Buprenorphine

What is Buprenorphine?

• Buprenorphine (Subutex), is a partial opioid agonist.

Buprenorphine

Buprenorphine molecule from xtal ball

Buprenorphine molecule from xtal spacefill

What are the uses of this medicine?

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• Buprenorphine (Subutex), sublingual tablets are a prescription medicine used to begin treatment in adults who are addicted to (dependent on) opioid drugs (either prescription or illegal drugs), as part of a complete treatment program that also includes counseling and behavioral therapy.
• Buprenorphine hydrochloride sublingual tablets are most often used for the first 1 or 2 days to help you start with treatment.

How does this medicine work?

• The hydrochloride salt form of buprenorphine, a synthetic phenanthrene with narcotic analgesic activity.
• Buprenorphine hydrochloride is a partial agonist at the mu-opioid receptor and an antagonist at the kapa-opioid receptor in the central nervous system.
• However, under the conditions of recommended use it behaves as a classic mu-opioid agonist, mimicking the actions of endogenous peptides at CNS opioid receptors.
• The agonist action results in a raised pain threshold and increased tolerance to pain.
• However, it also causes sedation, physical dependence, and respiratory depressant effects and decreases heart rate and blood pressure.

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• are allergic to buprenorphine.

What drug interactions can this medicine cause?

• Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Be sure to mention any of the following:

• pain medicines
• tranquilizers
• sleeping pills
• anxiety medicines
• antihistamines
• antipsychotics such as aripiprazole (Abilify), asenapine (Saphris), cariprazine (Vraylar), chlorpromazine, clozapine (Versacloz), fluphenazine, haloperidol (Haldol), iloperidone (Fanapt), loxapine, lurasidone (Latuda), molindone, olanzapine (Zyprexa), paliperidone (Invega), perphenazine, pimavanserin (Nuplazid), quetiapine (Seroquel), risperidone (Risperdal), thioridazine, thiothixene, trifluoperazine, and ziprasidone (Geodon)
• benzodiazepines such as alprazolam (Xanax), chlordiazepoxide (Librium), clobazam (Onfi), clonazepam (Klonopin), clorazepate (Gen-Xene, Tranxene), diazepam (Diastat, Valium), estazolam, flurazepam, lorazepam (Ativan), oxazepam, quazepam (Doral), temazepam (Restoril), and triazolam (Halcion)
• diuretics ('water pills')
• erythromycin (E.E.S., Eryc, Erythrocin, others)
• certain HIV medications such as atazanavir (Reyataz, in Evotaz), delavirdine (Rescriptor), efavirenz (Sustiva, in Atripla), etravirine (Intelence), indinavir (Crixivan), nelfinavir (Viracept), nevirapine (Viramune), and ritonavir (Norvir, in Kaletra, in Technivie)
• hypnotics
• ipratropium (Atrovent)
• medications for irritable bowel disease, motion sickness, Parkinson's disease, ulcers, or urinary problems
• ketoconazole
• medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Alsuma, Imitrex, in Treximet), and zolmitriptan (Zomig)
• mirtazapine (Remeron)
• muscle relaxants such as cyclobenzaprine (Amrix), dantrolene (Dantrium), and metaxalone (Skelaxin)
• opiate (narcotic) medications for pain control and cough
• rifampin (Rifadin, Rimactane, in Rifater, in Rifamate)
• medications for seizures such as carbamazepine (Epitol, Tegretol, Teril, others), phenobarbital, and phenytoin (Dilantin, Phenytek)
• sedatives
• 5HT3 serotonin blockers such as alosetron (Lotronex), granisetron (Sancuso, Sustol), ondansetron (Zofran, Zuplenz), or palonosetron (Aloxi)
• selective serotonin-reuptake inhibitors such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Prozac, Pexeva), and sertraline (Zoloft)
• serotonin and norepinephrine reuptake inhibitors such as duloxetine (Cymbalta), desvenlafaxine (Khedezla, Pristiq), milnacipran (Savella), and venlafaxine (Effexor)
• tramadol (Conzip)
• trazodone
• tricyclic antidepressants ('mood elevators') such as amitriptyline, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil).

• Also tell your doctor or pharmacist if you are taking or receiving the following monoamine oxidase (MAO) inhibitors or if you have stopped taking them within the past two weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate).

Is this medicine FDA approved?

• Buprenorphine was approved for treatment of opioid addiction in 2004 and is a schedule III controlled substance.

How should this medicine be used?

Recommended dosage:

• Administer buprenorphine hydrochloride sublingual tablets sublingually as a single daily dose.

