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The most common adverse reactions ( ≥ 1%) reported in clinical trials when all three components of this therapy were given concomitantly are listed in Table 1 below. The majority of the adverse reactions were related to the gastrointestinal tract, were reversible, and infrequently led to discontinuation of therapy.

Table 1: Incidence of Adverse Reactions Reported in Clinical Trials ( ≥ 1%)†

Adverse Reactions Bismuth Subsalicylate, Metronidazole, and Tetracycline ‡
(N = 266)
% Patients
Nausea 12
Diarrhea 6.8
Abdominal Pain 6.8
Melena 3
Upper Respiratory Infection 2.3
Constipation 1.9
Anorexia 1.5
Asthenia 1.5
Vomiting 1.5
Discolored Tongue* 1.5
Headache 1.5
Dyspepsia 1.5
Dizziness 1.5
Stool Abnormality** 1.1
Duodenal Ulcer 1.1
Sinusitis 1.1
Taste Perversion*** 1.1
Flatulence 1.1
GI Hemorrhage 1.1
Pain 1.1
Insomnia 1.1
Anal Discomfort 1.1
Paresthesia 1.1
* darkening of the tongue
** black or dark stools
*** metallic taste
† Includes reactions reported at ≥ 1% in patients taking bismuth subsalicylate, metronidazole, and tetracycline in Studies 1, 2, 3, and 4 (see Clinical Studies).
‡ In Studies 1, 2, and 3(N = 197), most patients were on concomitant acid suppression therapy.

The additional adverse reactions ( < 1%) reported in clinical trials when all three components of this therapy were given concomitantly are listed below and divided by body system:

Gastrointestinal: dry mouth, dysphagia, eructation, GI monilia, glossitis, intestinal obstruction, rectal hemorrhage, stomatitis

Skin: acne, ecchymosis, photosensitivity reaction (see WARNINGS), pruritus, rash

Cardiovascular: cerebral ischemia, chest pain, hypertension, myocardial infarction

CNS: nervousness, somnolence

Musculoskeletal: arthritis, rheumatoid arthritis, tendonitis

Metabolic:SGOT increase, SGPT increase

Urogenital: urinary tract infection

Other: conjunctivitis, flu syndrome, infection, malaise, neoplasm, rhinitis, syncope, tooth disorder

Other Important Adverse Reactions from Labeling for the Individual Components of HELIDAC Therapy

Metronidazole

Blood and Lymphatic system disorders: reversible neutropenia (leucopenia) in cases of prolonged treatment; rarely reversible thrombocytopenia however no persistent haematological abnormalities attributable to metronidazole have been observed. (See PRECAUTIONS)

Cardiac disorders: Flattening of the T-wave may be seen in electrocardiographic tracings.

Gastrointestinal disorders: Furry tongue, glossitis, stomatitis; these may be associated with a sudden overgrowth of candida which may occur during therapy; epigastric distress (See PRECAUTIONS)

Immune system disorders: Urticaria, erythematous rash, Stevens-Johnson Syndrome, toxic epidermal necrolysis, flushing, nasal congestion, dryness of the mouth (or vagina or vulva) and fever (See CONTRAINDICATIONS)

Metabolism and nutrition disorders: Cases of pancreatitis have been reported, which abated on withdrawal of the drug, have been reported.

Nervous system disorders: The most serious adverse reactions reported in patients treated with metronidazole have been convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity. In addition, patients have reported syncope, vertigo, incoordination, ataxia, confusion, dysarthria, irritability, depression, weakness, and insomnia. (See WARNINGS)

Renal disorders: Dysuria, cystitis, polyuria, incontinence, and a sense of pelvic pressure. Instances of darkened urine have been reported by approximately one patient in 100,000. Although the pigment which is probably responsible for this phenomenon has not been positively identified, it is almost certainly a metabolite of metronidazole and seems to have no clinical significance.

Other: Proliferation of Candida in the vagina, dyspareunia, decrease of libido, proctitis, and fleeting joint pains sometimes resembling “serum sickness.” Crohn's disease patients are known to have an increased incidence of gastrointestinal and certain extraintestinal cancers. There have been some reports in the medical literature of breast and colon cancer in Crohn's disease patients who have been treated with metronidazole at high doses for extended periods of time. A cause and effect relationship has not been established.

Tetracycline Hydrochloride

Blood and lymphatic system disorders: Hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, neutropenia, and eosinophilia.

Gastrointestinal disorders: Anorexia, nausea, epigastric distress, glossitis, black hairy tongue, dysphagia, enterocolitis, and inflammatory lesions (with monilial overgrowth) in the anogenital region. Rare instances of esophagitis and esophageal ulceration have been reported in patients taking the tetracycline-class antibiotics in capsule and tablet form. Most of the patients who experienced esophageal irritation took the medication immediately before going to bed. Permanent discoloration of teeth may be caused when tetracycline is used during tooth development. Enamel hypoplasia has also been reported. (See WARNINGS)

Hypersensitivity: urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, pericarditis, exacerbation of systemic lupus erythematosus and serum sickness-like reactions, as fever, rash, and arthralgia.

Liver disorders: Hepatotoxicity and liver failure have been observed in patients receiving large doses of tetracycline and in tetracycline-treated patients with renal impairment. Increases in liver enzymes and hepatic toxicity have been reported rarely.

Nervous system disorders: Pseudotumor cerebri (benign intracranial hypertension) in adults and bulging fontanels in infants, Visual disturbances. Tinnitus and myasthenic syndrome have been reported rarely.

Renal and urinary disorders: Rise in BUN has been reported and is possibly dose related (See CONTRAINDICATIONS)

Skin and subcutaneous tissue disorders: Maculopapular and erythematous rashes have been reported. Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme have been reported. Onycholysis, discoloration of the nails, exfoliative dermatitis, and photosensitivity have been rarely reported. (See PRECAUTIONS)

Other: When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of thyroid glands. No abnormalities of thyroid function studies are known to occur.