Zantak - instructions for use, doses, side effects, contraindications

Components	Ampoule content, in mg	Content in 1 ml, in mg
Active substance
Ranitidine hydrochloride	56,00	28,00
Excipients
Sodium chloride	3,20	1,60
Potassium dihydrogen phosphate	1,92	0,96
Sodium hydrophosphate anhydrous	4,80	2,40
Water for injections	up to 2 ml	up to 1 ml

Note:

This amount of ranitidine hydrochloride is equivalent to 50 mg and 25 mg ranitidine in a 2 ml vial and 1 ml solution, respectively.

Description:Transparent colorless or light yellow liquid.

Pharmacotherapeutic group:A drug that reduces the secretion of the glands of the stomach - H2-histamine receptor blocker

ATX: & nbsp

A.02.B.A Blockers of histamine H2-receptors

A.02.B.A.02 Ranitidine

Pharmacodynamics:

Mechanism of action

Ranitidine is a specific fast-acting blocker H₂-gistaminovyh receptors. Suppresses basal and stimulated gastric secretion, reducing its volume and content of hydrochloric acid and pepsin in secret.

Pharmacokinetics:

Suction

Suction ranitidine after intramuscular injection is rapid, the maximum concentration in the blood plasma is usually reached within 15 minutes after administration.

RAssignment

Ranitidine binds to blood plasma proteins to a small extent (15%), but has a large volume of distribution - ranging from 96 to 142 liters.

Metabolism

Ranitidine is not subjected to intensive metabolism. Part of the dose excreted in the form of ranitidine metabolites is practically the same for oral and intravenous administration. 6% of the dose is excreted by the kidneys in the form of N-oxide, 2% - in the form of S2% in the form of desmethylranitidine and 1 -2% in the form of an analogue of a furancarboxylic acid.

Excretion

The half-life of ranitidine is 2-3 hours with a two-phase decrease in its concentration in the plasma.

The main way of excretion is through the kidneys. After intravenous administration of 150 mg ³N-ranitidine was withdrawn 98 % from the dose of the drug, including 5% through the intestine and 93% - by the kidneys. The unchanged drug accounted for 70%. Less than 3% of the dose was excreted with bile. The renal clearance is approximately 500 ml / min, which is superior to the glomerular filtration, indicating a secretion in the tubule of the kidneys.

Special patient groups

- Children aged 1 month to 11 years

There is a limited number of pharmacokinetic data suggesting that the half-life (2-3 hours) and the clearance of ranitidine in the blood plasma (9- 13 ml / min / kg) in children aged from 1 months and older are similar to those in healthy adults who have received ranitidine orally.

- Patients over 50 years of age

In patients older than 50 years, the elimination half-life is extended (3-4 hours), and the clearance decreases according to the age-related decrease in kidney function.

At the same time, the level of systemic influence and accumulation is 50% higher. This difference can not be explained by a decrease in renal function and indicates an increase in bioavailability in patients the elderly.

- Newborn children (up to 1 month)

There is a limited number of pharmacokinetic data, suggesting that in newborns, the clearance of ranitidine in plasma may be reduced, and the elimination half-life is increased.

- Patients with impaired function of night

In patients with renal insufficiency (creatinine clearance less than 50 ml / min) cumulation and an increase in the concentration of ranitidine in plasma are noted.

Indications:Adults and adolescents (12 years and over):

Stomach ulcer and duodenal ulcer
Postoperative ulcers
Reflux-esophagitis
Zollinger-Allison syndrome
Prevention of stress ulcers in critically ill patients
Prevention of bleeding recurrences from peptic ulcers
Prevention of Mendelssohn syndrome

Children and newborns (from 1 month to 11 years)

Treatment of peptic ulcer
Treatment of gastroesophageal reflux, including reflux esophagitis, and alleviation of symptoms of gastroesophageal reflux disease
Prevention of stress ulcers in critically ill patients

Contraindications:Hypersensitivity to ranitidine or any other component of the drug.

Carefully:Caution should be exercised when using ranitidine in patients with renal and hepatic insufficiency, porphyria (including in anamnesis), suppression of immunity.

Pregnancy and lactation:

Fertility

There is no evidence of the effects of ranitidine on human fertility. AT Preclinical research did not reveal the impact of ranitidine on fertility.

Pregnancy

Ranitidine penetrates the placenta. Like any other medicine, ranitidine should be used during pregnancy only in cases where the potential benefit to the mother exceeds any possible risk to the fetus.

Breastfeeding period

Ranitidine is excreted in breast milk. Like any other medicine, ranitidine should be used during the period of breastfeeding only in cases where the potential benefit to the mother exceeds any possible risk to the child.

Dosing and Administration:

Adults and teens aged 12 years and older

The Zantac ® solution for intravenous and intramuscular administration can be administered as:

- slow (more than 2 minutes) intravenous injection at a dose of 50 mg, which is diluted to a volume of 20 ml and injected every 6-8 hours.

- intravenous infusion at a rate of 25 mg / hour for 2 hours, every 6-8 hours.

