Document
DailyMed Label: ENDODAN
Title
DailyMed Label: ENDODAN
Date
2011
Document type
DailyMed Prescription
Name
ENDODAN
Generic name
OXYCODONE and ASPIRIN
Manufacturer
STAT RX USA LLC
Product information
NDC: 16590-947
Product information
NDC: 16590-947
Description
Each ENDODAN Tablet contains:
Oxycodone Hydrochloride, USP 4.8355 mg 1
Aspirin, USP 325 mg
ENDODAN Tablets also contain the following inactive ingredients: D and C
Yellow 10, FD and C Yellow 6, microcrystalline cellulose and corn starch.
The oxycodone hydrochloride component is Morphinan-6-one,
4,5-epoxy-14-hydroxy-3-methoxy-17-methyl-, hydrochloride, (5a)-., a white to
off-white, hygroscopic crystals or powder, odorless, soluble in water; slightly
soluble in alcohol and is represented by the following structural formula:
The aspirin component is 2-(acetyloxy)-, Benzoic acid, a white crystal, commonly
tabular or needle-like, or white, crystalline powder. Is odorless or has a faint
odor. Is stable in dry air; in moist air it gradually hydrolyzes to salicylic
and acetic acids. Slightly soluble in water; freely soluble in alcohol; soluble
in chloroform and in ether; sparingly soluble in absolute ether and is
represented by the following structural formula:
1 4.8355 mg oxycodone HCl is equivalent to 4.3346 mg of oxycodone as the free
base.
Structure 1
Structure 2
Indications
ENDODAN tablets are indicated for the management of moderate to
moderately severe pain.
Dosage
Dosage should be adjusted according to the severity of the pain
and the response of the patient. It may occasionally be necessary to exceed the
usual dosage recommended below in cases of more severe pain or in those patients
who have become tolerant to the analgesic effect of opioids. If pain is
constant, the opioid analgesic should be given at regular intervals on an
around-the-clock schedule. ENDODAN tablets are given orally.
The usual dosage is one tablet every 6 hours as needed for pain. The maximum
daily dose of aspirin should not exceed 4 grams or 12 tablets.
Cessation of Therapy
In patients treated with ENDODAN tablets for more than a few
weeks who no longer require therapy, doses should be tapered gradually to
prevent signs and symptoms of withdrawal in the physically dependent patient.
Contraindications
ENDODAN tablets are contraindicated in patients with known
hypersensitivity to oxycodone or aspirin, and in any situation where opioids or
aspirin are contraindicated. Aspirin is contraindicated for patients with
hemophilia.
Reye Syndrome: Aspirin should not be used in children or
teenagers for viral infections, with or without fever, because of the risk of
Reye syndrome with concomitant use of aspirin in certain viral illnesses.
Allergy: Aspirin is contraindicated in patients with known allergy to
nonsteroidal anti-inflammatory drug products and in patients with the syndrome
of asthma, rhinitis, and nasal polyps. Aspirin may cause severe urticaria,
angioedema, or bronchospasm (asthma).
Oxycodone is contraindicated in patients with known hypersensitivity to
oxycodone. Oxycodone is contraindicated in any situation where opioids are
contraindicated including patients with significant respiratory depression (in
unmonitored settings or the absence of resuscitative equipment) and patients
with acute or severe bronchial asthma or hypercarbia. Oxycodone is
contraindicated in the setting of suspected or known paralytic ileus.
Precautions
General
Opioid analgesics should be used with caution when combined with
CNS depressant drugs, and should be reserved for cases where the benefits of
opioid analgesia outweigh the known risks of respiratory depression, altered
mental state, and postural hypotension.
ENDODAN tablets should be given with caution to patients with CNS depression,
elderly or debilitated patients, patients with severe impairment of hepatic,
pulmonary, or renal function, hypothyroidism, Addison's disease, prostatic
hypertrophy, urethral stricture, acute alcoholism, delirium tremens,
kyphoscoliosis with respiratory depression, myxedema, and toxic psychosis.
