REDWOOD CITY, Calif.,
Jan. 7, 2019 /PRNewswire/ -- AcelRx Pharmaceuticals, Inc.
(Nasdaq: ACRX), (AcelRx), a specialty pharmaceutical company
focused on the development and commercialization of innovative
therapies for use in medically supervised settings, today announced
the publication of a pooled analysis in the peer reviewed journal,
Pain Management, analyzing the results of AcelRx's clinical
studies to assess safety of sufentanil sublingual tablets for the
short-term treatment of moderate-to-severe acute pain in medically
supervised settings.
The objective of the safety analysis was to evaluate the pooled
data from AcelRx's clinical studies of sufentanil sublingual
tablets (SSTs) administered at 30 mcg dose equivalents over ≤ 72
hours for moderate-to-severe acute pain management in both
postoperative and emergency room patients. Analysis included a
subset of patients from SST 15 mcg studies where patients received
the first two doses of SST 15 mcg within the first 20–25 min
(representing a 30-mcg dose-equivalent). Overall, 804 patients were
evaluated in the pooled safety analysis, including 646 that had
received the active drug. Across all of the AcelRx studies, adverse
events (AEs) were experienced by 60.5% of patients in the SST
group, and 61.4% in the placebo group. The most common
treatment-related AEs experienced by patients treated with SST were
nausea (28.5%), vomiting (6.5%) and headache (5.0%). Findings from
the pooled analysis support that short-term (≤72 hours)
administration of SST is well tolerated, with most adverse events
considered mild or moderate in severity.
The publication also noted the additional safety assessment
measuring cognitive impairment, which AcelRx had performed in one
open-label SST 30 mcg study in emergency room patients (Study
SAP302). A total of 75 patients were dosed with SST 30 mcg and
evaluated predose and 1 hour postdose for cognitive impairment
using the validated Six-item Screener tool. In 97.3% of the
patients, the score stayed the same or improved following a dose of
SST 30 mcg.
"In my experience treating emergency trauma and injury patients
with DSUVIA, the overall adverse event profile, and lack of
cognitive impairment following treatment with DSUVIA, supports the
importance of this non-invasive opioid as a well-tolerated
treatment option for moderate-to-severe acute pain management in
hospitals," said Dr. James Miner,
Chief of Emergency Medicine at Hennepin Healthcare and lead
investigator in the DSUVIA Emergency Department Study SAP302.
Active-Comparator Study Design and Dosing Equivalence
This safety analysis also evaluated the morphine equivalence of
SSTs from 357 patients in AcelRx's active-comparator study
evaluating two patient-controlled analgesia (PCA) systems. Within
the first 5 hours after initiation of treatment with either SST 15
mcg PCA (20-minute lockout) or IV morphine 1 mg PCA (6-minute
lockout), SST 15 mcg was calculated to be dose-equivalent to
approximately 2.5 mg IV morphine based on drug utilization in each
treatment group over this 5 hour period (or 5 mg IV morphine for 30
mcg SST). Zalviso is not approved in the U.S.
About AcelRx Pharmaceuticals, Inc.
AcelRx
Pharmaceuticals, Inc. is a specialty pharmaceutical company
focused on the development and commercialization of innovative
therapies for use in medically supervised settings. AcelRx's
proprietary, non-invasive sublingual formulation technology
delivers sufentanil with consistent pharmacokinetic profiles. The
Company has one approved product in the U.S., DSUVIA (sufentanil
sublingual tablet, 30 mcg), known as DZUVEO in Europe,
indicated for the management of acute pain severe enough to require
an opioid analgesic for adult patients in certified medically
supervised healthcare settings, and one product candidate,
Zalviso®(sufentanil sublingual tablet system, SST system, 15 mcg)
being developed as an innovatively designed patient-controlled
analgesia (PCA) system for reduction of moderate-to-severe acute
pain in medically supervised settings. DZUVEO and Zalviso are both
approved products in Europe. Zalviso is not approved in the
U.S. For additional information about AcelRx, please visit
www.acelrx.com.