- intramuscular injection at a dose of 50 mg every 6-8 hours

Prevention of bleeding from stress ulcers in the upper gastrointestinal tract in severely ill patients and prevention of relapses bleeding from peptic ulcer

The initial dose is 50 mg in the form of a slow intravenous injection, and then a prolonged intravenous infusion at a rate of 0.125-0.250 mg / kg / h.

Parenteral therapy continues until the patient can not eat.Patients who are at risk of bleeding from an ulcer may continue to take Zantac in 150 mg tablets twice a day.

Prevention of Mendelssohn syndrome

The recommended dose is 50 mg intramuscularly or slowly intravenously 45-60 minutes prior to anesthesia.

Patients with renal disease insufficiency

For patients with renal insufficiency, the recommended dose of Zantac® is 25 mg.

Children and newborns (from 1 month to 11 years)

Data on the use of ranitidine in the form of a solution for intravenous and intramuscular administration in children are few. Ranitidine in the form of a solution can be used as a slow (lasting more than 2 min) intravenous injection at a maximum dose of 50 mg every 6-8 hours. This recommendation is based on the results of clinical studies, ndeveloped in adult patients, and also on the basis of the analysis of pharmacokinetics in patients of the pediatric group.

Urgent treatment of peptic ulcer and gastroesophageal reflux

The recommended intravenous dose of the drug in the form of a solution for intravenous and intramuscular administration in the treatment of peptic ulcer and gastroesophageal reflux in children is from 2 mg / kg / day to 4 mg / kg / day, divided into two or four injections.This recommendation is based on the results of clinical studies conducted in adult patients, as well as on the analysis of pharmacokinetics in patients in the pediatric group.

Prevention of stress ulcers the seriously ill patients

The recommended intravenous dose of the drug for the prevention of development of stress ulcers in seriously ill patients is from 2 mg / kg / day to 6 mg / kg / day, divided into two to four injections. In addition, to prevent the development of stress ulcers in critically ill patients ranitidine can also be used in the form of continuous infusion.

Newborns (up to 1 month)

The safety and effectiveness of the drug in newborns has not been investigated.

Instructions for the use of Zantac® for intravenous and intramuscular administration

The preparation "Zantac®" solution for intravenous and intramuscular injection is compatible with the following intravenous infusion solutions:

- 0,9 % solution of sodium chloride

- 5% dextrose solution

- a solution containing 0.18% chloride solution and 4% dextrose

- 4,2 % sodium bicarbonate solution

- Hartman's solution

Unused solutions should be disposed of within 24 hours after preparation.When the color changes or the presence of sediment, the solution should not be used.

Despite the fact that compatibility studies of solutions were carried out only with the use of polyvinyl chloride infusion packets (glass containers for sodium bicarbonate) and polyvinyl chloride systems, it is assumed that adequate stability can be achieved with the use of polyethylene bags.

Side effects:

The adverse events presented below are listed in accordance with the damage to organs and organ systems and frequency of occurrence. Frequency of occurrence is defined as follows: very often (≥ 1/10), often (≥ 1/100 and <1/10), infrequently (≥ 1/1 000 and <1/100), rarely (≥ 1/10 000 and <1/1 000), very rarely (<1/10 000, including individual cases).

Frequency categories were formed on the basis of post-registration observation.

Violations of the blood and lymphatic system

Very rarely: changes in the blood formula (leukopenia, neutropenia, thrombocytopenia), usually reversible. Agranulocytosis or pancytopenia, sometimes with bone marrow hypoplasia or aplasia. Immune hemolytic and aplastic anemia.

Immune system disorders

Rarely: hypersensitivity reactions (hives, angioedema, fever, bronchospasm, arterial hypotension, chest pain, eosinophilia).

Very rarely: anaphylactic shock.

These phenomena were observed after a single administration of the drug.

Disorders of the psyche

Very rarely: reversible violations mental activity: confusion, Depression and hallucinations (predominantly seriously ill and elderly patients), insomnia, irritability, emotional lability, anxiety, anxiety.

Disturbances from the nervous system

Rarely: agitation (predominantly in seriously ill patients of advanced age).

Very rarely: headache (in some cases strong), dizziness and reversible involuntary motor disorders, increased fatigue, drowsiness.

Heart Disease

Very rarely: a bradycardia, atrioventricular block, asystole, tachycardia.

Vascular disorders

Very rarely: vasculitis, arterial hypotension.

Disorders from the musculoskeletal andof the connective tissue

Very rarely: arthralgia and myalgia.

Disturbances on the part of the organ of sight

Very rarely: reversible blurred vision, which is supposedly associated with paresis accommodation.

Violations from the organ of hearing and labyrinthine disorders

Very rarely: noise in the ears.

Disorders from the gastrointestinal tract tract

Very rarely: acute pancreatitis, diarrhea, nausea, dry mouth, constipation, vomiting, abdominal pain.

Disorders from the liver and bile ducts

Rarely: transient reversible changes in functional liver tests.

Very rarely: hepatitis (hepatocellular, cholestatic or mixed), with or without jaundice, is usually reversible.

Violations from the skin and subcutaneous tissues

Rarely: rash.