ENDODAN tablets may obscure the diagnosis or clinical course in patients with
acute abdominal conditions. Oxycodone may aggravate convulsions in patients with
convulsive disorders, and all opioids may induce or aggravate seizures in some
clinical settings.
Following administration of ENDODAN tablets, anaphylactic reactions have been
reported in patients with a known hypersensitivity to codeine, a compound with a
structure similar to morphine and oxycodone. The frequency of this possible
cross-sensitivity is unknown.
Aspirin has been associated with elevated hepatic enzymes, blood urea
nitrogen and serum creatinine, hyperkalemia, proteinuria, and prolonged bleeding
time.
Hemorrhage
Aspirin may increase the likelihood of hemorrhage due to its
effect on the gastric mucosa and platelet function (prolongation of bleeding
time). Salicylates should be used with caution in the presence of peptic ulcer
or coagulation abnormalities.
Pregnancy
Aspirin can cause fetal harm when administered to a pregnant
woman. Salicylates readily cross the placenta and by inhibiting prostaglandin
synthesis, may cause constriction of ductus arteriosus, resulting in pulmonary
hypertension and increased fetal mortality and, possibly other untoward fetal
effects. Aspirin use in pregnancy can also result in alteration in maternal and
neonatal hemostasis mechanisms. Maternal aspirin use during later stages of
pregnancy may cause low birth weight, increased incidence of intracranial
hemorrhage in premature infants, stillbirths and neonatal death. The use of
aspirin during pregnancy especially in the third trimester should be avoided. If
ENDODAN tablets are used during pregnancy, or if the patient becomes pregnant
while taking this drug, the patient should be apprised of the potential hazard
to the fetus.
Renal Failure
Avoid aspirin in patients with severe renal failure (glomerular
filtration rate less than 10 mL/minute).
Hepatic Insufficiency
Avoid aspirin in patients with severe hepatic
insufficiency.
Interactions with Other CNS Depressants
Patients receiving other opioid analgesics, general anesthetics,
phenothiazines, other tranquilizers, centrally-acting anti-emetics,
sedative-hypnotics or other CNS depressants (including alcohol) concomitantly
with ENDODAN tablets may exhibit an additive CNS depression. When such combined
therapy is contemplated, the dose of one or both agents should be reduced.
Interactions with Mixed Agonist/Antagonist Opioid
Analgesics
Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and
butorphanol) should be administered with caution to a patient who has received
or is receiving a course of therapy with a pure opioid agonist analgesic such as
oxycodone. In this situation, mixed agonist/antagonist analgesics may reduce the
analgesic effect of oxycodone and/or may precipitate withdrawal symptoms in
these patients.
Ambulatory Surgery and Postoperative Use
Oxycodone and other morphine-like opioids have been shown to
decrease bowel motility. Ileus is a common postoperative complication,
especially after intra-abdominal surgery with use of opioid analgesia. Caution
should be taken to monitor for decreased bowel motility in postoperative
patients receiving opioids. Standard supportive therapy should be
implemented.
Use in Pancreatic/Biliary Tract Disease
Oxycodone may cause spasm of the sphincter of Oddi and should be
used with caution in patients with biliary tract disease, including acute
pancreatitis. Opioids like oxycodone may cause increases in the serum amylase
level.
Tolerance and Physical Dependence
Tolerance is the need for increasing doses of opioids to maintain
a defined effect such as analgesia (in the absence of disease progression or
other external factors). Physical dependence is manifested by withdrawal
symptoms after abrupt discontinuation of a drug or upon administration of an
antagonist. Physical dependence and tolerance are not unusual during chronic
opioid therapy.
The opioid abstinence or withdrawal syndrome is characterized by some or all
of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration,
chills, myalgia, and mydriasis. Other symptoms also may develop, including:
irritability, anxiety, backache, joint pain, weakness, abdominal cramps,
insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure,
respiratory, respiratory rate, or heart rate.
In general, opioids should not be abruptly discontinued (see DOSAGE AND ADMINISTRATION:
Cessation of Therapy ).
