Morphine and naltrexone (Oral)

Morphine and naltrexone combination is used to treat moderate to severe pain when you need pain relief all day and for a long time. This medicine should not be used for pain that happens only occasionally, or pain that can be managed with non-narcotic medication.

Morphine is a narcotic analgesic (pain medicine). It works on the central nervous system (CNS) to relieve pain.

Naltrexone is an opioid antagonist. It blocks the effects of narcotics, especially the "high" feeling that can lead to misuse. It will not create any narcotic-like effects or cause mental or physical dependence.

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 that your doctor checks your progress while you are taking this medicine, especially in the first 24 to 72 hours of treatment. This will help your doctor see if the medicine is working correctly and decide if you should keep taking it. Blood tests may be needed to look for unwanted effects.

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

It is against the law and dangerous for anyone else to use your medicine. Keep your unused medicine in a safe and secure place. People who are addicted to drugs may want to steal this medicine.

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

This medicine may be habit-forming. If you think the medicine is not working as well, do not use more than your prescribed dose. Call your doctor for instructions.

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

Using narcotics for a long time can cause severe constipation. To prevent this, your doctor may tell you to take laxatives, drink plenty of fluids, or eat more fiber. Be sure to follow these directions carefully, because ongoing constipation can lead to more serious issues.

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

Before any surgery (including dental surgery) or emergency treatment, tell the medical doctor or dentist that you are using this medicine. Serious side effects can happen if your medical doctor or dentist prescribes certain other medicines without knowing you are using morphine and naltrexone combination.

This medicine may make you dizzy, drowsy, or lightheaded. Do not drive or do anything else that could be dangerous until you know how this medicine affects you.

This medicine may cause a serious allergic reaction called anaphylaxis, which can be life-threatening and needs 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.

If you have been using this medicine regularly for several weeks or more, do not stop using it suddenly without first consulting your doctor. You may need to gradually reduce the amount you are using before stopping completely, or take another narcotic for a while, to reduce the chance of withdrawal side effects.

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

For nursing mothers taking this medicine:

• Talk to your doctor if you have any questions about taking morphine or how this medicine may affect your baby.
• Call your doctor if you become extremely tired and have trouble 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 hospital emergency room immediately if your baby shows signs of increased sleepiness (more than usual), trouble breastfeeding, trouble breathing, or limpness. These may be signs of an overdose and need immediate medical attention.

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 (the inability to have children). Talk with your doctor before using this medicine if you plan to have children.

Do not take other medicines unless you have discussed them with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

In deciding to use a drug, the risks of taking the drug must be weighed against the beneficial it will do. This is a decision you and your doctor will make. For this drug, 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 medications. 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 morphine and naltrexone 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 morphine and naltrexone combination in the elderly. Nevertheless, elderly patients are more likely to have age-related heart, kidney, liver, or lung problems, which may require caution and an adjustment in the dose for patients receiving morphine and naltrexone combination.

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 prior to taking this drug while breastfeeding.

Interactions with Medicines

Although certain drugs should not be used together at all, in other cases two different medications may be used together even if an interaction might occur. In these cases, your physician may want to change the dose, or other precautions may be necessary. When you are using this medicine, it is especially important that your healthcare professional know if you are using any of the medications 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 drugs is not recommended. Your doctor may decide not to treat you with this drug or change some of the other medicines you take.

• Alfentanil
• Alphaprodine
• Anileridine
• Benzhydrocodone
• Buprenorphine
• Butorphanol
• Codeine
• Diacetylmorphine
• Difenoxin
• Dihydrocodeine
• Diphenoxylate
• Ethylmorphine
• Fentanyl
• Hydrocodone
• Hydromorphone
• Ketobemidone
• Levorphanol
• Meperidine
• Methadone
• Morphine
• Morphine Sulfate Liposome
• Nalbuphine
• Nalmefene
• Naltrexone
• Nicomorphine
• Opium
• Opium Alkaloids
• Oxycodone
• Oxymorphone
• Papaveretum
• Paregoric
• Piritramide
• Propoxyphene
• Remifentanil
• Safinamide
• Samidorphan
• Sufentanil
• Tapentadol
• Tilidine
• Tramadol

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 clinician may change the dose or how frequently you use one or both of the medicines.

