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Primlev 1143A00 10-13_10-13 10/30/13 5:28 PM Page 1 extent with sulfuric acid and cysteine. After hepatic conjugation, 90 PRIMLEV TM should be given with caution to patients with CNS
to 100% of the drug is recovered in the urine within the first day.
depression, elderly or debilitated patients, patients with severe About 4% of acetaminophen is metabolized via cytochrome P450 impairment of hepatic, pulmonary, or renal function, hypothyroidism, oxidase to a toxic metabolite which is further detoxified by conjugation Addison's disease, prostatic hypertrophy, urethral stricture, acute with glutathione, present in a fixed amount. It is believed that the toxic alcoholism, delirium tremens, kyphoscoliosis with respiratory metabolite NAPQI (N-acetyl-p-benzoquinoneimine, N-acetylimidoquinone) depression, myxedema, and toxic psychosis.
is responsible for liver necrosis. High doses of acetaminophen may PRIMLEV TM
Available in 5/300, 7.5/300 & 10/300 mg may obscure the diagnosis or clinical course in patients deplete the glutathione stores so that inactivation of the toxic with acute abdominal conditions. Oxycodone may aggravate metabolite is decreased. At high doses, the capacity of metabolic convulsions in patients with convulsive disorders, and al opioids may pathways for conjugation with glucuronic acid and sulfuric acid induce or aggravate seizures in some clinical settings.
may be exceeded, resulting in increased metabolism of HEPATOTOXICITY
acetaminophen by alternate pathways.
Fol owing administration of PRIMLEV TM, anaphylactic reactions have
ACETAMINOPHEN HAS BEEN ASSOCIATED WITH CASES OF been reported in patients with a known hypersensitivity to codeine, a INDICATIONS AND USAGE
ACUTE LIVER FAILURE, AT TIMES RESULTING IN LIVER compound with a structure similar to morphine and oxycodone. The PRIMLEV TM (oxycodone and acetaminophen tablets, USP) is
TRANSPLANT AND DEATH. MOST OF THE CASES OF LIVER frequency of this possible cross-sensitivity is unknown.
indicated for the relief of moderate to moderately severe pain.
INJURY ARE ASSOCIATED WITH THE USE OF ACETAMINOPHEN Interactions with Other CNS Depressants
AT DOSES THAT EXCEED 4000 MILLIGRAMS PER DAY, AND CONTRAINDICATIONS
Patients receiving other opioid analgesics, general anesthetics, OFTEN INVOLVE MORE THAN ONE ACETAMINOPHEN- PRIMLEV TM should not be administered to patients with known
phenothiazines, other tranquilizers, central y-acting anti-emetics, hypersensitivity to oxycodone, acetaminophen, or any other sedative-hypnotics or other CNS depressants (including alcohol) concomitantly with PRIMLEV TM may exhibit an additive CNS
DESCRIPTION
Oxycodone is contraindicated in any situation where opioids are depression. When such combined therapy is contemplated, the dose Each tablet, for oral administration, contains oxycodone hydrochloride of one or both agents should be reduced.
and acetaminophen in the fol owing strengths: contraindicated including patients with significant respiratory depression (in unmonitored settings or the absence of resuscitative Interactions with Mixed Agonist/Antagonist Opioid Analgesics
equipment) and patients with acute or severe bronchial asthma or Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and hypercarbia. Oxycodone is contraindicated in the setting of suspected butorphanol) should be administered with caution to a patient who has *5 mg oxycodone HCl is equivalent to 4.4815 mg of oxycodone.
received or is receiving a course of therapy with a pure opioid agonist WARNINGS
analgesic such as oxycodone. In this situation, mixed agonist/antagonist Misuse, Abuse and Diversion of Opioids
analgesics may reduce the analgesic effect of oxycodone and/or may *7.5 mg oxycodone HCl is equivalent to 6.7228 mg of oxycodone.
Oxycodone is an opioid agonist of the morphine-type. Such drugs are precipitate withdrawal symptoms in these patients.
sought by drug abusers and people with addiction disorders and are Ambulatory Surgery and Postoperative Use
Oxycodone and other morphine-like opioids have been shown to *10 mg oxycodone HCl is equivalent to 8.9637 mg of oxycodone.
