ranitidine ahfs.docx

Ranitidine (Systemic)Introductory InformationHistamine H2 receptor antagonist.1

Class: 56:28.12 Histamine H2-Antagonists; ga301 (VA primary)

Brands*: Zantac®

*also available genericallyGeneric Name: Ranitidine HydrochlorideCAS Number: 66357-59-3Chemical Name: N-[2-[[[-5-[(Dimethylamino)methyl]-2-furanyl]methyl]thio]ethyl]-N´-methyl-

2-nitro-1,1-ethenediamine hydrochlorideInvestigational Drug Number: AH 19065

UsesDuodenal UlcerShort-term treatment of active duodenal ulcer (endoscopically or radiographically confirmed).1, 2

Maintenance of healing and reduction in recurrence of duodenal ulcer.1, 4, 120, 121, 136, 178

Pathologic GI Hypersecretory ConditionsLong-term treatment of Zollinger-Ellison syndrome, systemic mastocytosis, postoperative hypersecretion, "short-gut" syndrome.1, 48, 49, 100, 117

Gastric UlcerShort-term treatment of active benign gastric ulcer.1, 4, 44, 45, 80, 84, 119, 140

Maintenance of healing and reduction in recurrence of gastric ulcer.1

Gastroesophageal Reflux (GERD)Treatment of GERD to achieve acid suppression, control symptoms, and prevent complications.1, 4, 6, 86, 124, 126, 128, 132, 134, 135, 136, 137, 138, 179, 280

Treatment of erosive esophagitis (endoscopically diagnosed) in patients with GERD.1

Maintain healing and decrease recurrence of erosive esophagitis.1

Self-medication as initial therapy for less severe symptomatic GERD .280

Short-term self-medication for treatment of heartburn (pyrosis) symptoms associated with acid indigestion and sour stomach in adults and adolescents ≥12 years of age.287

Short-term self-medication for prevention of heartburn symptoms associated with acid indigestion and sour stomach brought on by ingestion of certain foods and beverages in adults and children ≥12 years of age.287

Increasing Gastric pH in Neonates Undergoing Extracorporeal Membrane Oxygenation (ECMO)May be useful for increasing gastric pH in neonates (<1 month of age) at risk for GI

hemorrhage during ECMO .b, c

Dosage and AdministrationAdministrationAdministered orally.1, 118

Administered by IM or slow IV injection, or by intermittent or continuous IV infusion in hospitalized patients with pathologic GI hypersecretory conditions or intractable duodenal ulcer, or when oral therapy is not feasible.117, 172

Administered by slow IV injection or intermittent IV infusion in children 1 month to 16 years of age for the treatment of duodenal ulcer.117, 172, 286

Administered by slow IV injection or intermittent or continuous IV infusion to decrease gastric pH in neonates <1 month of age receiving ECMO.117, 172, 286

Oral AdministrationAdminister antacids concomitantly as necessary for relief of pain.1

Dissolve each dose to be administered as 150-mg effervescent tablets in 180-240 mL (6-8 ounces) of water as directed prior to ingestion.1 Effervescent tablets should not be chewed, swallowed whole, or dissolved on the tongue.1

Dissolve each 25-mg effervescent tablet in ≥5 mL of water prior to administration.1 Allow tablet to completely dissolve before administering to the infant or child.1 May use a calibrated dropper or oral syringe to administer resultant solution in infants.1

Administer tablets for self-medication with a glass of water.287, 288

IM InjectionMay be administered undiluted.117

Intermittent Direct IV InjectionDilutionDilute 50-mg dose to a concentration no greater than 2.5 mg/mL (i.e., total of 20 mL) with 0.9% sodium chloride injection or other compatible IV solution before direct IV injection.117, 172

Rate of AdministrationInject the 20-mL diluted solution (containing 50 mg/20 mL) at rate ≤4 mL/minute (i.e., over at least 5 minutes).117, 172

Intermittent IV InfusionDilutionDilute 50-mg dose to a concentration ≤0.5 mg/mL (i.e., 100 mL total) in 5% dextrose injection or other compatible IV solution.117, 172

