Butrans Patch: The Ultimate Solution for Effective Pain Relief You Need to Know!

The buprenorphine transdermal patch, commonly known as Butrans, is a prescription medication used for the management of chronic pain. It offers a convenient, once-weekly application for patients requiring long-term opioid treatment. This article aims to provide a comprehensive overview of the Butrans patch, including its uses, mechanism of action, dosage, application, precautions, and potential adverse effects.

Introduction to Buprenorphine and its Transdermal Patch

With the ongoing public health crisis related to prescription opioids, safer alternatives for medication management in chronic pain patients are needed. Buprenorphine is a partial mu-opioid agonist commonly utilized to treat patients with opioid-use disorders and is also used as an analgesic. The buprenorphine transdermal patch may be a potential alternative for patients requiring around-the-clock opioid therapy.

Chronic pain continues to affect roughly 30% of Americans. The treatment algorithm for most chronic pain conditions typically requires a multimodal approach, generally beginning with conservative therapies, including physical therapy, cognitive behavioral therapy, pain psychology, and medication management. Common medications for chronic pain include acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), membrane stabilizers, antidepressants, and opioids.

Given the ongoing opioid crisis and known risks and side effects of opioids, patients should generally not be started on opioids early in the treatment process for chronic pain conditions. However, given the prevalence of chronic pain in the United States, a significant patient population is still prescribed opioids for pain management and quality of life. Opioids vary in their efficacy to provide analgesia as well as abuse potential.

What is Butrans?

The buprenorphine transdermal patch (Butrans) is FDA-indicated for use in patients with pain that is severe enough to require daily, around-the-clock, long-term opioid use for which other treatments are not adequate. Given the risks of addiction, abuse, and misuse with opioids, as well as the increased risk of overdose and death with use of extended-release opioids, the buprenorphine transdermal patch should be reserved for use in patients for whom alternative treatments, such as nonopioid options or immediate-release opioids, are not effective, not tolerated, or not adequate for pain management. The buprenorphine patch is also included in the Extended-Release and Long-Acting Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS). The goal of the REMS is to decrease serious adverse events due to inappropriate prescribing, misuse, and abuse of long-acting opioids. The REMS for these products requires that a medication guide be dispensed to patients.

How Butrans Works: Mechanism of Action

Buprenorphine, a lipophilic molecule derivative of the opium alkaloid thebaine, functions as a partial mu-opioid receptor (MOR) agonist and a weak kappa opioid receptor (KOR) antagonist. In addition, buprenorphine is also known to have agonist activity on the ORL-1 receptor, which aids in the analgesic effect of the drug while lowering adverse effects such as constipation. MOR receptors are critical receptors in the body that were one of the first discovered opioid receptors.

The pharmacodynamic properties of buprenorphine are measured by binding affinity and the equilibrium dissociation constant (Ki). The higher binding affinity of the drug results in a low Ki value. In the case of buprenorphine, the structure and binding position of the drug allows for strong binding affinity compared to other opioids such as hydromorphone, morphine, fentanyl, and oxycodone.

Mu-opioid receptors are associated with supraspinal analgesia in addition to respiratory depression, euphoria, sedation, decrease in gastrointestinal (GI) motility, and physical dependence. The affinity of a drug indicates the strength of receptor binding, whereas the intrinsic activity is associated with the degree to which the drug activates the receptor it is binding to. Buprenorphine has a high affinity at the mu-opioid receptor; however, it has low intrinsic activity. Buprenorphine has high lipophilicity and potency, which contributes to its overall effectiveness.

Buprenorphine demonstrates unique pharmacological properties that make it an attractive medication for chronic pain patients who require opioid medications. Buprenorphine displays a partial agonist at the mu-opioid receptor, allowing potent analgesia with a better safety profile. Additionally, the medication is a Schedule III opioid with less abuse potential than traditional Schedule II opioids typically used for chronic pain.

Advantages of the Buprenorphine Patch

Potential advantages for use of the buprenorphine patch include the convenience of the dosing interval, which allows for once-weekly patch application versus oral opioids that may need to be taken multiple times per day or the fentanyl patch, which is dosed every 72 hours.

Available Strengths and Dosing

There are now five buprenorphine patch strengths: 5, 7.5, 10, 15, and 20 mcg/h. The buprenorphine patch dosage may be titrated after at least 72 hours; the dosage may be adjusted by 5 mcg/h, 7.5 mcg/h, or 10 mcg/h increments. Up to two of the 5-mcg/h, 7.5-mcg/h, or 10-mcg/h patches may be used, and the total buprenorphine dosage should not exceed 20 mcg/h.