Oxycodone can be abused in a manner similar to other opioid decrease bowel motility. Ileus is a common postoperative Al strengths of PRIMLEVTM also contain the fol owing inactive
agonists, legal or il icit. This should be considered when prescribing complication, especial y after intra-abdominal surgery with use of ingredients: col oidal silicon dioxide, croscarmel ose sodium, opioid analgesia. Caution should be taken to monitor for decreased PRIMLEV TM in situations where the physician or
crospovidone, microcrystal ine cel ulose, povidone, pregelatinized pharmacist is concerned about an increased risk of misuse, abuse, bowel motility in postoperative patients receiving opioids. Standard supportive therapy should be implemented.
or diversion. Concerns about misuse, addiction, and diversion should In addition, the 5 mg/300 mg strength contains D&C Yel ow #10; the not prevent the proper management of pain.
Use in Pancreatic/Biliary Tract Disease
7.5 mg/300 mg strength contains FD&C Red #40 Aluminum Lake; the Oxycodone may cause spasm of the Sphincter of Oddi and should be 10 mg/300 mg strength contains FD&C Yel ow #6 Aluminum Lake. Healthcare professionals should contact their State Professional used with caution in patients with biliary tract disease, including acute Licensing Board or State Control ed Substances Authority for Oxycodone, 14-hydroxydihydrocodeinone, is a semisynthetic opioid pancreatitis. Opioids like oxycodone may cause increases in the information on how to prevent and detect abuse or diversion of analgesic which occurs as a white, odorless, crystal ine powder having a saline, bitter taste. The molecular formula for oxycodone Tolerance and Physical Dependence
Administration of PRIMLEV TM should be closely monitored for the
18H21NO4•HCl and the molecular weight is 351.82.
Tolerance is the need for increasing doses of opioids to maintain a It is derived from the opium alkaloid thebaine, and may be represented fol owing potential y serious adverse reactions and complications: defined effect such as analgesia (in the absence of disease Respiratory Depression
progression or other external factors). Physical dependence is Respiratory depression is a hazard with the use of oxycodone, one manifested by withdrawal symptoms after abrupt discontinuation of of the active ingredients in PRIMLEV TM, as with al opioid agonists.
a drug or upon administration of an antagonist. Physical dependence Elderly and debilitated patients are at particular risk for respiratory and tolerance are not unusual during chronic opioid therapy.
depression as are non-tolerant patients given large initial doses of The opioid abstinence or withdrawal syndrome is characterized by oxycodone or when oxycodone is given in conjunction with other some or al of the fol owing: restlessness, lacrimation, rhinorrhea, agents that depress respiration. Oxycodone should be used with yawning, perspiration, chil s, myalgia, and mydriasis. Other symptoms extreme caution in patients with acute asthma, chronic obstructive also may develop, including: irritability, anxiety, backache, joint pain, PRIMLEV TM
pulmonary disorder (COPD), cor pulmonale, or preexisting respiratory weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, Oxycodone and
impairment. In such patients, even usual therapeutic doses of diarrhea, or increased blood pressure, respiratory rate, or heart rate.
Acetaminophen
oxycodone may decrease respiratory drive to the point of apnea. In In general, opioids should not be abruptly discontinued (see DOSAGE Tablets, USP
these patients alternative non-opioid analgesics should be considered, AND ADMINISTRATION: Cessation of Therapy).
and opioids should be employed only under careful medical Acetaminophen, 4'-hydroxyacetanilide, is a non-opiate, non-salicylate Information for Patients/Caregivers
supervision at the lowest effective dose.
1143A00 ߑ Only 10/13
analgesic and antipyretic which occurs as a white, odorless, The fol owing information should be provided to patients receiving crystal ine powder, possessing a slightly bitter taste. The molecular In case of respiratory depression, a reversal agent such as naloxone PRIMLEVTM by their physician, nurse, pharmacist, or caregiver:
hydrochloride may be utilized (see OVERDOSAGE).
