Ranitidine Tablets, USP, Rx Only

/Ranitidine Tablets, USP, Rx Only
Ranitidine Tablets, USP, Rx Only2018-09-06T09:12:40+00:00

Prescription Drug Name:

Ranitidine Tablets, USP, Rx Only

ID:

9089cbd3-1eff-44fa-b12a-4d126058cb50

Code:

34391-3

DESCRIPTION


id: 38742014-b6dc-4dc5-b300-44e252b47bef
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

The active ingredient in Ranitidine Tablets, USP 150 mg and Ranitidine Tablets, USP 300 mg is ranitidine hydrochloride (HCl), USP, a histamine H2-receptor antagonist. Chemically it is N[2-[[[5-[(dimethylamino)methyl]-2-furanyl]methyl]thio]ethyl]-N’-methyl-2-nitro-1,1-ethenediamine, HCl. It has the following structure: The empirical formula is C13H22N4O3S·HCl, representing a molecular weight of 350.87. Ranitidine HCl is a white to pale yellow, granular substance that is soluble in water. It has a slightly bitter taste and sulfur like odor. Each Ranitidine Tablet, USP 150 mg for oral administration contains 167.4 mg of ranitidine HCl equivalent to 150 mg of ranitidine. Each tablet also contains the inactive ingredients colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, titanium dioxide, triethyl citrate and FD&C Yellow #6. Each Ranitidine Tablet, USP 300 mg for oral administration contains 334.8 mg of ranitidine HCl equivalent to 300 mg of ranitidine. Each tablet also contains the inactive ingredients colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, titanium dioxide, triethyl citrate and D&C Yellow #10.

CLINICAL PHARMACOLOGY


id: 79376009-42a8-4bac-afd6-8229bf3a3b9b
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

Ranitidine Tablets are a competitive, reversible inhibitor of the action of histamine at the histamine H2-receptors, including receptors on the gastric cells. Ranitidine Tablets do not lower serum Ca++ in hypercalcemic states. Ranitidine Tablets are not an anticholinergic agent.

CLINICAL TRIALS


id: 13ea0570-aced-4b76-b514-8a10363cd0ec
displayName: CLINICAL STUDIES SECTION
FDA Article Code: 34092-7


Active Duodenal Ulcer:
In a multicenter, double-blind, controlled, US study of endoscopically diagnosed duodenal ulcers, earlier healing was seen in the patients treated with Ranitidine Tablets as shown in Table 3.
Table 3. Duodenal Ulcer Patient Healing Rates  

Ranitidine Tablets *
Placebo*
Number

Entered

Healed /

Evaluable

Number

Entered

Healed /

Evaluable

Outpatients 195 69/182
(38%)
188 31/164
(19%)
Week 2
Week 4 137/187
(73%)
76/168
(45%)
*All patients were permitted antacids as needed for relief of pain.
P<0.0001.
In these studies, patients treated with Ranitidine Tablets reported a reduction in both daytime and nocturnal pain, and they also consumed less antacid than the placebo-treated patients.   Table 4. Mean Daily Doses of Antacid  
Ulcer Healed Ulcer Not Healed
Ranitidine 0.06 0.71
Placebo 0.71 1.43
  Foreign studies have shown that patients heal equally well with 150 mg twice daily and 300 mg at bedtime (85% versus 84%, respectively) during a usual 4-week course of therapy. If patients require extended therapy of 8 weeks, the healing rate may be higher for 150 mg twice daily as compared to 300 mg at bedtime (92% versus 87%, respectively). Studies have been limited to short-term treatment of acute duodenal ulcer. Patients whose ulcers healed during therapy had recurrences of ulcers at the usual rates.
Maintenance Therapy in Duodenal Ulcer:
Ranitidine has been found to be effective as maintenance therapy for patients following healing of acute duodenal ulcers. In 2 independent, double-blind, multicenter, controlled trials, the number of duodenal ulcers observed was significantly less in patients treated with Ranitidine Tablets (150 mg at bedtime) than in patients treated with placebo over a 12-month period.
Table 5. Duodenal Ulcer Prevalence  
Double-Blind, Multicenter, Placebo-Controlled Trials
Multicenter

