FDA Drug Safety Communication:
- 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.
Codeine may be habit forming. Take codeine exactly as directed. Do not take more of it, take it more often, or take it in a different way than directed by your doctor. While taking codeine, discuss with your healthcare 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 codeine if you have or have ever had any of these conditions. Talk to your healthcare 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.
Codeine 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 take codeine. 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, 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.
When codeine was used in children, serious and life-threatening breathing problems such as slow or difficulty breathing and deaths were reported. Codeine should never be used to treat pain or a cough in children younger than 18 years of age. If your child is currently prescribed a cough and cold medicine containing codeine, talk to your child's doctor about other treatments.
Taking certain medications during your treatment with codeine may increase the risk that you will experience breathing problems or other serious, life-threatening breathing problems, sedation, or coma. Tell your doctor if you are taking or plan to take any of the following medications: certain antibiotics such as erythromycin (Erytab, Erythrocin); certain antifungal medications including ketoconazole; benzodiazepines such as alprazolam (Xanax), diazepam (Diastat, Valium), estazolam, flurazepam, lorazepam (Ativan), and triazolam (Halcion); carbamazepine (Carbatrol, Epitol, Equetro, Tegretol, Teril); certain medications for human immunodeficiency virus (HIV) including indinavir (Crixivan), nelfinavir (Viracept), and ritonavir (Norvir, in Kaletra); medications for mental illness or nausea; other medications for pain; muscle relaxants; phenytoin (Dilantin, Phenytek); rifampin (Rifadin, Rimactane, in Rifamate); sedatives; sleeping pills; or tranquilizers. Your doctor may need to change the dosages of your medications and will monitor you carefully. If you take codeine with any of these medications and you develop any of the following symptoms, call your doctor immediately or seek emergency medical care: unusual dizziness, lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness. Be sure that your caregiver or family members know which symptoms may be serious so they can call the doctor or emergency medical care if you are unable to seek treatment on your own.
Drinking alcohol or using street drugs during your treatment with codeine also increases the risk that you will experience these serious, life-threatening side effects. Do not drink alcohol, take prescription or nonprescription medications that contain alcohol, or use street drugs during your treatment.
Tell your doctor if you are pregnant or plan to become pregnant. If you take codeine 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.
Do not allow anyone else to take your medication. Codeine may harm or cause death to other people who take your medication, especially children.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with codeine 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.
Why is this medication prescribed?
Codeine is used to relieve mild to moderate pain. It is also used, usually in combination with other medications, to reduce coughing. Codeine will help relieve symptoms but will not treat the cause of symptoms or speed recovery. Codeine belongs to a class of medications called opiate (narcotic) analgesics and to a class of medications called antitussives. When codeine is used to treat pain, it works by changing the way the brain and nervous system respond to pain. When codeine is used to reduce coughing, it works by decreasing the activity in the part of the brain that causes coughing.
Codeine is also available in combination with acetaminophen (Capital and Codeine, Tylenol with Codeine), aspirin, carisoprodol, and promethazine and as an ingredient in many cough and cold medications. This monograph only includes information about the use of codeine. If you are taking a codeine combination product, be sure to read information about all the ingredients in the product you are taking and ask your doctor or pharmacist for more information.
How should this medicine be used?
Codeine (alone or in combination with other medications) comes as a tablet, a capsule, and a solution (liquid) to take by mouth. It is usually taken every 4 to 6 hours as needed. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take codeine exactly as directed.
If you have taken codeine for several weeks or longer, do not stop taking the medication without talking to your doctor. Your doctor may decrease your dose gradually. If you suddenly stop taking codeine, you may experience withdrawal symptoms such as restlessness, widened pupils (black circles in the center of the eyes), teary eyes, irritability, anxiety, runny nose, difficulty falling asleep or staying asleep, yawning, sweating, fast breathing, fast heartbeat, chills, hair on your arms standing on end, nausea, loss of appetite, vomiting, diarrhea, stomach cramps, muscle aches, or backache.
Shake the solution well before each use to mix the medication evenly. Do not use a household spoon to measure your dose. Use the measuring cup or spoon that came with the medication or use a spoon that is made especially for measuring medication.