1. Patients should be aware that PRIMLEV TM contains oxycodone,
151.16. It may be represented by the fol owing structural formula: Head Injury and Increased Intracranial Pressure
which is a morphine-like substance.
The respiratory depressant effects of opioids include carbon dioxide 2. Patients should be instructed to keep PRIMLEV TM in a secure
retention and secondary elevation of cerebrospinal fluid pressure, and place out of the reach of children. In the case of accidental may be markedly exaggerated in the presence of head injury, other ingestions, emergency medical care should be sought immediately.
intracranial lesions or a pre-existing increase in intracranial pressure.
3. When PRIMLEV TM is no longer needed, the unused tablets
Oxycodone produces effects on pupil ary response and consciousness should be destroyed by flushing down the toilet.
which may obscure neurologic signs of worsening in patients with 4. Patients should be advised not to adjust the medication dose themselves. Instead, they must consult with their prescribing Hypotensive Effect
Oxycodone may cause severe hypotension particularly in individuals 5. Patients should be advised that PRIMLEV TM may impair mental
CLINICAL PHARMACOLOGY
whose ability to maintain blood pressure has been compromised by and/or physical ability required or the performance of potential y Central Nervous System
a depleted blood volume, or after concurrent administration with hazardous tasks (e.g., driving, operating heavy machinery).
Oxycodone is a semisynthetic pure opioid agonist whose principal drugs which compromise vasomotor tone such as phenothiazines.
therapeutic action is analgesia. Other pharmacological effects of 6. Patients should not combine PRIMLEVTM with alcohol, opioid
oxycodone include anxiolysis, euphoria and feelings of relaxation.
Oxycodone, like al opioid analgesics of the morphine-type, should analgesics, tranquilizers, sedatives, or other CNS depressants These effects are mediated by receptors (notably µ and k) in the be administered with caution to patients in circulatory shock, since unless under the recommendation and guidance of a physician. central nervous system for endogenous opioid-like compounds vasodilation produced by the drug may further reduce cardiac output When co-administered with another CNS depressant, PRIMLEVTM
such as endorphins and enkephalins. Oxycodone produces and blood pressure. Oxycodone may produce orthostatic hypotension can cause dangerous additive central nervous system or respiratory depression through direct activity at respiratory centers respiratory depression, which can result in serious injury or death.
in the brain stem and depresses the cough reflex by direct effect Hepatotoxicity
7. The safe use of PRIMLEV TM during pregnancy has not been
Acetaminophen has been associated with cases of acute liver failure, established; thus, women who are planning to become pregnant Acetaminophen is a non-opiate, non-salicylate analgesic and at times resulting in liver transplant and death. Most of the cases of or are pregnant should consult with their physician before taking antipyretic. The site and mechanism for the analgesic effect of liver injury are associated with the use of acetaminophen at doses PRIMLEV TM.
acetaminophen has not been determined. The antipyretic effect of that exceed 4000 mil igrams per day, and often involve more than one 8. Nursing mothers should consult with their physicians about acetaminophen is accomplished through the inhibition of endogenous acetaminophen-containing product. The excessive intake of whether to discontinue nursing or discontinue PRIMLEVTM because
pyrogen action on the hypothalamic heat-regulating centers.
acetaminophen may be intentional to cause self-harm or unintentional of the potential for serious adverse reactions to nursing infants.
Gastrointestinal Tract and Other Smooth Muscle
as patients attempt to obtain more pain relief or unknowingly take 9. Patients who are treated with PRIMLEV TM for more than a few
Oxycodone reduces motility by increasing smooth muscle tone in the other acetaminophen-containing products.
weeks should be advised not to abruptly discontinue the stomach and duodenum. In the smal intestine, digestion of food is The risk of acute liver failure is higher in individuals with underlying medication. Patients should consult with their physician for a delayed by decreases in propulsive contractions. Other opioid effects liver disease and in individuals who ingest alcohol while taking gradual discontinuation dose schedule to taper off the medication.