• Acepromazine
• Alfentanil
• Almotriptan
• Alprazolam
• Alvimopan
• Amifampridine
• Amineptine
• Amiodarone
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Anileridine
• Aripiprazole
• Asenapine
• Azithromycin
• Baclofen
• Benperidol
• Benzhydrocodone
• Benzphetamine
• Bremelanotide
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Bupropion
• Buspirone
• Butabarbital
• Butorphanol
• Calcium Oxybate
• Cannabidiol
• Cannabis
• Captopril
• Carbamazepine
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Carvedilol
• Cetirizine
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Cimetidine
• Citalopram
• Clarithromycin
• Clobazam
• Clomipramine
• Clonazepam
• Clopidogrel
• Clorazepate
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Conivaptan
• Cyclobenzaprine
• Cyclosporine
• Daridorexant
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diltiazem
• Diphenhydramine
• Diphenoxylate
• Dolasetron
• Donepezil
• Doxepin
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Doxylamine
• Dronedarone
• Droperidol
• Duloxetine
• Eletriptan
• Enflurane
• Erythromycin
• Escitalopram
• Esketamine
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Felodipine
• Fenfluramine
• Fentanyl
• Flibanserin
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fospropofol
• Frovatriptan
• Furazolidone
• Gabapentin
• Gabapentin Enacarbil
• Gepirone
• Granisetron
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Imipramine
• Iproniazid
• Isocarboxazid
• Isoflurane
• Itraconazole
• Ivacaftor
• Ketamine
• Ketobemidone
• Ketoconazole
• Lacosamide
• Lasmiditan
• Lemborexant
• Levocetirizine
• Levomilnacipran
• Levorphanol
• Linezolid
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lopinavir
• Lorazepam
• Lorcaserin
• Loxapine
• Magnesium Oxybate
• Meclizine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Methylene Blue
• Methylnaltrexone
• Metoclopramide
• Midazolam
• Milnacipran
• Mirtazapine
• Moclobemide
• Molindone
• Moricizine
• Nalbuphine
• Naldemedine
• Nalorphine
• Naloxegol
• Naloxone
• Naratriptan
• Nefazodone
• Nialamide
• Nicomorphine
• Nilotinib
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxycodone
• Oxymorphone
• Ozanimod
• Palonosetron
• Papaveretum
• Paregoric
• Paroxetine
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenelzine
• Phenobarbital
• Pimozide
• Piperacetazine
• Pipotiazine
• Piritramide
• Potassium Oxybate
• Prazepam
• Pregabalin
• Primidone
• Procarbazine
• Prochlorperazine
• Promazine
• Promethazine
• Propofol
• Protriptyline
• Quazepam
• Quercetin
• Quetiapine
• Quinidine
• Ramelteon
• Ranolazine
• Rasagiline
• Remifentanil
• Remimazolam
• Remoxipride
• Ritonavir
• Rizatriptan
• Ropeginterferon Alfa-2b-njft
• Scopolamine
• Secobarbital
• Selegiline
• Sertindole
• Sertraline
• Sibutramine
• Simeprevir
• Sodium Oxybate
• St John's Wort
• Sufentanil
• Sulpiride
• Sumatriptan
• Sunitinib
• Suvorexant
• Tapentadol
• Telaprevir
• Temazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Ticagrelor
• Tilidine
• Tizanidine
• Tocophersolan
• Tolonium Chloride
• Topiramate
• Tramadol
• Tranylcypromine
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Venlafaxine
• Verapamil
• Vilazodone
• Vortioxetine
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine
• Zuranolone

Using this medication with any of the following medicines may cause an increased risk of certain adverse effects, but using both drugs may be the best therapy for you. If both medications are prescribed together, your clinician may change the dose or how often you use one or both of the medicines.

