Active ingredients: Ranitidine (ranitidine hydrochloride)
RANIDIL 150 mg Film-coated tablets
RANIDIL 300 mg Film-coated tablets
Ranidil package inserts are available for pack sizes: - RANIDIL 150 mg Film-coated tablets, RANIDIL 300 mg Film-coated tablets
- RANIDIL 150 mg Effervescent tablets, RANIDIL 300 mg Effervescent tablets
- RANIDIL 150 mg / 10 ml Syrup
- RANIDIL 50 mg / 5 ml solution for injection for intravenous use
- Ranidil 75 mg film-coated tablets
Why is Ranidil used? What is it for?
Drug for the treatment of peptic ulcer and gastroesophageal reflux disease. H2 receptor antagonists.
THERAPEUTIC INDICATIONS
Adults (over 18 years of age)
Duodenal ulcer, benign gastric ulcer, including those associated with treatment with non-steroidal anti-inflammatory drugs, relapsing ulcer, post-operative ulcer, reflux oesophagitis, Zollinger-Ellison syndrome.
Ranitidine is also indicated in those conditions such as gastritis or duodenitis when associated with acid hypersecretion.
Children (from 3 to 18 years old)
- Short-term treatment of peptic ulcer
- Treatment of gastroesophageal reflux, including reflux esophagitis and relief of symptoms of gastroesophageal reflux disease
Contraindications When Ranidil should not be used
Hypersensitivity to the active substance or to any of the excipients.
Precautions for use What you need to know before taking Ranidil
Gastric cancer
Before initiating therapy with ranitidine in patients with gastric ulcer or in middle-aged or older patients presenting with recently onset or recently modified dyspeptic symptoms, its possible malignant nature should be excluded as ranitidine treatment may mask the symptoms. gastric cancer.
Kidney disease
Ranitidine is eliminated by the kidney and therefore plasma levels of the drug are increased in patients with renal impairment.
The dosage must be modified as indicated in the paragraph "DOSE, METHOD AND TIME OF ADMINISTRATION"
According to rare reports, ranitidine may favor the occurrence of acute attacks of porphyria. Therefore administration in patients with a history of acute attacks of porphyria should be avoided.
In patients such as the elderly, people with chronic lung disease, diabetes, or the immunocompromised, there may be an increased risk of developing community-acquired pneumonia. A large epidemiological study showed an increased risk of developing community acquired pneumonia in patients still on ranitidine alone compared with those who had stopped treatment, with an observed adjusted relative risk increase of 1.82% (95% CI 1.26-2.64).
Regular medical monitoring is recommended for patients on NSAID therapy concurrently with ranitidine treatment, especially if elderly or with a history of peptic ulcer.
Relapses of objective and subjective symptoms can occur both after drug withdrawal and during long-term maintenance treatment at a lower than full dose. Dosage and duration of administration must always be established by the physician, bearing in mind that usually the symptoms disappear before the ulcer has healed.
The administration of ranitidine, like all H2 receptor antagonists, favors intragastric bacterial development by decreasing gastric acidity.
Caution should be used in patients with liver function disorders.
Interactions Which drugs or foods can modify the effect of Ranidil
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Ranitidine may affect the absorption, metabolism or renal excretion of other drugs. Alteration of pharmacokinetic parameters may require dosage adjustment of the affected drug or discontinuation of treatment. Interactions occur through various mechanisms, including:
- Inhibition of the mixed function oxygenase system linked to hepatic cytochrome P450: ranitidine at the usual therapeutic doses does not potentiate the action of drugs that are inactivated by this enzyme system, such as diazepam, lidocaine, phenytoin, propranolol and theophylline. Cases have been reported. prothrombin time alteration with coumarin anticoagulants (eg warfarin) Due to the narrow therapeutic index, careful monitoring of increases and decreases in prothrombin time is recommended during concomitant treatment with ranitidine.
- Competition for renal tubular secretion: Ranitidine, being partially eliminated via the cationic system, may affect the clearance of other drugs eliminated by this route. High doses of ranitidine (eg those used in the treatment of Zollinger-Ellison syndrome) may reduce the excretion of procainamide and nacetylprocainamide, resulting in an increase in the plasma levels of these drugs.
- Alteration of gastric pH: the bioavailability of some drugs can be affected. This may result in both increased absorption (eg triazolam, midazolam, glipizide) and decreased absorption (eg ketoconazole, atazanavir, delaviridine, gefitnib).
