RANITIDINE- ranitidine tablet, film coated

United States - English - NLM (National Library of Medicine)

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Active ingredient:
RANITIDINE HYDROCHLORIDE (UNII: BK76465IHM) (RANITIDINE - UNII:884KT10YB7)
Available from:
Direct_Rx
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Ranitidine tablets USP 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-controlle
Product summary:
Ranitidine tablets USP 150 mg (ranitidine HCl USP equivalent to 150 mg of ranitidine) are pink colored, circular, biconvex, beveled edge film coated tablets with “G51” engraved on one side and “150” on the other side. They are available in bottles of 60 , 100, and 500 tablets. Ranitidine tablets USP 300 mg (ranitidine HCl USP equivalent to 300 mg of ranitidine) are pink colored, circular, biconvex, beveled edge film coated tablets with “G51” engraved on one side and “300” on the other side. They are available in bottles of 30 ,100 and 250 tablets.
Authorization status:
Abbreviated New Drug Application
Authorization number:
61919-455-30

RANITIDINE- ranitidine tablet, film coated

Direct_Rx

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RANITIDINE

The active ingredient in ranitidine tablets USP 150 mg and 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:

[structure-ranitidine]

The empirical formula is C13H22N4O3SHCl, representing a molecular weight of 350.87.

Ranitidine HCl USP 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 168 mg of ranitidine HCl USP

equivalent to 150 mg of ranitidine. Each tablet also contains the inactive ingredients microcrystalline

cellulose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, FD&C Red # 40

Aluminum Lake, hypromellose, titanium dioxide, triacetin.

Each ranitidine tablet USP 300 mg for oral administration contains 336 mg of ranitidine HCl USP

equivalent to 300 mg of ranitidine. Each tablet also contains the inactive ingredients microcrystalline

cellulose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, FD&C Red # 40

Aluminum Lake, hypromellose, titanium dioxide, triacetin.

Ranitidine is a competitive, reversible inhibitor of the action of histamine at the histamine H2-receptors,

including receptors on the gastric cells. Ranitidine does not lower serum Ca++ in hypercalcemic states.

Ranitidine is not an anticholinergic agent.

Pharmacokinetics:

Absorption:

Ranitidine is 50% absorbed after oral administration, compared to an intravenous (IV) injection with

mean peak levels of 440 to 545 ng/mL occurring 2 to 3 hours after a 150-mg dose. Absorption is not

significantly impaired by the administration of food or antacids. Propantheline slightly delays and

increases peak blood levels of ranitidine, probably by delaying gastric emptying and transit time. In one

study, simultaneous administration of high-potency antacid (150 mmol) in fasting subjects has been

reported to decrease the absorption of ranitidine.

Distribution:

The volume of distribution is about 1.4 L/kg. Serum protein binding averages 15%.

Metabolism:

In humans, the N-oxide is the principal metabolite in the urine; however, this amounts to <4% of the

dose. Other metabolites are the S-oxide (1%) and the desmethyl ranitidine (1%). The remainder of the

administered dose is found in the stool. Studies in patients with hepatic dysfunction (compensated

cirrhosis) indicate that there are minor, but clinically insignificant, alterations in ranitidine half-life,

distribution, clearance, and bioavailability.

Excretion:

The principal route of excretion is the urine, with approximately 30% of the orally administered dose

collected in the urine as unchanged drug in 24 hours. Renal clearance is about 410 mL/min, indicating

active tubular excretion. The elimination half-life is 2.5 to 3 hours. Four patients with clinically

significant renal function impairment (creatinine clearance 25 to 35 mL/min) administered 50 mg of

ranitidine intravenously had an average plasma half-life of 4.8 hours, a ranitidine clearance of 29

mL/min, and a volume of distribution of 1.76 L/kg. In general, these parameters appear to be altered in

proportion to creatinine clearance (see DOSAGE AND ADMINISTRATION ).

Geriatrics:

The plasma half-life is prolonged and total clearance is reduced in the elderly population due to a

decrease in renal function. The elimination half-life is 3 to 4 hours. Peak levels average 526 ng/mL

following a 150-mg twice-daily dose and occur in about 3 hours (see PRECAUTIONS: Geriatric Use

and DOSAGE AND ADMINISTRATION: Dosage Adjustment for Patients With Impaired Renal

Function).

