Ranitidine

Pronunciation: (ran-EYE-tih-DEEN)Class: Histamine H ₂ antagonist

Trade Names:Zantac- Injection 1 mg (as base)/mL- Injection 25 mg (as base)/mL- Syrup 15 mg (as base)/mL- Tablets 150 mg (as base)- Tablets 300 mg (as base)

Trade Names:Zantac 75- Tablets 75 mg (as base)

Trade Names:Zantac 150- Tablets 150 mg (as base)

Trade Names:Zantac EFFERdose- Tablets, effervescent 25 mg (as base)- Tablets, effervescent 150 mg (as base)

Apo-Ranitidine (Canada)CO Ranitidine (Canada)Gen-Ranitidine (Canada)Novo-Ranidine (Canada)Nu-Ranit (Canada)PMS-Ranitidine (Canada)ratio-Ranitidine (Canada)Sandoz Ranitidine (Canada)Zantac Maximum Strength Non-Prescription (Canada)

Pharmacology

Reversibly and competitively blocks histamine at H ₂ receptors, particularly those in gastric parietal cells, leading to inhibition of gastric acid secretion.

Pharmacokinetics

Absorption

Absorbed rapidly (IV and IM), 50% absorbed orally. C _max is 576 ng/mL (IM) or 440 to 545 ng/mL (oral). T _max is 15 min (IM) or 2 to 3 h (oral). Bioavailability is 90% to 100% (IV) or 50% (oral).

Distribution

Protein binding is 15%. Vd is 1.4 L/kg.

Metabolism

Hepatic to N-oxide (main metabolite), s-oxide and desmethyl ranitidine.

Elimination

Excreted in urine (70% unchanged when given IV, 30% unchanged when given orally), main metabolite is N-oxide (less than 4%), also S-oxide (1%), desmethyl ranitidine (1%), remainder found in feces. Renal Cl is 530 mL/min (IM), 410 mL/min (oral). Total Cl is 760 mL/min. Elimination t _½ is 2 to 2.5 h (IM) or 2.5 to 3 h (oral).

Special Populations

Renal Function Impairment

Plasma t _½ , Cl, Vd are all altered in proportion to creatinine Cl.

Hepatic Function Impairment

Alterations in t _½ , distribution, Cl, and bioavailability are minor but clinically insignificant.

Elderly

Plasma t _½ is prolonged and total Cl is lowered.

Indications and Usage

Treatment and maintenance therapy of duodenal ulcer; management of gastroesophageal reflux disease (GERD; including erosive or ulcerative disease); short-term treatment of benign gastric ulcer; treatment of pathologic hypersecretory conditions (Zollinger-Ellison); maintenance therapy for gastric ulcer patients at reduced dosage after healing of acute ulcers; treatment of endoscopically diagnosed erosive esophagitis; maintenance of healing of erosive esophagitis.

OTC

Treatment and prevention of heartburn.

Unlabeled Uses

Prevention of upper GI bleeding; treatment of aspiration pneumonia; stress ulcer; and gastric NSAID damage. Used as a part of a multi-drug regimen to eradicate Helicobacter pylori in the treatment of peptic ulcer; protection against aspiration of acid during anesthesia; prevention of gastroduodenal mucosal damage that may be associated with long-term NSAIDs; control of acute upper GI bleeding; prevention of stress ulcers.

Contraindications

Standard considerations.

Dosage and Administration

Duodenal Ulcer (Active)Adults

PO 150 mg twice daily or 300 mg at bedtime. Maintenance dose is 150 mg at bedtime. IM/IV/Intermittent IV 50 mg every 6 to 8 h.

Treatment of Duodenal and Gastric UlcersChildren 1 mo to 16 yr of age

PO 2 to 4 mg/kg twice daily (max, 300 mg/day).

Maintenance of Healing of Duodenal and Gastric UlcersChildren 1 mo to 16 yr of age

PO 2 to 4 mg/kg daily (max, 150 mg/day).

Acute Benign Gastric Ulcer and GERDAdults

PO 150 mg twice daily. IM/IV/Intermittent IV 50 mg every 6 to 8 h.

Treatment of GERD and Erosive EsophagitisChildren 1 mo to 16 yr of age

PO 5 to 10 mg/kg daily usually given in 2 divided doses.

