• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Buprenorphine is and what it is used for
2. What you need to know before you use Buprenorphine
3. How to use Buprenorphine
4. Possible side effects
5. How to store Buprenorphine
6. Contents of the pack and other information

• if you are allergic to buprenorphine or any of the other ingredients of this medicine (listed in section 6).
• if you have serious breathing problems.
• if you have serious problems with your liver.
• if you are intoxicated due to alcohol or suffer from alcohol-related trembling, heavy sweating, anxiety, confusion or hallucinations.
• if you take naltrexone or nalmefene for the treatment of alcohol or opioid dependence.

You may start treatment with Buprenorphine only if you have thoroughly discussed the treatment conditions with a specially trained doctor.

Tell your doctor if you suffer from one of the illnesses listed below or if you develop them during Buprenorphine treatment:

• head injuries, increased pressure in your head or diseases of the brain
• fits (epilepsy)
• low blood pressure
• urinary disorders (such as enlarged prostate in men and narrowed ureter)
• asthma or severe breathing problems
• kidney disease or kidney failure
• liver disease such as hepatitis or liver failure
• thyroid problems
• adrenocortical disorder (e.g. Addison’s Disease)
• depression or other conditions that are treated with antidepressants.
  The use of these medicines together with Buprenorphine can lead to serotonin syndrome, a potentially life-threatening condition (see “Other medicines and Buprenorphine”).

Buprenorphine can cause sleep-related breathing disorders such as sleep apnoea (breathing pauses during sleep) and sleep related hypoxemia (low oxygen level in the blood). The symptoms can include breathing pauses during sleep, night awakening due to shortness of breath, difficulties to maintain sleep or excessive drowsiness during the day. If you or another person observe these symptoms, contact your doctor. A dose reduction may be considered by your doctor.

• Additional monitoring
  If you are younger than 18 or older than 65 years your doctor will possibly monitor you more often. Patients younger than 15 years should not use this medicine.
• Improper use and misuse
  This medicine can be a target for individuals who abuse prescription medicines and should therefore be kept safe in a safe place to protect it from theft. Do not pass this medicine on to others. It can lead to death or otherwise harm them.
• Breathing difficulties
  Some people have died as a result of respiratory arrest because they misused buprenorphine or used it in combination with other central nervous system depressant substances, e.g. alcohol, benzodiazepines (tranquilizers) or other opioids. This medicine may lead to severe, probably lethal respiratory depression (reduced ability to breathe) in children and non-dependent persons, who use it accidentally or knowingly.
• Dependence
  This medicine can cause dependence.
• Withdrawal symptoms
  This medicine may induce withdrawal symptoms if you use it earlier than 6 hours after the use of a short-acting opioid (e.g. morphine, heroin) or less than 24 hours after the application of a long-acting opioid such as methadone.
  Buprenorphine can cause withdrawal symptoms if you stop taking it abruptly.
• Liver damage
  Liver damage has been reported after taking Buprenorphine, especially when the medicine is misused. This could also be due to viral infections (chronic hepatitis C), alcohol abuse, anorexia or use of other medicines with the ability to harm your liver (see section 4). Your doctor may perform regular blood tests to check the condition of your liver. Tell your doctor if you have any liver problems before you start treatment with Buprenorphine.
• Blood pressure
  Use of this medicine may cause a sudden drop in blood pressure, which causes dizziness if you get up too quickly from sitting or lying down.
• Diagnosis of unrelated medical conditions
  This medicine may mask symptoms of pain that may be important for the diagnosis of certain diseases. Do not forget to advise your doctor if you are taking this medicine.
  If necessary, your doctor will reduce Buprenorphine dose or initiate targeted treatment against this disease. The doctor will decide upon changes in your treatment.
  If pain occurs during treatment, talk to your doctor. He will take appropriate action.

Please follow the check-ups prescribed by your doctor (e.g. urine test). They are for your own safety and ensure effective treatment.

To reduce the misuse potential it is recommended to have the daily intake supervised in the doctor’s office or in the pharmacy. Only in justified cases (e.g. job), deviation from daily intake in the doctor’s office/the pharmacy is allowed.

You must not dissolve and inject the tablets as this may lead to severe side effects (breathing problems, severe liver damage) with a possible fatal outcome, and to severe reactions, even infections, at the injection site.