Other uses for this medicine
This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before taking codeine,
- tell your doctor and pharmacist if you are allergic to codeine, any other medications, or any of the ingredients in the codeine product you plan to take. Ask your doctor or pharmacist for a list of the ingredients.
- 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 2 weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate). Your doctor will probably tell you not to take codeine if you are taking one or more of these medications, or have taken them within the past 2 weeks.
- 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: bupropion (Aplenzin, Wellbutrin, Zyban); cyclobenzaprine (Amrix); diuretics ('water pills'); lithium (Lithobid); medications for cough, cold, or allergies; medications for anxiety or seizures; medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex, in Treximet), and zolmitriptan (Zomig); mirtazapine (Remeron); 5HT3serotonin 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); tramadol (Conzip); trazodone (Oleptro); and tricyclic antidepressants ('mood elevators') such as amitriptyline, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). Many other medications may also interact with codeine, 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 codeine.
- tell your doctor if you drink or have had recent abdominal or urinary tract surgery. Also tell your doctor if you have or have ever had seizures; mental illness; prostatic hypertrophy (enlargement of a male reproductive gland); urinary problems; low blood pressure; Addison's disease (condition in which the body does not make enough of certain natural substances); or thyroid, pancreatic, intestinal, gallbladder, liver, or kidney disease.
- you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of taking codeine.
- tell your doctor if you are breastfeeding. You should not breastfeed while taking codeine. Codeine can cause shallow breathing, difficulty or noisy breathing, confusion, more than usual sleepiness, trouble breastfeeding, or limpness in breastfed infants.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking codeine.
- you should know that this medication may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
- you should know that codeine 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 codeine. 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 codeine 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?
Codeine is usually taken as needed. If your doctor has told you to take codeine regularly, take 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 take a double dose to make up for a missed one.
What side effects can this medication cause?
Codeine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- stomach pain
- difficulty urinating
Some side effects can be serious. If you experience any of the following symptoms or those listed in the IMPORTANT WARNINGS section, stop taking codeine and 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
- noisy or shallow breathing
- difficulty breathing or swallowing
- changes in heartbeat
- changes in vision
Codeine may cause other side effects. Call your doctor if you have any unusual problems while you are 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).
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. http://www.upandaway.org
Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.
In case of emergency/overdose
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 taking codeine, 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:
- difficulty breathing
- slow or shallow breathing
- excessive drowsiness or sleepiness
- unable to respond or wake up
- loss of muscle tone
- cold and clammy skin
- slow 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 codeine.
Before having any laboratory test (especially those that involve methylene blue), tell your doctor and the laboratory personnel that you are taking codeine.
Selling or giving away this medication may cause death or harm to others and is illegal. Your prescription might not be refillable. Ask your pharmacist any questions you have about refilling your prescription.
