Caffeine Citrate 20 mg/mL Solution
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Central Nervous System Stimulant class.
Where does this data come from?
🏭 Manufacturer & labeler
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🩺 Clinical
- Caffeine citrate is a prescription medicine given in the hospital to premature babies who have apnea of prematurity — that means they sometimes stop breathing for short periods, wh...
- What exactly is caffeine citrate used for in babies, and is it safe?
- The medical team will be monitoring your baby closely, but it helps to know the signs to watch for. The most serious concern is necrotizing enterocolitis (NEC) — a severe intestina...
- What side effects should I watch for in my premature baby on caffeine citrate?
Patient education
Supplement & herbal interactions
Caffeine (OTC drug) may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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5 mg / 1 mL
UNII 2968PHW8QP
A weak organic acid derived from citrus fruits or made through fermentation. It works as a buffer to control pH, a preservative to extend shelf life, and a flavoring agent in medications.
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8.3 mg / 1 mL
UNII 1Q73Q2JULR
Sodium citrate is a salt derived from citric acid. It works as a buffer to maintain the medicine's pH level and may also help improve taste or act as a preservative in the formulation.
2 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| caffeine citrate 20 mg/mL 25021-0602-03 | Sagent | 10 vials | — | AA | FDA listed | — |
| Caffeine Citrate 60 mg/3mL 42571-0346-69 | Micro | 10 vials | — | AA | FDA listed | — |
| Caffeine Citrate 20 mg/mL 47335-0290-44 | Sun | 10 vials | — | — | FDA listed | — |
| caffeine citrate 20 mg/mL 51754-0501-02 | Exela | 5 vials | — | AA | FDA listed | — |
| Caffeine Citrate 20 mg/mLthis 63323-0406-03 | Fresenius | 5 vials | — | AA | FDA listed | — |
| Caffeine Citrate Oral Solution 60 mg/3mL 72485-0110-10 | Armas | 10 vials | — | AA | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 63323-0406-03 You're viewing this | 5 VIAL in 1 CARTON (63323-406-03) / 3 mL in 1 VIAL (63323-406-01) | 2009-11-19 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
INDICATIONS AND USAGE Caffeine citrate oral solution is indicated for the short term treatment of apnea of prematurity in infants between 28 and <33 weeks gestational age.
⏱️ Dosage and Administration ▾
DOSAGE AND ADMINISTRATION Prior to initiation of caffeine citrate oral solution, 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.
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** *using a syringe infusion pump **beginning 24 hours after the loading dose 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 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.
⛔ Contraindications ▾
CONTRAINDICATIONS Caffeine citrate is contraindicated in patients who have demonstrated hypersensitivity to any of its components.
⚠️ Warnings ▾
WARNINGS During the double-blind, placebo-controlled clinical trial, six cases of necrotizing enterocolitis developed among the 85 infants studied (caffeine=46, placebo=39), with three cases resulting in death. Five of the six patients with necrotizing enterocolitis were randomized to or had been exposed to caffeine citrate. Reports in the published literature have raised a question regarding the possible association between the use of methylxanthines and development of necrotizing enterocolitis, although a causal relationship between methylxanthine use and necrotizing enterocolitis has not been established.
Therefore, as with all preterm infants, patients being treated with caffeine citrate should be carefully monitored for the development of necrotizing enterocolitis.
🤒 Adverse Reactions ▾
ADVERSE REACTIONS Overall, the reported number of adverse events in the double-blind period of the controlled trial was similar for the 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 caffeine citrate treated patients than placebo. ADVERSE EVENTS THAT OCCURRED MORE FREQUENTLY IN CAFFEINE CITRATE TREATED PATIENTS THAN PLACEBO DURING DOUBLE-BLIND THERAPY Adverse Event (AE) Caffeine Citrate N=46 n (%) Placebo N=39 n (%) BODY AS A WHOLE Accidental Injury Feeding Intolerance Sepsis 1 (2.2) 4 (8.7) 2 (4.3) 0 (0) 2 (5.1) 0 (0) CARDIOVASCULAR SYSTEM Hemorrhage 1 (2.2) 0 (0) DIGESTIVE SYSTEM Necrotizing Enterocolitis Gastritis Gastrointestinal Hemorrhage 2 (4.3) 1 (2.2) 1 (2.2) 1 (2.6) 0 (0) 0 (0) HEMIC AND LYMPHATIC SYSTEM Disseminated Intravascular Coagulation 1 (2.2) 0 (0) METABOLIC AND NUTRITIVE DISORDERS Acidosis Healing Abnormal 1 (2.2) 1 (2.2) 0 (0) 0 (0) NERVOUS SYSTEM Cerebral Hemorrhage 1 (2.2) 0 (0) RESPIRATORY SYSTEM Dsypnea Lung Edema 1 (2.2) 1 (2.2) 0 (0) 0 (0) SKIN AND APPENDAGES Dry Skin Rash Skin Breakdown 1 (2.2) 4 (8.7) 1 (2.2) 0 (0) 3 (7.7) 0 (0) SPECIAL SENSES Retinopathy of Prematurity 1 (2.2) 0 (0) UROGENITAL SYSTEM Kidney Failure 1 (2.2) 0 (0) In addition to the cases above, three cases of necrotizing enterocolitis were diagnosed in patients receiving 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 (i.e., hypoglycemia and hyperglycemia) and renal effects (i.e., 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.
