数据
资源
版本对比
免费注册
预约演示
免费注册
Kowa Pharmaceuticals America,Inc.
Announces Publication of Phase 3 Data Supporting FDA Approval of
SEGLENTIS
®
2022-07-19
·
BioSpace
July 19, 2022 13:00 UTC Phase 3 clinical trial data in patients post-bunionectomy demonstrated SEGLENTIS as an efficacious and well-tolerated multimodal treatment option for appropriate adult patients with
acute pain
. MONTGOMERY, Ala.--(BUSINESS WIRE)--
Kowa Pharmaceuticals America, Inc.
announced the publication of Phase 3 clinical trial results in
Pain
Practice reinforcing that
SEGLENTIS
® a unique co-crystal combination of
celecoxib
56-mg and
tramadol hydrochloride
44-mg, and oral treatment for appropriate patients with
acute pain
, provided superior analgesic efficacy than
tramadol hydrochloride
or
celecoxib
individually, and a safety pro to
tramadol hydrochloride
, while meeting its primary endpoint. As a multimodal agent, SEGLENTIS leverages 4 complimentary mechanisms of analgesia involving peripheral and central pathways. There are ongoing efforts to ensure multimodal analgesia is standard care for appropriate patients with moderate-to-severe
acute pain
. As such,
SEGLENTIS
was developed as a multimodal treatment option for the management of
acute pain
severe enough to require an
opioid
. Because of the risks of addiction, abuse and misuse with opioids, even at recommended doses,
SEGLENTIS
should be reserved for use in patients with
acute pain
severe enough to require an
opioid
and for whom alternative treatment options (e.g.,
non-opioid analgesics
) have not been tolerated or are not expected to be tolerated and have not provided adequate analgesia or are not expected to provide adequate analgesia. Dr. Eugene R. Viscusi, Phase 3 trial clinical investigator and Vice Chair of
Pain
Management at
Jefferson Thomas University
said, “Now that multimodal analgesia has become the standard for
acute pain
treatment, we are excited that the results of this study demonstrate that
SEGLENTIS
is efficacious and safe in its unique co-crystal combination of
tramadol hydrochloride
and
celecoxib
. This novel multimodal form of analgesia may be an important alternative option for treating appropriate adults with certain types of
acute pain
.”
Acute pain
is characterized by a sudden sharp pain lasting less than 4 weeks, and
chronic pain
is characterized by
pain
which lasts more than 3 months.1,2 86% of the U.S. population undergoing surgery experiences
acute postoperative pain3
, with
acute pain
accounting for 42% of patients who experienced
pain
-related events in the U.S.4 “As a part of our continued efforts to ensure the safety and efficacy of our products, these results align with efforts and current guidance to offer physicians and their patients a treatment option that strives toward the lowest effective dose and shortest duration of therapy,” said Craig A. Sponseller Chief Medical Officer. “We are excited to publish the pivotal phase 3 data in adults post bunionectomy and osteotomy demonstrating that
SEGLENTIS
®, the first co-crystal, immediate-release, opioid combination agent with a unique dosage strength, had significantly better analgesia compared with each individual component at half the maximum daily doses for
acute pain
.”
SEGLENTIS
was approved as a Schedule IV controlled substance, which includes a Boxed Warning concerning addiction, abuse, and misuse. About the Pivotal Phase 3 Trial Study Design This randomized, double-blind, parallel-group, factorial, active- and placebo-controlled pivotal Phase 3 trial (NCT03108482), evaluated 637 adults, across 6 U.S.-based research centers, with moderate-to-severe
acute pain
(mean baseline NPRS score was 6.7) using an established model of
acute surgical pain
after bunionectomy and osteotomy. Trial participants (n=637) were randomized 2:2:2:1 to oral, 200 mg Q12H
SEGLENTIS
, 50 mg Q6H
tramadol hydrochloride
, 100 mg Q12H
celecoxib
, or Q6H placebo. Mean age of participants was 46 years, with most patients being female (86%) which is consistent with the clinical population seeking bunionectomy treatment. Rescue medication was allowed during the study, patients which required medical had a sequential offering of IV
Acetaminophen
1 g every 4 to 6 hours, up to 4 g/24 hours, or
oxycodone hydrochloride
5 mg immediate release tablet every 4 to 6 hours if needed, up to a total of 30 mg/24 hours. Primary and Secondary Endpoints The primary efficacy endpoint met and studied was summed
pain
intensity difference from 0 to 48 hours (SPID0-48).
