Symptoms and Signs
Ranitidine is very specific in action and no particular problems are expected following overdose with the drug. Up to 6g per day has been administered without untoward effect.
Treatment
Symptomatic and supportive therapy should be given as appropriate. If need be, the drug may be removed from the plasma by haemodialysis.
No information provided.
Symptoms and signs
Zantac is very specific in action and accordingly, no particular problems are expected following overdosage with the drug.
Treatment
Symptomatic and supportive therapy should be given as appropriate.
Ranitidine is contraindicated for people known to be hypersensitive to the drug or any of the ingredients of Fada Ranitidina 75 Relief tablets.
No information provided.
None known
The following convention has been utilised for the >
Blood & Lymphatic System Disorders
Very Rare:
Blood count changes (leucopenia, thrombocytopenia). These are usually reversible. Agranulocytosis or pancytopenia, sometimes with marrow hypoplasia or marrow aplasia.
Immune System Disorders
Rare:
Hypersensitivity reactions (urticaria, angioneurotic oedema, fever, bronchospasm, hypotension and chest pain).
Very Rare:
Anaphylactic shock
These events have been reported after a single dose.
Psychiatric Disorders
Very Rare:
Reversible mental confusion, depression and hallucinations.
These have been reported predominantly in severely ill and elderly patients.
Nervous System Disorders
Very Rare:
Headache (sometimes severe),dizziness and reversible involuntary movement disorders.
Eye Disorders
Very Rare:
Reversible blurred vision.
There have been reports of blurred vision, which is suggestive of a change in accommodation.
Cardiac Disorders
Very Rare:
As with other H2 receptor antagonists bradycardia and A-V Block.
Vascular Disorders
Very Rare:
Vasculitis.
Gastrointestinal Disorders
Very Rare:
Acute pancreatitis. Diarrhoea.
Uncommon:
Abdominal pain, constipation, nausea. (these symptoms mostly improved during continued treatment).
Hepatobiliary Disorders
Rare:
Transient and reversible changes in liver function tests.
Very Rare
Hepatitis (hepatocellular, hepatocanalicular or mixed) with or without jaundice, these were usually reversible.
Skin and Subcutaneous Tissue Disorders
Rare:
Skin Rash.
Very Rare:
Erythema multiforme, alopecia.
Musculoskeletal and Connective Tissue Disorders
Very Rare:
Musculoskeletal symptoms such as arthralgia and myalgia.
Renal and Urinary Disorders
Very rare:
Acute interstitial nephritis.
Rare:
Elevation of plasma creatinine (usually slight; normalised during continued treatment)
Reproductive System and Breast Disorders
Very Rare:
Reversible impotence. Breast symptoms and breast conditions (such as gynaecomastia and galactorrhea).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
Please see WARNINGS.
The following convention has been utilised for the classification of undesirable effects: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, ≤1/100), rare (>1/10,000, ≤1/1000), very rare (≤1/10,000). Adverse event frequencies have been estimated from spontaneous reports from post-marketing data.
Blood & Lymphatic System Disorders | |
Very Rare: | Blood count changes (leucopenia, thrombocytopenia). These are usually reversible. Agranulocytosis or pancytopenia, sometimes with marrow hypoplasia or marrow aplasia. |
Immune System Disorders | |
Rare: | Hypersensitivity reactions (urticaria, angioneurotic oedema, fever, bronchospasm, hypotension and chest pain). |
Very Rare: | Anaphylactic shock. |
Not known: | Dyspnoea |
These events have been reported after a single dose. | |
Psychiatric Disorders | |
Very Rare: | Reversible mental confusion, depression and hallucinations. These have been reported predominantly in severely ill patients, in elderly and nephropatic patients. |
Nervous System Disorders | |
Very Rare: | Headache (sometimes severe), dizziness and reversible involuntary movement disorders. |
Eye Disorders | |
Very Rare: | Reversible blurred vision. |
There have been reports of blurred vision, which is suggestive of a change in accommodation. | |
Cardiac Disorders | |
Very Rare: | As with other H2 receptor antagonists bradycardia, A-V block, asystole and tachycardia. |
Vascular Disorders | |
Very Rare: | Vasculitis. |
Gastrointestinal Disorders | |
Uncommon: | Abdominal pain, constipation, nausea (these symptoms mostly improved during continued treatment). |
Very Rare: | Acute pancreatitis, diarrhoea. |
Hepatobiliary Disorders | |
Rare: | Transient and reversible changes in liver function tests. |
Very Rare: | Hepatitis (hepatocellular, hepatocanalicular or mixed) with or without jaundice, these were usually reversible. |
Skin and Subcutaneous Tissue Disorders | |
Rare: | Skin Rash. |
Very Rare: | Erythema multiforme, alopecia. |
Musculoskeletal and Connective Tissue Disorders | |
Very Rare: | Musculoskeletal symptoms such as arthralgia and myalgia. |
Renal and Urinary Disorders | |
Rare: | Elevation of plasma creatinine (usually slight; normalised during continued treatment) |
Very Rare: | Acute interstitial nephritis. |
Reproductive System and Breast Disorders | |
Very Rare: | Reversible impotence, breast symptoms and breast conditions (such as gynaecomastia and galactorrhoea). |
Paediatric population
The safety of ranitidine has been assessed in children aged 0 to 16 years with acid-related disease and was generally well tolerated with an adverse event profile resembling that in adults. There are limited long term safety data available, in particular regarding growth and development.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
Extensive studies have been carried out in animals. The pharmacology of ranitidine hydrochloride shows it to be a surmountable H2 receptor antagonist which produces an inhibition of gastro acid secretion. Extensive toxicological investigators have been conducted which predicted a very safe profile for clinical use. This safety has been confirmed by extensive use in patients for many years.