Tolerance, dependence, and addiction

This medicine contains buprenorphine which is an opioid medicine. Repeated use of opioids can result in the drug being less effective (you become accustomed to it, known as tolerance). Repeated use of Buprenorphine can also lead to dependence, abuse, and addiction, which may result in life-threatening overdose.

Dependence or addiction can make you feel that you are no longer in control of how much medicine you need to take or how often you need to take it.

The risk of becoming dependent or addicted varies from person to person. You may have a greater risk of becoming dependent on or addicted to Buprenorphine if:

• You or anyone in your family have ever abused or been dependent on alcohol, prescription medicines or illegal drugs (“addiction”).
• You are a smoker.
• You have ever had problems with your mood (depression, anxiety, or a personality disorder) or have been treated by a psychiatrist for other mental illnesses.

If you notice any of the following signs whilst taking Buprenorphine, it could be a sign that you have become dependent or addicted:

• You need to take the medicine for longer than advised by your doctor
• You need to take more than the recommended dose
• You are using the medicine for reasons other than prescribed, for instance, ‘to stay calm’ or ‘help you sleep’
• You have made repeated, unsuccessful attempts to quit or control the use of the medicine
• When you stop taking the medicine you feel unwell, and you feel better once taking the medicine again (‘withdrawal effects’).

If you notice any of these signs, speak to your doctor to discuss the best treatment pathway for you, including when it is appropriate to stop and how to stop safely (See section 3, If you stop taking Buprenorphine).

Athletes should be aware that this medicine may produce positive results to anti-doping tests.

For the treatment of children and adolescents under 15 years of age with Buprenorphine, there is no data on efficacy and safety.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Concomitant use of Buprenorphine with certain medicines can lead to intensified side effects and sometimes very serious reactions. Talk to your doctor before using Buprenorphine with other medicines, especially the following:

• Certain sedatives such as benzodiazepines or related substances. Increases the risk of drowsiness, difficulties in breathing (respiratory depression) as well as coma and may be life-threatening. Because of this, concomitant use should only be considered, when other treatment options are not possible.
  However, if your doctor does prescribe Buprenorphine together with sedative medicines, the dose and duration of concomitant treatment should be limited by your doctor.
  Please tell your doctor about all sedative medicines you are taking, and follow your doctor’s dose recommendation closely. It could be helpful to inform friends or relatives to be aware of the signs and symptoms stated above. Contact your doctor when experiencing such symptoms.
• Gabapentin or pregabalin to treat epilepsy or pain due to nerve problems (neuropathic pain)
• MAO inhibitors for the treatment of depression. Taking MAO inhibitors within 14 days prior to the use of Buprenorphine can lead to an increased effect of Buprenorphine.
• Anti-depressants (for the treatment of depression) such as moclobemide tranylcypromine, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine, venlafaxine, amitriptyline, doxepine, or trimipramine. These medicines may interact with Buprenorphine and you may experience symptoms such as involuntary, rhythmic contractions of muscles, including the muscles that control movement of the eye, agitation, hallucinations, coma, excessive sweating, tremor, exaggeration of reflexes, increased muscle tension, body temperature above 38°C. Contact your doctor when experiencing such symptoms.
• Other medicines, which may make you sleepy and are used for the treatment of anxiety, sleeplessness, convulsions/fits or pain. This kind of medicine reduces your attention and aggravates driving and operating machinery. They may also lead to central nervous system depression, which is very serious. Below is a list of examples of these types of medicines:
  • Other opioid-containing medicines like methadone, certain pain killers and cough suppressants.
  • Antidepressants, such as isocarboxazid, phenelzine, selegiline, tranylcypromine and valproate, which can enhance the effect of this medicine.
  • Sedative H¹-receptor antagonists (for the treatment of allergic reactions), such as diphenhydramine and chlorphenamine.
  • Barbiturates (used as sleeping medicines and sedatives), such as phenobarbital, secobarbitale.
  • Tranquilizers (used as sleeping medicines and sedatives), such as chloralhydrate.
• Clonidine (for the treatment of high blood pressure) may extend the effect of this medicine.
• Antiretrovirals (used to treat AIDS), e.g. ritonavir, nelfinarvir and indinavir, may enhance the effect of this medicine.
• Some antifungal medicines (for the treatment of fungal infections), such as ketoconazole, itraconazole, and certain antibiotics (macrolide) may enhance the effect of this medicine.
• Some medicines may decrease the effect of Buprenorphine. These include medicines for the treatment of epilepsy (such as carbamazepine or phenytoin) and for the treatment of tuberculosis (rifampicin).
• Naltrexone and nalmefene (for the treatment of addictive disorders) may stop Buprenorphine from working. They must not be used concomitantly with Buprenorphine to avoid a sudden onset of long-lasting and severe withdrawal symptoms.
• Medicines used to treat allergies, travel sickness or nausea (antihistamines or antiemetics).
• Medicines to treat psychiatric disorders (antipsychotics or neuroleptics).
• Muscle relaxants.
• Medicines to treat Parkinson’s disease.

