FDA Safety Changes: Advicor, Rocephin, Tindamax

This activity is part of an ongoing CME/CE initiative todisplace bilirubin from binding to serum albumin,
provide information on label changes reported by thepotentially leading to bilirubin encephalopathy, the FDA
FDA. Activities of this nature will be posted onsaid. Use of ceftriaxone is therefore contraindicated in
Medscape on a weekly basis.neonates with hyperbilirubinemia, especially those who
August 16, 2007 — The US Food and Drugare premature.
Administration (FDA) has approved safety labelingBecause of the risk for particulate precipitation,
revisions to advise of drug interactions that increaseceftriaxone should not be mixed with
the risk for myopathy/rhabdomyolysis associated withcalcium-containing solutions/products or reconstituted
the lovastatin component of niacin extended-releasewith calcium-containing diluents such as Ringer's or
lovastatin tablets, the risks associated withHartmann's solution.
concomitant use of calcium or calcium-containingConcomitant administration of ceftriaxone with
solutions/products and ceftriaxone sodiumcalcium-containing solutions or products is also
manufacturer injection, drug interactions with tinidazolecontraindicated, even via different infusion lines; 48
tablets, and the risk for Candida vaginitis in patientshours should elapse between the last dose of
with bacterial vaginosis receiving a course ofceftriaxone and their use.
treatment with tinidazole.Ceftriaxone injection is indicated for the treatment of
Lovastatin Component of Advicor Linked to Druglower respiratory tract infections, urinary tract
Interactions That Increase Risk for Myopathyinfections, bacterial septicemia, skin and skin structure
On April 6, the FDA approved safety labeling revisionsinfections, bone and joint infections, pelvic inflammatory
for niacin extended-release/lovastatin tablets ( Advicor;disease, uncomplicated gonorrhea, intra-abdominal
KOS Pharmaceuticals, Inc) to advise of certain druginfections, acute bacterial otitis media, and meningitis
interactions that increase the risk for myopathycaused by susceptible microorganisms. It also is
rhabdomyolysis associated with the lovastatinapproved for surgical prophylaxis in patients undergoing
component.certain procedures classified as contaminated or
As with other 3-hydroxy-3-methylglutaryl coenzyme Apotentially contaminated.
reductase inhibitors, lovastatin may cause myopathyTinidazole ( Tindamax) Linked to Drug Interactions, Risk
that presents as muscle pain, tenderness, orfor Candida Vaginitis
weakness with creatine kinase levels greater than 10On May 21, the FDA approved revisions to the safety
times the upper limit of normal. Myopathy may alsolabeling for tinidazole tablets ( Tindamax; Mission
take the form of rhabdomyolysis with or without acutePharmacal Co) to advise of drug interactions, the risk
renal failure secondary to myoglobinuria, and rarefor Candida vaginitis in patients with bacterial vaginosis,
fatalities have occurred.and certain contraindications. ceftriaxone sodium
Because lovastatin is metabolized by the cytochromemanufacturer
P-450 isoform 3A4 (CYP 3A4) enzyme, concomitantAccording to clinical study data, patients receiving
administration of potent CYP 3A4 inhibitors results intinidazole for the treatment of bacterial vaginosis may
elevated 3-hydroxy-3-methylglutaryl coenzyme Abe at risk for Candida vaginitis. In the study, 11 (4.7%) of
plasma activity levels and may increase the risk for235 women developed a vaginal fungal infection.
myopathy. According to the FDA, serious skeletalBecause tinidazole is biotransformed mainly by the
muscle disorders (eg, rhabdomyolysis) have beencytochrome P-450 isoform 3A4 (CYP 3A4) enzyme,
reported during concomitant use of these drugs.simultaneous administration with CYP 3A4 inducers
Drugs considered to be potent CYP 3A4 inhibitors(eg, phenobarbital, rifampin, phenytoin, and fosphenytoin)
include cyclosporine, itraconazole, ketoconazole, andcan accelerate its elimination and decrease plasma
other antifungal azoles; the macrolide antibioticslevels. Similarly, administration of CYP 3A4 inhibitors
erythromycin and clarithromycin; the ketolide antibiotic(eg, cimetidine and ketoconazole) may prolong
telithromycin; HIV protease inhibitors; and nefazodone.tinidazole half-life and decrease plasma clearance,
Large quantities of grapefruit juice (> 1 quart daily)thereby increasing plasma levels.
may also exert this effect.Use of tinidazole is contraindicated in patients with a
Because of the additive effect on the risk forprevious history of having a reaction to tinidazole or
myopathy, the dose of niacin/lovastatin shouldother nitroimidazole derivatives, the FDA warned,
generally not exceed 1000 mg/20 mg in patientsnoting that reported reactions have ranged in severity
receiving concomitant therapy with cyclosporine,from urticaria to Stevens-Johnson syndrome.
danazol, or fibrates. Interruption of treatment should beBecause tinidazole is excreted in breast milk at serum
considered during use of a systemic antifungal azole,concentrations and can be detected in breast milk for
macrolide antibiotic, or ketolide antibiotic.up to 72 hours after administration, interruption of
Niacin/lovastatin tablets are indicated for the treatmentbreast-feeding during therapy and for 3 days after the
of hypercholesterolemia when use of bothlast dose is advised. ceftriaxone sodium manufacturer
components is appropriate.The FDA also warned that carcinogenicity has been
Ceftriaxone Sodium Injection ( Rocephin) Plus Calciumobserved in mice and rats treated long term with
Linked to Neonate Fatalitiesmetronidazole, another nitroimidazole antimicrobial.
On May 11, the FDA approved revisions to the safetyAlthough similar data have not been reported with
labeling for ceftriaxone sodium injection ( Rocephin;tinidazole, its use should be limited to approved
Roche Pharmaceuticals, Inc) to advise of the potentialindications because of the similar nature of these
risks associated with concomitant use of calcium ordrugs.
calcium-containing solutions and products.As with other antimicrobials, prescribing tinidazole in the
 absence of a proven or strongly suspected bacterial
Cases of fatal reactions with calcium-ceftriaxoneinfection or a prophylactic indication is unlikely to
precipitates in the lungs and kidneys of both term andprovide benefit to the patient and increases the risk for
premature neonates have been reported, some ofthe development of drug-resistant bacteria.
which occurred when ceftriaxone and theTinidazole is a nitroimidazole antimicrobial indicated for
calcium-containing products were administered bythe treatment of trichomoniasis; giardiasis and
different routes at different times.amebiasis in patients aged 3 years and older; and
In vitro studies have shown that ceftriaxone canbacterial vaginosis in nonpregnant adult women.