Respiratory Depression
Respiratory depression could be the chief hazard of OPANA (oxymorphone hydrochloride) . Respiratory depression
may occur more frequently in elderly or debilitated patients plus in those
being affected by conditions accompanied by hypoxia or hypercapnia, when even moderate
therapeutic doses may dangerously decrease pulmonary ventilation.
Administer OPANA (oxymorphone hydrochloride) with warning to patients with conditions accompanied
by hypoxia, hypercapnia, or decreased respiratory reserve such as: asthma, chronic
obstructive pulmonary disease or cor pulmonale, severe obesity, sleep apnea
syndrome, myxedema, kyphoscoliosis, CNS depression, or coma. During these patients,
even usual therapeutic doses of oxymorphone may decrease respiratory drive while
simultaneously increasing airway potential to deal with the aim of apnea. Consider
alternative non-opioid analgesics and rehearse OPANA (oxymorphone hydrochloride) only under careful medical supervision
at the smallest effective dose in such patients.
Misuse, Abuse, and Diversion of Opioids
OPANA (oxymorphone hydrochloride) contains oxymorphone, a mu opioid agonist as well as a Schedule II controlled
substance with an abuse liability similar to morphine. Opioid agonists are sought
by drug abusers the ones with addiction disorders and so are susceptible to criminal
diversion.
Oxymorphone can be abused in a very manner similar to other opioid agonists, legal
or illicit. This issue might be of interest when prescribing or dispensing oxymorphone
in situations the place that the physician or pharmacist is involved about a increased
probability of misuse, abuse, or diversion.
OPANA (oxymorphone hydrochloride) tablets may be abused by crushing, chewing, snorting, or injecting the
product. These practices pose a substantial risk towards the abuser that could result
in overdose and death [see Drug use and Dependence].
OPANA (oxymorphone hydrochloride) may be focused on theft and diversion. Healthcare professionals should
contact their State Medical Board, State Board of Pharmacy, or State Control
Board for information about how to detect or prevent diversion on this product,
and security requirements for storing and handling of OPANA (oxymorphone hydrochloride) .
Healthcare professionals should advise patients to hold OPANA (oxymorphone hydrochloride) in a good
place, preferably locked and out from the reach of kids along with other non-caregivers.
Concerns about abuse, misuse, diversion and addiction shouldnt steer clear of the
proper control over pain.
Additive CNS Depressant Effects
The concomitant use of other CNS depressants including other opioids, general
anesthetics, phenothiazines, other tranquilizers, sedatives, hypnotics, and
alcohol with oxymorphone may produce increased depressant effects including
hypoventilation, hypotension, profound sedation, coma and death [see DRUG
INTERACTIONS].
Use in Patients with Head Injury and Increased Intracranial Pressure
In the use of head injury, intracranial lesions or perhaps a preexisting increase
in intracranial pressure, the respiratory depressant connection between opioid analgesics
as well as their possible ways to elevate cerebrospinal fluid pressure (resulting from
vasodilation following CO2 retention) could possibly be markedly exaggerated. Furthermore,
opioid analgesics can produce effects on papillary response and consciousness,
which may obscure neurologic indications of further increases in intracranial pressure
in patients with head injuries.
Administer OPANA (oxymorphone hydrochloride) with extreme caution in patients who might be particularly susceptible
on the intracranial connection between CO2 retention, such as people that have evidence of
increased intracranial pressure or impaired consciousness.
Opioids may obscure the clinical lifetime of someone which has a head injury and
must be used as long as clinically warranted buy arimidex online no prescription.
Hypotensive Effect
OPANA (oxymorphone hydrochloride) , as with any opioid analgesics, could cause severe hypotension in a patient
whose capability to maintain blood pressure level has been compromised with a depleted
blood volume, or after concurrent administration with drugs including phenothiazines
and other agents that compromise vasomotor tone. Administer OPANA (oxymorphone hydrochloride) with caution
to patients in circulatory shock, since vasodilation created by the drug may
further reduce cardiac output and blood pressure level.
Hepatic Impairment
A study of extended-release oxymorphone tablets in patients with hepatic disease
indicated greater plasma concentrations than in those that have normal hepatic function
[see CLINICAL PHARMACOLOGY]. Use OPANA (oxymorphone hydrochloride) with caution in patients with
mild impairment, beginning with the minimum dose and titrating slowly while carefully
monitoring for side effects [see DOSAGE AND ADMINISTRATION]. OPANA (oxymorphone hydrochloride) is
contraindicated in patients with moderate or severe hepatic impairment.
Special Risk Groups
Use OPANA (oxymorphone hydrochloride) with caution within the following conditions: adrenocortical insufficiency
(e. g. , Addisons disease), prostatic hypertrophy or urethral stricture, severe
impairment of pulmonary or renal function, and toxic psychosis.
Opioids may aggravate convulsions in patients with convulsive disorders, and
may induce or aggravate seizures in certain clinical settings.