• Esmolol
• Lofexidine
• Rifampin
• Somatostatin
• Yohimbine

Interactions with Food/Tobacco/Alcohol

Certain medications 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 advised, 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 Issues

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

• Alcohol abuse, or history of or
• Adrenal problems or
• Brain tumor, history of or
• Breathing or lung issues (eg, low oxygen levels, sleep apnea) or
• Central nervous system (CNS) depression, history of or
• Chronic obstructive pulmonary disease (COPD) or
• Cor pulmonale (severe heart condition) or
• Drug dependence, especially with narcotics, history of or
• Head injury, history of or
• Mental illness, or history of or
• Problems with passing urine or
• Prostatic hypertrophy (enlarged prostate, BPH) or
• Thyroid issues or
• Weakened physical condition—Use with caution. May raise chance for more severe side effects.

• Asthma, acute or serious or
• Lung or breathing issues, serious or
• Stomach or bowel blockage (eg, paralytic ileus)—Should not be used in patients with these conditions.

• Gallbladder disease or
• 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—Use with caution. The effects may be increased because 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:

More common

• Bloating or swelling of the face, arms, hands, lower legs, or feet
• chills
• confusion
• constipation
• drowsiness
• feeling of warmth
• irritability
• mental depression
• rapid weight gain
• redness of the face, neck, arms, and occasionally, upper chest
• relaxed and calm feeling
• restlessness
• sleepiness
• sudden sweating
• tingling of the hands or feet
• trembling or shaking of the hands or feet
• unusual weight gain or loss

Rare

• Abnormal dreams
• being forgetful
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• clumsiness or unsteadiness
• confusion about identity, place, and time
• dark urine
• decrease in frequency or volume of urination
• decreased awareness or responsiveness
• difficult or labored breathing
• difficult or painful urination
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• false beliefs that cannot be changed by facts
• fast heartbeat
• feeling of warmth
• fever
• indigestion
• loss of appetite
• nausea
• nervousness
• pains in the stomach, side, or abdomen, possibly radiating to the back
• poor insight and judgment
• problems with memory or speech
• redness of the face, neck, arms, and occasionally, upper chest
• seeing, hearing, or feeling things that are not there
• severe nausea or vomiting
• severe sleepiness
• sweating
• tightness in the chest
• trouble recognizing objects
• trouble thinking and planning
• trouble walking
• unusual tiredness or weakness
• vomiting
• yellow eyes or skin

Incidence not known

• Agitation
• cough
• darkening of the skin
• diarrhea
• difficulty swallowing
• dizziness or fainting
• hives, itching, skin rash
• overactive reflexes
• poor coordination
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• shivering
• talking or acting with excitement you cannot control
• twitching

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:

More common

• Anxiety
• belching
• decreased appetite
• difficulty with moving
• excess air or gas in the stomach or bowels
• full feeling
• heartburn
• muscle pain, spasm, or stiffness
• pain in the joints
• sleepiness or unusual drowsiness
• stomach discomfort or upset
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness
• weight loss

Rare

• Cold sweats
• dizziness
• dry mouth
• general feeling of discomfort or illness
• headache
• inability to have or keep an erection
• increased sweating
• lack or loss of strength
• loss in sexual ability, desire, drive, or performance
• night sweats
• pressure in the stomach
• stomach tenderness
• swelling of the stomach area
• trouble sleeping
• upper abdominal or stomach pain

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.

• Embeda

Pharmacologic Class: Naltrexone

Chemical Class: Morphine

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.

Morphine and naltrexone combination extended-release capsules are for use in opioid-tolerant patients only. If you are uncertain whether or not you are opioid-tolerant, check with your doctor before using this medicine.

It is very important that you understand the rules of the Opioid Analgesic REMS program to prevent addiction, abuse, and misuse of morphine and naltrexone combination. 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 capsule whole. Do not break, crush, or chew it.

If you cannot swallow the extended-release capsule, you may open it and pour the contents into a small amount of applesauce. Stir this mixture well and swallow it without chewing. Drink a glass of water to make sure you have swallowed the pellets completely. Do not give this medicine through a nasogastric or gastric tube.

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 capsules):For pain: For patients taking Embeda® as the first pain medicine: Adults—At first, one capsule once a day. Your doctor may adjust your dose as needed. Children—Use and dose must be determined by your doctor. For patients switching from other oral morphine to Embeda®: Adults—The total daily dose is half of the total morphine dose that you were previously taking. The daily dose may be given once a day or as 2 divided doses given every 12 hours. Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, 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.

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