Source: FDA, National Drug Code (US) Revision Year: 2021
Oxymorphone hydrochloride tablets are contraindicated in patients with:
Oxymorphone hydrochloride tablets contains oxymorphone, a Schedule II controlled substance. As an opioid, oxymorphone hydrochloride tablets exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9)].
Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed oxymorphone hydrochloride tablets. Addiction can occur at recommended dosages and if the drug is misused or abused.
Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing oxymorphone hydrochloride tablets, and monitor all patients receiving oxymorphone hydrochloride tablets for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as oxymorphone hydrochloride tablets, but use in such patients necessitates intensive counseling about the risks and proper use of oxymorphone hydrochloride tablets along with intensive monitoring for signs of addiction, abuse, and misuse. Consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2), Warnings and Precautions (5.3)].
Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing oxymorphone hydrochloride tablets. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see Patient Counseling Information (17)]. 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.
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:
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.
Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see Overdosage (10)]. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of oxymorphone hydrochloride tablets, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of oxymorphone hydrochloride tablets.
To reduce the risk of respiratory depression, proper dosing and titration of oxymorphone hydrochloride tablets are essential [see Dosage and Administration (2)]. Overestimating the oxymorphone hydrochloride tablets dosage when converting patients fromanother opioid product can result in a fatal overdose with the first dose.
Accidental ingestion of even one dose of oxymorphone hydrochloride tablets, especially by children, can result in respiratory depression and death due to an overdose of oxymorphone.
Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see Patient Counseling Information (17)].
Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see Dosage and Administration (2.5)].
Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with oxymorphone hydrochloride tablets. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program). Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help, even if naloxone is administered [see Patient Counseling Information (17)].
Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient. Also consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose. If naloxone is prescribed, educate patients and caregivers on how to treat with naloxone. [see Warnings and Precautions (5.1, 5.4), Patient Counseling Information (17)].
Prolonged use of oxymorphone hydrochloride tablets during pregnancy can result in withdrawal in the neonate. 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 [see Use in Specific Populations (8.1), Patient Counseling Information (17)].
Patients must not consume alcoholic beverages or prescription or non-prescription products containing alcohol while on oxymorphone hydrochloride tablets therapy. The co-ingestion of alcohol with oxymorphone hydrochloride tablets may result in increased plasma levels and a potentially fatal overdose of oxymorphone [see Clinical Pharmacology (12.3)].
Profound sedation, respiratory depression, coma, and death may result from the concomitant use of oxymorphone hydrochloride tablets 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 [see Drug Interactions (7)].
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.
If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2), Warnings and Precautions (5.3)].
Advise both patients and caregivers about the risks of respiratory depression and sedation when oxymorphone hydrochloride tablets are used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy 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 [see Drug Interactions (7), Patient Counseling Information (17)].
The use of oxymorphone hydrochloride tablets 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: Oxymorphone hydrochloride tablets-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 oxymorphone hydrochloride tablets [see Warnings and Precautions (5.3)].
Elderly, Cachectic, or Debilitated Patients: Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients [see Warnings and Precautions (8.5)].
Monitor such patients closely, particularly when initiating and titrating oxymorphone hydrochloride tablets and when oxymorphone hydrochloride tablets are given concomitantly with other drugs that depress respiration [see Warnings and Precautions (5.3)]. Alternatively, consider the use of non-opioid analgesics in these patients.
Potentially life-threatening hypersensitivity reactions, including anaphylaxis and angioedema, have occurred in patients treated with oxymorphone hydrochloride tablets in the postmarket setting. The most commonly described clinical features in these reports were swelling of the face, eyes, mouth, lips, tongue, hands, and/or throat; dyspnea; hives, pruritus, and/or rash; and nausea/vomiting. If anaphylaxis or other hypersensitivity occurs, stop administration of oxymorphone hydrochloride tablets immediately, discontinue oxymorphone hydrochloride tablets permanently, and do not rechallenge with any formulation of oxymorphone. Advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction [see Patient Counseling Information (17)].
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.
Oxymorphone hydrochloride tablets may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Warnings and Precautions (5.5) and Drug Interactions (7)]. Monitor these patients for signs of hypotension after initiating or titrating the dosage of oxymorphone hydrochloride tablets. In patients with circulatory shock, oxymorphone hydrochloride tablets may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of oxymorphone hydrochloride tablets in patients with circulatory shock.
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), oxymorphone hydrochloride tablets 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 oxymorphone hydrochloride tablets.
Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of oxymorphone hydrochloride tablets in patients with impaired consciousness or coma.
