ZUBSOLV 11.4 mg/2.9 mg SUBLINGUAL TABLETS

2. What you need to know before you take Zubsolv

Do not take Zubsolv :

• if you are allergic 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 have 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

• Misuse, abuse, and diversion

Severe infections with potentially fatal outcomes may occur if Zubsolv is misused, administered intravenously.

This medication may be a target for people who abuse prescription medications, and it should be kept in a safe place to protect it from theft (see section 5). Do not give this medication to anyone else. It may cause them to die or suffer other harm.

• Respiratory problems(see also “Do not take Zubsolv” above)

Some people have died from respiratory failure (inability to breathe) because they have misused this medication or taken it in combination with other central nervous system depressants, such as alcohol, benzodiazepines (tranquilizers), or other opioids.

The medication should be used with caution in patients with pre-existing respiratory problems

This medication can cause severe, potentially life-threatening respiratory depression in children and in people who are not dependent on opioids if they ingest it accidentally or intentionally.

• Somnolence

This medication can cause somnolence, especially when taken with alcohol or other central nervous system depressants (such as tranquilizers, sedatives, or hypnotics).

• Dependence

This medication can cause dependence.

• Liver damage

Liver damage has been reported after taking buprenorphine/naloxone, especially when the medication is misused. This may also be due to viral infections (chronic hepatitis C), alcohol abuse, anorexia, or the use of other medications that can damage the liver (see section 4). Your doctor may perform blood tests regularly to monitor your liver function.

Tell your doctor if you have liver problems before starting treatment with Zubsolv.

• Withdrawal symptoms

This medication can cause withdrawal symptoms if you take it less than six hours after consuming a short-acting opioid (e.g., morphine, heroin) or less than 24 hours after consuming a long-acting opioid, such as methadone.

Zubsolv can also cause withdrawal symptoms if you stop taking it abruptly.

• Blood pressure

This medication can cause a sudden drop in your blood pressure, which can cause dizziness if you stand up too quickly when sitting or lying down.

• Children and adolescents

You may be under closer supervision by your doctor if you are under 18 years of age.

People under 15 years of age should not take this medication.

• Diagnosis of unrelated medical conditions

This medication can mask symptoms of pain that could help in the diagnosis of some diseases. Do not forget to tell your doctor if you are taking this medication.

Consult your doctor before starting treatment with Zubsolvif:

• you have depression or other diseases that are treated with antidepressants.

The use of these medications with Zubsolv can cause serotonin syndrome, a potentially life-threatening disease (see “Taking Zubsolv with other medications”)

• you have kidney problems
• you have recently suffered a head injury or a brain disease
• you have low blood pressure, enlarged prostate, or difficulty urinating due to a narrowing of the urethra

• you have little activity of the thyroid gland, which can cause fatigue or weight gain
• your adrenal gland does not work well (e.g., Addison's disease)
• you have problems in the bile ducts (e.g., gallbladder, common bile duct)
• you are an elderly person

• you are weakened

Taking Zubsolv with other medications

Tell your doctor if you are using, have recently used, or might use any other medication.

Some medications can increase the adverse effects of Zubsolv and, in some cases, can cause very serious reactions. Do not take other medications while taking Zubsolv without talking to your doctor first, especially:

• antidepressants such as moclobemide, tranylcypromine, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine, venlafaxine, amitriptyline, doxepin, or trimipramine. These medications can interact with Zubsolv and you may experience symptoms such as involuntary muscle contractions, including the muscles that control eye movement, agitation, hallucinations, coma, excessive sweating, tremors, exaggerated reflexes, increased muscle tension, body temperature above 38 °C. Contact your doctor if you experience these symptoms.

• Naltrexone and nalmefene(medications used to treat addictive disorders) as they may prevent the therapeutic effects of Zubsolv. They should not be taken at the same time as treatment with Zubsolv, as you may experience a sudden onset of intense and prolonged withdrawal.