include contraction of biliary tract smooth muscle, spasm of the 10. Patients should be advised that PRIMLEV TM is a potential drug
Sphincter of Oddi, increased ureteral and bladder sphincter tone, and Instruct patients to look for acetaminophen or APAP on package of abuse. They should protect it from theft, and it should never labels and not to use more than one product that contains be given to anyone other than the individual for whom it was Cardiovascular System
acetaminophen. Instruct patients to seek medical attention Oxycodone may produce a release of histamine and may be immediately upon ingestion of more than 4000 mil igrams of 11. Do not take PRIMLEVTM if you are al ergic to any of its ingredients.
associated with orthostatic hypotension, and other symptoms, such acetaminophen per day, even if they feel wel .
12. If you develop signs of al ergy such as a rash or difficulty as pruritus, flushing, red eyes, and sweating.
Serious Skin Reactions
breathing, stop taking PRIMLEV TM and contact your healthcare
Pharmacokinetics
Rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson 13. Do not take more than 4000 mil igrams of acetaminophen per day.
The mean absolute oral bioavailability of oxycodone in cancer patients Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be Cal your doctor if you took more than the recommended dose.
was reported to be about 87%. Oxycodone has been shown to be fatal. Patients should be informed about the signs of serious skin 45% bound to human plasma proteins in vitro. The volume of Laboratory Tests
distribution after intravenous administration is 211.9 ±186.6 L.
reactions, and use of the drug should be discontinued at the first Although oxycodone may cross-react with some drug urine tests, no appearance of skin rash or any other sign of hypersensitivity.
available studies were found which determined the duration of Absorption of acetaminophen is rapid and almost complete from the detectability of oxycodone in urine drug screens. However, based on GI tract after oral administration. With overdosage, absorption is Hypersensitivity/anaphylaxis
pharmacokinetic data, the approximate duration of detectability for a complete in 4 hours. Acetaminophen is relatively uniformly distributed There have been post-marketing reports of hypersensitivity and single dose of oxycodone is roughly estimated to be one to two days throughout most body fluids. Binding of the drug to plasma proteins anaphylaxis associated with use of acetaminophen. Clinical signs is variable; only 20% to 50% may be bound at the concentrations included swel ing of the face, mouth, and throat, respiratory distress, encountered during acute intoxication.
urticaria, rash, pruritus, and vomiting. There were infrequent reports Urine testing for opiates may be performed to determine il icit drug use and for medical reasons such as evaluation of patients with Metabolism and Elimination
of life-threatening anaphylaxis requiring emergency medical attention.
altered states of consciousness or monitoring efficacy of drug A high portion of oxycodone is N-dealkylated to noroxycodone during Instruct patients to discontinue PRIMLEVTM immediately and seek
rehabilitation efforts. The preliminary identification of opiates in urine first-pass metabolism. Oxymorphone, is formed by the O- medical care if they experience these symptoms. Do not prescribe involves the use of an immunoassay screening and thin-layer demethylation of oxycodone. The metabolism of oxycodone to PRIMLEV TM for patients with acetaminophen al ergy.
chromatography (TLC). Gas chromatography/mass spectrometry oxymorphone is catalyzed by CYP2D6. Free and conjugated PRECAUTIONS
(GC/MS) may be utilized as a third-stage identification step in the noroxycodone, free and conjugated oxycodone, and oxymorphone are medical investigational sequence for opiate testing after immunoassay excreted in human urine fol owing a single oral dose of oxycodone.
Opioid analgesics should be used with caution when combined with and TLC. The identities of 6-keto opiates (e.g., oxycodone) can further Approximately 8% to 14% of the dose is excreted as free oxycodone CNS depressant drugs, and should be reserved for cases where the be differentiated by the analysis of their methoxime-trimethylsilyl over 24 hours after administration. Fol owing a single, oral dose of benefits of opioid analgesia outweigh the known risks of respiratory oxycodone, the mean ± SD elimination half-life is 3.51 ± 1.43 hours.
depression, altered mental state, and postural hypotension.
