Caffeine; Caffeine and Sodium Benzoate Injection; Caffeine Citrate

Class: Respiratory and CNS Stimulants
VA Class: CN809
CAS Number: 58-08-2
Brands: Cafcit, No Doz, Vivarin

Introduction

CNS stimulant; a xanthine derivative.115 120 a

Uses for Caffeine; Caffeine and Sodium Benzoate Injection; Caffeine Citrate

CNS Stimulation

Used orally as an aid in staying awake and to restore mental alertness in fatigued patients.117 118 a

Used in combination with antihistamines to overcome the sedative properties of antihistamines; however, efficacy and dosage required not adequately established.a

Caffeine and sodium benzoate injection has been used in conjunction with supportive measures to treat respiratory depression associated with overdosage of CNS depressant drugs (e.g., opiate analgesics, alcohol) and with electric shock.120 a However, most authorities believe caffeine and other analeptics should not be used in these conditions and recommend other supportive therapy because of caffeine’s questionable benefit and transient action.120 a

Slideshow: View Frightful (But Dead Serious) Drug Side Effects

Apnea of Prematurity

Short-term (10–12 days) treatment (as oral or IV caffeine citrate) of apnea of prematurity in neonates who are 28 to <33 weeks of gestational age (designated an orphan drug by FDA for this use).115

Use only after other causes of apnea (e.g., CNS disorders, primary lung disease, anemia, sepsis, metabolic disturbances, cardiovascular abnormalities, obstructive apnea) have been ruled out or treated appropriately.115

Headache

Used in combination with ergotamine to prevent or abort vascular headaches (e.g., migraine and cluster headaches).116 a e However, there is conflicting evidence regarding efficacy of this combination in the treatment of acute migraine attacks.116

Used orally alone and in combination with analgesics (e.g., acetaminophen, aspirin) for treatment of headache,121 a d h l o including migraine attacks.116 g

Some evidence that analgesic-caffeine combinations may produce slightly more analgesia than analgesic agents alone and may have beneficial effect on mood; however, these results have not always been reproducible in well-controlled studies.a Additional studies needed to determine the role, if any, of caffeine as an analgesic adjuvant.a

Some experts state that the combination of acetaminophen, aspirin, and caffeine is a reasonable first-line therapy for mild to moderate migraine attacks or for severe migraine attacks that previously have responded to NSAIAs or nonopiate analgesics.116

Caffeine and sodium benzoate injection has been used for the symptomatic relief of headache following spinal puncture.a

Other Uses

Safety and efficacy of caffeine citrate in the prevention of sudden infant death syndrome (SIDS) or prior to extubation in mechanically ventilated infants not established.115

Has been used orally alone and in combination with other drugs (e.g., analgesics, diuretics) to relieve tension, fatigue, and fluid retention associated with menstruation.a Usefulness is questionable because caffeine’s diuretic activity in patients with fluid retention is minimal.a

Caffeine; Caffeine and Sodium Benzoate Injection; Caffeine Citrate Dosage and Administration

General

Apnea of Prematurity

  • Prior to initiating caffeine citrate therapy, determine baseline serum caffeine concentrations in neonates previously treated with theophylline (see Specific Drugs and Laboratory Tests under Interactions) and in infants born to mothers who consumed caffeine prior to delivery.115

  • May need to monitor serum caffeine concentrations periodically during therapy to avoid toxicity.115

Administration

Administer orally (caffeine tablets, caffeine citrate oral solution), by slow IV infusion (caffeine citrate), or by slow IV injection or IM or sub-Q injection (caffeine and sodium benzoate).115 117 118 120 a Administer rectally in combination with ergotamine tartrate.m

Consult manufacturer’s product labeling for complete directions for appropriate administration of preparations containing caffeine in combination with analgesics, antacids, antihistamines, antipyretics, antitussives, belladonna alkaloids, diuretics, ergotamine tartrate, expectorants, nasal decongestants, skeletal muscle relaxants, sympathomimetics, and vitamins.

