Buprenorphine Sublingual and Buccal (opioid dependence) : Uses, Side Effects, Interactions & More

TOPIC: Opioid Pain Relievers or Medicines to Treat Opioid Use Disorder: MedWatch Safety Alert – FDA Recommends Health Care Professionals Discuss Naloxone with All Patients when Prescribing.

AUDIENCE: Patient, Health Professional, Pharmacy

ISSUE: The FDA requires drug manufacturers for all opioid pain relievers and drugs to treat opioid use disorder (OUD) to add new naloxone recommendations to the prescribing information. This will help ensure that healthcare professionals discuss the availability of naloxone and assess each patient’s need for a prescription for naloxone when opioid pain relievers or medications are prescribed or refilled to treat OUD. The Medication Guides for Patients, available at: https://bit.ly/3hzDavc, will also be updated.

BACKGROUND:

Opioid pain relievers are medications that can help control pain when other treatments and medications cannot provide enough pain relief. Certain opioids are also used to treat OUD. Opioids have serious risks, including misuse and abuse, addiction, overdose, and death. Naloxone can help reverse opioid overdose to prevent death.

The misuse and abuse of prescription and illicit opioids and the risks of addiction, overdose and death are a public health crisis in the United States. As a result, the FDA is committed to encouraging healthcare professionals to raise awareness of the availability of naloxone when prescribing and dispensing opioid pain relievers or medications to treat OUD. The FDA held discussions about the availability of naloxone with the Advisory Committees for Analgesic and Anesthetic Drugs and Drug Safety and Risk Management, available at: https://bit.ly/3hx8tXG, which recommended that all patients being prescribed opioids for use in the outpatient setting would benefit from a conversation with their health care professional about the availability of naloxone.

RECOMMENDATION:

Patients:

• Talk to your health care professionals about the benefits of naloxone and how to obtain it.
• Recognize the signs and symptoms of a possible opioid overdose. These include slowed, shallow, or difficult breathing, severe sleepiness, or not being able to respond or wake up. If you know or think someone is overdosing, give the person naloxone if you have access to it, and always call 911 or go to an emergency room right away. Naloxone is a temporary treatment, so repeat doses may be required. Even if you give naloxone, you still need to get emergency medical help right away.
• If you have naloxone, make sure to tell your caregivers, household members, and other close contacts that you have it, where it is stored, and how to properly use it in the event of an overdose. When using opioid medicines away from home, carry naloxone with you and let those you are with know you have it, where it is, and how to use it. Read the Patient Information leaflet or other educational material and Instructions for Use that comes with your naloxone because it explains important information, including how to use the medicine.

Health Care Professionals:

• Discuss the availability of naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat OUD.
• Consider prescribing naloxone to patients prescribed medicines to treat OUD and patients prescribed opioid analgesics who are at increased risk of opioid overdose.
• Consider prescribing naloxone when a patient has household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose.
• Additionally, even if the patients are not receiving a prescription for an opioid analgesic or medicine to treat OUD, consider prescribing naloxone to them if they are at increased risk of opioid overdose.
• Educate patients and caregivers on how to recognize respiratory depression and how to administer naloxone. Inform them about their options for obtaining naloxone as permitted by their individual state, available at: https://www.usa.gov/state-health, dispensing and prescribing requirements or guidelines for naloxone. Emphasize the importance of calling 911 or getting emergency medical help right away, even if naloxone is administered.

For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.

Buprenorphine and the combination of buprenorphine and naloxone are used to treat opioid dependence (addiction to opioids, including heroin and narcotic pain relievers). Buprenorphine is in a class of drugs called opioid partial agonist-antagonists, and naloxone is in a class of drugs called opioid antagonists. Buprenorphine alone and the combination of buprenorphine and naloxone work to prevent withdrawal symptoms when someone stops taking opioid medications by producing effects similar to these medications.