The following information should be provided
to patients receiving ENDODAN tablets by their physician, nurse, pharmacist, or
caregiver:
Patients should be aware that ENDODAN tablets contain oxycodone, which is a
morphine-like substance.
Patients should be instructed to keep ENDODAN tablets in a secure place out
of the reach of children. In the case of accidental ingestions, emergency
medical care should be sought immediately.
When ENDODAN tablets are no longer needed, the unused tablets should be
destroyed by flushing down the toilet.
Patients should be advised not to adjust the medication dose themselves.
Instead, they must consult with their prescribing physician.
Patients should be advised that ENDODAN tablets may impair mental and/or
physical ability required for the performance of potentially hazardous tasks
(e.g., driving, operating heavy machinery).
Patients should not combine ENDODAN tablets with alcohol, opioid analgesics,
tranquilizers, sedatives, or other CNS depressants unless under the
recommendation and guidance of a physician. When co-administered with another
CNS depressant, ENDODAN tablets can cause dangerous additive central nervous
system or respiratory depression, which can result in serious injury or death.
The safe use of ENDODAN tablets during pregnancy has not been established;
thus, women who are planning to become pregnant or are pregnant should consult
with their physician before taking ENDODAN tablets.
Nursing mothers should consult with their physicians about whether to
discontinue nursing or discontinue ENDODAN tablets because of the potential for
serious adverse reactions to nursing infants.
Patients who are treated with ENDODAN tablets for more than a few weeks
should be advised not to abruptly discontinue the medication. Patients should
consult with their physician for a gradual discontinuation dose schedule to
taper off the medication.
Patients should be advised that ENDODAN tablets are a potential drug of
abuse. They should protect it from theft, and it should never be given to anyone
other than the individual for whom it was prescribed.
Patients should be advised that ENDODAN tablets may cause or worsen
constipation. They should discuss any past history of constipation with their
prescribing physician so a management plan may be initiated.
Although oxycodone may cross-react with some drug urine tests, no
available studies were found which determined the duration of detectability of
oxycodone in urine drug screens. However, based on pharmacokinetic data, the
approximate duration of detectability for a single dose of oxycodone is roughly
estimated to be one to two days following drug exposure.
Urine testing for opiates may be performed to determine illicit drug use and
for medical reasons such as evaluation of patients with altered states of
consciousness or monitoring efficacy of drug rehabilitation efforts. The
preliminary identification of opiates in urine involves the use of an
immunoassay screening and thin-layer chromatography (TLC). Gas
chromatography/mass spectrometry (GC/MS) may be utilized as a third-stage
identification step in the medical investigational sequence for opiate testing
after immunoassay and TLC. The identities of 6-keto opiates (e.g., oxycodone)
can further be differentiated by the analysis of their methoxime-trimethylsilyl
(MO-TMS) derivative.
Drug/Drug Interactions with Oxycodone
Opioid analgesics may enhance the neuromuscular-blocking action
of skeletal muscle relaxants and produce an increase in the degree of
respiratory depression.
Patients receiving CNS depressants such as other opioid analgesics, general
anesthetics, phenothiazines, other tranquilizers, centrally-acting anti-emetics,
sedative-hypnotics or other CNS depressants (including alcohol) concomitantly
with ENDODAN tablets may exhibit an additive CNS depression. When such combined
therapy is contemplated, the dose of one or both agents should be reduced.
Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, naltrexone, and
butorphanol) should be administered with caution to a patient who has received
or is receiving a pure opioid agonist such as oxycodone. These
agonist/antagonist analgesics may reduce the analgesic effect of oxycodone or
may precipitate withdrawal symptoms.
Drug/Drug Interactions with Aspirin
Angiotensin Converting Enzyme (ACE) Inhibitors: The hyponatremic
and hypotensive effects of ACE inhibitors may be diminished by the concomitant
administration of aspirin due to its indirect effect on the renin-angiotensin
conversion pathway.
Acetazolamide: Concurrent use of aspirin and acetazolamide can lead to high
serum concentrations of acetazolamide (and toxicity) due to competition at the
renal tubule for secretion.