About DSUVIA (sufentanil) sublingual tablet
Indications and Usage
DSUVIA is indicated for use in
adults in a certified medically supervised healthcare setting, such
as hospitals, surgical centers, and emergency departments, for the
management of acute pain severe enough to require an opioid
analgesic and for which alternative treatments are inadequate.
Limitations of Use:
- Not for home use or for use in children. Discontinue treatment
with DSUVIA before patients leave the certified medically
supervised healthcare setting.
- Not for use for more than 72 hours. The use of DSUVIA beyond 72
hours has not been studied.
- Only to be administered by a healthcare provider.
- Because of the risks of addiction, abuse, and misuse with
opioids, even at recommended doses, reserve DSUVIA for use in
patients for whom alternative treatment options [e.g., non-opioid
analgesics or opioid combination products]:
-
- Have not been tolerated, or are not expected to be
tolerated
- Have not provided adequate analgesia, or are not expected to
provide adequate analgesia.
PLEASE SEE BELOW FOR THE IMPORTANT SAFETY INFORMATION,
INCLUDING BOXED WARNING
IMPORTANT SAFETY INFORMATION
WARNING: ACCIDENTAL EXPOSURE AND DSUVIA REMS
PROGRAM; LIFE-THREATENING RESPIRATORY DEPRESSION; ADDICTION, ABUSE,
AND MISUSE; CYTOCHROME P450 3A4 INTERACTION; and RISKS FROM
CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS
DEPRESSANTS
Accidental Exposure and DSUVIA Risk Evaluation and Mitigation
Strategy (REMS) Program
Accidental exposure to or ingestion of DSUVIA, especially in
children, can result in respiratory depression and death. Because
of the potential for life-threatening respiratory depression due to
accidental exposure, DSUVIA is only available through a restricted
program called the DSUVIA REMS Program.
- DSUVIA must only be dispensed to patients in a certified
medically supervised healthcare setting.
- Discontinue use of DSUVIA prior to discharge or transfer
from the certified medically supervised healthcare
setting.
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may
occur with use of DSUVIA. Monitor for respiratory depression,
especially during initiation of DSUVIA.
Addiction, Abuse, and Misuse
DSUVIA exposes patients and other users to the risks of opioid
addiction, abuse, and misuse, which can lead to overdose and death.
Assess each patient's risk prior to prescribing DSUVIA, and monitor
all patients regularly for the development of these behaviors or
conditions.
Cytochrome P450 3A4 Interaction
The concomitant use of DSUVIA with all cytochrome P450 3A4
inhibitors may result in an increase in sufentanil plasma
concentrations, which could increase or prolong adverse drug
reactions and may cause potentially fatal respiratory depression.
In addition, discontinuation of a concomitantly used cytochrome
P450 3A4 inducer may result in an increase in sufentanil plasma
concentration. Monitor patients receiving DSUVIA and any CYP3A4
inhibitor or inducer.
Risks From Concomitant Use With Benzodiazepines Or Other CNS
Depressants
Concomitant use of opioids with benzodiazepines or other central
nervous system (CNS) depressants, including alcohol, may result in
profound sedation, respiratory depression, coma, and death.
- Reserve concomitant prescribing for use in patients for whom
alternative treatment options are inadequate.
- Limit dosages and durations to the minimum
required.
- Follow patients for signs and symptoms of respiratory
depression and sedation.
Contraindications
Use of DSUVIA is contraindicated in
patients with:
- Significant respiratory depression
- Acute or severe bronchial asthma in an unmonitored setting or
in the absence of resuscitative equipment
- Known or suspected gastrointestinal obstruction, including
paralytic ileus
- Known hypersensitivity to sufentanil or components of
DSUVIA.
Warnings and Precautions
- Accidental ingestion or exposure to even one dose of DSUVIA,
especially in children, can result in respiratory depression and
death due to an overdose of sufentanil.
