FDA Safety Labeling Changes: Minocin Gabitril, Tenormin

Yael Waknine

May 18, 2005

May 18, 2005 — The U.S. Food and Drug Administration (FDA) approved in February revisions to safety labeling to advise that use of minocycline in patients with significant renal impairment may cause liver toxicity; minocycline may cause fetal harm when administered during pregnancy; use of tiagabine HCl in nonepileptic patients has been associated with new-onset seizures; and atenolol is associated with a risk of hypoglycemia and bradycardia in neonates born to mothers receiving the drug at parturition or while breast-feeding.

Minocycline (Minocin) May Cause Hepatotoxicity in Patients With Significant Renal Impairment

On Feb. 17, the FDA approved revisions to the safety labeling for minocycline intravenous injection, and minocycline HCl pellet-filled capsules and oral suspension (Minocin, made by Wyeth Pharmaceuticals, Inc) to warn of potential complications associated with its use in patients with significantly impaired renal function and during pregnancy.

Minocycline is a tetracycline antibiotic, and as such its antianabolic action may cause an increase in serum urea nitrogen (BUN). While this is not a problem in patients with normal renal function, higher serum levels of the drug in patients with significantly impaired renal function may lead to azotemia, hyperphosphatemia, and acidosis.

Under such conditions, monitoring of creatinine and BUN is recommended, and the total daily dose of minocycline should not exceed 200 mg in 24 hours. The FDA notes that in a setting of renal impairment, even usual oral or parenteral doses may lead to excessive systemic accumulation of the drug and possible hepatotoxicity.

Tetracycline antibiotics such as minocycline cross the placenta and may cause fetal harm when administered during pregnancy. While no adequate and well-controlled trials have been conducted to this effect, postmarketing reports have included isolated cases of congenital anomalies, including limb reduction.

The FDA notes that regardless of drug exposure all pregnancies have a background risk of birth defect, loss, or other adverse outcome and that the causal role of minocycline in this regard remains inconclusive due to the limited nature of the postmarketing reports.

Patients who use minocycline during pregnancy or who become pregnant during treatment should be advised of the potential hazard to the fetus.

Minocycline is a tetracycline antibiotic indicated for the treatment of various infections caused by susceptible microorganisms.

Tiagabine HCl (Gabitril) May Cause Seizures in Nonepileptic Patients

On Feb. 14, the FDA approved revisions to the safety labeling for tiagabine HCl tablets (Gabitril, made by Cephalon, Inc) to warn of the risk of seizures associated with its use in nonepileptic patients.

Postmarketing reports have linked use of tiagabine HCl to new onset seizures and status epilipticus in patients without epilepsy. Dose may be an important predisposing factor for seizure development, although seizures have been reported in patients receiving daily doses as low as 4 mg.

Most incidents were associated with concurrent administration of medications that may have lowered the seizure threshold, such as antidepressants, antipsychotics, stimulants, and narcotics. Some seizures occurred near the time of dose escalation, even after periods of stable dosing.

Tiagabine HCl should be discontinued in nonepileptic patients who develop seizures during therapy, and the possibility of an underlying seizure disorder evaluated.

Tiagabine HCl is indicated for use as adjunctive therapy for the treatment of partial seizures in adults and children aged 12 years and older.

Atenolol (Tenormin) May Cause Bradycardia in Breast-Fed Infants

On Feb. 9, the FDA approved revisions to the safety labeling for atenololintravenous injection and tablets (Tenormin, made by AstraZeneca Pharmaceuticals LP) to warn of the risk of hypoglycemia and bradycardia in neonates born to mothers administered the drug at parturition or while breast-feeding.

The FDA notes that atenolol is secreted in human breast milk at a ratio of 1.5 to 6.8 relative to plasma concentration. Infants who are premature or have impaired renal function may be at increased risk of atenolol-related adverse events.

Caution should be exercised when atenolol is administered during pregnancy or to a woman who is breast-feeding.

Atenolol tablets are indicated for use alone or with other agents for the management of hypertension and for the long-term management of angina pectoris.

Atenolol tablets and intravenous injection are indicated in the management of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality.

Reviewed by Gary D. Vogin, MD

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