Buprenorphine Transdermal

Mechanism of Action

Semisynthetic narcotic mixed agonist-antagonist analgesic; exerts agonistic effects at the mu and delta opioid receptors in the CNS, and antagonistic effects at the kappa opioid receptor

Absorption

17 hr is the median time for 10mcg/hr to deliver quantifiable concentration (ie, >25 pg/mL)  

Peak plasma concentration: 176 pg/mL (5 mcg/hr); 191 pg/mL (10 mcg/hr); 471 pg/mL (20 mcg/hr)  

AUC: 12,087 pg•h/mL (5 mcg/hr); 27,035 pg•h/mL (10 mcg/hr); 54,294 pg•h/mL (20 mcg/hr)

Absolute bioavailability: 15%

Distribution

Vd: 430 L (after IV administration)

Protein bound: 96%  

Metabolism

Metabolism: via hepatic metabolism, with subsequent biliary excretion and renal excretion of soluble metabolites

Pharmacokinetics

Half-life, terminal: 26 hr (after patch removal)

Clearance: 55 L/hr

Excretion (within 7 days): Feces (70%), urine (27%)

In the U.S.

• Butrans

Available Dosage Forms:

• Patch, Extended Release

Therapeutic Class: Analgesic

Pharmacologic Class: Opioid Agonist/Antagonist

Chemical Class: Opioid

Your doctor will tell you how much of buprenorphine to use and how often. Your dose may need to be changed several times in order to find out what works best for you. Do not use more medicine or use it more often than your doctor tells you to.

Buprenorphine transdermal comes with a Medication Guide and patient instructions. Read the instructions carefully before using the product. If you do not receive any printed instructions with the medicine, or do not understand the instructions, check with your nurse or doctor.

To use the skin patch:

• Use buprenorphine exactly as directed by your doctor. It will work only if it has been applied correctly.
• buprenorphine should only be used on intact, non-irritated skin. Do not put the patch in your mouth, chew, or swallow it.
• Buprenorphine skin patches are packaged in sealed pouches. Do not use buprenorphine if the pouch seal is broken, or if the patch is cut, damaged, or changed in any way. Do not remove the patch from the sealed pouch until you are ready to apply it.
• buprenorphine is available in 3 different strengths and patch sizes. Make sure you have the right strength patch that has been prescribed for you.
• When handling the skin patch, be careful not to touch the adhesive (sticky) surface with your hand. The adhesive part of the system contains some buprenorphine, which can be absorbed into your body too fast through the skin of your hand. If any of the medicine does get on your hand, rinse the area right away with a lot of clear water. Do not use soap or other cleansers.
• Be careful not to tear the patch or make any holes in it. Damage to a patch may allow buprenorphine to pass into your skin too quickly. This can cause an overdose.
• Apply the patch to a dry, flat skin area on your upper arm, chest, back, or side of the chest. Choose a place where the skin is not very oily and is free of scars, cuts, burns, or any other skin irritations.
• The patch will stay in place better if it is applied to an area with little or no hair. If you need to apply the patch to a hairy area, you may first clip the hair with scissors, but do not shave it off.
• If you need to clean the area before applying the medicine, use only plain water. Do not use soaps, other cleansers, lotions, or anything that contains oils or alcohol. Be sure that the skin is completely dry before applying the medicine.
• Remove the liner covering the sticky side of the skin patch. Then press the patch firmly in place, using the palm of your hand, for a minimum of 15 seconds. Make sure that the entire adhesive surface is attached to your skin, especially around the edges. Do not rub the patch.
• If the patch becomes loose, tape the edges with first aid tape. Do not cover it with any other bandage or tape.
• If the patch falls off after applying it, throw it away and apply a new patch in a different area.
• Wash your hands with a lot of clear water after applying the medicine. Do not use soap or other cleansers.
• Remove the patch after 7 days, or as directed by your doctor. Choose a different place on your skin to apply the next patch. If possible, use a place on the other side of your body. Wait at least 3 weeks (21 days) before using the first area again.

Dosing

The dose of buprenorphine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of buprenorphine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For transdermal dosage form (skin patch):
  • For moderate to severe chronic pain:
    • Adults—If you are not using other narcotics regularly, your doctor will determine the correct dose. If you are using other narcotics regularly, your dose will be based on your present daily narcotic dose. Your doctor may adjust the dose if needed. The patch is applied to the skin and left in place for 7 days.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you forget to wear or change a patch, put one on as soon as you can. If it is almost time to put on your next patch, wait until then to apply a new patch and skip the one you missed. Do not apply extra patches to make up for a missed dose.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Buprenorphine can cause serious unwanted effects or a fatal overdose if taken by children, pets, or adults who are not used to strong narcotic pain medicines. Make sure you store the medicine in a safe and secure place to prevent others from getting it.