There is no evidence of an interaction between ranitidine and amoxicillin and metronidazole.
Absorption of ranitidine may be decreased if high doses (2 g) of sucralfate, magnesium or aluminum hydroxide are administered simultaneously.
This effect does not occur if these substances are administered after an interval of 2 hours.
Warnings It is important to know that:
Fertility, pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Fertility
There are no data on the effect of ranitidine on human fertility. Animal studies have shown no effects on male or female fertility.
Pregnancy
Ranitidine crosses the placental barrier. Like other drugs, it should be administered during pregnancy only if considered absolutely necessary.
Feeding time
Ranitidine is excreted in breast milk. Like other drugs, it should be administered during lactation only if considered absolutely necessary.
Effects on ability to drive and use machines
If, during therapy, you notice dizziness, drowsiness or dizziness, avoid driving or using machinery or otherwise carrying out activities that require prompt vigilance.
Dosage and method of use How to use Ranidil: Dosage
Adults (including the elderly) / Adolescents (12 years of age and older)
The usual dose is 300 mg per day:
150 mg in the morning and 150 mg in the evening.
In patients with gastric or duodenal ulcer, 300 mg can be administered alternatively, in a single administration, in the evening before bedtime (RANIDIL 300 mg, 1 tablet in the evening before bedtime).
In addition, in the following situations: patients with large ulcers and / or heavy smokers and in severe peptic esophagitis, it may be useful to increase the dosage up to 600 mg per day, returning as soon as possible to the standard dosage schedule and under direct medical supervision .
In the prophylaxis of stress ulcer haemorrhage in severe patients or recurrent haemorrhage in patients with bleeding peptic ulcer, patients on parenteral RANIDIL therapy considered to be still at risk as soon as they resume feeding by mouth, can be treated with Ranidil 150 mg tablets, twice a day.
Duodenal ulcer, gastric ulcer, relapsing ulcer, post-operative ulcer
The recommended daily dose of 300 mg for a period of 4 weeks is able to heal most ulcers. If necessary, the treatment can be extended up to 6-8 weeks.
In the event of ulcers resulting from treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and / or if continued therapy with these drugs is necessary, the recommended dosage is 300 mg for 8 weeks. Treatment may need to be continued for up to 12 weeks. In the case of patients with large ulcers and / or heavy smokers, administration of 300 mg, twice a day, may be more useful.
In patients in whom, after a positive response to short-term therapy, it is desirable to maintain the effect on gastric secretion, particularly in those with a tendency to relapse ulcerative episodes, maintenance therapy of 150 mg in the evening can be used. patients already on treatment with 600 mg per day, it may be useful to start maintenance therapy with a dosage of 300 mg in the evening for a period of 8-12 weeks, then continuing with the standard dose.
Smoking is associated with a higher incidence of ulcer recurrence. Therefore, smoking patients should be advised to abandon this habit; if this is not the case, the maintenance dose of 300 mg in the evening offers additional protection over the standard dose. of 150 mg.
Maintenance therapy (150 mg and 300 mg orally in the evening) should be prescribed and supervised by your doctor.
Reflux esophagitis
The recommended daily dose in esophageal reflux disease is 300 mg per day, divided into two doses of 150 mg, for a period of 8 weeks.
In moderate-severe peptic esophagitis, the dosage can be increased to 600 mg per day, divided into 2-4 administrations, up to 12 weeks, under the direct supervision of the physician, returning as soon as possible to the standard dosage.
In long-term treatment, for the prevention of relapse, the recommended dose is 150 mg twice a day.
Zollinger-Ellison syndrome
The initial daily dose is 450 mg (i.e. 150 mg 3 times a day), which can be increased if necessary to 600-900 mg (Ranidil 300 mg, 2-3 tablets a day).
Upper gastrointestinal bleeding
Oral treatment is 300 mg per day.
If oral therapy is not immediately possible, treatment can be started with Ranidil Solution for Injection (see relevant leaflet) and continued with oral therapy (300 mg per day for as long as necessary).
Premedication under anesthesia
Those patients who are at risk of developing acid aspiration syndrome (Mendelson's syndrome) can be given an oral dose of 150 mg 2 hours before induction of general anesthesia and preferably also a dose of 150 mg the evening before.
The parenteral route of administration may also be used (see package leaflet of Ranidil Solution for Injection).