Anticoagulant Therapy (Heparin and Warfarin): Patients on anticoagulation
therapy are at increased risk for bleeding because of drug-drug interactions and
the effect on platelets. Aspirin can displace warfarin from protein binding
sites, leading to prolongation of both the prothrombin time and the bleeding
time. Aspirin can increase the anticoagulant activity of heparin, increasing
bleeding risk.
Anticonvulsants: Salicylate can displace protein-bound phenytoin and valproic
acid, leading to a decrease in the total concentration of phenytoin and an
increase in serum valproic acid levels.
Beta Blockers: The hypotensive effects of beta blockers may be diminished by
the concomitant administration of aspirin due to inhibition of renal
prostaglandins, leading to decreased renal blood flow, and salt and fluid
retention.
Diuretics: The effectiveness of diuretics in patients with underlying renal
or cardiovascular disease may be diminished by the concomitant administration of
aspirin due to inhibition of renal prostaglandins, leading to decreased renal
blood flow and salt and fluid retention.
Methotrexate: Aspirin may enhance the serious side and toxicity of
methotrexate due to displacement from its plasma protein binding sites and/or
reduced renal clearance.
Nonsteroidal Anti-inflammatory Drugs (NSAID's): The concurrent use of aspirin
with other NSAID's should be avoided because this may increase bleeding or lead
to decreased renal function. Aspirin may enhance the serious side effects and
toxicity of ketorolac, due to displacement from its plasma protein binding sites
and/or reduced renal clearance.
Oral Hypoglycemics Agents: Aspirin may increase the serum glucose-lowering
action of insulin and sulfonylureas leading to hypoglycemia.
Uricosuric Agents: Salicylates antagonize the uricosuric action of probenecid
or sulfinpyrazone.
Drug/Laboratory Test Interactions
Depending on the sensitivity/specificity and the test
methodology, the individual components of ENDODAN tablets may cross-react with
assays used in the preliminary detection of cocaine (primary urinary metabolite,
benzoylecgonine) or marijuana (cannabinoids) in human urine. A more specific
alternate chemical method must be used in order to obtain a confirmed analytical
result. The preferred confirmatory method is gas chromatography/mass
spectrometry (GC/MS). Moreover, clinical considerations and professional
judgment should be applied to any drug-of-abuse test result, particularly when
preliminary positive results are used.
Salicylates may increase the protein bound iodine (PBI) result by competing
for the protein binding sites on pre-albumin and possibly thyroid-binding
globulins.
Carcinogenesis
Animal studies to evaluate the carcinogenic potential of oxycodone and
aspirin have not been performed.
Mutagenesis
The combination of oxycodone and aspirin has not been evaluated for
mutagenicity. Oxycodone alone was negative in a bacterial reverse mutation assay
(Ames), an in vitro chromosome aberration assay with
human lymphocytes without metabolic activation and an in
vivo mouse micronucleus assay. Oxycodone was clastogenic in the human
lymphocyte chromosomal assay in the presence of metabolic activation and in the
mouse lymphoma assay with or without metabolic activation. Aspirin induced
chromosome aberrations in cultured human fibroblasts.
Fertility
Animal studies to evaluate the effects of oxycodone on fertility have not
been performed. Aspirin has been shown to inhibit ovulation in rats.
Teratogenic Effects
Oxycodone: Pregnancy Category B Reproduction studies in rats and rabbits demonstrated that oral
administration of oxycodone was not teratogenic or embryo-fetal toxic.
Aspirin: Pregnancy Category D (see PRECAUTIONS )
Salicylates readily cross the placenta and by inhibiting prostaglandin
synthesis, may cause constriction of ductus arteriosus resulting in pulmonary
hypertension and increased fetal mortality and, possibly other untoward fetal
effects. Aspirin use in pregnancy can also result in alteration in maternal and
neonatal hemostasis mechanisms. Maternal aspirin use during later stages of
pregnancy may cause low birth weight, increased incidence of intracranial
hemorrhage in premature infants, stillbirths and neonatal death. Use during
pregnancy, especially in the third trimester, should be avoided.