Oxymorphone hydrochloride tablets are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.
The oxymorphone in oxymorphone hydrochloride tablets 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.
The oxymorphone in oxymorphone hydrochloride tablets 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 oxymorphone hydrochloride tablets therapy.
Do not abruptly discontinue oxymorphone hydrochloride tablets in a patient physically dependent on opioids. When discontinuing oxymorphone hydrochloride tablets in a physically dependent patient, gradually taper the dosage. Rapid tapering of oxymorphone in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain [see Dosage and Administration (2.8), Drug Abuse and Dependence (9.3)].
Additionally, avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including oxymorphone hydrochloride tablets. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms [see Drug Interactions (7)].
Oxymorphone hydrochloride tablets may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of oxymorphone hydrochloride tablets and know how they will react to the medication.
A study of extended-release oxymorphone tablets in patients with hepatic disease indicated greater plasma concentrations than in those with normal hepatic function [see Clinical Pharmacology (12.3)]. Use oxymorphone hydrochloride tablets with caution in patients with mild impairment, starting with the lowest dose and titrating slowly while carefully monitoring for side effects [see Dosage and Administration (2.3, 2.4)]. Oxymorphone hydrochloride tablets are contraindicated in patients with moderate or severe hepatic impairment.
The following serious adverse reactions are described, or described in greater detail, in other sections:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
A total of 591 patients were treated with oxymorphone hydrochloride tablets in controlled clinical trials. The clinical trials consisted of patients with acute post-operative pain (n=557) and cancer pain (n=34) trials.
The following table lists adverse reactions that were reported in at least 2% of patients receiving oxymorphone hydrochloride tablets in placebo-controlled trials (acute post-operative pain (N=557)).
Table 1. Adverse Reactions Reported in Placebo-Controlled Trials:
| MedDRA Preferred Term | Oxymorphone Hydrochloride Tablets (N=557) | Placebo (N=270) |
|---|---|---|
| Nausea | 19% | 12% |
| Pyrexia | 14% | 8% |
| Somnolence | 9% | 2% |
| Vomiting | 9% | 7% |
| Pruritus | 8% | 4% |
| Headache | 7% | 4% |
| Dizziness (Excluding Vertigo) | 7% | 2% |
| Constipation | 4% | 1% |
| Confusion | 3% | <1% |
The common (≥1% - <10%) adverse drug reactions reported at least once by patients treated with oxymorphone hydrochloride tablets in the clinical trials organized by MedDRA’s (Medical Dictionary for Regulatory Activities) System Organ Class were and not represented in Table 1:
Cardiac disorders: tachycardia
Gastrointestinal disorders: dry mouth, abdominal distention, and flatulence
General disorders and administration site conditions: sweating increased
Nervous system disorders: anxiety and sedation
Respiratory, thoracic and mediastinal disorders: hypoxia
Vascular disorders: hypotension
Other less common adverse reactions known with opioid treatment that were seen <1% in the oxymorphone hydrochloride tablets trials includes the following:
Abdominal pain, ileus, diarrhea, agitation, disorientation, restlessness, feeling jittery, hypersensitivity, allergic reactions, bradycardia, central nervous system depression, depressed level of consciousness, lethargy, mental impairment, mental status changes, fatigue, depression, clamminess, flushing, hot flashes, dehydration, dermatitis, dyspepsia, dysphoria, edema, euphoric mood, hallucination, hypertension, insomnia, miosis, nervousness, palpitation, postural hypotension, syncope, dyspnea, respiratory depression, respiratory distress, respiratory rate decreased, oxygen saturation decreased, difficult micturition, urinary retention, urticaria, vision blurred, visual disturbances, weakness, appetite decreased, and weight decreased.
The following adverse reactions have been identified during post approval use of opioids. 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.
Nervous system disorder: amnesia, convulsion, memory impairment.
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: Anaphylaxis has been reported with ingredients contained in oxymorphone hydrochloride tablets.
Immune System Disorders: Angioedema, and other hypersensitivity reactions:
Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see Clinical Pharmacology (12.2)].
Table 2 includes clinically significant drug interactions with oxymorphone hydrochloride tablets.