Oral Administration

Caffeine Citrate Oral Solution

Available as preservative-free oral solution in single-use vials; discard any unused portion.115

To administer a dose, remove the rubber stopper from the vial and then withdraw and administer the appropriate dose using a 1-mL or other appropriate syringe to ensure accurate measurement.115

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Caffeine citrate is available as a preservative-free injection in single-use vials; discard any unused portion.115 Use a syringe infusion pump to administer caffeine citrate injection to neonates.115

Rate of Administration

Caffeine citrate: For treatment of apnea of prematurity, administer loading dose by slow IV infusion over 30 minutes; infuse maintenance doses by slow IV infusion over 10 minutes.115 a

Caffeine and sodium benzoate: Administer by slow IV injection.120 a

Dosage

Available as caffeine, caffeine citrate, and caffeine and sodium benzoate; dosage of caffeine (alone or in fixed combination with sodium benzoate) expressed in terms of anhydrous caffeine; dosage of caffeine citrate expressed in terms of the salt.115 117 118 120 a

Caffeine also is commercially available in combination with analgesics, antacids, antihistamines, antipyretics, antitussives, belladonna alkaloids, diuretics, ergotamine tartrate, expectorants, nasal decongestants, skeletal muscle relaxants, sympathomimetics, and vitamins; consult manufacturer’s product labeling for appropriate dosage of the specific preparation.

Pediatric Patients

CNS Stimulation
Oral

Caffeine: 100–200 mg administered no more frequently than every 3–4 hours in children ≥12 years of age.117 118 a

IV, IM, or Sub-Q

Caffeine and sodium benzoate injection: 8 mg/kg (maximum 500 mg) (4 mg/kg when expressed in terms of anhydrous caffeine) or 250 mg/m2 (125 mg/m2 when expressed in terms of anhydrous caffeine) administered up to every 4 hours if necessary has been recommended;a however, most clinicians strongly discourage analeptic use of caffeine.120 a

Apnea of Prematurity
Loading Dose of Caffeine Citrate
Oral

Loading dose of 10–20 mg/kg (5–10 mg/kg when expressed in terms of anhydrous caffeine) as a single dose has been used.106 107 108 109 110

IV

Loading dose of 20 mg/kg (10 mg/kg when expressed in terms of anhydrous caffeine) as a single dose.115

Alternatively, loading dose of 10–20 mg/kg (5–10 mg/kg when expressed in terms of anhydrous caffeine) as a single dose has been used.105 106 107 108 109 110

IM

Loading dose of 10–20 mg/kg (5–10 mg/kg when expressed in terms of anhydrous caffeine) as a single dose has been used.105 106 107 108 109 110

Maintenance Therapy with Caffeine Citrate
Oral

5 mg/kg (2.5 mg/kg when expressed in terms of anhydrous caffeine) every 24 hours for no longer than 10–12 days, beginning 24 hours after loading dose.115 (See Prescribing Limits under Dosage and Administration.)

Alternatively, 5–10 mg/kg (2.5–5 mg/kg when expressed in terms of anhydrous caffeine) once daily, beginning 24 hours after loading dose, has been used.105 106 107 108 109 110 Adjust maintenance dosage according to the patient’s response and tolerance and plasma caffeine concentrations.105 106 107 108 109 110

IV

5 mg/kg (2.5 mg/kg when expressed in terms of anhydrous caffeine) every 24 hours for no longer than 10–12 days, beginning 24 hours after loading dose.115 (See Prescribing Limits under Dosage and Administration.)

Alternatively, 5–10 mg/kg (2.5–5 mg/kg when expressed in terms of anhydrous caffeine) once daily, beginning 24 hours after loading dose, has been used.105 106 107 108 109 110 Adjust maintenance dosage according to the patient’s response and tolerance and plasma caffeine concentrations.105 106 107 108 109 110

IM

5–10 mg/kg (2.5–5 mg/kg when expressed in terms of anhydrous caffeine) once daily, beginning 24 hours after loading dose, has been used.105 106 107 108 109 110 Adjust maintenance dosage according to the patient’s response and tolerance and plasma caffeine concentrations.105 106 107 108 109 110

Headache
Oral

Caffeine in fixed combination with analgesics (e.g., acetaminophen, aspirin, salicylamide) for self-medication: Combinations and dosage strengths vary; consult manufacturer’s product labeling for appropriate dosage of the specific preparation.d h l o

Tension Headache
Oral

Butalbital, acetaminophen, and caffeine in children ≥12 years of age: 1 or 2 capsules or tablets (each containing butalbital 50 mg, acetaminophen 325 mg, and caffeine 40 mg) every 4 hours (up to 6 capsules or tablets daily).c p Alternatively, 1 capsule or tablet (containing butalbital 50 mg, acetaminophen 500 mg, and caffeine 40 mg) every 4 hours in children ≥12 years of age.b i Avoid extended and repeated use.b c i p