Safe use of ENDODAN (Oxycodone and Aspirin Tablets, USP) in pregnancy has not
been established relative to possible adverse effects on fetal development.
Therefore, ENDODAN tablets should not be used in pregnant women unless, in the
judgment of the physician, the potential benefits outweigh the possible
hazards.
Nonteratogenic Effects Opioids can cross the placental barrier and have the potential to
cause neonatal respiratory depression. Opioid use during pregnancy may result in
a physically drug-dependent fetus. After birth, the neonate may suffer severe
withdrawal symptoms. Aspirin may produce anemia, ante- or postpartum hemorrhage,
prolonged gestation and labor, and oligohydramnios.
Labor and Delivery
ENDODAN tablets are not recommended for use in women during and
immediately prior to labor and delivery due to its potential effects on
respiratory function in the newborn. Aspirin should be avoided one week prior to
and during labor and delivery because it can result in excessive blood loss at
delivery. Prolonged gestation and prolonged labor due to prostaglandin
inhibition have been reported.
Nursing Mothers
Ordinarily, nursing should not be undertaken while a patient is
receiving ENDODAN tablets because of the possibility of sedation and/or
respiratory depression in the infant. Oxycodone is excreted in breast milk in
low concentrations, and there have been rare reports of somnolence and lethargy
in babies of nursing mothers taking an oxycodone/acetaminophen product.
Salicylic acid has also been detected in breast milk. Adverse effects on
platelet function in the nursing infant exposed to aspirin in breast milk may be
a potential risk. Furthermore, the risk of Reye Syndrome
caused by salicylate in breast milk is unknown. Because of the potential for
serious adverse reactions in nursing infants, a decision should be made whether
to discontinue nursing or to discontinue the drug, taking into account the
potential benefits to the woman and the possible hazards to the nursing
infant.
Pediatric Use
ENDODAN tablets should not be administered to pediatric patients.
Reye Syndrome is a rare but serious disease which can follow flu or chicken pox
in children and teenagers. While the cause of Reye Syndrome is unknown, some
reports claim aspirin (or salicylates) may increase the risk of developing this
disease.
Geriatric Use
Special precaution should be given when determining the dosing
amount and frequency of ENDODAN tablets for geriatric patients, since clearance
of oxycodone may be slightly reduced in this patient population when compared to
younger patients.
Hepatic Impairment
In a pharmacokinetic study of oxycodone in patients with
end-stage liver disease, oxycodone plasma clearance decreased and the
elimination half-life increased. Care should be exercised when oxycodone is used
in patients with hepatic impairment.
Renal Impairment
In a study of patients with end stage renal impairment, mean
elimination half-life was prolonged in uremic patients due to increased volume
of distribution and reduced clearance. Oxycodone should be used with caution in
patients with renal impairment.
Adverse reactions
Serious adverse reactions that may be associated with ENDODAN
tablet use include respiratory depression, apnea, respiratory arrest,
circulatory depression, hypotension, and shock (see
Drug interactions
Drug/Drug Interactions with Oxycodone
Opioid analgesics may enhance the neuromuscular-blocking action
of skeletal muscle relaxants and produce an increase in the degree of
respiratory depression.
Patients receiving CNS depressants such as other opioid analgesics, general
anesthetics, phenothiazines, other tranquilizers, centrally-acting anti-emetics,
sedative-hypnotics or other CNS depressants (including alcohol) concomitantly
with ENDODAN tablets may exhibit an additive CNS depression. When such combined
therapy is contemplated, the dose of one or both agents should be reduced.
Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, naltrexone, and
butorphanol) should be administered with caution to a patient who has received
or is receiving a pure opioid agonist such as oxycodone. These
agonist/antagonist analgesics may reduce the analgesic effect of oxycodone or
may precipitate withdrawal symptoms.