- DSUVIA is for use in adult patients only in a certified
medically supervised healthcare setting. Use of DSUVIA outside of
this setting can increase the risk of accidental exposure in others
for whom it is not prescribed, causing fatal respiratory
depression. Discontinue use of DSUVIA prior to discharge or
transfer from the certified medically supervised healthcare
setting. DSUVIA is not for home or pediatric use.
- DSUVIA contains sufentanil, a Schedule II controlled substance.
As an opioid, DSUVIA exposes users to the risks of addiction,
abuse, and misuse.
- Profound sedation, respiratory depression, coma, and death may
result from the concomitant use of DSUVIA with benzodiazepines or
other CNS depressants (e.g., non-benzodiazepine
sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants,
general anesthetics, antipsychotics, other opioids, alcohol).
Because of these risks, reserve concomitant prescribing of these
drugs for use in patients for whom alternative treatment options
are inadequate.
- Life-threatening respiratory depression in patients with
chronic pulmonary disease or in elderly, cachectic and debilitated
patients: monitor patients closely, particularly when initiating
DSUVIA therapy and when DSUVIA is used with other drugs that
depress respiration. Management of respiratory depression may
include close observation, supportive measures, and use of opioid
antagonists, depending on the patient's clinical status.
- A potentially life-threatening condition could result from
concomitant serotonergic drug administration. Discontinue DSUVIA if
serotonin syndrome is suspected. Cases of adrenal insufficiency
have been reported with opioid use (usually > 1 month).
Presentation and symptoms are non-specific and include nausea,
vomiting, anorexia, fatigue, weakness, dizziness and low blood
pressure. Confirm diagnosis with testing as soon as possible and,
if confirmed, treat with physiologic replacement of corticosteroids
and wean patient from opioid.
- As with all opioids, sufentanil may produce bradycardia or
hypotension in some patients. Therefore DSUVIA should be used with
caution in patients with bradyarrhythmias or hypovolemia.
- DSUVIA should not be used in patients who may be particularly
susceptible to the intracranial effects of CO2
retention, such as those with evidence of increased intracranial
pressure, impaired consciousness or coma.
- Prolonged use of DSUVIA during pregnancy can result in
withdrawal in the neonate, which can be life-threatening. Observe
newborns for signs of neonatal opioid withdrawal syndrome and
manage accordingly. Advise pregnant women using opioids for a
prolonged period of this risk and ensure that appropriate treatment
will be available.
- Insufficient data are available on the use of DSUVIA in
patients with severe liver or kidney impairment. DSUVIA should be
used with caution in such patients due to the importance of these
organs in the metabolism and excretion of sufentanil.
Adverse Reactions
Adverse reactions are described, or
described in greater detail, in other sections of the
Prescribing Information:
- Life-Threatening Respiratory Depression [see Warnings and
Precautions (5.3)]
- Addiction, Abuse, and Misuse [see Warnings and Precautions
(5.4)]
- Adrenal Insufficiency [see Warnings and Precautions
(5.9)]
- Severe hypotension [see Warnings and Precautions
(5.10)]
- Gastrointestinal Adverse Reactions [see Warnings and
Precautions (5.12)]
- Seizures [see Warnings and Precautions (5.13)]
- Neonatal Opioid Withdrawal Syndrome [see Warnings and
Precautions (5.15)]
The most commonly reported adverse reactions (≥ 2% and
higher than placebo) were nausea, headache, vomiting, dizziness,
and hypotension.
Medical Information
For medical inquiries or to report an adverse event, other
safety-related information or product complaints for a company
product, please contact the AcelRx Medical Information Contact
Center at 1-855-925-8476 or AcelRxMedInfo@rmpdc.org.
You are encouraged to report negative side effects of
prescription drugs to the FDA. Visit www.fda.gov/medwatch or call
1-800-FDA-1088.
Please see full Prescribing
Information and Directions For
Use.
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SOURCE AcelRx Pharmaceuticals, Inc.