SAFETY ALERT FOR ORAL BUPRENORPHINE

In January 2022, the Food and Drug Administration (FDA) issued a warning related to dental problems caused by buprenorphine when administered by dissolving in the mouth.

This warning follows reports of dental problems, including tooth decay, cavities, oral infections, and tooth loss. This serious adverse effect can occur whether or not you’ve had a history of dental problems. The FDA emphasizes that buprenorphine is an important treatment for opioid use disorder and that the benefits of treatment outweigh these dental risks.

If you currently take buprenorphine, continue taking it as prescribed. After the medication has completely dissolved in your mouth, take a large sip of water, swish it around gently, and then swallow. It is important to wait at least 1 hour before brushing your teeth. Contact your healthcare professional with any additional questions.

Opioids are a class of medications primarily used to help manage pain. They work by affecting specific receptors in your brain and other parts of the body.

Opioids are substances that can block pain signals in your nervous system. Due to their high risk for misuse and addiction, these drugs are prescription-only. Opioids are classified as controlled substances, meaning the federal government regulates their manufacturing, distribution, and use.

Natural opioids, also known as opiates, are made from the opium poppy plant and include drugs such as morphine and codeine. Opioids modified or made entirely in a laboratory are called semi-synthetic and synthetic, to reflect their manufacturing process.

The first opioid medication, morphine, was created in 1803. Since then, many different opioids have come onto the market. Some are added to products for more specific uses, such as cough treatment.

In the United States, many opioid-only and opioid combination drugs are used to treat sudden or short-term (acute) and chronic pain when other medications, such as ibuprofen or acetaminophen, aren’t strong enough.

Certain opioids are also used in the treatment of opioid use disorders. This is because they affect the brain differently from the drug that’s being misused.

Opioid products come in many forms. They differ in how you take them, how long they take to start working, and how long they keep working. Doctors can prescribe opioids as:

  • pills
  • lozenges
  • lollipops
  • suppositories
  • skin patches
  • injections

People can take most of these forms without assistance. Others, such as injectable forms, have to be administered by a healthcare professional.

How quickly opioids take effect can influence what conditions they’re used for. Immediate-release products start to work quickly after you take them, but they’re effective for shorter periods. Extended-release products release the medication over a longer period.

Immediate-release opioids treat acute and chronic pain. Extended-release opioids are typically only used to treat long-term, chronic pain when immediate-release opioids are no longer enough.

If your doctor prescribes extended-release opioids, they may also give you immediate-release opioids to treat breakthrough pain, particularly for cancer pain or pain during end-of-life care.

These products contain only opioids:

Buprenorphine

This drug is a long-acting opioid. Generic buprenorphine comes in a sublingual tablet (taken under the tongue), transdermal patch (for the skin), and injectable solution. The generic and brand-name injectable solutions are only given by a healthcare professional.

Examples of brand-name buprenorphine products include:

  • Belbuca, a buccal film
  • Probuphine, an intradermal implant
  • Butrans, a transdermal patch
  • Sublocade, a monthly injection

Some forms for chronic pain require round-the-clock treatment. Other forms of buprenorphine are available to treat opioid dependence.

Butorphanol

Butorphanol is a synthetic opioid that can provide a similar level of pain relief as morphine, but without many of the serious side effects. It comes in a nasal spray and injectable solution and is available in generic form only.

Butorphanol is an immediate-release product and is typically used for acute pain. It’s a common medication to manage pain after surgery, but doctors also prescribe it for acute migraine pain when other treatments aren’t effective.

Codeine sulfate

Codeine sulfate is only available as a generic drug in the United States. You might know it better as just “codeine.” It comes in a generic, immediate-release oral tablet, capsule, or oral syrup.

Codeine sulfate isn’t usually used for pain on its own. It’s typically combined with other medications like acetaminophen or ibuprofen to achieve a more comprehensive level of relief.

Many people know codeine as a cough medication, and that’s because cough suppression is its other primary use. It binds to receptors in your brainstem’s cough center and helps control your cough reflex.

Fentanyl

Fentanyl is a fully synthetic opioid that comes in generic and brand-name formulations. It’s used to manage severe pain and is available in immediate-release and extended-release products.

Generic fentanyl is prescribed as oral lozenges, extended-release transdermal patches, and an injectable solution that only a healthcare professional can administer. Brand-name fentanyl product Sublimaze is available as an injectable solution.