Pathologic Hypersecretory ConditionsAdults

PO 150 mg twice daily. Individualize.

Erosive EsophagitisAdults

PO 150 mg 4 times daily. IM/IV/Intermittent IV 50 mg every 6 to 8 h. Continuous IV 6.25 mg/h. For patients with Zollinger-Ellison, start infusion at rate of 1 mg/kg/h and adjust upward in 0.5 mg/kg/h increments according to gastric acid output (max, 2.5 mg/kg/h; infusion rate 220 mg/h).

Maintenance of Healing of Erosive EsophagitisAdults

PO 150 mg at bedtime.

Heartburn (OTC)Adults

PO Treatment: 75 to 150 mg with a glass of water. Prevention: 75 to 150 mg with a glass of water 30 to 60 min before eating food or drinking beverages that cause heartburn. Maintenance: Up to 150 mg twice daily.

Renal Insufficiency (Ccr less than 50 mL/min)Adults

PO 150 mg every 24 h. IM/IV 50 mg every 18 to 24 h.

General Advice

• Tablets, Effervescent Tablets, and Oral Syrup
• Tablets, effervescent tablets, and oral syrup are bioequivalent.
• Administer tablets, effervescent tablets, or syrup without regard to meals. Administer with food if GI upset occurs.
• Effervescent tablets contain phenylalanine. Do not administer effervescent tablet to patient with phenylketonuria without first discussing with health care provider.
• Effervescent tablets must be dissolved in water before administration. Effervescent tablets should not be chewed, swallowed whole, or dissolved on the tongue.
• Dissolve 25 mg effervescent tablet in no less than 5 mL of water in an appropriate measuring cup. Wait until tablet is completely dissolved before administering. Solution may be administered by medicine dropper for infants.
• Dissolve 150 mg effervescent tablet in 6 to 8 oz of water before administering.
• Measure and administer prescribed dose of oral syrup using dosing syringe, dosing spoon, or dosing cup.

• Injection
• For IM or IV administration only. Not for intradermal, subcutaneous, or intra-arterial administration.
• Premixed injection requires no dilution and is for IV infusion only. Do not mix with other parenteral medications. If used with a primary IV fluid system, discontinue primary solution during infusion of premixed ranitidine.
• Do not use if particulate matter, cloudiness, or discoloration is noted. Undiluted ranitidine injection tends to exhibit a yellow color that may intensify over time but this is normal and does not affect potency.
• Refer to manufacturer's guidelines for pediatric use and dosing.
• For administration as an intermittent IV bolus in adult patient, dilute 50 mg (2 mL) in a compatible IV solution to a concentration no greater than 2.5 mg/mL (20 mL) and inject at a rate no greater than 4 mL/min (over 5 min).
• For administration as an intermittent IV infusion in adult patient, dilute 50 mg (2 mL) in a compatible IV solution to a concentration no greater than 0.5 mg/mL (100 mL) and infuse at a rate no greater than 5 to 7 mL/min (over 20 to 30 min), or use 50 mL of 1 mg/mL premixed solution and administer over 15 to 20 min.
• For administration as a continuous IV infusion in adult patient, except patient with Zollinger-Ellison syndrome, dilute 150 mg (6 mL) in 250 mL of a compatible IV solution and infuse at a rate of 10.7 mL/h.
• For patient with Zollinger-Ellison syndrome dilute prescribed dose in compatible IV solution to a concentration of 2.5 mg/mL or less. Begin infusion at 1 mg/kg/h and adjust dose upwards based on patient's symptoms and measured gastric acid output.

Storage/Stability

Store tablets at controlled room temperature (59° to 86°F). Protect from moisture and light. Replace cap securely after each opening. Store effervescent tablets in refrigerator or at controlled room temperature. Store syrup between 39° and 77°F. Store premixed injection between 36° and 77°F. Store injection between 39° and 86°F. Protect from light. Ranitidine injection is stable for 24 h at room temperature when added to, or diluted with, compatible IV solutions.

Drug Interactions

Diazepam, midazolam, triazolam

Pharmacologic effects may be increased or decreased because of decreased GI absorption by ranitidine. Staggering administration times may avoid this reaction.

Ethanol

May increase plasma ethanol levels.

Glipizide

Possible increased hypoglycemia effect.

Ketoconazole

May decrease effects of ketoconazole.