Table 2. Clinically Significant Drug Interactions withOxymorphone Hydrochloride Tablets:
| Alcohol | |
|---|---|
| Clinical Impact: | The concomitant use of alcohol with oxymorphone hydrochloride tablets can result in an increase of oxymorphone plasma levels and potentially fatal overdose of oxymorphone. |
| Intervention: | Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products containing alcohol while on oxymorphone hydrochloride tablets therapy [see Clinical Pharmacology 12.3)]. |
| Benzodiazepines and Other Central Nervous System (CNS) Depressants | |
| Clinical Impact: | Due to additive pharmacologic effect, the concomitant use of benzodiazepines and other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. |
| Intervention: | Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2, 2.7), Warnings and Precautions (5.1, 5.3, 5.5)]. |
| Examples: | Benzodiazepines and other sedatives/hypnotics, anxiolytics tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol. |
| Serotonergic Drugs | |
| Clinical Impact: | The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome . |
| Intervention: | If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue oxymorphone hydrochloride tablets if serotonin syndrome is suspected. |
| Examples: | Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). |
| Monoamine Oxidase Inhibitors (MAOIs) | |
| Clinical Impact: | MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions (5.3)]. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. |
| Intervention: | The use of oxymorphone hydrochloride tablets is not recommended for patients taking MAOIs or within 14 days of stopping such treatment. |
| Examples: | phenelzine, tranylcypromine, linezolid |
| Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics | |
| Clinical Impact: | May reduce the analgesic effect of oxymorphone hydrochloride tablets and/or may precipitate withdrawal symptoms. |
| Intervention: | Avoid concomitant use. |
| Examples | Butorphanol, nalbuphine, pentazocine, buprenorphine |
| Muscle Relaxants | |
| Clinical Impact: | Oxymorphone may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. |
| Intervention: | Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of oxymorphone hydrochloride tablets and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2), Warnings and Precautions (5.3, 5.5)]. |
| Diuretics | |
| Clinical Impact: | Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. |
| Intervention: | Monitor patients for signs of urinary retention or reduced gastric motility when oxymorphone hydrochloride tablets are used concomitantly with anticholinergic drugs. |
| Anticholinergic Drugs | |
| Clinical Impact: | The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. |
| Intervention: | Monitor patients for signs of urinary retention or reduced gastric motility when oxymorphone hydrochloride tablets are used concomitantly with anticholinergic drugs. |
| Cimetidine | |
| Clinical Impact: | Cimetidine can potentiate opioid-induced respiratory depression. |
| Intervention: | Monitor patients for respiratory depression when oxymorphone hydrochloride tablets and cimetidine are used concurrently. |
Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.4) and Clinical Considerations]. Data from randomized controlled trials with oxymorphone use in pregnant women during labor and delivery have been conducted. However, these studies were not designed to identify a drug-associated risk for major birth defects and miscarriage because oxymorphone exposure occurred after the first trimester. There are reports of respiratory depression in infants in some of these trials [see Clinical Considerations].
In animal reproduction studies, reduced postnatal survival of pups and an increased incidence of stillborn pups were observed following oral treatment of pregnant rats with oxymorphone during gestation and through lactation at doses 2.4 and 12 times the human daily dose of 20 mg/day (HDD), respectively. Reduced fetal weights were observed with oral administration of oxymorphone to pregnant rats and rabbits during organogenesis at exposures up to 4.9 and 48.8 times the HDD, respectively [see Data]. Based on animal data, advise pregnant women of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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.
Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.
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 of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions (5.4)].
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. Oxymorphone hydrochloride tablets are not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including oxymorphone hydrochloride tablets, 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.
Pregnant rats were treated with oxymorphone hydrochloride from Gestation Day 6 to 17 via oral gavage doses of 5, 10, or 25 mg/kg/day (2.4, 4.9, or 12.2 times the HDD based on body surface area, respectively). Reduced mean fetal weights were observed at 4.9 times the HDD. Maternal toxicity was noted in all treatment groups (reduced food consumption and body weights in all groups and mortality in the high dose group).
Pregnant rabbits were treated with oxymorphone hydrochloride from Gestation Day 7 to 20 via oral gavage doses of 10, 25, or 50 mg/kg/day (9.8, 24.4, or 48.8 times the HDD based on body surface area, respectively). Decreased mean fetal weights were noted at 48.8 times the HDD. Maternal toxicity was noted in all treatment groups (reduced food consumption and body weights).
Pregnant rats were treated with oxymorphone hydrochloride from Gestation Day 6 to Lactation Day 20 via oral gavage doses of 1, 5, 10, or 25 mg/kg/day (0.5, 2.4, 4.9, or 12.2 times the HDD based on body surface area, respectively). Increased neonatal death (postnatal day 0-1) was noted at 2.4 times the HDD. Decreased pup survival over the first week of life, reduced pup birth weight, and reduced postnatal weight gain were noted at 4.9 times the HDD. Maternal toxicity was noted in all treatment groups (reduced food consumption and body weights in all groups and mortality in the 10 and 25 mg/kg/day groups).