No additional dilution required for commercially available infusion solution (50 mg ranitidine in 50 mL of 0.45% sodium chloride).117

Rate of AdministrationInfuse 50 mg/100 mL dilution at ≤5-7 mL/minute (i.e., over 15-20 minutes).117, 172

Infuse commercially available infusion solution (50 mg in 50 mL of 0.45% sodium chloride) over 15-20 minutes.117

Continuous IV InfusionDilutionDilute 150 mg in 250 mL of 5% dextrose injection or other compatible IV solution.91, 117, 172

Dilute to concentration ≤2.5 mg/mL in 5% dextrose injection or other compatible IV solution for Zollinger-Ellison syndrome or other pathologic GI hypersecretory conditions.91, 117, 172

Rate of AdministrationInfuse 150 mg/250 mL dilution at 6.25 mg/hour over 24 hours.91, 117, 172

Infuse dilution for Zollinger-Ellison syndrome or other pathologic GI hypersecretory conditions at initial rate of 1 mg/kg per hour; adjust subsequent rate to individual requirements.91, 117, 172

DosageAvailable as ranitidine hydrochloride; dosage expressed in terms of ranitidine.1, 117, 172

Pediatric PatientsDuodenal Ulcer>Treatment of Active Duodenal UlcerOral: Children 1 month to 16 years of age: 2-4 mg/kg twice daily.1

Maximum 300 mg daily.1

IV: Children 1 month to 16 years of age: 2-4 mg/kg daily given as divided doses every 6-8 hours.117, 172

Maximum 50 mg every 6-8 hours.117, 172

>Maintenance of Healing of Duodenal UlcerOral: Children 1 month to 16 years of age: 2-4 mg/kg once daily.1


Gastric Ulcer>TreatmentOral: Children 1 month to 16 years of age: 2-4 mg/kg twice daily.1


>Maintenance of Healing of Gastric UlcerOral: Children 1 month to 16 years of age: 2-4 mg/kg once daily.1


Gastroesophageal Reflux>Treatment of GERDOral: Children 1 month to 16 years of age: 5-10 mg/kg daily, usually administered as 2 equally divided doses.1

>Treatment of Erosive EsophagitisOral: Children 1 month to 16 years of age: 5-10 mg/kg daily, usually administered as 2 equally divided doses.1

>Self-medication for HeartburnOral: Children ≥12 years of age: 75 or 150 mg once or twice daily.287, 288

Maximum 150 mg (as 75-mg tablets) or 300 mg (as 150-mg tablets) in 24 hours; maximum 2 weeks of continuous use as self-medication.287, 288

>Self-medication for Prevention of HeartburnOral: Children ≥12 years of age: 75 or 150 mg once or twice daily; administer 30-60 minutes before ingestion of causative food or beverage.287, 288


Increase Gastric pH in Neonates Undergoing ECMO>IVNeonates (<1 month of age) at risk for GI hemorrhage: Consider 2 mg/kg every 12-24 hours (or as continuous infusion).117, 172

A dose of 2 mg/kg usually is sufficient to increase gastric pH to >4 for at least 15 hours.117, 172

AdultsGeneral Parenteral Dosage>Hospitalized Patients with Pathologic Hypersecretory Conditions or Intractable Duodenal Ulcer, or Short-term Use When Oral Therapy is not FeasibleIM: 50 mg every 6-8 hours.117, 172

Increase dosage when necessary by administering 50 mg more frequently.117, 172

Maximum 400 mg daily.117, 172

Intermittent Direct IV Injection: 50 mg every 6-8 hours.117, 172



Intermittent IV Infusion: 50 mg every 6-8 hours.117, 172



Continuous IV Infusion: 150 mg/24 hours (6.25 mg/hour).117, 172 See Pathologic GI Hypersecretory Conditions under Dosage.Duodenal Ulcer

>Treatment of Active Duodenal UlcerOral: Usual dosage: 150 mg twice daily.1, 118

Alternative: 300 mg daily after evening meal or at bedtime for optimum convenience and compliance.1, 123, 125, 139, 140

100 mg twice daily reported to be as effective in healing ulcers as 150 mg twice daily.1

