Package leaflet: Information for the patient

Prekisan 2 mg sublingual tablets, 4 mg sublingual tablets, 8 mg sublingual tablets

Buprenorphine
Generic medicine
Please read this leaflet carefully before using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Prekisan is and what it is used for
What you need to know before taking Prekisan
How to take Prekisan
Possible side effects
How to store Prekisan
Contents of the pack and other information

1. What Prekisan is and what it is used for

Prekisan is used to treat opioid dependence (narcotics) such as heroin or morphine in drug-dependent individuals who have agreed to undergo treatment for their addiction. Prekisan is used in adults and adolescents over 15 years of age who are also receiving medical, social, and psychological support.

2. What you need to know before using Prekisan

Do not use Prekisan

if you are allergic to buprenorphine or to any of the other ingredients of this medicine (listed in section 6).
if you have severe respiratory problems.
if you have severe liver problems.
if you are heavily dependent on alcohol, or suffer from tremors, excessive sweating, anxiety, confusion, or hallucinations caused by alcohol.
if you are currently taking naltrexone or nalmefene for the treatment of alcohol or opioid dependence.

Warnings and precautions
You may only start treatment with Prekisan after thoroughly discussing the treatment conditions with a doctor specially trained for this purpose.
Inform your doctor if you have or develop any of the following conditions during treatment with Prekisan:

head injury, increased intracranial pressure, or brain disorders
seizures (epilepsy)
low blood pressure
urinary disorders (such as enlarged prostate in men or narrowed ureter)
asthma or severe respiratory problems
kidney disorders or renal failure
liver disorders such as hepatitis or liver failure
thyroid problems
adrenal cortical disorders (e.g. Addison’s disease)
depression or other conditions treated with antidepressants. Using these medicines together with Prekisan may lead to serotonin syndrome, a potentially life-threatening condition (see "Other medicines and Prekisan").

Sleep-related breathing disorders
Prekisan may cause sleep-related breathing disorders such as sleep apnoea (breathing pauses during sleep) and sleep-related hypoxaemia (low blood oxygen levels during sleep). Symptoms may include breathing pauses during sleep, nighttime awakenings due to shortness of breath, difficulty maintaining sleep, or excessive daytime sleepiness. If you or someone else observes these symptoms, contact your doctor. Your doctor may consider reducing the dose.
Please note:

Additional monitoring If you are under 18 or over 65 years of age, your doctor may monitor you more closely. Patients under 15 years of age must not use this medicine.
Misuse and abuse This medicine may be attractive to individuals who misuse prescription medicines and should be stored securely to prevent theft. Do not give this medicine to other people. It could cause death or serious harm to others.
Breathing problems Some people have died from respiratory arrest due to misuse of buprenorphine or taking it together with other substances that depress the central nervous system, such as alcohol, benzodiazepines (tranquillisers), or other opioids. This medicine may cause severe respiratory depression (reduced ability to breathe), potentially fatal, in children and non-dependent individuals in case of accidental or intentional ingestion.
Dependence This medicine may cause dependence.
Withdrawal symptoms This medicine may cause withdrawal symptoms if taken within 6 hours after using a short-acting opioid (e.g. morphine, heroin) or within 24 hours after using a long-acting opioid such as methadone. Prekisan may also cause withdrawal symptoms if treatment is stopped abruptly.
Liver damage Cases of liver damage have been reported after taking Prekisan, particularly with misuse of the medicine. This may also be due to viral infections (chronic hepatitis C), alcohol abuse, anorexia, or use of other medicines that can damage the liver (see section 4). Your doctor may regularly perform blood tests to monitor your liver function. Inform your doctor if you have liver problems before starting treatment with Prekisan.
Blood pressure

This medicine may cause a sudden drop in blood pressure, causing dizziness when rising quickly from a sitting or lying position.

Diagnosis of medical conditions unrelated to dependence This medicine may mask painful symptoms that could be useful in diagnosing certain conditions. You must inform your doctor that you are taking this medicine.

