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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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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UNII B22547B95K
A salt derived from citric acid that helps maintain the proper acid-base balance in the medicine. It's used as a buffer to keep the product stable and at the right pH level.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
3 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 | $2.60 | $78.05 / 30 ml |
| 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/mLthis 51754-0501-03 | Exela | 10 vials | — | AA | FDA listed | — |
| Caffeine Citrate 20 mg/mL 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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🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
🔬 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 |
|---|---|---|---|
| 51754-0501-02 | 5 VIAL in 1 CARTON (51754-0501-2) / 3 mL in 1 VIAL | 2019-08-31 | Active |
| 51754-0501-03 You're viewing this | 10 VIAL in 1 CARTON (51754-0501-3) / 3 mL in 1 VIAL | 2015-03-30 | Active |
Pack size FAQ
What quantity is in NDC 51754-0501-03?
What NDC number is used to bill for this package of caffeine citrate 20 mg/mL Solution?
🧭 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) | ✓ Available |
Questions about this listing
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
INDICATIONS AND USAGE 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.
⏱️ Dosage and Administration ▾
DOSAGE AND ADMINISTRATION 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.
Dose of Caffeine Citrate Volume Dose of Caffeine Citrate mg/kg Route Frequency Loading Dose 1 mL/kg 20 mg/kg Intravenous using a syringe infusion pump (over 30 minutes) One Time Maintenance Dose 0.25 mL/kg 5 mg/kg Intravenous (over 10 minutes) or Orally Every 24 hours 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 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.
⛔ Contraindications ▾
CONTRAINDICATIONS Caffeine citrate injection and caffeine citrate oral solution are 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 3 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-BLINDED THERAPY Adverse Event (AE) Caffeine Citrate 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 1 (2.2) 0 (0.0) Coagulation 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 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 (ie, irritability, restlessness, jitteriness), cardiovascular effects (ie, tachycardia, increased left ventricular output, and increased stroke volume), gastrointestinal effects (ie, increased gastric aspirate, gastrointestinal intolerance), alterations in serum glucose (ie, 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 ▾
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.
🤰 Pregnancy ▾
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/m 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.
🆘 Overdosage ▾
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, tonicclonic 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; not caffeine citrate) 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 3-8% 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 3-4 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 citrate…
🧬 Mechanism of Action ▾
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.
📦 How Supplied / Storage and Handling ▾
HOW SUPPLIED 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 51754-0500-1: 3 mL vial, individually packaged in a carton. Caffeine citrate oral solution, USP NDC 51754-0501-2: 3 mL vial (NOT CHILD-RESISTANT), 5 vials per white polypropylene child- resistant container.
NDC 51754-0501-3: 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 and Distributed by: Exela Pharma Sciences, LLC Lenoir, NC 28645 USA Revised: May 2018 logo
📋 Description ▾
DESCRIPTION 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 to 5.0 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. Chemical Structure
💬 Information for Patients ▾
INFORMATION FOR PATIENTS Parents/caregivers of patients receiving caffeine citrate oral solution should receive the following instructions: 1. Caffeine citrate oral solution does not contain any preservatives and each vial is for single use only. Any unused portion of the medication should be discarded.
2. It is important that the dose of caffeine citrate oral solution be measured accurately, i.e., with a 1cc or other appropriate syringe. 3.
Consult your physician if the baby continues to have apnea events; do not increase the dose of caffeine citrate oral solution without medical consultation. 4. Consult your physician if the baby begins to demonstrate signs of gastrointestinal intolerance, such as abdominal distention, vomiting, or bloody stools, or seems lethargic.
5. Caffeine citrate oral solution should be inspected visually for particulate matter and discoloration prior to its administration. Vials containing discolored solution or visible particulate matter should be discarded.