Oxycodone and naloxone (Oral)

Oxycodone and naloxone combination is used to treat pain that is severe enough to need daily, around-the-clock, long-term opioid treatment, especially when other pain medicines did not work well enough or cannot be tolerated.

Oxycodone is part of a group of medicines called narcotic analgesics (pain medicines). It works on the central nervous system (CNS) to relieve pain. Naloxone is used to treat an opioid emergency, such as an overdose or a possible overdose of a narcotic medicine.

Oxycodone and naloxone combination should not be used if you need pain medicine for just a short time, like when recovering from surgery. Do not use this medicine to relieve mild pain or in situations where non-narcotic medication is effective. This medicine should not be used to treat pain that occurs only occasionally or "as needed."

When oxycodone is used for a long time, it may become habit-forming, leading to mental or physical dependence. However, people who have ongoing pain should not let the fear of dependence stop them from using narcotics to relieve their pain. Mental dependence (addiction) is not likely to happen when narcotics are used for this purpose. Physical dependence may cause withdrawal side effects if treatment is stopped suddenly. However, severe withdrawal side effects can usually be avoided by slowly reducing the dose over time before stopping treatment completely.

This medicine is available only through a restricted distribution program called the Opioid Analgesic REMS (Risk Evaluation and Mitigation Strategy) program.

It is very important for your doctor to check your progress while you are using this medicine, especially during the first 24 to 72 hours of treatment. This will help your doctor determine if the medicine is working correctly and decide if you should keep taking it. Blood tests may be needed to check for unwanted effects.

Do not use this medicine if you have taken an MAO inhibitor (MAOI) (for example, isocarboxazid [Marplan®], linezolid [Zyvox®], phenelzine [Nardil®], selegiline [Eldepryl®], tranylcypromine [Parnate®]) in the past 14 days.

This medicine may cause a serious allergic reaction called anaphylaxis, which can be life-threatening and requires immediate medical help. Call your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or swelling of your hands, face, or mouth while using this medicine.

Do not take more of this medicine or take it more often than your doctor advises. This can be life-threatening. Symptoms of an overdose include: extreme dizziness or weakness, slow heartbeat or breathing, seizures, trouble breathing, and cold, clammy skin. Call your doctor right away if you notice these symptoms.

This medicine will increase the effects of alcohol and other CNS depressants (medicines that can make you drowsy or less alert). Examples of CNS depressants include antihistamines or medicines for allergies or colds, sedatives, tranquilizers, sleeping medicines, other prescription pain medicines or narcotics, medicines for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics. Check with your doctor before taking any of these medicines while using this medicine.

This medicine may be habit-forming. If you feel that the medicine is not working as well, do not take more than your prescribed dose. Call your doctor for guidance.

Dizziness, lightheadedness, or fainting may happen when you get up suddenly from a lying or sitting position. Getting up slowly may help reduce this issue. Also, lying down for a while may relieve the dizziness or lightheadedness.

This medicine may cause dizziness, drowsiness, or lightheadedness. Do not drive or do anything else that could be dangerous until you know how this medicine affects you.

Using narcotics for a long time can cause severe constipation. To prevent this, your doctor may recommend taking laxatives, drinking plenty of fluids, or increasing fiber in your diet. Be sure to follow the directions carefully, as ongoing constipation can lead to more serious issues.

If you have been using this medicine regularly for several weeks or longer, do not change your dose or suddenly stop using it without checking with your doctor. Your doctor may want you to gradually reduce your dose before stopping completely. This can help prevent a worsening of your condition and reduce the chance of withdrawal symptoms, such as stomach cramps, anxiety, fever, nausea, runny nose, sweating, tremors, or trouble sleeping.

Using this medicine during pregnancy may cause serious unwanted effects, including neonatal opioid withdrawal syndrome in your newborn baby. Tell your doctor right away if you think you are pregnant or plan to become pregnant while using this medicine.

For nursing mothers taking Belbuca®:

• Talk to your doctor if you have questions about taking oxycodone and naloxone combination or how this medicine may affect your baby.
• Call your doctor if you become very tired and have difficulty caring for your baby.
• Your baby should generally nurse every 2 to 3 hours and should not sleep for more than 4 hours at a time.
• Check with your doctor or go to the hospital emergency room immediately if your baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, trouble breathing, or limpness. These may be signs of an overdose and need immediate medical help.

