Drug Information

FDA Public Health Advisory:
Safety of Topical Lindane Products
for the Treatment of Scabies and Lice

The Food and Drug Administration (FDA) has issued a Public Health Advisory (PHA) concerning the use of topical formulations of Lindane Lotion and Lindane Shampoo for the treatment of scabies and lice. In addition to this PHA:

• The boxed warning emphasizes that it is a second-line treatment, updates information about its potential risks especially in children and adults weighing less than 110 pounds, and reminds practitioners that reapplication of Lindane Lotion or Lindane Shampoo is not the appropriate treatment, if itching continues after the single treatment.
• Lindane product package sizes will be limited to 1 and 2 ounces in order to minimize the potential for patients to apply the product in excess and to minimize reapplication of Lindane. Pharmacists should dispense a quantity sufficient for a single treatment, not to exceed 2 fluid ounces.
• A Medication Guide, designed to inform patients of the risks of Lindane products and provide instructions for appropriate use of the drugs, must now be dispensed by the pharmacist with each new prescription.

Lindane Products are Second-Line Treatments for Scabies and Lice

Lindane (gamma-hexachlorocyclohexane) is approved for topical treatment of pediculosis and scabies in patients "who have either failed to respond to adequate doses, or are intolerant of, other approved therapies." Lindane has been on the market since 1951, but was labeled as second-line therapy in 1995 because there are safer alternative treatments that should be used first. Second-line therapy is defined as:

1. The patient cannot tolerate the first-line drug of choice or
2. The patient has used the first-line drug of choice as instructed and the treatment has failed.

Examples of other medications approved to treat scabies and lice include the following:

Current Issues

FDA has determined that Lindane products have benefits that outweigh risks when used as directed. Most serious adverse events reported in association with Lindane products have been due to misuse. However, there have been rare case reports of serious reactions with apparently normal use. These reports highlight the need to emphasize the potential toxicity of Lindane in the product labels and educate healthcare providers and patients about the risks and how to minimize them, as well as to develop mechanisms to facilitate safe use, once the drug is dispensed to patients. These mechanisms include having Lindane products available only in small packaged amounts to avoid excess application and requiring that the Medication Guide be given to the patient by the pharmacist with each new prescription.

Current Safety Information

Safety information for Lindane comes from the FDA’s Adverse Event Reporting System (AERS), which is derived from spontaneous adverse event reports through FDA’s MedWatch Program and literature reports submitted to the Agency. Rates of adverse events cannot be calculated from this system and underreporting is presumed, especially for older products like Lindane Lotion and Shampoo.

The adverse events of concern for Lindane are systemic events due to absorption of this lipophilic drug following topical application. The majority of events occurred in patients with contraindications to the use of Lindane, in patients who used the medication in excessive amounts, or in those who misused the Lindane product. Of the adverse event cases in the FDA database with a serious outcome (hospitalization, disability or death), only 20% used Lindane according to the directions in the label. All other patients did not use Lindane according to directions in the label. Most commonly, patients often reapplied Lindane because of continued itching after the treatment, either on their own volition or at their doctor’s recommendation.

Deaths

Three deaths due to Lindane use have been confirmed, although 17 deaths have been reported associated with Lindane use. The three confirmed deaths all included use of Lindane not in accordance with the label, including multiple topical applications or oral ingestion. Lindane toxicity was confirmed by autopsy in a child, and was diagnosed in an adult. The third death occurred in an adult who ingested Lindane for suicide purposes.

Of the remaining 14 deaths associated with Lindane, but not confirmed, there were 4 children, 9 adults and 1 patient of unknown age. All of these deaths occurred when Lindane was applied topically. In 9 cases, use was not in accordance with the label (exceeded label use - 7, oral administration – 1, use was contraindicated - 2). Scabies and head and/or pubic lice were the predominant indications for use.

Neurologic Risks

The risk of neurologic side effects associated with Lindane is known from clinical trials, spontaneous post-marketing reporting data and literature reports. These side effects have ranged from dizziness to seizures. In post-marketing reports, neurologic side effects occurred in patients who misused Lindane, as well as in patients who used Lindane according to labeled instructions. Among the adverse event reports in the FDA database, 70% reported neurologic events including seizure, dizziness, headache and paresthesia.

Increased Risk in Younger and/or Smaller Patients and the Elderly

Lindane is contraindicated for use in neonates and should be used with extreme caution in children and in individuals weighing less than 50 kg (110 lbs). Among adverse event reports in which the outcome was serious (resulted in hospitalization, disability or death), the very young and the elderly appeared to be more susceptible to Lindane’s adverse effects and had worse outcomes.

Animal studies have demonstrated that younger animals are more susceptible to the neurologic side effects seen with Lindane use. In addition, smaller children have a larger body surface to volume ratio that may result in proportionately larger risk of systemic exposure. For this reason, Lindane has long been contraindicated for use in neonates. It is not known whether the developing nervous system of children also increases their susceptibility to neurologic toxicity.

Other Populations with Increased Risk

Patients who have conditions, such as HIV infection, or take certain medications that may lower the seizure threshold should be prescribed Lindane with caution. They may be at greater risk for serious adverse events. The new Lindane label lists examples of some of these conditions and medications. The label also highlights special precautions for use of Lindane in women who are breastfeeding infants.

There are case reports of neurologic adverse events in nursing home patients treated with Lindane. Factors that may have increased their susceptibility to these adverse events include concomitant medications, underlying medical conditions, and advanced age. Special consideration should be given prior to treating this population with Lindane, even if they are greater than 50 kg.

Conclusion

Lindane products should be prescribed carefully, and quantities prescribed should be limited to amounts for a single application. Patients are at risk for serious neurologic adverse events, and even death, particularly with early retreatment. It is not known how soon after administering one dose of Lindane that a second dose can be safely administered. Post-treatment itching is common, especially in the treatment of scabies and does not necessarily indicate treatment failure.

The instructions for Lindane use have been clarified in the products’ professional labels and in the Medication Guides, which by law must be dispensed with all prescriptions of lindane. Because most of the serious adverse events reported have been because of misuse of Lindane Lotion and Lindane Shampoo, it is very important that patients understand the importance of using this medication in a manner consistent with product labeling.

The FDA wants healthcare providers to be aware of this new safety information and the changes that have occurred in the label for topical Lindane Lotion and Lindane Shampoo prescribed for the treatment of scabies and lice (both head and pubic lice), respectively. Healthcare providers should consider this new safety information when deciding whether to prescribe Lindane Lotion or Lindane Shampoo for patients who may be at risk for serious adverse drug sequelae.

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FDA/Center for Drug Evaluation and Research
Last Updated: March 28, 2003
Originator: OTCOM/DLIS
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