The transdermal patch is used for chronic pain in people who need round-the-clock treatment and who already regularly take opioid pain medications.

Other products are used for breakthrough pain in people who already receive round-the-clock opioids for severe pain conditions, such as cancer pain.

Hydrocodone bitartrate

Hydrocodone bitartrate is a semi-synthetic opioid. As a single ingredient, it’s available as a generic medication and as Hysingla, an extended-release oral tablet.

Hydrocodone is used for severe chronic pain in people who need round-the-clock treatment and aren’t helped by other first-line pain management options.

Hydromorphone

Hydromorphone is a semi-synthetic opioid used to treat severe pain. It’s not commonly prescribed due to its high potential for misuse and risk of serious side effects and overdose.

Generic hydromorphone comes in an oral solution, oral tablet, extended-release oral tablet, and rectal suppository. It’s also available in an injectable solution given by a healthcare professional.

Brand-name hydromorphone is Dilaudid, an oral solution or oral tablet.

The extended-release products are used for chronic pain in people who need around-the-clock treatment. The brand-name hydromorphone is Dilaudid, and it is an oral solution or oral tablet.

Levorphanol tartrate

Levorphanol is a long-acting opioid available in generic form.

It comes in an oral tablet or as an injectable solution to be used by medical professionals. Due to its broader mechanisms of action in the body compared to other opioids, levorphanol can be used for moderate to severe acute pain, including neuropathic pain.

Meperidine hydrochloride

Meperidine is typically used for moderate to severe acute pain and has a history of being used in surgical preparation to also help manage shivering. It’s available as a generic drug and as the brand-name drug Demerol.

Generic versions are available as an oral solution or oral tablet. Both are also available in an injectable solution for a healthcare professional to administer.

Methadone hydrochloride

Methadone hydrochloride is a synthetic, long-acting opioid. It’s available as a generic drug and under the brand names of:

  • Methadose, an oral solution, oral tablet, and dissolvable tablet
  • Methadone Diskets, a dissolvable tablet

It’s used for chronic pain in people who need round-the-clock treatment, and it’s also an opioid used in the treatment of opioid use disorders.

Methadone is available in an oral tablet, oral solution, dissolvable disket, and oral suspension. A healthcare professional can also administer it in an injectable solution.

Morphine sulfate

Morphine sulfate was the first opioid medication and remains the gold standard to which all other opioids’ effectiveness is compared. It’s available in an extended-release oral capsule, oral solution, oral tablet, extended-release oral tablet, rectal suppository, and solution for injection.

Morphine also comes in an opium tincture, which is dried opium poppy latex containing 1% morphine and codeine that’s mixed with alcohol. This form is used to reduce the number and frequency of bowel movements and can treat diarrhea in certain cases.

Brand-name morphine sulfate products include:

  • MS Contin, an extended-release oral tablet
  • Duramorph, a solution for injection
  • Roxanol, an immediate-release tablet and oral solution
  • Infumorph, an injectable solution

The extended-release products are used for chronic pain in people who need round-the-clock treatment. Immediate-release products are used for acute and chronic pain. Injectable products are only given by a healthcare professional.

Oxycodone

Oxycodone is a common semi-synthetic opioid. Some forms of oxycodone are available as generic drugs. Some are only available as brand-name drugs. Generic oxycodone comes in an oral capsule, oral solution, oral tablet, and extended-release oral tablet.

Brand-name versions include:

  • Oxaydo, an oral tablet
  • Roxicodone, an oral tablet
  • OxyContin, an extended-release oral tablet
  • Xtampza, an extended-release oral capsule
  • RoxyBond, an oral tablet

The extended-release products are used for chronic pain in people who need around-the-clock treatment. The immediate-release products are used for acute and chronic pain.

Oxymorphone

Generic oxymorphone is available in an oral tablet and an extended-release oral tablet. Brand-name oxymorphone is available as:

  • Opana, an oral tablet

The extended-release tablets are used for chronic pain in people who need around-the-clock treatment.

In June 2017, the Food and Drug Administration requested that manufacturers of the brand-name extended-release oxymorphone product, Opana ER, discontinue these drugs. They found that the benefit of taking this drug no longer outweighed the risk of serious complications related to misuse.

The immediate-release tablets are still used for acute and chronic pain, and extended-release tablets are still available in generic form.