Drug/Drug Interactions with Oxycodone
Acetaminophen is metabolized in the liver via cytochrome P450 Acute Abdominal Conditions
Opioid analgesics may enhance the neuromuscular-blocking action microsomal enzyme. About 80 to 85% of the acetaminophen in the The administration of PRIMLEV TM or other opioids may obscure the
of skeletal muscle relaxants and produce an increase in the degree of body is conjugated principal y with glucuronic acid and to a lesser diagnosis or clinical course in patients with acute abdominal conditions.
Primlev 1143A00 10-13_10-13 10/30/13 5:28 PM Page 2 Patients receiving CNS depressants such as other opioid analgesics, Hypersensitivity reactions may include: Skin eruptions, urticarial, OVERDOSAGE
general anesthetics, phenothiazines, other tranquilizers, central y-acting erythematous skin reactions. Hematologic reactions may include: Fol owing an acute overdosage, toxicity may result from the anti-emetics, sedative-hypnotics or other CNS depressants (including Thrombocytopenia, neutropenia, pancytopenia, hemolytic anemia.
alcohol) concomitantly with PRIMLEV TM may exhibit an additive CNS
Rare cases of agranulocytosis has likewise been associated with Signs and Symptoms
depression. When such combined therapy is contemplated, the dose acetaminophen use. In high doses, the most serious adverse effect Toxicity from oxycodone poisoning includes the opioid triad of: of one or both agents should be reduced. The concurrent use of is a dose-dependent, potential y fatal hepatic necrosis. Renal tubular pinpoint pupils, depression of respiration, and loss of consciousness.
anticholinergics with opioids may produce paralytic ileus.
necrosis and hypoglycemic coma also may occur.
Serious overdosage with oxycodone is characterized by respiratory Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, naltrexone, Other adverse reactions obtained from postmarketing experiences depression (a decrease in respiratory rate and/or tidal volume, Cheyne- and butorphanol) should be administered with caution to a patient who with PRIMLEV TM are listed by organ system and in decreasing order
Stokes respiration, cyanosis), extreme somnolence progressing to has received or is receiving a pure opioid agonist such as oxycodone.
stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and These agonist/antagonist analgesics may reduce the analgesic effect of Body as a Whole
sometimes bradycardia and hypotension. In severe overdosage, oxycodone or may precipitate withdrawal symptoms.
Anaphylactoid reaction, al ergic reaction, malaise, asthenia, fatigue, apnea, circulatory col apse, cardiac arrest, and death may occur.
Drug/Drug Interactions with Acetaminophen
chest pain, fever, hypothermia, thirst, headache, increased sweating, In acetaminophen overdosage: dose-dependent potential y fatal Alcohol, ethyl: Hepatotoxicity has occurred in chronic alcoholics accidental overdose, non-accidental overdose hepatic necrosis is the most serious adverse effect. Renal tubular fol owing various dose levels (moderate to excessive) of acetaminophen.
Cardiovascular
necrosis, hypoglycemic coma and coagulation defects may also Anticholinergics: The onset of acetaminophen effect may be delayed Hypotension, hypertension, tachycardia, orthostatic hypotension, occur. Early symptoms fol owing a potential y hepatotoxic overdose or decreased slightly, but the ultimate pharmacological effect is not may include: nausea, vomiting, diaphoresis, and general malaise.
significantly affected by anticholinergics.
Central and Peripheral Nervous System
Clinical and laboratory evidence of hepatic toxicity may not be Oral Contraceptives: Increase in glucuronidation resulting in increased Stupor, tremor, paraesthesia, hypoaesthesia, lethargy, seizures, anxiety, apparent until 48 to 72 hours post-ingestion.
plasma clearance and a decreased half-life of acetaminophen.
mental impairment, agitation, cerebral edema, confusion, dizziness Treatment
Charcoal (activated): Reduces acetaminophen absorption when Fluid and Electrolyte
A single or multiple drug overdose with oxycodone and acetaminophen administered as soon as possible after overdose.