Initiating Treatment

Per the manufacturer, opioid-naïve patients may be initiated on the buprenorphine patch at a dosage of 5 mcg/h. For patients who are already on opioid therapy, the total daily oral morphine (or morphine-equivalent) dosage must be calculated. If a patient was taking <30 mg of oral morphine or its equivalent, the 5-mcg/h patch may be initiated. If the total daily dosage of oral morphine (or morphine-equivalent) is 30 to 80 mg, the patient’s opioid(s) must be tapered for up to 7 days to no more than 30 mg of oral morphine (or its equivalent) per day prior to initiating the buprenorphine patch at 10 mcg/h; otherwise, there is a potential for withdrawal to occur. Short-acting analgesics may be used as needed in the interim until analgesia with the buprenorphine patch is obtained.

When the buprenorphine transdermal patch is initiated, all other around-the-clock opioids should be discontinued. Of note, patients using >80 mg of oral morphine (or morphine equivalent) per day may not achieve sufficient analgesia with the buprenorphine 20 mcg/h transdermal patch; providers should consider alternative analgesic options.

Titration

The buprenorphine patch dosage may be titrated after at least 72 hours; the dosage may be adjusted by 5 mcg/h, 7.5 mcg/h, or 10 mcg/h increments. Up to two of the 5-mcg/h, 7.5-mcg/h, or 10-mcg/h patches may be used, and the total buprenorphine dosage should not exceed 20 mcg/h.

How to Apply and Use the Butrans Patch

Patients should be educated on proper buprenorphine patch application, use, and disposal. The patch may be applied to the upper outer arm, upper chest, upper back, or the side of the chest. Either side of the body may be used, which allows for eight potential application sites. The patient should rotate the application site each time the patch is changed, ensuring that the same site is not used again for at least 21 days.

If the application site needs to be cleaned prior to applying the patch, the patient may only use water to clean the area (i.e., no lotion, soap, alcohol) and allow the site to dry. The patch should be placed on a hairless site; however, if hair is present, the hair may be cut (patients should not shave the site). In addition, advise patients not to apply the patch to irritated or broken skin. The buprenorphine transdermal patch should not be cut.

Patients should press the patch down firmly at the application site with the palm of the hand and hold for 15 seconds (without rubbing the patch) to ensure the patch sticks to the skin. Advise patients to wash their hands after touching or applying the buprenorphine transdermal patch. Inform patients to avoid exposing the patch to heat (e.g., through use of heating pads, electric blankets, or hot tubs), since this may result in greater absorption of the medication, resulting in an increased risk of overdose or even death. In order to help keep the patch in place, patients may use first-aid tape on the edges of the patch. Patients should be instructed to remove the old patch prior to applying the new one.

Detailed Application Instructions

Choose Application Site: Select a clean, dry area of skin on your upper outer arm, upper chest, upper back, or the side of the chest. The upper back is a good spot to put the patch on people who are confused because it will be hard for them to remove the patch. Do not apply the patch to oily, broken, burned, cut, or irritated skin. Wait at least 3 weeks before applying a new patch to same site.
Clean the Area: Clean the area where you plan to apply the patch with clear water and pat completely dry. Do not use any soaps, lotions, alcohols, or oils.
Prepare the Skin: If there is hair on the skin, use scissors to clip the hair as close to the skin as possible. Do not shave the area.
Open the Pouch: Use scissors to cut open the pouch containing the buprenorphine patch along the dotted line.
Apply the Patch: Remove the patch from the pouch and peel off the protective liner from the back of the patch. Try not to touch the sticky side of the patch. Immediately press the sticky side of the patch onto the chosen area of skin with the palm of your hand.
Secure the Patch: Press the patch firmly for at least 15 seconds. Be sure that the patch sticks well to your skin, especially around the edges. Do not rub the patch.
Wash Hands: When you are finished applying the patch, wash your hands with only clear water right away.
Record Application: Write down the date and time that the patch is applied.

What to Avoid While Using the Patch

Heat Exposure: Do not expose your patch or the skin around it to direct heat such as heating pads, electric blankets, heat lamps, saunas, hot tubs, and heated water beds. Do not take long, hot baths or sunbathe while you are wearing the patch.
Alcohol and Illicit Substances: Drinking alcohol or using street drugs during your treatment with buprenorphine transdermal 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.
Damaged Patches: Do not use a buprenorphine patch that is cut, damaged, or changed in any way. If you use cut or damaged patches, you may receive most or all of the medication at once, instead of slowly over 7 days. This may cause serious problems, including overdose and death.