Stress ulcer
In the prevention and treatment of stress ulcers in severe patients, the recommended daily dose is 300 mg.
If the patient's condition does not allow oral administration, treatment can be initiated with Ranidil Solution for Injection (see relevant leaflet) and then continued with oral therapy.
Patients with kidney damage
In patients with severe renal impairment (creatinine clearance less than 50 ml / min), accumulation of ranitidine occurs with consequent increase in plasma concentrations. It is recommended that the daily dose in such patients is 150 mg to be taken in the evening.
Children from 3 to 11 years of age and weighing more than 30 kg
Acute treatment of peptic ulcer
The recommended oral dose for the treatment of peptic ulcer in children is between 4 mg / kg per day and 8 mg / kg per day given in two divided doses up to a maximum of 300 mg ranitidine per day for a duration of 4 For patients with incomplete healing, an additional 4 weeks of therapy is indicated, as healing usually occurs after eight weeks of treatment.
Gastroesophageal reflux
The recommended oral dose for the treatment of gastroesophageal reflux in children is between 5 mg / kg per day and 10 mg / kg per day given in two divided doses up to a maximum of 600 mg (the maximum dose is likely to apply to children. and adolescents with heavier weight and severe symptoms).
Safety and efficacy in neonatal patients have not been established.
Overdose What to do if you have taken too much Ranidil
Symptoms and Signs
Ranitidine has a very specific pharmacological activity so no particular problems are expected following overdose with ranitidine formulations.
Treatment
Depending on the case, symptomatic and supportive therapy should be practiced.
In case of accidental ingestion / intake of an excessive dose of Ranidil, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of Ranidil, ask your doctor or pharmacist.
Side Effects What are the side effects of Ranidil
Like all medicines, Ranidil can cause side effects, although not everybody gets them.
The following convention has been used for the classification of the frequency of undesirable effects: very common (> 1/10), common (> 1/100, 1 / 1,000, 1 / 10,000,
The frequencies of adverse events were estimated based on post-marketing spontaneous reporting data.
Disorders of the blood and lymphatic system:
Very rare: changes in blood cell counts (leukopenia, thrombocytopenia). These are usually reversible. Agranulocytosis or pancytopenia sometimes accompanied by bone marrow hypoplasia or aplasia.
Immune system disorders:
Rare: hypersensitivity reactions (urticaria, bullous dermatitis, eczema, angioneurotic edema, fever, bronchospasm, hypotension, chest pain and eosinophilia).
Very rare: anaphylactic shock.
Not known: dyspnoea. The above events have been reported following administration of a single dose.
Psychiatric disorders:
Very rare: reversible mental confusion, depression, hallucinations and agitation. The above events have been reported mainly in seriously ill patients, elderly patients and renal patients. In such cases, the administration must be suspended.
Nervous system disorders:
Very rare: headache (sometimes severe), dizziness, somnolence, insomnia and reversible involuntary movements.
Eye disorders:
Very rare: reversible blurring of vision. Some cases of blurring of vision attributable to altered accommodation have been reported.
Cardiac disorders:
Very rare: As with other H2-receptor antagonists there have been rare cases of bradycardia, tachycardia, palpitations, extrasystoles, atrioventricular block and state of shock.
Vascular disorders:
Very rare: vasculitis.
Gastrointestinal disorders:
Very rare: acute pancreatitis, diarrhea, vomiting
Uncommon: abdominal pain, constipation, nausea (these symptoms almost always improve over the course of treatment)
Hepato-biliary disorders:
Rare: transient and reversible changes in liver function tests.
Very rare: usually reversible hepatitis (hepatocellular, hepatocanalicular or mixed) with or without jaundice.
Skin and subcutaneous tissue disorders:
Rare: skin rash.
Very rare: erythema multiforme, alopecia.
Musculoskeletal and connective tissue disorders:
Very rare: symptoms affecting the musculoskeletal system such as arthralgia and myalgia.
Renal and urinary disorders:
Rare: increase in plasma creatinine (usually mild; normalizes during treatment)
Very rare: acute interstitial nephritis.
Diseases of the reproductive system and breast:
Very rare: reversible impotence and libido alteration. Breast symptoms, pathologies and changes (such as gynecomastia and galactorrhea).
Pediatric population
The safety of ranitidine was evaluated in children aged 0-16 years with acid-related conditions and was generally well tolerated, with an adverse event profile similar to that of adults. Limited long-term safety data are available, particularly with respect to growth and development.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on safety. of this medicine.
