Metronidazole intravenous

Drug Interactions • Disulfiram Psychotic reactions and confusion have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently. Do not administer Metronidazole Injection to patients who have taken disulfiram within the last two weeks (see CONTRAINDICATIONS ). • Alcoholic Beverages Abdominal cramps, nausea, vomiting, headaches, tachycardia and flushing may occur if alcoholic beverages or products containing propylene glycol are consumed during or following metronidazole therapy. Discontinue consumption of alcohol or products containing propylene glycol before, during and up to 72 hours after therapy with Metronidazole Injection (see CONTRAINDICATIONS ).

• Warfarin and other Oral Anticoagulants Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time and increased risk of hemorrhages. When Metronidazole Injection is prescribed for patients on this type of anticoagulant therapy, prothrombin time and international normalized ratio (INR) should be carefully monitored and their anticoagulant dose adjusted accordingly. Monitor patients for signs and symptoms of bleeding.

• Lithium In patients stabilized on relatively high doses of lithium, short-term metronidazole therapy has been associated with elevation of serum lithium and, in a few cases, signs of lithium toxicity. Lithium toxicity may lead to renal damage. Frequent monitoring of serum lithium and serum creatinine levels is necessary. • Busulfan Metronidazole has been reported to increase plasma concentrations of busulfan, which can result in an increased risk for serious busulfan toxicity such as sinusoidal obstruction syndrome, gastrointestinal mucositis, and hepatic veno-occlusive disease.

Metronidazole Injection should not be administered concomitantly with busulfan unless the benefit outweighs the risk. If no therapeutic alternatives to metronidazole are available, and concomitant administration with busulfan is medically needed, frequent monitoring of busulfan plasma concentration should be performed and the busulfan dose should be adjusted accordingly. • Drugs that Inhibit CYP450 Enzymes The simultaneous administration of drugs that decrease microsomal liver enzyme activity, such as cimetidine, may decrease metabolism and reduce plasma clearance of metronidazole which may result in metronidazole toxicity.

• Drugs that Induce CYP450 Enzymes The simultaneous administration of drugs that induce microsomal liver enzyme activity, such as phenytoin or phenobarbital, may accelerate the elimination of metronidazole and therefore decrease its efficacy. • Cytochrome P450 3A4 (CYP3A4) substrates Concomitant use of Metronidazole Injection and CYP3A4 substrates (e.g., amiodarone, tacrolimus, cyclosporine, carbamazepine, phenytoin, and quinidine) may increase respective CYP3A4-substrate plasma levels. Monitoring of plasma concentrations of CYP3A4 substrates may be necessary. • 5-Fluorouracil Metronidazole Injection decreases the clearance of 5-fluorouracil and may therefore cause 5-fluorouracil toxicity.

• Vecuronium Metronidazole Injection may potentiate the effects of vecuronium. • Drugs that Prolong the QT interval QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval. • Drug/Laboratory Test Interactions Metronidazole may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), lactate dehydrogenase (LDH), triglycerides and glucose hexokinase. Metronidazole causes an increase in ultraviolet absorbance at 340 nm resulting in falsely decreased values.

Pregnancy Teratogenic Effects There are no adequate and well-controlled studies of Metronidazole Injection in pregnant women. There are published data from case-control studies, cohort studies, and 2 meta-analyses that include more than 5000 pregnant women who used metronidazole during pregnancy. Many studies included first trimester exposures. One study showed an increased risk of cleft lip, with or without cleft palate, in infants exposed to metronidazole in utero ; however, these findings were not confirmed.

In addition, more than ten randomized, placebo-controlled clinical trials enrolled more than 5000 pregnant women to assess the use of antibiotic treatment (including metronidazole) for bacterial vaginosis on the incidence of preterm delivery. Most studies did not show an increased risk for congenital anomalies or other adverse fetal outcomes following metronidazole exposure during pregnancy. Three studies conducted to assess the risk of infant cancer following metronidazole exposure during pregnancy did not show an increased risk; however, the ability of these studies to detect such a signal was limited.

Metronidazole crosses the placental barrier and its effects on the human fetal organogenesis are not known. Reproduction studies have been performed in rats, rabbits and mice at doses similar to the maximum recommended daily dose based on body surface area comparisons. There was no evidence of harm to the fetus due to metronidazole. Healthcare provider should carefully consider the potential risks and benefits for each specific patient before prescribing Metronidazole Injection.

Nursing Mothers Metronidazole is present in human milk at concentrations similar to maternal serum levels, and infant serum levels can be close to or comparable to infant therapeutic levels. Because of the potential for tumorigenicity shown for metronidazole in mouse and rat studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Alternatively, a nursing mother may choose to pump and discard human milk for the duration of metronidazole therapy, and for 24 hours after therapy ends and feed her infant stored human milk or formula.