• Benzodiazepines(used to treat anxiety or sleep disorders) such as diazepam, temazepam, alprazolam. Your doctor will indicate the correct dose for you. Taking incorrect doses of benzodiazepines can cause death from respiratory failure (inability to breathe).

• Other medications that can make you feel drowsyused to treat diseases such as anxiety, insomnia, seizures or epileptic fits, pain, and other mental disorders. This type of medication reduces your alertness, making it dangerous for you to drive and use machines. They can also cause central nervous system depression, which is very serious. The following is a list of examples of this type of medication:

• other medications that contain opioids, such as methadone, certain painkillers, and cough suppressants
• certain antidepressants (used to treat depression) such as isocarboxazid, phenelzine, selegiline, tranylcypromine, valproate, and monoamine oxidase inhibitors (MAOIs) as they may increase the effects of this medication

• antihistamines that produce sedation (used to treat allergic reactions) such as diphenhydramine and chlorphenamine
• barbiturates (used to induce sleep or sedation) such as phenobarbital, secobarbital
• sedatives (used to induce sleep or sedation) such as chloral hydrate

• clonidine (used to treat high blood pressure) and related medications as they may prolong the effects of this medication

• antiretrovirals (used to treat HIV) such as ritonavir, nelfinavir, indinavir, as they may increase the effects of this medication

• certain antifungal medications (used to treat fungal infections) such as ketoconazole, itraconazole, and certain antibiotics, as they may prolong the effects of this medication

• some medications may decrease the effect of Zubsolv. These include medications used to treat epilepsy (such as carbamazepine and phenytoin) and medications used to treat tuberculosis (rifampicin)

Using Zubsolv with food, drinks, and alcohol

Alcohol can increase somnolence and may increase the risk of respiratory failure if taken with Zubsolv. Do not take Zubsolv with alcohol.Do not swallow or ingest food or drinks until the tablet has completely dissolved.

Pregnancy and breastfeeding

The risks of using Zubsolv in pregnant women are not known. Tell your doctor if you are pregnant or plan to become pregnant. Your doctor will decide whether you should continue treatment with an alternative medication.

When taken during pregnancy, especially at the end of pregnancy, medications like Zubsolv can cause withdrawal symptoms, including respiratory problems, in your newborn baby. This may appear several days after birth.

Do not breastfeed while taking this medication, as Zubsolv passes into breast milk.

Ask your doctor or pharmacist before taking any medication.

Driving and using machines

Zubsolv can cause somnolence, dizziness, or altered thinking. This can occur more frequently in the first weeks of treatment, when the dose is being adjusted, but it can also occur if you drink alcohol or take other sedative medications at the same time as taking Zubsolv. Do not drive, use tools or machines, or engage in hazardous activities until you know how this medication affects you.

Zubsolv contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per dose; this is, essentially “sodium-free”.

3. How to take Zubsolv

Your treatment is prescribed and supervised by doctors with experience in the treatment of drug addiction.

Your doctor will determine the best dose for you. During treatment, the doctor may adjust the dose based on your response.

Follow the administration instructions of this medication exactly as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist.

Starting treatment

The recommended starting dose in adults and adolescents over 15 years of age is:

• one Zubsolv 1.4 mg / 0.36 mg tablet per day, or

• one Zubsolv 2.9 mg / 0.71 mg tablet per day

An additional Zubsolv 1.4 mg / 0.36 mg or 2.9 mg / 0.71 mg tablet may be administered on day 1, depending on your needs.

Other concentrations are available for use by your doctor, who will decide what the best treatment is for you. This may involve taking a combination of different concentrations, but your daily dose should not exceed 17.2 mg of buprenorphine.

Clear signs of withdrawal must be evident before taking your first dose of Zubsolv. Your doctor's assessment of whether you are ready for treatment will guide the timing of your first dose of Zubsolv.