SEGLENTIS
had a significantly greater effect on SPID0-48 (least-squares mean: −139.1 [95% confidence interval: −151.8, −126.5]) than
tramadol
(−109.1 [−121.7, −96.4]; P<0.001),
celecoxib
(−103.7 [−116.4, −91.0]; P<0.001) or placebo (−74.6 [−92.5, −56.6]; P<0.001). Secondary efficacy endpoints supported primary findings and included: SPID over 4, 6, 12 and 24 hours Total
pain
relief over 4, 6, 12, 24 and 48 hours
Pain
intensity and change from baseline in
pain
intensity at each time point Response rates Time to onset of analgesia Proportion of patients using rescue medication Time to first use of rescue medication Patients’ overall assessment of study drug. Safety Pro Total Emergent Adverse Events The overall rates of treatment emergent adverse events (TEAEs) were similar in the
SEGLENTIS
(63.4%) and
tramadol
(63.4%) groups, and lower in both the
celecoxib
(52.2%) and placebo (57.3%) groups. The most common AEs reported were
nausea
(30%),
dizziness
(17%),
vomiting
(16%),
headache
(12%) and
somnolence
(8%). There were no serious TEAEs or death. TEAEs leading to study medication discontinuation were experienced by 6 patients, 3 in the SEGLENTIS group (
nausea
, n=2;
pruritus
and
rash
, n=1) and 3 in the
tramadol
group (
vomiting
, n=2;
supraventricular tachycardia
, n=1). Overall, the safety pro SEGLENTIS was similar to that of
tramadol hydrochloride
and no additional safety concerns were observed during the study period. About
SEGLENTIS
Approved by the U.S. Food and Drug Administration in October 2021,
SEGLENTIS
is a co-crystal formulation of two commonly prescribed analgesics,
celecoxib
and
tramadol hydrochloride
.
SEGLENTIS
provides
celecoxib
and
tramadol hydrochloride
as a lower maximum daily dose than each of the individual agent at maximum doses for
acute pain
(224-mg and 176-mg in
SEGLENTIS
vs ≥400-mg and 400-mg for
celecoxib
and
tramadol
, respectively).
SEGLENTIS
was developed by
Esteve Pharmaceuticals
and is commercialized and available from
Kowa Pharmaceuticals America, Inc.
within the U.S. Indication
SEGLENTIS
contains
tramadol hydrochloride
, an
opioid agonist
, and
celecoxib
, a nonsteroidal anti-inflammatory drug, and is indicated for the management of
acute pain
in adults that is severe enough to require an
opioid analgesic
and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve
SEGLENTIS
for use in patients for whom alternative treatment options [e.g.,
non-opioid analgesics
]: Have not been tolerated, or are not expected to be tolerated. Have not provided adequate analgesia, or are not expected to provide adequate analgesia. Important
Safety Information
, including Boxed Warning WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING
RESPIRATORY DEPRESSION
; ACCIDENTAL INGESTION; CARDIOVASCULAR (CV) THROMBOTIC EVENTS;
GASTROINTESTINAL (GI) BLEEDING
, ULCERATION, AND PERFORATION; ULTRA-RAPID METABOLISM OF
TRAMADOL
AND OTHER RISK FACTORS FOR LIFE-THREATENING
RESPIRATORY DEPRESSION
IN CHILDREN;
NEONATAL OPIOID WITHDRAWAL SYNDROME
; INTERACTIONS WITH DRUGS AFFECTING
CYTOCHROME P450
ISOENZYMES; RISKS FROM CONCOMITANT USE WITH
BENZODIAZEPINES
OR OTHER CENTRAL NERVOUS SYSTEM (CNS) DEPRESSANTS Addiction, Abuse, and Misuse SEGLENTIS 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
SEGLENTIS
and monitor all patients regularly for the development of these behaviors and conditions. Opioid Analgesic REMS To ensure that the benefits of
opioid analgesics
outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved
opioid analgesic
products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to complete a REMS-compliant education program, counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products, emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and consider other tools to improve patient, household, and community safety. Life-threatening
Respiratory Depression
Serious, life-threatening, or fatal
respiratory depression
may occur with use of SEGLENTIS. Monitor for
respiratory depression
, especially during initiation of SEGLENTIS. Accidental Ingestion Accidental ingestion of even one dose of SEGLENTIS, especially by children, can be fatal. CV Thrombotic Events
Nonsteroidal anti-inflammatory drugs (NSAIDs)
cause an increased risk of serious
CV thrombotic events
, including
myocardial infarction (MI)
, and
stroke
, which can be fatal. This risk may occur early in the treatment and may increase with duration of use.