Check with your doctor right away if you have anxiety, restlessness, a fast heartbeat, fever, sweating, muscle spasms, twitching, nausea, vomiting, diarrhea, or see or hear things that are not there. These may be signs of a serious condition called serotonin syndrome. Your risk may be higher if you also take certain other medicines that affect serotonin levels in your body.

Using too much of this medicine may cause infertility (unable to have children). Talk with your doctor before using this medicine if you plan to have children.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or over-the-counter (OTC) medicines and herbal or vitamin supplements.

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

Allergies

Inform your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Additionally 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 oxycodone and naloxone combination in the pediatric population. Safety and efficacy have not been established.

Geriatric

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

Breast Feeding

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

Interactions with Medications

Although certain medications 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 clinician may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are using 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 drug with any of the following medications is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Levoketoconazole
• Nalmefene
• Naltrexone
• Safinamide
• Samidorphan

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

• Abiraterone Acetate
• Acepromazine
• Aclidinium
• Adagrasib
• Alfentanil
• Almotriptan
• Alosetron
• Alprazolam
• Alvimopan
• Amantadine
• Amifampridine
• Amineptine
• Amiodarone
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Amprenavir
• Anileridine
• Apalutamide
• Aprepitant
• Aripiprazole
• Aripiprazole Lauroxil
• Armodafinil
• Asciminib
• Asenapine
• Atazanavir
• Atropine
• Avacopan
• Baclofen
• Belladonna
• Belzutifan
• Benperidol
• Bentazepam
• Benzhydrocodone
• Benzphetamine
• Benztropine
• Berotralstat
• Biperiden
• Boceprevir
• Bosentan
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Bupropion
• Buspirone
• Butabarbital
• Butorphanol
• Calcium Oxybate
• Cannabidiol
• Cannabis
• Carbamazepine
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Cenobamate
• Ceritinib
• Cetirizine
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Cimetidine
• Cinacalcet
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clemastine
• Clidinium
• Clobazam
• Clomipramine
• Clonazepam
• Clopidogrel
• Clorazepate
• Cloxazolam
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Conivaptan
• Crizotinib
• Cyclobenzaprine
• Cyclopentolate
• Cyclosporine
• Cyproheptadine
• Dabrafenib
• Dantrolene
• Daridorexant
• Darifenacin
• Darunavir
• Delavirdine
• Delorazepam
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexamethasone
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diacetylmorphine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Dicyclomine
• Difenoxin
• Dihydrocodeine
• Diltiazem
• Dimenhydrinate
• Diphenhydramine
• Diphenoxylate
• Dolasetron
• Donepezil
• Doxepin
• Doxylamine
• Dronedarone
• Droperidol
• Duloxetine
• Efavirenz
• Elagolix
• Eletriptan
• Enflurane
• Enzalutamide
• Erdafitinib
• Erythromycin
• Escitalopram
• Esketamine
• Eslicarbazepine Acetate
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Etravirine
• Fedratinib
• Fenfluramine
• Fentanyl
• Fesoterodine
• Fexinidazole
• Flavoxate
• Flibanserin
• Fluconazole
• Flunitrazepam
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fosamprenavir
• Fosaprepitant
• Fosnetupitant
• Fosphenytoin
• Fospropofol
• Frovatriptan
• Furazolidone
• Gabapentin
• Gabapentin Enacarbil
• Gepirone
• Glycopyrrolate
• Glycopyrronium Tosylate
• Granisetron
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Homatropine
• Hydrocodone
• Hydromorphone
• Hydroxyamphetamine
• Hydroxytryptophan
• Hydroxyzine
• Hyoscyamine
• Idelalisib
• Imatinib
• Imipramine
• Indinavir
• Ipratropium
• Iproniazid
• Isocarboxazid
• Isoflurane
• Itraconazole
• Ivacaftor
• Ketamine
• Ketazolam
• Ketobemidone
• Ketoconazole
• Lacosamide
