Buprenorphine and naloxone G.L. Pharma

Patient Information Leaflet: Instructions for the User

Buprenorphine and Naloxone G.L. Pharma 2 mg/0.5 mg sublingual tablets, 4 mg/1 mg sublingual tablets, 8 mg/2 mg sublingual tablets

buprenorphine/naloxone
Generic medicine
Please read all of this leaflet carefully before taking 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 to them.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Buprenorfina e Naloxone G.L. Pharma is and what it is used for

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

2. What you should know before taking Buprenorphine and Naloxone G.L. Pharma

Do not take Buprenorphine and Naloxone G.L. Pharma

• if you are allergic (hypersensitive) to buprenorphine, naloxone, or 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 have alcohol intoxication, or tremors, sweating, anxiety, confusion, or hallucinations caused by alcohol.
• if you are taking naltrexone or nalmefene for the treatment of alcohol or opioid dependence.

Warnings and precautions
Talk to your doctor before taking Buprenorphine and Naloxone G.L. Pharma if you have:

• asthma or other respiratory problems
• liver problems, e.g. hepatitis
• low blood pressure
• recent head trauma or brain disease
• urinary disorders (particularly related to prostate enlargement in men)
• any kidney disease
• thyroid problems
• adrenal cortical disorder (e.g. Addison's disease)
• depression or other conditions treated with antidepressants.

Taking these medicines together with Buprenorphine and Naloxone G.L. Pharma may cause serotonin syndrome, a condition that can be fatal (see “Other medicines and Buprenorphine and Naloxone G.L. Pharma”).
Important information to be aware of:

• Additional monitoring If you are under 18 or over 65 years of age, your doctor may monitor you more closely. This medicine must not be taken by individuals under 15 years of age.
• Misuse and abuse This medicine may be attractive to people 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.
• Respiratory problems Some people have died from respiratory failure (inability to breathe) due to misuse of this medicine or taking it together with other substances that depress the central nervous system, such as alcohol, benzodiazepines (tranquillisers), or other opioids. This medicine can cause severe respiratory depression (reduced ability to breathe), potentially fatal, in children and non-dependent individuals in case of accidental or intentional ingestion.
• Sleep-related breathing disorders Buprenorphine and Naloxone G.L. Pharma 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 notices these symptoms, contact your doctor. Your doctor may consider reducing the dose.
• Dependence This medicine may cause dependence.
• Withdrawal symptoms This medicine may cause withdrawal symptoms if taken less than 6 hours after using a short-acting opioid (e.g. morphine, heroin) or less than 24 hours after using a long-acting opioid such as methadone.

Buprenorphine and Naloxone G.L. Pharma may also cause withdrawal symptoms if treatment is stopped abruptly.

• Liver damage Liver damage has been reported after taking Buprenorphine and Naloxone G.L. Pharma, 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 Buprenorphine and Naloxone G.L. Pharma.
• Blood pressure This medicine may cause a sudden drop in blood pressure, leading to dizziness when rising quickly from a sitting or lying position.
• Diagnosis of unrelated medical conditions This medicine may mask painful symptoms that could be useful in diagnosing certain diseases. You must inform your doctor that you are taking this medicine.

For athletes: using the drug without therapeutic need constitutes doping and may result in a positive anti-doping test.
Other medicines and Buprenorphine and Naloxone G.L. Pharma
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
Some medicines may increase the side effects of Buprenorphine and Naloxone G.L. Pharma, which can be serious. Do not take other medicines during treatment with Buprenorphine and Naloxone G.L. Pharma without first consulting your doctor, especially:

