Zantac Injection

Generic Name: ranitidine hydrochloride

Dosage Form: injection
ZANTAC®

(ranitidine hydrochloride)

Injection

Pharmacy Bulk Package—Not for Direct Infusion

Zantac Injection Description

The active ingredient in Zantac Injection is ranitidine hydrochloride (HCl), 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, hydrochloride. 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.

Zantac Injection is a clear, colorless to yellow, nonpyrogenic liquid. The yellow color of the liquid tends to intensify without adversely affecting potency. The pH of the injection solution is 6.7 to 7.3.

Each 1 mL of aqueous solution contains ranitidine 25 mg (as the hydrochloride); phenol 5 mg as preservative; and 0.96 mg of monobasic potassium phosphate and 2.4 mg of dibasic sodium phosphate as buffers.

A pharmacy bulk package is a container of a sterile preparation for parenteral use that contains many single doses. The contents are intended for use in a pharmacy admixture program and are restricted to the preparation of admixtures for intravenous (IV) infusion.

Zantac Injection - Clinical Pharmacology

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

Pharmacokinetics

Absorption: ZANTAC is absorbed very rapidly after intramuscular (IM) injection. Mean peak levels of 576 ng/mL occur within 15 minutes or less following a 50-mg IM dose. Absorption from IM sites is virtually complete, with a bioavailability of 90% to 100% compared with intravenous (IV) administration. Following oral administration, the bioavailability of ZANTAC Tablets is 50%.

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: Following IV injection, approximately 70% of the dose is recovered in the urine as unchanged drug. Renal clearance averages 530 mL/min, with a total clearance of 760 mL/min. The elimination half-life is 2.0 to 2.5 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 3.1 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 pharmacokinetics of ZANTAC in pediatric patients are summarized in Table 1.

Table 1. Ranitidine Pharmacokinetics in Pediatric Patients Following IV Dosing

Population (age)	n	Dose (mg/kg)	t½ (hours)	Vd (L/kg)	CLp (mL/min/kg)
Peptic ulcer disease
(<6 years)	6	1.25 or 2.5	2.2	1.29	11.41
(6 − 11.9 years)	11	1.25 or 2.5	2.1	1.14	8.96
(>12 years)	6	1.25 or 2.5	1.7	0.98	9.89
Adults	6	2.5	1.9	1.04	8.77
Peptic ulcer disease (3.5 − 16 years)	12	0.13 − 0.80	1.8	2.3	795 mL/min/1.73/m2
Children in intensive care (1 day − 12.6 years)	17	1.0	2.4	2	11.7
Neonates receiving ECMO	12	2	6.6	1.8	4.3

T½= Terminal half-life; CLp = Plasma clearance of ranitidine.

ECMO = extracorporeal membrane oxygenation.

Plasma clearance in neonatal patients (less than 1 month of age) receiving ECMO was considerably lower (3 to 4 mL/min/kg) than observed in children or adults. The elimination half-life in neonates averaged 6.6 hours as compared to approximately 2 hours in adults and pediatric patients.

Pharmacodynamics

Serum concentrations necessary to inhibit 50% of stimulated gastric acid secretion are estimated to be 36 to 94 ng/mL. Following single IV or IM 50-mg doses, serum concentrations of ranitidine are in this range for 6 to 8 hours.

Antisecretory Activity: 1. Effects on Acid Secretion: Zantac Injection inhibits basal gastric acid secretion as well as gastric acid secretion stimulated by betazole and pentagastrin, as shown in Table 2.

Table 2. Effect of Intravenous ZANTAC on Gastric Acid Secretion

	Time After Dose, hours	% Inhibition of Gastric Acid Output by Intravenous Dose, mg
		20 mg	60 mg	100 mg
Betazole	Up to 2	93	99	99
Pentagastrin	Up to 3	47	66	77

In a group of 10 known hypersecretors, ranitidine plasma levels of 71, 180, and 376 ng/mL inhibited basal acid secretion by 76%, 90%, and 99.5%, respectively.

It appears that basal- and betazole-stimulated secretions are most sensitive to inhibition by ZANTAC, while pentagastrin-stimulated secretion is more difficult to suppress.

2. Effects on Other Gastrointestinal Secretions:

Pepsin: ZANTAC does not affect pepsin secretion. Total pepsin output is reduced in proportion to the decrease in volume of gastric juice.

Intrinsic Factor: ZANTAC has no significant effect on pentagastrin-stimulated intrinsic factor secretion.

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

Other Pharmacologic Actions

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


2. Prolactin levels−no effect in recommended oral or IV dosage, but small, transient, dose-related increases in serum prolactin have been reported after IV bolus injections of 100 mg or more.


3. Other pituitary hormones−no effect on serum gonadotropins, TSH, or GH. Possible impairment of vasopressin release.


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


5. No antiandrogenic action.


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

Pediatrics: The ranitidine concentration necessary to suppress basal acid secretion by at least 90% has been reported to be 40 to 60 ng/mL in pediatric patients with duodenal or gastric ulcers.

In a study of 20 critically ill pediatric patients receiving ranitidine IV at 1 mg/kg every 6 hours, 10 patients with a baseline pH≥4 maintained this baseline throughout the study. Eight of the remaining 10 patients with a baseline of pH≤2 achieved pH≥4 throughout varying periods after dosing. It should be noted, however, that because these pharmacodynamic parameters were assessed in critically ill pediatric patients, the data should be interpreted with caution when dosing recommendations are made for a less seriously ill pediatric population.

