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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
XARTEMIS XR (NDA-204031)
(ACETAMINOPHEN; OXYCODONE HYDROCHLORIDE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
09/18/2018 (SUPPL-5)
Boxed Warning
Boxed Warning(Additions and/or revisions are underlined)
WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION
STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL
INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4
INTERACTION; HEPATOTOXICITY; and RISKS FROM CONCOMITANT USE WITH
BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
Addiction, Abuse, and Misuse
XARTEMIS XR 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
XARTEMIS XR, and monitor all patients regularly for the development of these behaviors and
Conditions.
Opioid Analgesic Risk Evaluation and Mitigation Strategy (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.
...
5 Warnings and Precautions
5.2 Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)(Newly added subsection)
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 Risk Evaluation and Mitigation Strategy (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 do all of the following:
- Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain.
Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG.
Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them.
Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities.
To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint.
12/16/2016 (SUPPL-3)
Boxed Warning
Underlined additions to box warning heading title; ingestion replaces exposure throughout section
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; HEPATOTOXICITY; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
Newly added:
Cytochrome P450 3A4 Interaction
The concomitant use of XARTEMIS XR with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. Monitor patients receiving XARTEMIS XR and any CYP3A4 inhibitor or inducer.
Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants
Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
Reserve concomitant prescribing of XARTEMIS XR and benzodiazepines or other CNS
depressants for use in patients for whom alternative treatment options are inadequate.
Limit dosages and durations to the minimum required.
Follow patients for signs and symptoms of respiratory depression and sedation.
4 Contraindications
Additions and/or revisions underlined:
Significant respiratory depression
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
Known or suspected gastrointestinal obstruction, including paralytic ileus
Hypersensitivity to oxycodone or acetaminophen (e.g., anaphylaxis)
5 Warnings and Precautions
Additions and/or revisions underlined throughout section, unless otherwise noted.
Patients at increased risk may be prescribed opioids such as XARTEMIS XR, but use in such patients necessitates intensive counseling about the risks and proper use of XARTEMIS XR along with intensive monitoring for signs of addiction, abuse, and misuse ...
Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing XARTEMIS XR. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.
Abuse or misuse of XARTEMIS XR by crushing, chewing, snorting …
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), XARTEMIS XR 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 XARTEMIS XR.
Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of XARTEMIS XR in patients with impaired consciousness or coma.
XARTEMIS XR is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.
The oxycodone in XARTEMIS XR 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.
Newly added subsection:
The oxycodone in XARTEMIS XR may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during XARTEMIS XR therapy.
Newly added subsection:
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 XARTEMIS XR. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms.
When discontinuing XARTEMIS XR, gradually taper the dosage. Do not abruptly discontinue XARTEMIS XR.
ARTEMIS XR may impair the mental and/or physical abilities required 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 XARTEMIS XR and know how they will react to the medication.
… While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of XARTEMIS XR, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially during the first 24-72 hours of initiating therapy with XARTEMIS XR and following dose increases ...
… Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Entire subsection revised as below:
Concomitant use of XARTEMIS XR with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of oxycodone and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of XARTEMIS XR is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in XARTEMIS XR-treated patients may increase oxycodone plasma concentrations and prolong adverse reactions. When using XARTEMIS XR with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in XARTEMIS XR-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of XARTEMIS XR until stable drug effects are achieved.
Concomitant use of XARTEMIS XR with CYP3A4 inducers or discontinuation of an CYP3A4 inhibitor could decrease oxycodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to oxycodone. When using XARTEMIS XR with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur.
Profound sedation, respiratory depression, coma, and death may result from the concomitant use of XARTEMIS XR 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.
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics.
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. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.
Advise both patients and caregivers about the risks of respiratory depression and sedation when XARTEMIS XR is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate dangerous machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs.
Revised subsection as below:
The use of XARTEMIS XR in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.
Patients with Chronic Pulmonary Disease: XARTEMIS XR-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 recommended dosages of XARTEMIS XR.
Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients.
Monitor such patients closely, particularly when initiating and titrating XARTEMIS XR and when XARTEMIS XR is given concomitantly with other drugs that depress respiration. Alternatively, consider the use of non-opioid analgesics in these patients.
Newly added subsection:
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.
Revised subsection as below:
XARTEMIS XR may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an 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 or triturating the dosage of XARTEMIS XR. In patients with circulatory shock, XARTEMIS XR may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of XARTEMIS XR in patients with circulatory shock.