Expiry and Retention
Expiry: see the expiry date printed on the package.
The expiry date refers to the product in intact packaging, correctly stored.
Warning: do not use the medicine after the expiry date shown on the package.
No special storage conditions are required. Ranitidine is stable in the original package at room temperature.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep this medicine out of the reach and sight of children.
COMPOSITION
Ranidil 150 mg film-coated tablets
One film-coated tablet contains:
Active ingredient: ranitidine hydrochloride 167.40 mg equal to ranitidine 150 mg
Excipients: microcrystalline cellulose; magnesium stearate; hypromellose; titanium dioxide (E171)
Ranidil 300 mg film-coated tablets
One film-coated tablet contains:
Active ingredient: ranitidine hydrochloride 334.80 mg equal to ranitidine 300 mg
Excipients: microcrystalline cellulose; magnesium stearate; hypromellose; titanium dioxide (E171)
PHARMACEUTICAL FORM AND CONTENT
Film-coated tablets: 20 film-coated tablets of 150 mg 20 film-coated tablets of 300 mg
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
RANIDIL TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
RANIDIL 150 mg Film-coated tablets
One film-coated tablet contains:
Active principle:
ranitidine hydrochloride 167.40 mg equal to ranitidine 150 mg.
RANIDIL 300 mg Film-coated tablets
One film-coated tablet contains:
Active principle:
ranitidine hydrochloride 334.80 mg equal to ranitidine 300 mg.
For the full list of excipients see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Adults (over 18 years of age)
Duodenal ulcer, benign gastric ulcer, including those associated with treatment with non-steroidal anti-inflammatory drugs, relapsing ulcer, post-operative ulcer, reflux oesophagitis, Zollinger-Ellison syndrome.
Ranitidine is also indicated in those conditions such as gastritis or duodenitis when associated with acid hypersecretion.
Children (from 3 to 18 years old)
• Short-term treatment of peptic ulcer
• Treatment of gastroesophageal reflux, including reflux esophagitis and relief of symptoms of gastroesophageal reflux disease.
04.2 Posology and method of administration
Adults (including the elderly) / Adolescents (12 years of age and older)
The usual dose is 300 mg per day:
150 mg in the morning and 150 mg in the evening.
In patients with gastric or duodenal ulcer, 300 mg can be administered alternatively, in a single administration, in the evening before bedtime (RANIDIL 300 mg, 1 tablet in the evening before bedtime).
In addition, in the following situations: patients with large ulcers and / or heavy smokers and in severe peptic esophagitis, it may be useful to increase the dosage up to 600 mg per day, returning as soon as possible to the standard dosage schedule and under direct medical supervision .
In the prophylaxis of stress ulcer haemorrhage in severe patients or recurrent haemorrhage in patients with bleeding peptic ulcer, patients on parenteral RANIDIL therapy considered to be still at risk as soon as they resume feeding by mouth, can be treated with Ranidil 150 mg tablets, twice a day.
Duodenal ulcer, gastric ulcer, relapsing ulcer, post-operative ulcer
The recommended daily dose of 300 mg for a period of 4 weeks is able to heal most ulcers. If necessary, the treatment can be extended up to 6-8 weeks.
In the event of ulcers resulting from treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and / or if continued therapy with these drugs is necessary, the recommended dosage is 300 mg for 8 weeks. Treatment may need to be continued for up to 12 weeks.
In the case of patients with large ulcers and / or heavy smokers, administration of 300 mg, twice a day, may be more useful.
In patients in whom, after a positive response to short-term therapy, it is desirable to maintain the effect on gastric secretion, particularly in those with a tendency to relapse ulcerative episodes, maintenance therapy of 150 mg in the evening can be used. patients already on treatment with 600 mg per day, it may be useful to start maintenance therapy with a dosage of 300 mg in the evening for a period of 8-12 weeks, then continuing with the standard dose.
Smoking is associated with a higher incidence of ulcer recurrence. Therefore, smoking patients should be advised to abandon this habit; if this is not the case, the maintenance dose of 300 mg in the evening offers additional protection over the standard dose. of 150 mg.
Maintenance therapy (150 mg and 300 mg orally in the evening) should be prescribed and supervised by your doctor.
Reflux esophagitis
The recommended daily dose in oesophageal reflux disease is 300 mg / day, divided into two doses of 150 mg, for a period of 8 weeks.