SEGLENTIS
is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
GI Bleeding
, Ulceration, and Perforation
NSAIDs
cause an increased risk of serious GI adverse events including
bleeding
, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of
peptic ulcer disease
and/or
GI bleeding
are at greater risk for serious (GI) events. Ultra-Rapid Metabolism of
Tramadol
and Other Risk Factors for Life-threatening
Respiratory Depression
in Children Life-threatening
respiratory depression
and death have occurred in children who received
tramadol
. Some of the reported cases followed tonsillectomy and/or adenoidectomy; in at least one case, the child had evidence of being an ultra-rapid metabolizer of
tramadol
due to a
CYP2D6
polymorphism. SEGLENTIS is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of SEGLENTIS in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of
tramadol
.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of SEGLENTIS during pregnancy can result in
neonatal opioid withdrawal syndrome
, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If
opioid
use is required for a prolonged period in a pregnant woman, advise the patient of the risk of
neonatal opioid withdrawal syndrome
and ensure that appropriate treatment will be available. Interactions with Drugs Affecting
Cytochrome P450
Isoenzymes The effects of concomitant use or discontinuation of
cytochrome P450 3A4
inducers, 3A4 inhibitors, or 2D6 inhibitors with
tramadol
are complex. Use of
cytochrome P450 3A4
inducers, 3A4 inhibitors, or 2D6 inhibitors with
SEGLENTIS
requires careful consideration of the effects on the parent drug,
tramadol
, and the active metabolite, M1. Risks from Concomitant Use with
Benzodiazepines
or Other CNS Depressants Concomitant use of opioids with
benzodiazepines
or other CNS depressants, including
alcohol
, may result in profound
sedation
,
respiratory depression
,
coma
, and death. Reserve concomitant prescribing of
SEGLENTIS
and
benzodiazepines
or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit treatment to the minimum duration. Follow patients for signs and symptoms of
respiratory depression
and sedation. Contraindications Children younger than 12 years of age. Postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Significant
respiratory depression
. In the setting of CABG surgery. Acute or severe
bronchial asthma
in an unmonitored setting or in absence of resuscitative equipment. Known or suspected
GI obstruction
, including
paralytic ileus
. Hypersensitivity to
tramadol
,
celecoxib
, any other component of this product, or
sulfonamides
, or opioids. Concurrent use of
monoamine oxidase inhibitors (MAOIs)
or use of MAOIs within the last 14 days. History of
asthma
,
urticaria
, or other allergic-type reactions after taking
aspirin
or other
NSAIDs
. Warnings and Precautions Addiction, Abuse, and Misuse: Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed SEGLENTIS. Addiction can occur at recommended dosages and if the drug is misused or abused. Life-threatening
Respiratory Depression
: Serious, life-threatening, or fatal
respiratory depression
has been reported with the use of opioids, even when used as recommended.
Respiratory depression
, if not immediately recognized and treated, may lead to
respiratory arrest
and death. Management of
respiratory depression
may include close observation, supportive measures, and use of
opioid antagonists
, depending on the patient’s clinical status. Carbon dioxide (CO2) retention from
opioid-induced respiratory depression
can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal
respiratory depression
can occur at any time during the use of SEGLENTIS, the risk is greatest during the initiation of therapy. Monitor patients closely for
respiratory depression
, especially within the first 24-72 hours of initiating therapy with SEGLENTIS. Consider prescribing
naloxone
, based on the patient’s risk factors for overdose, such as concomitant use of CNS depressants, a history of
opioid use disorder
, or prior
opioid overdose
. CV Thrombotic Events: To minimize the potential risk for an adverse CV event in NSAID-treated patients, use SEGLENTIS for the shortest duration possible. Avoid the use of
SEGLENTIS
in patients with a recent
MI
unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If
SEGLENTIS
is used in patients with a recent
MI
, monitor patients for signs of
cardiac ischemia
.
