Butorphanol Injection

FDA Drug Safety Communication:

[Posted 4/13/2023]

• As part of its ongoing efforts to address the nation's opioid crisis, FDA is requiring several updates to the prescribing information of opioid pain medicines. The changes are being made to provide additional guidance for safe use of these drugs while also recognizing the important benefits when used appropriately. The changes apply to both immediate-release (IR) and extended-release/long-acting preparations (ER/LA).
• Updates to the IR opioids state that these drugs should not be used for an extended period unless the pain remains severe enough to require an opioid pain medicine and alternative treatment options are insufficient, and that many acute pain conditions treated in the outpatient setting require no more than a few days of an opioid pain medicine.
• Updates to the ER/LA opioids recommend that these drugs be reserved for severe and persistent pain requiring an extended period of treatment with a daily opioid pain medicine and for which alternative treatment options are inadequate.
• A new warning is being added about opioid-induced hyperalgesia (OIH) for both IR and ER/LA opioid pain medicines. This includes information describing the symptoms that differentiate OIH from opioid tolerance and withdrawal.
• Information in the boxed warning for all IR and ER/LA opioid pain medicines will be updated and reordered to elevate the importance of warnings concerning life-threatening respiratory depression, and risks associated with using opioid pain medicines in conjunction with benzodiazepines or other medicines that depress the central nervous system (CNS).
• Other changes will also be required in various other sections of the prescribing information to educate clinicians, patients, and caregivers about the risks of these drugs.

Butorphanol injection may be habit forming, especially with prolonged use. Use butorphanol injection exactly as directed. Do not use more of it, use it more often, or use it in a different way than directed by your doctor. While using butorphanol injection, discuss with your health care provider your pain treatment goals, length of treatment, and other ways to manage your pain. Tell your doctor if you or anyone in your family drinks or has ever drunk large amounts of alcohol, uses or has ever used street drugs, or has overused prescription medications, or has had an overdose, or if you have or have ever had depression or another mental illness. There is a greater risk that you will overuse butorphanol if you have or have ever had any of these conditions. Talk to your health care provider immediately and ask for guidance if you think that you have an opioid addiction or call the U.S. Substance Abuse and Mental Health Services Administration (SAMHSA) National Helpline at 1-800-662-HELP.

Butorphanol injection may cause serious or life-threatening breathing problems, especially during the first 24 to 72 hours of your treatment and any time your dose is increased. Your doctor will monitor you carefully during your treatment. Tell your doctor if you have or have ever had slowed breathing or asthma. Your doctor will probably tell you not to use butorphanol injection. Also tell your doctor if you have or have ever had lung disease such as chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways), a head injury a brain tumor, or any condition that increases the amount of pressure in your brain. The risk that you will develop breathing problems may be higher if you are an older adult or are weak or malnourished due to disease. If you experience any of the following symptoms, call your doctor immediately or get emergency medical treatment: slowed breathing, long pauses between breaths, or shortness of breath.

Taking certain other medications with butorphanol injection may increase the risk of serious or life-threatening breathing problems. Tell your doctor and pharmacist if you are taking or plan to take any of the following medications: medications for anxiety, mental illness or nausea; benzodiazepines such as alprazolam (Xanax), chlordiazepoxide (Librium), clonazepam (Klonopin), diazepam (Diastat, Valium), estazolam, flurazepam, lorazepam (Ativan), oxazepam, temazepam (Restoril), and triazolam (Halcion); muscle relaxants; other narcotic pain medications; sedatives; sleeping pills; or tranquilizers. Your doctor may need to change the doses of your medication and will monitor you carefully.

Drinking alcohol, taking prescription or nonprescription medications that contain alcohol, or using street drugs during your treatment with butorphanol injection also increases the risk that you will experience these serious, life-threatening side effects. Do not drink alcohol or use street drugs during your treatment.

Tell your doctor if you are pregnant or plan to become pregnant. If you use butorphanol injection regularly during your 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: irritability, hyperactivity, abnormal sleep, high-pitched cry, uncontrollable shaking of a part of the body, vomiting, diarrhea, or failure to gain weight.

Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with butorphanol injection and each time you fill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (https://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication Guide.

Butorphanol injection is used to relieve moderate to severe pain. Butorphanol injection is also used to relieve pain during labor and to prevent pain and decrease awareness before or during surgery. Butorphanol is in a class of medications called opioid agonist-antagonists. It works by changing the way the body senses pain.

Butorphanol injection comes as a liquid to be injected into a muscle or vein. When butorphanol injection is used to relieve pain, it is usually given once every 3 to 4 hours as needed. When butorphanol injection is used to relieve pain during surgery, it may be given 60 to 90 minutes before surgery and then as needed during the surgery. When butorphanol injection is used to relieve pain during labor, it may be given once every 4 hours but should not be given less than 4 hours before delivery is expected.

You may receive butorphanol injection in a hospital, or you may be given the medication to use at home. If you have been told to administer butorphanol injection at home, it is very important that you use the medication exactly as directed. Follow the directions that you are given carefully, and ask your doctor, pharmacist or nurse if you have any questions or do not understand the directions.