Dehydration, hyperkalemia, metabolic acidosis, respiratory alkalosis is a potential y lethal polydrug overdose, and consultation with a Beta Blockers (Propranolol): Propranolol appears to inhibit the regional poison control center is recommended. Immediate treatment enzyme systems responsible for the glucuronidation and oxidation of Gastrointestinal
includes support of cardiorespiratory function and measures to reduce acetaminophen. Therefore, the pharmacologic effects of Dyspepsia, taste disturbances, abdominal pain, abdominal distention, drug absorption. Oxygen, intravenous fluids, vasopressors, and other sweating increased, diarrhea, dry mouth, flatulence, gastro-intestinal supportive measures should be employed as indicated. Assisted or disorder, nausea, vomiting, pancreatitis, intestinal obstruction, ileus Loop diuretics: The effects of the loop diuretic may be decreased control ed ventilation should also be considered.
because acetaminophen may decrease renal prostaglandin excretion Transient elevations of hepatic enzymes, increase in bilirubin, Primary attention should be given to the reestablishment of adequate hepatitis, hepatic failure, jaundice, hepatotoxicity, hepatic disorder Lamotrigine: Serum lamotrigine concentrations may be reduced, respiratory exchange through provision of a patent airway and the producing a decrease in therapeutic effects.
Hearing and Vestibular
institution of assisted or control ed ventilation. The narcotic antagonist naloxone hydrochloride is a specific antidote against respiratory Probenecid: Probenecid may increase the therapeutic effectiveness depression which may result from overdosage or unusual sensitivity Hematologic
to narcotics, including oxycodone. Since the duration of action of Zidovudine: The pharmacologic effects of zidovudine may be oxycodone may exceed that of the antagonist, the patient should be decreased because of enhanced non-hepatic or renal clearance of Hypersensitivity
kept under continued surveil ance, and repeated doses of the antagonist Acute anaphylaxis, angioedema, asthma, bronchospasm, laryngeal should be administered as needed to maintain adequate respiration. A Drug/Laboratory Test Interactions
narcotic antagonist should not be administered in the absence of Depending on the sensitivity/specificity and the test methodology, the Metabolic and Nutritional
clinical y significant respiratory or cardiovascular depression.
individual components of PRIMLEV TM may cross-react with assays
Hypoglycemia, hyperglycemia, acidosis, alkalosis used in the preliminary detection of cocaine (primary urinary Musculoskeletal
Gastric decontamination with activated charcoal should be metabolite, benzoylecgonine) or marijuana (cannabinoids) in human administered just prior to N-acetylcysteine (NAC) to decrease systemic urine. A more specific alternate chemical method must be used in absorption if acetaminophen ingestion is known or suspected to have order to obtain a confirmed analytical result. The preferred occurred within a few hours of presentation. Serum acetaminophen confirmatory method is gas chromatography/mass spectrometry levels should be obtained immediately if the patient presents 4 hours (GC/MS). Moreover, clinical considerations and professional Psychiatric
or more after ingestion to assess potential risk of hepatotoxicity; judgment should be applied to any drug-of-abuse test result, Drug dependence, drug abuse, insomnia, confusion, anxiety, acetaminophen levels drawn less than 4 hours post-ingestion may be particularly when preliminary positive results are used.
agitation, depressed level of consciousness, nervousness, misleading. To obtain the best possible outcome, NAC should be Acetaminophen may interfere with home blood glucose measurement hal ucination, somnolence, depression, suicide administered as soon as possible where impending or evolving liver systems; decreases of > 20% in mean glucose values may be noted.
Respiratory System
injury is suspected. Intravenous NAC may be administered when This effect appears to be drug, concentration and system dependent.
Bronchospasm, dyspnea, hyperpnea, pulmonary edema, tachypnea, circumstances preclude oral administration.
Carcinogenesis, Mutagenesis, Impairment of Fertility
aspiration, hypoventilation, laryngeal edema Vigorous supportive therapy is required in severe intoxication.
Skin and Appendages
Procedures to limit the continuing absorption of the drug must be Animal studies to evaluate the carcinogenic potential of oxycodone readily performed since the hepatic injury is dose dependent and and acetaminophen have not been performed.
Urogenital
occurs early in the course of intoxication.
