Pylera (bismuth subcitrate potassium, metronidazole, and tetracycline hydrochloride)

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.

Common side effects of Pylera include:

• nausea,
• diarrhea,
• upset stomach,
• abdominal pain,
• changes in taste,
• headache,
• dizziness,
• vaginal itching or discharge, or
• diarrhea or other changes in your stools.

Tell your doctor if you have unlikely but serious side effects of Pylera including:

• numbness and tingling of arms or legs,
• discolored teeth,
• mental/mood changes (such as confusion, anxiety, irritability, depression),
• difficult or painful swallowing, heartburn,
• fast or pounding heartbeat,
• ringing in the ears, or
• frequent or painful urination.

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

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.

Methoxyflurane

• Do not administer methoxyflurane to patients taking Pylera. The concurrent use of tetracycline hydrochloride, a component of Pylera, with methoxyflurane has been reported to result in fatal renal toxicity.

Disulfiram

• Psychotic reactions have been reported in alcoholic patients who are using metronidazole, a component of Pylera and disulfiram concurrently.
• Pylera should not be given to patients who have taken disulfiram within the last two weeks.

Alcohol

• Consumption of alcoholic beverages or administration of other products containing propylene glycol during treatment with Pylera and for at least 3 days afterwards may cause a disulfiram-like reaction (abdominal cramps, nausea, vomiting, headaches, and flushing) due to the interaction between alcohol or propylene glycol and metronidazole, a component of Pylera.
• Discontinue alcoholic beverage or other products containing propylene glycol during and for at least 3 days after therapy with Pylera.

Oral Contraceptives

• Concurrent use of Pylera with oral contraceptive may make oral contraceptives less effective due to an interaction with the tetracycline component of Pylera. Breakthrough bleeding has been reported.
• Women of child-bearing potential should use a different or additional form of contraception while taking Pylera.

Anticoagulants

• Pylera may alter the anticoagulant effects of warfarin and other oral coumarin anticoagulants.
• Metronidazole has been reported to potentiate the anticoagulant effect of warfarin, and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time.
• Tetracycline has been shown to depress plasma prothrombin activity.
• Prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests should be closely monitored if Pylera is administered concomitantly with warfarin. Patients should also be monitored for evidence of bleeding.

Lithium

• In patients stabilized on relatively high doses of lithium, short-term use of Pylera may cause elevation of serum lithium concentrations and signs of lithium toxicity due to the interaction between metronidazole and lithium.
• Serum lithium and serum creatinine concentrations should be monitored several days after beginning treatment with Pylera to detect any increase that may precede clinical symptoms of lithium toxicity.

Antacids, Multivitamins, Or Dairy Products

• The absorption of Pylera may be reduced if administered with antacids containing aluminium, calcium, or magnesium; preparations containing iron, zinc, or sodium bicarbonate; or milk or dairy products due to the interaction between these products and tetracycline.
• These products should not be consumed concomitantly with Pylera. However, the clinical significance of reduced tetracycline systemic exposure is unknown as the relative contribution of systemic versus local antimicrobial activity against Helicobacter pylori has not been established.

Busulfan

• Metronidazole has been reported to increase plasma concentrations of busulfan, which can result in an increased risk for serious busulfan toxicity.
• Do not administer Pylera concomitantly with busulfan unless the benefit outweighs the risk.
• If no therapeutic alternatives to Pylera are available, and concomitant administration with busulfan is medically needed, monitor for busulfan toxicity and busulfan plasma concentrations and adjust the busulfan dose accordingly.

Inhibitors Of CYP450 Liver Enzymes

• The simultaneous administration of Pylera and drugs that inhibit microsomal liver enzymes, such as cimetidine, may result in a prolonged half-life and decreased plasma clearance of metronidazole.

Inducers Of CYP450 Liver Enzymes

• The simultaneous administration of Pylera and drugs that induce microsomal liver enzymes, such as phenytoin or phenobarbital, may accelerate the elimination of metronidazole, resulting in reduced plasma concentrations of metronidazole.
• Impaired clearance of phenytoin has also been reported in this situation. Monitor phenytoin concentrations during treatment with Pylera.

• Pylera is contraindicated in women who are pregnant because treatment of Helicobacter pylori infection can be delayed in pregnant women, and the use of drugs of the tetracycline class during the second and third trimester pregnancy can also cause permanent discoloration of the teeth (yellow-gray brown) and possibly inhibit bone development.
• Two of the individual components of Pylera, tetracycline and metronidazole, are present in human milk at concentrations similar to maternal serum levels.
• It is not known whether bismuth subcitrate, the third component of Pylera is present in human milk.
• It is not known what effect metronidazole, tetracycline or bismuth has on the breastfed infant or on milk production. Tetracycline binds with calcium in human milk.
• Data indicate that oral absorption of tetracycline in infants is low due to the calcium binding in human milk.
• Metronidazole transfers to human milk, and infant serum levels can be close to or comparable to infant therapeutic levels.
• Because of the potential risk of tumorigenicity shown in animal studies with metronidazole, a woman should pump and discard human milk for the duration of Pylera therapy, and for 2 days after therapy ends, and feed her infant stored human milk (collected prior to therapy) or formula.