AUDIENCE: Pharmacy, Internal Medicine, Psychiatry, Neurology, Family Practice
ISSUE: FDA review has found that the growing combined use of opioid medicines with benzodiazepines or other drugs that depress the central nervous system (CNS) has resulted in serious side effects, including slowed or difficult breathing and deaths. Opioids are used to treat pain and cough; benzodiazepines are used to treat anxiety, insomnia, and seizures. In an effort to decrease the use of opioids and benzodiazepines, or opioids and other CNS depressants, together, FDA is adding Boxed Warnings, our strongest warnings, to the drug labeling of prescription opioid pain and prescription opioid cough medicines, and benzodiazepines. See the Drug Safety Communication, available at: http://www.fda.gov/Drugs/DrugSafety/ucm518473.htm, for a listing of all approved prescription opioid pain and cough medicines, and benzodiazepines and other CNS depressants.
FDA conducted and reviewed several studies showing that serious risks are associated with the combined use of opioids and benzodiazepines, other drugs that depress the CNS, or alcohol (see the FDA Drug Safety Communication, available at: http://www.fda.gov/Drugs/DrugSafety/ucm518473.htm, for a Data Summary). Based on these data, FDA is requiring several changes to reflect these risks in the opioid and benzodiazepine labeling, and new or revised patient Medication Guides. These changes include the new Boxed Warnings and revisions to the Warnings and Precautions, Drug Interactions, and Patient Counseling Information sections of the labeling.
FDA is continuing to evaluate the evidence regarding combined use of benzodiazepines or other CNS depressants with medication-assisted therapy (MAT) drugs used to treat opioid addiction and dependence. FDA is also evaluating whether labeling changes are needed for other CNS depressants, and will update the public when more information is available.
BACKGROUND: Opioids are powerful prescription medicines that can help manage pain when other treatments and medicines cannot be taken or are not able to provide enough pain relief. Benzodiazepines are a class of medicines that are widely used to treat conditions including anxiety, insomnia, and seizures.
RECOMMENDATION: Health care professionalsshould limit prescribing opioid pain medicines with benzodiazepines or other CNS depressants only to patients for whom alternative treatment options are inadequate. If these medicines are prescribed together, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. Warn patients and caregivers about the risks of slowed or difficult breathing and/or sedation, and the associated signs and symptoms. Avoid prescribing prescription opioid cough medicines for patients taking benzodiazepines or other CNS depressants, including alcohol.
Patients taking opioids with benzodiazepines, other CNS depressant medicines, or alcohol, and caregivers of these patients, should seek medical attention immediately if they or someone they are caring for experiences symptoms of unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Hydrocodone may be habit-forming. Do not take more of it, take it more often, or take it in a different way than directed by your doctor. 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, has overused prescription medications, or if you have or have ever had depression or another mental illness. There is a greater risk that you will overuse hydrocodone if you have or have ever had any of these conditions.
Do not allow anyone else to take your medication. Hydrocodone may harm or cause death to other people who take your medication, especially children. Keep hydrocodone in a safe place so that no one else can take it accidentally or on purpose. Be especially careful to keep hydrocodone out of the reach of children. Keep track of how many capsules or tablets are left so you will know if any medication is missing.
Hydrocodone may cause slowed or stopped breathing, 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. Your doctor will adjust your dose to control your pain and decrease the risk that you will experience serious breathing problems. Tell your doctor if you have or have ever had slowed breathing or asthma. Your doctor will probably tell you not to take hydrocodone. 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, 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 weakened 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.
Drinking alcohol, taking prescription or nonprescription medications that contain alcohol, or using street drugs during your treatment with hydrocodone increases the risk that you will experience breathing problems or other serious, life-threatening side effects. It is especially important that you do not drink any drinks that contain alcohol or take any prescription or nonprescription medications that contain alcohol during your treatment with hydrocodone extended-release capsules and extended-release tablets. Talk to your doctor about the risks of drinking alcohol or using street drugs during your treatment with hydrocodone products.