In moderate-severe peptic esophagitis, the dosage can be increased to 600 mg / day, divided into 2-4 administrations, up to 12 weeks, under the direct supervision of the physician, returning as soon as possible to the standard dosage.
In long-term treatment, for the prevention of relapse, the recommended dose is 150 mg twice a day.
Zollinger-Ellison syndrome
The initial daily dose is 450 mg (i.e. 150 mg 3 times a day), which can be increased if necessary to 600-900 mg (Ranidil 300 mg, 2-3 tablets a day).
Upper gastrointestinal bleeding
Oral treatment is 300 mg per day.
If oral therapy is not immediately possible, treatment can be initiated with Ranidil Solution for Injection (see relevant Summary of Product Characteristics) and continued with oral therapy (300 mg per day for as long as necessary).
Premedication under anesthesia
Those patients who are at risk of developing acid aspiration syndrome (Mendelson's syndrome) can be given an oral dose of 150 mg 2 hours before induction of general anesthesia and preferably also a dose of 150 mg the evening before.
The parenteral route of administration may also be used (see the relevant Summary of Product Characteristics of Ranidil Solution for Injection).
Stress ulcer
In the prevention and treatment of stress ulcers in severe patients, the recommended daily dose is 300 mg.
If the patient's condition does not allow oral administration, treatment can be initiated with RANIDIL Solution for injection (see the relevant Summary of Product Characteristics) and then continued with oral therapy.
Patients with kidney damage
In patients with severe renal impairment (creatinine clearance less than 50 ml / min), accumulation of ranitidine occurs with consequent increase in plasma concentrations. It is recommended that the daily dose in such patients is 150 mg to be taken in the evening.
Children from 3 to 11 years of age and weighing more than 30 kg
See section 5.2 Pharmacokinetic properties - Special patient populations.
Acute treatment of peptic ulcer
The recommended oral dose for the treatment of peptic ulcer in children is between 4 mg / kg / day and 8 mg / kg / day administered in two divided doses up to a maximum of 300 mg ranitidine per day for a duration of 4 For patients with incomplete healing, an additional 4 weeks of therapy is indicated, as healing usually occurs after 8 weeks of treatment.
Gastroesophageal reflux
The recommended oral dose for the treatment of gastroesophageal reflux in children is between 5 mg / kg / day and 10 mg / kg / day given in two divided doses up to a maximum of 600 mg (the maximum dose is likely to apply. to children and adolescents with heavier weight and severe symptoms).
Safety and efficacy in neonatal patients have not been established.
04.3 Contraindications
Ranitidine products are contraindicated in patients with known hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
04.4 Special warnings and appropriate precautions for use
Gastric cancer
Before initiating therapy with ranitidine in patients with gastric ulcer or in middle-aged or older patients presenting with recently onset or recently modified dyspeptic symptoms, its possible malignant nature should be excluded as ranitidine treatment may mask the symptoms. gastric cancer.
Kidney disease
Ranitidine is eliminated by the kidney and therefore plasma levels of the drug are increased in patients with renal impairment.
Dosage should be adjusted as indicated in section 4.2 "Patients with renal impairment".
According to rare reports, ranitidine may favor the occurrence of acute attacks of porphyria.
Therefore administration in patients with a history of acute attacks of porphyria should be avoided.
In patients such as the elderly, people with chronic lung disease, diabetic or immunocompromised, there may be an increased risk of developing community-acquired pneumonia. A large epidemiological study showed an increased risk of developing community acquired pneumonia in patients still on ranitidine alone compared with those who had stopped treatment, with an observed adjusted relative risk increase of 1.82% (95% CI, 1.26 - 2.64).
Regular medical monitoring is recommended for patients on NSAID therapy concurrently with ranitidine treatment, especially if elderly or with a history of peptic ulcer.
Relapses of objective and subjective symptoms can occur both after drug withdrawal and during long-term maintenance treatment at a lower than full dose. Dosage and duration of administration must always be established by the physician, bearing in mind that usually the symptoms disappear before the ulcer has healed.
The administration of ranitidine, like all receptor antagonists, favors intragastric bacterial development by decreasing gastric acidity.
Caution should be used in patients with liver function disorders.
04.5 Interactions with other medicinal products and other forms of interaction
Ranitidine may affect the absorption, metabolism or renal excretion of other drugs. Alteration of pharmacokinetic parameters may require dosage adjustment of the affected drug or discontinuation of treatment.
