FDA Updates Rocephin WarningsApr 14, 2009 | Parker Waichman LLP
U.S. regulators have released new recommendations regarding the use of Rocephin, and its generic equivalents, in combination with calcium. The guidance released today by the Food & Drug Administration
(FDA) updates two 2007 alerts in which the agency added warnings to the label of Rocephin about the risk of crystal formation in both neonates and adults when the drug was used concomitantly with calcium-containing products.
Rocephin (ceftriaxone) is a prescription antibiotic that is licensed to treat a number of common infections. It is part of a class of antibiotics called cephalosporins, and it is given either as a shot or through an intravenous line. Rocephin is used to treat community-acquired or mild to moderate health care-associated pneumonia. It is also a choice drug for treatment of bacterial meningitis. In pediatrics, it is commonly used in febrile infants between 4 and 8 weeks of age who are admitted to the hospital to exclude sepsis. It has also been used in the treatment of Lyme disease, Typhoid Fever and gonorrhea.
The FDA issued the 2007 Rocephin alerts after its manufacturer, Roche, provided the agency with post-marketing reports of five neonatal deaths related to the interaction between Rocephin and calcium-containing products. According to the reports, the deaths occurred suddenly. In four neonates, Rocephin was co-administered with calcium-containing fluids using the same infusion line and in the fifth neonate Rocephin and calcium gluconate were administered by different routes and at different times (the exact time difference was not reported). Two autopsies found evidence of crystalline material in the renal and pulmonary vasculature. In a third neonate there was evidence of a precipitate in the intravenous tubing and the neonate’s death occurred soon after the crystalline material was injected.
In addition to the five post-marketing reports provided by Roche, FDA has received four additional post-marketing reports of interactions between Rocephin and calcium-containing products in patients up to one year of age since the FDA first approved Rocephin in 1984. Three of the interactions resulted in death; in one instance the patient was receiving parenteral nutrition. An autopsy in one patient revealed evidence of crystals in the lungs.
After the FDA issued the 2007 Rocephin alerts, Roche conducted two in vitro studies to assess the potential for precipitation of Rocephin-calcium when Rocephin and calcium-containing products are mixed in vials and in infusion lines. According to the FDA, these two in vitro studies were conducted in neonatal and adult plasma.
Based on the results from these studies, the FDA issued the following updated recommendations:
- Concomitant use of Rocephin and intravenous calcium-containing products is contraindicated in neonates (less than 28 days of age). Rocephin should not be used in neonates less 28 days of age) if they are receiving (or are expected to receive) calcium-containing intravenous products.
- In patients older than 28 days of age, Rocephin and calcium-containing products may be administered sequentially, provided the infusion lines are thoroughly flushed between infusions with a compatible fluid.
- Rocephin must not be administered simultaneously with intravenous calcium-containing solutions via a Y-site in any age group.
- The FDA now recommends that Rocephin and calcium-containing products may be used concomitantly in patients older than 28 days of age, using the precautionary steps above because the risk of precipitation is low in this population. the agency had previously recommended, but no longer recommends, that in all age groups Rocephin and calcium-containing products should not be administered within 48 hours of one another.
The FDA also reiterated the previous recommendations and considerations from the 2007 alert:
- Do not reconstitute or mix Rocephin with a calcium-containing product, such as Ringer's or Hartmann's solution or parenteral nutrition containing calcium, because particulate formation can result.
- There are no data on interactions between IV Rocephin and oral calcium-containing products or between intramuscular Rocephin and IV or oral calcium-containing products.
The new information will be reflected in the sections of the drug's label dealing with warnings, dosage and administration, contraindications, and clinical pharmacology, the FDA said.