• Starting treatment with Zubsolv if you are dependent on heroin:

If you are dependent on heroin or a short-acting opioid, your first dose of Zubsolv should be taken when withdrawal symptoms appear, but not less than 6 hours after your last opioid use

• Starting treatment with Zubsolv if you are dependent on methadone:

If you have been taking methadone or a long-acting opioid, it is recommended to reduce the methadone dose to below 30 mg/day before starting treatment with Zubsolv. The first dose of Zubsolv should be taken when withdrawal symptoms appear, but not less than 24 hours after your last methadone use

Taking Zubsolv

• Take the dose once a day or as your doctor has indicated.

• Remove the tablet as described below. Open the blister pack immediately before taking the dose. Do not open it in advance, as the tablet is sensitive to moisture.

• Place the tablets under your tongue.

• Keep the tablets under your tongue until they have completely dissolved.

• Do not chew or swallow the tablets, as the medication will not work and withdrawal symptoms may appear.

• Do not consume food or drinks until the tablet has completely dissolved. Although you may notice that most of the tablet disintegrates in 40 seconds, the tablet may take between 5 and 10 minutes to completely disappear from your mouth.

How to remove the tablet from the blister pack

Dose adjustment and maintenance treatment

Your doctor may increase the dose of Zubsolv you are taking, based on your needs. If you think the effect of Zubsolv is too strong or too weak, talk to your doctor or pharmacist. The maximum daily dose is 17.2 mg.

After a successful treatment period, you may agree with your doctor to gradually reduce the dose to a lower maintenance dose.

Stopping treatment

Do not change your treatment in any way or stop treatment without the authorization of the doctor who is treating you.

Depending on your situation, the dose of Zubsolv may continue to be reduced under close medical supervision until it is discontinued.

If you take more Zubsolv than you should

If you or someone else takes an excessive amount of this medication, you should go or be taken immediately to an emergency center or hospital for treatment, as an overdose of Zubsolv can cause serious, potentially life-threatening respiratory problems.

Symptoms of overdose may include slower and weaker breathing than normal, more somnolence than usual, decreased pupil size, low blood pressure, nausea, vomiting, and/or difficulty speaking.

If you forget to take Zubsolv

Tell your doctor as soon as possible if you forget to take a dose.

If you stop treatment with Zubsolv

Do not change your treatment in any way or stop it without the authorization of the doctor who is treating you. Stopping treatment suddenly can cause withdrawal symptoms.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Tell your doctor immediately or seek urgent medical attentionif you experience severe adverse effects, such as:

• swelling of the face, lips, tongue, or throat, which may cause difficulty swallowing or breathing, urticaria/severe skin rash. These could be signs of a life-threatening allergic reaction

• drowsiness and lack of coordination, blurred vision, difficulty speaking, inability to think clearly, or breathing much slower than normal for you

• severe fatigue, itching with yellowing of the skin or eyes. These may be symptoms of liver damage

• seeing or hearing things that do not exist (hallucinations)

Other Adverse Effects

Very Common Adverse Effects(may affect more than 1 in 10 people):

• insomnia (difficulty sleeping)
• headache
• constipation, nausea
• excessive sweating
• withdrawal syndrome

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

• flu-like symptoms, infection, sore throat, and difficulty swallowing, nasal discharge

• anxiety, depression, decreased sexual desire, nervousness, abnormal thoughts
• migraines, dizziness, fainting, increased muscle tension, tingling, drowsiness
• increased tear production (tearful eyes) or other lacrimal disorders
• increased blood pressure, flushing
• increased coughing
• abdominal pain, stomach pain, or other stomach discomfort, diarrhea, flatulence, vomiting
• skin rash, itching, urticaria
• back pain, joint pain, muscle pain, leg cramps (muscle spasms)
• urinary disorders
• difficulty achieving or maintaining an erection
• weakness, chest pain, chills, fever, general feeling of discomfort, pain, swelling (hands and feet)
• altered liver function, weight loss
• accidental injuries caused by loss of alertness or coordination