• Lanreotide
• Larotrectinib
• Lasmiditan
• Lefamulin
• Lemborexant
• Lenacapavir
• Letermovir
• Levocetirizine
• Levomilnacipran
• Levorphanol
• Linezolid
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lomitapide
• Lopinavir
• Loprazolam
• Lorazepam
• Lorcaserin
• Lorlatinib
• Lormetazepam
• Loxapine
• Lumacaftor
• Magnesium Oxybate
• Mavacamten
• Meclizine
• Medazepam
• Melitracen
• Melperone
• Mepenzolate
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaclazepam
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Methylene Blue
• Methylnaltrexone
• Metoclopramide
• Mibefradil
• Midazolam
• Mifepristone
• Milnacipran
• Mirabegron
• Mirtazapine
• Mitotane
• Mobocertinib
• Moclobemide
• Modafinil
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nafcillin
• Nalbuphine
• Naldemedine
• Nalorphine
• Naloxegol
• Naloxone
• Naratriptan
• Nefazodone
• Nelfinavir
• Netupitant
• Nevirapine
• Nialamide
• Nicomorphine
• Nilotinib
• Nitrazepam
• Nitrous Oxide
• Nordazepam
• Nortriptyline
• Octreotide
• Olanzapine
• Omaveloxolone
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxcarbazepine
• Oxitropium Bromide
• Oxybutynin
• Oxycodone
• Oxymorphone
• Ozanimod
• Palbociclib
• Palonosetron
• Papaveretum
• Paregoric
• Paroxetine
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenelzine
• Phenobarbital
• Phenytoin
• Pimozide
• Pinazepam
• Pipenzolate Bromide
• Piperacetazine
• Pipotiazine
• Pirenzepine
• Piritramide
• Pirtobrutinib
• Posaconazole
• Potassium Oxybate
• Prazepam
• Prednisone
• Pregabalin
• Primidone
• Procarbazine
• Prochlorperazine
• Procyclidine
• Promazine
• Promethazine
• Propantheline
• Propiverine
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Quinidine
• Quinine
• Ramelteon
• Ranitidine
• Ranolazine
• Rasagiline
• Remifentanil
• Remimazolam
• Remoxipride
• Ribociclib
• Rifabutin
• Rifampin
• Rifapentine
• Ritlecitinib
• Ritonavir
• Rizatriptan
• Rolapitant
• Ropeginterferon Alfa-2b-njft
• Saquinavir
• Scopolamine
• Secobarbital
• Selegiline
• Selpercatinib
• Sertindole
• Sertraline
• Sibutramine
• Sodium Oxybate
• Solifenacin
• Sotorasib
• Stramonium
• Sufentanil
• Sulpiride
• Sumatriptan
• Suvorexant
• Tapentadol
• Taurursodiol
• Telaprevir
• Telithromycin
• Temazepam
• Terbinafine
• Terodiline
• Tetrazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Thiothixene
• Tianeptine
• Tilidine
• Tiotropium
• Tizanidine
• Tocilizumab
• Tolonium Chloride
• Tolterodine
• Topiramate
• Tramadol
• Tranylcypromine
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trihexyphenidyl
• Trimeprazine
• Trimipramine
• Trofinetide
• Tropicamide
• Trospium
• Tryptophan
• Tucatinib
• Umeclidinium
• Venlafaxine
• Verapamil
• Vilazodone
• Voriconazole
• Vortioxetine
• Voxelotor
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine
• Zuranolone

Using this drug with any of the following drugs may cause an increased chance of certain side effects, but using both drugs may be the best therapy for you. If both medications are prescribed together, your physician may change the dose or how frequently you use one or both of the drugs.

• Clonidine
• St John's Wort
• Yohimbine

Interactions with Food/Tobacco/Alcohol

Certain drugs 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 drugs may additionally 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 medication with any of the following is normally not recommended, but may be unavoidable in some cases. If used together, your clinician 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
• Grapefruit Juice

Other Medical Problems

The presence of other medical issues may affect the use of this medicine. Make sure you inform your clinician if you have any other medical issues, especially:

• Adrenal problems or
• Alcohol abuse, or history of or
• Brain tumor, history of or
• Breathing problems (eg, hypoxia) or
• Chronic obstructive pulmonary disease (COPD) or
• Cor pulmonale (severe heart condition) or
• Depression or
• Drug dependence, especially with narcotics, or history of or
• Gallbladder disease or gallstones or
• Head injuries, history of or
• Weakened physical condition—Use with caution. May raise risk for more severe side effects.