Interactions occur through various mechanisms, including:
1) Inhibition of the mixed function oxygenase system linked to hepatic cytochrome P450:
ranitidine at the usual therapeutic doses does not potentiate the action of drugs which are inactivated by this enzyme system, such as diazepam, lidocaine, phenytoin, propranolol and theophylline.
There have been reports of altered prothrombin time with coumarin anticoagulants (e.g. warfarin). Due to the narrow therapeutic index, careful monitoring of increases and decreases in prothrombin time is recommended during concomitant treatment with ranitidine.
2) Competition for renal tubular secretion:
ranitidine, being partially eliminated by the cationic system, can influence the clearance of other drugs eliminated in this way. High doses of ranitidine (eg those used in the treatment of Zollinger-Ellison syndrome) may reduce the excretion of procainamide and N-acetylprocainamide, resulting in an increase in the plasma levels of these drugs.
3) Alteration of gastric pH:
the bioavailability of some drugs can be affected. This may result in both increased absorption (eg triazolam, midazolam, glipizide) and decreased absorption (eg ketoconazole, atazanavir, delaviridine, gefitnib).
There is no evidence of an interaction between ranitidine and amoxicillin and metronidazole.
Absorption of ranitidine may be decreased if high doses (2 g) of sucralfate, magnesium or aluminum hydroxide are administered simultaneously.
This effect does not occur if these substances are administered after an interval of 2 hours.
04.6 Pregnancy and lactation
Fertility
There are no data on the effect of ranitidine on human fertility. Animal studies have shown no effects on male and female fertility (see section 5.3).
Pregnancy
Ranitidine crosses the placental barrier. Like other drugs, it should be administered during pregnancy only if considered absolutely necessary.
Feeding time
Ranitidine is excreted in breast milk. Like other drugs, it should be administered during lactation only if considered absolutely necessary.
04.7 Effects on ability to drive and use machines
If, during therapy, you notice dizziness, drowsiness or dizziness, avoid driving or using machinery or otherwise carrying out activities that require prompt vigilance.
04.8 Undesirable effects
The following convention has been used for the classification of the frequency of undesirable effects: very common (≥1 / 10), common (≥1 / 100,
The frequencies of adverse events were estimated based on post-marketing spontaneous reporting data.
Disorders of the blood and lymphatic system:
Very rare: changes in blood cell counts (leukopenia, thrombocytopenia). These are usually reversible. Agranulocytosis or pancytopenia sometimes accompanied by bone marrow hypoplasia or aplasia.
Disorders of the immune system:
Rare: hypersensitivity reactions (urticaria, bullous dermatitis, eczema, angioneurotic edema, fever, bronchospasm, hypotension, chest pain and eosinophilia).
Very rare: anaphylactic shock.
Not known: dyspnoea
The above events have been reported following administration of a single dose.
Psychiatric disorders:
Very rare: reversible mental confusion, depression, hallucinations and agitation.
The above events have been reported mainly in seriously ill patients, elderly patients and renal patients. In such cases, the administration must be suspended.
Nervous system disorders:
Very rare: headache (sometimes severe), dizziness, somnolence, insomnia and reversible involuntary movements.
Eye disorders:
Very rare: reversible blurring of vision.
Some cases of blurring of vision attributable to altered accommodation have been reported.
Cardiac disorders:
Very rare: As with other H2 receptor antagonists there have been rare cases of bradycardia, tachycardia, palpitations, extrasystoles, atrio-ventricular block and state of shock.
Vascular disorders:
Very rare: vasculitis.
Gastrointestinal disorders:
Very rare: acute pancreatitis, diarrhea, vomiting
Uncommon: abdominal pain, constipation, nausea (these symptoms almost always improve with continued treatment)
Hepato-biliary disorders:
Rare: transient and reversible changes in liver function tests.
Very rare: generally reversible hepatitis (hepatocellular, hepatocanalicular or mixed) with or without jaundice.
Skin and subcutaneous tissue disorders:
Rare: skin rash.
Very rare: erythema multiforme, alopecia.
Musculoskeletal and connective tissue disorders:
Very rare: symptoms affecting the musculoskeletal system such as arthralgia and myalgia.
Renal and urinary disorders:
Rare: increase in plasma creatinine (usually mild; normalizes during treatment).