• Concomitant use of Buprenorphine and Naloxone G.L. Pharma with sedative medicines, such as benzodiazepines (used to treat anxiety or sleep disorders) or related drugs, increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and may be fatal. For this reason, concomitant use should only be considered when no other treatment options are possible. However, if your doctor prescribes Buprenorphine and Naloxone G.L. Pharma 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 for treating epilepsy or nerve-related pain (neuropathic pain).
• Other medicines that may cause drowsiness, used to treat conditions such as anxiety, insomnia, seizures/epileptic fits, or pain. These types of medicines may reduce alertness, making driving and operating machinery difficult. They may also cause central nervous system depression, a very serious condition. Below are some examples of these types of medicines:
  • Other medicines containing opioids, such as methadone, some painkillers, and cough suppressants.
  • Antidepressants (used to treat depression), 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 chlorphenamine.
  • 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, indinavir, may increase the effects of this medicine.
• Some antifungal agents (used to treat fungal infections), such as ketoconazole, itraconazole, and certain antibiotics, may prolong the effects of this medicine.
• Some medicines may reduce the effects of Buprenorphine and Naloxone G.L. Pharma. 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 substance dependence) may block the therapeutic effects of Buprenorphine and Naloxone G.L. Pharma. They must not be taken during treatment with Buprenorphine and Naloxone G.L. Pharma, as they may cause sudden onset of intense and prolonged withdrawal symptoms.
• Antidepressants such as moclobemide, tranylcypromine, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine, venlafaxine, amitriptyline, doxepin, or trimipramine. These medicines may interact with Buprenorphine and Naloxone G.L. Pharma and may cause symptoms such as involuntary rhythmic muscle contractions, including muscles controlling eye movements, agitation, hallucinations, coma, excessive sweating, tremor, exaggerated reflexes, increased muscle tone, and fever above 38°C. Contact your doctor if you experience such symptoms.

Buprenorphine and Naloxone G.L. Pharma with food, drinks, and alcohol
Alcohol may increase drowsiness and the risk of respiratory failure when taken with Buprenorphine and Naloxone G.L. Pharma. Do not consume alcohol during treatment with Buprenorphine and Naloxone G.L. Pharma. Do not eat or drink anything 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 before taking this medicine.
The risks of using Buprenorphine and Naloxone G.L. Pharma in pregnant women are not known.
Inform your doctor if you are pregnant or planning a pregnancy. Your doctor will decide whether to continue treatment with an alternative medicine.
If taken during pregnancy, especially in the later stages, medicines such as Buprenorphine and Naloxone G.L. Pharma may cause withdrawal symptoms, including breathing problems, in the newborn. These may appear several days after birth.
Do not breastfeed during treatment with this medicine, as Buprenorphine and Naloxone G.L. Pharma passes into breast milk.
Ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
Buprenorphine and Naloxone G.L. Pharma may cause drowsiness. This is more likely during the first weeks of treatment or when the dose is changed, but may also occur if you drink alcohol or take other sedative medicines together with Buprenorphine and Naloxone G.L. Pharma. Do not drive, operate tools or machinery, or engage in hazardous activities until you know how this medicine affects you.
Buprenorphine and Naloxone G.L. Pharma contains lactose and sodium
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 tablet, i.e. essentially 'sodium-free'.

3. How to take Buprenorphine and Naloxone G.L. Pharma

Your treatment will be prescribed and monitored by doctors experienced in treating substance dependence.
Your doctor will determine the optimal dose for you. During treatment, your doctor may adjust the dose according to your response to therapy.
Always take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

Starting treatment

The recommended initial dose for adults and adolescents over 15 years of age is generally one to two tablets of Buprenorphine and Naloxone G.L. Pharma 2 mg/0.5 mg. One or two additional tablets of Buprenorphine and Naloxone G.L. Pharma 2 mg/0.5 mg may be administered on day 1, depending on your needs.
You must be aware of clear signs of withdrawal before taking the first dose of Buprenorphine and Naloxone G.L. Pharma. Your doctor will tell you when to take the first dose.

• Starting treatment with Buprenorphine and Naloxone G.L. Pharma during heroin dependence
  In case of dependence on heroin or another short-acting opioid, the first dose of Buprenorphine and Naloxone G.L. Pharma should be taken when withdrawal signs appear, at least 6 hours after the last use of opioids.

• Starting treatment with Buprenorphine and Naloxone G.L. Pharma during methadone dependence
  If you are taking methadone or another long-acting opioid, the methadone dose should ideally be reduced to less than 30 mg/day before starting treatment with Buprenorphine and Naloxone G.L. Pharma. The first dose of Buprenorphine and Naloxone G.L. Pharma should be taken when withdrawal signs appear and at least 24 hours after the last methadone dose.

Taking Buprenorphine and Naloxone G.L. Pharma

• Take the dose once daily by placing the tablets under the tongue.
• Keep the tablets under the tongue until they are completely dissolved. This may take 5–10 minutes.
• Do not chew or swallow the tablets, as the medicine will not work and you may experience withdrawal symptoms.
• Do not eat or drink until the tablets are completely dissolved.