Butalbital, aspirin, and caffeine in children ≥12 years of age: 1 or 2 tablets (each containing butalbital 50 mg, aspirin 325 mg, and caffeine 40 mg) every 4 hours (up to 6 tablets daily).f Avoid extended and repeated use.f

Adults

CNS Stimulation
Mild CNS Stimulation
Oral

Caffeine: 100–200 mg administered no more frequently than every 3–4 hours.117 118 120 a

Emergency Respiratory Failure
IV

Caffeine and sodium benzoate: 500 mg–1 g (250–500 mg when expressed in terms of anhydrous caffeine); however, most clinicians strongly discourage analeptic use of caffeine.120 a

Respiratory Depression Associated with Overdosage of CNS Depressants and with Electric Shock
IM

Caffeine and sodium benzoate: 500 mg–1 g (250–500 mg when expressed in terms of anhydrous caffeine); however, most clinicians strongly discourage analeptic use of caffeine.120 a

Headache
Oral

Caffeine in fixed combination with analgesics (e.g., acetaminophen, aspirin, salicylamide) for self-medication: Combinations and dosage strengths vary; consult manufacturer’s product labeling for appropriate dosage of the specific preparation.d h l o

Tension Headache
Oral

Butalbital, acetaminophen, and caffeine: 1 or 2 capsules or tablets (each containing butalbital 50 mg, acetaminophen 325 mg, and caffeine 40 mg) every 4 hours (up to 6 capsules or tablets daily).c p Alternatively, 1 capsule or tablet (containing butalbital 50 mg, acetaminophen 500 mg, and caffeine 40 mg) every 4 hours.b i Avoid extended and repeated use.b c i p

Butalbital, aspirin, and caffeine: 1 or 2 capsules or tablets (each containing butalbital 50 mg, aspirin 325 mg, and caffeine 40 mg) every 4 hours (up to 6 capsules or tablets daily).f j Avoid extended and repeated use.f

Butalbital, acetaminophen, caffeine, and codeine phosphate: 1 or 2 capsules (each containing butalbital 50 mg, acetaminophen 325 mg, caffeine 40 mg, and codeine phosphate 30 mg) every 4 hours (up to 6 capsules daily).121 Avoid extended and repeated use.121

Butalbital, aspirin, caffeine, and codeine phosphate: 1 or 2 capsules (each containing butalbital 50 mg, aspirin 325 mg, caffeine 40 mg, and codeine phosphate 30 mg) every 4 hours (up to 6 capsules daily).k Avoid extended and repeated use.k

Vascular Headache
Oral

Acetaminophen, aspirin, and caffeine: 2 tablets (each containing acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg) for treatment of migraine.g

Ergotamine and caffeine: 2 tablets (each containing ergotamine tartrate 1 mg and caffeine 100 mg) initially, followed by 1 tablet at 30-minute intervals until attack has abated (maximum 6 tablets per attack).e

Rectal

Ergotamine and caffeine: 1 suppository (containing ergotamine tartrate 2 mg and caffeine 100 mg) initially;m if necessary, may give a second dose (1 suppository) in 1 hour.m

In some patients with cluster headaches in the morning, 1–2 suppositories may be given at bedtime on a short-term basis.m n

Prescribing Limits

Pediatric Patients

CNS Stimulation
Oral

Caffeine in children ≥12 years of age: Maximum 200 mg every 3–4 hours.117 118 a

IV, IM, or Sub-Q

Caffeine and sodium benzoate injection: Maximum 500 mg (250 mg when expressed as anhydrous caffeine) per dose.a

Apnea of Prematurity
Maintenance Therapy with Caffeine Citrate
Oral, IV, or IM

Safety and efficacy of dosing periods exceeding 10–12 days not established.115

Headache
Tension Headache
Oral

Butalbital, acetaminophen, and caffeine in children ≥12 years of age: Maximum 6 capsules or tablets (each containing butalbital 50 mg, acetaminophen 325 or 500 mg, and caffeine 40 mg) daily.b c i p

Butalbital, aspirin, and caffeine in children ≥12 years of age: Maximum 6 tablets (each containing butalbital 50 mg, aspirin 325 mg, and caffeine 40 mg) daily.f

