Rabeprazole: Worldwide, over 2900 patients have been treated with rabeprazole in Phase II-III clinical trials involving various dosages and durations of treatment. In general, rabeprazole treatment has been well tolerated in both short- and long-term trials. The adverse events rates were generally similar between the 10 and 20 mg doses.
In short- and long-term studies, the following adverse events, regardless of causality, were reported in rabeprazole-treated patients. Rare events are those reported in ≤1/1000 patients.
Body as a Whole: Asthenia, fever, allergic reaction, chills, malaise, substernal chest pain, neck rigidity, photosensitivity reaction.
Cardiovascular System: Hypertension, myocardial infarct, abnormal electrocardiogram (ECG), migraine, syncope, angina pectoris, bundle branch block, palpitation, sinus bradycardia, tachycardia. Rare: Bradycardia, pulmonary embolus, supraventricular tachycardia, thrombophlebitis, vasodilation, QT prolongation and ventricular tachycardia.
Digestive System: Diarrhea, nausea, vomiting, abdominal pain, dyspepsia, flatulence, constipation, dry mouth, eructation, gastroenteritis, rectal hemorrhage, melena, anorexia, cholelithiasis, mouth ulceration, stomatitis, dysphagia, gingivitis, cholecystitis, increased appetite, abnormal stools, colitis, esophagitis, glossitis, pancreatitis, proctitis. Rare: Bloody diarrhea, cholangitis, duodenitis, gastrointestinal hemorrhage, hepatic encephalopathy, hepatitis, hepatoma, liver fatty deposit, salivary gland enlargement, thirst.
Endocrine System: Hyperthyroidism, hypothyroidism.
Hemic and Lymphatic System: Anemia, ecchymosis, lymphadenopathy, hypochromic anemia.
Metabolic & Nutritional Disorders: Peripheral edema, edema, weight gain, gout, dehydration, weight loss.
Musculoskeletal System: Myalgia, arthritis, leg cramps, bone pain, arthrosis, bursitis. Rare: Twitching.
Nervous System: Insomnia, anxiety, dizziness, depression, nervousness, somnolence, hypertonia, neuralgia, vertigo, convulsion, abnormal dreams, decreased libido, neuropathy, paraesthesia, tremor. Rare: Agitation, amnesia, confusion, extrapyramidal syndrome, hyperkinesia.
Respiratory System: Dyspnea, asthma, epistaxis, laryngitis, hiccup, hyperventilation. Rare: Apnea, hypoventilation.
Skin and Appendages: Rash, pruritus, sweating, urticaria, alopecia. Rare: Dry skin, herpes zoster, psoriasis, skin discoloration.
Special Senses: Cataract, amblyopia, glaucoma, dry eyes, abnormal vision, tinnitus, otitis media. Rare: Corneal opacity, blurred vision, diplopia, deafness, eye pain, retinal degeneration, strabismus.
Urogenital System: Cystitis, urinary frequency, dysmenorrhea, dysuria, kidney calculus, metrorrhagia, polyuria. Rare: Breast enlargement, hematuria, impotence, leukorrhea, menorrhagia, orchitis, urinary incontinence.
Laboratory Values: The following changes in laboratory parameters were reported as adverse events: Abnormal platelets, albuminuria, increased creatinine phosphokinase, abnormal erythrocytes, hypercholesterolemia, hyperglycemia, hyperlipemia, hypokalemia, hyponatremia, leukocytosis, leukorrhea, abnormal liver function tests, increase prostatic specific antigen and SGPT, urine abnormality, abnormal WBC.
Combination Treatment with Amoxicillin and Clarithromycin: In clinical trials using combination therapy with rabeprazole plus amoxicillin and clarithromycin (RAC), no adverse events unique to this drug combination were observed. In the U.S. multicenter study, the most frequently reported drug-related adverse events for patients who received RAC therapy for 7 or 10 days were diarrhea (8% and 7%) and taste perversion (6% and 10%), respectively.
No clinically significant laboratory abnormalities particular to the drug combinations were observed.
Post-Marketing Adverse Events: Additional adverse events reported from worldwide marketing experience with rabeprazole sodium are: Sudden death, coma and hyperammonemia, jaundice, rhabdomyolysis, disorientation and delirium , anaphylaxis, angioedema, bullous and other drug eruptions of the skin, interstitial pneumonia and nephritis; and TSH elevations. In most instances, the relationship to rabeprazole sodium was unclear. In addition, agranulocytosis, hemolytic anemia, leukopenia, pancytopenia and thrombocytopenia have been reported. Increases in prothrombin time/INR in patients treated with concomitant warfarin have been reported.
Domperidone: The frequency of adverse reactions listed as follow is defined using the following convention: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare <1/10,000).
Immune System Disorder: Very Rare: Allergic reaction.
Endocrine Disorder: Rare: Increased prolactin levels.
Nervous System Disorders: Very Rare: Extrapyramidal side effects.
Gastrointestinal Disorders: Rare: GI disorders, including very rare transient intestinal cramps.
Skin and Subcutaneous Tissue Disorders: Very Rare: Urticaria.
Reproductive System and Breast Disorders: Rare: Galactorrhea, gynaecomastia, amenorrhea.
As the hypophysis is outside the blood-brain barrier, domperidone may cause an increase in prolactin levels. In rare cases, this hyperprolactinaemia may lead to neuro-endocrinological side effects eg, galactorrhea, gynaecomastia and amenorrhea.
Extrapyramidal side effects are very rare in neonates and infants, and exceptional in adults. These side effects reverse spontaneously and completely as soon as the treatment is stopped.