Zantac (Ranitidine)

What Is Zantac (Ranitidine)?

This medicine contains Ranitidine Hydrochloride, which belongs to a group of medicines called histamine H2 antagonists. They work by reducing the amount of acid in your stomach.

It can be used to relieve the symptoms of indigestion and heartburn caused by too much acid in the stomach.

Pharmacokinetics

Ranitidine is readily absorbed from the gastrointestinal tract, with peak concentrations in plasma occurring about 2 to 3 hours after oral doses. Food does not significantly impair absorption. The bioavailability of ranitidine after oral doses is about 50%. Ranitidine is rapidly absorbed on intramuscular injection, with peak plasma concentrations occurring in about 15 minutes. It is weakly bound, about 15%, to plasma proteins. The elimination half-life is about 2 to 3 hours and is increased in renal impairment.

A small proportion of ranitidine is metabolized in the liver to the N-oxide, the N-oxide, and desmethyl ranitidine, and the S-oxide is the major metabolite but accounts for only about 4 to 6% of a dose. About 30% of an oral dose and 70% of an intravenous dose are excreted unchanged in the urine in 24 hours, primarily by active tubular secretion; there is some excretion in the feces. Ranitidine crosses the placental barrier and is distributed into breast milk.

Distribution into Breast Milk

A study of a mother given multiple doses of ranitidine showed higher concentrations in breast milk than in serum. The minimum milk concentration occurred between 1 and 2 hours after a dose, and the highest concentration was towards the end of the 12-hour dosing interval. The amount the infant would ingest could not be reliably estimated because of the variable milk-to-serum ratio.

Enterohepatic Recycling

Some individuals have a second peak in the plasma concentration of ranitidine, which could be due to enterohepatic recirculation. However, only 0.7 to 2.6% and 0.3 to 1.0% of a ranitidine dose was excreted into the bile of 3 patients in 24 hours after 50 mg was given intravenously or 300 mg by mouth, respectively, indicating that significant recirculation did not occur.

Neonates

Renal function is limited in the first month of life, and reduced clearance of ranitidine would be expected. Blood samples taken from 27 full-term neonates given a single intravenous dose of ranitidine 2.4mg/kg revealed the following pharmacokinetic data:

• elimination half-life;
• 3.45 hours total volume of distribution;
• 1.52 liters/kg total plasma clearance;
• 5.02 mL/kg per minute.

None of the infants had renal or hepatic impairment. Another study found an elimination half-life of 6.61 hours in 13 full-term neonates given ranitidine 2 mg/kg. See also Administration in Children section.

Uses and Administration

Ranitidine is a histamine H2-antagonist with actions and uses similar to those of Cimetidine. Ranitidine may be given orally or parenterally by the intravenous or intramuscular routes. Although most preparations contain ranitidine hydrochloride, strengths, and doses are expressed in terms of the base. Ranitidine hydrochloride 111.6 mg is equivalent to about 100 mg of ranitidine.

In managing benign gastric and duodenal ulceration, a single oral dose of 300 mg at bedtime or 150 mg twice daily (in the morning and at bedtime) is given initially for at least four weeks. A dose of 300 mg twice daily may also be used for duodenal ulcers. Where appropriate, a maintenance dose of 150 mg daily may be given at bedtime. Ranitidine 150 mg twice daily may be given during therapy with NSAIDs for prophylaxis against duodenal ulceration. A suggested dose for the treatment of peptic ulcer in children is 2 to 4 mg/kg twice daily to a maximum of 300 mg in 24 hours. A maintenance dose of 2 to 4 mg/kg once daily may be used, to a maximum of 150 mg daily.

For duodenal ulcer associated with Helicobacter pylori infection, ranitidine in a usual oral dose of 300 mg once daily or 150 mg twice daily may be given as part of triple therapy with amoxicillin 750 mg and metronidazole 500 mg, both three times daily, for two weeks. Therapy with ranitidine should then be continued for a further two weeks.

