FDA Safety Labeling Changes: Maxaquin, Temodar, Trileptal

Yael Waknine

June 15, 2005

June 15, 2005 — The U.S. Food and Drug Administration (FDA) approved in March revisions to safety labeling to advise that use of lomefloxacin HCl tablets is associated with a risk of peripheral neuropathy and tendon effects; use of temozolomide capsules is associated rarely with the development of secondary malignancies; and use of oxcarbazepine tablets and oral solution is associated with a risk of serious hypersensitivity reactions in adults and children.

Lomefloxacin HCl (Maxaquin) Linked to Risk of Peripheral Neuropathy, Tendon Effects

On March 16, the FDA approved revisions to the safety labeling for lomefloxacin HCl (Maxaquin tablets, made by Pfizer, Inc.), warning of the risk of peripheral neuropathy and tendon effects associated with its use.

The FDA has received rare postmarketing reports of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons and resulting in paresthesias, hypoesthesias, dysesthesias, and weakness in patients receiving quinolones, including lomefloxacin.

To prevent the development of an irreversible condition, lomefloxacin should be discontinued in patients experiencing symptoms of neuropathy, including pain, burning, tingling, numbness, and/or weakness, or having deficits in light touch, pain, temperature, position sense, vibratory sensation, and/or motor strength.

Ruptures of shoulder, hand, Achilles, and other tendons resulting in prolonged disability or requiring surgical repair have also been reported in patients receiving quinolones such as lomefloxacin. According to the FDA, the reports indicate that risk of tendon rupture may be increased in patients receiving concomitant steroids, particularly in those of advanced age.

Lomefloxacin should be discontinued in patients experiencing pain, inflammation, or tendon rupture. Patients should rest and refrain from exercise until tendonitis and tendon rupture have been excluded from the diagnosis.

Lomefloxacin HCl is a fluoroquinolone antibiotic indicated for the treatment of adults with mild to moderate lower respiratory tract and urinary tract infections caused by susceptible Gram-negative and Gram-positive bacterial strains, and preoperatively for the prevention of urinary tract infection from transrectal prostate biopsy and transurethral surgical procedure.

Temozolomide (Temodar) Linked Rarely to Secondary Malignancies

On March 30, the FDA approved revisions to the safety labeling for temozolomide (Temodar capsules, made by Schering Corp.), warning of the potential risk of malignancies associated with its use.

The FDA has received rare reports of myelodysplastic syndrome and secondary malignancies, including myeloid leukemia, in patients receiving temozolomide therapy.

Temozolomide capsules are indicated for the treatment of adults with newly diagnosed glioblastoma multiforme, concomitantly with radiotherapy and then as maintenance treatment.

Oxcarbazepine (Trileptal) May Cause Serious Hypersensitivity Reactions

On March 25, the FDA approved revisions to the safety labeling for oxcarbazepine (Trileptal tablets and oral solution, made by Novartis Pharmaceuticals, Inc.), warning of the risk of serious hypersensitivity reactions associated with its use.

The FDA has received reports of serious dermatologic reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with a median onset time of 19 days in children and adults treated with oxcarbazepine. Such reactions may be life-threatening and some patients have required hospitalization; fatal outcomes have been reported rarely. Recurrence of the skin reactions also has been reported on rechallenge with the drug.

The reporting rate for incidences of SJS and TEN in patients treated with oxcarbazepine is 3 to 10 times greater than that expected in the general population (0.5 - 6 cases/million person-years) and as such is generally considered to be an underestimate due to underreporting.

Substitution of another antiepileptic drug should be considered in patients who develop skin reactions while receiving treatment with oxcarbazepine.

In addition, multiorgan hypersensitivity reactions have been reported in close temporal association (median time to detection, 13 days; range, 4 - 60 days) with oxcarbazepine therapy initiation in adults and children.

Although reports are limited, many of these reactions were considered life-threatening and resulted in hospitalization. Patients typically presented with fever and rash, and diverse symptoms associated with other organ involvement including lymphadenopathy, hepatitis, liver function test and hematologic abnormalities (eosinophilia, thrombocytopenia, and neutropenia), pruritus, nephritis, oliguria, hepato-renal syndrome, arthralgia, asthenia, and other symptoms.

Oxcarbazepine therapy should be discontinued if a multiorgan hypersensitivity reaction is suspected and another drug substituted in its place. The FDA notes that while there are no case reports to indicate cross-reactivity with other drugs that cause this syndrome, experience exists among such drugs to suggest the possibility.

Oxcarbazepine tablets and oral solution are indicated as monotherapy or adjunctive therapy for the treatment of partial seizures in epileptic adults and children aged 4 to 16 years.

Reviewed by Gary D. Vogin, MD


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