Non-clinical data revealed no special hazard for humans based on conventional studies of safety pharmacology, repeated-dose toxicity, genotoxicity, carcinogenic potential and toxicity to reproduction and development.
Symptomaticreliefofheartburn, indigestion,acidindigestionand hyperacidity.
Adults:
Fada Ranitidina is indicated for the treatment of duodenal ulcer, benign gastric ulcer, post - operative ulcer, reflux oesophagitis, Zollinger - Ellison Syndrome and the following conditions where reduction of gastric secretion and acid output is desirable:
The prophylaxis of gastrointestinal haemorrhage from stress ulceration in seriously ill patients, the prophylaxis of recurrent haemorrhage in patients with bleeding peptic ulcers and before general anaesthesia in patients considered to be at risk of acid aspiration (Mendelson's Syndrome), particularly obstetric patients during labour. For appropriate cases, Zantac tablets are also available.
Children (6 months to 18 years):
Fada Ranitidina is indicated for the short term treatment of peptic ulcer and the treatment of gastro-oesophageal reflux, including reflux oesophagitis and symptomatic relief of gastro-oesophageal reflux disease.
ATC Code
Pharmacotherapeutic group: H2-receptor antagonist, ATC code: A02BA02
Pharmacotherapeutic group
H2-receptor antagonists, ATC code: A02BA02
Mechanism of Action
Ranitidine is a specific, rapidly acting histamine H2-antagonist. It inhibits basal and stimulated secretion of gastric acid, reducing both the volume and the acid and pepsin content of the secretion
Pharmacodynamic Effects
Ranitidine has a long duration of action and a single 75 mg dose effectively suppresses gastric acid secretion for at least 12 hours.
Pharmacotherapeutic group: H2-receptor antagonists
ATC code: A02BA02
Mechanism of action
Ranitidine is a specific, rapidly acting histamine H2-antagonist. It inhibits basal and stimulated secretion of gastric acid, reducing both the volume and the acid and pepsin content of the secretion.
The clinical data available mentions the use of ranitidine in children to prevent stress ulcers. No direct evidence for prevention of stress ulcers is available. Treatment for these patients is based on the observation that pH is above 4 after administration of ranitidine. The value of this surrogate parameter in children with stress ulcers remains to be established.
Absorption
Following oral administration of 150 mg ranitidine, maximum plasma concentrations (300 to 550 ng/mL) occurred after 1-3 hours. Two distinct peaks or a plateau in the absorption phase result from reabsorption of drug excreted into the intestine. The absolute bioavailability of ranitidine is 50-60%, and plasma concentrations increase proportionally with increasing dose up to 300 mg.
Absorption is not significantly impaired by food or antacids.
Distribution
Ranitidine is not extensively bound to plasma proteins (15%), but exhibits a large volume of distribution ranging from 96 to 142 L.
Metabolism
Ranitidine is not extensively metabolised. The fraction of the dose recovered as metabolites includes 6% of the dose in urine as the N-Oxide, 2% as the S-Oxide, 2% as desmethyl ranitidine and 1-2% as the furoic acid analogue.
Elimination
Plasma concentrations decline bi-exponentially, with a terminal half-life of 2-3 hours. The major route of elimination is renal. After IV administration of 150 mg 3H- ranitidine, 98% of the dose was recovered, including 5% in the faeces and 93% in the urine, of which 70% was unchanged parent drug. After oral administration of 150 mg 3H-ranitidine, 96% of the dose was recovered, 26% in the faeces and 70% in urine of which 35% was unchanged parent drug. Less than 3% of the dose is excreted in bile. Renal clearance is approximately 500mL/min, which exceeds glomerular filtration indicating net renal tubular secretion.