In another small study of neonatal patients (n = 5) receiving ECMO, gastric pH<4 pretreatment increased to >4 after a 2-mg/kg dose and remained above 4 for at least 15 hours.

Clinical Trials

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 oral ZANTAC as shown in Table 3.

Table 3. Duodenal Ulcer Patient Healing Rates

	Oral ZANTAC*		Oral Placebo*
	Number Entered	Healed/Evaluable	Number Entered	Healed/Evaluable
Outpatients
Week 2		69/182 (38%)†		31/164 (19%)
	195		188
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 oral ZANTAC 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
Oral ZANTAC	0.06	0.71
Oral placebo	0.71	1.43

Pathological Hypersecretory Conditions (such as Zollinger-Ellison syndrome): ZANTAC 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 oral ZANTAC was followed by healing of ulcers in 8 of 19 (42%) patients who were intractable to previous therapy.

In a retrospective review of 52 Zollinger-Ellison patients given ZANTAC as a continuous IV infusion for up to 15 days, no patients developed complications of acid-peptic disease such as bleeding or perforation. Acid output was controlled to ≤10 mEq/h.

Indications and Usage for Zantac Injection

Zantac Injection is indicated in some hospitalized patients with pathological hypersecretory conditions or intractable duodenal ulcers, or as an alternative to the oral dosage form for short-term use in patients who are unable to take oral medication.

Contraindications

Zantac Injection is contraindicated for patients known to have hypersensitivity to the drug.

Precautions

General

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


2. Since ZANTAC 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 ZANTAC is metabolized in the liver.


3. In controlled studies in normal volunteers, elevations in SGPT have been observed when H2-antagonists have been administered intravenously at greater-than-recommended dosages for 5 days or longer. Therefore, it seems prudent in patients receiving IV ranitidine at dosages ≥100 mg 4 times daily for periods of 5 days or longer to monitor SGPT daily (from day 5) for the remainder of IV therapy.


4. Bradycardia in association with rapid administration of Zantac Injection has been reported rarely, usually in patients with factors predisposing to cardiac rhythm disturbances. Recommended rates of administration should not be exceeded (see DOSAGE AND ADMINISTRATION).


5. Rare reports suggest that ZANTAC may precipitate acute porphyric attacks in patients with acute porphyria. ZANTAC 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 ZANTAC, 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 oral 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 oral doses up to 160 times the human oral dose and have revealed no evidence of impaired fertility or harm to the fetus due to ZANTAC. 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 ZANTAC is administered to a nursing mother.

Pediatric Use

The safety and effectiveness of Zantac Injection have been established in the age-group of 1 month to 16 years for the treatment of duodenal ulcer. Use of ZANTAC 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.

Safety and effectiveness in pediatric patients for the treatment of pathological hypersecretory conditions have not been established.

Limited data in neonatal patients (less than 1 month of age) receiving ECMO suggest that ZANTAC may be useful and safe for increasing gastric pH for patients at risk of gastrointestinal hemorrhage.

Geriatric Use

Clinical studies of Zantac Injection did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. However, in clinical studies of oral formulations of ZANTAC, of the total number of subjects enrolled in US and foreign controlled clinical trials, 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: Geriatric Use and DOSAGE AND ADMINISTRATION: Dosage Adjustment for Patients With Impaired Renal Function).

Adverse Reactions

Transient pain at the site of IM injection has been reported. Transient local burning or itching has been reported with IV administration of ZANTAC.

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

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, asystole, atrioventricular block, and premature ventricular beats.

Gastrointestinal

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

Hepatic

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. 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.

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 humans have shown no stimulation of any pituitary hormone by ZANTAC and no antiandrogenic activity, and cimetidine-induced gynecomastia and impotence in hypersecretory patients have resolved when ZANTAC has been substituted. However, occasional cases of impotence, and loss of libido have been reported in male patients receiving ZANTAC, 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.

Overdosage

There has been virtually no experience with overdosage with Zantac Injection and limited experience with oral doses of ranitidine. 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, clinical monitoring and supportive therapy should be employed.

Studies in dogs receiving dosages of ZANTAC 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.

Zantac Injection Dosage and Administration

Parenteral Administration

In some hospitalized patients with pathological hypersecretory conditions or intractable duodenal ulcers, or in patients who are unable to take oral medication, Zantac Injection may be administered parenterally according to the following recommendations:

Intramuscular Injection: 50 mg (2 mL) every 6 to 8 hours. (No dilution necessary.)

Intermittent Intravenous Injection:

a. Intermittent Bolus: 50 mg (2 mL) every 6 to 8 hours. Dilute Zantac Injection, 50 mg, in 0.9% sodium chloride injection or other compatible IV solution (see Stability) to a concentration no greater than 2.5 mg/mL (20 mL). Inject at a rate no greater than 4 mL/min (5 minutes).

b. Intermittent Infusion: 50 mg (2 mL) every 6 to 8 hours. Dilute Zantac Injection, 50 mg, in 5% dextrose injection or other compatible IV solution (see Stability) to a concentration no greater than 0.5 mg/mL (100 mL). Infuse at a rate no greater than 5 to 7 mL/min (15 to 20 minutes).

In some patients it may be necessary to increase dosage. When this is necessary, the increases should be made by more frequent administration of the dose, but generally should not exceed 400 mg/day.