If necessary, your doctor may reduce the dose of Prekisan or initiate specific treatment for the condition. Your doctor will decide on any changes to your treatment.
If you experience pain during treatment, consult your doctor. Your doctor will take appropriate measures.
Please attend all medical check-ups prescribed by your doctor (e.g. urine tests). These checks are essential for your safety and ensure effective treatment.
To reduce the potential for misuse, daily administration under medical supervision or at a pharmacy is recommended. Deviation from daily supervised administration at a clinic/pharmacy is permitted only in justified cases (e.g. due to work).
Do not dissolve and inject the tablets, as this may cause serious adverse effects, possibly fatal (respiratory problems, severe liver damage), and severe reactions, including infections at the injection site.
Tolerance, dependence, and addiction
This medicine contains buprenorphine, which is an opioid medicine. Repeated use of opioids may lead to reduced effectiveness of the medicine (you become accustomed to the medicine, known as tolerance). Repeated use of Prekisan may also lead to dependence, abuse, and addiction, with a consequent risk of potentially fatal overdose.
Dependence or addiction may make you feel unable to control the amount of medicine you take or how often you take it.
The risk of dependence or addiction varies from person to person. You may have a higher risk of developing dependence or addiction to Prekisan if:

you or someone in your family has ever abused or been dependent on alcohol, prescription medicines, or illegal drugs (“addiction”).
you are a smoker.
you have ever had mood disorders (depression, anxiety, or personality disorders) or have been treated by a psychiatrist for other mental illnesses.

You may be experiencing signs of dependence or addiction if, during treatment with Prekisan, you notice any of the following:

you need to use the medicine for longer than recommended by your doctor
you need to use a higher dose than recommended
you are using the medicine for reasons other than those prescribed, e.g. to “stay calm” or “help you sleep”
you have made repeated unsuccessful attempts to stop or control medicine use
you feel unwell when stopping the medicine and feel better once you restart (“withdrawal effects”)

If you notice any of these signs, consult your doctor to discuss the best treatment approach for you, including when and how to stop safely (see section 3. If you stop taking Prekisan).
Children and adolescents
There are no data on the efficacy and safety of Prekisan in children and adolescents under 15 years of age.
Other medicines and Prekisan
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Concomitant use of Prekisan with certain medicines may lead to intensified adverse effects and sometimes very serious reactions. Inform your doctor before using Prekisan with other medicines, especially the following:

Certain sedatives such as benzodiazepines or related substances. These increase the risk of drowsiness, breathing difficulties (respiratory depression), coma, and can be life-threatening. Therefore, concomitant use should only be considered when no other treatment options are available. However, if your doctor prescribes Prekisan together with sedative medicines, the dose and duration of concomitant treatment must be limited by your doctor. Inform your doctor about all sedative medicines you are taking and follow their dose recommendations carefully. It may be helpful to inform friends or family members to watch for the signs and symptoms listed above. Contact your doctor if such symptoms occur.
Gabapentin or pregabalin used to treat epilepsy or nerve-related pain (neuropathic pain).
MAO inhibitors for the treatment of depression. Taking MAO inhibitors within 14 days before Prekisan may increase the effect of Prekisan.
Antidepressants (for the treatment of depression) such as moclobemide, tranylcypromine, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine, venlafaxine, amitriptyline, doxepin, or trimipramine. These medicines may interact with Prekisan and cause symptoms such as involuntary rhythmic muscle contractions, including muscles controlling eye movement, agitation, hallucinations, coma, excessive sweating, tremor, exaggerated reflexes, increased muscle tension, fever above 38°C. Contact your doctor if you experience these symptoms.
Other medicines that may cause drowsiness, used to treat conditions such as anxiety, insomnia, seizures/convulsions, or pain. These medicines may reduce alertness, making driving and operating machinery difficult. They may also cause central nervous system depression, a very serious condition. Examples of such medicines include:
Other medicines containing opioids, such as methadone, certain painkillers, and cough sedatives.
Antidepressants such as isocarboxazid, phenelzine, selegiline, tranylcypromine, and valproate, which may increase the effects of this medicine.
Sedating H-\receptor antagonists (used to treat allergic reactions), such as diphenhydramine and chlorpheniramine.
Barbiturates (used to induce sleep or sedation), such as phenobarbital, secobarbital.
Tranquillisers (used to induce sleep or sedation), such as chloral hydrate.
Clonidine (used to treat high blood pressure) may prolong the effects of this medicine.
Antiretrovirals (used to treat HIV), such as ritonavir, nelfinavir, and indinavir, may increase the effects of this medicine.
Certain antifungal agents (used to treat fungal infections), such as ketoconazole, itraconazole, and certain antibiotics (macrolides), may prolong the effects of this medicine.
Some medicines may reduce the effects of Prekisan. These include medicines used to treat epilepsy (such as carbamazepine and phenytoin) and medicines used to treat tuberculosis (rifampicin).
Naltrexone and nalmefene (medicines used to treat addiction disorders) may block the therapeutic effects of Prekisan. They must not be taken during treatment with Prekisan because they may cause sudden onset of severe and prolonged withdrawal symptoms.
Medicines used to treat allergies, motion sickness, or nausea (antihistamines or antiemetics);
Medicines for psychiatric disorders (antipsychotics or neuroleptics);
Muscle relaxants;
Medicines for Parkinson’s disease;