Adults

CNS Stimulation
Mild CNS Stimulation
Oral

Caffeine: Maximum 200 mg every 3–4 hours.117 118 a

Emergency Respiratory Failure
IV

Caffeine and sodium benzoate: Maximum 1 g (500 mg when expressed in terms of anhydrous caffeine) as a single dose.120 a Maximum 2.5 g (1.25 g when expressed in terms of anhydrous caffeine) daily.120

Respiratory Depression Associated with Overdosage of CNS Depressants and with Electric Shock
IM

Caffeine and sodium benzoate: Maximum 1 g (500 mg when expressed in terms of anhydrous caffeine) as a single dose.120 a Maximum 2.5 g (1.25 g when expressed in terms of anhydrous caffeine) daily.120

Headache
Tension Headache
Oral

Butalbital, acetaminophen, and caffeine: Maximum 6 capsules or tablets (each containing butalbital 50 mg, acetaminophen 325 or 500 mg, and caffeine 40 mg) daily.b c i p

Butalbital, aspirin, and caffeine: Maximum 6 capsules or tablets (each containing butalbital 50 mg, aspirin 325 mg, and caffeine 40 mg) daily.f j

Butalbital, acetaminophen, caffeine, and codeine phosphate: Maximum 6 capsules (each containing butalbital 50 mg, acetaminophen 325 mg, caffeine 40 mg, and codeine phosphate 30 mg) daily.121

Butalbital, aspirin, caffeine, and codeine phosphate: Maximum 6 capsules (each containing butalbital 50 mg, aspirin 325 mg, caffeine 40 mg, and codeine phosphate 30 mg) daily.k

Vascular Headache
Oral

Acetaminophen, aspirin, and caffeine: Maximum 2 tablets (each containing acetaminophen 250 mg, aspirin 250 mg, and caffeine 65 mg) within any 24-hour period unless otherwise directed by a clinician.g

Ergotamine and caffeine: Maximum 6 tablets (each containing ergotamine tartrate 1 mg and caffeine 100 mg) per attack or 10 tablets per week.e

Rectal

Ergotamine and caffeine: Maximum 2 suppositories (each containing ergotamine tartrate 2 mg and caffeine 100 mg) per attack and 5 suppositories per week.m

Special Populations

Hepatic Impairment

Apnea of Prematurity
Oral or IV

Adjust caffeine citrate dosage to avoid toxicity; use with caution and monitor serum caffeine concentrations.115

Renal Impairment

Apnea of Prematurity
Oral or IV

Adjust caffeine citrate dosage to avoid toxicity; use with caution and monitor serum caffeine concentrations.115

Cautions for Caffeine; Caffeine and Sodium Benzoate Injection; Caffeine Citrate

Contraindications

  • Known hypersensitivity to caffeine or any ingredient in the formulation.115 a e

Warnings/Precautions

Warnings

Necrotizing Enterocolitis

Potentially fatal necrotizing enterocolitis reported in neonates receiving caffeine citrate.115 Careful monitoring for the development of necrotizing enterocolitis (as is recommended for all preterm infants) is recommended for those receiving caffeine citrate.115

General Precautions

Cardiac Effects

Tachycardia, extrasystoles, and possibly other cardiac arrhythmias may be associated with large doses;115 117 120 generally recommended that caffeine be avoided in patients with symptomatic cardiac arrhythmias and/or palpitations and during the first several days to weeks after an AMI.100

Use with caution in infants with cardiovascular disease.115

Nervous System Effects

Large doses may result in insomnia, restlessness, nervousness, mild delirium, headache, excitement, agitation, a condition resembling anxiety neurosis, scintillating scotoma, hyperesthesia, tinnitus, and muscle tremors or twitches. 115 120

Seizures reported with caffeine overdosage; use with caution in infants with seizure disorders.115

Overly vigorous treatment with caffeine and sodium benzoate may increase CNS depression in already depressed patients.a

GI Effects

Chronic administration in animals associated with gastric ulceration; causal relationship in humans not adequately established.a Use with caution in patients with history of peptic ulcer.a

Blood Glucose Abnormalities

Hypoglycemia and hyperglycemia reported in patients receiving caffeine; periodic monitoring of blood glucose concentrations may be necessary in neonates receiving caffeine citrate.115 a