Trial

Drug Duodenal Ulcer Prevalence No. of Patients
0 to 4
Months
0 to 8
Months
0 to 12
Months
USA RAN 20%* 24%* 35%* 138
PLC 44% 54% 59% 139
Foreign RAN 12%* 21%* 28%* 174
PLC 56% 64% 68% 165
% = Life table estimate. * = P<0.05 (Ranitidine Tablets versus comparator). RAN = ranitidine (Ranitidine Tablets) PLC = placebo.
  As with other H2-antagonists, the factors responsible for the significant reduction in the prevalence of duodenal ulcers include prevention of recurrence of ulcers, more rapid healing of ulcers that may occur during maintenance therapy, or both. Gastric Ulcer: In a multicenter, double-blind, controlled, US study of endoscopically diagnosed gastric ulcers, earlier healing was seen in the patients treated with Ranitidine Tablets as shown in Table 6. Table 6. Gastric Ulcer Patient Healing Rates  
Ranitidine Tablets * Placebo*
Number

Entered

Healed /

Evaluable

Number

Entered

Healed /

Evaluable

Outpatients 92 16/83
(19%)
94 10/83
(12%)
Week 2
Week 6 50/73
(68%) †
35/69
(51%)
*All patients were permitted antacids as needed for relief of pain. †P = 0.009.
In this multicenter trial, significantly more patients treated with Ranitidine Tablets became pain free during therapy.
Maintenance of Healing of Gastric Ulcers:
In two multicenter, double-blind, randomized, placebo-controlled, 12-month trials conducted in patients whose gastric ulcers had been previously healed, Ranitidine Tablets 150 mg at bedtime was significantly more effective than placebo in maintaining healing of gastric ulcers.

Pathological Hypersecretory Conditions (such as Zollinger-Ellison syndrome):
Ranitidine Tablets inhibit gastric acid secretion and reduces occurrence of diarrhea, anorexia, and pain in patients with pathological hypersecretion associated with Zollinger-Ellison syndrome, systemic mastocytosis, and other pathological hypersecretory conditions (e.g., postoperative, “short-gut” syndrome, idiopathic). Use of Ranitidine Tablets was followed by healing of ulcers in 8 of 19 (42%) patients who were intractable to previous therapy.
Gastroesophageal Reflux Disease (GERD):
In 2 multicenter, double-blind, placebo-controlled, 6-week trials performed in the United States and Europe, Ranitidine Tablets 150 mg twice daily was more effective than placebo for the relief of heartburn and other symptoms associated with GERD. Ranitidine-treated patients consumed significantly less antacid than did placebo-treated patients.
The US trial indicated that Ranitidine Tablets 150 mg twice daily significantly reduced the frequency of heartburn attacks and severity of heartburn pain within 1 to 2 weeks after starting therapy. The improvement was maintained throughout the 6-week trial period. Moreover, patient response rates demonstrated that the effect on heartburn extends through both the day and night time periods. In two additional US multicenter, double-blind, placebo-controlled, 2-week trials, Ranitidine Tablets 150 mg twice daily was shown to provide relief of heartburn pain within 24 hours of initiating therapy and a reduction in the frequency of severity of heartburn.
Erosive Esophagitis:
In two multicenter, double-blind, randomized, placebo-controlled, 12-week trials performed in the United States, Ranitidine Tablets 150 mg 4 times daily was significantly more effective than placebo in healing endoscopically diagnosed erosive esophagitis and in relieving associated heartburn.
The erosive esophagitis healing rates were as follows: Table 7. Erosive Esophagitis Patient Healing Rates  
Healed / Evaluable
Placebo*

n=229

Ranitidine Tablets

150 mg 4 times daily*

n=215

Week 4 43/198 (22%) 96/206 (47%) †
Week 8 63/176 (36%) 142/200 (71%) †
Week 12 92/159 (58%) 162/192 (84%) †
*All patients were permitted antacids as needed for relief of pain. †P<0.001 versus placebo. No additional benefit in healing of esophagitis or in relief of heartburn was seen with a ranitidine dose of 300 mg 4 times daily.

