Bismuthinteractions

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. CYP inducers and CYP inhibitors: Prolonged or accelerated half-life of metronidazole or concomitant medications; use with caution.

7.1 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.

7.2 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.

7.3 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. 7.4 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.

7.5 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.

7.6 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.

7.7 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.

7.8 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.

7.9 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.