Self-medication

Intended for occasional use only; should not be used as a substitute for sleep.117 118

Use of Fixed Combinations

When used in fixed combination with other drugs (see Preparations), consider the cautions, precautions, and contraindications associated with the concomitant agent(s).121 e g

Specific Populations

Pregnancy

Category C.115 120

Lactation

Distributed into milk;119 a milk-to-plasma ratios of 0.5–0.76 reported.119 Amount of caffeine ingested from usual quantities of caffeinated beverages is considered compatible with breast-feeding; caffeine may accumulate in nursing infants following moderate to heavy maternal consumption.119

Pediatric Use

Use of caffeine tablets for self-medication in children <12 years of age is not recommended.117 118 Possible increased severity of CNS effects in children compared with adults.a (See Nervous System Effects under Cautions.)

Avoid use of caffeine and sodium benzoate injection in neonates; sodium benzoate may produce kernicterus.a

Use caffeine citrate with caution in premature neonates with impaired renal or hepatic function, cardiovascular disease, or seizure disorders (see Cardiac Effects and also Nervous System Effects, under Cautions; also see Special Populations under Dosage and Administration).115 Consider possible need for monitoring serum caffeine concentrations (see General under Dosage and Administration).115 Monitor blood glucose concentrations periodically; hypoglycemia and hyperglycemia reported in neonates.115

Long-term follow-up studies have not shown caffeine administration in premature neonates to adversely affect neurologic development or growth.115

Hepatic Impairment

Pharmacokinetics of caffeine citrate not evaluated in premature neonates with hepatic impairment; use with caution.115 (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Pharmacokinetics of caffeine citrate not evaluated in premature neonates with renal impairment; use with caution.115 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

CNS stimulation (e.g., insomnia, restlessness, nervousness, mild delirium), GI irritation (e.g., nausea, vomiting, gastric irritation).a

In neonates with apnea of prematurity: Rash, feeding intolerance, sepsis, necrotizing enterocolitis.115

Interactions for Caffeine; Caffeine and Sodium Benzoate Injection; Caffeine Citrate

Appears to be metabolized principally by CYP1A2.115

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs metabolized by CYP1A2 or with CYP1A2 inducers or inhibitors.115

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Anticonvulsants (phenobarbital, phenytoin)

Possible increased elimination of caffeine and decreased serum caffeine concentrations115

Possible increased metabolism of phenobarbital120

Increased caffeine dosage may be required115

β-Adrenergic agonists

May increase cardiac inotropic effects120 a

Cimetidine

Possible decreased elimination of caffeine and increased serum caffeine concentrations115

Reduced caffeine dosage may be required115

Disulfiram

Potential inhibition of caffeine metabolism and substantially decreased clearance of caffeine;103 possible exaggerated or prolonged caffeine effects103 104

Clinical importance unknown103 104

Ketoconazole

Possible decreased elimination of caffeine and increased serum caffeine concentrations115 a

Reduced caffeine dosage may be required115 a

Ketoprofen

Possible decreased urine volume115

Clinical importance unknown115

Tests for serum urate

False-positive elevations of serum urate as measured by the Bittner method120 a

Tests for urinary 5-hydroxyindoleacetic acid (5-HIAA)

Slight increase in urine 5-HIAA concentrations120 a

Tests for urinary catecholamines and vanillylmandelic acid (VMA)

Slight increase in urine concentrations of VMA and catecholamines; possible false-positive results on tests for pheochromocytoma and neuroblastoma120 a

Avoid caffeine intake during test120

Theophylline

Interconversion between caffeine and theophylline reported in premature neonates115

Concurrent use not recommended in premature neonates115

Monitor serum caffeine concentrations prior to initiating caffeine therapy in neonates previously treated with theophylline115

Caffeine; Caffeine and Sodium Benzoate Injection; Caffeine Citrate Pharmacokinetics

Absorption

Caffeine and caffeine citrate are well absorbed following oral administration.a

Absorption following oral administration may be more rapid than that following IM injection of caffeine and sodium benzoate.a

Absolute bioavailability of orally administered caffeine in preterm neonates not fully determined.115

Onset

Following oral administration of 100 mg of caffeine (as coffee), peak plasma concentrations reached after 50–75 minutes.a

Following oral administration of 10 mg/kg of caffeine to preterm neonates, mean time to peak plasma concentration was 0.5–2 hours.115