• Asthma, acute or severe or
• Liver disease, moderate to serious or
• Respiratory depression (extremely slow breathing) or
• Stomach or bowel blockage (eg, paralytic ileus), known or suspected—Should not be used in patients with these conditions.

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

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

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Incidence not known

• Agitation
• blurred vision
• confusion
• cough
• darkening of the skin
• diarrhea
• difficult or troubled breathing
• difficulty swallowing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fast heartbeat
• fever
• hives, itching, skin rash
• irregular, fast or slow, or shallow breathing
• loss of appetite
• mental depression
• nausea
• overactive reflexes
• pale or blue lips, fingernails, or skin
• poor coordination
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• restlessness
• seizures
• shivering
• sweating
• talking or acting with excitement you cannot control
• tightness in the chest
• trembling or shaking
• twitching
• unusual tiredness or weakness
• vomiting

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

• Bigger, dilated, or enlarged pupils (black part of the eye)
• change in consciousness
• chest pain or discomfort
• cold, clammy skin
• coughing that sometimes produces a pink frothy sputum
• decreased awareness or responsiveness
• difficult, fast, noisy breathing
• increased sensitivity of the eyes to light
• increased sweating
• loss of consciousness
• severe sleepiness
• sleepiness or unusual drowsiness
• slow or irregular heartbeat
• swelling in the legs and ankles

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

• Back pain
• difficulty having a bowel movement
• difficulty with moving
• fear or nervousness
• feeling of warmth
• headache
• muscle pain or stiffness
• pain in the joints
• redness of the face, neck, arms, and occasionally, upper chest
• stomach pain
• sudden sweating
• trouble sleeping

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

In the U.S.

• Targiniq ER

In Canada

• Targin

Pharmacologic Class: Naloxone

Chemical Class: Oxycodone

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. This is especially important for elderly patients, who may be more sensitive to the effects of pain medicines. If too much of this medicine is taken for a long time, it may become habit-forming (causing mental or physical dependence).

It is very important that you understand the rules of the Opioid Analgesic REMS program to prevent addiction, abuse, and misuse of oxycodone. This medicine should also come with a Medication Guide. Read and follow these instructions carefully. Read it again each time you refill your prescription in case there is new information. Ask your doctor if you have any questions.

Swallow the extended-release tablet whole. Do not break, crush, cut, chew, or dissolve it.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (extended-release tablets):For moderate to severe pain: Patients who are not taking narcotic medicines: Adults—At first, 10 milligrams (mg) of oxycodone and 5 mg of naloxone every 12 hours. Your doctor may adjust your dose as needed. Children—Use and dose must be determined by your doctor. Patients who are taking regular oxycodone: Adults—The tablet is given every 12 hours. The total amount of milligrams (mg) per day is half of the total amount of regular oxycodone that is taken per day. The total amount per day will be given as 2 divided doses during the day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 80 mg of oxycodone and 40 mg of naloxone per day. Children—Use and dose must be determined by your doctor. Patients switching from other narcotic medicines: Adults—The tablet is given every 12 hours. The total amount of milligrams (mg) per day will be determined by your doctor and depends on which narcotic you were using. The total amount per day will be given as 2 divided doses during the day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 80 mg of oxycodone and 40 mg of naloxone per day. Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Oxycodone can cause serious unwanted effects if taken by adults who are not used to strong narcotic pain medicines, children, or pets. Make sure you store the medicine in a safe and secure place to prevent others from getting it.

Drop off any unused narcotic medicine at a drug take-back location right away. If you do not have a drug take-back location near you, flush any unused narcotic medicine down the toilet. Check your local drug store and clinics for take-back locations. You can also check the DEA web site for locations. Here is the link to the FDA safe disposal of medicines website: www.fda.gov/drugs/resourcesforyou/consumers/buyingusingmedicinesafely/ensuringsafeuseofmedicine/safedisposalofmedicines/ucm186187.htm