Continuous Intravenous Infusion: Add Zantac Injection to 5% dextrose injection or other compatible IV solution (see Stability). Deliver at a rate of 6.25 mg/hour (e.g., 150 mg [6 mL] of Zantac Injection in 250 mL of 5% dextrose injection at 10.7 mL/hour).

For Zollinger-Ellison patients, dilute Zantac Injection in 5% dextrose injection or other compatible IV solution (see Stability) to a concentration no greater than 2.5 mg/mL. Start the infusion at a rate of 1.0 mg/kg/hour. If after 4 hours either a measured gastric acid output is >10 mEq/hour or the patient becomes symptomatic, the dose should be adjusted upward in 0.5-mg/kg/hour increments, and the acid output should be remeasured. Dosages up to 2.5 mg/kg/hour and infusion rates as high as 220 mg/hour have been used.

Pediatric Use

While limited data exist on the administration of IV ranitidine to children, the recommended dose in pediatric patients is for a total daily dose of 2 to 4 mg/kg, to be divided and administered every 6 to 8 hours, up to a maximum of 50 mg given every 6 to 8 hours. This recommendation is derived from adult clinical studies and pharmacokinetic data in pediatric patients. Limited data in neonatal patients (less than 1 month of age) receiving ECMO have shown that a dose of 2 mg/kg is usually sufficient to increase gastric pH to >4 for at least 15 hours. Therefore, doses of 2 mg/kg given every 12 to 24 hours or as a continuous infusion should be considered.

Dosage Adjustment for Patients With Impaired Renal Function

The administration of ranitidine as a continuous infusion has not been evaluated in patients with impaired renal function. On the basis of experience with a group of subjects with severely impaired renal function treated with ZANTAC, the recommended dosage in patients with a creatinine clearance <50 mL/min is 50 mg every 18 to 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: Geriatric Use and PRECAUTIONS: Geriatric Use).

Stability

Undiluted, Zantac Injection tends to exhibit a yellow color that may intensify over time without adversely affecting potency. Zantac Injection is stable for 48 hours at room temperature when added to or diluted with most commonly used IV solutions, e.g., 0.9% sodium chloride injection, 5% dextrose injection, 10% dextrose injection, lactated ringer's injection, or 5% sodium bicarbonate injection.

Note: Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.

Directions for Dispensing

Pharmacy Bulk Package—Not for Direct Infusion: The pharmacy bulk package is for use in a pharmacy admixture service only under a laminar flow hood. The closure should be penetrated only once with a sterile transfer set or other sterile dispensing device, which allows measured distribution of the contents, and the contents dispensed in aliquots using aseptic technique. CONTENTS SHOULD BE USED AS SOON AS POSSIBLE FOLLOWING INITIAL CLOSURE PUNCTURE. DISCARD ANY UNUSED PORTION WITHIN 24 HOURS OF FIRST ENTRY. Following closure puncture, container should be maintained below 30°C (86°F) under a laminar flow hood until contents are dispensed.

How is Zantac Injection Supplied

Zantac Injection, 25 mg/mL, containing phenol 0.5% as preservative, in a 40-mL pharmacy bulk package (NDC 0173-0363-00).

Store between 4° and 25°C (39° and 77°F); excursions permitted to 30°C (86°F). Protect from light. Store vial in carton until time of use.

GlaxoSmithKline

Research Triangle Park, NC 27709

ZANTAC is a registered trademark of Warner-Lambert Company, used under license.

MULTISTIX is a registered trademark of Bayer Healthcare LLC.

©2009, GlaxoSmithKline. All rights reserved.

April 2009

ZNP:4PI

Principal Display Panel

NDC 0173-0363-00

Zantac®

(ranitidine hydrochloride)

Injection

25 mg/mL*

40-mL Pharmacy Bulk Package – Not for Direct Infusion

Sterile

Rx only

Contents should be used as soon as possible following initial closure puncture. Discard any unused portion within 24 hours of first entry.

*Each 1 mL of aqueous solution contains ranitidine 25 mg (as the hydrochloride); phenol 5 mg as preservative; monobasic potassium phosphate and dibasic sodium phosphate as buffers.

See package insert for Dosage and Administration and directions for use of Pharmacy Bulk Package.

Store between 4o and 25oC (39o and 77oF); excursions permitted to 30oC (86oF). Protect from light. Store vial in carton until time of use.

Zantac® Injection tends to exhibit a yellow color that may intensify over time without adversely affecting potency.

Zantac is a registered trademark of Warner-Lambert Company, used under license.

GlaxoSmithKline, Research Triangle Park, NC 27709

Made in England

10000000022283 Rev. 12/05

ZANTAC  ranitidine hydrochloride  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0173-0363 Route of Administration INTRAVENOUS, INTRAMUSCULAR DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength RANITIDINE HYDROCHLORIDE (RANITIDINE) RANITIDINE HYDROCHLORIDE 25 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength PHENOL   POTASSIUM PHOSPHATE, MONOBASIC   SODIUM PHOSPHATE, DIBASIC

Product Characteristics Color YELLOW (colorless to yellow) Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0173-0363-00 40 mL In 1 VIAL, PHARMACY BULK PACKAGE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA019090	10/01/1989

Labeler - GlaxoSmithKline LLC (167380711)

Revised: 05/2011GlaxoSmithKline LLC

More Zantac Injection resources

• Zantac Injection Use in Pregnancy & Breastfeeding
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• Zantac Injection Drug Interactions
• Zantac Injection Support Group
• 32 Reviews for Zantac Injection - Add your own review/rating

Compare Zantac Injection with other medications

• Duodenal Ulcer
• Duodenal Ulcer Prophylaxis
• Erosive Esophagitis
• Gastric Ulcer Maintenance Treatment
• Gastrointestinal Hemorrhage
• GERD
• Indigestion
• Pathological Hypersecretory Conditions
• Stomach Ulcer
• Stress Ulcer Prophylaxis
• Surgical Prophylaxis
• Zollinger-Ellison Syndrome

Phenergan 10mg Tablets

1. Name Of The Medicinal Product

Phenergan 10 mg Tablets

2. Qualitative And Quantitative Composition

Each tablet contains 10mg of the active substance Promethazine hydrochloride.