Very rare: acute interstitial nephritis.
Diseases of the reproductive system and breast :
Very rare: reversible impotence and libido alteration. Breast symptoms, pathologies and changes (such as gynecomastia and galactorrhea).
Pediatric population
The safety of ranitidine was evaluated in children aged 0-16 years with acid-related conditions and was generally well tolerated, with an adverse event profile similar to that of adults. Limited long-term safety data are available, particularly with respect to growth and development.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
04.9 Overdose
Symptoms and signs
Ranitidine has a very specific pharmacological activity so no particular problems are expected following overdose with ranitidine formulations.
Treatment
Depending on the case, symptomatic and supportive therapy should be practiced.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: drug for the treatment of peptic ulcer and gastroesophageal reflux disease. H2 receptor antagonists.
ATC code: A02BA02.
RANIDIL is a specific and rapid antagonist of histamine H2 receptors. It inhibits basal and stimulated gastric acid secretion with reduction of both the volume and the acid and pepsin content of the secretion. RANIDIL has a relatively long duration of action and a single dose. from 150mg effectively suppresses gastric acid secretion for 12 hours.
05.2 Pharmacokinetic properties
Absorption
Following oral administration of 150 mg ranitidine, the maximum plasma concentration (300 to 550 ng / ml) is reached within 1-3 hours. The absorption phase consists of two distinct peaks or a plateau due to the reabsorption of the drug excreted in the intestine. The absolute bioavailability of ranitidine is 50-60%, and the plasma concentration increases proportionally with the increase in dose up to 300 mg.
Distribution
Ranitidine is not extensively bound to plasma proteins (15%), but exhibits a very wide range of volume of distribution from 96 to 142.
Metabolism
Ranitidine is not extensively metabolised. The dose fraction found as metabolites is similar after oral or intravenous administration and includes 6% dose in urine. As N-oxide, 2% as S-oxide, 2% as desmethylranitidine and 1 to 2% as furoic acid analog.
Elimination
Plasma concentration drops bi-exponentially, with a "terminal half-life of 2-3 hours." Elimination of the drug occurs mainly via the kidney. After i.v. of 150 mg of 3H-ranitidine 98% of the dose is excreted 93% in the urine and 5% in the faeces, 70% as unchanged drug. After oral administration of 150 mg of 3H-ranitidine 96% of the dose is excreted, 26% in the faeces and 70% in the urine, 35% as unchanged drug. Less than 3% of the dose is excreted in the bile. There clearance renal is approximately 500ml / min, i.e. the drug passes the glomerular filtration, which indicates a net tubular secretion.
Special patient populations
Children (aged 3 years and over)
Limited pharmacokinetic data showed that there are no significant differences in the half-life (range in children from 3 years of age: 1.7 - 2.2 hours) and in the clearance plasma (range in children 3 years and older: 9-22 ml / min / kg) between children and healthy adults receiving oral ranitidine, when correction for body weight was made.
Patients over 50 years of age
In patients over 50, the half-life is prolonged (3-4 h) and the clearance is reduced, congruently with age-related decreased renal function. However, systemic exposure and accumulation were increased by 50%, resulting in increased effects of decreased renal function and increased bioavailability in patients Senior citizens.
05.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, reproductive and developmental toxicity
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Microcrystalline cellulose; magnesium stearate; hypromellose; titanium dioxide (E171).
06.2 Incompatibility
None.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
No special storage conditions are required. Ranitidine is stable in the original package at room temperature.
06.5 Nature of the immediate packaging and contents of the package
Aluminum / polyethylene strips, or blisters thermoformed with aluminum-PVC tape and OPA / Al / PVC tape, contained in cardboard boxes.
20 film-coated tablets of 150 mg.
20 film-coated tablets of 300 mg.
Not all packs can be on the market.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
A. Menarini Industrie Farmaceutiche Riunite srl - Via Sette Santi 3 - Florence
Licensed by GlaxoSmithKline S.p.A.
08.0 MARKETING AUTHORIZATION NUMBER
RANIDIL 150 mg Film-coated tablets - 20 film-coated tablets A.I.C .: 024447029
RANIDIL 300 mg Film-coated tablets - 20 film-coated tablets A.I.C .: 024447056
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
150 mg tablet - June 1981 / January 2009
300 mg tablet - April 1985 / January 2009
10.0 DATE OF REVISION OF THE TEXT
December 2014