6 Adverse Reactions
Additions and/or revisions underlined:
The following serious adverse reactions are described, or described in greater detail, in other sections:
Addiction, Abuse, and Misuse
Life-Threatening Respiratory Depression
Neonatal Opioid Withdrawal Syndrome
Hepatotoxicity
Interactions with Benzodiazepines and Other CNS Depressants
Adrenal Insufficiency
Severe Hypotension
Gastrointestinal Adverse Reactions
Seizures
Withdrawal
Newly added subsection:
The following adverse reactions have been identified during post-approval use of XARTEMIS XR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.
Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.
Anaphylaxis: Anaphylactic reaction has been reported with ingredients contained in XARTEMIS XR.
Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids.
7 Drug Interactions
Table 2: Clinically Significant Drug Interactions with XARTEMIS XR
Information has been converted to a table format; please refer to label.
8 Use in Specific Populations
8.1 PregnancyPLLR conversion:
Risk Summary
Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. Available data with XARTEMIS XR are insufficient to inform a drug-associated risk for major birth defects and miscarriage.
There are no adequate and well-controlled studies of XARTEMIS XR tablets …
… In mice treated with acetaminophen at doses within the clinical dosing range, a reduction in number of litters of the parental mating pair was observed as well as retarded growth and abnormal sperm in their offspring and reduced birth weight in the next generation.
Animal reproduction studies with oral administrations of oxycodone HCl in in rats and rabbits during the period of organogenesis at doses 2.6 and 8.1 times, respectively, the human dose of 60 mg/day did not reveal evidence of teratogenicity or embryo-fetal toxicity. In several published studies, treatment of pregnant rats with oxycodone at clinically relevant doses and below, resulted in neurobehavioral effects in offspring [see Data]. Based on animal data, advise pregnant women of the potential risk to a fetus.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Clinical Considerations
Fetal/Neonatal Adverse Reactions
Prolonged maternal use of opioid analgesics during pregnancy …
Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms and signs of neonatal opioid withdrawal syndrome and manage accordingly.
Labor or Delivery
Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone must be available for reversal of opioid-induced respiratory depression in the neonate. XARTEMIS XR is not recommended for use in women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including XARTEMIS XR, can 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 an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.
Data
Human Data
Two large population based studies have evaluated …
Animal Data
No reproductive or developmental studies were conducted …
In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of oxycodone HCl administered during the period of organogenesis up to 16 mg/kg/day and up
25 mg/kg/day, respectively. These studies revealed no evidence of teratogenicity or embryo-fetal toxicity due to oxycodone. The highest doses tested in rats and rabbits were equivalent to approximately 2.6 and 8.1 times an adult human dose of 60 mg/day, respectively, on a mg/m2 basis. In published studies, offspring of pregnant rats administered oxycodone during gestation have been reported to exhibit neurobehavioral effects including altered stress responses, increased anxiety-like behavior (2 mg/kg/day IV from Gestation Day 8 to 21 and Postnatal Day 1, 3, and 5; 0.3-times an adult human dose of 60 mg/day, on a mg/m2 basis) and altered learning and memory (15 mg/kg/day orally from breeding through parturition; 2.4 times an adult human dose of 60 mg/day, on a mg/m2 basis).
Risk Summary
Oxycodone is present in breast milk. Published lactation studies report variable concentrations of oxycodone in breast milk with administration of immediate-release oxycodone to nursing mothers in the early postpartum period. The lactation studies did not assess breastfed infants for potential adverse reactions. Lactation studies have not been conducted with extended-release oxycodone, including XARTEMIS XR, and no information is available on the effects of the drug on the breastfed infant or the effects of the drug on milk production. Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with XARTEMIS XR ...
Clinical Considerations
Monitor infants exposed to XARTEMIS XR through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.
PLLR conversion; newly added:
Infertility
Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible.
Additions and/or revisions underlined:
Of the 607 subjects in the Phase 3 studies treated …
Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of XARTEMIS XR slowly in geriatric patients and monitor closely for signs of respiratory depression.
Oxycodone and acetaminophen are known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
XARTEMIS XR contains oxycodone and acetaminophen, which are extensively metabolized in the liver. Their clearance may be decreased in patients with hepatic impairment. In patients with hepatic impairment a dosage adjustment is recommended. Monitor closely for respiratory depression, sedation, and hypotension.
Information from oxycodone HCl indicates that patients with renal impairment had higher plasma concentrations of oxycodone than subjects with normal renal function. In patients with renal impairment, a dosage adjustment is recommended. Monitor closely for respiratory depression, sedation, and hypotension.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDEXARTEMIS XR is:
XARTEMIS XR is used to treat certain types of short term (acute) pain when other pain treatments such as non-opioid pain medicines do not treat your pain well enough or you cannot tolerate them.