Important Precautions and Warnings

There are four black box warnings for the buprenorphine transdermal patch: 1) addiction, abuse, and misuse potential; 2) accidental exposure; 3) life-threatening respiratory depression; and 4) neonatal opioid withdrawal syndrome. Other warnings and precautions are similar to those for other opioids. These include caution with use in elderly, cachectic, and debilitated patients; in chronic pulmonary disease, hepatotoxicity, GI conditions, convulsive or seizure disorders, fever, head injury or increased intracranial pressure; with alcohol, CNS depressants, and illicit substances; in risk of QTc prolongation or hypotension; and in application site, allergic, and anaphylactic reactions.

General Precautions

Buprenorphine patches can be habit forming, especially with prolonged use.
Use buprenorphine patches exactly as directed. Do not apply more patches, apply the patches more often, or use the patches in a different way than prescribed by your doctor.
While using buprenorphine patches, discuss with your health care 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 buprenorphine if you have or have ever had any of these conditions. Your doctor will monitor you carefully during your treatment.
Your doctor will adjust your dose carefully to control your pain and decrease the risk that you will experience serious breathing problems. Tell your doctor if you have or have ever had breathing difficulties, asthma, chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways), or other lung disease. Your doctor may tell you not to use buprenorphine patches. Also tell your doctor if you have or have ever had a head injury, a brain tumor, or any condition that increases the amount of pressure in your brain.
The risk that you will develop breathing problems may also be higher if you are an older adult or are weakened or malnourished due to disease.

Specific Warnings

Addiction, Abuse, and Misuse: The buprenorphine transdermal patch has a potential for addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing and monitor regularly for development of these behaviors or conditions.
Accidental Exposure: Accidental exposure to even one dose of buprenorphine transdermal patch, especially in children, can result in a fatal overdose.
Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur with use of buprenorphine transdermal patch. Monitor for respiratory depression, especially during initiation or following a dosage increase.
Neonatal Opioid Withdrawal Syndrome: Prolonged use of buprenorphine transdermal patch during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated.
QTc Prolongation: The use of the buprenorphine transdermal patch at the dosage of 40 mcg/h was found to prolong the mean QTc interval by up to 9.2 msec.

Who Shouldn't Use Buprenorphine Patches

Buprenorphine patches should not be used to treat mild or moderate pain, short-term pain, or pain that can be controlled by medication that is taken as needed.

When to Seek Immediate Medical Attention

If you have any of the following symptoms, call your doctor immediately: difficulty breathing, shortness of breath, extreme drowsiness, fainting, or loss of consciousness.

Taking certain medications with buprenorphine patches may increase the risk of serious or life-threatening breathing problems, sedation, or coma. Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Your doctor may need to change the dosages of your medications and will monitor you carefully. If you use buprenorphine transdermal with other 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.

Potential Side Effects

Adverse effects are consistent with those of other opioids and include, but are not limited to, nausea and vomiting, dizziness, constipation, and somnolence. Patients should be educated on proper buprenorphine patch application, use, and disposal. Practitioners should be aware that this medication is associated with a high proportion of side effects such as nausea, vomiting, and constipation. It is also associated with QTc prolongation, especially at higher doses.

Common Side Effects

Difficulty falling asleep or staying asleep
Headache
Dry mouth
Stomach pains
Skin irritation, itching, swelling, or redness in the area where you wore the patch
Constipation
Dizziness
Drowsiness
Nausea
Vomiting

Serious Side Effects

Difficulty breathing or swallowing
Shortness of breath
Changes in heartbeat
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, or diarrhea
Nausea, vomiting, loss of appetite, weakness, or dizziness
Inability to get or keep an erection
Irregular menstruation
Decreased sexual desire
Chest pains
Swelling of your face, tongue or throat
Rash
Hives
Itching

Effects on Hormone Levels

Opioid use has been noted to lead to hypogonadism; however, there are some published studies that suggest that buprenorphine may be less likely to cause hypogonadism compared to other opioids. Two studies compared hormonal effects of oral methadone and sublingual buprenorphine used for maintenance treatment. One study found no difference in testosterone levels in patients taking between 8 and 20 mg of sublingual buprenorphine per day versus the control group. Another study also evaluated patients on methadone and buprenorphine maintenance treatment and compared the findings to control groups. The mean daily methadone dose was 106 mg while the mean buprenorphine dose was 10.2 mg. While patients on both methadone and buprenorphine were found to have lower free testosterone when compared to the reference groups, patients on methadone had lower total testosterone levels versus the buprenorphine group. In addition, one study assessed the effects of the buprenorphine patch (35 mcg/h every 72 hours) on hormone levels in women of reproductive age and in menopausal women.