If you have been treated with methadone or other medicines for substitution therapy and are switching to Prekisan, carefully follow your doctor’s instructions for both medicines.
Prekisan with food, drinks, and alcohol
Alcohol may increase drowsiness and the risk of respiratory failure (inability to breathe) when taken together with Prekisan. Do not take Prekisan with alcohol.
Do not consume food or drinks until the tablet is completely dissolved.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
The risks of using Prekisan in pregnant women are not known. Your doctor will decide whether you can use Prekisan during pregnancy.
If used towards the end of pregnancy, Prekisan may cause withdrawal symptoms and breathing problems in the newborn. This may occur even a few days after birth. If buprenorphine is used during pregnancy, a detailed neonatal examination is recommended to prevent any risk of respiratory depression (inadequate breathing with slow respiration) or withdrawal syndromes.
Breastfeeding
Since buprenorphine passes into breast milk, breastfeeding must be discontinued during treatment with Prekisan.
Driving and using machines
Prekisan may cause drowsiness, dizziness, or altered thinking. These effects may be enhanced if you drink alcohol or take other sedatives during treatment with Prekisan. Do not use tools or machinery and avoid dangerous activities until you know how Prekisan affects you. Exercise maximum caution when driving vehicles or operating dangerous machinery if buprenorphine affects your ability to perform these tasks.
Prekisan contains lactose and sodium
This medicine contains lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per sublingual tablet, i.e. essentially ‘sodium-free’.
For athletes: using this medicine without medical need constitutes doping and may result in a positive anti-doping test.

3. How to use Prekisan

Prekisan must be administered in accordance with national requirements (e.g., under the supervision of a physician specialized in the treatment of drug-dependent patients and, whenever possible, in specialized centers for the treatment of drug addiction).
Use this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.
The dose of Prekisan depends on the onset of withdrawal symptoms and must be individually adjusted for each patient based on their individual situation and subjective feelings. In general, after selecting the initial dose, the lowest possible maintenance dose should be achieved.

Preparation for the first dose of Prekisan
There must be clear evidence of withdrawal before the first dose of Prekisan is administered. If your doctor determines, based on your condition, that the timing for the first dose of Prekisan is appropriate, treatment may begin.

Starting Prekisan treatment during heroin dependence: If you are dependent on heroin or another short-acting opioid, you must take your first dose of Prekisan at the first clear sign of withdrawal, but not earlier than 6 hours after the last use of opioids.
Starting Prekisan treatment during methadone dependence: If you are already taking methadone or another long-acting opioid, the methadone dose should ideally be reduced to less than 30 mg/day before starting Prekisan treatment. The first dose of Prekisan should be taken at the first clear symptoms of withdrawal, but not earlier than 24 hours after the last methadone dose. With higher methadone doses, a longer waiting period may be required.

Starting treatment
When you are ready to begin treatment, your doctor will determine the appropriate initial dose for you based on your individual needs. The goal of treatment is to find the dose that prevents the onset of withdrawal symptoms, thus helping to avoid the use of illegal opioids. Honestly inform your doctor about the dose of Prekisan that effectively suppresses withdrawal symptoms, and report whether you feel the effect of Prekisan is too strong or too weak. Drowsiness and sedation are not treatment goals.

Stabilization and maintenance therapy
Your doctor may adjust the dose according to your needs in the days following the start of treatment. For many patients, the daily dose ranges from 12 to 16 mg of buprenorphine once daily and should not exceed 24 mg per day.

Alternate-day dosing
The clinical effect of Prekisan may last from 48 to 72 hours, depending on the dose. Therefore, after reaching a stable dose of buprenorphine, your doctor may alternatively administer you double the daily dose every two days or triple the daily dose every three days. Dose adjustments must be made under medical supervision. During administration of double or triple doses, you will be monitored for 3–4 hours for possible signs of overdose. Before increasing the buprenorphine dose, the use of other centrally acting sedatives (e.g., benzodiazepines) must be ruled out. Optimal doses should be used on an individual basis. In specific cases, lower doses may be sufficient.