Also contains 69.41mg of lactose monohydrate.

For full list of excipients, see section 6.1

3. Pharmaceutical Form

Film-coated tablet (Tablet)

Pale blue film coated tablets marked PN 10 on one side..

4. Clinical Particulars

4.1 Therapeutic Indications

As symptomatic treatment for allergic conditions of the upper respiratory tract and skin including allergic rhinitis, urticaria and anaphylactic reactions to drugs and foreign proteins.

As an adjunct in preoperative sedation in surgery and obstetrics.

As an antiemetic.

For short term use:

Sedation and treatment of insomnia in adults.

As a paediatric sedative.

4.2 Posology And Method Of Administration

Route of administration: Oral.

Not for use in children under the age of 2 years (see section 4.3)

As an antihistamine in allergy:

Children 2-5 years	The use of Phenergan Elixir is recommended for this age group.
Children 5-10 years	Either 10 or 20 mg as a single dose*. Or 10 mg bd. Maximum daily dose 20 mg.
Children over 10 years and adults (including elderly)	Initially 10 mg bd. Increasing to a maximum of 20 mg tds as required.

*Single doses are best taken at night.

As an antiemetic:

Children 2-5 years	The use of Phenergan Elixir is recommended for this age group.
Children 5-10 years	10 mg to be taken the night before the journey. To be repeated after 6–8 hours as required.
Children over 10 years and adults (including elderly)	20 mg to be taken the night before the journey. To be repeated after 6–8 hours as required.

Short term sedation:

Children 2-5 years	The use of Phenergan Elixir is recommended for this age group.
Children 5-10 years	20 mg as a single night time dose.
Children over 10 years and adults (including elderly)	20 to 50 mg as a single night time dose.

4.3 Contraindications

Phenergan should not be used in patients in coma or suffering from CNS depression of any cause.

Phenergan should not be given to patients with a known hypersensitivity to promethazine or to any of the excipients.

Promethazine is contraindicated for use in children less than two years of age because of the potential for fatal respiratory depression.

Phenergan should be avoided in patients taking monoamine oxidase inhibitors up to 14 days previously.

4.4 Special Warnings And Precautions For Use

Phenergan may thicken or dry lung secretions and impair expectoration. It should therefore be used with caution in patients with asthma, bronchitis or bronchiectasis.

Use with care in patients with severe coronary artery disease, narrow angle glaucoma, epilepsy or hepatic and renal insufficiency.

Caution should be exercised in patients with bladder neck or pyloro-duodenal obstruction.

The use of promethazine should be avoided in children and adolescents with signs and symptoms suggestive of Reye's Syndrome.

Promethazine may mask the warning signs of ototoxicity caused by ototoxic drugs e.g. salicylates. It may also delay the early diagnosis of intestinal obstruction or raised intracranial pressure through the suppression of vomiting.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Phenergan should not be used for longer than 7 days without seeking medical advice.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Phenergan will enhance the action of any anticholinergic agent, tricyclic antidepressant, sedative or hypnotic. Alcohol should be avoided during treatment. Phenergan may interfere with immunological urine pregnancy tests to produce false-positive or false-negative results. Phenergan should be discontinued at least 72 hours before the start of skin tests as it may inhibit the cutaneous histamine response thus producing false-negative results.

4.6 Pregnancy And Lactation

Phenergan should not be used in pregnancy unless the physician considers it essential. The use of Phenergan is not recommended in the 2 weeks prior to delivery in view of the risk of irritability and excitement in the neonate.

Available evidence suggests that the amount excreted in milk is insignificant. However, there are risks of neonatal irritability and excitement.

4.7 Effects On Ability To Drive And Use Machines

Because the duration of action may be up to 12 hours, patients should be advised that if they feel drowsy they should not drive or operate heavy machinery.

4.8 Undesirable Effects

Side effects may be seen in a few patients: drowsiness, dizziness, restlessness, headaches, nightmares, tiredness, and disorientation. Anticholinergic side effects such as blurred vision, dry mouth and urinary retention occur occasionally. Infants are susceptible to the anticholinergic effects of promethazine, while other children may display paradoxical hyperexcitability. The elderly are particularly susceptible to the anticholinergic effects and confusion due to promethazine. Other side-effects include urticaria, rash, pruritus, anorexia, gastric irritation, palpitations, hypotension, arrhythmias, extrapyramidal effects, muscle spasms and tic-like movements of the head and face. Anaphylaxis, jaundice and blood dyscrasias including haemolytic anaemia rarely occur. Photosensitive skin reactions have been reported. Strong sunlight should be avoided during treatment.