Special Patient Populations
- Patients over 50 years of age
In patients over 50 years of age, half-life is prolonged (3-4 h) and clearance is reduced, consistent with the age-related decline of renal function. However, systemic exposure and accumulation are 50% higher. This difference exceeds the effect of declining renal function, and indicates increased bioavailability in older patients.
Absorption
Absorption of ranitidine after intramuscular injection is rapid and peak plasma concentrations are usually achieved within 15 minutes of administration.
Distribution
Ranitidine is not extensively bound to plasma proteins (15%), but exhibits a large volume of distribution ranging from 96 to 142 L.
Metabolism
Ranitidine is not extensively metabolised. The fraction of the dose recovered as metabolites is similar after both oral and i.v. dosing; and includes 6% of the dose in urine as the N-oxide, 2& as the S-oxide, 2% as desmethylranitidine and 1 to 2% as the furoic acid analogue.
Elimination
Plasma concentrations decline bi-exponentially, with a terminal half-life of 2-3 hours. The major route of elimination is renal. After IV administration of 150 mg 3H-ranitidine, 98% of the dose was recovered, including 5% in faeces and 93% in urine, of which 70% was unchanged parent drug. After oral administration of 150 mg 3H-ranitidine, 96% of the dose was recovered, 26% in faeces and 70% in urine of which 35% was unchanged parent drug. Less than 3% of the dose is excreted in bile. Renal clearance is approximately 500 mL/min, which exceeds glomerular filtration indicating net renal tubular secretion.
Other special populations
Children/infants (6 months and above)
Limited pharmacokinetic data show that there were no significant differences in half-life (range for children 3 years and above: 1.7 - 2.2 h) and plasma clearance (range for children 3 years and above: 9 - 22 ml/min/kg) between children and healthy adults receiving intravenous ranitidine when correction is made for body weight. Pharmacokinetic data in infants is extremely limited but appears to be in line with that for older children.
Patients over 50 years of age
In patients over 50 years of age, half-life is prolonged (3-4 h) and clearance is reduced, consistent with the age-related decline of renal function. However, systemic exposure and accumulation are 50% higher. This difference exceeds the effect of declining renal function, and indicates increased bioavailability in older patients.
Neonates (under 1 month)
Limited pharmacokinetic data from term babies undergoing treatment with Extracorporeal Membrane Oxygenation (EMCO) suggests that plasma clearance following iv administration may be reduced (1.5-8.2 ml/min/kg) and the half-life increased in the new-born. Clearance of ranitidine appeared to be related to the estimated glomerular filtration rate in the neonates.
Treatment with a histamine H2-antagonist such as Fada Ranitidina 75 Relief may mask symptoms associated with carcinoma of the stomach and may therefore delay diagnosis of the condition.
Ranitidine is excreted via the kidney and so plasma levels of the drug are increased in patients with renal impairment (creatinine clearance less than 50 ml/min). Fada Ranitidina 75 Relief is not suitable for these patients without medical supervision.
People taking non-steroidal anti-inflammatory drugs, especially those with a history of peptic ulcer and the elderly, should not self-medicate with Fada Ranitidina 75 Relief but seek their doctor's advice before use.
People with a history of porphyria should avoid use of the product.
Consumers will be advised not to purchase a second pack of tablets without the advice of a pharmacist of doctor.
The product is not indicated in the following people without seeking their doctor's advice:
- Patients with renal impairment (creatinine clearance less than 50ml/min) and/or hepatic impairment.
- Patients under regular medical supervision for other reasons.
- Patients taking medications either physician prescribed or self-prescribed.
- Those with difficulty swallowing, persistent stomach pain or unintended weight loss in association with symptoms of indigestion.
- Those who are middle-aged or elderly with new or recently changed symptoms of indigestion.
In patients such as the elderly, persons 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 current users of ranitidine alone versus those who had stopped treatment, with an observed adjusted relative risk increase of 1,82 (95% CI 1,26-2,64).
WARNINGSAllergy alert: Do not use if you are allergic to ranitidine or other acid reducers
Do Not UseIf pregnant or breast-feeding, ask a health professional before use.
Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away.
DirectionsSee above.
Malignancy
The possibility of malignancy should be excluded before commencement of therapy in patients with gastric ulcer as treatment with ranitidine may mask symptoms of gastric carcinoma.
Renal Disease
Ranitidine is excreted via the kidney and so plasma levels of the drug are increased in patients with renal impairment.
Bradycardia in association with rapid administration of Fada Ranitidina has been reported rarely, usually in patients with factors predisposing to cardiac rhythm disturbances. Recommended rates of administration should not be exceeded.