If you have been treated with methadone or other medicines for substitution treatment and you are switched to Buprenorphine, follow your doctor's instructions for both medicines carefully.

Alcohol may increase drowsiness and the risk of respiratory failure (inability to breathe) when taken with Buprenorphine. Do not take Buprenorphine together with alcohol.

Do not consume food or drink until the tablet is completely dissolved.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Pregnancy

The risks of using Buprenorphine by pregnant women are not known. Your doctor will decide if you can use Buprenorphine during pregnancy.

When used at the end of pregnancy, Buprenorphine, may lead to withdrawal symptoms and respiratory problems in the newborn. This is still possible a few days after birth. If buprenorphine is used during pregnancy, a detailed neonatal examination is recommended to avoid any risk of respiratory depression (inadequate breathing during reduced breathing work) or withdrawal syndromes.

Breast-feeding

As buprenorphine passes into breast milk, breast-feeding should be discontinued during treatment with Buprenorphine.

Buprenorphine can cause drowsiness, dizziness or impairment of thinking. This effect can be enhanced when drinking alcohol or taking other sedatives during treatment with Buprenorphine. Do not operate tools or machinery and do not carry out dangerous activities until you know how you respond to Buprenorphine. Take the utmost care when driving vehicles and using dangerous machinery if buprenorphine affects how you perform these activities.

Buprenorphine can affect your ability to drive as it may make you sleepy or dizzy.

• Do not drive while taking this medicine until you know how it affects you.
• It is an offence to drive if this medicine affects your ability to drive.
• However, you would not be committing an offence if:
  • The medicine has been prescribed to treat a medical or dental problem and
  • You have taken it according to the instructions given by the prescriber or in the information provided with the medicine and
  • It was not affecting your ability to drive safely

Talk to your doctor or pharmacist if you are not sure whether it is safe for you to drive while taking this medicine.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before using this medicine.

This medicine contains less than 1 mmol (23 mg) sodium per sublingual tablet, that is to say essentially ‘sodium-free’.

Patients in advanced age as well as patients with poor physical condition may be more sensitive to opioids. Therefore, special care should be taken when adjusting the dose.

Your doctor will consider liver and/or kidney dysfunction during dose adjustment. If you have severe liver problems, Buprenorphine must not be used. Patients with viral hepatitis (an inflammatory process that causes death of liver cells), and/or patients with liver diseases receiving concomitant drug therapies have an increased risk of liver damage. The doctor will recommend regular monitoring of liver conditions.

Buprenorphine is for sublingual use.

Put the tablet under your tongue. This is the only way to use Buprenorphine. Keep the tablet under your tongue until it has completely dissolved (this takes approximately 5 to 10 minutes).

You must not swallow the tablet or consume food or drink until the tablet is completely dissolved, otherwise it may not work properly.

You can use the tablet at any time of the day.

The duration of treatment will be determined individually by the doctor.

If you or any other person has used too much of this medicine, you must go or must be brought to an emergency department or in a hospital immediately, as an overdose of Buprenorphine can cause serious and life-threatening respiratory problems.

Particularly in people with a low tolerance threshold (especially children), poisoning (intoxications) that is already threatening can be caused by lower doses than those customary in substitution therapy.

Signs of overdose are e.g. drowsiness and coordination problems with slowed reflexes, blurred vision and/or speech disorders. It may be difficult for you to think clearly, and your breathing may be much slower than it would be otherwise. In some circumstances, these severe breathing problems (respiratory depression) may lead to stopping breathing and death.

Do not use a double dose to make up for a forgotten dose. Contact your doctor.

Do not change the treatment on your own account and do not stop the treatment without the consent of your doctor. Stopping the treatment suddenly may cause withdrawal symptoms. After a time of successful treatment, your doctor may reduce the dose gradually to a lower maintenance dose. Depending on your condition, the dose may continue to be reduced under careful medical supervision, until it may be stopped eventually. Do not change and do not discontinue treatment without the consent of the attending physician.