4.9 Overdose

Symptoms of severe overdosage are variable. They are characterised in children by various combinations of excitation, ataxia, incoordination, athetosis and hallucinations, while adults may become drowsy and lapse into coma. Convulsions may occur in both adults and children: coma or excitement may precede their occurrence. Cardiorespiratory depression is uncommon. If the patient is seen soon enough after ingestion, it should be possible to induce vomiting with ipecacuanha despite the antiemetic effect of promethazine; alternatively, gastric lavage may be used.

Treatment is otherwise supportive with attention to maintenance of adequate respiratory and circulatory status. Convulsions should be treated with diazepam or other suitable anticonvulsant.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Anthihistamines for systemic use; Phenothiazine derivatives, ATC code: R06AD02

Potent, long acting, antihistamine with additional anti-emetic central sedative and anti-cholinergic properties.

5.2 Pharmacokinetic Properties

Promethazine is distributed widely in the body. It enters the brain and crosses the placenta. Promethazine is slowly excreted via urine and bile. Phenothiazines pass into the milk at low concentrations.

5.3 Preclinical Safety Data

No additional preclinical data of relevance to the prescriber.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactose monohydrate

Maize starch

Povidone K30

Magnesium stearate

Polyethylene glycol 200

Hypromellose (Pharmacoat 606)

Colouring agent: Opaspray M-1-4210A

Titanium dioxide (E 171)

Hypromellose (E464)

Indigo carmine aluminium lake FD&C Blue no 2 (E132)

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

5 years

6.4 Special Precautions For Storage

Store below 30°C. Store in the original carton in order to protect from light.

6.5 Nature And Contents Of Container

Opaque white 250µm uPVC coated with 40gsm PVdC, 20µm hard temper aluminium foil (coated with vinyl heat seal lacquer) backing, in cartons of 56 tablets.

6.6 Special Precautions For Disposal And Other Handling

No special requirements

7. Marketing Authorisation Holder

Sanofi-aventis

One Onslow Street

Guildford

Surrey, GU1 4YS, UK

8. Marketing Authorisation Number(S)

PL 04425/0631

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of first authorisation: 3 October 2008

10. Date Of Revision Of The Text

17 October 2011

LEGAL CATEGORY

P

Galenphol Linctus

1. Name Of The Medicinal Product

Galenphol Linctus

Care Pholcodine 5mg/5ml Oral Solution Sugar Free

2. Qualitative And Quantitative Composition

Pholcodine 5.0mg (Per 5ml Dose)

For excipients, see 6.1.

3. Pharmaceutical Form

Oral liquid

A viscous red coloured liquid.

4. Clinical Particulars

4.1 Therapeutic Indications

Used for the relief of an unproductive dry cough.

4.2 Posology And Method Of Administration

For oral administration

Adult and children over 12 years:

Two or three 5ml spoonfuls three or four times daily.

Not more than 4 doses should be given in any 24 hours

Elderly:

Adult dose is appropriate.

Do not exceed the stated dose.

Keep out of the sight and reach of children.

4.3 Contraindications

Liver failure.

Should not be administered to patients in or at risk of developing respiratory failure or during an attack of asthma.

Patients receiving monoamine oxidase inhibitors or within 2 weeks of cessation of their use.

Patients with chronic bronchitis, COPD, bronchiolitis or bronchiectasis due to sputum retention.

Known hypersensitivity to any of the ingredients.

Children under 12 years of age.

4.4 Special Warnings And Precautions For Use

Should be used with caution in patients with renal, hepatic or respiratory disease, including a history of asthma. Galenphol and other cough suppressants may cause sputum retention and this may be harmful in patients with chronic bronchitis and bronchiectasis.

Ask a doctor before use if you suffer from a chronic or persistent cough, if you have asthma, are suffering from an acute asthma attack or where cough is accompanied by excessive secretions.

Use of pholcodine with alcohol or other CNS depressants may increase the effects on the CNS and cause toxicity in relatively smaller doses.

This medicine contains 1.2 vol% ethanol, i.e. up to 144 mg per 15 ml dose, equivalent to 4 ml beer or 2 ml wine. Harmful for those suffering from alcoholism. To be taken into account in pregnant or breastfeeding women, children and high risk groups such as patients with liver disease or epilepsy.

It also contains sodium hydroxybenzoates and amaranth dye which may cause allergic reactions (possibly delayed).

Do not exceed the stated dose.

Do not take with other cough and cold medicines.

If symptoms persist consult your doctor.

Do not give to children under 12 years.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Monoamine oxidase inhibitors: Galenphol should not be used within 14 days of treatment.

Interaction with neuromuscular blocking agents (anaphylaxis) has been reported.

The reduction of blood pressure caused by antihypertensives may accentuate the hypotensive effects of pholcodine. Diuretics may have the same effect.

Pholcodine may enhance the sedative effect of central nervous system depressants including alcohol, barbiturates, hypnotics, narcotic analgesics, sedatives and tranquillisers (phenothiazines and tricyclic antidepressants).

4.6 Pregnancy And Lactation

No data available on the use of Galenphol in pregnancy or lactation.

Galenphol should be avoided during pregnancy unless considered necessary by the physician and should be avoided during the first trimester. Opioid administration near term in the third trimester may cause respiratory depression in the newborn, withdrawal effects in neonates of dependent mothers, gastric stasis and risk of inhalation pneumonia in the mother during labour.

Pholcodine has been detected in human milk but in amounts usually too small to be harmful; however mothers may vary considerably in their capacity to metabolise pholcodine with a risk of morphine overdose in the infant.

4.7 Effects On Ability To Drive And Use Machines

Using the dose recommended, it is not considered to be a hazard, however, the use of pholcodine may cause sedation, dizziness and nausea. If affected, driving or operation of machinery would not be advised.

