Ranitidine Immediate Release: Package Insert and Label Information (Page 2 of 3)

INDICATIONS AND USAGE

Ranitidine tablets, USP is indicated in:

  1. Short-term treatment of active duodenal ulcer. Most patients heal within 4 weeks. Trials available to date have not assessed the safety of ranitidine in uncomplicated duodenal ulcer for periods of more than 8 weeks.
  2. Maintenance therapy for duodenal ulcer patients at reduced dosage after healing of acute ulcers. No placebo-controlled comparative studies have been carried out for periods of longer than 1 year.
  3. The treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome and systemic mastocytosis).
  4. Short-term treatment of active, benign gastric ulcer. Most patients heal within 6 weeks and the usefulness of further treatment has not been demonstrated. Trials available to date have not assessed the safety of ranitidine in uncomplicated, benign gastric ulcer for periods of more than 6 weeks.
  5. Maintenance therapy for gastric ulcer patients at reduced dosage after healing of acute ulcers. Placebo-controlled trials have been carried out for 1 year.
  6. Treatment of GERD. Symptomatic relief commonly occurs within 24 hours after starting therapy with ranitidine 150 mg twice daily.
  7. Treatment of endoscopically diagnosed erosive esophagitis. Symptomatic relief of heartburn commonly occurs within 24 hours of therapy initiation with ranitidine 150 mg 4 times daily.
  8. Maintenance of healing of erosive esophagitis. Placebo-controlled trials have been carried out for 48 weeks.

Concomitant antacids should be given as needed for pain relief to patients with active duodenal ulcer; active, benign gastric ulcer; hypersecretory states; GERD; and erosive esophagitis.

CONTRAINDICATIONS

Ranitidine tablets, USP is contraindicated for patients known to have hypersensitivity to the drug or any of the ingredients (see PRECAUTIONS).

PRECAUTIONS

General:

  1. Symptomatic response to therapy with ranitidine does not preclude the presence of gastric malignancy.
  2. Since ranitidine is excreted primarily by the kidney, dosage should be adjusted in patients with impaired renal function (see DOSAGE AND ADMINISTRATION). Caution should be observed in patients with hepatic dysfunction since ranitidine is metabolized in the liver.
  3. Rare reports suggest that ranitidine may precipitate acute porphyric attacks in patients with acute porphyria. Ranitidine should therefore be avoided in patients with a history of acute porphyria.

Laboratory Tests: False-positive tests for urine protein with MULTISTIX ® may occur during therapy with ranitidine, and therefore testing with sulfosalicylic acid is recommended.

Drug Interactions: Ranitidine has been reported to affect the bioavailability of other drugs through several different mechanisms such as competition for renal tubular secretion, alteration of gastric pH, and inhibition of cytochrome P450 enzymes.

Procainamide: Ranitidine, a substrate of the renal organic cation transport system, may affect the clearance of other drugs eliminated by this route. High doses of ranitidine (e.g., such as those used in the treatment of Zollinger-Ellison syndrome) have been shown to reduce the renal excretion of procainamide and N-acetylprocainamide resulting in increased plasma levels of these drugs. Although this interaction is unlikely to be clinically relevant at usual ranitidine doses, it may be prudent to monitor for procainamide toxicity when administered with oral ranitidine at a dose exceeding 300 mg per day.

Warfarin: There have been reports of altered prothrombin time among patients on concomitant warfarin and ranitidine therapy. Due to the narrow therapeutic index, close monitoring of increased or decreased prothrombin time is recommended during concurrent treatment with ranitidine.

Ranitidine may alter the absorption of drugs in which gastric pH is an important determinant of bioavailability. This can result in either an increase in absorption (e.g., triazolam, midazolam, glipizide) or a decrease in absorption (e.g., ketoconazole, atazanavir, delavirdine, gefitinib). Appropriate clinical monitoring is recommended.

Atazanavir: Atazanavir absorption may be impaired based on known interactions with other agents that increase gastric pH. Use with caution. See atazanavir label for specific recommendations.