Drug/Drug Interactions with Aspirin
Angiotensin Converting Enzyme (ACE) Inhibitors: The hyponatremic
and hypotensive effects of ACE inhibitors may be diminished by the concomitant
administration of aspirin due to its indirect effect on the renin-angiotensin
conversion pathway.
Acetazolamide: Concurrent use of aspirin and acetazolamide can lead to high
serum concentrations of acetazolamide (and toxicity) due to competition at the
renal tubule for secretion.
Anticoagulant Therapy (Heparin and Warfarin): Patients on anticoagulation
therapy are at increased risk for bleeding because of drug-drug interactions and
the effect on platelets. Aspirin can displace warfarin from protein binding
sites, leading to prolongation of both the prothrombin time and the bleeding
time. Aspirin can increase the anticoagulant activity of heparin, increasing
bleeding risk.
Anticonvulsants: Salicylate can displace protein-bound phenytoin and valproic
acid, leading to a decrease in the total concentration of phenytoin and an
increase in serum valproic acid levels.
Beta Blockers: The hypotensive effects of beta blockers may be diminished by
the concomitant administration of aspirin due to inhibition of renal
prostaglandins, leading to decreased renal blood flow, and salt and fluid
retention.
Diuretics: The effectiveness of diuretics in patients with underlying renal
or cardiovascular disease may be diminished by the concomitant administration of
aspirin due to inhibition of renal prostaglandins, leading to decreased renal
blood flow and salt and fluid retention.
Methotrexate: Aspirin may enhance the serious side and toxicity of
methotrexate due to displacement from its plasma protein binding sites and/or
reduced renal clearance.
Nonsteroidal Anti-inflammatory Drugs (NSAID's): The concurrent use of aspirin
with other NSAID's should be avoided because this may increase bleeding or lead
to decreased renal function. Aspirin may enhance the serious side effects and
toxicity of ketorolac, due to displacement from its plasma protein binding sites
and/or reduced renal clearance.
Oral Hypoglycemics Agents: Aspirin may increase the serum glucose-lowering
action of insulin and sulfonylureas leading to hypoglycemia.
Uricosuric Agents: Salicylates antagonize the uricosuric action of probenecid
or sulfinpyrazone.
Drug/Laboratory Test Interactions
Depending on the sensitivity/specificity and the test
methodology, the individual components of ENDODAN tablets may cross-react with
assays used in the preliminary detection of cocaine (primary urinary metabolite,
benzoylecgonine) or marijuana (cannabinoids) in human urine. A more specific
alternate chemical method must be used in order to obtain a confirmed analytical
result. The preferred confirmatory method is gas chromatography/mass
spectrometry (GC/MS). Moreover, clinical considerations and professional
judgment should be applied to any drug-of-abuse test result, particularly when
preliminary positive results are used.
Salicylates may increase the protein bound iodine (PBI) result by competing
for the protein binding sites on pre-albumin and possibly thyroid-binding
globulins.
How supplied
ENDODAN (oxycodone and aspirin tablets, USP), supplied as a
yellow round tablet, with one face scored and the other debossed with “Endo” and
“610”.
Available in:
Bottles of 100 NDC 60951-310-70
Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F). [See USP
Controlled Room Temperature.]
Dispense in a tight, light-resistant container as defined in the USP, with a
child-resistant closure (as required).
DEA Order Form Required.
Manufactured for:
Endo Pharmaceuticals Inc.
Chadds Ford, Pennsylvania 19317
ENDODAN ® is a Registered Trademark of Endo
Pharmaceuticals
© 2009 Endo Pharmaceuticals
Printed in U.S.A. 2005701/September, 2009
Clinical pharmacology
Central Nervous System
Oxycodone is a semisynthetic pure opioid agonist whose principal
therapeutic action is analgesia. Other pharmacological effects of oxycodone
include anxiolysis, euphoria and feelings of relaxation. These effects are
mediated by receptors (notably μ and κ) in the central nervous system for
endogenous opioid-like compounds such as endorphins and enkephalins. Oxycodone
produces respiratory depression through direct activity at respiratory centers
in the brain stem and depresses the cough reflex by direct effect on the center
of the medulla.