GI Bleeding
, Ulceration, and Perforation: Use the approved dosage for the shortest possible duration. Ultra-Rapid Metabolism of
Tramadol
and Other Risk Factors for Life-threatening
Respiratory Depression
in Children: Even at labeled dosage regimens, individuals who are ultra-rapid metabolizers may have life-threatening or fatal
respiratory depression
or experience signs of overdose (such as extreme sleepiness,
confusion
, or shallow breathing). Therefore, individuals who are ultra-rapid metabolizers should not use
SEGLENTIS
. Risk from Concomitant Use with
Benzodiazepines
or Other CNS Depressants: Profound
sedation
,
respiratory depression
,
coma
, and death may result from the concomitant use of SEGLENTIS 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. If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an
opioid analgesic
, prescribe the lowest effective dosages and minimum durations of concomitant use.
Serotonin Syndrome
Risk: Cases of
serotonin syndrome
, a potentially life-threatening condition, have been reported with the use of
tramadol
, a component of SEGLENTIS, particularly during concomitant use with serotonergic drugs. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs),
triptans
,
5-HT3 receptor
antagonists, drugs that affect the serotonergic neurotransmitter system (e.g.,
mirtazapine
,
trazodone
,
tramadol
), certain
muscle relaxants
(i.e.,
cyclobenzaprine
,
metaxalone
), and drugs that impair metabolism of serotonin (including MAOIs, both those intended to treat
psychiatric disorders
and also others, such as
linezolid
and intravenous methylene blue). This may occur within the recommended dosage range. The onset of symptoms generally occurs within several hours to a few days of concomitant use but may occur later than that. Discontinue SEGLENTIS if
serotonin syndrome
is suspected. Increased Risk of
Seizure
: Can occur at the recommended dose of
tramadol
. Concomitant use of
SEGLENTIS
increases the
seizure
risk in patients taking: SSRIs and SNRIs,
antidepressants
or anorectics, TCAs, and other tricyclic compounds (e.g.,
cyclobenzaprine
,
promethazine
, etc.), other opioids, MAOIs, neuroleptics, or other drugs that reduce the
seizure
threshold. Risk may increase in patients with
epilepsy
, a history of
seizures
, and in patients with a recognized risk for
seizures
. Suicide Risk: Prescribe
SEGLENTIS
with caution for patients with a history of misuse and/or who are currently taking CNS-active drugs including tranquilizers, or antidepressant drugs, alcohol in excess, and patients who suffer from
emotional disturbance
or
depression
. Adrenal Insufficiency: Cases of
adrenal insufficiency
have been reported with
opioid
use, more often following greater than one month of use. Presentation of
adrenal insufficiency
may include non-specific symptoms and signs including
nausea
,
vomiting
,
anorexia
,
fatigue
, weakness,
dizziness
, and low blood pressure. If
adrenal insufficiency
is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If
adrenal insufficiency
is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different
opioid
without recurrence of
adrenal insufficiency
. The information available does not identify any particular opioids as being more likely to be associated with
adrenal insufficiency
. Life-threatening
Respiratory Depression
in Patients with
Chronic Pulmonary Disease
or in Elderly, Cachectic, or Debilitated Patients: SEGLENTIS-treated patients with significant
chronic obstructive pulmonary disease
or
cor pulmonale
, and those with a substantially decreased respiratory reserve,
hypoxia
,
hypercapnia
, or pre-existing
respiratory depression
, are at increased risk of decreased respiratory drive including
apnea
, even at the recommended dosage of SEGLENTIS. Elderly, Cachectic, or Debilitated Patients Life-threatening
respiratory depression
is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics, or altered clearance, compared to younger, healthier patients. Monitor such patients closely, particularly when initiating SEGLENTIS and when SEGLENTIS is given concomitantly with other drugs that depress respiration. Severe Hypotension:
Tramadol
, a component of SEGLENTIS, may cause severe
hypotension
including
orthostatic hypotension
and
syncope
in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics). Monitor these patients for signs of
hypotension
after initiating dosage of SEGLENTIS. In patients with
circulatory shock
,
tramadol
