Buprenorphine Warnings, Risks, and Complications

RISK OF OPIOID ADDICTION AND OPIOID MISUSE: Buprenorphine is a Schedule III controlled substance. It can be abused similar to full opioid agonists (narcotic pain medications and heroin). Do not take this medicine at a higher dose or more frequently than prescribed. Misuse and abuse of buprenorphine can put you at risk of opioid overdose and death. 

SERIOUS BREATHING PROBLEMS: Patients taking buprenorphine and other opioids can develop irregular, slow, or shallow breathing at any time during treatment, but especially when they first start taking the medicine or after an increase in the dose. Respiratory depression can lead to death. Accidental ingestion of buprenorphine by a child can cause fatal respiratory depression and death. Older adults (age 65 years and above) and those on high doses of buprenorphine are at a higher risk of developing breathing problems. 

Tell your doctor if you have asthma, chronic obstructive pulmonary disease (COPD), or other respiratory conditions before starting buprenorphine treatment. Make sure you know how to recognize the signs and symptoms of breathing difficulties (slow or shallow breathing or a bluish tinge to the toes or fingers). Seek emergency medical care if you develop these symptoms. 

You should know that alcohol and certain other medications, such as sedatives, anti-anxiety medicines (benzodiazepines), skeletal muscle relaxants, and other opioids, can also cause slowed breathing. Using these medications during buprenorphine treatment can result in profound sedation, CNS depression, and respiratory depression. 

NEONATAL ABSTINENCE SYNDROME: Taking buprenorphine for opioid addiction treatment during pregnancy can result in a potentially life-threatening condition called neonatal abstinence syndrome or neonatal opioid withdrawal syndrome in the baby after birth. This happens because the baby is exposed to the opioid medicine from the mother while in the womb and becomes dependent on opioids. After birth, the baby experiences withdrawal effects due to the sudden removal of exposure to the opioid. However, the benefits of treatment for opioid dependence in pregnant women need to be weighed against the risks of neonatal opioid withdrawal. 

Signs and symptoms of this complication include high-pitched crying, fussiness, poor feeding, trembling, irritability, sleep difficulties, and convulsions. If you take buprenorphine to treat opioid use disorder during your pregnancy, be on the lookout for these signs in your baby after birth and seek immediate medical help if they occur.

ADRENAL INSUFFICIENCY: There are reports of adrenal insufficiency in people who take opioids, especially if they take opioids for more than one month. Adrenal insufficiency is when the adrenal glands don’t make enough hormones. The symptoms of this condition can be non-specific and may include nausea, vomiting, loss of appetite, tiredness, weakness, dizziness, and low blood pressure. If this happens, you may require treatment with replacement corticosteroids. You may also need to stop taking the opioid to allow your adrenal function to recover. Currently, available information does not specify which particular opioids are more likely to cause adrenal insufficiency.

WITHDRAWAL SYMPTOMS: Suddenly stopping buprenorphine after using it for a long time can result in withdrawal effects such as yawning, sweating, chills, restlessness, irritability, anxiety, runny nose, widened pupils, and suicidal thoughts. These symptoms tend to be milder after stopping a partial agonist compared to a full opioid agonist. Nonetheless, do not stop taking buprenorphine without talking to your doctor first. Your doctor will guide you on a medically supervised withdrawal (lowering the dose gradually) to prevent acute withdrawal.

LIVER DAMAGE: Based on clinical trials and post-marketing reports on adverse events, buprenorphine appears to cause liver injury, including hepatitis (inflammation) and jaundice, in some people. The degree of liver injury can range from a temporary asymptomatic increase in liver enzymes to severe hepatic necrosis, liver failure, hepatorenal syndrome, hepatic encephalopathy, and death. 

Tell your doctor if you have a history of liver problems, hepatitis B or hepatitis C virus infections, or are taking other hepatotoxic drugs that can damage the liver. It is unclear what role ongoing injection drug use plays in contributing to liver injury. Lowering the dose or stopping buprenorphine may result in an improvement in liver function. Your healthcare provider may order liver function tests before starting buprenorphine treatment to establish a baseline and thereafter for periodic monitoring during treatment. If you have hepatic impairment, you may need to take a lower dose of buprenorphine.

ALLERGIC REACTIONS: Rarely, a hypersensitivity to buprenorphine products can result in throat closing, swelling, and anaphylactic shock. Seek emergency medical attention if you develop skin rash, hives, itching, swelling, or difficulty breathing while on this opioid partial agonist.

OVERDOSE IN OPIOID-NAIVE PATIENTS: Taking even a 2-mg dose of buprenorphine sublingual tablet for pain control can result in overdose and death in patients who are opioid naive (no prior exposure to opioid drugs). Never use buprenorphine sublingual tablets for pain relief.

PRECIPITATION OF WITHDRAWAL SYMPTOMS : Buprenorphine has partial agonist properties and can precipitate opioid withdrawal signs and symptoms in people who are physically dependent on full opioid agonists if buprenorphine is administered sublingually or parenterally before the effects of other opioids have subsided. Opioid-dependent patients should take buprenorphine at least 48-72 hours after the last dose of a long-acting opioid such as methadone and at least 12 hours after the last dose of a short-acting opioid such as heroin. 

DENTAL PROBLEMS: There are reports of serious dental problems, including cavities, tooth decay, infections, and tooth loss after using buprenorphine products such as sublingual tablets and buccal films, even in people with no prior dental issues. However, despite these risks, buprenorphine is an important treatment option for opioid use disorder, and its benefits outweigh the risks. 

Before starting buprenorphine therapy, tell your doctor if you have a history of dental problems such as cavities or gum disease. Schedule a visit with your dentist soon after starting buprenorphine and tell them you are on this medicine. Your dentist will recommend regular checkups and develop a customized prevention plan. 

Continue taking buprenorphine as prescribed if you develop dental problems, but seek evaluation without delay. Do not suddenly stop taking buprenorphine without consulting your prescribing physician. Abrupt cessation of buprenorphine treatment can have serious health consequences, including withdrawal symptoms, relapse to opioid use, overdose, and death. 

Take extra precautions to lower the risk of dental issues. Take a big sip of water after the buprenorphine dissolves. Swish the water gently in your mouth before swallowing it. Wait at least 60 minutes before brushing your teeth to avoid causing damage. 

QT PROLONGATION: Studies have shown that people taking buprenorphine-containing products can develop a heart abnormality called QT prolongation. This is more likely in patients with other risk factors. Tell your doctor if you have a personal or family history of QT prolongation, hypokalemia (low potassium levels), severe hypomagnesemia (very low magnesium levels), slow heart rate, recent conversion from atrial fibrillation (a heart rhythm abnormality), congestive heart failure, or are taking a medication called digitalis.

IMPAIRED ABILITY TO DRIVE OR OPERATE MACHINERY: Taking buprenorphine can cause mental and physical impairments and affect your ability to drive or operate machinery safely. This risk is especially high when you first start taking the medicine and after a dose adjustment. Be careful when driving or operating hazardous machinery until you are reasonably sure that buprenorphine does not adversely affect your ability to safely perform these activities.

ORTHOSTATIC HYPOTENSION: Buprenorphine, like other opioid drugs, can cause orthostatic hypotension (low blood pressure) when going from a lying or sitting position to standing. Get up slowly from bed to lower your risk of falls. 

INCREASED INTRACRANIAL PRESSURE: Buprenorphine and other opioids can lead to an increase in the CSF (cerebrospinal fluid) pressure. Tell your doctor if you have a history of head injury or brain lesions before starting treatment.