Prospect: information for the patient

Zubsolv 0.7 mg / 0.18 mg sublingual tablets

Zubsolv 1.4 mg / 0.36 mg sublingual tablets

Zubsolv 2.9 mg / 0.71 mg sublingual tablets

Zubsolv 5.7 mg / 1.4 mg sublingual tablets

Zubsolv 8.6 mg / 2.1 mg sublingual tablets

Zubsolv 11.4 mg / 2.9 mg sublingual tablets

buprenorphine/naloxone

Read this prospect carefully before starting to take this medication, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribed only to you, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they do not appear in this prospect. See section 4.

1. Possible adverse effects
2. Storage of Zubsolv

1. Contents of the package and additional information

Zubsolv contains the active ingredients buprenorphine and naloxone. Zubsolv is used to treat opioid dependence (narcotics), such as heroin or morphine, in individuals with addiction who have accepted treatment for their addiction. Zubsolv is used in adults and adolescents over 15 years of age, who are also receiving medical, social, and psychological support.

How does Zubsolv work?

The tablet contains buprenorphine, which is responsible for treating opioid dependence (narcotics). It also contains naloxone, which is used to make misuse of the medication through intravenous use more difficult.

Do not take Zubsolv:

• if you are allergic to buprenorphine, naloxone, or any of the other ingredients in this medication (listed in section 6)

• if you havesevere respiratory problems

• if you havesevere liver problems

• if you have alcohol intoxication or experience 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

• Abuse, misuse, and diversion

Severe infections with potentially fatal outcomes may occur if Zubsolv is misused by injecting it intravenously.

This medication may be a target for individuals who abuse prescription medications, and it should be stored in a secure location to protect it from theft (see section 5). Do not give this medication to anyone else. It may cause them death or other harm.

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

Some individuals have died from respiratory failure (inability to breathe) due to misuse of this medication or taking 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 may cause severe respiratory depression (difficulty breathing) and potentially fatal outcomes in children and individuals not dependent on opioids if ingested accidentally or intentionally.

• Drowsiness

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

• Dependence

This medication may 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 chronic hepatitis C infection, alcohol abuse, anorexia, or use of other medications that can damage the liver (see section 4). Your doctor may perform regular blood tests to monitor your liver function.

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

• Withdrawal symptoms

This medication may cause withdrawal symptoms if taken 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 may also cause withdrawal symptoms if stopped abruptly.

• Blood pressure

This medication may cause a sudden drop in blood pressure, which may 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.

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

• Diagnosis of unrelated medical conditions

This medication may mask pain symptoms that could aid in the diagnosis of certain diseases. Do not forget to inform your doctor if you are taking this medication.

Consult your doctor before starting Zubsolvif:

• you have depression or other conditions treated with antidepressants.

The use of these medications with Zubsolv may cause serotonin syndrome, a potentially fatal condition (see “Taking Zubsolv with other medications”)

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

• you have low thyroid activity, which may cause fatigue or weight gain
• your adrenal gland does not function properly (e.g., Addison's disease)
• you have bile duct problems (e.g., gallbladder, common bile duct)
• you are an elderly person

• you are debilitated

Taking Zubsolv with other medications

Inform your doctor if you are using, have recently used, or may need to use any other medication.

Some medications may increase the adverse effects of Zubsolv and, in some cases, may cause severe reactions. Do not take other medications while taking Zubsolv without first speaking with your doctor, especially:

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

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

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

• Other medications that may cause drowsinessused to treat diseasessuch as anxiety, insomnia, seizures, or mental disorders. This type of medication reduces your alertness, making it dangerous for you to drive and use machines. They may also cause severe central nervous system depression, which is very serious. The following is a list of examples of this type of medication:

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

• some 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 may increase drowsiness and 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 unknown. Inform 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 towards the end of pregnancy, medications like Zubsolv may cause withdrawal symptoms, including respiratory problems, in your newborn baby. This may occur 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 operating machines

Zubsolv may cause drowsiness, dizziness, or altered thinking. This may occur more frequently in the first weeks of treatment, when the dose is being adjusted, but it may also occur if you drink alcohol or take other sedatives 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; it is essentially “sodium-free”.

Your treatment is prescribed and monitored by experienced doctors in the treatment of addiction.

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

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist.

Start of treatment

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

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

• one Zubsolv tablet 2.9 mg / 0.71 mg per day

An additional Zubsolv tablet 1.4 mg / 0.36 mg or 2.9 mg / 0.71 mg may be taken on day 1, as needed.

Other concentrations are available for use by your doctor, who will decide the best treatment 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 should be evident before taking your first dose of Zubsolv. Your doctor's evaluation of whether you are ready for treatment will guide the timing of your first dose of Zubsolv.

• Start of Zubsolv treatment if dependent on heroin:

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

• Start of Zubsolv treatment if dependent on methadone:

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

Take Zubsolv

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

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 believe 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.

Discontinuation of treatment

Do not change the treatment in any way or discontinue treatment without the authorization of the doctor treating you.

Depending on your situation, the Zubsolv dose may continue to be reduced under close medical supervision, until withdrawal.

If you take more Zubsolv than you should

If you or someone else takes an excessive amount of this medication, seek immediate medical attention or be transported to an emergency center or hospital for treatment, as a Zubsolv overdose can cause severe and potentially fatal respiratory problems.

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

If you forget to take Zubsolv

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

If you interrupt Zubsolv treatment

Do not change the treatment in any way or discontinue treatment without the authorization of the doctor treating you.Stopping treatment abruptly may cause withdrawal symptoms.

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

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

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

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

• drowsiness and lack of coordination, blurred vision, difficulty speaking, inability tothink clearly or well, or abnormally slow breathing for you

• intense fatigue, pruritus with yellowish discoloration of the skin or eyes. These may be symptoms of liver damage

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

Other side effects

Frequent side effects(may affect more than 1 in 10 people):

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

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

• symptoms similar to the flu, infection, sore throat, and difficulty swallowing, nasal discharge

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

Rare side effects(may affect up to 1 in 100 people):

• abnormal blood test results, inflamed lymph nodes (lymphadenopathy)
• abnormal dreams, agitation, loss of interest, depersonalization (not feeling like oneself), dependence on medication, exaggerated sense of well-being, hostile feelings

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

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

• heatstroke
• excessive muscle activity

• loss of appetite

Unknown frequency(cannot be estimated from available data):

• slow breathing or difficulty breathing
• liver damage with or without jaundice
• hallucinations
• swelling of the face and throat or potentially life-threatening allergic reactions

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

The misuse of this medication by injection may cause symptoms of withdrawal, infections, other skin reactions, and potentially serious liver problems (see section 2, Warnings and precautions).

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Usewww.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

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

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

Zubsolv may be a target for individuals who misuse prescription medications. Keep this medication in a secure location to prevent theft.

Store the blister pack safely.

Never open the blister pack prematurely.

Do not take this medication in front of children.

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

Medications should not be disposed of through drains or trash. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

Composition of Zubsolv

The active ingredients are buprenorphine and naloxone.

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

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

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

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

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

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

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

Appearance of Zubsolv and packaging contents

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

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

Only some doses and packaging sizes may be commercially available.

Marketing Authorization Holder

Orexo AB

Box 303

751 05 Uppsala

Sweden

Responsible for manufacturing

Orexo AB

Virdings allé 32 A Uppsala 751 05

Sweden

Last review date of this leaflet:

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu/.