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.
- Tuzistra XR® (as a combination product containing Chlorpheniramine, Codeine)
Brand names of combination products
- Airacof® (containing Codeine, Diphenhydramine, Phenylephrine)¶
- Ala-Hist AC® (containing Codeine, Phenylephrine)¶
- Allfen CD® (containing Codeine, Guaifenesin)¶
- Ambenyl® (containing Bromodiphenhydramine, Codeine)¶
- Ambophen® (containing Bromodiphenhydramine, Codeine)¶
- Antituss AC® (containing Codeine, Guaifenesin)¶
- Bitex® (containing Codeine, Guaifenesin)¶
- Bromanyl® (containing Bromodiphenhydramine, Codeine)¶
- Bromotuss® with Codeine (containing Bromodiphenhydramine, Codeine)¶
- Brontex® (containing Codeine, Guaifenesin)
- Bron-Tuss® (containing Codeine, Guaifenesin)¶
- Brovex CB® (containing Brompheniramine, Codeine)¶
- Brovex PBC® (containing Brompheniramine, Codeine, Phenylephrine)¶
- Calcidrine® (containing Anhydrous Calcium Iodide, Codeine)¶
- Cheracol® with Codeine (containing Codeine, Guaifenesin)¶
- Cheratussin® (containing Codeine, Guaifenesin)¶
- Codafen® (containing Codeine, Guaifenesin)¶
- Codimal PH® (containing Codeine, Phenylephrine, Pyrilamine)¶
- Cotab A® (containing Chlorpheniramine, Codeine)¶
- Demi-Cof® (containing Chlorpheniramine, Codeine, Phenylephrine, Potassium Iodide)¶
- Dex-Tuss® (containing Codeine, Guaifenesin)¶
- Diabetic Tussin C® (containing Codeine, Guaifenesin)¶
- Dicomal-PH® (containing Codeine, Phenylephrine, Pyrilamine)¶
- Duraganidin NR® (containing Codeine, Guaifenesin)¶
- EndaCof AC® (containing Brompheniramine, Codeine)¶
- Endal CD® (containing Codeine, Diphenhydramine, Phenylephrine)¶
- ExeClear-C® (containing Codeine, Guaifenesin)¶
- Gani-Tuss NR® (containing Codeine, Guaifenesin)¶
- Giltuss Ped-C® (containing Codeine, Guaifenesin, Phenylephrine)¶
- Glydeine® (containing Codeine, Guaifenesin)¶
- Guaifen AC® (containing Codeine, Guaifenesin)¶
- Guiatuss AC® (containing Codeine, Guaifenesin)
- Guiatussin® with Codeine (containing Codeine, Guaifenesin)¶
- Halotussin AC® (containing Codeine, Guaifenesin)¶
- Iophen® (containing Codeine, Guaifenesin)¶
- Mar-cof CG® (containing Codeine, Guaifenesin)¶
- Maxiphen CD® (containing Codeine, Guaifenesin, Phenylephrine)¶
- M-Clear WC® (containing Codeine, Guaifenesin)¶
- M-End PE® (containing Brompheniramine, Codeine, Phenylephrine)¶
- Mytussin AC® (containing Codeine, Guaifenesin)¶
- Nalex® AC (containing Brompheniramine, Codeine)
- Notuss AC® (containing Chlorpheniramine, Codeine)¶
- Notuss PE® (containing Codeine, Phenylephrine)¶
- Pediacof® (containing Chlorpheniramine, Codeine, Phenylephrine, Potassium Iodide)¶
- Pedituss® (containing Chlorpheniramine, Codeine, Phenylephrine, Potassium Iodide)¶
- Pentazine VC® (containing Codeine, Phenylephrine, Promethazine)¶
- Pentazine® with Codeine (containing Codeine, Promethazine)¶
- Phenergan® VC with Codeine (containing Codeine, Phenylephrine, Promethazine)
- Phenergan® with Codeine (containing Codeine, Promethazine)¶
- Poly-Tussin AC® (containing Brompheniramine, Codeine, Phenylephrine)¶
- Prometh® with Codeine (containing Codeine, Guaifenesin, Promethazine)¶
- Robafen AC® (containing Codeine, Guaifenesin)¶
- Robichem AC® (containing Codeine, Guaifenesin)¶
- Robitussin® AC (containing Codeine, Guaifenesin)
- Rolatuss® (containing Ammonium Chloride, Chlorpheniramine, Codeine, Phenylephrine)¶
- Romilar AC® (containing Codeine, Guaifenesin)¶
- Tusnel C® (containing Brompheniramine, Codeine, Guaifenesin)¶
- Tussi Organidin® (containing Codeine, Guaifenesin)¶
- Tussiden C® (containing Codeine, Guaifenesin)¶
- Tussirex® (containing Caffeine, Codeine, Pheniramine, Phenylephrine, Salicylic Acid)¶
- Tusso-C® (containing Codeine, Guaifenesin)¶
- Vanacof® (containing Codeine, Dexchlorpheniramine, Phenylephrine)
- Z Tuss AC® (containing Chlorpheniramine, Codeine)¶
- Zodryl AC® (containing Chlorpheniramine, Codeine)¶
- Zotex C® (containing Codeine, Phenylephrine, Pyrilamine)¶
¶ This branded product is no longer on the market. Generic alternatives may be available.