Healing usually within 4 weeks; may occur in 2 weeks.124

Additional 4 weeks of therapy may be beneficial.1, 91, 124

>Maintenance of Healing of Duodenal UlcerOral: 150 mg daily at bedtime.1, 136, 178

Gastric UlcerOral: 150 mg twice daily.1, 118

Healing usually within 6 weeks.1

>Maintenance of Gastric Ulcer HealingOral: 150 mg daily at bedtime.1

Gastroesophageal Reflux>Treatment of GERDOral: 150 mg twice daily.1, 136, 179

>Treatment of Erosive EsophagitisOral: 150 mg 4 times daily.1

>Maintenance of Healing of Erosive EsophagitisOral: 150 mg twice daily.1

>Self-medication for HeartburnOral: 75 mg or 150 mg once or twice daily.287, 288


>Self-medication for Prevention of HeartburnOral: 75 or 150 mg once or twice daily; administer 30-60 minutes before ingestion of causative food or beverage.287, 288


Pathologic GI Hypersecretory ConditionsOral: 150 mg twice daily; may administer more frequently, if needed.1, 100

Adjust dosage according to patient response.1, 100

Dosages up to 6 g daily have been used for severe disease.1, 100

Continue as long as necessary.1, 98, 100

>Continuous IV InfusionInitiate at 1 mg/kg per hour.91, 117, 172

Titrate upward in 0.5 mg/kg per hour increments and redetermine gastric acid secretion if symptoms occur or gastric acid output is >10 mEq per hour after 4 hours.117, 172

Dosages up to 2.5 mg/kg per hour and infusion rates up to 220 mg/hour have been used.117, 172

Prescribing LimitsPediatric PatientsGastroesophageal Reflux>Self-medication for HeartburnOral: Adolescents ≥12 years of age: Maximum 150 mg (as 75-mg tablets) or 300 mg (as 150-mg tablets) in 24 hours; maximum 2 weeks of continuous use as self-medication.287, 288

>Self-medication for Prevention of HeartburnOral: Adolescents ≥12 years of age: Maximum 150 mg (as 75-mg tablets) or 300 mg (as 150-mg tablets) in 24 hours; maximum 2 weeks of continuous use as self-medication.287, 288

Duodenal Ulcer

>Treatment of Active Duodenal UlcerOral: Children 1 month to 16 years of age: Maximum 300 mg daily.1

IV: Children 1 month to 16 years of age: Maximum 50 mg every 6-8 hours.117, 172

>Maintenance of Healing of Duodenal Ulcer:Oral: Children 1 month to 16 years of age: Maximum 150 mg daily.1

Gastric Ulcer>Treatment of Gastric UlcerOral: Children 1 month to 16 years of age: Maximum 300 mg daily.1

>Maintenance of Healing of Gastric UlcerOral: Children 1 month to 16 years of age: Maximum 150 mg daily.1

AdultsGeneral Parenteral Dosage>Hospitalized Patients with Pathologic Hypersecretory Conditions or Intractable Duodenal Ulcer, or Short-term Use When Oral Therapy is not FeasibleIM: Maximum 400 mg daily.117, 172

Maximum 50 mg per dose.117, 172

Intermittent Direct IV: Maximum 400 mg daily.117, 172


Maximum concentration 2.5 mg/mL (50 mg/20 mL).117, 172

Maximum injection rate: 4 mL/minute (i.e., over 5 minutes).117, 172

Intermittent IV Infusion: Maximum 400 mg daily.117, 172


Maximum concentration 0.5 mg/mL (50 mg/100 mL).117, 172

Maximum infusion rate: 5-7 mL/minute (100 mL over 15-20 minutes).117, 172

Commercially available infusion solution (50 mg in 50 mL of 0.45% sodium chloride): over 15-20 minutes.117

Gastroesophageal Reflux>Self-Medication for HeartburnOral: Maximum 150 mg (as 75-mg tablets) or 300 mg (as 150-mg tablets) in 24 hours; maximum 2 weeks of continuous use as self-medication.287, 288