Dose adjustment and maintenance therapy:
In the days following the start of treatment, your doctor may increase the dose of Buprenorphine and Naloxone G.L. Pharma according to your needs. If you feel the effect of Buprenorphine and Naloxone G.L. Pharma is too strong or too weak, consult your doctor or pharmacist. The maximum daily dose is 24 mg of buprenorphine.
After a period of successful treatment, you may agree with your doctor to gradually reduce the dose down to a lower maintenance dose.

Stopping treatment
Depending on your condition, the dose of Buprenorphine and Naloxone G.L. Pharma may be gradually reduced under close medical supervision until treatment is completely discontinued.
Do not change or stop treatment in any way without the consent of your treating doctor. An abrupt interruption of treatment may cause withdrawal symptoms.

If you take more Buprenorphine and Naloxone G.L. Pharma than you should
If you or someone else takes an excessive amount of this medicine, go or be taken immediately to the emergency room or hospital for treatment, as overdose of Buprenorphine and Naloxone G.L. Pharma can cause serious and potentially life-threatening breathing problems.
Symptoms of overdose may include drowsiness, lack of coordination, slowed reflexes, blurred vision and/or speech difficulties. You may be unable to think clearly, and breathing may be slower than normal.

If you forget to take Buprenorphine and Naloxone G.L. Pharma
Inform your doctor as soon as possible if you miss a dose.

If you stop treatment with Buprenorphine and Naloxone G.L. Pharma
Do not change or stop treatment in any way without the consent of your treating doctor. An abrupt interruption of treatment may cause withdrawal symptoms.
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Contact your doctor immediately or seek urgent medical attention if any of the following side effects occur:

• swelling of the face, lips, tongue or throat, which may cause difficulty swallowing or breathing, severe hives/rash. These may be signs of a potentially life-threatening allergic reaction.
• feeling drowsy and uncoordinated, blurred vision, difficulty speaking, inability to think clearly or properly, or if breathing becomes much slower than normal.

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

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

Side effects reported with Buprenorphine and Naloxone G.L. Pharma
Very common side effects (may affect more than 1 in 10 people):
Insomnia (inability to sleep), constipation, nausea, excessive sweating, headache, substance abuse withdrawal syndrome
Common side effects (may affect up to 1 in 10 people):
Weight loss, swelling (of hands and feet), drowsiness, anxiety, nervousness, tingling, depression, decreased libido, increased muscle tension, abnormal thinking, increased tear production (watery eyes) or other tear disorders, blurred vision, flushing, increased blood pressure, migraine, runny nose, sore throat and painful swallowing, increased cough, stomach discomfort or other stomach upset, diarrhoea, abnormal liver function, flatulence, vomiting, rash, itching, hives, pain, joint pain, muscle pain, leg cramps (muscle spasm), difficulty achieving or maintaining an erection, changes in urine, abdominal pain, back pain, weakness, infection, chills, chest pain, fever, flu-like symptoms, general discomfort, accidental injury due to loss of alertness or coordination, malaise and dizziness
Uncommon side effects (may affect up to 1 in 100 people):
Swollen glands (lymph nodes), restlessness, tremor, abnormal dreams, excessive muscle activity, depersonalization (feeling detached from oneself), drug dependence, amnesia (memory disorder), loss of interest, exaggerated feeling of well-being, seizures (fits), speech disorder, constricted pupils, difficulty urinating, eye inflammation or infection, rapid or slow heartbeat, low blood pressure, palpitations, myocardial infarction (heart attack), chest tightness, shortness of breath, asthma, yawning, mouth pain and sores, change in tongue colour, acne, skin nodule, hair loss, dryness or peeling of the 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, heat stroke, loss of appetite, feelings of hostility.
Not known (frequency cannot be estimated from the available data):
Sudden withdrawal syndrome caused by taking Buprenorphine and Naloxone G.L. Pharma too soon after using illicit opioids, substance abuse withdrawal syndrome in newborns, slow or difficult breathing, dental caries, liver injury with or without jaundice, hallucinations, swelling of the face and throat or potentially life-threatening allergic reactions, drop in blood pressure when standing up from sitting or lying down.
Improper use of this medicine by injection may cause withdrawal symptoms, infections, other skin reactions and potentially serious liver problems (see "Warnings and precautions").
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor. You can 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 Buprenorfina e Naloxone G.L. Pharma

