Bismuth subcitrate, Metronidazole and Tetracycline

PYLERA is a combination of metronidazole, a nitroimidazole antimicrobial, tetracycline,- a tetracycline class antimicrobial and bismuth subcitrate potassium, indicated for use, in combination with omeprazole, for the treatment of patients with Helicobacter pylori infection and duodenal ulcer disease (active or history of within the past 5 years) to eradicate H. pylori. To reduce the development of drug-resistant bacteria and maintain the effectiveness of PYLERA and other antibacterial drugs, PYLERA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

PYLERA is a combination of antibacterial agents (metronidazole and tetracycline hydrochloride) and bismuth subcitrate potassium.

Administer three PYLERA capsules 4 times a day (after meals and at bedtime) for 10 days. One omeprazole 20 mg capsule should be taken twice a day with PYLERA after the morning and evening meal for 10 days ( Table 1 ). Table 1: Daily Dosing Schedule for PYLERA Time of dose Number of capsules of PYLERA Number of capsules of omeprazole 20 mg After morning meal 3 1 After lunch 3 0 After evening meal 3 1 At bedtime 3 0 Instruct patients to swallow the PYLERA capsules whole with a full glass of water (8 ounces). Ingestion of adequate amounts of fluid, particularly with the bedtime dose, is recommended to reduce the risk of esophageal irritation and ulceration by tetracycline hydrochloride. If a dose is missed, patients should continue the normal dosing schedule until medication is gone. Patients should not take double doses. If more than 4 doses are missed, the prescriber should be contacted.

Disulfiram usage within the last two weeks. Alcoholic beverage consumption for at least three days during or after therapy. Patients with Cockayne syndrome. Severe renal impairment. Women who are pregnant. Known hypersensitivity to product components.

Boxed warning (potential for carcinogenicity): Metronidazole has been shown to be carcinogenic in mice and rats. It is unknown whether metronidazole is associated with carcinogenicity in humans. Fetal Toxicity: Advise pregnant women of the risk throughout pregnancy for retardation of skeletal development seen in animal studies and permanent discoloration of teeth with tetracycline if used during the second or third trimester. Maternal Toxicity: Risk of hepatotoxicity in pregnant women with high doses of intravenous tetracycline also resulting in stillborn or premature birth. Tooth Enamel discoloration and hypoplasia: permanent discoloration may develop with use during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years).

Most frequently reported adverse reactions (≥5%): abnormal feces, diarrhea, nausea, and headache.

Disulfiram: Psychotic reactions can occur, do not take concurrently or within the last 2 weeks of disulfiram. Alcohol: Abdominal cramps, nausea, vomiting, headaches, and flushing can occur, do not consume during therapy and for at least 3 days afterwards. Oral Contraceptives: Decreased efficacy possibly resulting in pregnancy, use a different or additional form of contraception. Anticoagulants: Potentiation of the anticoagulant effect, Prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests should be closely monitored. Lithium: Increased lithium serum concentrations, measure serum lithium and serum creatinine concentrations during therapy. Antacids, Multivitamins or Dairy Products: Decreased absorption of PYLERA, do not take concomitantly. Busulfan: Increased busulfan serum concentrations, avoid concomitant use, monitor for busulfan toxicity.

Store at controlled room temperature [68° to 77°F or 20° to 25°C].