In gastro-oesophageal reflux disease, the oral dose is 150 mg twice daily or 300 mg at bedtime for up to 8 weeks or, if required, 12 weeks. In severe cases, this may be increased to 150 mg four times daily for up to 12 weeks. A dose of 150 mg twice daily may be used to maintain healing erosive oesophagitis. Although there is limited data on the use of ranitidine for gastro-oesophageal reflux disease and erosive oesophagitis in children, a dose of 5 to 10 mg/kg daily, usually given in 2 divided doses, has been used.

In pathological hypersecretory conditions, such as the Zollinger-Ellison syndrome, the initial oral dose is usually 150 mg twice or three times daily and may be increased if necessary doses of up to 6 g daily have been used. Alternatively, an intravenous infusion may be given, initially at a rate of 1 mg/kg per hour; the rate may be increased by increments of 500 micrograms/kg per hour, beginning after 4 hours, if required.

For the management of patients at risk from stress ulceration of the upper gastrointestinal tract, parenteral therapy may be given as a slow intravenous injection of a 50-mg priming dose followed by a continuous intravenous infusion of 125 to 250 micrograms/kg per hour. Once oral feeding is resumed, oral doses of 150 mg twice daily may be given.

In patients at risk of developing acid aspiration syndrome during general anesthesia, an oral dose of 150 mg may be given 2 hours before the induction of anesthesia and preferably also 150 mg the previous evening. Alternatively, a dose of 50 mg may be given by intramuscular or slow intravenous injection 45 to 60 minutes before the induction of anesthesia. In obstetric patients, at the start of labor, an oral dose of 150 mg may be given and repeated at intervals of 6 hours if required.

In patients with chronic episodic dyspepsia, a dose of 150 mg twice daily orally for up to 6 weeks may be given. For the short-term symptomatic relief of dyspepsia, a dose of 75 mg, repeated if necessary, up to a maximum of 4 doses daily, may be taken. Treatment should be restricted to a maximum of 2 weeks of continuous use at one time.

Parenteral Dosage

The usual dose of ranitidine by intramuscular or intravenous injection is 50 mg, which may be repeated every 6 to 8 hours. The intravenous injection should be given slowly over not less than 2 minutes and should be diluted to contain 50 mg in 20 mL. For an intermittent intravenous infusion, the recommended dose in the UK is 25 mg/hour for 2 hours, which may be repeated every 6 to 8 hours. A rate of 6.25 mg/hour has been suggested for continuous intravenous infusion. However, higher rates may be used for conditions such as Zollinger-Ellison syndrome or in patients at risk from stress ulceration.

Dosage In Renal Impairment

For dosage in renal impairment, see below.

Administration in Сhildren

The disposition of ranitidine in children is not significantly different from that in young adults, and an oral dose of 2 mg/kg (about equal to an adult dose of 150 mg) has been used to prevent acid aspiration in children undergoing surgery. A study in premature infants being treated with dexamethasone for bronchopulmonary dysplasia found that infusion of ranitidine 62.5 micrograms/kg per hour was sufficient to raise and maintain gastric pH above 4 to help protect against gastrointestinal bleeding and perforation. Another study found 500 micrograms/kg twice daily sufficient for preterm infants, but 1.5 mg/kg three times daily was needed for full-term infants. A daily minimum dosage of 3 mg/kg was suggested for stress ulcer prophylaxis in older infants and children.

Administration in Renal Impairment

A study in patients with varying degrees of renal impairment found that the mean terminal half-life of ranitidine was increased from 2.09 hours in subjects with normal renal function to between 4.23 and 8.45 hours in patients with renal impairment, the degree of prolongation being proportional to the degree of impairment as measured by glomerular filtration rate. As a result of these findings, the ranitidine dose should be halved in patients with a glomerular filtration rate of 20 mL/minute or less. Licensed drug information, therefore, recommends that the dosage of ranitidine be reduced in patients with severe renal impairment. For patients with a creatinine clearance of less than 50 ml/minute, an oral dose of 150 mg daily is recommended, which may be cautiously increased to 150 mg every 12 hours if needed.