>Self-medication for Prevention of HeartburnOral: Maximum 150 mg (as 75-mg tablets) or 300 mg (as 150-mg tablets) in 24 hours; maximum 2 weeks of continuous use as self-medication.287, 288

Duodenal Ulcer>Treatment of Active Duodenal UlcerOral: Safety and efficacy for >8 weeks have not been established.1

Gastric Ulcer>Treatment of Active Benign Gastric UlcerOral: Safety and efficacy for >6 weeks have not been established.1

Pathologic GI Hypersecretory Conditions>Continuous IV InfusionZollinger-Ellison Syndrome: Maximum concentration 2.5 mg/mL.91, 117, 172

Up to 2.5 mg/kg per hour or 220 mg/hour has been used.117, 172

Special PopulationsRenal ImpairmentClcr <50 mL/minuteOral: 150 mg once every 24 hours.1 If necessary, may cautiously increase dosage frequency to every 12 hours or more frequently.1

>IM

50 mg every 18-24 hours.117, 172 If necessary, may cautiously increase dosage frequency to every 12 hours or more frequently.117, 172

>Intermittent Direct IV50 mg every 18-24 hours.117, 172 If necessary, may cautiously increase dosage frequency to every 12 hours or more frequently.117, 172

>Intermittent IV Infusion50 mg every 18-24 hours.117, 172 If necessary, may cautiously increase dosage frequency to every 12 hours or more frequently.117, 172

>Continuous IV InfusionNot evaluated.117, 172

HemodialysisDecreases blood levels; administer at the end of hemodialysis.1, 4, 117, 124, 172

Geriatric PatientsCareful dosage selection recommended because of possible age-related decrease in renal function.a, b, c (See Geriatric Use under Cautions.)CautionsContraindications

• Known hypersensitivity to ranitidine or any ingredient in the formulation.1, 91, 124

• Do not use for self-medication if swallowing is difficult.287

• Do not use for self-medication with other drugs that decrease gastric acid secretion.287, 288

• Do not use for self-medication if difficulty or pain occurs when swallowing food, if experiencing vomiting with blood, or if passing bloody or blackened stools.288 Instead, consult a clinician since such manifestations may indicate presence of a serious condition requiring alternative treatment.288

Warnings/PrecautionsGeneral PrecautionsGastric MalignancyResponse to ranitidine does not preclude presence of gastric malignancy.1

Hepatic EffectsDiscontinue immediately in patients with hepatitis.1, 117, 124, 172 Occasional hepatotoxicity, rarely, hepatic failure and death have been reported.1, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, b, c

Increased serum ALT concentrations have occurred with ≥5 days of histamine H2-receptor antagonist therapy at higher than recommended IV dosages.117 Monitor serum ALT from day 5 to end of therapy when ranitidine is administered IV at dosages ≥400 mg daily for ≥5 days.117

Cardiovascular EffectsRapid IV administration: associated rarely with bradycardia.117, 172 Avoid rapid administration.117, 172

Acute Intermittent PorphyriaRanitidine may precipitate acute porphyric attacks.1, 117, 172 Avoid use in such patients.1, 117, 172

Respiratory EffectsAdministration of H2-receptor antagonists has been associated with an increased risk for developing certain infections (e.g., community-acquired pneumonia).283, 284

PhenylketonuriaZantac® EFFERdose® tablets for solution contain aspartame (NutraSweet®), which is metabolized in the GI tract to provide 2.81 or 16.84 mg of phenylalanine per 25- or 150-mg tablet, respectively.1

Specific PopulationsPregnancy

Category B.1, 117, 172

Self-medication in pregnant women: Consult clinician before using.287, 288

LactationDistributed into milk; use with caution.1, 124

Self-medication in nursing women: Consult clinician before using.287, 288

Pediatric UseOral: Safety and efficacy for erosive esophagitis healing maintenance or pathologic hypersecretory condition treatment not established in pediatric patients.1

Oral: Safety and efficacy not established in neonates (< 1 month of age).1

Oral: Safety and efficacy established in infants, children, and adolescents 1 month to 16 years of age for duodenal and gastric ulcer treatment and healing maintenance, GERD treatment, and erosive esophagitis treatment.1

