Numorphan

Interactions with Other Central Nervous System Depressants

Patients receiving other opioid analgesics, general anesthetics, phenothiazines, other tranquilizers, sedatives, hypnotics or other CNS depressants (including alcohol) concomitantly with NUMORPHAN (oxymorphone) may exhibit an additive CNS depression (see PRECAUTIONS: DRUG INTERACTIONS).

Respiratory Depression

NUMORPHAN (oxymorphone) should be administered with extreme caution to patients with conditions accompanied by hypoxia, hypercapnia or decreased respiratory reserve such as: asthma, chronic obstructive pulmonary disease or cor pulmonale, severe obesity, sleep apnea syndrome, myxedema, kyphoscoliosis, CNS depression or coma.

Head Injury and Increased Intracranial Pressure

The possible respiratory depressant effects of potent analgesics and their potential to elevate cerebrospinal fluid pressure (resulting from vasodilation following CO2 retention) may be markedly exaggerated in the presence of head injury, intracranial lesions or a preexisting increase in intracranial pressure. Furthermore, potent analgesics can produce effects which may obscure the clinical course of patients with head injuries. Therefore, NUMORPHAN (oxymorphone) should be used in these circumstances only when essential, and then should be administered with extreme caution.

Acute Abdominal Conditions

The administration of opioids may obscure the diagnosis or clinical course of patients with acute abdominal conditions.

Drug Dependence

NUMORPHAN (oxymorphone) , as with other opioid drugs, can produce tolerance, psychological dependence, and physical dependence and has the potential for being abused (see Drug Abuse And Dependence).

Pregnancy

Safe use in pregnancy has not been established (relative to possible adverse effects on fetal development). As with other analgesics, the use of NUMORPHAN (oxymorphone) in pregnancy, in nursing mothers, or in women of child-bearing potential requires that the possible benefits of the drug be weighed against the possible hazards to the mother and the child (see PRECAUTIONS).

Patients should be cautioned regarding the following:

Drowsiness, dizziness, or lightheadedness related to the use of this medication may impair mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car, operating machinery, etc.

This medication, like other opioid analgesics, will add to the effect of alcohol and other CNS depressants [such as antihistamines, sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, tricyclic antidepressants, and monoamine oxidase (MAO) inhibitors]. Alcohol should not be consumed while taking NUMORPHAN (oxymorphone) .

Withdrawal side effects may be precipitated by suddenly stopping this drug after prolonged use (regular use for several weeks or more). The medication should be gradually reduced before completely discontinuing use.

Elderly patients are more sensitive to opioid analgesics, especially the respiratory depressant effects and opioid induced urinary retention. Lower doses or longer dosing intervals may be required.

Orthostatic hypotension may occur with the use of this medication, especially in ambulatory patients. Patients should get up slowly from a lying or sitting position.

NUMORPHAN (oxymorphone hydrochloride, USP) may be habit forming and has the potential for being abused. Tolerance, psychological and physical dependence can occur.

Safe use in pregnancy has not been established. Prolonged use of opioid analgesics during pregnancy may cause fetal-neonatal physical dependence, and neonatal withdrawal may occur.

As with all potent opioid analgesics, possible side effects when using NUMORPHAN (oxymorphone) include:

Central Nervous System

Drowsiness, sedation, lightheadedness, unusual tiredness or weakness, headache, dysphoria, euphoria, miosis, diplopia, blurred vision, nervousness, restlessness, confusion, mental clouding, trouble sleeping, paradoxical CNS stimulation, hallucinations, mental depression.

Gastrointestinal System

Nausea, vomiting, dry mouth, constipation, biliary tract spasm, cramps or pain, loss of appetite, paralytic ileus or toxic megacolon in patients with inflammatory bowel disease.

Cardiovascular System

Hypotension, orthostatic hypotension particularly in ambulatory patients, tachycardia, bradycardia, palpitations, flushing.

Respiratory System

Respiratory depression, atelectasis, allergic bronchospastic reaction, allergic laryngeal edema, allergic laryngospasm.

Genitourinary System

Ureteral spasm, urinary hesitancy or retention, antidiuretic effect.

Dermatologic

Itching, sweating, injection site reaction, allergic reaction (such as skin rash, hives, and/or itching, swelling of the face).

Drug Abuse And Dependence

NUMORPHAN (oxymorphone) is a Schedule II opioid and is subject to the Federal Controlled Substances Act.

NUMORPHAN (oxymorphone) , as with other opioid drugs, can produce tolerance, psychological dependence, and physical dependence and has the potential for being abused. The addiction potential of the drug appears to be about the same as for morphine.