Pediatrics:

There are no significant differences in the pharmacokinetic parameter values for ranitidine in pediatric

patients (from 1 month up to 16 years of age) and healthy adults when correction is made for body

weight. The average bioavailability of ranitidine given orally to pediatric patients is 48% which is

comparable to the bioavailability of ranitidine in the adult population. All other pharmacokinetic

parameter values (t1/2, Vd, and CL) are similar to those observed with intravenous ranitidine use in

pediatric patients. Estimates of Cmax and Tmax are displayed in Table 1.

Table 1. Ranitidine Pharmacokinetics in Pediatric Patients Following Oral Dosing

Population (age)

Dosage Form (dose)

Cmax (ng/mL)

Tmax (hours)

Gastric or duodenal ulcer (3.5 to 16 years)

Tablets (1 to 2 mg/kg)

54 to 492

Plasma clearance measured in 2 neonatal patients (less than 1 month of age) was considerably lower (3

mL/min/kg) than children or adults and is likely due to reduced renal function observed in this population

(see PRECAUTIONS: Pediatric Use and DOSAGE AND ADMINISTRATION: Pediatric Use ).

Pharmacodynamics:

Serum concentrations necessary to inhibit 50% of stimulated gastric acid secretion are estimated to be

36 to 94 ng/mL. Following a single oral dose of 150 mg, serum concentrations of ranitidine are in this

range up to 12 hours. However, blood levels bear no consistent relationship to dose or degree of acid

inhibition.

Antisecretory Activity:

1. Effects on Acid Secretion:

Ranitidine inhibits both daytime and nocturnal basal gastric acid secretions as well as gastric acid

secretion stimulated by food, betazole, and pentagastrin, as shown in Table 2.

Table 2. Effect of Oral Ranitidine on Gastric Acid Secretion

Time After Dose, hours

% Inhibition of Gastric Acid Output by Dose, mg

75 - 80

Basal

Up to 4

Nocturnal

Up to 13

Betazole

Up to 3

Pentagastrin

Up to 5

Meal

Up to 3

It appears that basal-, nocturnal-, and betazole-stimulated secretions are most sensitive to inhibition by

ranitidine, responding almost completely to doses of 100 mg or less, while pentagastrin- and food-

stimulated secretions are more difficult to suppress.

2. Effects on Other Gastrointestinal Secretions:

Pepsin: Oral ranitidine does not affect pepsin secretion. Total pepsin output is reduced in proportion to

the decrease in volume of gastric juice.

Intrinsic Factor: Oral ranitidine has no significant effect on pentagastrin-stimulated intrinsic factor

secretion.

Serum Gastrin: Ranitidine has little or no effect on fasting or postprandial serum gastrin.

Other Pharmacologic Actions:

Gastric bacterial flora - increase in nitrate-reducing organisms, significance not known.

Prolactin levels - no effect in recommended oral or intravenous (IV) dosage, but small, transient, dose-

related increases in serum prolactin have been reported after IV bolus injections of 100 mg or more.

Other pituitary hormones - no effect on serum gonadotropins, TSH, or GH. Possible impairment of

vasopressin release.

No change in cortisol, aldosterone, androgen, or estrogen levels.

No antiandrogenic action.

No effect on count, motility, or morphology of sperm.

Pediatrics:

Oral doses of 6 to 10 mg/kg/day in 2 or 3 divided doses maintain gastric pH>4 throughout most of the

dosing interval.

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 as shown in Table 3.

Table 3. Duodenal Ulcer Patient healing Rates

All patients were permitted antacids as needed for relief of pain.

p < 0.0001.

Ranitidine*

Placebo*

Number Entered

Healed/Evaluable

Number Entered

Healed/Evaluable

Outpatients

69/182 (38%) †

31/164 (19%)

Week 2

Week 4

137/187 (73%)†

76/168 (45%)

In these studies, patients treated with ranitidine 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 (150 mg at bedtime) than in

patients treated with placebo over a 12-month period.

Table 5. Duodenal Ulcer Prevalence

% = Life table estimate.

RAN = ranitidine (ranitidine tablets USP)

PLC = placebo

p < 0.05 (ranitidine tablets USP versus comparator)

Double-Blind, Multicenter, Placebo-Controlled Trials

Multicenter trial

Drug

Duodenal Ulcer Prevalence

No. of Patients

0 - 4 Months

0 - 8 Months

0 - 12 Months

20%*

24%*

35%*

Foreign

12%*

21%*

28%*

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 as shown in Table 6.

Table 6. Gastric Ulcer Patient Healing Rates

All patients were permitted antacids as needed for relief of pain.

p = 0.009.