Use the patch-disposal unit that was provided with your prescription to dispose of the patches. Read and follow the printed instructions on the disposal unit and use one unit for each patch. Peel off the liner of the disposal unit to reveal the sticky surface. Place the sticky side of the used patch on the disposal unit and seal the entire package. If the patch has not been used, take it out of the pouch and remove the liner that covers the sticky side before placing it on the disposal unit. Throw the sealed disposal unit in a trash can. Talk to your pharmacist if you have questions about how to use the disposal unit. Do not flush the pouch or the protective liner down the toilet. Put them in a trash can.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Bloating or swelling of the face, arms, hands, lower legs, or feet
• rapid weight gain
• swelling, burn, or blisters at the patch site
• tingling of the hands or feet
• unusual weight loss

• Bladder pain
• bloody or cloudy urine
• blurred vision
• body aches or pain
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest pain
• chills
• cough producing mucus
• diarrhea
• difficult or labored breathing
• difficult, burning, or painful urination
• difficulty with moving
• dizziness
• ear congestion
• fever
• frequent urge to urinate
• general feeling of discomfort or illness
• headache
• increased sweating
• joint pain
• loss of appetite
• loss of voice
• lower back or side pain
• muscle aches and pains
• muscle stiffness
• nasal congestion
• nausea
• nervousness
• pain
• pain in the arms or legs
• pounding in the ears
• runny nose
• shakiness in the legs, arms, hands, or feet
• shivering
• slow or fast heartbeat
• sneezing
• sore throat
• sweating
• tightness in the chest
• trembling or shaking of the hands or feet
• trouble sleeping
• unusual tiredness or weakness
• vomiting

• Abdominal or stomach pain or tenderness
• arm, back, or jaw pain
• blistering, burning, crusting, dryness, or flaking of the skin
• blue lips, fingernails, or skin
• chest tightness or heaviness
• confusion
• decreased urination
• deep or fast breathing with dizziness
• difficulty with swallowing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• dry mouth
• extremely shallow or slow breathing
• fainting
• fast, irregular, pounding, or racing heartbeat or pulse
• feeling of warmth or heat
• flushing or redness of the skin, especially on the face and neck
• increase in heart rate
• irregular, fast or slow, or shallow breathing
• itching, scaling, severe redness, soreness, or swelling of the skin
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• lightheadedness, dizziness, or fainting
• loss of bladder control
• loss of consciousness
• numbness of the feet, hands, and around the mouth
• rapid breathing
• slow or irregular heartbeat
• sunken eyes
• sweating
• swelling or puffiness of the face
• thirst
• trouble with walking
• wrinkled skin

Get emergency help immediately if any of the following symptoms of overdose occur:

• Change in consciousness
• cold and clammy skin
• convulsions (seizures)
• drowsiness that is so severe you are not able to answer when spoken to or, if asleep, cannot be awakened
• pale or blue lips, fingernails, or skin
• pinpoint (small) pupils in the eyes
• sleepiness or unusual drowsiness
• slow heartbeat
• unable to speak
• very slow or troubled breathing
• weak muscle tone

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Constipation
• itching, redness, or rash at the patch site

• Acid or sour stomach
• anxiety
• back pain
• belching
• depression
• headache, severe and throbbing
• heartburn
• indigestion
• irritation at the patch site
• itching skin or rash
• lack or loss of strength
• muscle spasms
• neck pain
• pain or tenderness around the eyes and cheekbones
• stomach discomfort, upset, or pain
• swelling of the joints
• upper abdominal or stomach pain
• weight loss

• Agitation
• being forgetful
• blurred or loss of vision
• change in taste
• changes in patterns and rhythms of speech
• clumsiness or unsteadiness
• confusion about identity, place, and time
• cramps
• decreased interest in sexual intercourse
• decreased weight
• disturbed color perception
• double vision
• dry eyes or skin
• excess air or gas in the stomach or intestines
• feeling of constant movement of self or surroundings
• feeling of unreality
• full feeling
• general feeling of discomfort or illness
• halos around lights
• heavy bleeding
• inability to have or keep an erection
• lack of feeling or emotion
• loss in sexual ability, desire, drive, or performance
• loss of taste
• muscle weakness
• night blindness
• nightmares
• overbright appearance of lights
• passing gas
• pressure in the stomach
• relaxed and calm
• restlessness
• sensation of spinning
• sense of detachment from self or body
• sleepiness
• slurred speech
• swelling of the abdominal or stomach area
• trouble with speaking
• tunnel vision
• uncaring

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also Warning section.

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: certain pain medications (mixed opioid agonist-antagonists such as pentazocine, nalbuphine, butorphanol), naltrexone.

Many drugs besides buprenorphine may affect the heart rhythm (QT prolongation), including amiodarone, dofetilide, disopyramide, quinidine, procainamide, sotalol, among others.

The risk of serious side effects (such as slow/shallow breathing, severe drowsiness/dizziness) may be increased if this medication is used with other products that may also cause drowsiness or breathing problems. Tell your doctor or pharmacist if you are taking other products such as other opioid pain or cough relievers (such as codeine, hydrocodone), alcohol, marijuana, drugs for sleep or anxiety (such as alprazolam, lorazepam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), or antihistamines (such as cetirizine, diphenhydramine).

Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

This medication may interfere with certain laboratory tests (including amylase/lipase levels), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.