E-drug: FDA public health advisory on Lindane products
-------------------------------------------------------------------------
Safety of topical Lindane products for 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:
Scabies: permethrin cream 5% ( Acticine, Elimite, Nix)
crotamiton cream (Eurax)
Lice: malathion lotion 0.5% (Ovide, prescription only)
pyrethrum 0.33% with piperonyl butoxide shampoo
and cream rinse
permethrin cream rinse 1% (Nix and Rid)
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.
--
To send a message to E-Drug, write to: e-drug@usa.healthnet.org
To subscribe or unsubscribe, write to: majordomo@usa.healthnet.org
in the body of the message type: subscribe e-drug OR unsubscribe e-drug
To contact a person, send a message to: e-drug-help@usa.healthnet.org
Information and archives: http://www.essentialdrugs.org/edrug