Food

Feeding formula does not affect time to peak plasma concentration in infants.115

Plasma Concentrations

Serum caffeine concentrations >50 mcg/mL associated with serious toxicity.115

Distribution

Extent

Rapidly distributed into body tissues; readily crosses the blood-brain barrier.115 120

Concentrations in the CSF of preterm neonates approximates plasma concentration.115

Readily crosses the placenta and is distributed into milk.115 a

Mean volume of distribution in infants is slightly larger than that in adults (0.6 L/kg).115

Plasma Protein Binding

Approximately 17–36% in adults; data not available for neonates or infants.115 120

Elimination

Metabolism

Metabolized in the liver, principally via CYP1A2, to 1-methyluric acid, 1-methylxanthine, and 7-methylxanthine.115 120 May induce own metabolism; clinical importance of autoinduction is unknown.120 a

Neonates: Limited hepatic metabolism due to immature hepatic enzyme systems.115 Interconversion between caffeine and theophylline reported.115 (See Specific Drugs and Laboratory Tests under Interactions.)

Metabolism of caffeine by 9 months of age approximates that seen in adults.115

Elimination Route

Adults: Excreted principally in urine as metabolites (<1% recovered in urine as unchanged drug).120 a

Neonates: Excreted principally in urine as unchanged drug (approximately 86%).115 Mean fraction excreted unchanged in urine in infants is inversely related to gestational/postconceptional age;115 by 9 months of age, fraction excreted as unchanged drug approximates that seen in adults.115

Half-life

Adults: 3–5 hours.120 a

Neonates: Approximately 3–4 days.115 Elimination slower in young infants than in adults because of immature hepatic and/or renal function.115 Mean half-life in infants is inversely related to gestational/postconceptional age;115 by 9 months of age, half-life approximates that seen in adults.115

Special Populations

Pharmacokinetics in neonates with renal or hepatic insufficiency not evaluated.115

Stability

Storage

Oral

Tablets

Room temperature.117 118

Solution

15–30°C.115 Caregivers should store vials of the oral solution in the child-resistant container provided by the manufacturer.115

Parenteral

Caffeine Citrate Injection

15–30°C.115

Caffeine and Sodium Benzoate Injection

15–30°C.120

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility (for Caffeine Citrate)

Compatible

Amino acids 8.5%

Dextrose 5 or 50% in water

Fat emulsion 20%, IV

Drug Compatibility (for Caffeine Citrate)
Admixture Compatibility

Compatible

Calcium gluconate

Dopamine HCl

Fentanyl citrate

Heparin sodium

Actions

  • Competitively inhibits phosphodiesterase, the enzyme that degrades cyclic 3′,5′-adenosine monophosphate (AMP), increasing levels of intracellular cyclic AMP.120 a

  • Stimulates all levels of the CNS.120 a Stimulates the cerebral cortex and produces a more rapid and clearer thought flow, wakefulness or arousal in fatigued patients; also improves psychomotor coordination.a

  • Stimulates medullary vagal, vasomotor, and respiratory centers in slightly larger doses, promoting bradycardia, vasoconstriction, and increased respiratory rate.120 a

  • Produces a positive inotropic effect on the myocardium and a positive chronotropic effect at the SA node, causing transient increases in heart rate, force of contraction, cardiac output, and heart work.115 120 a

  • Constricts cerebral vasculature; also directly dilates peripheral blood vessels, decreasing peripheral vascular resistance.120 a Overall effect on heart rate and BP depends on whether CNS or peripheral effects predominate.120 a

  • Stimulates voluntary skeletal muscle, increasing the force of contraction and decreasing muscular fatigue.120 a

  • Stimulates gastric acid secretion from parietal cells.120 a

  • Increases renal blood flow and GFR; decreases proximal tubular reabsorption of sodium and water, resulting in mild diuresis.120 a

Advice to Patients

  • Risk of adverse CNS and cardiac effects if excessive doses are taken.115

  • Risk of necrotizing enterocolitis in premature infants; importance of informing clinician if signs of GI intolerance (e.g., abdominal distention, vomiting, bloody stools) or lethargy develops.115 a

  • Importance of informing clinician if premature infant continues to experience apneic events despite caffeine therapy; do not increase dosage without advice of clinician.115 a

  • Importance of adhering to directions for use of caffeine citrate oral solution, including directions for storage, measurement and withdrawal of the prescribed dose, and administration.115 Provide copy of manufacturer’s patient information.115

