Abstract
This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a quarterly publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. A summary of the most relevant data is provided, including background, study design, patient population, dosage information, therapy duration, results, safety, and therapeutic considerations. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to hospital
Background
Pruritus, a common adverse effect of opioid administration, is usually limited to the face and neck, but also may be generalized. Typically, this adverse effect is more common after epidural or intrathecal administration, occurring in 30% to 100% of patients. Narcotic antagonists, such as naloxone or nalmefene, have been used but may interfere with pain control. Serotonin type 3 receptors, as potent stimulants of nociceptive nerve endings, have been reported to enhance pain perception and pruritus symptoms. Thus, 5-HT3 antagonists have been suggested as effective therapy for pruritus caused by opiate administration. 1
Patient Population
Adults with pruritus related to spinal morphine administered during anesthesia for various surgeries.
Dosage and Duration
Dolasetron 12.5 mg intravenously (IV) (diluted in normal saline to a volume of 5 mL) administered approximately 30 minutes before administration of spinal anesthesia (hyperbaric bupivacaine 0.5% 10 to 17.5 mg/morphine 0.25 mg).
Results
Use of dolasetron for prevention of opioid-related pruritus has been evaluated in a small, controlled trial enrolling approximately 100 patients. 2
Controlled Trial
In a small, double-blind, placebo-controlled trial, 119 adults undergoing various surgeries (eg, orthopedic, urologic, vascular) and receiving spinal anesthesia with hyperbaric bupivacaine 0.5% 10 to 17.5 mg/morphine 0.25 mg were randomized to receive dolasetron 12.5 mg IV, ondansetron 4 mg IV, or saline IV as placebo administered 30 minutes prior to the administration of spinal anesthesia. The occurrence of pruritus, nausea, sedation, pain, and adverse effects of treatment were followed for 24 hours after surgery. Pruritus was graded on a 4-point scale (0 = no pruritus and 3 = severe pruritus). Treatment for severe pruritus included nalbuphine IV 3 mg. Fourteen patients dropped out of the study, none because of the study drug. The trial was completed by 105 patients, with 35 in each study group. The pruritus sites were mainly in the trigeminal, cervical, thoracic, and lumbar dermatomes. The overall incidence of pruritus was significantly lower in the dolasetron and ondansetron groups compared with placebo (20% vs 34% vs 66%; P < 0.01) but there was no difference between the active treatment groups (P = 0.18). Severe pruritus requiring rescue treatment with nalbuphine was observed only within the placebo group (11%). The authors concluded that the prophylactic use of ondansetron and dolasetron was effective in reducing the incidence and severity of intrathecal morphine-related pruritus. 2
Safety
This is a limited safety profile. Refer to package labeling for complete prescribing information (eg, Warnings/Precautions, Adverse Reactions, Drug Interactions).
In the reviewed controlled trial, dolasetron and ondansetron were well tolerated. 2
Therapy Considerations
Initial data suggest that dolasetron may be beneficial in the prevention of spinal opioid-related pruritus. These data are limited by a small population, and further study in larger, controlled settings is needed.