Maintenance of Healing of Erosive Esophagitis:
In 2 multicenter, double-blind, randomized, placebo-controlled, 48-week trials conducted in patients whose erosive esophagitis had been previously healed, Ranitidine Tablets 150 mg twice daily was significantly more effective than placebo in maintaining healing of erosive esophagitis.

INDICATIONS AND USAGE


id: a613797a-3b45-4db6-9c02-dedf98f09972
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Ranitidine Tablets are indicated in: 1.   Short-term treatment of active duodenal ulcer. Most patients heal within 4 weeks. Studies 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. Studies 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 studies have been carried out for 1 year. 6.   Treatment of GERD. Symptomatic relief commonly occurs within 24 hours after starting therapy with Ranitidine Tablets 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 Tablets 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


id: db49fbfb-c53a-4c67-95a8-a3a44c8e1646
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Ranitidine Tablets are contraindicated for patients known to have hypersensitivity to the drug or any of the ingredients (see PRECAUTIONS ).

ADVERSE REACTIONS


id: 100cdb69-72af-488c-9676-af31740f7f60
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

The following have been reported as events in clinical trials or in the routine management of patients treated with Ranitidine Tablets. The relationship to therapy with Ranitidine Tablets has been unclear in many cases. Headache, sometimes severe, seems to be related to administration of Ranitidine Tablets. 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 H2-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 Tablets and no antiandrogenic activity, and cimetidine-induced gynecomastia and impotence in hypersecretory patients have resolved when Ranitidine Tablets have been substituted. However, occasional cases of impotence and loss of libido have been reported in male patients receiving Ranitidine Tablets, 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 (H2RAs) compared to patients who had stopped H2RA treatment, with an observed adjusted relative risk of 1.63 (95% CI, 1.07 to 2.48). However, a causal relationship between use of H2RAs 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. To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

OVERDOSAGE


id: fb40b2a5-c7aa-4c91-9802-2b3af9b12100
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

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 Tablets 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 LD50 values in mice and rats were 77 and 83 mg/kg, respectively.

DOSAGE AND ADMINISTRATION


id: d66593be-0fbf-4ef3-9298-81e199d59fd5
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

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 studies, 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 Tablets 150-mg doses more frequently. Dosages should be adjusted to individual patient needs, and should continue as long as clinically indicated. Dosages up to 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 four 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 Tablets have been established in the age-group of 1 month to 16 years. There is insufficient information about the pharmacokinetics of Ranitidine Tablets in neonatal patients (less than 1 month of age) 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 studies 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 studies 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 two 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 Tablets, 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


id: 9bae187c-9087-49f2-8b76-3253adf973fe
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Ranitidine Tablets, USP 150 mg (ranitidine HCl equivalent to 150 mg of ranitidine) are supplied as orange, round, biconvex aqueous film-coated tablets debossed “IP 253” on one side and plain on the reverse.  They are available as follows: Bottles of 30:              NDC 42708-118-30 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature] in a dry place. Dispense in a tight, light-resistant container as defined in the USP.  Protect from light. Replace cap securely after each opening. Manufactured by: Amneal Pharmaceuticals Pvt. Ltd. Ahmedabad, INDIA 382220 Or Manufactured by: Amneal Pharmaceuticals Pvt. Ltd. Oral Solid Dosage Unit Ahmedabad, India 382213 Distributed by: Amneal Pharmaceuticals Bridgewater, NJ 08807 Rev. 09-2016-01

PRINCIPAL DISPLAY PANEL


id: 4a802228-3391-4785-8878-951532e3cee7
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

NDC 42708-118-30 Ranitidine Tablets USP, 150 mg Rx only 30 Tablets QPHARMA