For intravenous use, licensed recommendations vary between countries. In the UK, individual doses may be reduced to 25 mg. In comparison, the frequency is adjusted in the USA to give a recommended usual dose of 50 mg every 18 to 24 hours, which may be cautiously increased to every 12 hours or more often if necessary. Ranitidine 150 mg daily provided adequate serum concentrations without excessive accumulation in 20 patients undergoing regular hemodialysis. The serum-ranitidine concentrations fell by about 50% during a 4-hour hemodialysis session, but less than 3% of the dose was removed, and supplemental doses after dialysis were considered unnecessary.

Cystic Fibrosis

A comparative study involving 29 patients with cystic fibrosis found that ranitidine was more effective than cisapride in improving dyspeptic symptoms and gastric emptying and distension. Antisecretory drugs are also used in this condition to decrease the inactivation of oral pancreatic enzyme therapy.

Immunomodulation

Like Cimetidine, ranitidine has been proposed to have immunoregulatory effects. However, ranitidine 300 mg twice daily did not affect absolute CD4 cell counts or plasma HIV RNA in patients with HIV infection in a placebo-controlled study. Similarly, ranitidine had no significant benefit in patients with gastric cancer.

Skin Disorders

As with Cimetidine, ranitidine has been tried in various skin disorders. Ranitidine 300 mg twice daily by mouth has been reported to be beneficial as an adjuvant to local treatment with corticosteroids and a moisturizing ointment in patients with atopic dermatitis. There are reports of improvements in psoriasis after the use of ranitidine. However, this field is notoriously difficult to evaluate because of the chronic relapsing and remitting nature of the disease, and others have failed to show benefit.

Adverse Effects

As for Cimetidine. But unlike Cimetidine, ranitidine has little or no anti-androgenic effect despite isolated reports of gynaecomastia and impotence.

Carcinogenicity

For a discussion of the possible association between histamine H2-antagonists and cancer, including mention of a study with ranitidine, see Cimetidine.

Effects on the Blood

For a discussion of the adverse hematological effects of H2-antagonists, see Cimetidine.

Effects on the Cardiovascular System

Similarly to Cimetidine, bradycardia, AV block, and cardiac arrest have been reported rarely during ranitidine therapy. A positive inotropic effect, without significant changes in heart rate or blood pressure, has also been reported in healthy subjects, and pretreatment with ranitidine has blocked the cardiac depressant effects seen in some subjects given famotidine or nizatidine. Although studies in critically ill patients and healthy subjects have found no adverse hemodynamic effects associated with ranitidine, a small proportion of patients are likely more susceptible to the cardiovascular effects of ranitidine. Caution is recommended when ranitidine is given intravenously, particularly in patients with cardiovascular disease.

Effects on the Endocrine System

Unlike Cimetidine, ranitidine does not bind to androgen receptors and has little or no anti-androgenic effect. Studies in men taking ranitidine for the management of duodenal ulcers reported no significant changes in the plasma concentrations of testosterone, luteinizing hormone, follicle-stimulating hormone, or prolactin after up to 2 years of treatment, no significant changes in sperm concentration, motility, or morphology were noted. There have been isolated reports of gynecomastia, loss of libido, and impotence associated with ranitidine. Still, in 9 patients with cimetidine-induced breast changes and impotence, transfer to ranitidine resulted in the resolution of these symptoms.

Effects on the Eyes

For a report of an increase in intra-ocular pressure associated with ranitidine, see under Cimetidine. A cohort study involving 140 128 patients receiving anti-ulcer therapy, 70 389 of whom received ranitidine, found no evidence that any drugs studied were associated with a significantly increased risk of vascular or inflammatory eye disorders.

For the loss of color vision in a child receiving ranitidine, see the Effects on the Nervous System section.

Effects on the Kidneys

For interstitial nephritis associated with H2-antagonists, including ranitidine, see the Cimetidine section.

Effects on the Liver

There have been some case reports of ranitidine hepatotoxicity. The increase in relative risk seen in a large cohort study involving 108 891 patients receiving antisecretory therapy was less for ranitidine (1.7:1) than for Cimetidine.