Parenteral: Safety and efficacy not established in pediatric patients for treatment of pathologic hypersecretory conditions.117, 172

Parenteral: Safety and efficacy established in infants, children, and adolescents 1 month to 16 years of age for duodenal ulcer treatment.117, 172

Parenteral (IV) use in neonates (< 1 month of age) receiving extracorporeal membrane oxygenation (ECMO): Limited data in neonates suggest that ranitidine may be safe and useful to increase gastric pH in infants at risk of GI hemorrhage.117, 172

Geriatric UseNo substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1, 117, 172

Use with caution due to greater frequency of decreased renal function observed in the elderly.1, 117, 172

Select dosage with caution; monitoring renal function may be useful.1, 117, 172

Hepatic ImpairmentUse with caution.1 (See Hepatic Effects under Cautions.)Renal ImpairmentUse with caution; dosage adjustment necessary based on degree of renal impairment.1 (See Renal Impairment under Dosage and Administration.)Common Adverse EffectsOral or parenteral therapy: Headache, sometimes severe.1, 2, 4, 5, 81, 88, 97, 117, 124, 147, 172

IM therapy: Transient pain at injection site.117, 172

IV therapy: Transient local burning or itching.117, 172

InteractionsBinds weakly to hepatic CYP isoenzyme system in vitro.1, 117, 172

Affinity for CYP isoenzyme system is about 10% that of cimetidine; inhibition of CYP isoenzyme system is 2.4 times less than cimetidine.54, 101

Does not inhibit CYP isoenzymes at recommended dosages.1, 117, 172

May minimally inhibit hepatic metabolism of some drugs,1, 2, 4, 5, 74, 101, 105, 112 or affect bioavailability by another mechanism (e.g., pH-dependent absorption, altered volume of distribution).1, 117, 172

Specific Drugs, Foods, and Laboratory TestsDrug, Food, or Test Interaction Comments

AcetaminophenDose-dependent inhibition of acetaminophen metabolism in vitro96, 108

Alcohol Moderate alcohol consumption by individuals receiving concurrent ranitidine unlikely to result in clinically

Controversy about psychomotor impairment potential;238, 239, 240, 241, 242, 243, 248 observe usual

important alterations of blood alcohol concentration and/or alcohol metabolism77, 238, 239, 240, 241, 244, 247

precautions about alcohol intake and hazardous tasks requiring mental alertness or physical coordination239, 240, 243

Antacids

Low doses (10-15 mEq HCl neutralizing capacity/10 mL) do not appear to decrease absorption or plasma concentrations of ranitidine1, 2, 4, 5, 6, 38, 76 Higher doses (e.g., 150 mEq HCl neutralizing capacity/30 mL) decrease absorption by 33%, decrease plasma concentrations, and AUC76

AtenololAtenolol pharmacokinetics apparently not affected72

Benzodiazepines (e.g., diazepam, lorazepam, midazolam, triazolam)

Diazepam AUC, mean half-life not substantially affected2

Lorazepam elimination half-life, volume of distribution, clearance unaffected106

Midazolam oral bioavailability may be increased by ranitidinef

Triazolam oral bioavailability may be increased by elevated gastric pH 1, 117, 124, 172 clinical importance unknown1, b, c

Observe carefully for signs of midazolam-induced respiratory and CNS depression; decrease midazolam dosage if requiredf

FoodDoes not appear to decrease absorption or plasma concentrations of ranitidine1, 2, 4, 5, 6, 38, 76

MetoprololIncreased metoprolol AUC, peak serum concentration, elimination half-life72, 73

Multistix®, test for urine protein

False positive1

Use sulfosalicylic acid reagent for urinary protein determinations while using ranitidine1

Nifedipine Nifedipine AUC increased by 30%72

PhenytoinPhenytoin serum concentrations unaffected107

Propantheline

Appears to delay absorption and increases peak serum concentrations of ranitidine; biovailability increased about 23% with concomitant administration2

PropranololPropranolol mean serum concentrations not substantially affected2, 101