It has been reported that the use of higher than recommended doses of intravenous H2-antagonists has been associated with rises in liver enzymes when treatment has been extended beyond five days.
Rare clinical reports suggest that ranitidine may precipitate acute porphyric attacks. Ranitidine should therefore be avoided in patients with a history of acute porphyria.
In patients such as the elderly, persons 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 current users of ranitidine alone versus those who had stopped treatment, with an observed adjusted relative risk increase of 1.82 (95% CI 1.26-2.64).. Post-marketing data indicate reversible mental confusion, depression, and hallucinations have been reported most frequently in severely ill and elderly patients.
No known effect
None reported.
Route of Administration
Oral
Dosage
Adults (Including the elderly) and children 16 years of age and older:
Swallow one Fada Ranitidina 75 Relief tablet whole, with a drink of water, as soon as you have symptoms. If symptoms persist for more than one hour or return, take another tablet. Do not take more than two tablets in 24 hours.
Do not take the tablets for more than 6 days without the advice of a pharmacist or doctor.
Children under 16 years
Not recommended for children under 16 years of age.
Directions(- Other special - populations)
Posology
Adults (including elderly) / Adolescents (12 years and over)
Fada Ranitidina may be given either as a slow (over 2 minutes) intravenous injection up to a maximum of 50 mg, after dilution to a volume of 20 ml per 50 mg dose, which may be repeated every 6 to 8 hours; or as an intermittent intravenous infusion at a rate of 25 mg per hour for two hours; the infusion may be repeated at 6 to 8 hour intervals, or as an intramuscular injection of 50 mg (2 ml) every 6 to 8 hours.
Prophylaxis of haemorrhage from stress ulceration or recurrent haemorrhage:
In the prophylaxis of haemorrhage from stress ulceration in seriously ill patients or the prophylaxis of recurrent haemorrhage in patients bleeding from peptic ulceration, parenteral administration may be continued until oral feeding commences. Patients considered to be still at risk may then be treated with Zantac tablets 150 mg twice daily.
In the prophylaxis of upper gastro-intestinal haemorrhage from stress ulceration in seriously ill patients a priming dose of 50 mg as a slow intravenous injection followed by a continuous intravenous infusion of 0.125 - 0.250 mg/kg/hr may be preferred.
Prophylaxis of Mendleson's syndrome:
In patients considered to be at risk of developing acid aspiration syndrome, Fada Ranitidina 50 mg may be given intramuscularly or by slow intravenous injection 45 to 60 minutes before induction of general anaesthesia.
Children / Infants (6 months to 11 years)
() - Other special populations
Fada Ranitidina may be given as a slow (over 2 minutes) i.v. injection up to a maximum of 50 mg every 6 to 8 hours.
Peptic Ulcer Acute Treatment and Gastro-Oesophageal Reflux
Intravenous therapy in children with peptic ulcer disease is indicated only when oral therapy is not possible.
For acute treatment of peptic ulcer disease and gastro-oesophageal reflux in paediatric patients, Fada Ranitidina may be administered at doses that have been shown to be effective for these diseases in adults and effective for acid suppression in critically ill children. The initial dose (2.0 mg/kg or 2.5 mg/kg, maximum 50 mg) may be administered as a slow intravenous infusion over 10 minutes, either with a syringe pump followed by a 3 mL flush with normal saline over 5 min, or following dilution with normal saline to 20 mL. Maintenance of pH > 4.0 can be achieved by intermittent infusion of 1.5 mg/kg every 6 h to 8 h. Alternatively treatment can be continuous, administering a loading dose of 0.45 mg/kg followed by a continuous infusion of 0.15 mg/kg/hr.
Neonates (under 1 month)
(- Pharmacokinetic properties - Other special populations)
Patients over 50 years of age
- Other special populations
Patients with renal impairment
Accumulation of ranitidine with resulting elevated plasma concentrations will occur in patients with renal impairment (creatinine clearance less than 50 ml/min). Accordingly, it is recommended in such patients that ranitidine be administered in doses of 25 mg.
Method of administration
Intravenous or intramuscular injection
No special instructions
Fada Ranitidina has been shown to be compatible with the following intravenous infusion fluids:-
0.9% Sodium Chloride BP
5% Dextrose BP
0.18% Sodium Chloride and 4% Dextrose BP
4.2% Sodium Bicarbonate BP
Hartmann's Solution.
All unused admixtures of Fada Ranitidina with infusion fluids should be discarded 24 hours after preparation.
Although compatibility studies have only been undertaken in polyvinyl chloride infusion bags (in glass for Sodium Bicarbonate BP) and a polyvinyl chloride administration set it is considered that adequate stability would be conferred by the use of a polyethylene infusion bag.