Administration:

• Buprenorphine comes as a sublingual tablet.
• Always take buprenorphine hydrochloride sublingual tablets exactly as your doctor tells you. Your doctor may change your dose after seeing how it affects you. Do not change your dose unless your doctor tells you to change it.
• Do not take buprenorphine hydrochloride sublingual tablets more often than prescribed by your doctor.
• Put the tablets under your tongue. Let them dissolve completely.
• While buprenorphine hydrochloride sublingual tablets are dissolving, do not chew or swallow the tablet because the medicine will not work as well.
• Talking while the tablet is dissolving can affect how well the medicine in buprenorphine hydrochloride sublingual tablets is absorbed.
• If you miss a dose of buprenorphine hydrochloride sublingual tablets, take your medicine when you remember. If it is almost time for your next dose, skip the missed dose and take the next dose at your regular time. Do not take 2 doses at the same time unless your doctor tells you to. If you are not sure about your dosing, call your doctor.
• Do not stop taking buprenorphine hydrochloride sublingual tablets suddenly. You could become sick and have withdrawal symptoms because your body has become used to the medicine. Physical dependence is not the same as drug addiction. Your doctor can tell you more about the differences between physical dependence and drug addiction. To have fewer withdrawal symptoms, ask your doctor how to stop using buprenorphine hydrochloride sublingual tablets the right way.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Sublingual tablet: 2 mg buprenorphine and 8 mg buprenorphine.
• 1 mL ampules of 0.3 mg/mL for intravenous (iv) or intramuscular (im) injection under the brand name Buprenex

This medicine is available in fallowing brand namesː Subutex

What side effects can this medication cause?

The most common side effects of this medicine include:

• Nausea
• Vomiting
• Drug withdrawal syndrome
• Headache
• Sweating
• Numb mouth
• Constipation
• Swollen and/or painful tongue
• The inside of your mouth is more red than normal
• Intoxication (feeling lightheaded or drunk)
• Disturbance in attention
• Irregular heart beat (palpitations)
• Decrease in sleep (insomnia)
• Blurred vision
• Back pain
• Fainting
• Dizziness
• Sleepiness

Less common,but serious side effects may include:

• life-threatening breathing problems
• Feel sleepy and uncoordinated
• Have blurred vision
• Have slurred speech
• Cannot think well or clearly
• Have slowed reflexes and breathing

• Injecting buprenorphine hydrochloride sublingual tablets may cause serious withdrawal symptoms such as pain, cramps, vomiting, diarrhea, anxiety, sleep problems, and cravings.

What special precautions should I follow?

• Do not drive, operate heavy machinery, or perform any other dangerous activities until you know how this medication affects you. Buprenorphine can cause drowsiness and slow reaction times. This may happen more often in the first few weeks of treatment when your dose is being changed, but can also happen if you drink alcohol or take other sedative drugs when you take buprenorphine hydrochloride sublingual tablets.
• You should not drink alcohol while using buprenorphine hydrochloride sublingual tablets, as this can lead to loss of consciousness or death.
• Buprenorphine can be abused in a manner similar to other opioids, legal or illicit. Prescribe and dispense buprenorphine with appropriate precautions to minimize risk of misuse, abuse, or diversion, and ensure appropriate protection from theft, including in the home.
• Buprenorphine, particularly when taken by the IV route, in combination with benzodiazepines or other CNS depressants (including alcohol), has been associated with significant respiratory depression and death. Patients should be warned of the potential danger of self-administration of benzodiazepines or other depressants while under treatment with buprenorphine hydrochloride sublingual tablets.
• Buprenorphine hydrochloride sublingual tablets should be used with caution in patients with compromised respiratory function (e.g., chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression).
• Patients receiving buprenorphine in the presence of opioid analgesics, general anesthetics, benzodiazepines, phenothiazines, other tranquilizers, sedative/hypnotics or other CNS depressants (including alcohol) may exhibit increased CNS depression. Consider dose reduction of CNS depressants, buprenorphine hydrochloride sublingual tablets.
• Buprenorphine can cause severe, possibly fatal, respiratory depression in children who are accidentally exposed to it. Store buprenorphine-containing medications safely out of the sight and reach of children and destroy any unused medication appropriately.
• Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy.
• Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their healthcare providers if they are taking, or plan to take serotonergic medications.
• Inform patients that opioids could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms.
• Patients should be advised never to give buprenorphine hydrochloride sublingual tablets to anyone else, even if he or she has the same signs and symptoms. It may cause harm or death.
• Patients should be advised that selling or giving away this medication is against the law.
• Patients should be advised not to change the dosage of buprenorphine hydrochloride sublingual tablets without consulting their healthcare providers.
• Patients should be advised to take buprenorphine hydrochloride sublingual tablets once a day.
• Patients should be informed that buprenorphine hydrochloride sublingual tablets can cause drug dependence and that withdrawal signs and symptoms may occur when the medication is discontinued.
• Patients seeking to discontinue treatment with buprenorphine for opioid dependence should be advised to work closely with their healthcare providers on a tapering schedule and should be apprised of the potential to relapse to illicit drug use associated with discontinuation of opioid agonist/partial agonist medication-assisted treatment.
• Patients should be cautioned that, like other opioids, buprenorphine hydrochloride sublingual tablets may produce orthostatic hypotension in ambulatory individuals.
• Patients should inform their healthcare providers if any other prescription medications, over-the-counter medications, or herbal preparations are prescribed or currently being used.
• Advise women that if they are pregnant while being treated with buprenorphine hydrochloride sublingual tablets, the baby may have signs of withdrawal at birth and that withdrawal is treatable.
• Patients should be warned that buprenorphine passes into breast milk. Breastfeeding is therefore not advised in mothers treated with buprenorphine products.
• Patients should inform their family members that, in the event of emergency, the treating healthcare providers or emergency room staff should be informed that the patient is physically dependent on an opioid and that the patient is being treated with buprenorphine hydrochloride sublingual tablets.
• Therapy with buprenorphine has not been associated with serum enzyme elevations, and clinically apparent liver injury has been reported largely with overdose and abuse (intravenous administration of the sublingual formulation).

