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 professionals should 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.
Why is this medication prescribed?
The combination of chlordiazepoxide and clidinium bromide is used to treat peptic ulcers and irritable bowel syndrome. It helps relieve stomach spasms and abdominal cramps.
How should this medicine be used?
The combination of chlordiazepoxide and clidinium bromide comes as a capsule to be taken by mouth. It usually is taken three or four times a day, before meals and at bedtime. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take chlordiazepoxide and clidinium bromide exactly as directed.
Chlordiazepoxide can be habit-forming. Therefore, when taking chlordiazepoxide and clidinium bromide, do not take a larger dose, take it more often, or for a longer time than your doctor tells you to. Tolerance may develop with long-term or excessive use, making this medication less effective. This medication must be taken regularly to be effective. Do not skip doses even if you feel that you do not need them. Do not take chlordiazepoxide and clidinium bromide for more than 4 months or stop taking this medication without talking to your doctor. Stopping the drug suddenly can worsen your condition and cause withdrawal symptoms (anxiousness, sleeplessness, and irritability). Your doctor probably will 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 chlordiazepoxide and clidinium bromide,
- tell your doctor and pharmacist if you are allergic to chlordiazepoxide, clidinium , alprazolam (Xanax), clonazepam (Klonopin), clorazepate (Tranxene), diazepam (Valium), estazolam (ProSom), flurazepam (Dalmane), lorazepam (Ativan), oxazepam (Serax), prazepam (Centrax), temazepam (Restoril), triazolam (Halcion), or any other drugs.
- tell your doctor and pharmacist what prescription and nonprescription drugs you are taking, especially amantadine (Symadine, Symmetrel); antihistamines; atenolol (Tenormin); cimetidine (Tagamet); digoxin (Lanoxin); disulfiram (Antabuse); fluoxetine (Prozac); isoniazid (INH, Laniazid, Nydrazid); ketoconazole (Nizoral); levodopa (Larodopa, Sinemet); medications for depression, thyroid, high blood pressure, seizures, Parkinson's disease, asthma, colds, or allergies; oral contraceptives; muscle relaxants; probenecid (Benemid, Probalan); propoxyphene (Darvon); propranolol (Inderal); rifampin (Rifadin); sedatives; theophylline (Theo-Dur); tranquilizers; sleeping pills; valproic acid (Depakene); or vitamins. These medications may add to the drowsiness caused by chlordiazepoxide and clidinium bromide.
- tell your doctor if you have or have ever had glaucoma; prostate problems; high blood pressure; seizures; or lung, thyroid, kidney, heart, or liver disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking this medication, call your doctor immediately.
- talk to your doctor about the risks and benefits of taking chlordiazepoxide and clidinium bromide if you are 65 years of age or older. Older adults should not usually take chlordiazepoxide and clidinium bromide because it is not as safe or effective as other medication(s) that can be used to treat the same condition.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking chlordiazepoxide and clidinium bromide.
- you should know that this medication may make you drowsy. Do not drive a car or operate machinery until you know how it affects you.
- ask your doctor about the safe use of alcohol while you are taking this medication. Alcohol can make the side effects of this medication worse.
- tell your doctor if you use tobacco products. Cigarette smoking may decrease the effectiveness of this medication.
What should I do if I forget a dose?
If you take several doses per day and miss a 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?
Side effects from chlordiazepoxide and clidinium bromide are common and include:
- upset stomach
- weakness or tiredness
- dry mouth
- bloated feeling
- eyes more sensitive to sunlight than usual
- taste changes
- changes in appetite
Tell your doctor if any of these symptoms are severe or do not go away:
- difficulty urinating
- frequent urination
- blurred vision
- dilated pupils
- changes in sex drive or ability
If you experience any of the following symptoms, call your doctor immediately:
- jaw, neck, and back muscle spasms
- slow or difficult speech
- shuffling walk
- persistent, fine tremor or inability to sit still
- difficulty breathing or swallowing
- severe skin rash
- yellowing of the skin or eyes
- irregular heartbeat
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).
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 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.
What other information should I know?
Keep all appointments with your doctor.
Do not let anyone else take your medication. 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.
Brand names of combination products
- Clindex® (containing Chlordiazepoxide, Clidinium)¶
- Librax® (containing Chlordiazepoxide, Clidinium)
¶ This branded product is no longer on the market. Generic alternatives may be available.