Very rarely: multiform erythema (including Stevens-Johnson syndrome), exfoliative dermatitis, toxic epidermal necrolysis, alopecia.

Violation of the kidneys and urinededucingx paths

Very rarely: acute interstitial nephritis.

Violations of the genitals and mammary gland

Very rarely: reversible impotence, breaches from the breast (such as gynecomastia and galactorrhea), hyperprolactinaemia, amenorrhea, decreased libido.

Overdose:

Symptoms

There may be seizures, bradycardia, ventricular arrhythmia.

Treatment

In case of an overdose, symptomatic and maintenance therapy is recommended. If necessary, hemodialysis is possible.

Interaction:

Ranitidine can affect absorption, metabolism, or renal excretion of other drugs. As a consequence, dose adjustment or drug withdrawal may be necessary, the pharmacokinetics of which are affected ranitidine.

Interactions are carried out through several mechanisms:

1. The suppressing effect on cytochrome-R₄₅₀-oxygenase system.

Ranitidine increases AUC and the concentration of metoprolol in the blood serum (respectively, by 80 and 50%), while T_1/2 metoprolol increased from 4.4 to 6.5 hours. Inhibits the metabolism in the liver of phenazone, aminophenazone, diazepam, hexobarbital, propranolol, metoprolol, nifedipine, diazepam, lidocaine, phenytoin, theophylline, aminophylline, glipizide, bouformin, metronidazole, BCCC. However, when used in recommended doses ranitidine does not potentiate the effect of those drugs that are inactivated by the enzyme system of cytochrome-R_450.

There have been recorded cases of prothrombin time change in the background of treatment with coumarin anticoagulants (for example, warfarin). Taking into account the narrow therapeutic index, against the background of concomitant treatment with ranitidine, careful monitoring of prothrombin time is recommended.

2. Competitive renal tubular secretion:

Due to the fact that ranitidine partially excreted by the cationic system, it can affect the clearance of those drugs that are eliminated in the same way. The use of high doses of ranitidine (for example, in the treatment of Zollinger-Ellison syndrome) can reduce the excretion of procainamide and its active metabolite (N-acetylprocainamide), which leads to an increase in the concentration of this drug and its metabolite in plasma.

3. Effect on pH of gastric contents:

Possible influence on the bioavailability of certain drugs, which can lead to either increased absorption (eg, triazolam, midazolam, glipizide), or to a decrease in absorption (for example, ketoconazole, atazanavir, delavirdine, gefitnib).

Drugs that depress the bone marrow increase the risk of neutropenia.

Smoking reduces the effectiveness of ranitidine.

Special instructions:

Treatment with ranitidine may mask the symptoms of stomach cancer, so patients with gastric ulcers, middle-aged and elderly patients with dyspeptic manifestations and recently changed symptoms should, before starting ranitidine treatment, exclude the presence of a malignant tumor.

Ranitidine is excreted through the kidneys, and therefore the concentration of the drug in the plasma increases with a severe degree of renal failure. In this case, the dose should be selected according to the recommendations (see section "Method of administration and dose").

It is known about rare cases of bradycardia with rapid parenteral administration of Zantac, which was usually observed in patients with predisposing factors to the development of cardiac arrhythmias. Do not exceed the recommended rate of drug administration.

With increasing doses of intravenous antagonists H₂-receptors and the duration of their treatment for more than 5 days, there may be an increase in the level of hepatic enzymes.

In rare cases ranitidine contributes to the development of an acute attack of porphyria, therefore, it should be avoided for patients with acute porphyria in the anamnesis.

In a large epidemiological study, it was shown that in some patient groups (elderly patients, patients with chronic lung diseases, diabetes mellitus, immunocompromised patients) taking antagonists of Hg-histamine receptors, the risk of community-acquired pneumonia is higher compared to patients who discontinued treatment with ranitidine.

Ranitidine, undesirably sharply to cancel, in view of risk of development of a syndrome of "ricochet".

Ranitidine can cause a false positive reaction when carrying out a sample for protein in the urine.

Ranitidine counteracts the influence of pentagastrin and histamine on the acid-forming function of the stomach, therefore, it is not recommended to apply it for 24 hours preceding the study of gastric secretion.

Ranitidin It inhibits the skin reaction to histamine, therefore, in order to avoid false negative results before the diagnostic skin tests to identify allergic skin reaction of immediate type use of the drug is recommended to stop.

The effectiveness of the drug in inhibiting night secretion of acid in the stomach can withnoras a result of smoking.

Effect on the ability to drive transp. cf.and fur:

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:Solution for intravenous and intramuscular injection 25 mg / ml.

Packaging:For 2 ml in ampoules of transparent glass type I with two colored rings applied to the tip of the ampoule. 5 ampoules per plastic tray without coating, with instructions for use in a cardboard box.

Storage conditions:

Store at temperatures below 25 ° C in a dark place.

Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014716 / 01

Date of registration:16.10.2008 / 18.02.2010

Expiration Date:Unlimited

The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia

Manufacturer: & nbsp

GlaxoSmithKline Manufacturing, S.p.A. Italy

Information update date: & nbsp10.10.2017

Illustrated instructions

Instructions

Zantac® (Zantac®)