If you have been told to use butorphanol injection at home, do not stop using the medication without talking to your doctor. If you suddenly stop using butorphanol injection, you may experience withdrawal symptoms such as nervousness, agitation, shakiness, diarrhea, chills, sweats, difficulty falling asleep or staying asleep, confusion, loss of coordination, or hallucinations (seeing things or hearing voices that do not exist). Your doctor will probably decrease your dose gradually.

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

Before using butorphanol injection,

• tell your doctor and pharmacist if you are allergic to butorphanol, any other medications, or ingredients in butorphanol injection. Ask your pharmacist 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 or plan to take. Be sure to mention any of the following: antidepressants; antihistamines; barbiturates such as butabarbital (Butisol), pentobarbital (Nembutal), phenobarbital, or secobarbital (Seconal); cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; in Nuedexta); erythromycin (E.E.S., Eryc, Erythrocin, others); medications for seizures; lithium (Lithobid); medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Alsuma, Imitrex, in Treximet), and zolmitriptan (Zomig); mirtazapine (Remeron); 5HT₃ serotonin blockers such as alosetron (Lotronex), dolasetron (Anzemet), granisetron (Kytril), 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); or tricylic antidepressants ('mood elevators') such as amitriptyline, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil); theophylline (Theochron, Uniphyl, others); and trazodone (Oleptro). 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 within the past two weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate). Many other medications may also interact with butorphanol, 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 carefully for side effects.
• tell your doctor what herbal products you are taking, especially St. John's wort or tryptophan.
• tell your doctor if you have or have ever had problems urinating; a heart attack; high blood pressure; or heart, kidney, or liver disease.
• tell your doctor if you are breastfeeding. Some women who use butorphanol injection may have increased amounts of the medication in their breast milk, which can cause serious or life-threatening side effects in their breastfed babies. You should also call your baby's doctor or get emergency help if your baby is sleepier than usual, has trouble breastfeeding or breathing, or becomes limp.
• you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of using butorphanol.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are using butorphanol injection.
• you should know that butorphanol injection may make you drowsy and dizzy. Do not drive a car or operate machinery for at least one hour after you receive a dose. After one hour has passed, do not drive until you are certain that you are not dizzy, drowsy, or less alert than usual.

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

Butorphanol injection is usually used as needed. If your doctor has told you to use butorphanol injection regularly, use the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not use a double dose to make up for a missed one.

Butorphanol injection may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• excessive tiredness
• difficulty falling asleep or staying asleep
• unusual dreams
• headache
• constipation
• stomach pain
• feeling hot
• flushing
• pain, burning, numbness, or tingling in the hands or feet
• uncontrollable shaking of a part of your body
• nervousness
• hostility
• intense happiness
• feeling of floating
• sad mood
• blurred vision
• ringing in the ears
• ear pain
• unpleasant taste
• dry mouth
• difficulty urinating

Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNINGS section, call your doctor immediately or get emergency medical attention:

• 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
• difficulty breathing
• changes in heartbeat
• fainting
• rash
• hives

Butorphanol injection may cause other side effects. Call your doctor if you have any unusual problems while using this medication.

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

If you are using butorphanol injection at home, keep the medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from light, excess heat, and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

Store butorphanol injection in a safe place so that no one else can use it accidentally or on purpose. Keep track of how much medication is left so you will know if any is missing.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. https://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 has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

While using butorphanol injection, you should talk to your doctor about having a rescue medication called naloxone readily available (e.g., home, office). Naloxone is used to reverse the life-threatening effects of an overdose. It works by blocking the effects of opiates to relieve dangerous symptoms caused by high levels of opiates in the blood. Your doctor may also prescribe you naloxone if you are living in a household where there are small children or someone who has abused street or prescription drugs. You should make sure that you and your family members, caregivers, or the people who spend time with you know how to recognize an overdose, how to use naloxone, and what to do until emergency medical help arrives. Your doctor or pharmacist will show you and your family members how to use the medication. Ask your pharmacist for the instructions or visit the manufacturer's website to get the instructions. If symptoms of an overdose occur, a friend or family member should give the first dose of naloxone, call 911 immediately, and stay with you and watch you closely until emergency medical help arrives. Your symptoms may return within a few minutes after you receive naloxone. If your symptoms return, the person should give you another dose of naloxone. Additional doses may be given every 2 to 3 minutes, if symptoms return before medical help arrives.

Symptoms of overdose may include the following:

• slow or shallow breathing
• difficulty breathing
• sleepiness
• unable to respond or wake up

Keep all appointments with your doctor and laboratory. Your doctor will order certain lab tests to check your body's response to butorphanol.

Before having any laboratory test (especially those that involve methylene blue), tell your doctor and the laboratory personnel that you are receiving butorphanol.

Do not let anyone use your medication. If you continue to have pain after you finish the butorphanol injection, call your doctor.

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

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