Interstitial nephritis, papil ary necrosis, proteinuria, renal insufficiency DOSAGE AND ADMINISTRATION
The combination of oxycodone and acetaminophen has not been Dosage should be adjusted according to the severity of the pain and evaluated for mutagenicity. Oxycodone alone was negative in a DRUG ABUSE AND DEPENDENCE
the response of the patient. It may occasional y be necessary to bacterial reverse mutation assay (Ames), an in vitro chromosome PRIMLEVTM is a Schedule II control ed substance. Oxycodone is a
exceed the usual dosage recommended below in cases of more aberration assay with human lymphocytes without metabolic mu-agonist opioid with an abuse liability similar to morphine.
severe pain or in those patients who have become tolerant to the activation and an in vivo mouse micronucleus assay. Oxycodone was Oxycodone, like morphine and other opioids used in analgesia, can analgesic effect of opioids. If pain is constant, the opioid analgesic clastogenic in the human lymphocyte chromosomal assay in the be abused and is subject to criminal diversion.
should be given at regular intervals on an around-the-clock schedule.
presence of metabolic activation and in the mouse lymphoma assay Drug addiction is defined as an abnormal, compulsive use, use for non- PRIMLEV TM is given oral y.
with or without metabolic activation.
medical purposes of a substance despite physical, psychological, The usual adult dosage of PRIMLEVTM is as fol ows. The total daily
occupational or interpersonal difficulties resulting from such use, and dose of acetaminophen should not exceed 4 grams.
Animal studies to evaluate the effects of oxycodone on fertility have continued use despite harm or risk of harm. Drug addiction is a treatable disease, utilizing a multi-disciplinary approach, but relapse is common.
Pregnancy
Opioid addiction is relatively rare in patients with chronic pain but may be more common in individuals who have a past history of alcohol or substance abuse or dependence. Pseudoaddiction refers to pain relief Animal reproductive studies have not been conducted with seeking behavior of patients whose pain is poorly managed. It is PRIMLEV TM. It is also not known whether PRIMLEV TM can cause
considered an iatrogenic effect of ineffective pain management. The fetal harm when administered to a pregnant woman or can affect health care provider must assess continuously the psychological and reproductive capacity. PRIMLEV TM should not be given to a pregnant
clinical condition of a pain patient in order to distinguish addiction from woman unless in the judgment of the physician, the potential benefits pseudoaddiction and thus, be able to treat the pain adequately.
Physical dependence on a prescribed medication does not signify addiction. Physical dependence involves the occurrence of a withdrawal Opioids can cross the placental barrier and have the potential to cause syndrome when there is sudden reduction or cessation in drug use or Cessation of Therapy
neonatal respiratory depression. Opioid use during pregnancy may if an opiate antagonist is administered. Physical dependence can be In patients treated with PRIMLEVTM for more than a few weeks who
result in a physical y drug-dependent fetus. After birth, the neonate detected after a few days of opioid therapy. However, clinical y no longer require therapy, doses should be tapered gradual y to prevent may suffer severe withdrawal symptoms.
significant physical dependence is only seen after several weeks of signs and symptoms of withdrawal in the physical y dependent patient.
Labor and Delivery
relatively high dosage therapy. In this case, abrupt discontinuation of HOW SUPPLIED
the opioid may result in a withdrawal syndrome. If the discontinuation PRIMLEV TM is not recommended for use in women during and
PRIMLEV TM is supplied as fol ows:
immediately prior to labor and delivery due to its potential effects on of opioids is therapeutical y indicated, gradual tapering of the drug over PRIMLEV TM 5 mg/300 mg
respiratory function in the newborn.
a 2-week period wil prevent withdrawal symptoms. The severity of the withdrawal syndrome depends primarily on the daily dosage of the Yel ow, capsule-shaped, convex face tablets, debossed “A” score “P” Nursing Mothers
opioid, the duration of therapy and medical status of the individual.
on one side and “681” on the other side.
Ordinarily, nursing should not be undertaken while a patient is The withdrawal syndrome of oxycodone is similar to that of morphine.