may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of SEGLENTIS in patients with
circulatory shock
. Risks of Use in Patients with Increased Intracranial Pressure,
Brain Tumors
,
Head Injury
, or Impaired Consciousness: In patients who may be susceptible to the intracranial effects of
CO2 retention
(e.g., those with evidence of increased intracranial pressure or
brain tumors
), SEGLENTIS may reduce respiratory drive, and the resultant
CO2 retention
can further increase intracranial pressure. Monitor such patients for signs of sedation and
respiratory depression
, particularly when initiating therapy with SEGLENTIS. Opioids may also obscure the clinical course in a patient with a
head injury
. Avoid the use of SEGLENTIS in patients with impaired consciousness or coma. Risk of Use in Patients with GI Conditions: The
tramadol
in SEGLENTIS may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum
amylase
. Monitor patients with
biliary tract disease
, including
acute pancreatitis
, for worsening symptoms. Anaphylactic Reactions: Seek emergency help if an anaphylactic reaction occurs. Hepatotoxicity: As
tramadol
and
celecoxib
are both extensively metabolized by the liver, the use of
SEGLENTIS
in patients with moderate and severe hepatic impairment is not recommended. Inform patients of the warning signs and symptoms of hepatotoxicity (e.g.,
nausea
,
fatigue
,
lethargy
,
diarrhea
,
pruritus
,
jaundice
, right upper quadrant tenderness, and "
flu-like" symptoms
). If clinical signs and symptoms consistent with
liver disease
develop, or if systemic manifestations occur (e.g.,
eosinophilia
,
rash
, etc.), discontinue SEGLENTIS immediately, and perform a clinical evaluation of the patient. Inform patients of warning signs and symptoms of hepatotoxicity.
Hypertension
:
NSAIDs
, including
celecoxib
, a component in SEGLENTIS, can lead to new onset of
hypertension
or worsening of preexisting
hypertension
, either of which may contribute to the increased incidence of CV events. Patients taking
angiotensin converting enzyme (ACE) inhibitors
angiotensin converting enzyme (ACE)
inhibitors, thiazide diuretics or loop diuretics may have impaired response to these therapies when taking
NSAIDs
. Monitor blood pressure during the initiation of NSAID treatment and throughout the course of therapy.
Heart Failure
and
Edema
: Avoid the use of
SEGLENTIS
in patients with severe
heart failure
unless the benefits are expected to outweigh the risk of worsening
heart failure
. If
SEGLENTIS
is used in patients with severe
heart failure
, monitor patients for signs of worsening
heart failure
. Renal Toxicity and
Hyperkalemia
: Long-term administration of
NSAIDs
has resulted in
renal papillary necrosis
and other
renal injury
. Renal toxicity has been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function,
dehydration
,
hypovolemia
,
heart failure
, or
liver dysfunction
; those taking diuretics,
ACE inhibitors
ACE
inhibitors, or angiotensin receptor blockers (ARBs); and the elderly. Increases in serum potassium concentration, including
hyperkalemia
, have been reported with use of
NSAIDs
, even in some patients without
renal impairment
. Exacerbation of
Asthma
Related to
Aspirin
Sensitivity: SEGLENTIS is contraindicated in patients with
aspirin-sensitive asthma
. Monitor patients with preexisting
asthma
(without
aspirin
sensitivity). Serious Skin Reactions: Serious skin reactions have occurred following treatment with
celecoxib
, a component of SEGLENTIS, including
erythema multiforme
,
exfoliative dermatitis
,
Stevens-Johnson syndrome
,
toxic epidermal necrolysis
,
drug reaction
with
eosinophilia
and systemic symptoms
(DRESS)
, and
acute generalized exanthematous pustulosis
. These serious events may occur without warning and can be fatal. Discontinue SEGLENTIS at first appearance of
skin rash
or other signs of
hypersensitivity
. DRESS: Discontinue and evaluate clinically. Fetal Toxicity: Limit use of
NSAIDs
, including SEGLENTIS, between about 20 to 30 weeks in pregnancy due to the risk of
oligohydramnios
/
fetal renal dysfunction
. Avoid use of
NSAIDs
in women at about 30 weeks gestation and later in pregnancy due to the risks of
oligohydramnios
/
fetal renal dysfunction
and premature closure of the fetal ductus arteriosus. Hematologic Toxicity:
Anemia
has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If a patient treated with SEGLENTIS has any signs or symptoms of
anemia
, monitor hemoglobin or hematocrit.