Taking certain other medications or stopping treatment with certain other medications while you are taking hydrocodone may increase the risk that you will experience breathing problems or other serious, life-threatening side effects. Tell your doctor if you are taking, plan to take or plan to stop taking any of the following medications: certain antifungal medications including itraconazole (Onmel, Sporanox), ketoconazole (Extina, Nizoral, Xolegel), and voriconazole (Vfend); carbamazepine (Carbatrol, Epitol, Equetro, Tegretol, others); cimetidine; clarithromycin (Biaxin, in Prevpac); erythromycin (E.E.S., Erythromycin, others); other narcotic pain medications; medications for anxiety, seizures, mental illness, or nausea; certain medications for human immunodeficiency virus (HIV) including ritonavir (Norvir, in Kaletra, in Viekira Pak); muscle relaxants; phenytoin (Dilantin, Phenytek); rifampin (Rifadin, Rimactane, in Rifamate, in Rifater); sedatives; sleeping pills; or tranquilizers.
Swallow hydrocodone extended-release capsules or extended-release tablets whole; do not chew, break, divide, crush, or dissolve them. Hydrocodone extended-release capsules and extended-release tablets are difficult to crush, break or dissolve. If you swallow broken, chewed, or crushed extended-release capsules or extended-release tablets, you may receive too much hydrocodone at once. This may cause serious problems, including overdose and death.
Tell your doctor if you are pregnant or plan to become pregnant. If you take hydrocodone 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 hydrocodone and each time you refill 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 (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication Guide.
Talk to your doctor about the risks of taking hydrocodone.
Why is this medication prescribed?
Hydrocodone is used to relieve severe pain. Hydrocodone is only used to treat people who are expected to need medication to relieve severe pain around-the-clock for a long time and who cannot be treated with other medications or treatments. Hydrocodone extended-release (long-acting) capsules or extended-release tablets should not be used to treat pain that can be controlled by medication that is taken as needed. Hydrocodone is in a class of medications called opiate (narcotic) analgesics. It works by changing the way the brain and nervous system respond to pain.
This monograph only includes information about the use of hydrocodone alone. If you are taking a hydrocodone combination product, be sure to read information about all the ingredients in the hydrocodone-combination monograph and ask your doctor or pharmacist for more information.
How should this medicine be used?
Hydrocodone comes as an extended-release (long-acting) capsule and an extended-release (long-acting) tablet to take by mouth. The extended-release capsule is usually taken once every 12 hours. The extended-release tablet is usually taken once daily. Take hydrocodone at around the same time(s) every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take hydrocodone exactly as directed by your doctor.
Swallow the extended-release capsules or extended-release tablets one at a time with plenty of water. Swallow each capsule or tablet as soon as you put it in your mouth. Do not presoak, wet, or lick the extended-release tablets before you put them in your mouth.
Your doctor will probably start you on a low dose of hydrocodone and may gradually increase your dose, not more than once every 3 to 7 days if needed to control your pain. After your take hydrocodone for a period of time, your body may become used to the medication. If this happens, your doctor may increase your dose of hydrocodone or may prescribe a different medication to help control your pain. Talk to your doctor about how you are feeling during your treatment with hydrocodone.
Do not stop taking hydrocodone without talking to your doctor. If you suddenly stop taking hydrocodone, you may experience withdrawal symptoms such as restlessness, teary eyes, runny nose, yawning, sweating, chills, hair standing on end, muscle pain, widened pupils (black circles in the middle of the eyes), irritability, anxiety, back or joint pain, weakness, stomach cramps, difficulty falling asleep or staying asleep, nausea, loss of appetite, vomiting, diarrhea, fast breathing, or fast heartbeat. Your doctor will probably decrease your dose gradually.