PRIMLEV TM because of the possibility of sedation and/or
respiratory depression in the infant. Oxycodone is excreted in breast This syndrome is characterized by yawning, anxiety, increased heart PRIMLEV TM 7.5 mg/300 mg
milk in low concentrations, and there have been rare reports of rate and blood pressure, restlessness, nervousness, muscle aches, Red, capsule-shaped, flat face, beveled edge tablets, debossed “A P” somnolence and lethargy in babies of nursing mothers taking an tremor, irritability, chil s alternating with hot flashes, salivation, on one side and “682” on the other side.
oxycodone/acetaminophen product. Acetaminophen is also excreted anorexia, severe sneezing, lacrimation, rhinorrhea, dilated pupils, in breast milk in low concentrations.
diaphoresis, piloerection, nausea, vomiting, abdominal cramps, diarrhea and insomnia, and pronounced weakness and depression.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
“Drug-seeking” behavior is very common in addicts and drug PRIMLEV TM 10 mg/300 mg
abusers. Drug-seeking tactics include emergency cal s or visits near Orange, oval-shaped, convex face tablets, debossed “A P” on one Geriatric Use
the end of office hours, refusal to undergo appropriate examination, side and “683” on the other side.
Special precaution should be given when determining the dosing testing or referral, repeated “loss” of prescriptions, tampering with PRIMLEV TM for geriatric patients, since
prescriptions and reluctance to provide prior medical records or clearance of oxycodone may be slightly reduced in this patient contact information for other treating physician(s). “Doctor Shopping” population when compared to younger patients.
to obtain additional prescriptions is common among drug abusers Store at 20° to 25°C (68° to 77°F). [see USP Control ed Room Hepatic Impairment
and people suffering from untreated infection.
In a pharmacokinetic study of oxycodone in patients with end-stage Abuse and addiction are separate and distinct from physical Dispense in a tight, light-resistant container as defined in the USP, liver disease, oxycodone plasma clearance decreased and the dependence and tolerance. Physicians should be aware that addiction with a child-resistant closure (as required).
elimination half-life increased. Care should be exercised when may not be accompanied by concurrent tolerance and symptoms of oxycodone is used in patients with hepatic impairment.
physical dependence in al addicts. In addition, abuse of opioids can For further product information, please visit www.akrimax.com or cal Renal Impairment
occur in the absence of true addiction and is characterized by misuse our medical communications department tol -free at 1-888-383-1733.
In a study of patients with end stage renal impairment, mean for non-medical purposes, often in combination with other psychoactive elimination half-life was prolonged in uremic patients due to increased substances. Oxycodone, like other opioids, has been diverted for non- volume of distribution and reduced clearance. Oxycodone should be medical use. Careful record-keeping of prescribing information, used with caution in patients with renal impairment.
including quantity, frequency, and renewal requests is strongly advised.
ADVERSE REACTIONS
Proper assessment of the patient, proper prescribing practices, Manufactured for Akrimax Pharmaceuticals, LLC, Cranford, NJ 07016 Serious adverse reactions that may be associated with PRIMLEVTM
periodic reevaluation of therapy, and proper dispensing and storage use include respiratory depression, apnea, respiratory arrest, are appropriate measures that help to limit abuse of opioid drugs.
circulatory depression, hypotension, and shock (see OVERDOSAGE).
Like other opioid medications, PRIMLEVTM is subject to the Federal
The most frequently observed non-serious adverse reactions include Control ed Substances Act. After chronic use, PRIMLEVTM should
lightheadedness, dizziness, drowsiness or sedation, nausea, and not be discontinued abruptly when it is thought that the patient has vomiting. These effects seem to be more prominent in ambulatory become physical y dependent on oxycodone.
than in nonambulatory patients, and some of these adverse reactions Interactions with Alcohol and Drugs of Abuse
may be al eviated if the patient lies down. Other adverse reactions Oxycodone may be expected to have additive effects when used in include euphoria, dysphoria, constipation, and pruritus.
conjunction with alcohol, other opioids, or il icit drugs that cause

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