Ranitidine*

Placebo*

Number Entered

Healed/Evaluable

Number Entered

Healed/Evaluable

Outpatients

16/83 (19%)

10/83 (12%)

Week 2

Week 6

50/73 (68%)†

35/69 (51%)

In this multicenter trial, significantly more patients treated with ranitidine became pain free during

therapy.

Maintenance of Healing of Gastric Ulcers:

In 2 multicenter, double-blind, randomized, placebo-controlled, 12-month trials conducted in patients

whose gastric ulcers had been previously healed, ranitidine 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 inhibits 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 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 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 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 2 additional US multicenter, double-blind, placebo-controlled, 2-week trials, ranitidine 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 2 multicenter, double-blind, randomized, placebo-controlled, 12-week trials performed in the United

States, ranitidine 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

All patients were permitted antacids as needed for relief of pain.

p < 0.001 versus placebo.

Healed/Evaluable

Placebo* n=229

Ranitidine 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%)†

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 150 mg twice daily was significantly

more effective than placebo in maintaining healing of erosive esophagitis.

Ranitidine tablets USP are indicated in:

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.

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.

The treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome and systemic

mastocytosis).

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.

Maintenance therapy for gastric ulcer patients at reduced dosage after healing of acute ulcers. Placebo-

controlled studies have been carried out for 1 year.

Treatment of GERD. Symptomatic relief commonly occurs within 24 hours after starting therapy with

ranitidine 150 mg twice daily.

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.

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.

Ranitidine tablets USP are contraindicated for patients known to have hypersensitivity to the drug or any

of the ingredients (see PRECAUTIONS ).

General:

Symptomatic response to therapy with ranitidine does not preclude the presence of gastric malignancy.

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.

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 H2-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 study

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 per 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 studies 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 (less than 1 month of age) 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 65 and over, while 899 were 75 and

over. 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).

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 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 intavenously 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 (H2RAs) compared to patients who had stopped H2RA treatment, with

an observed adjusted relative risk of 1.63 (95% CI, 1.07 - 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.

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

Active Duodenal Ulcer:

The current recommended adult oral dosage of ranitidine tablets USP 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 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 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

(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 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 PHARMACOLGOY:

Pharmacokinetics: Geriatrics and PRECAUTIONS: Geriatric Use ).

Ranitidine tablets USP 150 mg (ranitidine HCl USP equivalent to 150 mg of ranitidine) are pink colored,

circular, biconvex, beveled edge film coated tablets with “G51” engraved on one side and “150” on the

other side. They are available in bottles of 60 , 100, and 500 tablets.

Ranitidine tablets USP 300 mg (ranitidine HCl USP equivalent to 300 mg of ranitidine) are pink colored,

circular, biconvex, beveled edge film coated tablets with “G51” engraved on one side and “300” on the

other side. They are available in bottles of 30 ,100 and 250 tablets.

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15 o to 30 o C (59 o to 86 o F) [see USP

Controlled Room Temperature]. Protect from light. Replace cap securely after each opening.

Manufactured by:

Shasun Pharmaceuticals Limited,

Unit-II,

R.S. No. 32, 33 & 34, Shasun Road, Periyakalapet,

Puducherry - 605 014. India.

Manufactured for:

[glenmark-logo]

Glenmark Pharmaceuticals Inc., USA

Mahwah, NJ 07430

Questions? 1 (888)721-7115

www.glenmarkpharma.com

December 2018

MULTISTIX is a registered trademark of Bayer Healthcare LLC.

RANITIDINE

ranitidine tablet, film coated

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 19 19 -455(NDC:6 8 46 2-249 )

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

RANITIDINE HYDRO CHLO RIDE (UNII: BK76 46 5IHM) (RANITIDINE - UNII:8 8 4KT10 YB7)

RANITIDINE

30 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

HYPRO MELLO SE, UNSPECIFIED (UNII: 3NXW29 V3WO)

TRIACETIN (UNII: XHX3C3X6 73)

FD&C RED NO . 4 0 (UNII: WZB9 127XOA)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

CRO SCARMELLO SE SO DIUM (UNII: M28 OL1HH48 )

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

Product Characteristics

Color

pink

S core

no sco re

S hap e

ROUND ((Circular, bico nvex, beveled edge))

S iz e

13mm

Flavor

Imprint Code

G51;30 0

Contains

Packag ing

Dire ct_Rx

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 19 19 -455-30

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /12/20 19

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 78 542

0 8 /12/20 19

Labeler -

Direct_Rx (079254320)

Registrant -

Direct_Rx (079254320)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Dire c t_Rx

0 79 254320

re pa c k(6 19 19 -455)

Revised: 8/2019

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