Effects on the Nervous System

Ranitidine has been associated with adverse neurological effects, including confusion, loss of color vision, aggressiveness, lethargy, tiredness, disorientation, depression, hallucinations, and severe headache. As with Cimetidine, these reactions occur mainly in senior patients, the severely ill, or patients with renal or hepatic impairment. Single-dose studies in young, healthy subjects have found no adverse changes in performance, CNS function, or subjective assessment of mood after oral doses of ranitidine 150 or 300 mg.

Effects on the Skin

A report of vasculitic rash occurring in 3 patients undergoing ranitidine therapy. In each case, the rash cleared after withdrawal of the drug.

See also the Hypersensitivity and Cimetidine sections.

Fever

A report of pyrexia associated with ranitidine. Apart from the raised temperature, the patient was otherwise well. The fever resolved on stopping ranitidine and recurred on rechallenge.

Hypersensitivity

Respiratory stridor and an urticarial rash occurred in a patient shortly after taking the first dose of ranitidine. The symptoms responded to adrenaline subcutaneously.

Meningitis

A 30-year-old man developed aseptic meningitis on three occasions after the use of ranitidine. In each case, symptoms resolved rapidly upon withdrawal of the drug.

Precautions

As for Cimetidine.

Hepatic Impairment

Sixteen of 27 patients with cirrhosis of the liver and indications for treatment with an H2-antagonist (peptic ulcer, gastritis, or reflux oesophagitis) failed to respond to ranitidine 300 mg compared with six failures from 32 patients without cirrhosis. Famotidine 40 mg was given to 10 of the cirrhotic nonresponders, and eight still had no response 7 of these patients were given Cimetidine 800 mg, and only one responded. In the control group, all three patients given famotidine did not respond, and only one responded when given Cimetidine. It was concluded that the incidence of non-response to H2-antagonists is increased in patients with liver cirrhosis, but no explanation could be given for this effect. Interestingly, there is an earlier report of patients with cirrhosis demonstrating increased bioavailability and decreased clearance of ranitidine.

Porphyria

Ranitidine is considered to be unsafe in patients with porphyria, although there is conflicting experimental evidence of porphyrinogenicity.

Renal Impairment

For evidence of reduced clearance of ranitidine in patients with renal impairment, see Administration in Renal Impairment section.

Interactions

Unlike Cimetidine, ranitidine does not seem to affect cytochrome P450 to any great extent and, therefore, is considered to have little effect on the metabolism of other drugs. However, as with other H2 antagonists, its effects on gastric pH may alter the absorption of some other drugs.

Cisapride

Peak plasma ranitidine concentrations were achieved more rapidly in 12 healthy subjects taking cisapride. The clinical significance is questionable, and such combinations have been used clinically, although cisapride is now restricted in most countries.

How to Store This Medicine

Do not store above 25°C.

Please keep it in the original carton and protect it from light.

Keep this medicine safe out of the sight and reach of children, preferably in a locked cupboard.

Use until the expiration date indicated on the pack.

Drug Approvals

(British Approved Name, US Adopted Name, rINN)

(British Approved Name, US Adopted Name, rINN)

Synonyms: AH-19065; Ranitidiini; Ranitidin; Ranitidina; Ranitidinum

BAN: Ranitidine

USAN: Ranitidine

INN: Ranitidine [rINN (en)]

INN: Ranitidina [rINN (es)]

INN: Ranitidine [rINN (fr)]

INN: Ranitidinum [rINN (la)]

INN: Ранитидин [rINN (ru)]

Chemical name: NN-Dimethyl-5-[2-(1-methylamino-2-nitrovinylamino)ethylthiomethyl]furfurylamine

Molecular formula: C13H22N4O3S =314.4

CAS: 66357-35-5

ATC code: A02BA02

Ranitidine Hydrochloride

(British Approved Name Modified, rINNM)

Drug Nomenclature

Synonyms: AH-19065; Ranitidiinihydrokloridi; Ranitidin-hidroklorid; Ranitidin-hydrochlorid; Ranitidina, hidrocloruro de; Ranitidinhydroklorid; Ranitidini Hydrochloridum; Ranitidino hidrochloridas

BAN: Ranitidine Hydrochloride [BANM]

INN: Ranitidine Hydrochloride [rINNM (en)]

INN: Hidrocloruro de ranitidina [rINNM (es)]

INN: Ranitidine, Chlorhydrate de [rINNM (fr)]

INN: Ranitidine Hydrochloridum [rINNM (la)]

INN: Ранитидина Гидрохлорид [rINNM (ru)]

Molecular formula: C13H22N4O3S,HCl =350.9

CAS: 66357-59-3

ATC code: A02BA02

Read code: y01Ph

Pharmacopoeias. In China, Europe, Japan, and the US.

