PREKISAN 4 MG SUBLINGUAL TABLETS - patient leaflet, side effects, dosage

1. what prekisan is and what it is used for

Prekisan is used to treat dependence on opioid (narcotic) drugs such as heroin or morphine in drug addicts who have agreed to be treated 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 you use prekisan do not use prekisan

• – 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 heavily alcoholised 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.

Warnings and precautions

You may start treatment with Prekisan 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 Prekisan 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 Prekisan can lead to serotonin syndrome, a potentially lifethreatening condition (see “Other medicines and Prekisan”).

Sleep-related breathing disorders

Prekisan 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.

Please note:

• - Additional monitoring

If you are younger than 18 or older than 65 years your doctor will possibly control you more often. Patients younger than 15 years should not use this medicine.

• - Improper use and misuse

This medicine may be of interest to individuals who abuse prescription medicines and should therefore be kept safe from theft. Do not pass this medicine on to others. It can lead to death or other harm to other people.

• - 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.

Prekisan can cause withdrawal symptoms if you stop taking it abruptly.

• - Liver damage

Liver damage has been reported after taking Prekisan, 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 Prekisan.

• - 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 not addiction-related diseases

This medicine may mask symptoms of pain that may be important for the diagnosis of certain diseases. Do not forget to advice your doctor if you are taking this medicine.

If necessary, your doctor will reduce Prekisan 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 serve 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 with possible fatal course (breathing problems, severe liver damage) and to severe reactions, even infections, at the injection site. Athletes should be aware of the fact that this medicine may produce positive results to anti-doping tests.

Children and adolescents

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

Other medicines and Prekisan

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

Concomitant use of Prekisan with certain medicines can lead to intensified side effects and sometimes very serious reactions. Tell to your doctor before using Prekisan 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 Prekisan together with sedative medicines, 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.

• - MAO inhibitors for the treatment of depression. Taking MAO inhibitors within 14 days prior to the use of Prekisan can lead to an increased effect of Prekisan.

• - 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 Prekisan 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 states, 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. For a listing of medicines like that, see below:

• – Other opioid containing medicines like methadone, certain pain killers and cough suppressants.

• – Antidepressants, such as isocarboxazid, phenelzine, selegeline, 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.

• – Tranquilizer (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 Prekisan. 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) can inhibit the therapeutic effect of Prekisan. They must not be used concomitantly with Prekisan to avoid suddenly occurring long-lasting and severe withdrawal symptoms.

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

Prekisan with food, drink and alcohol

Alcohol may increase drowsiness and the risk of respiratory failure (inability to breathe) when taken with Prekisan. Do not take Prekisan together with alcohol. Do not consume food or drink until the tablet is completely dissolved.

Pregnancy and breast-feeding

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 Prekisan by pregnant women are not known. Your doctor will decide, if you can use Prekisan during pregnancy.

When used at the end of pregnancy, Prekisan, 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, breastfeeding should be discontinued during treatment with Prekisan.

Driving and using machines

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

Prekisan contains lactose and sodium

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’.

GI17200GB, Prekisan 2/4/8 mg Tab.

3. how to use prekisan

Prekisan should be administered according to national requirements (e.g. under the supervision of a doctor who has experience in the treatment of drug addicts and, whenever possible, in centres specializing in the treatment of drug addiction).

Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

The dose of Prekisan is based on the occurrence of withdrawal symptoms and must be set for each patient according to the individual situation and subjective feeling. In general, the lowest possible maintenance dose should be sought after setting the dose.

Preparation for the administration of the first dose of Prekisan

There must be clear evidence of withdrawal prior to the first Prekisan dose. If the doctor determines on the basis of your constitution that the time for the administration of your first dose of Prekisan is appropriate, the treatment begins.

• - Initiation of treatment with Prekisan with an existing heroin addiction: If you are dependent on heroin or a short-acting opioid, you should use your first dose of Prekisan at the first clear sign of withdrawal, but not earlier than 6 hours after the last opioid use.