Delavirdine: Delavirdine absorption may be impaired based on known interactions with other agents that increase gastric pH. Chronic use of H 2 -receptor antagonists with delavirdine is not recommended.

Gefitinib: Gefitinib exposure was reduced by 44% with the coadministration of ranitidine and sodium bicarbonate (dosed to maintain gastric pH above 5.0). Use with caution.

Glipizide: In diabetic patients, glipizide exposure was increased by 34% following a single 150-mg dose of oral ranitidine. Use appropriate clinical monitoring when initiating or discontinuing ranitidine.

Ketoconazole: Oral ketoconazole exposure was reduced by up to 95% when oral ranitidine was coadministered in a regimen to maintain a gastric pH of 6 or above. The degree of interaction with usual dose of ranitidine (150 mg twice daily) is unknown.

Midazolam: Oral midazolam exposure in 5 healthy volunteers was increased by up to 65% when administered with oral ranitidine at a dose of 150 mg twice daily. However, in another interaction trial in 8 volunteers receiving IV midazolam, a 300-mg oral dose of ranitidine increased midazolam exposure by about 9%. Monitor patients for excessive or prolonged sedation when ranitidine is coadministered with oral midazolam.

Triazolam: Triazolam exposure in healthy volunteers was increased by approximately 30% when administered with oral ranitidine at a dose of 150 mg twice daily. Monitor patients for excessive or prolonged sedation.

Carcinogenesis, Mutagenesis, Impairment of Fertility: There was no indication of tumorigenic or carcinogenic effects in life-span studies in mice and rats at dosages up to 2,000 mg/kg/day.

Ranitidine was not mutagenic in standard bacterial tests ( Salmonella, Escherichia coli) for mutagenicity at concentrations up to the maximum recommended for these assays.

In a dominant lethal assay, a single oral dose of 1,000 mg/kg to male rats was without effect on the outcome of 2 matings per week for the next 9 weeks.

Pregnancy: Teratogenic Effects: Pregnancy Category B. Reproduction studies have been performed in rats and rabbits at doses up to 160 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to ranitidine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers: Ranitidine is secreted in human milk. Caution should be exercised when ranitidine is administered to a nursing mother.

Pediatric Use: The safety and effectiveness of ranitidine have been established in the age-group of 1 month to 16 years for the treatment of duodenal and gastric ulcers, gastroesophageal reflux disease and erosive esophagitis, and the maintenance of healed duodenal and gastric ulcer. Use of ranitidine in this age-group is supported by adequate and well-controlled trials in adults, as well as additional pharmacokinetic data in pediatric patients and an analysis of the published literature (see CLINICAL PHARMACOLOGY: Pediatrics and DOSAGE AND ADMINISTRATION: Pediatric Use)

Safety and effectiveness in pediatric patients for the treatment of pathological hypersecretory conditions or the maintenance of healing of erosive esophagitis have not been established

Safety and effectiveness in neonates (aged younger than 1 month) have not been established (see CLINICAL PHARMACOLOGY: Pediatrics).

Geriatric Use: Of the total number of subjects enrolled in US and foreign controlled clinical trials of oral formulations of ranitidine, for which there were subgroup analyses, 4,197 were aged 65 and older, while 899 were aged 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

This drug is known to be substantially excreted by the kidney and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, caution should be exercised in dose selection, and it may be useful to monitor renal function (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Geriatrics and DOSAGE AND ADMINISTRATION: Dosage Adjustment for Patients With Impaired Renal Function).

ADVERSE REACTIONS

The following have been reported as events in clinical trials or in the routine management of patients treated with ranitidine. The relationship to therapy with ranitidine has been unclear in many cases. Headache, sometimes severe, seems to be related to administration of ranitidine.

Central Nervous System: Rarely, malaise, dizziness, somnolence, insomnia, and vertigo. Rare cases of reversible mental confusion, agitation, depression, and hallucinations have been reported, predominantly in severely ill elderly patients. Rare cases of reversible blurred vision suggestive of a change in accommodation have been reported. Rare reports of reversible involuntary motor disturbances have been received.

