Precipitated Withdrawal

Precipitated opioid withdrawal, or POW, is an avoidable condition frequently caused by drug interactions with opioids. Learn what drugs affect that type of withdrawal to avoid it.

Opioid withdrawal symptoms often start when someone stops taking an opioid cold turkey. However, in some cases, withdrawal can start even when you keep taking the opioid. This occurrence is called precipitated withdrawal and can be caused by taking medications that interact with opioids. If you take opioids, it is important to know how to avoid precipitated withdrawal.

What is Precipitated Withdrawal?

Precipitated opioid withdrawal (POW) occurs when taking another medication causes you to go into opioid withdrawal. Opioids work by binding to receptors on cells in your brain. These receptors are called mu receptors. When you take a drug that also binds to the mu receptor, the new drug can displace the opioid. Sometimes, the new drug can block the opioid from binding to the receptor altogether. This process causes withdrawal symptoms. Because the withdrawal is caused, or precipitated, by the new drug, this phenomenon is called precipitated withdrawal.

Acute vs. Precipitated Withdrawal

Acute withdrawal and precipitated withdrawal have similar symptoms. However, precipitated withdrawal symptoms may be more intense. A possible reason for this reaction is that all the opioid receptors are blocked all at once in POW. Conversely, in acute withdrawal, the opioid wears off naturally. Therefore, acute withdrawal symptoms may have a slower start before they fully kick in.

Drugs That Can Cause Precipitated Withdrawal

Many different drugs can cause precipitated withdrawal because they work on the same mu-opioid receptors on cells that opioids use. As such, they prevent the opioid from having access to the receptor, leading to POW symptoms. Such drugs include:

• Buprenorphine: This drug is the active agent in various drugs for medication-assisted therapy for opioid use. After opioid detox, taking a drug like buprenorphine can help to control opioid cravings. It is a partial opioid agonist, meaning that it binds to the mu-opioid receptor but does not have the full effect of other opioids. It is sold under several brand names including Subutex and Suboxone.
• Butorphanol: This drug is sometimes used for pain. It is a partial opioid agonist. Therefore, it can cause POW.
• Nalbuphine: Similar to butorphanol, this agent can be used for pain. It is also a partial opioid agonist and can cause POW.
• Naloxone: Also known as Narcan, naloxone is a life-saving opioid reversal drug. It is mainly used when someone is having an overdose. It is an opioid antagonist, meaning that it displaces opioids and stops them from binding to the mu receptor. As such, by blocking opioids, it can cause POW.
• Naltrexone: Also known by its brand name Vivitrol, naltrexone can be used for both alcohol and opioid addiction. It is an opioid antagonist that can cause POW.
• Alvimopan: Also known as Entereg, this drug is used in hospitals for certain bowel problems that can happen after surgery. It is an opioid antagonist. Alvimopan cannot be used if you have just taken opioids for more than seven straight days.
• Naloxegol: Sold under the brand name Movantik, naloxegol is used to stop opioid-induced constipation (OIC). It was created for people who use opioids and is designed to work only in the intestines. Naloxegol is an opioid antagonist. It is made from naloxone combined with another compound so that it does not cross into the brain to cause withdrawal. However, doctors have found it can cause POW if you have problems with their blood-brain barrier, which blocks drugs from entering the brain.
• Naldemidine: Also known by its brand name Symproic, naldemedine is used to treat OIC. It is an opioid antagonist. It can cause POW in people with blood-brain barrier problems.
• Methylnaltrexone: Also known as Relistor, methylnaltrexone is an opioid antagonist for OIC. In people with blood-brain barrier problems, it can cause POW.

However, other drugs can also cause withdrawal symptoms by causing the body to clear some opioids more quickly than it otherwise would. These drugs include:

• Rifampin, a tuberculosis drug
• Phenytoin, a seizure drug
• St. John’s Wort, an over-the-counter supplement used for mood
• Phenobarbital, a seizure drug
• Carbamazepine, a seizure drug

Symptoms of Precipitated Withdrawal

Symptoms of POW are similar to those of acute withdrawal and can include:

• Agitation
• Anxiety
• Muscle aches and pains
• Tear production
• Problems sleeping
• Runny nose
• Sweat
• Yawning
• Stomach cramps
• Diarrhea
• Big pupils
• Goosebumps
• Nausea and vomiting

How Long Does Precipitated Withdrawal Last?

The amount of time precipitated withdrawal lasts is based on multiple factors. Based on your situation, your doctor will be able to give you a good idea of how long you should expect symptoms to last. Factors include:

• If the drug that caused the withdrawal is short-acting or long-acting
• How much of the drug you took
• Which opioid you use, how much you take and how long you have taken it

How to Stop Precipitated Withdrawal

If POW symptoms have started, it is not too late to treat them. Doctors can treat precipitated withdrawal in the emergency room. They will work with you to manage your symptoms. The exact treatment they use depends on:

• What kind of opioid you were taking
• How many opioids you were taking
• How long you have been taking the opioid
• What drug precipitated the withdrawal
• How much of the drug caused the withdrawal

Avoiding Precipitated Withdrawal

The best way to avoid precipitated withdrawal is to make sure your doctor and pharmacist know all the medicines you are taking. Even if you are using illicit opioids, it is important to tell your doctor. People have gotten POW when they did not tell their doctor they were taking illicit opioids, and the doctor prescribed a medication that inadvertently caused POW. It is also important to get all your medicines from a single pharmacy. By doing so, the pharmacist will have a record of all your medications in their computer. The pharmacist can then check for drug interactions and advise you on the best way to take your medications to avoid precipitated withdrawal.

When Is Safe to Start Opioid Antagonists?

When to start opioid antagonists depends on a variety of factors. If someone is overdosing, it is important to give them an opioid antagonist like naloxone right away to save their life. However, some antagonists, like naltrexone, should only be used after you have not taken opioids for 7 to 10 days. Others drugs, like buprenorphine, depend on which opioids you were taking. Based on your current situation, your doctor will be able to advise you on the safest antagonist to take and when you should start taking it.

Editor – Thomas Christiansen

With over a decade of content experience, Tom produces and edits research articles, news and blog posts produced for Advanced Recovery Systems. Read more

Medically Reviewed By – Dr. Jessica Pyhtila, PharmD

Dr. Jessica Pyhtila is a Clinical Pharmacy Specialist based in Baltimore, Maryland with practice sites in inpatient palliative care and outpatient primary care at the Department of Veteran Affairs. Read more