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular disease).115

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.a

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Caffeine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

100 mg*

200 mg*

Tablets, film-coated

200 mg*

No Doz Maximum Strength Caplets (with povidone and propylene glycol)

Novartis

Vivarin

GlaxoSmithKline

Also commercially available in combination with analgesics, antacids, antihistamines, antipyretics, antitussives, belladonna alkaloids, diuretics, ergotamine tartrate, expectorants, nasal decongestants, skeletal muscle relaxants, sympathomimetics, and vitamins.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Caffeine and Sodium Benzoate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

250 mg/mL (equivalent to caffeine anhydrous 125 mg/mL and sodium benzoate 125 mg/mL)*

Caffeine and Sodium Benzoate Injection

American Regent, Bedford

Caffeine Citrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

20 mg/mL (equivalent to 10 mg/mL caffeine anhydrous)

Cafcit

MeadJohnson

Caffeine Citrate Oral Solution

Paddock, PharmaForce

Parenteral

Injection

20 mg/mL (equivalent to 10 mg/mL caffeine anhydrous)

Cafcit

MeadJohnson

Caffeine Citrate Injection

American Regent, Paddock, PharmaForce

Bulk

Powder

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Butalbital-APAP-Caffeine 50-325-40MG Capsules (QUALITEST): 100/$59.53 or 300/$163.69

Butalbital-APAP-Caffeine 50-325-40MG Tablets (WEST-WARD): 30/$15.99 or 90/$41.97

Butalbital-APAP-Caffeine 50-500-40MG Tablets (WEST-WARD): 30/$18.99 or 90/$46.99

Butalbital-ASA-Caffeine 50-325-40MG Capsules (LANNETT): 30/$32.99 or 90/$95.97

Butalbital-Aspirin-Caffeine 50-325-40MG Tablets (WEST-WARD): 30/$19.99 or 90/$29.97

Cafergot 1-100MG Tablets (SANDOZ): 30/$105.99 or 90/$309.96

Dolgic Plus 50-750-40MG Tablets (SHIONOGI PHARMA): 100/$380.13 or 300/$1,069.19

Esgic 50-325-40MG Tablets (FOREST): 30/$69.99 or 90/$205.97

Esgic-Plus 50-500-40MG Tablets (FOREST): 30/$61.72 or 90/$175.24

Fioricet 50-325-40MG Tablets (WATSON LABS): 30/$72.23 or 90/$188.07

Fioricet/Codeine 50-325-40-30MG Capsules (WATSON LABS): 30/$132.78 or 90/$396.07

Fiorinal 50-325-40MG Capsules (WATSON LABS): 100/$228.94 or 200/$440.71

Zebutal 50-500-40MG Capsules (SHIONOGI PHARMA): 30/$67.59 or 90/$181.95

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions November 20, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

100. Council on Scientific Affairs. Caffeine labeling. JAMA. 1984; 252:803-6. [IDIS 188218] [PubMed 6748182]

101. Robertson D, Wade D, Workman R et al. Tolerance to the humoral and hemodynamic effects of caffeine in man. J Clin Invest. 1981; 67:1111-7. [IDIS 142876] [PubMed 7009653]

102. Robertson D, Hollister AS, Kincaid D et al. Caffeine and hypertension. Am J Med. 1984; 77:54-60. [IDIS 187520] [PubMed 6377891]

103. Beach CA, Mays DC, Guiler RC et al. Inhibition of elimination of caffeine by disulfiram in normal subjects and recovering alcoholics. Clin Pharmacol Ther. 1986; 39:265-70. [IDIS 213983] [PubMed 3948467]

104. Mangini RJ, ed. Drug interaction facts. St. Louis: JB Lippincott Co; 1986(Jul):123a.

105. Aranda JV, Cook CE, Gorman W. Pharmacokinetic profile of caffeine in the premature newborn infant with apnea. J Pediatr. 1979; 94:663-8. [IDIS 103742] [PubMed 430317]

106. Murat I, Moriette G, Blin MC et al. The efficacy of caffeine in the treatment of recurrent idiopathic apnea in premature infants. J Pediatr. 1981; 99:984-9. [IDIS 143136] [PubMed 7310594]

107. Brouard C, Moriette G, Murat I et al. Comparative efficacy of theophylline and caffeine in the treatment of idiopathic apnea in premature infants. Am J Dis Child. 1985; 139:698-700. [IDIS 201254] [PubMed 4014092]

108. Le Guennec JC, Billon B, Paré C. Maturational changes of caffeine concentrations and disposition in infancy during maintenance therapy for apnea of prematurity: influence of gestational age, hepatic disease, and breast-feeding. Pediatrics. 1985; 76:834-40. [IDIS 209484] [PubMed 4058995]

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111. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414), to June 28, 1996. Rockville, MD; 1996 Jul.