Cardiovascular: As with other H 2 -blockers, rare reports of arrhythmias such as tachycardia, bradycardia, atrioventricular block, and premature ventricular beats.

Gastrointestinal: Constipation, diarrhea, nausea/vomiting, abdominal discomfort/pain, and rare reports of pancreatitis.

Hepatic: There have been occasional reports of hepatocellular, cholestatic, or mixed hepatitis, with or without jaundice. In such circumstances, ranitidine should be immediately discontinued. These events are usually reversible, but in rare circumstances death has occurred. Rare cases of hepatic failure have also been reported. In normal volunteers, SGPT values were increased to at least twice the pretreatment levels in 6 of 12 subjects receiving 100 mg intravenously 4 times daily for 7 days, and in 4 of 24 subjects receiving 50 mg intravenously 4 times daily for 5 days.

Musculoskeletal: Rare reports of arthralgias and myalgias.

Hematologic: Blood count changes (leukopenia, granulocytopenia, and thrombocytopenia) have occurred in a few patients. These were usually reversible. Rare cases of agranulocytosis, pancytopenia, sometimes with marrow hypoplasia, and aplastic anemia and exceedingly rare cases of acquired immune hemolytic anemia have been reported.

Endocrine: Controlled studies in animals and man have shown no stimulation of any pituitary hormone by ranitidine and no antiandrogenic activity, and cimetidine-induced gynecomastia and impotence in hypersecretory patients have resolved when ranitidine has been substituted. However, occasional cases of impotence and loss of libido have been reported in male patients receiving ranitidine, but the incidence did not differ from that in the general population. Rare cases of breast symptoms and conditions, including galactorrhea and gynecomastia, have been reported in both males and females.

Integumentary: Rash, including rare cases of erythema multiforme. Rare cases of alopecia and vasculitis.

Respiratory: A large epidemiological study suggested an increased risk of developing pneumonia in current users of histamine-2-receptor antagonists (H 2 RAs) compared with patients who had stopped H 2 RA treatment, with an observed adjusted relative risk of 1.63 (95% CI, 1.07 to 2.48). However, a causal relationship between use of H 2 RAs and pneumonia has not been established.

Other: Rare cases of hypersensitivity reactions (e.g., bronchospasm, fever, rash, eosinophilia), anaphylaxis, angioneurotic edema, acute interstitial nephritis, and small increases in serum creatinine.

OVERDOSAGE

There has been limited experience with overdosage. Reported acute ingestions of up to 18 g orally have been associated with transient adverse effects similar to those encountered in normal clinical experience (see ADVERSE REACTIONS). In addition, abnormalities of gait and hypotension have been reported.

When overdosage occurs, the usual measures to remove unabsorbed material from the gastrointestinal tract, clinical monitoring, and supportive therapy should be employed.

Studies in dogs receiving dosages of ranitidine in excess of 225 mg/kg/day have shown muscular tremors, vomiting, and rapid respiration. Single oral doses of 1,000 mg/kg in mice and rats were not lethal. Intravenous LD 50 values in mice and rats were 77 and 83 mg/kg, respectively.

DOSAGE AND ADMINISTRATION

Active Duodenal Ulcer: The current recommended adult oral dosage of ranitidine tablets for duodenal ulcer is 150 mg twice daily. An alternative dosage of 300 mg once daily after the evening meal or at bedtime can be used for patients in whom dosing convenience is important. The advantages of one treatment regimen compared to the other in a particular patient population have yet to be demonstrated (see Clinical Trials: Active Duodenal Ulcer ). Smaller doses have been shown to be equally effective in inhibiting gastric acid secretion in US trials, and several foreign trials have shown that 100 mg twice daily is as effective as the 150-mg dose.

Antacid should be given as needed for relief of pain (see CLINICAL PHARMACOLOGY: Pharmacokinetics).