🆘 Overdosage ▾
OVERDOSAGE Following overdose, serum caffeine levels have ranged from approximately 24 mg/L (a post marketing 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.
🧬 Clinical Pharmacology ▾
CLINICAL PHARMACOLOGY 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 A 1 and A 2 subtypes, by caffeine, which has been demonstrated in receptor binding assays and observed at concentrations approximating those achieved therapeutically.
Pharmacokinetics Absorption After oral administration of 10 mg caffeine base/kg to preterm neonates, the peak plasma level (C max ) for caffeine ranged from 6 to 10 mg/L and the mean time to reach peak concentration (T max ) ranged from 30 minutes to 2 hours. The T max was not affected by formula feeding. The absolute bioavailability, however, was not fully examined in preterm neonates.
Distribution Caffeine is rapidly distributed into the brain. Caffeine levels in the cerebrospinal fluid of preterm neonates approximate their plasma levels. The mean volume of distribution of caffeine in infants (0.8 to
0.9L/kg) is slightly higher than that in adults (0.6 L/kg). Plasma protein binding data are not available for neonates or infants. In adults, the mean plasma protein binding in vitro is reported to be approximately 36%.
Metabolism Hepatic cytochrome P450 1A2 (CYP1A2) is involved in caffeine biotransformation. Caffeine metabolism in preterm neonates is limited due to their immature hepatic enzyme systems. Interconversion between caffeine and theophylline has been reported in preterm neonates; caffeine levels are approximately 25% of theophylline levels after theophylline administration and approximately 3 to 8% of caffeine administered would be expected to convert to theophylline.
Elimination In young infants, the elimination of caffeine is much slower than that in adults due to immature hepatic and/or renal function. Mean half-life (T 1/2 ) and fraction excreted unchanged in urine (A e ) of caffeine in infants have been shown to be inversely related to gestational/postconceptual age. In neonates, the T 1/2 is approximately 3 to 4 days and the A e is approximately 86% (within 6 days).
By 9 months of age, the metabolism of caffeine approximates that seen in adults (T 1/2 = 5 hours and A e = 1%). Special Populations Studies examining the pharmacokinetics of caffeine in neonates with hepatic or renal insufficiency have not been conducted. Caffeine citrate should be administered with caution in preterm neonates with impaired renal or hepatic function.
Serum concentrations of caffeine should be monitored and dose administration of caffeine citrate should be adjusted to avoid toxicity in this population. Clinical Studies One multicenter, randomized, double-blind trial compared caffeine citrate 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 caffeine citrate 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 ci…
📦 How Supplied / Storage and Handling ▾
HOW SUPPLIED Caffeine Citrate Oral Solution, USP is available as a clear, colorless, sterile, non-pyrogenic, preservative-free, aqueous solution in colorless glass vials. The vials contain 3 mL of 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 Oral Solution, USP Product Code Unit of Sale Strength Each 400603 NDC 63323-406-03 Unit of 5 60 mg per 3 mL (20 mg per mL) NDC 63323-406-01 3 mL in a 6 mL Single Dose Vial Store at 20° to 25°C (68° to 77°F)[see USP Controlled Room Temperature].
Preservative Free. For single use only. Discard unused portion.
The container closure is not made with natural rubber latex. PHARMACIST: Dispense the “Patient Information” leaflet with the drug product.
📋 Description ▾
DESCRIPTION Caffeine Citrate Oral Solution, USP is a clear, colorless, sterile, non-pyrogenic, preservative-free, aqueous solution 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 to 5 mg citric acid monohydrate, 8.3 mg sodium citrate dihydrate and Water for Injection. 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-1 H -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. structure
💬 Medication Guide ▾
Med Guide CAFFEINE CITRATE Oral Solution, USP Rx only Each bottle (vial) of Caffeine Citrate Oral Solution, USP contains a total of 60 mg of caffeine citrate in 3 mL (20 mg/mL). Information and Instructions for Use 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 oral solution 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 must be discarded. 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 prematurity - short 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. Five (5) 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 child-resistant container. Follow the instructions below to open the child-resistant carton, to open a vial of caffeine citrate oral solution, and to remove a dose of medicine from the vial. To open the child-resistant carton for caffeine citrate oral solution: (Instructions with pictures are also printed on the top of the container) 1.
Holding base with one hand, squeeze semicircular section with your thumb. 2. With your other hand, push up cover until you hear two clicks.
3. Grasp narrow sides of the top. Using the index finger and thumb, press the two semicircular locking tabs on the sides of the cover.
Lift cover completely. 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 bott…