Buprenorphine – Uses, Interactions, and Overdose

What is Buprenorphine?

Buprenorphine is the first medication to treat opioid use disorder (OUD) that can be prescribed or dispensed in physician offices, significantly increasing access to treatment. As with all medications used in treatment, buprenorphine should be prescribed as part of a comprehensive treatment plan that includes counseling and other services to provide patients with a whole-person approach.

Buprenorphine offers several benefits to those with OUD and to others for whom treatment in an Opioid Treatment Clinic is not appropriate or is less convenient.

Properties and characteristics of Buprenorphine

Drug class	Schedule III drugs
Brand Names	Belbuca, Brixadi, Buprenex, Buprenorphine, Butrans, Sublocade, Suboxone, Subutex, Zubsolv
Synonyms	Buprenophine, Buprenorfina, Buprenorphine, Buprenorphinum
Molecular Formula	C29H41NO4
Molecular Weight	467.6 g/mol
IUPAC Name	(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylbutan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol
Structural formula of main components
Pure active ingredient	Buprenorphine
Appearance	Solid
Melting point	217 °C
Solubility	1.68e-02 g/L
Excretion	Buprenorphine and norbuprenorphine are metabolized through glucuronidation and eliminated in the bile
Storage	Store at room temperature between 20°C and 25°C (68°F and 77°F) and protected from light, excessive heat above 40°C (104°F), and freezing.
Available Forms	Injectable solution, plaster, and film
Prescription	Do not consume without the doctors’ advice

What is buprenorphine used for?

Buprenorphine is prescribed for the medical treatment of people with an opioid drug dependence. This could include a dependency on heroin or other opioid medicines. Buprenorphine can help people safely withdraw from the opioid medicine they are dependent on.

Buprenorphine can also be prescribed for the short-term treatment of severe, acute pain. There are significant risks associated with the use of opioids. Your doctor will only prescribe buprenorphine if they think that other treatment options are not able to effectively manage your pain, or if other pain medicines are not suitable for your situation.

Common and serious side effects of Buprenorphine

Patients who are considering buprenorphine for treatment, should be sure they fully understand the medication and its side effects before they take the medication. Their health care practitioner or pharmacist can provide this information. Patients should tell their health care practitioner about any side effects that are bothersome, or do not go away.

Common side effects of buprenorphine include:

• Constipation, headache, nausea, and vomiting
• Dizziness
• Drowsiness and fatigue
• Sweating
• Dry mouth
• Tooth decay
• Muscle aches and cramps
• Inability to sleep
• Fever
• Blurred vision or dilated pupils
• Tremors
• Palpitations
• Disturbance in attention

Serious side effects of buprenorphine include:

• Respiratory distress
• Overdose
• Adrenal insufficiency
• Dependence
• Withdrawal
• Itching, pain, swelling, and nerve damage (implant)
• Pain at injection site (injection)
• Neonatal abstinence syndrome (in newborns)

Mechanism of action

Buprenorphine is a partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor. It demonstrates a high affinity for the mu-opioid receptor but has lower intrinsic activity compared to other full mu-opioid agonists such as heroin, oxycodone, or methadone. This means that buprenorphine preferentially binds the opioid receptor and displaces lower affinity opioids without activating the receptor to a comparable degree. Clinically, this results in a slow onset of action and a clinical phenomenon known as the “ceiling effect” where once a certain dose is reached buprenorphine’s effects plateau. This effect can be beneficial, however, as dose-related side effects such as respiratory depression, sedation, and intoxication also plateau at around 32mg, resulting in a lower risk of overdose compared to methadone and other full agonist opioids. It also means that opioid-dependent patients do not experience sedation or euphoria at the same rate that they might experience with more potent opioids, improving quality of life for patients with severe pain and reducing the reinforcing effects of opioids which can lead to drug-seeking behaviours.

Buprenorphine’s high affinity, but low intrinsic activity for the mu-opioid receptor also means that if it is started in opioid-dependent individuals, it will displace the other opioids without creating an equal opioid effect and cause a phenomenon known as “precipitated withdrawal” which is characterized by a rapid and intense onset of withdrawal symptoms (i.e. anxiety, restlessness, gastrointestinal distress, diaphoresis, intense drug cravings, and tachycardia). Individuals must therefore be in a state of mild to moderate withdrawal before starting therapy with buprenorphine.

Buprenorphine is commercially available as the brand name product Suboxone which is formulated in a 4:1 fixed-dose combination product along with naloxone, a non-selective competitive opioid receptor antagonist. Combination of an opioid agonist with an opioid antagonist may seem counterintuitive, however this combination with naloxone is intended to reduce the abuse potential of Suboxone, as naloxone is poorly absorbed by the oral route (and has no effect when taken orally), but would reverse the opioid agonist effects of buprenorphine if injected intravenously.

Mixing buprenorphine with other drugs

Mixing buprenorphine with other drugs can have unpredictable effects and increase the risk of harm.

• Buprenorphine and alcohol/benzos/GHB/Ketamine: high risk of overdose, impaired coordination, passing out, difficulty breathing, nausea, vomiting, memory loss, and possible death.
• Bupenorphine and ice/speed/cocaine: buprenorphine lowers your heart rate while stimulants speed it up, masking the effects of each other. Depending on how much you take, you could overdose on either drug if one wears off before the other.

What is buprenorphine’s dosage?