Oxymorphone is also available in a form that’s injected into your body as the brand-name product Opana. It’s only given by a healthcare professional.

Tapentadol

Tapentadol is an opioid used because of its flexible treatment options. It can be used on its own or in combination with other pain drugs to help provide complete relief.

Tapentadol is only available in the brand-name versions Nucynta and Nucynta ER. It is an oral tablet or oral solution used for acute and chronic pain. Nucynta ER is an extended-release oral tablet used for chronic pain or severe pain caused by diabetic neuropathy (nerve damage) in people who need around-the-clock treatment.

Tramadol

Tramadol is an opioid analgesic that’s typically less potent than other opioids. The pain medication is also used off-label for conditions like premature ejaculation and restless leg syndrome. Generic tramadol comes in an extended-release oral capsule, oral tablet, and extended-release oral tablet. Brand-name tramadol comes as:

  • Conzip, an extended-release oral capsule
  • Ultram and Ultram ER, an oral tablet
  • Tramal, an oral tablet, oral capsule, liquid drops

The oral tablet is typically used for moderate to moderately severe acute pain. Extended-release products are used for chronic pain in people who need around-the-clock treatment. The external cream is used for musculoskeletal pain.

The following products combine an opioid with other drugs. Similar to the opioid-only products, these drugs come in different forms and have different uses:

Acetaminophen-caffeine-dihydrocodeine

This drug is typically only used for moderate to moderately severe acute pain. Generic acetaminophen-caffeine-dihydrocodeine comes in an oral tablet and an oral capsule. Common brand names include:

  • Trezix, an oral capsule
  • Dvorah, an oral tablet

Acetaminophen-codeine

This drug is typically only used for mild to moderate acute pain. Generic acetaminophen-codeine comes in an oral tablet and an oral solution. Brand-name acetaminophen-codeine comes as:

  • Capital and Codeine, an oral suspension
  • Tylenol with Codeine No. 3, an oral tablet
  • Tylenol with Codeine No. 4, an oral tablet

Aspirin-caffeine-dihydrocodeine

Aspirin-caffeine-dihydrocodeine is no longer available in the United States. It was once sold as a generic and under the brand-name Synalgos-DC. Prescribed as an oral capsule, it was typically only used for moderate to moderately severe acute pain.

In 2014, the FDA discontinued this formulation in all generic and brand-name forms due to limited past safety data and research.

Hydrocodone-acetaminophen

This drug is typically used for moderate to moderately severe acute pain. Generic hydrocodone-acetaminophen comes as an oral tablet and oral solution. Brand-name versions include:

  • Norco, an oral tablet
  • Zyfrel, an oral solution
  • Vicodin, an oral tablet

Hydrocodone-ibuprofen

Hydrocodone-ibuprofen is available as an oral tablet. It comes as a generic medication and is typically used for acute pain.

Morphine-naltrexone

Morphine-naltrexone is no longer available in the United States. It was once marketed under the brand name Embeda as an extended-release oral capsule. Developed for chronic pain in people who need around-the-clock treatment, FDA approval was withdrawn in 2020.

Oxycodone-acetaminophen

This drug is used for both acute and chronic pain. Generic oxycodone-acetaminophen is available as an oral solution and oral tablet. Brand-name versions include:

  • Oxycet, an oral tablet
  • Percocet, an oral tablet

Oxycodone-aspirin

Oxycodone-aspirin is available as a generic oral tablet. It’s typically used for moderate to moderately severe acute pain.

Oxycodone-ibuprofen

Oxycodone-ibuprofen is available as a generic drug but was once available under the brand name of Combunox. It comes in an oral tablet, and is typically used for no more than 7 days to treat short-term severe pain.

Oxycodone-naltrexone

Oxycodone-naltrexone was approved by the FDA in 2016, but the manufacturer withdrew plans to release it as the brand-name drug Troxyca ER. Developed as an extended-release oral capsule, it was indicated for chronic pain in people who need around-the-clock treatment.

Pentazocine-naloxone

This product is available as a generic drug and comes in an oral tablet. It’s used for both acute and chronic pain.

Tramadol-acetaminophen

Tramadol-acetaminophen is available as a generic drug and the brand-name drug Ultracet. It comes in an oral tablet. This form is typically used for no longer than 5 days to treat short-term severe pain.