NSAIDs
, including SEGLENTIS, may increase the risk of bleeding events. Co-morbid conditions such as
coagulation disorders
or concomitant use of
warfarin
, other
anticoagulants
, antiplatelet agents (e.g.,
aspirin
), SSRIs, and SNRIs may increase this risk. Monitor these patients for signs of
bleeding
. Withdrawal: Do not abruptly discontinue SEGLENTIS in a patient physically dependent on opioids. When discontinuing SEGLENTIS in a physically dependent patient, gradually taper the dosage. Rapid tapering of
tramadol
in a patient physically dependent on opioids may lead to a
withdrawal syndrome
and return of
pain
. Additionally, avoid the use of mixed agonist/antagonist (e.g.,
pentazocine
,
nalbuphine
, and
butorphanol
) or partial agonist (e.g.,
buprenorphine
) analgesics in patients who are receiving a full
opioid agonist analgesic
, including SEGLENTIS. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms. Driving and Operating Machinery: SEGLENTIS may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of SEGLENTIS and know how they will react to the medication. Masking of
Inflammation
and
Fever
: The pharmacological activity of SEGLENTIS in reducing
inflammation
, and possibly
fever
, may diminish the utility of diagnostic signs in detecting
infections
.
Hyponatremia
:
Hyponatremia
(serum sodium <135 mmol/L) has been reported with the use of
tramadol
, a component of SEGLENTIS, and many cases are severe (sodium level <120 mmol/L). Most cases of
hyponatremia
occurred in females over the age of 65 and within the first week of therapy. In some reports,
hyponatremia
resulted from the syndrome of inappropriate antidiuretic hormone secretion. Monitor for signs and symptoms of
hyponatremia
(e.g.,
confusion
, disorientation) during treatment with SEGLENTIS, especially during initiation of therapy. If signs and symptoms of
hyponatremia
are present, initiate appropriate treatment (e.g., fluid restriction) and discontinue SEGLENTIS. Hypoglycemia: Cases of
tramadol-associated hypoglycemia
have been reported, some resulting in hospitalization. In most cases, patients had predisposing risk factors (e.g.,
diabetes
). If
hypoglycemia
is suspected, monitor blood glucose levels and consider drug discontinuation as appropriate. Adverse Reactions Most common adverse reactions (incidence >5% and > placebo) for SEGLENTIS are
nausea
(30%),
vomiting
(16%),
dizziness
(17%),
headache
(12%), and
somnolence
(8%). Select Drug Interactions Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics: Avoid use with
SEGLENTIS
because they may reduce analgesic effect of
SEGLENTIS
or precipitate withdrawal symptoms. Drugs that Interfere with Hemostasis (e.g.,
warfarin
,
aspirin
, SSRIs/SNRIs): Monitor patients for
bleeding
who are concomitantly taking SEGLENTIS with drugs that interfere with hemostasis. Concomitant use of SEGLENTIS and analgesic doses of
aspirin
is not generally recommended.
ACE Inhibitors
ACE
Inhibitors, ARBs, or
Beta Blockers
: Concomitant use with SEGLENTIS may diminish the antihypertensive effect of these drugs. Monitor blood pressure.
ACE Inhibitors
ACE
Inhibitors and ARBs: Concomitant use with SEGLENTIS in elderly, volume depleted, or those with
renal impairment
may result in deterioration of renal function. In such high-risk patients, monitor for signs of worsening renal function. Diuretics:
NSAIDs
can reduce natriuretic effect of
furosemide
and thiazide diuretics. Monitor patients to assure diuretic efficacy including antihypertensive effects.
Digoxin
: Concomitant use with
SEGLENTIS
can increase serum concentration and prolong half-life of
digoxin
. Monitor serum digoxin levels. Drug Abuse and Dependence SEGLENTIS contains
tramadol
, a Schedule IV controlled substance with a high potential for abuse similar to other opioids and can be abused and is subject to misuse, addiction, and criminal diversion. All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. Physical dependence is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Overdosage SEGLENTIS is a combination drug composed of
tramadol
and
celecoxib
. The clinical presentation of overdose may include the signs and symptoms of
tramadol
toxicity,
celecoxib
toxicity, or both.