Your doctor will recommend the dosage of buprenorphine that’s right for you. Below are commonly used dosages, but always follow the dosage your doctor prescribes.

Forms and strengths

Buprenorphine comes in several forms. These include:

• Extended-release transdermal patches. Buprenorphine transdermal patches are applied to your skin. These are available in several different strengths. Your doctor will recommend the strength of patch that’s right for you. This will depend on whether you’ve taken an opioid in the past.
• Solution for injection. Buprenorphine injections are given by healthcare professionals. These can be given as either an injection into your muscle or an injection into your vein that’s given slowly over a period of 2 minutes.
• Sublingual tablets. Sublingual tablets are pills that dissolve under your tongue. These come in strengths of 2 milligrams (mg) and 8 mg.

Recommended dosages

The dosage and form of buprenorphine that your doctor prescribes for you depends on:

• the reason you’re taking buprenorphine
• any other medications you’re taking
• any other health conditions you may have, such as liver or lung problems

Below are typical dosages for buprenorphine’s uses.

Dosage for opioid dependence

Buprenorphine sublingual tablets are used for opioid dependence, which is now called opioid use disorder (OUD). Opioids are strong pain medications. With dependence, your body needs a drug for you to feel as you usually would.

There are two phases to treatment for opioid dependence. The beginning phase is called the induction phase. And the ongoing phase is called the maintenance phase.

How often you’ll take buprenorphine depends on which phase of treatment you’re currently in and what type of opioids you’d been taking before your treatment.

A typical starting dosage for buprenorphine tablets is 2 mg to 8 mg each day. You’ll take your first dose when you start to have withdrawal symptoms after stopping other opioids.

The suggested dosage range of buprenorphine tablets for maintenance phase treatment varies. Your doctor will prescribe the dosage that’s right for you.

Dosage for pain

Buprenorphine injection and patches are used for pain treatment.

Dosage of buprenorphine patches

For buprenorphine patches, the recommended starting dosage depends on whether you’ve already been taking other opioid pain relievers. Your doctor may gradually increase the strength of buprenorphine patch you use until the dose that’s right for you is reached.

This is the dosage that controls your pain, but causes minimum side effects. But, dosage changes should not be made until you’ve worn a buprenorphine patch for at least 72 hours.

Each buprenorphine patch is usually worn for 7 days.

Dosage of buprenorphine injection

Buprenorphine injections will be given by your healthcare professional as needed to control pain.

Adults and children ages 12 years and older may be given one dose, followed by a second dose 30 to 60 minutes later, if needed.

Your doctor will decide how often to give injectable buprenorphine doses based on your level of pain.

In case of emergency/overdose

In case of overdose, call the poison control helpline. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call emergency services.

While taking buprenorphine or buprenorphine and naloxone, you should talk to your doctor about having a rescue medication called naloxone readily available (e.g., home, office). Naloxone is used to reverse the life-threatening effects of an overdose. It works by blocking the effects of opiates to relieve dangerous symptoms caused by high levels of opiates in the blood. Your doctor may also prescribe you naloxone if you are living in a household where there are small children or someone who has abused street or prescription drugs. You should make sure that you and your family members, caregivers, or the people who spend time with you know how to recognize an overdose, how to use naloxone, and what to do until emergency medical help arrives. If symptoms of an overdose occur, a friend or family member should give the first dose of naloxone, call emergency service number immediately, and stay with you and watch you closely until emergency medical help arrives. Your symptoms may return within a few minutes after you receive naloxone. If your symptoms return, the person should give you another dose of naloxone. Additional doses may be given every 2 to 3 minutes, if symptoms return before medical help arrives.

Symptoms of overdose may include the following:

• Pinpoint pupils
• Sleepiness or extreme drowsiness
• Dizziness
• Blurred vision
• Slow or shallow breathing
• Difficulty breathing
• Unable to respond or wake up

Warnings

Misuse of opioid medicine can cause addiction, overdose, or death. Keep buprenorphine in a place where others cannot get to it.

Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose. Patients should have access to naloxone to treat opioid overdose based on the patient’s risk factors for overdose, such as currently using a CNS depressant, a history of an opioid use disorder, or previous opioid overdose.  Having naloxone available is important if the patient has household members (including children) or other close contacts at risk for accidental exposure or overdose.

Taking this medicine during pregnancy may cause life-threatening withdrawal symptoms in the newborn.

Fatal side effects can occur if you use this medication with alcohol or with other drugs that cause drowsiness or slow your breathing.

Before taking this medicine

You should not use this medicine if you are allergic to buprenorphine or:

• If you have used another narcotic drug within the past 4 hours.

To make sure this medication is safe for you, tell your doctor if you have ever had:

• Methadone treatment;
• Breathing problems, sleep apnea;
• Abnormal curvature of the spine that affects breathing;
• Liver disease (especially hepatitis B or C);
• Kidney disease;
• Enlarged prostate, urination problems;
• A head injury or brain tumor;
• Alcoholism, hallucinations, mental illness; or
• Problems with your stomach, gallbladder, adrenal gland, or thyroid.

Pregnancy

If you use buprenorphine while you are pregnant, your baby could become dependent on the drug. This can cause life-threatening withdrawal symptoms in the baby after it is born. Babies born dependent on habit-forming medicine may need medical treatment for several weeks.

Infertility

Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible

Breastfeeding

Buprenorphine can pass into breast milk and may cause drowsiness and breathing problems in a nursing baby. Ask your doctor about any risk to your baby.