Signs and symptoms of excessive buprenorphine use
Signs and symptoms of excessive buprenorphine effects include feeling "strange," difficulty concentrating, drowsiness, and possibly dizziness upon standing. In such cases, your doctor will generally reduce the dose of Prekisan.

Buprenorphine withdrawal
If the prescribed buprenorphine dose is too low, withdrawal symptoms such as nasal congestion, abdominal discomfort, diarrhea, muscle aches, and feelings of anxiety may occur during the 24-hour interval between doses. In such cases, your doctor may adjust the dose of Prekisan.

Elderly patients (over 65 years of age)
Elderly patients, as well as patients with poor physical condition, may be more sensitive to the effects of opioids. Therefore, particular caution should be exercised when adjusting the dose.

Patients with hepatic and/or renal impairment
Your doctor will take into account any hepatic and/or renal dysfunction when adjusting the dose. Prekisan must not be used if you have severe liver problems. Patients with viral hepatitis (an inflammatory process causing liver cell death) and/or patients with liver disease receiving concomitant pharmacological therapy are at increased risk of liver damage. Your doctor will recommend regular monitoring of liver function.

Method of administration
Prekisan is for sublingual use only.
Place the tablet under the tongue. This is the only way to use Prekisan. Keep the tablet under the tongue until it is completely dissolved (this takes approximately 5 to 10 minutes).
Do not swallow the tablet or consume food or drinks until the tablet has completely dissolved, as doing so may reduce the medicine’s effectiveness.
You may take the tablet at any time of day.

Duration of treatment
The duration of treatment will be determined individually by your doctor.

If you use more Prekisan than you should
If you or anyone else has taken an excessive amount of this medicine, go or be taken immediately to the emergency room or hospital, as an overdose of Prekisan can cause severe and potentially life-threatening breathing problems.
In particular, in individuals with low tolerance (especially children), poisoning (intoxication), which is already inherently dangerous, can occur with doses lower than those typically used in substitution therapy.
Signs of overdose include, for example, drowsiness and coordination problems with slowed reflexes, blurred vision and/or speech disturbances. It may be difficult for you to think clearly, and your breathing may become much slower than normal. In some cases, these severe breathing problems (respiratory depression) can lead to respiratory arrest and death.

If you forget to use Prekisan
Do not take a double dose to make up for the missed dose. Contact your doctor.

If you stop using Prekisan
Do not change your treatment regimen or stop treatment without your doctor’s consent. Abruptly stopping treatment may cause withdrawal symptoms.
After a satisfactory stabilization period has been achieved, your doctor may gradually reduce the dose to a lower maintenance dose. Depending on your condition, the dose may be further reduced under close medical supervision until treatment is eventually discontinued. Do not change or stop treatment without the consent of your treating physician.
The availability of different sublingual tablet strengths, as well as the alternate-day dosing schedule, allows for a gradual and appropriate dose reduction, if agreed upon with your doctor.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Contact your doctor immediately and request emergency medical assistance,
respectively, if any of the following symptoms occur:

swelling of the face, lips, tongue or throat, which may cause difficulty swallowing or breathing, hives/severe skin rash. These may be signs of a potentially life-threatening allergic reaction.
drowsiness and lack of coordination, blurred vision, speech disturbances, thought disturbances, or slower than normal breathing.

Also, inform your doctor immediately if any of the following side effects occur:

severe tiredness, itching with yellowing of the skin or eyes. These may be symptoms of liver damage.
seeing or hearing things that are not there (hallucinations).