European Pharmacopoeia, 6th ed. (Ranitidine Hydrochloride). A white or pale yellow crystalline powder. It exhibits polymorphism. Freely soluble in water, sparingly or slightly soluble in dehydrated alcohol, and very slightly soluble in dichloromethane. A 1% solution in water has a pH of 4.5 to 6.0. Store in airtight containers. Protect from light.

The United States Pharmacopeia 31, 2008 (Ranitidine Hydrochloride). A white to pale yellow, practically odorless, crystalline powder. It is sensitive to light and moisture. Very soluble in water, sparingly soluble in alcohol. A 1% solution in water has a pH of 4.5 to 6.0. Store in airtight containers. Protect from light.

Preparations

British Pharmacopoeia 2008: Ranitidine Injection; Ranitidine Oral Solution; Ranitidine Tablets

The United States Pharmacopeia 31, 2008: Ranitidine in Sodium Chloride Injection; Ranitidine Injection; Ranitidine Oral Solution; Ranitidine Tablets

Proprietary Preparations

The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.

Argentina: Acidex; Aludrox AC¤; Aprical; Ciscomax; Dualid; Espaven; Faboacid-R; Fendibina; Gastrial; Gastrolets; Gastrosedol; Gastrozac; Insuflen¤; Luvier; Notrab; Ranimed; Ranitic; Ranitidi GNO¤; Ranitral; Ranitul; Raticina; Reco; Reflux; Sustac; Taural; Telus¤; Teogrand; Tomag; Ulcotenk; Urgis; Vingional; Vizerul; Zantac;
Australia: Ausran; Heartburn Relief; Rani 2; Ranihexal; Ranitic; Ranoxyl; Zantac;
Austria: Digestosan¤; Ranic; Raninorm; Ranityrol; Ulsal; Zantac; Zantarac; Belgium: Ranic¤; Zantac;
Brazil: Antagon; Antak; Antanidina¤; Antidin; Aziliv; Gastrat; Label; Logat; Neosac; Nititom; Prevulcer; Rabiodina; Radan; Raniclor; Ranidin; Ranidina; Ranidine; Raniflex; Ranitak; Ranitil; Ranitin; Ranitinol; Ranition; Ranitrat; Ranitzen; Ranizol; Ranytisan; Regalil¤; Rhanitak; Tazepin; Ulcerit; Ulcerocin; Ulcoren; Zadine; Zilak¤; Zylium;
Canada: Acid Reducer; Novo-Ranidine; Nu-Ranit; Peptic Relief¤; Zantac; Chile: Aciflux; Ranicel; Ranitax; Tipac; Zantac;
Czech Republic: Arnetin; Histac; Raniberl; Ranisan; Ranital; Ranitin; Ulcosan; Ulran; Zantac;
Denmark: Aducin¤; Kuracid; Ranicodan; Ranikur¤; Zantac;
Finland: Esofex; Inside Brus; Ranicur; Ranil; Ranimex; Ranixal; Zantac;
France: Azantac; Raniplex; Ulcirex¤; Zidac¤;
Germany: Azuranit¤; Junizac; Phamoranit¤; Ran Lich; Rani-nerton; Rani; Raniberl; Ranibeta; Ranibloc; Ranicux; Ranidura T; Ranimerck; Raniprotect; Ranitab; Ranitic; Ranitidoc; Sostril; Ulcolind Rani¤; Zantic;