4.8 Undesirable Effects

The following side effects may be associated with the use of pholcodine:

Occasional drowsiness, dizziness, excitation, confusion, sputum retention, vomiting, gastrointestinal disturbances (nausea and constipation) and skin reactions including rash.

Immune system disorders have been noted including hypersensitivity reactions and anaphylaxis.

4.9 Overdose

It is thought to be of low toxicity, but the effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.

Symptoms of overdose include respiratory depression, nausea, drowsiness, restlessness, excitement and ataxia. Treatment should be symptomatic to maintain vital functions. Respiratory distress should be treated by supportive means. Airways protective gastric lavage may be used.

In severe cases a narcotic antagonist such as naloxone may be considered. Naloxone has been used successfully to reverse central or peripheral opioid effects in children (0.01mg/kg body weight). Other treatment option is activated charcoal (1g/kg body weight) if more than 4mg/kg has been ingested within 1 hour, provided the airway can be protected.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

R05D A08 - Opium alkaloids and derivatives.

Galenphol contains pholcodine which is a centrally acting cough suppressant. It has none of the other properties of opiate agents.

5.2 Pharmacokinetic Properties

None stated.

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Citric acid monohydrate

Nipasept sodium [containing Sodium Methyl Parahydroxybenzoate (E219), Sodium Ethyl Parahydroxybenzoate (E215) & Sodium Propyl Parahydroxybenzoate (E217)

Alcohol 96%

Amaranth (E123)

Blanose cellulose gum (7HOF)

Saccharin sodium

Menthol

Condensed milk flavour (F12516)

Aniseed flavour (545008E)

Glycerol

Purified water

6.2 Incompatibilities

None stated.

6.3 Shelf Life

Two years from the date of manufacture.

6.4 Special Precautions For Storage

Store in a cool place.

6.5 Nature And Contents Of Container

200ml amber glass bottles with 28mm tamper evident child resistant closure with EPE/Saranex liner.

Amber HDPE 2 litre Winchester with a polypropylene cap.

6.6 Special Precautions For Disposal And Other Handling

None stated.

ADMINISTRATION DETAILS

7. Marketing Authorisation Holder

Thornton & Ross Ltd

Linthwaite

Huddersfield

HD7 5QH

United Kingdom

8. Marketing Authorisation Number(S)

PL 00240/0101

9. Date Of First Authorisation/Renewal Of The Authorisation

30 August 2002

10. Date Of Revision Of The Text

08/08/2011

Metopirone Capsules 250 mg

1. Name Of The Medicinal Product

Metopirone^® Capsules 250mg

2. Qualitative And Quantitative Composition

Metyrapone BP 250mg.

3. Pharmaceutical Form

Yellowish-white, oblong, opaque, soft gelatin capsules printed 'CIBA' on one side and 'LN' on the other in brown ink.

4. Clinical Particulars

4.1 Therapeutic Indications

A diagnostic aid in the differential diagnosis of ACTH-dependent Cushing's syndrome. The management of patients with Cushing's syndrome.

In conjunction with glucocorticosteroids in the treatment of resistant oedema due to increased aldosterone secretion in patients suffering from cirrhosis, nephrosis and congestive heart failure.

4.2 Posology And Method Of Administration

Adults:

The capsules should be taken with milk or after a meal, to minimise nausea and vomiting, which can lead to impaired absorption.

For use as a diagnostic aid: the patient must be hospitalised. Urinary 17-oxygenic steroid excretion is measured over 24 hours on each of 4 consecutive days. The first 2 days serve as a control period. On the third day, 750mg Metopirone (3 capsules) must be given at four-hourly intervals to give a total of 6 doses (ie 4.5g). Maximum urine steroid excretion may occur on the fourth day. If urinary steroid excretion increases in response to Metopirone, this suggests the high levels of circulatory cortisol are due to adrenocortical hyperplasia following excessive ACTH production rather than a cortisol-producing adrenal tumour.

For therapeutic use: for the management of Cushing's syndrome, the dosage must be adjusted to meet the patient's requirements; a daily dosage from 250mg to 6g may be required to restore normal cortisol levels.

For the treatment of resistant oedema: The usual daily dose of 3g (12 capsules) should be given in divided doses in conjunction with a glucocorticoid.

Children: Children should be given a smaller amount based upon 6 four-hourly doses of 15mg/kg, with a minimum dose of 250mg every four hours.

Elderly: Clinical evidence would indicate that no special dosage regimen is necessary.

4.3 Contraindications

Primary adrenocorticol insufficiency. Hypersensitivity to Metopirone or to any of the excipients. Pregnancy.

4.4 Special Warnings And Precautions For Use

In relation to use as a diagnostic aid: anticonvulsants (eg phenytoin, barbiturates), anti-depressants and neuroleptics (eg amitriptyline, chlorpromazine), hormones that affect the hypothalamo-pituitary axis and anti-thyroid agents may influence the results of the Metopirone test. If these drugs cannot be withdrawn, the necessity of carrying out the Metopirone test should be reviewed.

If adrenocortical or anterior pituitary function is more severely compromised than indicated by the results of the test, Metopirone may trigger transient adrenocortical insufficiency. This can be rapidly corrected by giving appropriate doses of corticosteroids.

Long-term treatment with Metopirone can cause hypertension as the result of excessive secretion of desoxycorticosterone.