Buprenorphine comes as a sublingual tablet. The combination of buprenorphine and naloxone comes as a sublingual tablet (Zubsolv) and as a sublingual film (Suboxone) to take under the tongue and as a buccal film (Bunavail) to apply between the gum and cheek. Once the proper dosage is determined by your doctor, these products are generally taken once a day. To help you remember to take or apply buprenorphine or buprenorphine and naloxone, take or apply it at around the same time every day. Follow the directions on your prescription label carefully and ask your doctor or pharmacist to explain any parts you do not understand. Take or apply buprenorphine or buprenorphine and naloxone exactly as directed. Do not take or apply more or less, take it or apply it more often than prescribed by your doctor.

Your doctor may decide to start your treatment with buprenorphine, which you will take in the doctor’s office. You will start with a low dose of buprenorphine and your doctor will increase your dose for 1 to 2 days before switching you to buprenorphine and naloxone. Depending on the type of opioid you were taking, a different option your doctor may choose is to start buprenorphine and naloxone treatment right away. Your doctor may increase or decrease your dose of buprenorphine and naloxone depending on your response.

If you are taking the sublingual tablets, place them under your tongue until they are completely melted. If you are taking more than two tablets, put them all under the tongue at the same time or put them under the tongue up to two at a time. Do not chew the tablets or swallow them whole. Do not eat, drink, or speak until the tablet has completely dissolved.

If you are using the buccal film, use your tongue to moisten the inside of your cheek or rinse your mouth with water before applying the film. Apply the film with a dry finger against the inside of the cheek. Then remove your finger and the film will stick to the inside of your cheek. If you are using two films, put another film on the inside of the other cheek at the same time. Do not apply films one on top of the other and do not apply more than two films to the inside of the mouth at a time. Leave the film (s) in your mouth until it dissolves. Do not cut, tear, chew, swallow, touch, or move the film as it dissolves. Do not eat or drink anything until the film dissolves completely.

If you are using the sublingual film, rinse your mouth with water before applying the film. Place the film with a dry finger under your tongue to the right or left of the center and hold the film in place for 5 seconds. If you are using two films, place the other on the opposite side under the tongue. Do not place the films on top of each other or close to each other. Do not use more than two films at a time. Do not cut, tear, chew, swallow, touch, or move the film as it dissolves. Do not eat or drink anything until the film dissolves completely.

If you need to switch from one buprenorphine or buprenorphine and naloxone product to another, your doctor may need to adjust your dose. Each time you receive your medication, make sure you have received the buprenorphine product that was prescribed for you. Ask your pharmacist if you are not sure you have received the correct medicine.

Do not stop taking or using buprenorphine or buprenorphine and naloxone without consulting your doctor. Stopping buprenorphine or buprenorphine and naloxone too quickly can cause withdrawal symptoms. Your doctor will tell you when and how to stop taking or using buprenorphine or buprenorphine and naloxone. If you suddenly stop taking or using buprenorphine or buprenorphine and naloxone, you may experience withdrawal symptoms such as hot flashes or flushes, restlessness, watery eyes, runny nose, sweating, chills, muscle pain, vomiting, or diarrhea.

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Before taking or using buprenorphine or buprenorphine and naloxone,