Withdrawal symptoms may occur when opioids are abruptly discontinued after prolonged use. Withdrawal symptoms may be characterized by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, gooseflesh, restless sleep, and mydriasis during the first 24 hours. These symptoms often increase in severity and over the next 72 hours may be accompanied by increasing irritability, anxiety, weakness, twitching, and spasms of muscles; kicking movements; severe backaches; abdominal and leg pains; abdominal and muscle cramps; hot and cold flashes; insomnia; nausea, anorexia, vomiting, intestinal spasm, diarrhea, coryza, and repetitive sneezing; increase in body temperature, blood pressure, respiratory rate and heart rate. Because of excessive loss of fluids through sweating, vomiting and diarrhea, there is usually marked weight loss, dehydration, ketosis, and disturbances in acid-base balance. Cardiovascular collapse can occur. Without treatment most observable symptoms disappear in 5-14 days; however, there appears to be a phase of secondary or chronic abstinence which may last for 2-6 months characterized by decreasing insomnia, irritability, and muscular aches. In addition, the patient may have miosis and a slight lowering of blood pressure, pulse rate, and body temperature;respiratory centers exhibit a decreased response to the stimulatory effects of carbon dioxide.

The dose of NUMORPHAN (oxymorphone) should be gradually reduced before discontinuation in those patients who require treatment for physical dependence.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms (see PRECAUTIONS; Usage in Pregnancy).

Read the entire FDA prescribing information for Numorphan (Oxymorphone)

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of oxymorphone injection in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of oxymorphone injection in the elderly. However, elderly patients are more likely to have age-related liver, kidney, heart, or lung problems, which may require caution and an adjustment in the dose for patients receiving oxymorphone injection.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Nalmefene
• Naltrexone
• Safinamide

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acepromazine
• Alfentanil
• Almotriptan
• Alprazolam
• Alvimopan
• Amineptine
• Amisulpride
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Anileridine
• Aripiprazole
• Asenapine
• Baclofen
• Benperidol
• Benzphetamine
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Buspirone
• Butabarbital
• Butorphanol
• Carbamazepine
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Cimetidine
• Citalopram
• Clobazam
• Clomipramine
• Clonazepam
• Clorazepate
• Clozapine
• Cocaine
• Codeine
• Cyclobenzaprine
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diphenhydramine
• Diphenoxylate
• Dolasetron
• Donepezil
• Doxepin
• Doxylamine
• Droperidol
• Duloxetine
• Eletriptan
• Enflurane
• Escitalopram
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Fentanyl
• Flibanserin
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fospropofol
• Frovatriptan
• Furazolidone
• Granisetron
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Imipramine
• Iproniazid
• Isocarboxazid
• Isoflurane
• Ketamine
• Ketazolam
• Ketobemidone
• Levomilnacipran
• Levorphanol
• Linezolid
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lorazepam
• Lorcaserin
• Loxapine
• Meclizine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Methylene Blue
• Methylnaltrexone
• Midazolam
• Milnacipran
• Mirtazapine
• Moclobemide
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nalbuphine
• Nalorphine
• Naloxone
• Naratriptan
• Nefazodone
• Nialamide
• Nicomorphine
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxycodone
• Paliperidone
• Palonosetron
• Papaveretum
• Paregoric
• Paroxetine
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenelzine
• Phenobarbital
• Pimozide
• Piperacetazine
• Pipotiazine
• Piritramide
• Prazepam
• Primidone
• Procarbazine
• Prochlorperazine
• Promazine
• Promethazine
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Ramelteon
• Rasagiline
• Remifentanil
• Remoxipride
• Rizatriptan
• Samidorphan
• Secobarbital
• Selegiline
• Sertindole
• Sertraline
• Sibutramine
• Sodium Oxybate
• St John's Wort
• Sufentanil
• Sulpiride
• Sumatriptan
• Suvorexant
• Temazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Topiramate
• Tramadol
• Tranylcypromine
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Venlafaxine
• Vilazodone
• Vortioxetine
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Addison's disease (adrenal gland problem) or
• Alcohol abuse, or history of or
• Brain tumor, history of or
• Breathing or lung problems (eg, COPD, cor pulmonale, hypercapnia, hypoxia) or
• Depression, history of or
• Drug dependence, especially with narcotics, or history of or
• Enlarged prostate (BPH, prostatic hypertrophy) or
• Gallbladder disease or gallstones or
• Head injuries, history of or
• Heart disease or
• Hypothyroidism (an underactive thyroid) or
• Hypovolemia (low blood volume) or
• Kyphoscoliosis (curvature of the spine with breathing problems) or
• Obesity, severe or
• Problems with passing urine or
• Weakened physical condition—Use with caution. May increase risk for more serious side effects.

• Hypotension (low blood pressure) or
• Pancreatitis (inflammation of the pancreas) or
• Seizures, history of—Use with caution. May make these conditions worse.

• Liver disease, moderate or severe or
• Lung or breathing problems, severe or
• Stomach or bowel blockage (eg, paralytic ileus)—Should not be used in patients with these conditions.

