What is Embeda?

Use of morphine sulfate/naltrexone hydrochloride extended-release capsules increases the risk of opioid addiction, abuse, or misuse, which may cause overdose or death. Assess the risk prior to therapy and monitor for signs of addiction, abuse, or misuse during therapy. 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. Serious, life-threatening, or fatal respiratory depression may occur, particularly at treatment initiation and with dose increases. Monitor for signs of respiratory depression during treatment. Instruct patients on proper administration to reduce the risk of accidental overdose. Accidental ingestion can result in a fatal overdose, especially in children. Prolonged use during pregnancy may result in neonatal opioid withdrawal syndrome, which may be life-threatening if unnoticed and untreated. If prolonged use is required in a pregnant woman, advise the patient of the risk to the fetus. Instruct patients to avoid alcohol and alcohol-containing products as concomitant use may increase exposure and potentially cause a fatal overdose. Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients with inadequate alternative treatment options. Limit dosages and durations to the minimum required, and follow patients for signs and symptoms of respiratory depression and sedation .

Morphine and naltrexone combination is used to treat moderate to severe pain when around-the-clock pain relief is needed for a long period of time. This medicine should not be used to treat pain that you only have once in a while, or pain that can be relieved with non-narcotic medication.

Morphine is a narcotic analgesic (pain medicine). It acts 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 makes you want to use them. It will not produce any narcotic-like effects or cause mental or physical dependence.

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

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.

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.

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.

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.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Do not throw unused medicine in the trash. Flush the unused extended-release capsules down the toilet.

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:

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.

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.

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of morphine and naltrexone combination in the elderly. However, 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.

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.

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 taking 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.

• 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
• 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 doctor may change the dose or how often you use one or both of the medicines.

• Acepromazine
• Alfentanil
• Almotriptan
• Alprazolam
• Alvimopan
• Amineptine
• Amiodarone
• Amisulpride
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Anileridine
• Aripiprazole
• Asenapine
• Azithromycin
• Baclofen
• Benperidol
• Benzhydrocodone
• Benzphetamine
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Buspirone
• Butabarbital
• Butorphanol
• Captopril
• Carbamazepine
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Carvedilol
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Cimetidine
• Citalopram
• Clarithromycin
• Clobazam
• Clomipramine
• Clonazepam
• Clopidogrel
• Clorazepate
• Clozapine
• Cobicistat
• Cocaine
• Codeine
• Conivaptan
• Cyclobenzaprine
• Cyclosporine
• 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
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Felodipine
• Fentanyl
• Flibanserin
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fospropofol
• Frovatriptan
• Furazolidone
• Granisetron
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Imipramine
• Iproniazid
• Isocarboxazid
• Isoflurane
• Itraconazole
• Ivacaftor
• Ketamine
• Ketobemidone
• Ketoconazole
• Levomilnacipran
• Levorphanol
• Linezolid
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lofexidine
• Lopinavir
• Lorazepam
• Lorcaserin
• Loxapine
• 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
• 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
• Quercetin
• Quetiapine
• Quinidine
• Ramelteon
• Ranolazine
• Rasagiline
• Remifentanil
• Remoxipride
• Ritonavir
• Rizatriptan
• Samidorphan
• 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
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Venlafaxine
• Verapamil
• Vilazodone
• Vortioxetine
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

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

• Esmolol
• Gabapentin
• Gabapentin Enacarbil
• Lofexidine
• Rifampin
• Somatostatin
• Yohimbine

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

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:

• Alcohol abuse, or history of or
• Adrenal problems or
• Brain tumor, history of or
• Breathing or lung problems (eg, low oxygen levels, sleep apnea) or
• Central nervous system (CNS) depression, history of or
• Chronic obstructive pulmonary disease (COPD) or
• Cor pulmonale (serious 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 problems or
• Weakened physical condition—Use with caution. May increase risk for more serious side effects.

• Asthma, acute 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.

• 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.

It is very important that your doctor check your progress while you are taking this medicine, especially within the first 24 to 72 hours of treatment. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood tests may be needed to check for unwanted effects.

Do not use this medicine if you are using or have used an MAO inhibitor (eg, isocarboxazid [Marplan®], linezolid [Zyvox®], phenelzine [Nardil®], selegiline [Eldepryl®], tranylcypromine [Parnate®]) within 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 might want to steal this medicine.

This medicine will add to 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 medicine for allergies or colds, sedatives, tranquilizers, or sleeping medicine, other prescription pain medicine or narcotics, medicine for seizures or barbiturates, muscle relaxants, or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the other medicines listed above while you are using this medicine.

This medicine may be habit-forming. If you feel that 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 occur when you get up suddenly from a lying or sitting position. Getting up slowly may help lessen 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 direct you to take laxatives, drink a lot of fluids, or increase the amount of fiber in your diet. Be sure to follow the directions carefully, because continuing constipation can lead to more serious problems.

Do not use 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 right away if you notice these symptoms.

Before having any kind of surgery (including dental surgery) or emergency treatment, tell the medical doctor or dentist in charge that you are using this medicine. Serious side effects can occur if your medical doctor or dentist gives you certain other medicines without knowing that 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 type of allergic reaction called anaphylaxis, which can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth while you are using this medicine.

If you have been using this medicine regularly for several weeks or more, do not suddenly stop using it without first checking with your doctor. You may be directed to gradually reduce the amount you are using before stopping treatment completely, or to take another narcotic for a while, to lessen 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 baby. 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 about how this medicine may affect your baby.
• Call your doctor if you become extremely 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 hospital emergency room immediately if your baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, difficulty breathing, or limpness. These may be symptoms 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 symptoms 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 nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.