Tramadol
: Acute overdosage with
tramadol
can be manifested by
respiratory depression
,
somnolence
progressing to
stupor
or
coma
, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases,
pulmonary edema
,
bradycardia
,
QT prolongation
,
hypotension
, partial or complete airway obstruction,
atypical snoring
,
seizures
, and death. Marked mydriasis rather than
miosis
may be seen with
hypoxia
in overdose situations. Deaths due to overdose have been reported with abuse and misuse of
tramadol
. Review of case reports has indicated that the risk of fatal overdose is further increased when
tramadol
is abused concurrently with
alcohol
or other CNS depressants, including other opioids. Celecoxib: Symptoms following acute NSAID overdosages have been typically limited to
lethargy
,
drowsiness
,
nausea
,
vomiting
, and
epigastric pain
, which have been generally reversible with supportive care.
GI bleeding
has occurred.
Hypertension
,
acute renal failure
,
respiratory depression
, and
coma
have occurred, but were rare. For more information on appropriate treatment of overdose with
SEGLENTIS
, see the full Prescribing Information. Opioid Analgesic Risk Evaluation and
Mitigation Strategy
(REMS) To ensure that the benefits of
opioid analgesics
, including
SEGLENTIS
, outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products. Under the requirements of the REMS, drug companies with approved
opioid analgesic
products must make REMS-compliant education programs available to healthcare providers. To obtain further information on the
opioid analgesic
REMS and for a list of accredited REMS continuing education, call 1-800-503-0784, or log on to . To report SUSPECTED ADVERSE REACTIONS, contact
Kowa Pharmaceuticals America, Inc.
at 1-888-SEGLENTIS or the FDA at 1-800-FDA-1088 or . For additional information please see full Prescribing Information, including Boxed Warning, and Medication Guide, for SEGLENTIS. Intended for healthcare professionals of the United States of America only.
SEGLENTIS
is a registered trademark of
Esteve Pharmaceuticals
, S.A., and is used under license.
© Kowa Pharmaceuticals America, Inc.
(2022) References: Dowell D. Draft Updated CDC Guidelines for Prescribing Opioids: Background, Overview, and Progress. . Published July 16, 2021. Accessed January 25, 2022 DHHS Pain Management Best Practices Inter-Agency Task Report, May 2019. . Accessed November 17, 2021 Gan TJ, Habib AS, Miller TE, White W, Apfelbaum JL. Incidence, patient satisfaction, and perceptions of
post-surgical pain
: results from a US national survey. Curr Med Res Opin. 2014;30:149-160. Aggregated claims data deliverable from Symphony’s APLD offering.
更多内容,
请访问原始网站
文中所述内容并不反映新药情报库及其所属公司任何意见及观点,如有版权侵扰或错误之处,请及时联系我们,我们会在24小时内配合处理。
机构
The Strategy Group LLC
Esteve Pharmaceuticals Ltd.
Thomas University
[+2]
适应症
出血
肾上腺皮质功能不全
急性泛发性发疹性脓疱病
[+91]
靶点
CYPs
CYP2D6
CYP3A4
[+4]
药物
对乙酰氨基酚
Opioid Abuse Therapeutics (Axim Biotech)
AF-4025
[+31]
标准版
¥
16800
元/账号/年
新药情报库 | 省钱又好用!
立即使用
热门报告
肿瘤领域药物开发早期热门靶点研究报告(AACR 2023-2024)
智慧芽生物医药
siRNA药物Amvuttra专利调研实务指南
智慧芽生物医药
2024年4月全球首批及特殊审评药物报告
智慧芽生物医药
立即开始免费试用!
智慧芽新药情报库是智慧芽专为生命科学人士构建的基于AI的创新药情报平台,助您全方位提升您的研发与决策效率。
开始免费试用
立即开始数据试用!
智慧芽新药库数据也通过智慧芽数据服务平台,以API或者数据包形式对外开放,助您更加充分利用智慧芽新药情报信息。
试用数据服务