Special Populations

Renal and Hepatic Impairment

There are no specific dosage adjustments defined for patients with renal or hepatic impairment, or for elderly patients. In patients with severe hepatic impairment, it is recommended to consider alternative options. Use of buprenorphine in patients with liver impairment has also been extensively studied and has shown that mild to moderate liver impairment does not affect the clearance of buprenorphine. However, mild to moderate liver impairment may impair clearance of naloxone and increase levels; thus, buprenorphine-naloxone combination therapy should be avoided in these patients. In severe hepatic failure, patients can have increased buprenorphine bioavailability.

Elderly Patients

Pergolizzi et al. determined that buprenorphine is an essential opioid for use in elderly patients, as its clearance is not affected by age. Similarly, Al-Tawil et al. decided that there was no difference in clearance of buprenorphine between elderly patients over the age of 70 and younger patients with the average age of 32 who were receiving BTDS 10 mcg/hr.

Drug Interactions

The pharmacokinetics of buprenorphine metabolism via CYP3A4 isoenzymes may lead to drug interactions with CYP3A4 inhibitors. Drugs associated with decreased hepatic blood flow may contribute to decreased hepatic clearance of buprenorphine and increased bioavailability. Protease inhibitors, specifically atazanavir, cause increased bioavailability of buprenorphine, leading to increased CNS depressant effects.

Medications to Avoid

Do not take this medication with any of the following:

Cisapride
Dronedarone
Pimozide
Safinamide
Samidorphan
Thioridazine

This medication may also interact with the following:

Alcohol
Antihistamines for allergy, cough, and cold
Atropine
Benzodiazepines, such as alprazolam, diazepam, or lorazepam
Certain antibiotics, such as clarithromycin, erythromycin
Certain antivirals for hepatitis or HIV
Certain medications for bladder problems, such as oxybutynin or tolterodine
Certain medications for depression or mental health conditions
Certain medications for fungal infections, such as fluconazole, ketoconazole, posaconazole
Certain medications for migraine headache like almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan
Certain medications for nausea or vomiting like dolasetron, ondansetron, palonosetron
Certain medications for seizures, such as carbamazepine, phenobarbital, phenytoin
Certain medications for stomach problems, such as dicyclomine or hyoscyamine
Certain medications for travel sickness, such as scopolamine
Certain medications for Parkinson disease, such as benztropine or trihexyphenidyl
Ipratropium
Linezolid
MAOIs, such as Marplan, Nardil, and Parnate
Medications that cause drowsiness before a procedure, such as propofol
Medications that help you fall asleep
Medications that relax muscles
Methylene blue (injected into a vein)
Other medications that cause heart rhythm changes
Opioid medications for pain or cough
Phenothiazines, such as chlorpromazine, prochlorperazine
Rifampin

Proper Disposal of Used Patches

Patients should be educated on proper buprenorphine patch application, use, and disposal. After you remove your patch, use the Patch Disposal Unit provided to you by the manufacturer to safely dispose of the used patch in the trash. Close the Patch Disposal Unit by folding the sticky sides together, then press firmly and smoothly over the entire Unit so that the patch is sealed within. Do not place used patches in the trash without first sealing them in the Patch Disposal Unit. Alternatively, you may also may fold the sticky sides of a used patch together and flush it down the toilet. Used patches may still contain some medication and may be dangerous to children, pets, or adults who have not been prescribed buprenorphine patches.

Detailed Disposal Instructions

When you change your patch, fold the used patch in half with the sticky side inwards and put it in the empty packet from your new patch. You'll then need to return both the packet and the used patch to your pharmacist who will destroy them safely.

Clinical Studies and Efficacy

There were two pivotal phase III trials that led to the approval of the buprenorphine patch for use in pain. One trial was conducted in opioid-naïve patients and the other in opioid-tolerant patients. Numerous studies have been conducted about buprenorphine and its efficacy and safety as an analgesic for patients with chronic pain. A systematic review of ten trials involving 1,190 patients demonstrated that sublingual buprenorphine is effective as an analgesic. Raffa et al. reviewed 24 studies to better understand the efficacy of buprenorphine as an analgesic.

Studies of low-dose transdermal buprenorphine patches have found patches were better tolerated than sublingual buprenorphine and were effective in managing chronic low back pain, osteoarthritis, and other forms of chronic pain.

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