Greece: Alphadine; Aova; B-Alcerin¤; Baroxal; Bindazac; Blumol; Brixoral; Ceftrinal; Epadoren; Ezopta; Galebiron¤; Gaproxen; Gertocalm; Lomadryl; Lumaren; Narigen; Nipodur; Nitised; Odanet¤; Ptinolin; Raniclon; Ranizac; Restopon; Ribolin; Rothonal; Semuele; Smaril; Soredine¤; Specinor; Sveltanet; Synthomanet; Tupast; Verlost; Yara; Zantac; Zoliden; Zurfix;
Hong Kong: Gastril; Hyzan; LAtac; Novo-Ranidine; Radin; Ranolta; Simetac; Synitidine; Zantac; Zendhin;
Hungary: Histac; Huma-Ranidine; Ranitic; Ulceran; Ulcosin; Umaren; Xanomel; Zantac;
India: Aciloc; Consec; Histac; R-Loc; Rantac¤; Ultac; Zinetac;
Ireland: Gertac; Ranitic; Ranopine; Xanomel; Zandine¤; Zantac;
Israel: Apozan¤; Zanidex; Zantab¤; Zantac; Italy: Dolilux; Duoran; Mauran¤; Nodol¤; Raniben; Ranibloc; Ranidil; Sensigard; Trigger¤; Ulcex; Ulkobrin¤; Zantac;
Malaysia: Arnetin; Histac; Hyzan; Rintac¤; Vesyca; X’tac; Zantac; Zendhin;
Mexico: Acloral; Agrisen; Aldivina; Alter-H2¤; Alvidina¤; Anistal; Anticina; Apoprin; Avintac; Azantac; Cauteridol¤; Credaxol; Danitin¤; Dinaxin; Flatmed; Galidrin; Gastrec; Gastridin; Gasyran¤; Iqfadina; Katalem; Microdit; Microtid¤; Midaven; Neugal; Offentina; Radyn; Ranepal; Ranifarm; Ranifur; Raniger; Ranisen; Ranulin¤; Ranzil; Raudil; Redacid; Serranit; Serviradine; Sinhcloran; Sirani¤; Suronit¤; Terodul; Tianak; Ulcedin¤; Ulcevit; Ulkodin; Ulmodhyl; Ulsaven; Ultran; Unitin; Zerandin¤;
Netherlands: Zantac; Norway: Inside Brus; Noktone¤; Ranacid¤; Zantac;
New Zealand: Zanidin¤; Zantac; Portugal: Gastridina; Gastrolav; Gastrulcer; Pep-Rani; Peptab; Peptifar; Quardin; Ran; Ranitine; Stacer; Ulcecur; Ulcerol; Zantac;
Russia: Histac (Гистак); Ranigast (Ранигаст); Ranisan (Ранисан); Rantac (Рантак); Ulran (Ульран); Zantac (Зантак); Zoran (Зоран);
South Africa: GI-Tak; Histak; Ranihexal; Ranteen; Ulcaid; Ultak; Zantac;
Singapore: Gastran¤; Histac; Hyzan; Lumaren; Neoceptin-R; Rani¤; Ranidine; Ratic; Xanidine; Zantac; Zendhin; Zoran¤;
Spain: Alquen; Arcid; Ardoral; Coralen; Denulcer; Fagus; Lake; Meticel; Quantor; Ran H2; Ranidin; Ranilonga¤; Ranivel¤; Ranix; Ranuber; Rubiulcer; Tanidina; Terposen; Toriol; Underacid; Zantac;
Sweden: Artonil; Inside; Rani-Q; Zantac;
Switzerland: Ranimed; Ranisifar; Ulcidine; Zantic;
Thailand: Aciloc; Histac; Radine¤; Ranicid; Ranidine; Ratic; Ratica; Utac; Xanidine; Zanamet; Zantac; Zantidon; United Arab Emirates: Rantag;
United Kingdom: Gavilast; Indigestion Relief¤; Ranaps¤; Ranitic; Ranitil; Rantec; Ranzac; Vivatak¤; Zaedoc¤; Zantac;
United States: Zantac;
Venezuela: Aplom; Enteral; Gastac; Ranibloc; Ranifesa; Ranix; Ranizan; Retamin; Vizerul; Zantac; Zoran