• - Initiation of treatment with Prekisan with an existing methadone addiction: If you are already on methadone or a long-acting opioid, the dose of methadone should ideally be reduced to below 30 mg/day before starting Prekisan treatment. The first dose of Prekisan should be used at the first definite withdrawal symptoms, but at the earliest 24 hours after the last dose of methadone. At high doses of methadone, a longer waiting period may be necessary.

Initiation of treatment

When you are ready to start the treatment, the doctor will determine the appropriate initiation dose for you according to your needs. The aim of the treatment is to determine the dose that prevents the onset of withdrawal symptoms in order to avoid the use of illegal opioids. Please tell your doctor honestly, what dose of Prekisan suppresses your withdrawal symptoms, and tell your doctor if you think the effect of Prekisan is too strong or too weak. Drowsiness and sedation are not the goal of the treatment.

Stabilisation and maintenance therapy

Your doctor can 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 buprenorphine once daily and should not exceed 24 mg per day.

Alternate dosing

The clinical effectiveness of Prekisan can last 48 to 72 hours depending on the dose. Therefore, after you have reached a stable dose of buprenorphine, your doctor may alternately give you double the dose for a 2-day interval or triple the dose for a 3-day interval. The dose setting must be carried out under medical supervision. While setting the double or triple dose, you are monitored for 3–4 hours for possible overdose symptoms. Before increasing the buprenorphine dose, the use of other central depressant substances (e.g. benzodiazepines) must be excluded. Optimized doses are to be used individually. In individual cases, lower doses may be sufficient.

Signs and symptoms of excessive buprenorphine use Signs and symptoms of excessive buprenorphine effects include symptoms such as “feeling strange”, poor concentration, sleepiness and possibly standing up. In these cases, your doctor will usually lower the dose of Prekisan.

Buprenorphine withdrawal

If the prescribed buprenorphine dose is too low, withdrawal symptoms such as the nose, abdominal discomfort, diarrhoea, muscle pain, feelings of anxiety may occur during the 24-hour dose interval. In these cases, your doctor may change the dose of Prekisan.

Elderly (over 65 years)

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

Patients with liver and/or kidney impairment

Your doctor will consider liver and/or kidney dysfunction during dose adjustment. If you have severe liver problems, Prekisan 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.

Method of administration

Prekisan is for sublingual use.

Put the tablet under your tongue. This is the only way how to use Prekisan. 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, because it will lose its efficacy by doing so.

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

Duration of treatment

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

If you use more Prekisan than you should

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 over-administration of Prekisan 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 breathing arrest and death.

If you forget to use Prekisan

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

If you stop using Prekisan

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.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

GEROTjJ LANNACH

4. possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Contact a doctor immediately and get prompt emergency care , respectively, if the following symptoms develop:

• – Swelling of face, lips, tongue or throat, which may cause difficulty in swallowing or breathing, severe skin rash/hives. These could be signs of a lifethreatening allergic reaction.

• – Drowsiness and coordination disorders, blurred vision, speech disorders, thought disorders or significantly slower breathing than it would be otherwise.

Also contact your doctor immediately , if you suffer from the following side effects:

• – Severe tiredness, itching with yellowing of the skin or eyes. These could be signs of liver damage.

• – Seeing or hearing things that are not real (hallucinations).

Other side effects

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 Prekisan 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.

If Prekisan 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 Prekisan less than 4 hours after having taken addictive drugs (morphine, heroin etc.) or less than 24 hours after the last dose of methadone as Prekisan may partly abolish the efficacy of these substances. Prekisan does not reverse persisting opiate dependence.

Reporting of side effects

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 national reporting system:

Yellow Card Scheme

Website: 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.

5. how to store prekisan

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated after “EXP” on the blister and the carton. The expiry date refers to the last day of that month.

Do not store above 30°C.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. contents of the pack and other information

What Prekisan contains

Prekisan 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

Prekisan 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

Prekisan 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:

What Prekisan looks like and contents of the pack

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 blisters of 7, 10 and 28 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer G.L. Pharma GmbH

Schlossplatz 1, 8502 Lannach, Austria

This leaflet was last revised in 03/2022.

GI17200GB, Prekisan 2/4/8 mg Tab.

GI17200GB_uk_­Prekisan_Tab_Bli­.indd 2

21.03.22 12:10