MAXIMUM STRENGTH ACID REDUCER WITHOUT PRESCRIPTION

Adverse Drug Reaction Overview Ranitidine hydrochloride has been shown to be generally very well-tolerated. In various clinical trials involving either 75 mg or 150 mg of ranitidine hydrochloride the adverse reaction rates were comparable with the most frequently reported adverse events being: headache, nausea, vomiting, and diarrhea: common [frequent] > 1% and < 10%.

Overall adverse event incidence among ranitidine-treated subjects was comparable to that seen in placebo-treated subjects, (no statistical difference) independent of demographic characteristics. The following adverse reactions have been reported as events in clinical trials, in post-marketing surveillance, or in the routine management of patients treated with prescription doses of ranitidine hydrochloride.

The majority of these events have been observed following oral administration of higher prescription doses of ranitidine, and a causal relationship to ranitidine hydrochloride has not always been established. Blood and Lymphatic System Disorders Blood count changes (anemia, leukopenia, granulocytopenia and thrombocytopenia) have occurred in a few patients.

These are usually reversible. Rare cases of agranulocytosis, pancytopenia, or neutropenia, sometimes with marrow hypoplasia or marrow aplasia, aplastic anemia and cases of acquired immune hemolytic anemia have been reported. Cardiac Disorders As with other H2 receptor antagonists, there have been rare reports of arrhythmias such as tachycardia, premature ventricular beats, sinus bradycardia, asystole, extrasystole, atrioventricular block with sinus pauses, premature ventricular beats and state of shock and very rare reports of blood pressure increases and palpitations.

Central Nervous System Headache (sometimes severe); malaise, dizziness, somnolence, insomnia, vertigo, dystonia, nervousness, meningitis. Rare cases of reversible involuntary motor disturbances have been reported (tremors, myoclonus or involuntary eye movements).

Endocrine Disorders No clinically significant interference with endocrine or gonadal function has been reported. There have been rare reports of breast symptoms and hyperprolactinemia in men taking ranitidine. Eye Disorders Reversible blurred vision suggestive of a change in accommodation has been reported.

Rare cases of intraocular pressure changes have been reported. MAXIMUM STRENGTH ACID REDUCER WITHOUT PRESCRIPTION Product Monograph Page 7 of 33 Gastrointestinal Disorders Constipation, diarrhea, nausea/vomiting, abdominal discomfort/pain, dysgeusia, acute pancreatitis and dry mouth.

Rebound hypersecretion has been reported upon withdrawal of ranitidine therapy. General Disorders and Administration Site Conditions Very rare reports of asthenia. Hepatobiliary Disorders Transient and reversible changes in liver function tests can occur (increase in ALT and AST values).

With oral administration, there have been occasional reports of hepatitis, hepatocellular or hepatocanalicular or mixed with or without jaundice, and cholestatic jaundice. In such circumstances, ranitidine should be discontinued immediately.

These are usually reversible, but in exceedingly rare circumstances, death has occurred. Cases of liver failure have also been reported. Immune System Disorders Rare cases of hypersensitivity reactions (including angina, chest pain, hypotension, bronchospasm, fever, rash, eosinophilia, anaphylaxis (anaphylactic shock) urticarial, angioneurotic edema (Quincke's edema), hypotension, bullous dermatitis, eczema and dyspnea).

These events have been reported after administration of a single dose of ranitidine. Musculoskeletal and Connective Tissue Disorders Rare reports of arthralgia and myalgia. Psychiatric Disorders Isolated cases of reversible mental confusion, depression, hallucinations and agitation, reported predominantly in severely ill and elderly patients or those with renal impairment.

In such cases, treatment must be discontinued. Renal and Urinary disorders Acute interstitial nephritis and small increase in serum creatinine have occasionally occurred after a single dose. Nephrotoxicity has been reported rarely. Reproductive System and Breast Disorders Reversible impotence, loss of libido, breast symptoms and conditions including gynecomastia and galactorrhea.