Important information about XARTEMIS XR:
Taking XARTEMIS XR with other opioid medicines, benzodiazepines, alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, decreased awareness, breathing problems, coma, and death.
Tell your healthcare provider if you are:
breastfeeding. Not recommended during treatment with XARTEMIS XR passes into breast milk and. It may harm your baby.
taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking XARTEMIS XR with certain other medicines can cause serious side effects that could lead to death.
When taking XARTEMIS XR:
Do not change your dose. Take XARTEMIS XR exactly as prescribed by your healthcare provider. Use the lowest dose possible for the shortest time needed.
Take XARTEMIS XR 1 tablet at a time. Do not pre-soak, lick, or wet the tablet before placing in your mouth. Take each XARTEMIS XR tablet with enough water to be sure that you swallow it completely as soon as you place it in your mouth. Do not take more than your prescribed dose. If you miss a dose, take our next dose at your usual time.
While taking XARTEMIS XR:
Do not drink alcohol or use prescription or over-the-counter medicines that contain alcohol. Using products containing alcohol during treatment with XARTEMIS XR may cause you to overdose and die.
The possible side effects of XARTEMIS XR are:
nausea, dizziness, headache, vomiting, • constipation, nausea, sleepiness., vomiting, tiredness, headache, dizziness, abdominal pain ...
Get emergency medical help if you have:
trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue, or throat, extreme drowsiness, low blood pressure, light-headedness when changing positions, or you are feeling faint, agitation, high body temperature, trouble walking, stiff muscles, or mental changes such as confusion.
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Important Administration Instructions
Instruct patients how to properly take XARTEMIS XR, including the following:
XARTEMIS XR is not interchangeable with other forms of oxycodone/acetaminophen.
XARTEMIS XR is a narcotic pain reliever and must be taken only as directed.
Take each tablet with enough water to ensure complete swallowing immediately after placing in the mouth, and not to pre-soak, lick, or otherwise wet the tablet prior to placing in the mouth.
Swallow each XARTEMIS XR tablet whole. Do not crush or dissolve. Do not use XARTEMIS XR for administration via nasogastric, gastric, or other feeding tubes as it may cause obstruction of feeding tubes.
If they miss a dose to take it as soon as possible. If it is almost time for the next dose, skip the missed dose and take the next dose at the regularly scheduled time. Do not take more than 2 tablets at once unless instructed by their healthcare provider. If they are not sure about their dosing, call their healthcare provider.
Do not adjust the dose of XARTEMIS XR without consulting with a physician or other healthcare provider.
Do not take more than 4000 milligrams of acetaminophen per day and to call their healthcare provider if they took more than the recommended dose.
If physically dependent, do not to discontinue XARTEMIS XR without first discussing the need for a tapering regimen with a physician or other healthcare provider.
Accidental Ingestion
Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death. Instruct patients to take steps to store XARTEMIS XR securely and to dispose of unused XARTEMIS XR by flushing the tablets down the toilet.
Interactions with Benzodiazepines and Other CNS Depressants
Inform patients and caregivers that potentially fatal additive effects may occur if XARTEMIS XR is used with benzodiazepines or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a health care provider.
Serotonin Syndrome
Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications.
MAOI Interaction Inform patients to avoid taking XARTEMIS XR while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking Oxycodone Hydrochloride Oral Solution.
Adrenal Insufficiency
Inform patients that opioids could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms.
Hypotension
Inform patients that XARTEMIS XR may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position).
Anaphylaxis
Inform patients that anaphylaxis have been reported with ingredients contained in XARTEMIS XR. Advise patients how to recognize such a reaction and when to seek medical attention.
Pregnancy
Neonatal Opioid Withdrawal Syndrome
Embryo-Fetal Toxicity
Inform female patients of reproductive potential that XARTEMIS XR can cause fetal harm, and to inform their healthcare provider of a known or suspected pregnancy.
Lactation
Advise patients that breastfeeding is not recommended during treatment with XARTEMIS XR.
Driving or Operating Machinery
Inform patients that XARTEMIS XR may impair the ability to perform potentially hazardous activities such as driving a car or operating dangerous machinery. Advise patients not to perform such tasks until they know how they will react to the medication.
Constipation
Advise of the potential for severe constipation, including management instructions and when to seek medical attention.
Disposal of Unused XARTEMIS XR
Advise patients to flush the unused tablets down the toilet when XARTEMIS XR is no longer needed.