Lidocaine

May cause increased lidocaine levels.

Warfarin

Ranitidine may interfere with warfarin Cl. Hypoprothrombinemic effects may increase; may need adjustment.

Laboratory Test Interactions

False-positive test results for urine protein with Multistix may occur during ranitidine therapy; testing with sulfosalicylic acid is recommended.

Adverse Reactions

Cardiovascular

AV block; bradycardia; cardiac arrhythmias; premature ventricular beats.

CNS

Agitation; confusion; depression; dizziness; fatigue; hallucinations; headache; insomnia; malaise; motor disturbances; somnolence; vertigo.

Dermatologic

Alopecia; erythema multiforme; rash; vasculitis.

EENT

Blurred vision.

GI

Abdominal discomfort; constipation; diarrhea; nausea; pancreatitis; vomiting.

Hematologic

Acquired immune hemolytic anemia; agranulocytosis; autoimmune hemolytic or aplastic anemia; granulocytopenia; leukopenia; pancytopenia; thrombocytopenia.

Hepatic

Cholestatic or hepatocellular effects.

Musculoskeletal

Arthralgias; myalgias.

Miscellaneous

Anaphylaxis; angioneurotic edema; hypersensitivity reactions.

Precautions

Pregnancy

Category B .

Lactation

Excreted in breast milk.

Children

Safety and efficacy of ranitidine have been established in children 1 mo to 16 yr of age for the treatment of duodenal and gastric ulcers, GERD and erosive esophagitis, and the maintenance of healed duodenal and gastric ulcer. Safety and efficacy have not been established for the treatment of pathological hypersecretory conditions or the maintenance of healing of erosive esophagitis in children or in neonates less than 1 mo of age.

Elderly

May have reduced renal function; therefore, decreased drug Cl may be more common.

Hypersensitivity

Rare cases of anaphylaxis have occurred as well as rare episodes of hypersensitivity.

Renal Function

Decreased Cl may occur; dosage reduction may be needed. Hemodialysis reduces level of ranitidine-dosage; timing must be adjusted so that scheduled dose coincides with end of hemodialysis.

Hepatic Function

Use drug with caution; decreased Cl may occur.

Hepatocellular injury

May occur, manifested as reversible hepatitis, hepatocellular or hepatocanalicular or mixed, with or without jaundice.

Rapid IV administration

May rarely result in bradycardia, tachycardia, or premature ventricular beats, usually in patients predisposed to cardiac rhythm disturbances.

Overdosage

Symptoms

Collapse, diarrhea, hypotension, lacrimation, miosis, muscle tremors, pallor of mucous membranes, rapid redness of mouth and ears, respiration, respiratory failure, restlessness, salivation, tachycardia, vomiting.

Patient Information

• Injection
• Advise patient or caregiver that medication will be prepared and administered by a health care professional in a health care setting when oral therapy is not feasible, but that oral therapy will be resumed when a health care provider believes it is appropriate.

• OTC Ranitidine
• Instruct patient using OTC ranitidine tablets to carefully read package instructions regarding warnings and dosing instructions.

• Tablets, Effervescent Tablets, and Oral Syrup
• Advise patient using tablets, effervescent tablets, or syrup to take prescribed dose without regard to meals, but to take with food if stomach upset occurs.
• Caution patient or caregiver that effervescent tablets must be dissolved in water before administration. Caution patient or caregiver that effervescent tablets should not be chewed, swallowed whole, or dissolved on the tongue.
• Advise patient or caregiver using 25 mg effervescent tablet to dissolve the tablet in no less than 5 mL of water in an appropriate measuring cup and wait until tablet is completely dissolved before administering. Advise caregiver that solution may be administered by medicine dropper for infant.
• Advise patient using 150 mg effervescent tablet to dissolve tablet in 6 to 8 oz of water before administering.
• Advise patient or caregiver using oral syrup to measure and administer prescribed dose using dosing syringe, dosing spoon, or dosing cup.
• Inform patient that antacids may be taken concurrently with ranitidine.
• Instruct patient to report any of the following to health care provider: bloody or coffee ground vomit; black tarry stools; recurrent heartburn; recurrent indigestion or abdominal pain; increasing need for antacid use; bothersome side effects (eg, headache, constipation, gas).

Copyright © 2009 Wolters Kluwer Health.