Other side effects
Very common (may affect more than 1 in 10 people):
Insomnia, congestion, nausea, excessive sweating, headache
Common (may affect up to 1 in 10 people):
Weight loss, swelling (of the hands and feet), anxiety, nervousness, skin tingling,
depression, decreased sexual drive, increased muscle tension, abnormal thinking,
increased tear production (watery eyes) or other tear disorders, feeling of warmth,
increased blood pressure, migraine, runny nose, sore throat and painful swallowing,
increased coughing, stomach discomfort or other stomach problems, diarrhoea, liver
function disorders, flatulence, vomiting, itching, pain, joint pain, muscle pain, leg cramps (muscle spasms), difficulty achieving or maintaining an erection, changes in urine,
abdominal pain, back pain, weakness, infections, chills, chest pain, fever, flu-like symptoms, malaise, accidental injury due to loss of alertness or coordination,
fainting and dizziness.
Uncommon (may affect up to 1 in 100 people):
Swollen glands (lymph nodes), agitation, tremor, abnormal dreams, excessive muscle activity,
depersonalization (feeling detached from oneself), amnesia (memory disorder), loss of interest,
exaggerated feeling of well-being (euphoria), seizures (fits), reduced pupil size,
difficulty urinating, eye inflammation or infection, fast or slow heartbeat,
low blood pressure, palpitations, myocardial infarction (heart attack), chest tightness,
shortness of breath, asthma, yawning, mouth pain and sores, changes in tongue colour, acne,
skin nodules, hair loss, dry or peeling skin, joint inflammation, urinary tract infection,
abnormal blood tests, blood in urine, abnormal ejaculation, menstrual or vaginal problems,
kidney stones, protein in urine, pain or difficulty urinating, sensitivity to heat or cold,
heatstroke, loss of appetite, feelings of hostility.
Not known (frequency cannot be estimated from the available data):
Sudden withdrawal syndrome caused by taking Prekisan too soon after using illicit opioids, neonatal withdrawal syndrome, liver damage with or without jaundice, hallucinations,
drop in blood pressure when standing up from sitting or lying down, dental caries.
Misuse of Prekisan by intravenous injection may cause withdrawal symptoms, infections,
other skin reactions and potentially serious liver problems (see "Warnings and precautions").
Withdrawal symptoms may occur after the first dose, or even if you took Prekisan less
than 4 hours after taking addictive substances (morphine, heroin, etc.) or less than 24 hours
after the last dose of methadone, because Prekisan can partially reverse the effects of these substances.
Prekisan does not eliminate persistent opioid dependence.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Prekisan

Keep this medicine out of the sight and reach of children. Store this medicine
in a safe and secure place, inaccessible to others. The medicine can cause serious
harm and may be fatal if taken accidentally or intentionally by someone for whom it has not
been prescribed.
Do not use this medicine after the expiry date stated on the blister and carton after
Exp. The expiry date refers to the last day of that month.
Do not store above 30°C.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Prekisan contains
Prekisan 2 mg sublingual tablets

The active substance is buprenorphine. One tablet contains 2.16 mg of buprenorphine hydrochloride, equivalent to 2 mg of buprenorphine.
The other components are: Monohydrate lactose, Mannitol, Maize starch, Povidone K 27.0-32.4, Monohydrate citric acid, Sodium citrate, Magnesium stearate

Prekisan 4 mg sublingual tablets

The active substance is buprenorphine. One tablet contains 4.32 mg of buprenorphine hydrochloride, equivalent to 4 mg of buprenorphine.
The other components are: Monohydrate lactose, Mannitol, Maize starch, Povidone K 27.0-32.4, Monohydrate citric acid, Sodium citrate, Magnesium stearate

Prekisan 8 mg sublingual tablets

The active substance is buprenorphine. One tablet contains 8.64 mg of buprenorphine hydrochloride, equivalent to 8 mg of buprenorphine.
The other components are: Monohydrate lactose, Mannitol, Maize starch, Povidone K 27.0-32.4, Monohydrate citric acid, Sodium citrate, Magnesium stearate

Description of the appearance of Prekisan and pack contents
Prekisan 2 mg sublingual tablets are white, oval, flat tablets with bevelled edges.
Prekisan 4 mg sublingual tablets are white, oval, flat tablets with bevelled edges and a score line on both sides.
Prekisan 8 mg sublingual tablets are white, oval, flat tablets with bevelled edges and a score line on both sides.
Prekisan is available in blister packs containing 7, 10 or 28 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
G.L. Pharma GmbH, Schlossplatz 1, 8502 Lannach, Austria

Marketing Authorization Holder in Italy:
G.L. Pharma Italy S.r.l., [email protected]

This medicinal product is authorized in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Germany
Prekisan 2 mg Sublingual Tablets
Prekisan 4 mg Sublingual Tablets
Prekisan 8 mg Sublingual Tablets

France
BUPENSAN 2 mg, comprimé sublingual
BUPENSAN 4 mg, comprimé sublingual
BUPENSAN 8 mg, comprimé sublingual

Italy
Prekisan

United Kingdom (Northern Ireland)
Buprenorphine 2 mg sublingual tablets
Buprenorphine 4 mg sublingual tablets
Buprenorphine 8 mg sublingual tablets