Gastrointestinal Effects
Opioids diminish propulsive peristaltic waves within the gastrointestinal tract. Monitor for decreased bowel motility in post-operative patients receiving opioids. The administration of OPANA (oxymorphone hydrochloride) may obscure the verification or clinical course in
patients with acute abdominal conditions. OPANA (oxymorphone hydrochloride) is contraindicated in patients
with paralytic ileus.
Use in Pancreatic/Biliary Tract Disease
OPANA (oxymorphone hydrochloride) , like other opioids, could potentially cause spasm of the sphincter of Oddi and really should
provide with caution in patients with biliary tract disease, including acute
pancreatitis.
Driving and Operating Machinery
Opioid analgesics impair the mental and physical abilities had to perform
potentially hazardous activities such as the worry or operating machinery.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Long-term numerous studies have been completed to gauge the carcinogenic potential
of oxymorphone both in Sprague-Dawley rats and CD-1 mice. Oxymorphone was administered
to Sprague-Dawley rats (2. 5, 5, and 10 mg/kg/day of males and 5, 10, and 25
mg/kg/day in ladies) for 2 years by oral gavage. The systemic drug exposure
(AUC ng•h/mL) on the 10 mg/kg/day dose in male rats was 0. 34-fold at the
25 mg/kg/day dose in female rats was 1. 5fold the human exposure in a dose of
260 mg/day. No proof of carcinogenic potential was observed in rats. Oxymorphone
was administered to CD-1 mice (10, 25, 75 and 150 mg/kg/day) for two years by
oral gavage. The systemic drug exposure (AUC ng•h/mL) on the 150 mg/kg/day dose
in mice was 14. 5-fold (of males) and 17. 3-fold (ladies) times the human
exposure at the dose of 260 mg/day. No proof carcinogenic potential was
seen in mice.
Mutagenesis
Oxymorphone hydrochloride wasnt mutagenic when tested within the in vitro
bacterial reverse mutation assay (Ames test) at concentrations of ≤ 5270
μg/plate, or in an in vitro mammalian cell chromosome aberration assay
performed with human peripheral blood lymphocytes at concentrations ≤ 5000
μg/ml without or with metabolic activation. Oxymorphone hydrochloride tested
positive in the rat and mouse in vivo micronucleus assays. A growth
in micronucleated polychromatic erythrocytes happened in mice given doses of
≥ 250 mg/kg as well as in rats given doses of 20 and 40 mg/kg. A subsequent study
demonstrated that oxymorphone hydrochloride has not been aneugenic in mice following
administration of up to 500 mg/kg. Additional research indicates that this increased
incidence of micronucleated polychromatic erythrocytes in rats could possibly be secondary
to increased body temperature following oxymorphone administration. Doses associated
to comprehend micronucleated polychromatic erythrocytes also create a marked,
rapid boost in bodys temperature. Pretreatment of animals with sodium salicylate
minimized the rise in temperature and prevented the increase in micronucleated
polychromatic erythrocytes after administration of 40 mg/kg oxymorphone.
Impairment of fertility
Oxymorphone would not affect reproductive function or sperm parameters in male
rats at any dose tested ( ≤ 50 mg/kg/day). In female rats, a rise in the
length of the estrus cycle and decrease inside the mean quantity of viable embryos,
implantation sites and corpora lutea were observed at doses of oxymorphone ≥ 10
mg/kg/day. The dose of oxymorphone linked to reproductive findings in
female rats is 0. 8 times an overall human daily dose of 120 mg based on a body
floor. The dose of oxymorphone that produced no uncomfortable side effects on reproductive
findings in female rats (i. e. , NOAEL) is 0. 4-times an overall human daily dose
of 120 mg determined by body surface.
Use within Specific Populations
Pregnancy
The safety of employing oxymorphone while being pregnant hasnt been established with
regard to possible side effects on fetal development. The application of OPANA (oxymorphone hydrochloride) in
pregnancy, in nursing mothers, or in women of child-bearing potential requires
how the possible benefits of the drug be weighted from the possible hazards
for the mother and also the child.
Teratogenic Effects - Pregnancy Category C
There arent any adequate and well-controlled studies of oxymorphone in pregnant
women. In animal studies, oxymorphone caused decreased fetal and pup weights,
an increase in stillbirth, and a reduction in postnatal pup survival at maternal
oxymorphone doses comparable to 0. 4 to 4 times the human daily dose of 120 mg
(Determined by body area). OPANA (oxymorphone hydrochloride) should be utilized in pregnancy as long as
the opportunity benefit justifies the potential risk on the fetus.