Aspirin (acetylsalicylic acid) works by inhibiting the body’s production of
prostaglandins, including prostaglandins involved in inflammation.
Prostaglandins cause pain sensations by stimulating muscle contractions and
dilating blood vessels throughout the body. In the CNS, aspirin works on the
hypothalamus heat-regulating center to reduce fever, however, other mechanisms
may be involved.
Gastrointestinal Tract and Other Smooth Muscle
Oxycodone reduces motility by increasing smooth muscle tone in
the stomach and duodenum. In the small intestine, digestion of food is delayed
by decreases in propulsive contractions. Other opioid effects include
contraction of biliary tract smooth muscle, spasm of the Sphincter of Oddi,
increased ureteral and bladder sphincter tone, and a reduction in uterine tone.
Aspirin can produce gastrointestinal injury (lesions, ulcers) through a
mechanism that is not yet completely understood, but may involve a reduction in
eicosanoid synthesis by the gastric mucosa. Decreased production of
prostaglandins may compromise the defenses of the gastric mucosa and the
activity of substances involved in tissue repair and ulcer healing.
Cardiovascular System
Oxycodone may produce a release of histamine and may be
associated with orthostatic hypotension, and other symptoms, such as pruritus,
flushing, red eyes, and sweating.
Platelet Aggregation
Aspirin affects platelet aggregation by irreversibly inhibiting
prostaglandin cyclo-oxygenase. This effect lasts for the life of the platelet
and prevents the formation of the platelet aggregating factor thromboxane A2.
Nonacetylated salicylates do not inhibit this enzyme and have no effect on
platelet aggregation. At somewhat higher doses, aspirin reversibly inhibits the
formation of prostaglandin 12 (prostacyclin), which is an arterial vasodilator
and inhibits platelet aggregation.
Pharmacokinetics
Absorption and Distribution
The mean absolute oral bioavailability of oxycodone in cancer patients was
reported to be about 87%. Oxycodone has been shown to be 45% bound to human
plasma proteins in vitro . The volume of distribution
after intravenous administration is 211.9 ±186.6 L.
Aspirin is hydrolyzed primarily to salicylic acid in the gut wall and during
first-pass metabolism through the liver. Salicylic acid is absorbed rapidly from
the stomach, but most of the absorption occurs in the proximal small intestine.
Following absorption, salicylate is distributed to most body tissues and fluids,
including fetal tissues, breast milk, and the CNS. High concentrations are found
in the liver and kidneys. Salicylate is variably bound to serum proteins,
particularly albumin.
Metabolism and Elimination
A high portion of oxycodone is N-dealkylated to noroxycodone during
first-pass metabolism. Oxymorphone, is formed by the O-demethylation of
oxycodone. The metabolism of oxycodone to oxymorphone is catalyzed by CYP2D6.
Free and conjugated noroxycodone, free and conjugated oxycodone, and oxymorphone
are excreted in human urine following a single oral dose of oxycodone.
Approximately 8% to 14% of the dose is excreted as free oxycodone over 24 hours
after administration. Following a single, oral dose of oxycodone, the mean ± SD
elimination half-life is 3.51 ± 1.43 hours.
The biotransformation of aspirin occurs primarily in the liver by the
microsomal enzyme system. With a plasma half-life of approximately 15 minutes,
aspirin is rapidly hydrolyzed to salicylate. At low doses, salicylate
elimination follows first-order kinetics. The plasma half-life of salicylate is
approximately 2 to 3 hours.
Approximately 10% of aspirin is excreted as unchanged salicylate in the
urine. The major metabolites excreted in the urine are salicyluric acid (75%),
salicyl phenolic glucuronide (10%), salicyl acyl glucuronide (5%), and gentisic
and gentisuric acid (less than 1%) each. Eighty to 100% of a single dose is
excreted in the urine within 24 to 72 hours.
Package label
LABEL IMAGE
1 organization
1 product
Product
ENDODANOrganization
STAT RX USA LLC