Skin and Subcutaneous Tissue Disorders Pruritis, skin rash, including cases suggestive of mild erythema multiforme. Alopecia, contact dermatitis, photosensitivity. Vascular Disorders Vasculitis MAXIMUM STRENGTH ACID REDUCER WITHOUT PRESCRIPTION Product Monograph Page 8 of

Gastrointestinal Treatment with a histamine H2-antagonist may mask symptoms associated with carcinoma of the stomach and, therefore, may delay diagnosis of that condition. Accordingly, patients should be advised to consult a physician if they have difficulty or pain on swallowing, experience choking or persistent abdominal discomfort or if symptoms get worse or persist for more than 2 weeks or new symptoms develop.

The administration of H2 receptor antagonists promotes intragastric bacterial growth by reducing gastric acidity. Regular medical supervision is recommended to patients receiving NSAIDs in concurrent treatment with ranitidine, especially if with a history of peptic ulcer.

Hematologic Rare clinical reports suggest that ranitidine may precipitate acute porphyric attacks. Therefore, ranitidine should be avoided in patients with a history of acute porphyria. Hepatic/Biliary/Pancreatic In case of severe hepatocellular impairment, especially if associated renal impairment exists, it is preferable to reduce the dosage.

Immune In patients such as the elderly, subjects with chronic lung disease, diabetes, or immunocompromised people, there may be an increased risk of developing community acquired pneumonia. Renal Ranitidine is excreted via the kidneys and, in the presence of severe renal impairment, plasma levels of ranitidine are increased and elimination prolonged.

In case of renal impairment, it is recommended to reduce the dosage based on creatinine clearance or creatinine levels. In elderly patients with renal impairment, interrupt treatment if a state of mental confusion arises. Accordingly, MAXIMUM STRENGTH ACID REDUCER WITHOUT PRESCRIPTION should be used under physician supervision for these patients.

MAXIMUM STRENGTH ACID REDUCER WITHOUT PRESCRIPTION Product Monograph Page 5 of 33 Special Populations Pregnant Women The safety of ranitidine hydrochloride in the treatment of conditions where a controlled reduction of gastric secretion is required during pregnancy has not been established.

Reproduction studies performed in rats and rabbits at higher doses have revealed no evidence of ranitidine induced impaired fertility or harm to the fetus. In the absence of any teratogenic effect in animals, malformations are not expected in humans.

Clinically, the use of ranitidine in a limited number of pregnancies has apparently not revealed any specific malformations or fetotoxic effects to date. Nevertheless, if the administration of ranitidine is considered to be necessary, its use requires that the potential benefits be weighed against possible hazards to the patient and to the fetus.

Nursing Women The passage of H2 antagonists through breast milk is documented, with an elevated milk/plasma concentration ratio, but the doses ingested by the child remain low (about 1% of the maternal dose). Nonetheless, only kinetic data are available.

The a fortiori tolerance in the child in case of prolonged or high-dose maternal treatment is unknown. Consequently, as a precautionary measure, it is best to avoid this medication while breastfeeding. Pediatrics (< 16 years of age) The safety of ranitidine has been assessed in children aged 0 to 16 years with acid-related disease.

Ranitidine has an undesirable effect profile resembling that in adults. There are limited long-term safety data available, in particular regarding growth and development. Children under 16 years of age should be supervised by a physician.

Geriatrics (> 65 years of age) Since malignancy is more common in the elderly, particular consideration must be given to this before therapy with MAXIMUM STRENGTH ACID REDUCER WITHOUT PRESCRIPTION is instituted. Elderly patients receiving NSAIDs concomitantly with MAXIMUM STRENGTH ACID REDUCER WITHOUT PRESCRIPTION should be closely supervised.

As with all medication, in the elderly, consideration should be given to concurrent drug therapy. Driving a Vehicle or Performing Other Hazardous Tasks If, during treatment, dizziness, drowsiness or vertigo would be noticed, avoid driving or operating machinery or tasks that require prompt vigilance.

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