In embryo-fetal developmental toxicity studies, pregnant rats and rabbits received
oxymorphone hydrochloride at doses approximately a couple of times (rats) and 8 times (rabbits)
total human daily dose of 120 mg (based on body area). No malformations
occurred, but reduced fetal weights occurred at maternal doses of 0. 8 (rat)
and 4 (rabbit) times the entire human daily dose of 120 mg (depending on body surface
area). There were no adverse developmental effects in rats that received 0. 4
times or rabbits that received less than Four times the entire human dose. There
were no effects of oxymorphone hydrochloride on intrauterine survival at doses
in rats ≤ 2 times, or in rabbits at ≤ 8 times the human dose (see Non-teratogenic
Effects, below). In a very study conducted prior to the establishment of fine
Laboratory Practices (GLP) and never based on current recommended methodology,
an individual subcutaneous injection of oxymorphone hydrochloride on gestation day
8 produced malformations in offspring of hamsters that received a dose equivalent
to Much the whole human daily dose of 120 mg (determined by body floor). This dose also produced 83% maternal lethality.
Non-teratogenic Effects
Oxymorphone hydrochloride administration to female rats during gestation in
a pre- and postnatal developmental toxicity study reduced mean litter size (18%)
at the dose of 25 mg/kg/day, due to an increase in the incidence of stillborn
pups. An increase in neonatal death occurred at doses ≥ 5 mg/kg/day (0. Four times
an overall total human daily dose of 120 mg, determined by body area). Low pup birth
weight, decreased post-natal putting on weight, and reduced post-natal survival of
pups occurred following treatments for the dams with 25 mg/kg/day (a couple of times
a total human daily dose of 120 mg, according to body area).
Prolonged usage of opioid analgesics during pregnancy could potentially cause fetal-neonatal
physical dependence. Neonatal withdrawal may occur. Symptoms usually appear
throughout the first events of life and may even include convulsions, irritability, excessive
crying, tremors, hyperactive reflexes, fever, vomiting, diarrhea, sneezing,
yawning, and increased respiratory rate.
Labor and Delivery
Opioids cross the placenta and may even produce respiratory depression in neonates. OPANA (oxymorphone hydrochloride) is not suggested for use in ladies during and immediately prior to labor,
when use of shorter acting analgesics or other analgesic techniques will be more
appropriate. Occasionally, opioid analgesics may prolong labor through actions
which temporarily reduce the strength, duration, and frequency of uterine contractions. However this effect is not consistent and may be offset by a heightened rate
of cervical dilatation, which tends to shorten labor. Neonates whose mothers
received opioid analgesics during labor needs to be observed closely for signs
of respiratory depression. A specific opioid antagonist, such as naloxone or
nalmefene, needs to be designed for reversal of opioid-induced respiratory depression
inside the neonate.
Nursing Mothers
It is not known whether oxymorphone is excreted in human milk. Because many
drugs, including some opioids, are excreted in human milk, caution should be
exercised when OPANA (oxymorphone hydrochloride) is administered to your nursing woman. Infants confronted with
OPANA (oxymorphone hydrochloride) through breast milk should be monitored for excess sedation and respiratory
depression. Withdrawal symptoms can take place in breast-fed infants when maternal
administration of an opioid analgesic is stopped, or when breast-feeding is
stopped.
Pediatric Use
Safety and effectiveness of OPANA (oxymorphone hydrochloride) in pediatric patients below age 18
years havent been established.
Geriatric Use
OPANA (oxymorphone hydrochloride) should be utilized with caution in elderly patients [see CLINICAL PHARMACOLOGY].
Of the entire quantity of subjects in scientific studies of OPANA (oxymorphone hydrochloride) , 31% were 65 and
over, while 7% were 75 and over. No overall differences in effectiveness were
observed between these subjects and younger subjects. There are several adverse
events which are more often affecting subjects 65 and also over compared to
younger subjects. These adverse events included dizziness, somnolence, confusion,
and nausea. buy elavil online without prescription Generally, dose choice for elderly patients should be cautious,
usually starting in the low end from the dosing range, reflecting the harder
frequency of decreased hepatic, renal or cardiac function, as well as concomitant
disease or another drug therapy
Hepatic Impairment
In a report of extended-release oxymorphone tablets, patients with mild hepatic
impairment were demonstrated to provide an increase in bioavailability of merely one. 6 fold. OPANA (oxymorphone hydrochloride)
should be used with caution in patients with mild impairment. These patients
should be started with the lowest dose and titrated slowly while carefully monitoring
for side effects. OPANA (oxymorphone hydrochloride) is contraindicated for patients with more persistant
hepatic impairment [see CONTRAINDICATIONS,
and DOSAGE AND ADMINISTRATION].
Renal Impairment
In a report of extended-release oxymorphone tablets, patients with moderate
to severe renal impairment were proven to offer an increase in bioavailability
starting from 57-65% [see CLINICAL PHARMACOLOGY]. Such patients should
be started cautiously with lower doses of OPANA (oxymorphone hydrochloride) and titrated slowly while monitoring
for unwanted side effects [see DOSAGE AND ADMINISTRATION].
Last reviewed on RxList: 3/28/2011
This monograph continues to be modified to include the generic and brand in many cases.