Maintenance of Healing of Duodenal Ulcers: The current recommended adult oral dosage is 150 mg at bedtime.

Pathological Hypersecretory Conditions (such as Zollinger-Ellison syndrome): The current recommended adult oral dosage is 150 mg twice daily. In some patients it may be necessary to administer ranitidine 150-mg doses more frequently. Dosages should be adjusted to individual patient needs, and should continue as long as clinically indicated. Dosages upto 6 g/day have been employed in patients with severe disease.

Benign Gastric Ulcer: The current recommended adult oral dosage is 150 mg twice daily.

Maintenance of Healing of Gastric Ulcers: The current recommended adult oral dosage is 150 mg at bedtime.

GERD: The current recommended adult oral dosage is 150 mg twice daily.

Erosive Esophagitis: The current recommended adult oral dosage is 150 mg 4 times daily.

Maintenance of Healing of Erosive Esophagitis: The current recommended adult oral dosage is 150 mg twice daily.

Pediatric Use: The safety and effectiveness of ranitidine have been established in the age-group of 1 month to 16 years. There is insufficient information about the pharmacokinetics of ranitidine in neonatal patients (aged younger than 1 month) to make dosing recommendations.

The following 3 subsections provide dosing information for each of the pediatric indications.

Treatment of Duodenal and Gastric Ulcers: The recommended oral dose for the treatment of active duodenal and gastric ulcers is 2 to 4 mg/kg twice daily to a maximum of 300 mg/day. This recommendation is derived from adult clinical trials and pharmacokinetic data in pediatric patients.

Maintenance of Healing of Duodenal and Gastric Ulcers: The recommended oral dose for the maintenance of healing of duodenal and gastric ulcers is 2 to 4 mg/kg once daily to a maximum of 150 mg/day.

This recommendation is derived from adult clinical trials and pharmacokinetic data in pediatric patients.

Treatment of GERD and Erosive Esophagitis: Although limited data exist for these conditions in pediatric patients, published literature supports a dosage of 5 to 10 mg/kg/day, usually given as 2 divided doses.

Dosage Adjustment for Patients with Impaired Renal Function: On the basis of experience with a group of subjects with severely impaired renal function treated with ranitidine, the recommended dosage in patients with a creatinine clearance <50 ml/min is 150 mg every 24 hours. Should the patient’s condition require, the frequency of dosing may be increased to every 12 hours or even further with caution. Hemodialysis reduces the level of circulating ranitidine. Ideally, the dosing schedule should be adjusted so that the timing of a scheduled dose coincides with the end of hemodialysis.

Elderly patients are more likely to have decreased renal function, therefore caution should be exercised in dose selection, and it may be useful to monitor renal function (see CLINICAL PHARMACOLOGY: Pharmacokinetics: Geriatrics and PRECAUTIONS: Geriatric Use).

HOW SUPPLIED

Ranitidine tablets, USP 150 mg (ranitidine HCI USP equivalent to 150 mg of ranitidine) are brown coloured, circular shaped, biconvex, beveled edge film-coated tablets debossed with “S/429″ on one side and plain on the other side. They are available in bottles of 60 (NDC 51407-244-60), 180 (NDC 51407-244-18), and 1000 (NDC 51407-244-10) tablets.

Ranitidine tablets, USP 300 mg (ranitidine HCI USP equivalent to 300 mg of ranitidine) are brown coloured, circular shaped, biconvex, beveled edge film-coated tablets debossed with “S/430″ on one side and plain on the other side. They are available in bottles of 30 (NDC 51407-245-30) and 250 (NDC 51407-245-25) tablets.

Store at 20° to 25° C (68° and 77°F); excursions permitted between 15° and 30° C (59° and 86°F) [see USP Controlled Room Temperature]. Protect from light. Replace cap securely after each opening.

Distributed by:

Strides Pharma Inc.

East Brunswick, NJ 08816

Marketed/Packaged by:

GSMS, Inc.

Camarillo, CA 93012 USA

Revised: 06/ 2019

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