What to do in case of emergency/overdose?

Symptoms of overdose may include:

• pinpoint pupils, sedation, hypotension, respiratory depression, and death

Management of overdosage:

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.
• In the event of overdose, the respiratory and cardiac status of the patient should be monitored carefully.
• When respiratory or cardiac functions are depressed, primary attention should be given to the re-establishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation.
• Oxygen, IV fluids, vasopressors, and other supportive measures should be employed as indicated.
• In the case of overdose, the primary management should be the re-establishment of adequate ventilation with mechanical assistance of respiration, if required.
• Naloxone may be of value for the management of buprenorphine overdose.
• Higher than normal doses and repeated administration may be necessary.
• The long duration of action of buprenorphine should be taken into consideration when determining the length of treatment and medical surveillance needed to reverse the effects of an overdose.
• Insufficient duration of monitoring may put patients at risk.

Can this medicine be used in pregnancy?

• There are no adequate and well-controlled studies of buprenorphine hydrochloride sublingual tablets or buprenorphine in pregnant women.
• If you take buprenorphine hydrochloride sublingual tablets while pregnant, your baby may have symptoms of opioid withdrawal or respiratory depression at birth. Talk to your doctor if you are pregnant or plan to become pregnant.

Can this medicine be used in children?

• It is not known if buprenorphine hydrochloride sublingual tablets are safe or effective in children.

What are the active and inactive ingredients in this medicine?

• Active Ingredient: buprenorphine hydrochloride
• Inactive Ingredients: anhydrous citric acid, anhydrous lactose, colloidal silicon dioxide, corn starch, crospovidone, lactose monohydrate, magnesium stearate, mannitol, microcrystalline cellulose and sodium citrate

Who manufactures and distributes this medicine?

• Mylan Pharmaceuticals Inc.
• Morgantown, WV U.S.A.

Repackaged by:

• Contract Pharmacy Services-PA
• 125 Titus Ave Suite 200
• Warrington, PA USA

What should I know about storage and disposal of this medication?

• Store buprenorphine hydrochloride sublingual tablets at room temperature between 20º to 25ºC (68º to 77ºF).
• Keep buprenorphine hydrochloride sublingual tablets in a safe place, out of the sight and reach of children.
• Dispose of unused buprenorphine hydrochloride sublingual tablets as soon as you no longer need them.
• Unused tablets should be flushed down the toilet.

Substance abuse treatment agents

• Acamprosate, Buprenorphine, Disulfiram, Methadone, Nalmefene, Naloxegol, Naloxone, Naltrexone, Nicotine, Varenicline.

• Dailymed label info on Buprenorphine
• FDA Buprenorphine

Buprenorphine Resources
Latest articles Most recent articles Ongoing trials	Wikipedia

The following are antidepressant subclasses and drugs

MAO Inhibitors Isocarboxazid, Phenelzine, Tranylcypromine

SNRIs Duloxetine, Levomilnacipran, Venlafaxine

SSRIs Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Vilazodone, Vortioxetine

Tricyclics Amitriptyline, Amoxapine, Clomipramine, Desipramine, Doxepin, Imipramine, Nortriptyline, Protriptyline, Trimipramine

Miscellaneous Bupropion, Flibanserin, Mirtazapine, Nefazodone, Trazodone