Other uses for this medicine
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before taking hydrocodone,
- tell your doctor and pharmacist if you are allergic to hydrocodone, any other medications, or any of the ingredients in hydrocodone extended-release capsules or extended-release tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
- tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following medications: antihistamines (found in cough and cold medications); amiodarone (Cordarone, Nexterone, Pacerone); azithromycin (Zithromax, Zmax); butorphanol; chlorpromazine; citalopram (Celexa); cyclobenzaprine (Amrix); dextromethorphan (found in many cough medications; in Nuedexta); dronedarone (Multaq); haloperidol (Haldol); laxatives such as lactulose (Cholac, Constulose, Enulose, others); levofloxacin (Levaquin); lithium (Lithobid); medications for irritable bowel disease, Parkinson's disease, ulcers, and urinary problems; 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); nalbuphine; pentazocine (Talwin); 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 desvenlafaxine (Khedezla, Pristiq), duloxetine (Cymbalta), milnacipran (Savella), and venlafaxine (Effexor); trazodone (Oleptro); or tricyclic antidepressants ('mood elevators') such as amitriptyline, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). Also tell your doctor or pharmacist if you are taking or receiving the following medications or have stopped taking them within the past two weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate). Many other medications may also interact with hydrocodone, 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 and tryptophan.
- tell your doctor if you have any of the conditions mentioned in the IMPORTANT WARNING section, a blockage or narrowing of your stomach or intestines, or paralytic ileus (condition in which digested food does not move through the intestines). Your doctor may tell you not to take hydrocodone.
- tell your doctor if you have or have ever had low blood pressure, difficulty urinating, seizures, or thyroid, gall bladder, pancreas, liver, or kidney disease. If you are taking the extended-release tablets, also tell your doctor if you have or have ever had difficulty swallowing, colon cancer (cancer that begins in the large intestine), esophageal cancer (cancer that begins in the tube that connects the mouth and stomach), heart failure (HF; condition in which the heart cannot pump enough blood to other parts of the body), or heart rhythm problems such long QT syndrome (condition that increases the risk of developing an irregular heartbeat that may cause fainting or sudden death).
- tell your doctor if you are breastfeeding.
- you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking hydrocodone.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking hydrocodone.
- you should know that hydrocodone may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
- you should know that hydrocodone may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start taking hydrocodone. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up.
- you should know that hydrocodone may cause constipation. Talk to your doctor about changing your diet and using other medications to treat or prevent constipation.
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What should I do if I forget a dose?
Skip the missed dose and continue your regular dosing schedule. Do not take more than one dose of hydrocodone extended-release capsules in 12 hours or extended-release tablets in 24 hours.
What side effects can this medication cause?
Hydrocodone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- stomach pain
- dry mouth
- back pain
- tightening of the muscles
- difficult, frequent, or painful urination
- ringing in the ears
- difficulty falling asleep or staying asleep
- foot, leg, or ankle swelling
- uncontrollable shaking of a part of the body
Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING or SPECIAL PRECAUTIONS sections, call your doctor immediately or get emergency medical treatment:
- chest pain
- 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
- swelling of your eyes, face, lips, tongue, or throat
- changes in heartbeat
- difficulty swallowing or breathing
Hydrocodone may cause other side effects. Call your doctor if you have any unusual problems while taking 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 (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
What should I know about storage and disposal of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Flush any medication that is outdated or no longer needed down the toilet. Talk to your pharmacist about the proper disposal of your medication.
In case of emergency/overdose
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
Symptoms of overdose may include the following:
- slowed breathing
- muscle weakness
- cold, clammy skin
- narrowed or widened pupils
- slowed heartbeat
What other information should I know?
Keep all appointments with your doctor and laboratory. Your doctor will order certain lab tests to check your body's response to hydrocodone.
Before having any laboratory test (especially those that involve methylene blue), tell your doctor and the laboratory personnel that you are taking hydrocodone.
This prescription is not refillable. Be sure to schedule appointments with your doctor on a regular basis so that you do not run out of hydrocodone if your doctor wants you to continue taking this medication. If you continue to have pain after you finish your hydrocodone prescription, 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.
- Zohydro ER®