• Kidney disease or
• Liver disease, mild—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Numorphan should not be administered to patients who are hypersensitive to oxymorphone hydrochloride or to any of the other ingredients in Numorphan, or hypersensitive to morphine analogs.

Numorphan should not be administered to individuals during an acute asthmatic attack or to patients with severe respiratory depression, upper airway obstruction, or any patient who has or is suspected of having a paralytic ileus. Numorphan should not be used in the treatment of pulmonary edema secondary to a chemical respiratory irritant. Opioid analgesics cause pooling of blood in the extremities by decreasing peripheral vascular resistance. This effect results in decreases in venous return, cardiac work, and pulmonary venous pressure, and blood is shifted from the central to peripheral circulation which would not be beneficial in the treatment of pulmonary edema secondary to a chemical respiratory irritant.

Numorphan is a Schedule II opioid and is subject to the Federal Controlled Substances Act.

Numorphan, as with other opioid drugs, can produce tolerance, psychological dependence, and physical dependence and has the potential for being abused. The addiction potential of the drug appears to be about the same as for morphine.

Withdrawal symptoms may occur when opioids are abruptly discontinued after prolonged use. Withdrawal symptoms may be characterized by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, gooseflesh, restless sleep, and mydriasis during the first 24 hours. These symptoms often increase in severity and over the next 72 hours may be accompanied by increasing irritability, anxiety, weakness, twitching, and spasms of muscles; kicking movements; severe backaches; abdominal and leg pains; abdominal and muscle cramps; hot and cold flashes; insomnia; nausea, anorexia, vomiting, intestinal spasm, diarrhea, coryza, and repetitive sneezing; increase in body temperature, blood pressure, respiratory rate and heart rate. Because of excessive loss of fluids through sweating, vomiting and diarrhea, there is usually marked weight loss, dehydration, ketosis, and disturbances in acid-base balance. Cardiovascular collapse can occur. Without treatment most observable symptoms disappear in 5-14 days; however, there appears to be a phase of secondary or chronic abstinence which may last for 2-6 months characterized by decreasing insomnia, irritability, and muscular aches. In addition, the patient may have miosis and a slight lowering of blood pressure, pulse rate, and body temperature; respiratory centers exhibit a decreased response to the stimulatory effects of carbon dioxide.

The dose of Numorphan should be gradually reduced before discontinuation in those patients who require treatment for physical dependence.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms (see PRECAUTIONS; Usage in Pregnancy).

Signs and Symptoms

Serious overdosage with Numorphan is characterized by respiratory depression, (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur.

Treatment

Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. The opioid antagonist naloxone hydrochloride (NARCAN®) is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to opioids including oxymorphone. Therefore, an appropriate dose of naloxone hydrochloride should be administered (usual initial adult dose 0.4 mg-2 mg) preferably by the intravenous route and simultaneously with efforts at respiratory resuscitation. Since the duration of action of oxymorphone may exceed that of the antagonist, the patient should be kept under continued surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration.

Naloxone hydrochloride should not be administered in the absence of clinically significant respiratory or cardiovascular depression. In addition, it should be considered that the use of an opioid antagonist in patients physically dependent on opioids may precipitate an acute withdrawal syndrome that cannot be readily suppressed while the action of the antagonist persists. If respiratory depression is associated with muscular rigidity, administration of a neuromuscular blocking agent may be necessary to facilitate assisted or controlled ventilation. Muscular rigidity may also respond to opioid antagonist therapy.

Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed as indicated.

This drug should be used during pregnancy only if the benefit clearly outweighs the risk to the fetus. US FDA pregnancy category: C Comments: -Prolonged use of opioids during pregnancy can result in physical dependence in the neonate; women should be advised of the risk of neonatal abstinence syndrome and ensure that appropriate treatment will be available. -Long-acting opioids should not be used during and immediately prior to labor, when short acting analgesics or other analgesic techniques are more appropriate.

Animal studies have shown that oxymorphone exposure during pregnancy is associated with reduced fetal weight. In a pre and postnatal developmental toxicity study, administration to female rats during gestation showed reduced litter size at a dose of 25 mg/kg/day (attributed to an increase in the incidence of still born pups) and an increase in neonatal death at 5 mg/kg/day or more (0.4 times a total human daily dose). Low pup birth weight, decreased post-natal weight gain, and reduced post-natal survival of pups occurred when born of dams treated with 25 mg/kg/day (about 2 times a total human dose). There are no adequate and well-controlled studies in pregnant women. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Caution is advised; generally other agents are preferred over this drug during breastfeeding. Excreted into human milk: Unknown Excreted into animal milk: Data not available Comments: Breastfed infants should be closely monitored for excess sedation and respiratory depression; withdrawal symptoms can occur when maternal administration of this drug is stopped.