Zantac

Generic Name: Ranitidine Hydrochloride
Class: Histamine H2-Antagonists
VA Class: GA301
Chemical Name: N - [2 - [[[ - 5 - [(Dimethylamino)methyl] - 2 - furanyl]methyl]thio]ethyl] - N′ - methyl - 2 - nitro - 1,1 - ethenediamine hydrochloride
CAS Number: 66357-59-3

Introduction

Histamine H₂ receptor antagonist.¹

Uses for Zantac

Duodenal Ulcer

Short-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 Conditions

Long-term treatment of Zollinger-Ellison syndrome, systemic mastocytosis, postoperative hypersecretion, “short-gut” syndrome.^{1 48 49 100 117}

Gastric Ulcer

Short-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}

Zantac Dosage and Administration

Administration

Administered 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 Administration

Administer 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 Injection

May be administered undiluted.¹¹⁷

Intermittent Direct IV Injection

Dilution

Dilute 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 Administration

Inject 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 Infusion

Dilution

Dilute 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 Administration

Infuse 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 Infusion

Dilution

Dilute 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 Administration

Infuse 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}

Dosage

Available as ranitidine hydrochloride; dosage expressed in terms of ranitidine.^{1 117 172}

Pediatric Patients

Duodenal Ulcer

Treatment of Active Duodenal Ulcer

Oral

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 Ulcer

Oral

Children 1 month to 16 years of age: 2–4 mg/kg once daily.¹

Maximum 150 mg daily.¹

Gastric Ulcer

Treatment

Oral

Children 1 month to 16 years of age: 2–4 mg/kg twice daily.¹

Maximum 300 mg daily.¹

Maintenance of Healing of Gastric Ulcer

Oral

Children 1 month to 16 years of age: 2–4 mg/kg once daily.¹

Maximum 150 mg daily.¹

Gastroesophageal Reflux

Treatment of GERD

Oral

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

Treatment of Erosive Esophagitis

Oral

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

Self-medication for Heartburn

Oral

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 Heartburn

Oral

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}

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}

Increase Gastric pH in Neonates Undergoing ECMO

IV

Neonates (<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}

Adults

General Parenteral Dosage

Hospitalized Patients with Pathologic Hypersecretory Conditions or Intractable Duodenal Ulcer, or Short-term Use When Oral Therapy is not Feasible

IM

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}

Increase dosage when necessary by administering 50 mg more frequently.^{117 172}

Maximum 400 mg daily.^{117 172}

Intermittent IV Infusion

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}

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 Ulcer

Oral

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 Ulcer

Oral

150 mg daily at bedtime.^{1 136 178}

Gastric Ulcer

Oral

150 mg twice daily.^{1 118}

Healing usually within 6 weeks.¹

Maintenance of Gastric Ulcer Healing

Oral

150 mg daily at bedtime.¹

Gastroesophageal Reflux

Treatment of GERD

Oral

150 mg twice daily.^{1 136 179}

Treatment of Erosive Esophagitis

Oral

150 mg 4 times daily.¹

Maintenance of Healing of Erosive Esophagitis

Oral

150 mg twice daily.¹

Self-medication for Heartburn

Oral

75 mg 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 Heartburn

Oral

75 or 150 mg once or twice daily; administer 30–60 minutes before ingestion of causative food or beverage.^{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}

Pathologic GI Hypersecretory Conditions

Oral

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 Infusion

Initiate 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 Limits

Pediatric Patients

Gastroesophageal Reflux

Self-medication for Heartburn

Oral

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 Heartburn

Oral

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 Ulcer

Oral

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 Ulcer

Oral

Children 1 month to 16 years of age: Maximum 300 mg daily.¹

Maintenance of Healing of Gastric Ulcer

Oral

Children 1 month to 16 years of age: Maximum 150 mg daily.¹

Adults

General Parenteral Dosage

Hospitalized Patients with Pathologic Hypersecretory Conditions or Intractable Duodenal Ulcer, or Short-term Use When Oral Therapy is not Feasible

IM

Maximum 400 mg daily.^{117 172}

Maximum 50 mg per dose.^{117 172}

Intermittent Direct IV

Maximum 400 mg daily.^{117 172}

Maximum 50 mg per dose.^{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 50 mg per dose.^{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 Heartburn