The ability of the adrenal cortex to respond to exogenous ACTH should be demonstrated before Metopirone is employed as a test, as Metopirone may induce acute adrenal insufficiency in patients with reduced adrenal secretory capacity, as well as in patients with gross hypopituitarism.

Patients with liver cirrhosis often show a delayed response to Metopirone, due to liver damage delaying the metabolism of cortisol.

In cases of thyroid hypofunction, urinary steroid levels may rise very slowly, or not at all, in response to Metopirone.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

In some cases concomitant medication may affect the results of the Metopirone test (see Section 4.4, Special warnings and precautions for use).

4.6 Pregnancy And Lactation

No data are available from animal reproduction studies. Metopirone should not be administered during pregnancy since the drug can impair the biosynthesis of foetal-placental steroids. It is not known whether metyrapone passes into the breast milk, therefore nursing mothers should refrain from breast-feeding their infants during treatment with Metopirone.

4.7 Effects On Ability To Drive And Use Machines

Patients should be warned of the potential hazards of driving or operating machinery if they experience side effects such as dizziness and sedation.

4.8 Undesirable Effects

Gastrointestinal tract: Occasional: nausea, vomiting. Rare: abdominal pain.

Central nervous system: Occasional: dizziness, sedation, headache.

Cardiovascular system: Occasional: hypotension.

Skin: Rare: allergic skin reactions.

Endocrine system: Rare: hypoadrenalism, hirsutism.

4.9 Overdose

Signs and symptoms: The clinical picture of acute Metopirone poisoning is characterised by gastrointestinal symptoms and acute adrenocortical insufficiency. Laboratory findings: hyponatraemia, hypochloraemia, hyperkalaemia. In patients under treatment with insulin or oral antidiabetics, the signs and symptoms of acute poisoning with Metopirone may be aggravated or modified.

Treatment: There is no specific antidote. Gastric lavage and forced emesis should be employed to reduce the absorption of the drug. In addition to general measures, a large dose of hydrocortisone should be administered at once, together with iv saline and glucose. This should be repeated as necessary in accordance with the patient's clinical condition. For a few days, blood pressure and fluid and electrolyte balance should be monitored.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Metopirone inhibits the enzyme responsible for the 11β-hydroxylation stage in the biosynthesis of cortisol and to a lesser extent, aldosterone. The fall in plasma concentration of circulating glucocorticoids stimulates ACTH secretion, via the feedback mechanism which accelerates steroid biosynthesis. As a result, 11-desoxycortisol, the precursor of cortisol, is released into the circulation, metabolised by the liver and excreted in the urine. Unlike cortisol, 11-desoxycortisol does not suppress ACTH secretion and its urinary metabolites may be measured.

These metabolites can easily be determined by measuring urinary 17-hydroxycorticosteroids (17-OHCS) or 17-ketogenic steroids (17-KGS). Metopirone is used as a diagnostic test on the basis of these properties, with plasma 11-desoxycortisol and urinary 17-OHCS measured as an index of pituitary ACTH responsiveness. Metopirone may also suppress biosynthesis of aldosterone, resulting in mild natriuresis.

5.2 Pharmacokinetic Properties

Metyrapone is rapidly absorbed and eliminated from the plasma. Peak plasma levels usually occur one hour after ingestion of Metopirone; after a dose of 750mg Metopirone, plasma drug levels average 3.7μg/ml. Plasma drug levels decrease to a mean value of 0.5μg/ml 4 hours after dosing. The half-life of elimination of Metopirone from the plasma is 20 to 26 minutes.

Metyrapol, the reduced form of metyrapone, is the main active metabolite. Eight hours after a single oral dose, the ratio of metyrapone to metyrapol in the plasma is 1:1.5. Metyrapol takes about twice as long as metyrapone to be eliminated in the plasma.

Seventy-two hours after a first daily dose of 4.5g Metopirone (750mg every 4 hours), 5.3% of the total dose was excreted in the urine as metyrapone (9.2% in free form and 90.8% conjugated with glucuronic acid), and 38.5% in the form of metyrapol (8.1% in free form and 91.9% conjugated with glucuronic acid).

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to those already included in other sections of the Summary of Product Characteristics.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Capsule contents: Glycerin, polyethylene glycol 400, polyethylene glycol 4000 and water. Capsule shell: Sodium ethylparaben, ethyl vanillin, gelatin, glycerin 85%, p-methoxy acetophenone, sodium propylparaben and titanium oxide (E171).

6.2 Incompatibilities

None stated.

6.3 Shelf Life

3 years

6.4 Special Precautions For Storage

Protect from moisture and heat. Store below 30°C.

6.5 Nature And Contents Of Container

High density polyethylene bottles of 100 capsules.

6.6 Special Precautions For Disposal And Other Handling

None stated.

Administrative Details

7. Marketing Authorisation Holder

Alliance Pharmaceuticals Ltd

Avonbridge House

Bath Road

Chippenham

Wiltshire

SN15 2BB

8. Marketing Authorisation Number(S)

PL16853/0010

9. Date Of First Authorisation/Renewal Of The Authorisation

June 1998

10. Date Of Revision Of The Text

30th June 2009

Legal status

POM

Alliance, Alliance Pharmaceuticals and associated devices are registered Trademarks of Alliance Pharmaceuticals Ltd.

cytarabine

sye-TAYR-a-been

Pharmacologic Class: Antimetabolite

Uses For cytarabine

Cytarabine belongs to the group of medicines called antimetabolites. It is used to treat some kinds of cancers of the blood. It may also be used to treat other kinds of cancer, as determined by your doctor.

