loading dose
	Dose of Caffeine Citrate Volume	Dose of 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†

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 and Caffeine Citrate Oral Solution 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 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, 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 µg/mL diluted to 10 µg/mL with Dextrose Injection, USP 5%

Both caffeine citrate Injection and Caffeine Citrate Oral Solution are available as clear, colorless, sterile, nonpyrogenic, preservative-free, aqueous solutions in 3 mL colorless glass vials. The vials of caffeine citrate injection are sealed with a teflon-faced gray rubber stopper and an aluminum overseal with a white flip-off polypropylene disk inset. The vials of Caffeine Citrate Oral Solution are sealed with a teflon-faced gray rubber stopper and a peel-off aluminum overseal with a blue flip-off polypropylene disk inset.

Both the injection and oral solution 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
NDC 51754-0502-1 3 mL vial, individually packaged in a carton.

Caffeine Citrate Oral Solution, USP
NDC 51754-0503-3 3 mL vial (NOT CHILD-RESISTANT), 10 vials per white polypropylene child-resistant container.

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

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

ATTENTION PHARMACIST: Detach "Instructions for Use" from the package insert and dispense with Caffeine Citrate Oral Solution prescription.

Manufactured by:
Exela Pharma Sciences
Lenoir, NC 28645 USA

N+ and NOVAPLUS are registered
trademarks of Novation, LLC.

This leaflet tells you about Caffeine Citrate Oral Solution and how to give it to your baby. Read the following information before giving this medicine to your baby. Completely discuss caffeine citrate with your baby’s doctor. Continue to discuss any questions you have about this medicine at your baby’s checkups.

After you remove your baby’s dose, throw away the open bottle (vial) and all medicine left in it. Use each vial of Caffeine Citrate Oral Solution for only one dose. There will be extra medicine left in the vial after one dose is removed. Leftover medicine should not be used because Caffeine Citrate Oral Solution does not contain preservatives. Once the vial is open, any medicine that is not used right away may not be safe to use for the next dose.

What is Caffeine Citrate Oral Solution?

The main ingredient of Caffeine Citrate Oral Solution is caffeine citrate. Caffeine Citrate Oral Solution is a clear, colorless, medicine to treat apnea of prematurityshort periods when premature babies stop breathing. Apnea of prematurity is due to the baby’s breathing centers not being fully developed.

How do I give Caffeine Citrate Oral Solution to my baby?

Give Caffeine Citrate Oral Solution to your baby once a day, at about the same time each day. Your baby’s doctor will prescribe the right amount of Caffeine Citrate Oral Solution based on your baby’s weight and age. Carefully follow the doctor’s dosing instructions.

Measure the dose of Caffeine Citrate Oral Solution carefully. Your baby’s doctor, nurse, or pharmacist will give you a suitable syringe or supply of syringes to measure small but accurate doses of Caffeine Citrate Oral Solution.

Never change (increase or decrease) your baby’s dose without speaking to your baby’s doctor.

If your baby continues to have periods of apnea, call your baby’s doctor right away.

Caffeine Citrate Oral Solution can be swallowed by mouth or given through a feeding tube. Based on your baby’s own situation, your baby’s doctor or other healthcare professional should teach you how to give Caffeine Citrate Oral Solution correctly.

Caffeine Citrate Oral Solution should be clear and colorless. Before giving Caffeine Citrate Oral Solution, look for small particles, cloudiness, or discoloration in the medicine. Do not use vials that contain cloudy or discolored medicine, or any visible particles

Caffeine Citrate Oral Solution does NOT contain any preservatives. Do not open the vial until it is time for your baby to receive the dose of medicine. Use each vial only once. After you remove your baby’s dose, throw away the vial and all medicine left in the opened vial.

Ten (10) vials of Caffeine Citrate Oral Solution are packaged in a child-resistant container. Caffeine Citrate Oral Solution vials are NOT CHILD-RESISTANT. Always store vials of Caffeine Citrate Oral Solution in the childresistant container. Follow the instructions below to open the child-resistant container, to open a vial of Caffeine Citrate Oral Solution, and to remove a dose of medicine from the vial.

To open the child-resistant container that holds the vials of Caffeine Citrate Oral Solution:

(Instructions with pictures are also printed on the top of the container.)

1. Hold the bottom-half of the child-resistant container with one hand and push the lower semicircular section on the front of the container with your thumb.
2. With your other hand, pull the cover up until you hear it click.
3. While holding the ends of the bottom half of the container with both hands, place both index fingers on the two semicircular locking tabs on the sides of the container.
4. Press the two tabs and raise the cover up.

To open a vial of Caffeine Citrate Oral Solution:

1. Hold the blue plastic top between the thumb and index finger. Use your thumb to flip the blue plastic top completely off the vial.
2. Carefully lift up the metal ring.
3. Pull the metal ring away from the vial and then pull it down towards the bottom of the vial without twisting the ring.
4. After you pull the ring down and the metal band around the top of the vial is completely broken through, carefully remove the rest of the metal band by pulling it out and away from the vial.
5. Being careful not to spill any medicine, remove the rubber stopper from the top of the vial.

To remove the prescribed dose from the vial:

You will need a small syringe to measure the exact amount of medicine that your baby’s doctor prescribed. Your baby’s doctor, nurse or pharmacist will give you this small syringe. Note that a milliliter (mL) is the same as a cubic centimeter (cc).

1. Insert the tip of the syringe in the medicine and pull up on the plunger to draw the medicine into the syringe. Remove slightly more of the medicine than the exact amount to be given to your baby.
2. Turn the syringe tip up so that any air in it rises to the top. Remove the air by gently pushing up on the syringe plunger. Continue to push the syringe plunger up to remove any extra medicine in the syringe, until only the exact number of milliliters (or cubic centimeters) that your baby’s doctor prescribed remains in the syringe.
3. Give the Caffeine Citrate Oral Solution to your baby as your baby’s doctor instructed.
4. Throw away the sharp metal pieces, the rubber stopper, the open vial, and any medicine that remains in it after your baby receives the dose.

What are possible side effects of caffeine citrate?

Your baby may or may not develop side effects from taking caffeine citrate. Each baby is different. If your baby develops one or more of the following symptoms, speak with your baby’s doctor right away:

• restlessness, jitteriness, or shakiness
• faster heart beat
• increased urination (increased diaper wetting)

The following symptoms may be caused by serious bowel or stomach problems. Call your baby’s doctor right away if your baby develops:

• bloated abdomen (stomach area)
• vomiting
• bloody stools (bloody bowel movements)
• loss of energy, lethargy (acting sluggish)

This is not a complete list of side effects reported with Caffeine Citrate Oral Solution. If you have a concern about your baby, speak with your baby’s doctor. If you want more information about Caffeine Citrate Oral Solution, speak with your baby’s doctor or pharmacist.

Manufactured by:
Exela Pharma Sciences
Lenoir, NC 28645 USA

N+ and NOVAPLUS are registered
trademarks of Novation, LLC.