Smoking Adversely affects duodenal ulcer healing and decreases ranitidine efficacy;67, 87 number of cigarettes/day apparently does not influence healing

rate67

TheophyllineRanitidine apparently does not alter theophylline clearance71, 105

Vitamin B12

Vitamin B12 malabsorption and deficiency may occur with long-term ranitidine therapy16

WarfarinIncreased or decreased PT reported1, 91, 117, 122, 172

Pharmacokinetic studies: up to 400 mg daily had no effect on warfarin clearance or PT1, 91, 117, 122, 172

PharmacokineticsAbsorptionBioavailabilityRapidly absorbed after oral2, 5, 6, 37, 40 or IM117 administration.Oral bioavailability: About 50%;1, 2, 4, 5, 6, 39, 42, 88, 139 similar in children 3.5-16 years of age.160

Oral: Peak plasma concentration attained within 2-3 hours in adults and geriatric patients and within 1.6-2 hours in children 1 month to 16 years of age.1

IM: about 90-100% absorption.117

Commercially available oral solution, effervescent tablets, and conventional tablets are bioequivalent.1

DurationFollowing oral administration of a single 150-mg dose, substantial inhibition of gastric acid secretion reportedly continues for about 9.5 hours.5

In pediatric patients, oral administration of 6-10 mg/kg daily (in 2 or 3 divided doses), maintained gastric pH throughout the dosing interval.1

Following a single 150-mg oral dose, serum concentrations required to inhibit 50% of stimulated gastric acid secretion are maintained for up to 12 hours.1, 4

IM or IV: Following a 50-mg dose, serum concentrations required to inhibit 50% of stimulated gastric acid secretion are maintained for 6-8 hours.117

FoodFood does not appear to substantially affect absorption or peak plasma concentrations.1, 2, 4, 5, 6, 38

Special PopulationsOral: In geriatric individuals, AUC may be substantially increased.159

In individuals with cirrhosis, oral bioavailability appears to increase to about 70% and peak serum ranitidine concentrations appear to be higher because of reduced first-pass metabolism;2, 6, 42 considered minor, clinically unimportant.1

DistributionExtentWidely distributed throughout body.1, 2, 4, 39, 88, 103, 249

Distributed into CSF following oral administration;4, 5, 33, 158 CSF concentrations in individuals with uninflamed meninges are about 3-5% of concurrent peak serum concentrations.4, 5, 33, 158

Distributed into human milk;1 milk concentrations appear to be 25-100% of concurrent serum concentrations.4

Plasma Protein Binding10-19%.1, 2, 4, 39, 88, 103, 249

Special Populations

In individuals with cirrhosis, minor but clinically unimportant alterations in distribution occur following oral administration.1

EliminationMetabolismExtensive first-pass metabolism after oral administration.1, 2, 4, 5, 6, 39, 42, 88, 103

Metabolized in the liver to ranitidine N-oxide, desmethyl ranitidine, and ranitidine S-oxide.1, 2,

3

Elimination RouteExcreted principally in urine.1, 3, 37, 88

Following oral administration, excretion of unchanged ranitidine in urine is dose-dependent; about 16-36% (unchanged) is excreted in urine within 24 hours.1, 3, 37, 43

Following oral administration, about 4% as ranitidine N-oxide, 1-2% as desmethyl ranitidine, and 1% as ranitidine S-oxide is excreted in urine within 24 hours.1, 3, 4, 5, 249

Most of the urinary excretion occurs within the first 6 hours after administration.4

The remainder of an orally administered dose is eliminated in feces.1, 3

Following IV administration, approximately 70% is excreted in urine as unchanged drug.117

Half-lifeAdults: Averages 1.7-3.2 hours1, 2, 4, 5, 6, 37, 39, 40, 41, 88, 103, 104, 159 and may be positively correlated with age.159

Children 3.5-16 years of age: Averages 1.8-2 hours (range: 1.4-2.9 hours).117, 160, 172

Neonates (<1 month of age): Averages 6.6 hours.117, 172

Special PopulationsIn patients with renal impairment, plasma clearance appears to be decreased94 and elimination half-life prolonged.2, 94

In patients with cirrhosis, minor but clinically unimportant alterations in half-life and reduced clearance occur following oral administration.1, 42

