Zifam CS1/CS2 Special Precautions

General: Those precautions that pertain to sulbactam and cefoperazone will also pertain to the combination as follows.
Cefoperazone is extensively excreted in bile. The serum half-life of cefoperazone is usually prolonged and urinary excretion of the drug increased in patients with hepatic disease and/or biliary obstruction. Even with severe hepatic dysfunction, therapeutic concentrations of cefoperazone are obtained in bile and only a 2- to 4-fold increase in half-life is seen.
Dose modification may be necessary in cases of severe biliary obstruction, severe hepatic disease or in cases of renal dysfunction coexistent with either of those conditions.
In patients with hepatic dysfunction and concomitant renal impairment, cefoperazone serum concentration should be monitored and dosage adjusted as necessary. In these cases, dosage should not exceed 2 g/day of cefoperazone without close monitoring of serum concentrations. The serum half-life of cefoperazone is reduced slightly during hemodialysis. Thus, dosing should be scheduled to follow a dialysis period.
As with other antibiotics, vitamin K deficiency has occurred in a few patients treated with cefoperazone. The mechanism is most probably related to the suppression of gut flora which normally synthesize this vitamin. Those at risk include patients with poor diet, malabsorption states (eg, cystic fibrosis) and patients on prolonged IV alimentation regimens. Prothrombin time should be monitored in these patients and exogenous vitamin K administered as indicated.
As with other antibiotics, overgrowth of nonsusceptible organisms may occur during prolonged use of Zifam CS1/CS2. Patients should be observed carefully during treatment.
As with any potent systemic agent, it is advisable to check periodically for organ system dysfunction during extended therapy including renal, hepatic and hematopoietic systems. This is particularly important in neonates, especially when premature and other infants.
A reaction characterized by flushing, sweating, headache and tachycardia has been reported when alcohol was ingested during and as late as the 5th day after cefoperazone administration. A similar reaction has been reported within certain other cephalosporins and patients should be cautioned concerning ingestion of alcoholic beverages in conjunction with administration of sulbactam/cefoperazone. For patients requiring artificial feeding orally or parenterally, solutions containing ethanol should be avoided.
Drug-Laboratory Test Interactions: A false-positive reaction for glucose in the urine may occur with Benedict's or Fehling's solution.
Use in pregnancy & lactation: Reproduction studies have been performed in rats at doses up to 10 times the human dose and have revealed no evidence of impaired fertility and no teratological findings. Sulbactam and cefoperazone cross the placental barrier. There are; however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Zifam CS1/CS2 should be used during pregnancy only if clearly needed.
Only small quantities of sulbactam and cefoperazone are excreted in human milk. Although both drugs pass poorly into breast milk of nursing mothers, caution should be exercised when Zifam CS1/CS2 is administered to a nursing mother.