Cytarabine interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by cytarabine, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects, like hair loss, may not be serious but may cause concern. Some effects may not occur for months or years after the medicine is used.

Before you begin treatment with cytarabine, you and your doctor should talk about the good cytarabine will do as well as the risks of using it.

Cytarabine is to be administered only by or under the immediate supervision of your doctor.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, cytarabine is used in certain patients with the following medical conditions:

• Cancer of the lymph system


• Cancer of the brain and spinal cord


• Myelodysplastic syndromes (MDS)

Before Using cytarabine

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For cytarabine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to cytarabine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Although there is no specific information comparing use of cytarabine in children with use in other age groups, cytarabine is not expected to cause different side effects or problems in children than it does in adults.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing use of cytarabine in the elderly with use in other age groups, cytarabine is not expected to cause different side effects or problems in older people than it does in younger adults.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	D	Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking cytarabine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using cytarabine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Rotavirus Vaccine, Live

Using cytarabine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Adenovirus Vaccine Type 4, Live


• Adenovirus Vaccine Type 7, Live


• Bacillus of Calmette and Guerin Vaccine, Live


• Influenza Virus Vaccine, Live


• Measles Virus Vaccine, Live


• Mumps Virus Vaccine, Live


• Rotavirus Vaccine, Live


• Rubella Virus Vaccine, Live


• Smallpox Vaccine


• Typhoid Vaccine


• Varicella Virus Vaccine


• Yellow Fever Vaccine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of cytarabine. Make sure you tell your doctor if you have any other medical problems, especially:

• Chickenpox (including recent exposure) or


• Herpes zoster (shingles)—Risk of severe disease affecting other parts of the body

• Gout (history of) or


• Kidney stones (history of)—Cytarabine may increase levels of uric acid in the body, which can cause gout or kidney stones

• Infection—Cytarabine can decrease your body's ability to fight infection

• Kidney disease or


• Liver disease—Effects of cytarabine may be increased because of slower removal from the body

Proper Use of cytarabine

cytarabine is sometimes given together with certain other medicines. If you are using a combination of medicines, it is important that you receive each one at the proper time. If you are taking some of these medicines by mouth, ask your health care professional to help you plan a way to take them at the right times.

While you are receiving cytarabine, your doctor may want you to drink extra fluids so that you will pass more urine. This will help prevent kidney problems and keep your kidneys working well.

cytarabine often causes nausea and vomiting. However, it is very important that you continue to receive the medicine even if you begin to feel ill. Ask your health care professional for ways to lessen these effects.

Dosing

The dose of cytarabine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of cytarabine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

Precautions While Using cytarabine

It is very important that your doctor check your progress at regular visits to make sure that cytarabine is working properly and to check for unwanted effects.

While you are being treated with cytarabine, and after you stop treatment with it, do not have any immunizations (vaccinations) without your doctor's approval. Cytarabine may lower your body's resistance and there is a chance you might get the infection the immunization is meant to prevent. In addition, other persons living in your household should not take oral polio vaccine since there is a chance they could pass the polio virus on to you. Also, avoid persons who have taken oral polio vaccine. Do not get close to them and do not stay in the same room with them for very long. If you cannot take these precautions, you should consider wearing a protective face mask that covers the nose and mouth.

Cytarabine can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.


• Check with your doctor immediately if you notice any unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on your skin.


• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.


• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.


• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.


• Avoid contact sports or other situations where bruising or injury could occur.

cytarabine Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Less common

• Black, tarry stools


• blood in urine


• cough or hoarseness


• fever or chills


• lower back or side pain


• painful or difficult urination


• pinpoint red spots on skin


• unusual bleeding or bruising

Check with your doctor as soon as possible if any of the following side effects occur:

More common

• Sores in mouth and on lips

Less common

• Joint pain


• numbness or tingling in fingers, toes, or face


• swelling of feet or lower legs


• unusual tiredness

Rare

• Bone or muscle pain


• chest pain


• decrease in urination


• difficulty in swallowing


• fainting spells


• general feeling of discomfort or illness or weakness


• heartburn


• irregular heartbeat


• pain at place of injection


• reddened eyes


• shortness of breath


• skin rash


• weakness


• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Loss of appetite


• nausea and vomiting

Less common or rare

• Diarrhea


• dizziness


• headache


• itching of skin


• skin freckling

cytarabine may cause a temporary loss of hair in some people. After treatment with cytarabine has ended, normal hair growth should return.

After you stop using cytarabine, it may still produce some side effects that need attention. During this period of time, check with your doctor immediately if you notice the following side effects:

• Black, tarry stools


• blood in urine or stools


• cough or hoarseness


• fever or chills


• lower back or side pain


• painful or difficult urination


• pinpoint red spots on skin


• unusual bleeding or bruising

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More cytarabine resources

• Cytarabine Use in Pregnancy & Breastfeeding
• Cytarabine Drug Interactions
• Cytarabine Support Group
• 0 Reviews for Cytarabine - Add your own review/rating

• cytarabine Concise Consumer Information (Cerner Multum)


• Cytarabine Prescribing Information (FDA)


• Cytarabine Professional Patient Advice (Wolters Kluwer)


• Cytarabine MedFacts Consumer Leaflet (Wolters Kluwer)


• Cytarabine Monograph (AHFS DI)

Compare cytarabine with other medications

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• Leukemia
• Meningeal Leukemia
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