In geriatric individuals, clearance appears to be reduced and half-life prolonged because of decreased renal function; although half-life reported to be 3-4 hours following oral or parenteral administration in geriatric patients, 1, 117, 172 in one clinical study it was about 6 hours following an oral 100-mg dose.42

StabilityStorageOralTablets and Tablets for Self-medicationTablets: 15-30°C in tight, light resistant container.1 Replace cap securely after opening.1

Tablets for self-administration: 20-25°C.287, 288

Tablets, Effervescent for Solution (foil-packaged)2-30°C.1, 157

Solution4-30°C in tight, light resistant container.1, 124, 157

ParenteralInjection4-25°C; may be exposed to temperatures up to 30°C.172

Protect from light.117, 157, 172

Protect from freezing.117, 157

Darkening of undiluted injection does not affect potency.117, 172

Dilutions in most IV solutions: stable for up to 48 hours at room temperature.117, 157, 172

Injection for IV infusion only2-25°C.117, 157 Brief exposure to temperatures up to 40°C does not affect stability.117

Protect from light.117, 157

Protect from freezing.117, 157

CompatibilityFor information on systemic interactions resulting from concomitant use, see Interactions.ParenteralSolution CompatibilityHID

CompatibleAmino acids 8.5%Dextrose 5% in sodium chloride 0.45%Dextrose 5 or 10% in waterFat emulsion 10%, IVSodium chloride 0.9%VariableDextrose 5% in Ringer's injection, lactated. (stable for 48 hours)117

Drug Compatibility>Admixture CompatibilityHID

CompatibleAcetazolamide sodiumAmikacin sulfateAminophyllineChloramphenicol sodium succinateChlorothiazide sodiumCiprofloxacinColistimethate sodiumDexamethasone sodium phosphateDigoxinDobutamine HClDopamine HClDoxycycline hyclateEpinephrine HClErythromycin lactobionateFluconazole with ondansetron HClFlumazenilFurosemideGentamicin sulfateHeparin sodiumIsoproterenol HClLidocaine HClLincomycin HClMeropenemMethylprednisolone sodium succinateMidazolam HClPenicillin G potassiumPenicillin G sodiumPolymyxin B sulfatePotassium chloride

Protamine sulfateQuinidine gluconateSodium nitroprussideTobramycin sulfateVancomycin HClZidovudineIncompatibleAmphotericin BAtracurium besylateCefoxitin sodiumCeftazidimeEthacrynate sodiumPhytonadioneVariableAmpicillin sodiumCefazolin sodiumCefuroxime sodiumClindamycin phosphateNorepinephrine bitartrate

>Y-Site CompatibilityHID

CompatibleAcyclovir sodiumAlcohol 10% in dextrose 5%AldesleukinAllopurinol sodiumAmifostineAminophyllineAmsacrineAtracurium besylateAztreonamBivalirudinBretylium tosylateCefazolin sodiumCefepime HClCefoxitin sodiumCeftazidimeCeftizoxime sodiumCiprofloxacinCisplatinCladribineClarithromycinCyclophosphamideCytarabineDexmedetomidine HCl

Diltiazem HClDobutamine HClDocetaxelDopamine HClDoxapram HClDoxorubicin HClDoxorubicin HCl liposome injectionEnalaprilatEpinephrine HClEsmolol HClEtoposide phosphateFenoldopam mesylateFentanyl citrateFilgrastimFluconazoleFludarabine phosphateFoscarnet sodiumFurosemideGallium nitrateGemcitabine HClGranisetron HClHeparin sodiumHetastarch in lactated electrolyte injection (Hextend)Hydromorphone HClIdarubicin HClLabetalol HClLinezolidLorazepamMelphalan HClMeperidine HClMethotrexate sodiumMidazolam HClMilrinone lactateMorphine sulfateNicardipine HClNitroglycerinNorepinephrine bitartrateOndansetron HClOndansetron HCl with paclitaxelOxaliplatinPaclitaxelPancuronium bromidePemetrexed disodiumPiperacillin sodium-tazobactam sodiumProcainamide HCl