• Tell your doctor and pharmacist if you are allergic to buprenorphine, naloxone, any other medications, or any of the other ingredients in buprenorphine or buprenorphine and naloxone sublingual tablets or films. Ask your pharmacist or see the Medication Guide for a list of the ingredients.
• Tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking. Be sure to mention any of the following: antihistamines (found in cold and allergy medicines); antipsychotics such as aripiprazole (Abilify), asenapine (Saphris), cariprazine (Vraylar), chlorpromazine, clozapine (Versacloz), fluphenazine, haloperidol (Haldol), iloperidone (Fanapt), loxapine, lurasidone (Zprey, pavega), molperindone (Zprey), molidone (Invega) perphenazine, pimavanserin (Nuplazid), quetiapine (Seroquel), risperidone (Risperdal), thioridazine, thiothixene, trifluoperazine, and ziprasidone (Geodon); Benzodiazepines such as alprazolam (Xanax), chlordiazepoxide (Librium), clobazam (Onfi), clonazepam (Klonopin), clorazepate (Gen-Xene, Tranxene), diazepam (Diastat, Valium), estazolam, flurazepam, lorazepam (Ativan) quaralzepam (Ativan) quaralzepam (Ativan) quaralzepam (Ativan) quaral) , temazepam (Restoril) and triazolam (Halcion); diuretics (‘water pills’); erythromycin (E.E.S., Eryc, Erythrocin, others); certain HIV medications such as atazanavir (Reyataz, in Evotaz), delavirdine (Rescriptor), efavirenz (Sustiva, in Atripla), etravirine (Intelence), indinavir (Crixivan), nelfinavir (Viracept), nevirapine (Viramune), and ritonavir (Norvir , in Kaletra, in Technivie); Ipratropium (Atrovent); medications for irritable bowel disease, motion sickness, Parkinson’s disease, ulcers, or urinary problems; ketoconazole; medications for migraines such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Alsuma, Imitrex, in Treximet), and zolmitriptan (Zomig); mirtazapine (Remeron); muscle relaxants; opioid (narcotic) medications to control pain and cough; rifampicin (Rifadin, Rimactane, in Rifater, in Rifamate); medications for seizures such as carbamazepine (Epitol, Tegretol, Teril, others), phenobarbital, and phenytoin (Dilantin, Phenytek); 5HT3 serotonin blockers such as alosetron (Lotronex), granisetron (Sancuso, Sustol), ondansetron (Zofran, Zuplenz), or palonosetron (Aloxi); selective serotonin reuptake inhibitors such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Prozac, Pexeva), and sertraline (Zoloft); serotonin and norepinephrine reuptake inhibitors such as duloxetine (Cymbalta), desvenlafaxine (Khedezla, Pristiq), milnacipran (Savella), and venlafaxine (Effexor); sleeping pills; tramadol (Conzip); trazodone; or tricyclic antidepressants (‘mood elevators’) such as amitriptyline, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine. Also tell your doctor or pharmacist if you are taking or receiving the following monoamine oxidase (MAO) inhibitors or if you have stopped taking them in the last two weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine ( Nardil). , selegiline (Eldepryl, Emsam, Zelapar) or tranylcypromine (Parnate). Many other medications can also interact with buprenorphine or buprenorphine and naloxone, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you closely for side effects.
• Tell your doctor what herbal products you are taking, especially St. John’s wort and tryptophan.
• Tell your doctor if you drink or have ever drunk large amounts of alcohol and if you have or have ever had adrenal problems such as Addison’s disease (condition in which the adrenal gland produces less hormones than normal); benign prostatic hypertrophy (BPH, enlarged prostate gland); difficulty urinating a head injury; hallucinations (seeing things or hearing voices that are not there); a curve in the spine that makes breathing difficult; gallbladder disease; chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways); or thyroid, kidney, liver, or lung disease.
• Tell your doctor if you are pregnant or plan to become pregnant. If you become pregnant while taking or using buprenorphine or buprenorphine and naloxone, call your doctor. If you take or use buprenorphine or buprenorphine and naloxone tablets or films regularly during pregnancy, your baby may experience life-threatening withdrawal symptoms after birth. Tell your baby’s doctor right away if your baby experiences any of the following symptoms: fussiness, seizures, uncontrollable shaking of a part of the body, vomiting, diarrhea, or lack of weight gain.
• Tell your doctor if you are breastfeeding. Tell your baby’s doctor right away if your baby is more sleepy than usual or has trouble breathing while taking this medicine.
• If you are having surgery, including dental surgery, tell the doctor or dentist that you are taking or using buprenorphine or buprenorphine and naloxone.
• You should know that this medicine can decrease fertility in men and women. Talk to your doctor about the risks of using buprenorphine or buprenorphine and naloxone.
• You should know that buprenorphine or buprenorphine and naloxone can make you drowsy. Do not drive a car or operate machinery until you know how this medicine affects you.
• You should not drink alcohol or take prescription or over-the-counter medicines that contain alcohol while taking or using this medicine.
• You should know that buprenorphine or buprenorphine and naloxone can cause dizziness, lightheadedness, and fainting when you get up too quickly from lying down. This is more common when you start taking or using buprenorphine or buprenorphine and naloxone. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.

