Questions for PCNS Discussion

Xyrem®, Orphan Medical, Inc.

June 6, 2001


  1. Has the sponsor demonstrated efficacy of Xyrem® for the proposed indication to treat cataplexy and excessive daytime sleepiness in patients with narcolepsy?
  1. If no, is there any reasonable claim for which the sponsor has presented substantial evidence of effectiveness?
  1. Has the sponsor established the safety of Xyrem® when used for the proposed indication for which substantial evidence of effectiveness has been submitted?

3. Is the adoption of a risk management plan necessary for the safe use of Xyrem®?

Please evaluate the following components of the Risk Management Program:

4. Safe Use in Home

a. Should there be a requirement for additional safeguards in patient's homes, e.g., keeping drugs in a locked storage space?

  1. Should there be additional warnings on the labeling of the dose cups and/or bottle of GHB?
  2. Is there any special concern or advice regarding limitations on the quantity of Xyrem supplied at any one time?
  3. What special concerns should be communicated in the product label and other printed materials?

5. Safe Use by Patient

  1. Should patients sign an informed consent form before receiving the initial shipment of the drug?
  2. Should patients be required to return a registry form before receiving the first shipment?



6. Appropriate Prescribing

  1. Should physicians document that they read the materials sent to them before the pharmacy fills the initial prescription?
  2. Should physicians be required to demonstrate safe use and appropriate dosage preparation to patients before the first prescription and be required to document that it has been accomplished?
  3. Should there be restricted prescribing for the product? (e.g., only to those who have a diagnosis of cataplexy)
  4. Does the Risk Management Program assure appropriate prescribing or sufficiently reduce the risks of misuse or overdose from Xyrem?
  5. Should certification of physicians for prescribing Xyrem be required?


7. Central Pharmacy

  1. Is the institution of the sponsor's central pharmacy adequate?
  2. Should the central pharmacy be described in the product labeling, as well as educational and promotional material?

8. Post Market Surveillance

a. Should there be a requirement for post-marketing reporting of cases of misuse, abuse, overdose, dependence, and diversion?

b. Should the role of the central pharmacy include providing post-marketing and surveillance reports to the Agency in addition to the sponsor?

c. Should these reports be provided on a regular basis and include monitoring prescribing and dispensing patterns?

9. Other recommendations

  1. Any other recommendations on how to protect the family of the patient, on the handling, storage, and disposal of GHB, on labeling and on post market follow-up for misuse and overdose?