Keep this medicine out of the sight and reach of children and any other family members.
It may cause serious harm or be fatal to individuals who take this medicine
accidentally or intentionally when it has not been prescribed for them.
Do not use this medicine after the expiry date stated on the blister and on the carton after "Exp."
The expiry date refers to the last day of that month.
Do not store above 30°C.
Buprenorfina e Naloxone G.L. Pharma may be attractive to individuals who abuse
prescription medicines. Store this medicine in a secure place to protect it from theft.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how
to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Buprenorphine and Naloxone G.L. Pharma contains

• The active substances are buprenorphine and naloxone. Each 2 mg/0.5 mg sublingual tablet contains 2 mg of buprenorphine (as hydrochloride) and 0.5 mg of naloxone (as dihydrate hydrochloride). Each 4 mg/1 mg sublingual tablet contains 4 mg of buprenorphine (as hydrochloride) and 1 mg of naloxone (as dihydrate hydrochloride). Each 8 mg/2 mg sublingual tablet contains 8 mg of buprenorphine (as hydrochloride) and 2 mg of naloxone (as dihydrate hydrochloride).
• The other components are: monohydrate lactose, mannitol, maize starch, povidone (K = 29.7), monohydrate citric acid, sodium citrate, magnesium stearate, potassium acesulfame, lemon flavour (contains: flavouring preparations, maltodextrins, Acacia), lime flavour (contains: flavouring preparations, maltodextrins, Acacia).

Description of the appearance of Buprenorphine and Naloxone G.L. Pharma and contents of the pack
Buprenorphine and Naloxone G.L. Pharma 2 mg/0.5 mg
Tablets are white to off-white, round and biconvex, with a score line on one side and
a diameter of approximately 6.5 mm. The tablet can be divided into equal doses.

Buprenorphine and Naloxone G.L. Pharma 8 mg/2 mg
Tablets, white to off-white in colour, round and biconvex, with a score line on one side and a diameter of approximately 11.5 mm. The tablet can be divided into equal doses.
The tablets are packaged in blisters within cardboard cartons containing 7, 28, 49 or 56 tablets or in unit-dose blisters of 7x1, 28x1, 49x1 or 56x1 tablets.
It is possible that not all pack sizes are marketed.
Marketing Authorisation Holder and Manufacturer
G.L. Pharma GmbH, Schlossplatz 1, 8502 Lannach, Austria
Distribution Authorisation Holder:
G.L. Pharma Italy S.r.l., [email protected]
This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Germany Buprenorphin/Naloxon G.L. Pharma 2 mg/0.5 mg Sublingualtabletten
Buprenorphin/Naloxon G.L. Pharma 4 mg/1 mg Sublingualtabletten
Buprenorphin/Naloxon G.L. Pharma 8 mg/2 mg Sublingualtabletten
Denmark Buprenorphin/Naloxon G.L. Pharma 2 mg/0.5 mg sublinguale resoriblet
Buprenorphine/Naloxon G.L. Pharma 4 mg/1 mg sublinguale resoriblet
Buprenorphine/Naloxon G.L. Pharma 8 mg/2 mg sublinguale resoriblet
Finland Buprenorphine/Naloxone G.L. Pharma 2 mg/0.5 mg resoribletti
Buprenorphine/Naloxone G.L. Pharma 4 mg/1 mg resoribletti
Buprenorphine/Naloxone G.L. Pharma 8 mg/2 mg resoribletti
Sweden Buprenorphine/Naloxone G.L. Pharma 2 mg/0.5 mg resoriblett, sublingual
Buprenorphine/Naloxone G.L. Pharma 4 mg/1 mg resoriblett, sublingual
Buprenorphine/Naloxone G.L. Pharma 8 mg/2 mg resoriblett, sublingual
United Kingdom (Northern Ireland) Buprenorphine/Naloxone G.L. Pharma 2 mg/0.5 mg sublingual tablet
Buprenorphine/Naloxone G.L. Pharma 4 mg/1 mg sublingual tablet
Buprenorphine/Naloxone G.L. Pharma 8 mg/2 mg sublingual tablet
France BUPRENORPHINE/NALOXONE G.L. PHARMA 2 mg/0.5 mg, comprimé sublingual sécable
BUPRENORPHINE/NALOXONE G.L. PHARMA 4 mg/1 mg, comprimé sublingual sécable
BUPRENORPHINE/NALOXONE G.L. PHARMA 8 mg/2 mg, comprimé sublingual sécable
Italy Buprenorphine and Naloxone G.L. Pharma