Unless your doctor tells you otherwise, continue your normal diet.

Take or apply the missed dose as soon as you remember. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take or double dose to make up for a missed one.

Buprenorphine or buprenorphine and naloxone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• headache
• stomach pain
• constipation
• difficulty falling asleep or staying asleep
• mouth numbness or redness
• tongue pain
• blurred vision
• back pain

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNINGS or SPECIAL PRECAUTIONS sections, call your doctor immediately:

• hives
• rash
• itching
• difficulty breathing or swallowing
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination, nausea, vomiting, or diarrhea
• nausea, vomiting, loss of appetite, weakness, or dizziness
• inability to get or keep an erection
• irregular menstruation
• decreased sexual desire
• slowed breathing
• upset stomach
• extreme tiredness
• confusion
• blurred vision
• slurred speech
• unusual bleeding or bruising
• lack of energy
• pain in the upper right part of the stomach
• yellowing of the skin or eyes
• dark-colored urine
• light-colored stools

Buprenorphine or buprenorphine and naloxone can cause other side effects. Call your doctor if you have any unusual problems while taking or using this medicine.

If you experience a serious side effect, you or your doctor can submit a report online to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medicine in the package it came in, tightly closed, and out of the reach of children. Buprenorphine or buprenorphine and naloxone may be a target for people who abuse prescription drugs or illegal drugs. Please keep it in a safe place so that no one else can use it accidentally or intentionally. Store buprenorphine or buprenorphine and naloxone at room temperature and away from excess heat and moisture (not in the bathroom). Do not freeze buprenorphine or buprenorphine and naloxone.

You should immediately dispose of any medications that are out of date or no longer needed through a drug take-back program. If you don’t have a take-back program nearby or one that you can access right away, dispose of unnecessary tablets or films by taking them out of the package and flushing them down the toilet. Call your pharmacist or manufacturer if you have questions or need help disposing of unnecessary medications.

It is important to keep all medicines out of the sight and reach of children, since many containers (such as those containing weekly pills and those for eye drops, creams, patches and inhalers) are not resistant to children and small children can easily open them. To protect young children from poisoning, always close the safety caps and immediately place the medicine in a safe place, one that is upright and out of their sight and reach. http://www.upandaway.org

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim collapsed, had a seizure, is having trouble breathing, or is unable to wake up, immediately call 911 for emergency services.

Symptoms of overdose may include the following:

• pinpoint pupils
• extreme drowsiness
• dizziness
• blurred vision
• slowed breathing

Keep all appointments with your doctor and the laboratory. Your doctor will order certain laboratory tests to check your body’s response to buprenorphine and naloxone.

Before having any laboratory test (especially those that involve methylene blue), tell your doctor and the laboratory personnel that you are using buprenorphine or buprenorphine and naloxone.

In the event of an emergency, you or a member of your family should inform the treating physician or emergency room staff that you are taking or using buprenorphine or buprenorphine and naloxone.

Do not inject buprenorphine or buprenorphine and naloxone sublingual film or tablets. Serious reactions can occur, including withdrawal symptoms.

Do not let anyone else take or use your medicine. Ask your pharmacist any questions you have about refilling your prescription.

It is important that you keep a written list of all prescription and over-the-counter (over-the-counter) medications you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should take this list with you each time you visit a doctor or if you go into hospital. It is also important information to take with you in case of emergencies.