In a published study, neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of 153 mg/kg oxymorphone hydrochloride (62.2 times the HDD) on Gestation Day 8 to pregnant hamsters. This dose also produced significant maternal toxicity (20% maternal deaths).
There is no information regarding the presence of oxymorphone in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for oxymorphone hydrochloride tablets and any potential adverse effects on the breastfed child from oxymorphone hydrochloride tablets or from the underlying maternal condition.
Monitor infants exposed to oxymorphone hydrochloride tablets through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breast-fed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for oxymorphone hydrochloride tablets and any potential adverse effects on the breastfed infant from oxymorphone hydrochloride tablets or from the underlying maternal condition.
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 [see Clinical Pharmacology (12.2), Nonclinical Toxicology (13.1)].
Safety and effectiveness for pediatric patients, 0 to 17 years, have not been established.
An open-label study was conducted in 58 pediatric patients 12 years of age and older with postoperative pain using Oxymorphone Hydrochloride Tablets. Efficacy was not demonstrated in this population treated with doses expected to be comparable to effective starting doses in adults. In addition, pharmacokinetic results demonstrated that treatment with Oxymorphone Hydrochloride Tablets resulted in substantially higher systemic exposures to oxymorphone in 2 out of 24 patients.
Oxymorphone Hydrochloride Tablets are not recommended for use in the pediatric population.
Oxymorphone hydrochloride tablets should be used with caution in elderly patients [see Clinical Pharmacology (12.3)].
Of the total number of subjects in clinical studies of oxymorphone hydrochloride tablets, 31% were 65 and over, while 7% were 75 and over. No overall differences in effectiveness were observed between these subjects and younger subjects. There were several adverse events that were more frequently observed in subjects 65 and over compared to younger subjects. These adverse events included dizziness, somnolence, confusion, and nausea. In general, dose selection for elderly patients should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.
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 oxymorphone hydrochloride tablets slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.6)].
Oxymorphone is 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 the 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.
In a study of extended-release oxymorphone tablets, patients with moderate to severe renal impairment were shown to have an increase in bioavailability compared to the subjects with normal renal function [see Clinical Pharmacology (12.3)] Such. patients should be started be started with the lowest dose (5 mg) and titrated slowly while monitoring for signs of respiratory and central nervous system depression [see Dosage and Administration (2.5) Clinical Pharmacology (12.3)].
In a study of extended-release oxymorphone tablets, patients with mild hepatic impairment were shown to have an increase in bioavailability compared to the subjects with normal hepatic function. Oxymorphone hydrochloride tablets should be used with caution in patients with mild impairment. These patients should be started with the lowest dose (5 mg) and titrated slowly while carefully monitoring for signs of respiratory and central nervous system depression. Oxymorphone hydrochloride tablets are contraindicated for patients with moderate and severe hepatic impairment [see Dosage and Administration (2.4), Contraindications (4), Warnings and Precautions (5.15), and Clinical Pharmacology 12.3].
Oxymorphone hydrochloride tablets contains oxymorphone, a Schedule II controlled substance.
Oxymorphone hydrochloride tablets contains oxymorphone, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone and tapentadol. Oxymorphone hydrochloride tablets can be abused and is subject to misuse, addiction, and criminal diversion [see Warnings and Precautions (5.1)].
All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use.
Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects.
Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.
“Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.
Abuse and addiction are separate and distinct from physical dependence and tolerance. Health care providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.
Oxymorphone hydrochloride tablets, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.
Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.
Oxymorphone hydrochloride tablets are for oral use only. Abuse of oxymorphone hydrochloride tablets poses a risk of overdose and death. This risk is increased with concurrent abuse of oxymorphone hydrochloride tablets with alcohol and other central nervous system depressants.
Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.
Both tolerance and physical dependence can develop during chronic opioid therapy. 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). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.
Physical dependence is a physiological state in which the body adapts to the drug after a period of regular exposure, resulting in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.
Do not abruptly discontinue oxymorphone hydrochloride tablets in a patient physically dependent on opioids. Rapid tapering of oxymorphone hydrochloride tablets in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.
When discontinuing oxymorphone hydrochloride tablets, gradually taper the dosage using a patient-specific plan that considers the following: the dose of oxymorphone hydrochloride tablets the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for a long duration at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see Dosage and Administration (2.8), Warnings and Precautions (5.13)].
Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see Warnings and Precautions (5.4), Use in Specific Populations (8.1)].
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