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

• abnormal blood tests, inflamed glands (lymph nodes)
• abnormal dreams, agitation, loss of interest, depersonalization (feeling not like oneself), drug dependence, exaggerated sense of well-being, feelings of hostility

• amnesia (memory disorders), convulsions (seizures), speech disorders, tremors
• eye inflammation or infection, small pupil
• rapid or slow heartbeat, myocardial infarction (heart attack), palpitations, chest tightness

• low blood pressure
• asthma, shortness of breath, yawning
• pain and sores in the mouth, tongue discoloration
• acne, hair loss, dry or flaky skin, skin nodules
• joint inflammation
• protein in the urine, urinary tract infection, difficulty urinating, painful or difficult urination, blood in the urine, kidney stones
• menstrual or vaginal problems, abnormal ejaculation
• sensitivity to heat or cold

• heat stroke
• excessive muscle activity

• loss of appetite

Frequency Not Known(cannot be estimated from available data):

• slow or difficult breathing
• liver damage with or without jaundice
• hallucinations
• swelling of the face and throat or potentially life-threatening allergic reactions, decreased blood pressure when changing position from sitting or lying down to standing

• sudden withdrawal syndrome, caused by taking the medication too soon after illicit opioid use
• withdrawal syndrome in newborn babies

Misuse of this medication by injection can cause withdrawal symptoms, infections, other skin reactions, and potentially serious liver problems (see section 2, Warnings and Precautions).

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the Spanish Medicines Agency's website: http://www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Zubsolv

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the box and blister pack after CAD. The expiration date is the last day of the month indicated.

Store in the original package below 25 °C to protect it from moisture.

Zubsolv may be a target for people who misuse prescription medications. Keep this medication in a safe place to prevent theft.

Store the blister pack safely.

Never open the blister pack before its time.

Never take this medication in front of children.

In case of accidental ingestion or suspected ingestion, contact an emergency unit immediately.

Medicines should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of packaging and medications that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Zubsolv Composition

The active ingredients are buprenorphine and naloxone.

Each 0.7 mg / 0.18 mg sublingual tablet contains 0.7 mg of buprenorphine (as hydrochloride) and 0.18 mg of naloxone (as hydrochloride dihydrate).

Each 1.4 mg / 0.36 mg sublingual tablet contains 1.4 mg of buprenorphine (as hydrochloride) and 0.36 mg of naloxone (as hydrochloride dihydrate).

Each 2.9 mg / 0.71 mg sublingual tablet contains 2.9 mg of buprenorphine (as hydrochloride) and 0.71 mg of naloxone (as hydrochloride dihydrate).

Each 5.7 mg / 1.4 mg sublingual tablet contains 5.7 mg of buprenorphine (as hydrochloride) and 1.4 mg of naloxone (as hydrochloride dihydrate).

Each 8.6 mg / 2.1 mg sublingual tablet contains 8.6 mg of buprenorphine (as hydrochloride) and 2.1 mg of naloxone (as hydrochloride dihydrate).

Each 11.4 mg / 2.9 mg sublingual tablet contains 11.4 mg of buprenorphine (as hydrochloride) and 2.9 mg of naloxone (as hydrochloride dihydrate).

The other ingredients are mannitol, anhydrous citric acid, sodium citrate, microcrystalline cellulose, sodium croscarmellose, sucralose, levomenthol, anhydrous colloidal silica, and sodium stearyl fumarate.

Zubsolv Appearance and Package Contents

Zubsolv sublingual tablets are available in six different doses, differentiated by shape and engraved inscription:

All tablets will be available in packs of 7, 28, and 30 tablets, in aluminum blisters.

Only some doses and package sizes may be marketed.

Marketing Authorization Holder

Orexo AB

Box 303

751 05 Uppsala

Sweden

Manufacturer

Orexo AB

Virdings allé 32 A Uppsala 751 05

Sweden

Date of Last Revision of this Leaflet:

Detailed information on this medicine is available on the European Medicines Agency's website: http://www.ema.europa.eu/.