Oral

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 Heartburn

Oral

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 Ulcer

Oral

Safety and efficacy for >8 weeks have not been established.¹

Gastric Ulcer

Treatment of Active Benign Gastric Ulcer

Oral

Safety and efficacy for >6 weeks have not been established.¹

Pathologic GI Hypersecretory Conditions

Continuous IV Infusion

Zollinger-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 Populations

Renal Impairment

Cl_cr <50 mL/minute

Oral

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 IV

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 IV Infusion

50 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 Infusion

Not evaluated.^{117 172}

Hemodialysis

Decreases blood levels; administer at the end of hemodialysis.^{1 4 117 124 172}

Geriatric Patients

Careful dosage selection recommended because of possible age-related decrease in renal function.^{a b c} (See Geriatric Use under Cautions.)

Cautions for Zantac

Contraindications

• 
  

  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/Precautions

General Precautions

Gastric Malignancy

Response to ranitidine does not preclude presence of gastric malignancy.¹

Hepatic Effects

Discontinue 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 Effects

Rapid IV administration: associated rarely with bradycardia.^{117 172} Avoid rapid administration.^{117 172}

Acute Intermittent Porphyria

Ranitidine may precipitate acute porphyric attacks.^{1 117 172} Avoid use in such patients.^{1 117 172}

Respiratory Effects

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

Phenylketonuria

Zantac 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 Populations

Pregnancy

Category B.^{1 117 172}

Self-medication in pregnant women: Consult clinician before using.^{287 288}

Lactation

Distributed into milk; use with caution.^{1 124}

Self-medication in nursing women: Consult clinician before using.^{287 288}

Pediatric Use

Oral: 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 Use

No 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 Impairment

Use with caution.¹ (See Hepatic Effects under Cautions.)

Renal Impairment

Use with caution; dosage adjustment necessary based on degree of renal impairment.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Oral 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}

Interactions for Zantac

Binds 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 Tests

Drug, Food, or Test	Interaction	Comments
Acetaminophen	Dose-dependent inhibition of acetaminophen metabolism in vitro96 108
Alcohol	Moderate alcohol consumption by individuals receiving concurrent ranitidine unlikely to result in clinically important alterations of blood alcohol concentration and/or alcohol metabolism77 238 239 240 241 244 247	Controversy about psychomotor impairment potential;238 239 240 241 242 243 248 observe usual 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
Atenolol	Atenolol 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
Food	Does not appear to decrease absorption or plasma concentrations of ranitidine1 2 4 5 6 38 76
Metoprolol	Increased 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
Phenytoin	Phenytoin serum concentrations unaffected107
Propantheline	Appears to delay absorption and increases peak serum concentrations of ranitidine; biovailability increased about 23% with concomitant administration2
Propranolol	Propranolol 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
Theophylline	Ranitidine apparently does not alter theophylline clearance71 105
Vitamin B12	Vitamin B12 malabsorption and deficiency may occur with long-term ranitidine therapy16
Warfarin	Increased 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

Zantac Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed after oral^{2 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

Duration

Following 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

Food

Food does not appear to substantially affect absorption or peak plasma concentrations.^{1 2 4 5 6 38}

Special Populations

Oral: 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

Distribution

Extent

Widely 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 Binding

10–19%.^{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

Elimination

Metabolism

Extensive 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 Route

Excreted 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-life

Adults: Averages 1.7–3.2 hours^{1 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 Populations

In 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

Stability

Storage

Oral

Tablets and Tablets for Self-medication

Tablets: 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}

Solution

4–30°C in tight, light resistant container.^{1 124 157}

Parenteral

Injection

4–25°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 only

2–25°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}

Compatibility

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

Parenteral

Solution Compatibility^HID

Compatible
Amino acids 8.5%
Dextrose 5% in sodium chloride 0.45%
Dextrose 5 or 10% in water
Fat emulsion 10%, IV
Sodium chloride 0.9%
Variable
Dextrose 5% in Ringer’s injection, lactated. (stable for 48 hours)117

Drug Compatibility

Admixture CompatibilityHID

Compatible
Acetazolamide sodium
Amikacin sulfate
Aminophylline
Chloramphenicol sodium succinate
Chlorothiazide sodium
Ciprofloxacin