PropofolRemifentanil HClSargramostimTacrolimusTeniposideTheophyllineThiopental sodiumThiotepaVecuronium bromideVinorelbine tartrateWarfarin sodiumZidovudineIncompatibleAmphotericin B cholesteryl sulfate complexLansoprazoleVariableHetastarch in sodium chloride 0.9%

Actions• Inhibits daytime and nocturnal basal gastric acid secretion, stimulated gastric acid secretion.1, 5,

5, 12

• Competitively inhibits histamine at parietal cell H2 receptors.1

Advice to Patients• Importance of patients informing clinician of existing or contemplated concomitant therapy,

including prescription and OTC drugs.1

• Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing patients with phenylketonuria that oral effervescent tablets for solution contain aspartame.1

• When used for self-medication, importance of reading the product labeling and carefully reviewing the warning information provided by the manufacturer.287, 288

• Importance of following dosage instructions, unless otherwise directed by a clinician, when ranitidine is administered for self-medication.287, 288

• Importance of promptly informing clinician of persistent abdominal pain or difficulty swallowing.287, 288

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

PreparationsExcipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.Ranitidine HydrochlorideRoutes Dosage Forms Strengths Brand Names ManufacturerOral Capsules, liquid-

filled150 mg (of ranitidine)*

Ranitidine Hydrochloride

Sandoz, Teva

Capsules

300 mg (of ranitidine)*

Ranitidine Hydrochloride Capsules

Sandoz, Teva

Solution75 mg (of ranitidine) per 5 mL

Zantac® Syrup (with alcohol 7.5% and parabens)

GlaxoSmithKline

Tablets, film-coated


Ranitidine Hydrochloride Tablets

Ranbaxy, Sandoz, Teva, Watson

Zantac® 75 Pfizer


Zantac® GlaxoSmithKline

Zantac® Maximum Strength 150

GlaxoSmithKline


Zantac® GlaxoSmithKline

Tablets, for solution

25 mg (of ranitidine)Zantac® EFFERdose® (with aspartame and povidone)

GlaxoSmithKline

150 mg (of ranitidine)

Zantac® EFFERdose® (with aspartame and povidone)

GlaxoSmithKline

Parenteral Injection25 mg (of ranitidine) per mL*

Ranitidine Injection (with phenol 0.5%)

Bedford

Zantac® (with phenol 0.5%)

GlaxoSmithKline

Injection, for preparation of IV admixtures

25 mg (of ranitidine) per mL (1 g) pharmacy bulk package

Zantac® (with phenol 0.5%)

GlaxoSmithKline

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) nameRanitidine Hydrochloride in Sodium Chloride

RoutesDosage Forms

Strengths Brand Names Manufacturer

Parenteral Injection1 mg (of ranitidine) per mL (50 mg) in 0.45% Sodium Chloride

Zantac® Premixed (in flexible plastic container; preservative-free)

GlaxoSmithKline

Comparative PricingThis pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.Ranitidine HCl 15MG/ML Syrup (ACTAVIS MID ATLANTIC): 30/$29.99 or 90/$62.97Ranitidine HCl 150MG Capsules (PAR): 60/$50.99 or 90/$70.97Ranitidine HCl 150MG Tablets (AMNEAL PHARMACEUTICALS): 90/$17.99 or 180/$25.97

Ranitidine HCl 300MG Capsules (SANDOZ): 30/$30.99 or 90/$80Ranitidine HCl 300MG Tablets (AMNEAL PHARMACEUTICALS): 30/$14.99 or 90/$24.84Zantac 15MG/ML Syrup (GLAXO SMITH KLINE): 300/$224.99 or 900/$656.97Zantac 150MG Tablets (GLAXO SMITH KLINE): 60/$248.99 or 180/$714.99Zantac 300MG Tablets (GLAXO SMITH KLINE): 30/$240.99 or 90/$684.94Zantac 75 75MG Tablets (J & J HEALTHCARE/CONSUMER): 30/$17.99 or 60/$26.98Zantac EFFERdose 25MG Effervescent Tablets (GLAXO SMITH KLINE): 60/$241 or 180/$705.95

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

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