The availability of the different strengths of the sublingual tablets as well as the alternate dosing scheme allows a gradual and smooth decrease of the dose if mutually agreed with your doctor.

Very common (may affect more than 1 in 10 people):

Sleeplessness, congestion, nausea, excessive sweating, headache

Common (may affect up to 1 in 10 people):

Weight loss, swelling (of hands or feet), anxiety, nervousness, tingling on the skin, depression, reduced sexual desire, increased muscle tension, abnormal thinking, increased flow of tears (watery eyes) or other tear flow disorders, feeling of heat, increased blood pressure, migraine, runny nose, sore throat and painful swallowing, intensified cough, upset stomach or other stomach problems, diarrhoea, liver function disorder, wind, vomiting, itching, pain, joint pain, muscle pain, cramps in the legs (muscle cramps), difficulties getting or holding an erection, abnormality of urine, abdominal pain, back pain, weakness, infections, chills, chest pain, fever, flu-like symptoms, malaise, accidental injury due to reduced attention or coordination, fainting and dizziness

Uncommon (may affect up to 1 in 100 people):

Swelling of the glands (lymph nodes), restlessness, trembling (tremor), abnormal dreams, excessive muscle activity, depersonalisation (feeling of alienation), amnesia (memory disorder), loss of interest, exaggerated feeling of well-being, convulsions (fits), small pupils, urination problems, inflammation or infection of the eyes, accelerated or slowed heartbeat, low blood pressure, palpitations, myocardial infarction (heart attack), tightness in the chest, breathlessness, asthma, yawing, pain and sores in the mouth, tongue discoloration, acne, skin knots, hair loss, dry or scaly skin, join inflammation, urinary tract infection, abnormal blood tests, blood in urine, abnormal ejaculation, menstrual or vaginal problems, kidney stones, protein in the urine, pain or problems urinating, sensitivity to heat or cold, heat stroke, loss of appetite, hostility

Not known (frequency cannot be estimated from the available data):

Suddenly appearing withdrawal syndrome due to too early administration of Buprenorphine after the use of illegal opioids, neonatal withdrawal syndrome, liver damage with or without jaundice, hallucinations, drop in blood pressure when getting up from lying or sitting, dental caries.

If Buprenorphine has been misused by i.v. injection, withdrawal symptoms, infections, other skin reactions, and potentially severe liver problems may occur (see section "Warnings and precautions").

Withdrawal symptoms may occur after the first dose, but also if you have been using Buprenorphine less than 4 hours after having taken addictive drugs (morphine, heroin etc.) or less than 24 hours after the last dose of methadone as Buprenorphine may partly abolish the efficacy of these substances. Buprenorphine does not reverse persisting opiate dependence.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme; Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

By reporting side effects you can help provide more information on the safety of this medicine.

Buprenorphine 2 mg sublingual tablets:

• The active substance is Buprenorphine. 1 tablet contains 2.16 mg Buprenorphine hydrochloride equivalent to 2 mg buprenorphine.
• The other ingredients are:
  Lactose monohydrate
  Mannitol
  Maize starch
  Povidone K 27.0-32.4
  Citric acid monohydrate
  Sodium citrate
  Magnesium stearate

Buprenorphine 4 mg sublingual tablets:

• The active substance is Buprenorphine. 1 tablet contains 4.32 mg Buprenorphine hydrochloride equivalent to 4 mg buprenorphine.
• The other ingredients are:
  Lactose monohydrate
  Mannitol
  Maize starch
  Povidone K 27.0-32.4
  Citric acid monohydrate
  Sodium citrate
  Magnesium stearate

Buprenorphine 8 mg sublingual tablets:

• The active substance is Buprenorphine. 1 tablet contains 8.64 mg Buprenorphine hydrochloride equivalent to 8 mg Buprenorphine.
• The other ingredients are:
  Lactose monohydrate
  Mannitol
  Maize starch
  Povidone K 27.0-32.4
  Citric acid monohydrate
  Sodium citrate
  Magnesium stearate

Buprenorphine 2 mg sublingual tablets are white, oval, flat tablets with bevelled edges.

Buprenorphine 4 mg sublingual tablets are white, oval, flat tablets with bevelled edges and a score-line on both sides.

Buprenorphine 8 mg sublingual tablets are white, oval, flat tablets with bevelled edges and a score-line on both sides.

Buprenorphine is available in blisters of 7, 10 and 28 tablets.

Not all pack sizes may be marketed.