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114. Food and Drug Administration. Dietary supplements containing ephedrine alkaloids. Proposed rule. [21 FR Part 111] Fed Regist. 1997; 62:30678-724.

115. Mead Johnson and Co. Cafcit (caffeine citrate) injection and oral solution prescribing information. Evansville, IN: 2003 May.

116. Matchar DB, Young WB, Rosenberg JH et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management of acute attacks. St. Paul, MN; 2001. From the American Academy of Neurology web site.

117. GlaxoSmithKline Consumer Healthcare. Vivarin (caffeine) tablets patient information. Pittsburgh, PA; 2003. From website. Accessed 2007 May 17.

118. Novartis Consumer Health, Inc. Maximum Strength NoDoz (caffeine) tablets patient information. Parsippany, NJ; 2007.

119. Caffeine. In: Briggs GG, Freeman RK, Yaffe SJ, eds. Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. 7th ed. Philadelphia: Lippincott, Williams & Wilkins; 2005:201-7.

120. American Regent Laboratories, Inc. Caffeine and sodium benzoate injection prescribing information. Shirley, NY: 1998 Nov.

121. Watson Laboratories, Inc. Butalbital, acetaminophen, caffeine, and codeine phosphate capsules prescribing information. Corona, CA; 2007 Jan.

a. AHFS drug information 2007. McEvoy GK, ed. Caffeine. Bethesda, MD: American Society of Health-System Pharmacists; 2007:2478-2481.

b. Forest Pharmaceuticals, Inc. Esgic-Plus (butalbital, acetaminophen, and caffeine) capsules prescribing information. St. Louis, MO; 2002 Aug.

c. Mikart, Inc. Butalbital, acetaminophen, and caffeine tablets prescribing information. Atlanta, GA; 2002 Aug.

d. Novartis Consumer Health, Inc. Excedrin Tension Headache (acetaminophen and caffeine) tablets patient information. Parsippany, NJ; 2007.

e. Mikart, Inc. Ergotamine tartrate and caffeine tablets prescribing information. Atlanta, GA; 2005 Feb.

f. Actavis Elizabeth LLC. Butalbital, aspirin, and caffeine tablets prescribing information. Elizabeth, NJ; 2006 Jan.

g. Novartis Consumer Health, Inc. Excedrin Migraine (acetaminophen, aspirin, and caffeine) tablets patient information. Parsippany, NJ; 2007.

h. GlaxoSmithKline. Original Formula BC (aspirin, caffeine, and salicylamide) powder patient information. Pittsburgh, PA; 2007.

i. Mikart, Inc. Butalbital, acetaminophen, and caffeine tablets prescribing information. Atlanta, GA; 2002 Aug.

j. Watson Laboratories, Inc. Butalbital, aspirin, and caffeine capsules prescribing information. Corona, CA; 2006 Mar.

k. Watson Laboratories, Inc. Butalbital, aspirin, caffeine, and codeine phosphate capsules prescribing information. Corona, CA; 2007 Jan.

l. Novartis Consumer Health, Inc. Extra Strength Excedrin (acetaminophen, aspirin, and caffeine) tablets patient information. Parsippany, NJ; 2007.

m. Novartis Pharmaceuticals Corporation. Cafergot (ergotamine tartrate and caffeine) suppositories prescribing information. East Hanover, NJ. Undated. Available from website. Accessed 2007 Dec 5.

n. AHFS drug information 2007. McEvoy GK, ed. Ergotamine tartrate. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1359-61.

o. Insight Pharmaceuticals. Anacin Max Strength (aspirin and caffeine) tablets patient information. Langhorne, PA. Undated. Available from website. Accessed 2007 Dec 12.

p. Mikart, Inc. Butalbital, acetaminophen, and caffeine capsules prescribing information. Atlanta, GA; 2003 Feb.

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