Some opioids can be taken alone or in combination products to treat conditions other than acute and chronic pain. These drugs include:

  • codeine
  • hydrocodone
  • buprenorphine
  • methadone

For example, both codeine and hydrocodone are combined with other drugs in products that treat cough.

Buprenorphine (alone or combined with naloxone) and methadone are used in products to treat opioid use disorders.

There are many opioids and opioid combination products. They each have different treatment uses. It’s important to take the right opioid and use it correctly.

You and your doctor will need to consider many factors before selecting the best opioid product or products for your individual treatment. These factors include:

  • the severity of your pain
  • your pain treatment history
  • other conditions you have
  • other drugs you take
  • your age
  • whether you have a history of substance use disorders
  • your health insurance coverage

Pain severity

Your doctor will consider how severe your pain is when recommending an opioid treatment. Some opioid medications are stronger than others.

Certain combination products, such as codeine-acetaminophen, are only used for mild to moderate pain. Others, such as the more potent hydrocodone-acetaminophen, are used for moderate to moderately severe pain.

Immediate-release opioid-only products are typically used for moderate to severe pain. Extended-release products are only meant to be used for severe pain that requires around-the-clock treatment after other medications haven’t worked.

Pain treatment history

Your doctor will take into account whether you already take medication to manage your pain before recommending further treatment. Some opioid medications, such as fentanyl and methadone, are only appropriate for people who are already taking opioids and require long-term therapy.

Other conditions

Opioids aren’t right for everyone. If you live with certain medical conditions, your doctor may want to explore other pain management options.

If you have limited kidney function, for example, you might have a higher risk for side effects from these drugs. Your kidneys remove some opioid medications from your body, and if your kidneys aren’t working properly, you may end up with higher levels of opioids in your system.

Examples of opioids that might not be right for someone with kidney disease include:

  • codeine
  • morphine
  • hydromorphone
  • oxymorphone
  • meperidine

Drug interactions

Some drugs should be avoided or used with caution because of how they interact with certain opioids. It’s important to let your doctor know about all medications you take so your doctor can select the safest opioid for you. This includes any over-the-counter products, supplements, and herbs.

Age

Not all opioid products are appropriate for all age groups.

Children younger than 12 years shouldn’t take products containing tramadol and codeine.

Additionally, these products are not suitable for people between the ages of 12 and 18 years if they have:

History of substance misuse

It’s important to let your doctor know if you’ve faced substance use challenges. Some opioid products are formulated to reduce the risk of misuse. These products include:

  • OxyContin
  • Hysingla ER
  • Xtampza ER
  • RoxyBond

Insurance coverage

Individual insurance plans may not cover all opioid products, but most plans cover some immediate-release and extended-release products. Generic-branded medications generally cost less. Talk with your healthcare professional or pharmacist to help determine which product your insurance will cover.

Many insurance companies limit the amount of opioid product you can obtain each month. Your insurance company may also require prior approval from your healthcare team before approving your prescription.

Using opioids, even for short periods, can lead to addiction and overdose. There are a few things you can do to take opioids safely:

  • Tell your healthcare professional about any history of substance misuse so they can carefully monitor you during treatment with opioids.
  • Follow the directions on your prescription. Taking too much or taking a dose incorrectly can lead to more side effects, including difficulty breathing and overdose.
  • Talk with your healthcare team about what substances you should avoid while taking an opioid. Mixing opioids with alcohol, sedating antihistamines (such as diphenhydramine), benzodiazepines (such as Xanax or Valium), muscle relaxants (such as Soma or Flexeril), or sleep aids (such as Ambien or Lunesta) can increase your risk for dangerously slowed breathing.
  • Store your medication safely and out of reach of children. If you have any leftover opioid pills, take them to a community drug take-back program.

Tolerance and withdrawal

Your body can become tolerant to the effects of opioids the longer you take them. This means that if you take them for longer periods, you may need higher and higher doses to get the same pain relief. It’s important to let your doctor know if this happens to you.

Stopping opioids suddenly can cause withdrawal symptoms. To avoid this, talk with your healthcare professional about the best way to stop. Many people need to taper off opioids gradually under medical supervision.

There are many opioids available to treat acute and chronic pain.

After starting an opioid, meet with your doctor regularly to discuss any side effects or concerns. Because dependence can develop over time, ask your doctor about what to do if you notice signs of it. If you decide to stop taking the medication, your doctor can help you create a safe tapering plan.