ZUBSOLV 0.7 mg/0.18 mg Сублингвальная таблетка

Содержание инструкции

1. Zubsolv 0.7 mg/0.18 mg sublingual tablets, 1.4 mg/0.36 mg sublingual tablets, 2.9 mg/0.71 mg sublingual tablets, 5.7 mg/1.4 mg sublingual tablets, 8.6 mg/2.1 mg sublingual tablets, 11.4 mg/2.9 mg sublingual tablets
   1. What is Zubsolv and what it is used for
   2. How to take Zubsolv
   3. Possible side effects
   4. How to store Zubsolv
   5. Package contents and other information

Zubsolv 0.7 mg/0.18 mg sublingual tablets, 1.4 mg/0.36 mg sublingual tablets, 2.9 mg/0.71 mg sublingual tablets, 5.7 mg/1.4 mg sublingual tablets, 8.6 mg/2.1 mg sublingual tablets, 11.4 mg/2.9 mg sublingual tablets

Buprenorphine/naloxone

Read this leaflet carefully before you start to take 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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Zubsolv is and what it is used for
• 2. What you need to know before you take Zubsolv
• 3. How to take Zubsolv
• 4. Possible side effects
• 5. How to store Zubsolv
• 6. Contents of the pack and other information

1. What is Zubsolv and what it is used for

Zubsolv contains the active ingredients buprenorphine and naloxone. Zubsolv is used to treat
opioid dependence (narcotic drugs) such as heroin or morphine in people with drug dependence
who have agreed to be treated 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 Zubsolv works
The tablet contains buprenorphine, which is responsible for the treatment of opioid
(narcotic drugs) dependence. It also contains naloxone which is used to discourage the
intravenous abuse of the product.

• 2.What you need to know before you takeZubsolv

Do not take Zubsolvif you:

• are allergic to buprenorphine, naloxone or any of the other ingredients of this medicine (listed in section 6).
• suffer from severe breathing problems
• suffer from severe liver problems
• are intoxicated due to alcohol or suffer from tremors, sweating, anxiety, confusion or hallucinations caused by alcohol
• are taking naltrexone or nalmefene for the treatment of alcohol abuse or opioid dependence.

Warnings and precautions

• Improper use, abuse and diversionSerious infections with potentially fatal outcomes may occur if Zubsolv is misused, by taking it intravenously. This medicine may be a target for people who abuse prescription drugs and should be stored in a safe place to protect it from theft. Do not give this medicine to other people (see section 5). It may cause death or otherwise be dangerous for them.
• Breathing problems(see also ‘Do not take Zubsolv if above’) Some people have died from respiratory failure (inability to breathe) due to the misuse of this medicine or because they took it in combination with other central nervous system depressants, such as alcohol, benzodiazepines (tranquilizers) or other opioids.

This medicine must be used with caution in patients with asthma or respiratory
insufficiency.
This medicine can cause severe respiratory depression (reduced ability to breathe),
potentially fatal, in children and people who do not have an opioid dependence who
take it accidentally or deliberately.

• DrowsinessThis medicine can cause drowsiness, especially when taken with alcohol or other central nervous system depressants (such as tranquilizers, sedatives or hypnotics).
• DependenceThis product can cause dependence.
• Liver damageLiver damage has been reported after taking buprenorphine/naloxone, especially when the medicine is misused. 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). Periodic blood tests may be performed by the doctor to monitor the condition of your liver. Tell your doctor if you experience any liver problems before you start
  treatment with Zubsolv.
• Withdrawal symptomsThis product can cause withdrawal symptoms if you take it less than 6 hours after using a short-acting opioid (e.g., morphine, heroin) or less than 24 hours after you have used a long-acting opioid, such as methadone.

Zubsolv can also cause withdrawal symptoms if you suddenly stop taking this
medicine.

• Blood pressureThis product can cause a sudden drop in your blood pressure, causing dizziness, if you get up quickly from a lying position.
• Sleep-related breathing disorders

Zubsolv can cause sleep-related breathing disorders such as sleep apnea (pauses in breathing
during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). Symptoms
may include pauses in breathing during sleep, nighttime awakenings due to shortness of breath,
difficulty staying asleep, or excessive daytime sleepiness. If you or another person
observe these symptoms, contact your doctor. The doctor may consider a
reduction in the dose

• Children and adolescentsYou may be monitored more closely by the doctor if you are under 18 years of age. This

medicine should not be taken by people under 15 years of age.

• Diagnosis of unrelated medical conditionsThis medicine can mask the symptoms of pain that can facilitate the diagnosis of some diseases. Do not forget to inform your doctor if you are taking this medicine.

Talk to your doctor before taking Zubsolvif you:

• Suffer from depression or other conditions that are treated with antidepressants. The use of these medicines together with Zubsolv may lead to serotonin syndrome, a condition that can cause death (see “Other medicines and Zubsolv”)
• Have kidney problems
• Have recently suffered a head injury or suffer from a brain disease
• Suffer from low blood pressure, enlarged prostate gland or difficulty passing urine due to a narrowing of the urethra
• Have an underactive thyroid gland that can cause fatigue or weight gain
• Have poor functioning of the adrenal gland (e.g. Addison's disease)
• Have problems with the bile duct (e.g. gallbladder, bile duct)
• are elderly
• are debilitated

Other medicines and Zubsolv
Tell your doctor if you are taking, have recently taken or might take any other
medicines.
Some medicines can increase the side effects of Zubsolv and can sometimes cause
serious reactions. Do not take any other medicines while taking Zubsolv without first
talking to your doctor, especially:

• antidepressants such as moclobemide, tranylcypromine, citalopram, escitalopram, fluoxetine,fluvoxamine, paroxetine, sertraline, duloxetine, venlafaxine, amitriptyline, doxepin ortrimipramine. These medicines may interact with Zubsolv and symptoms such as involuntary and rhythmic muscle contractions, including the muscles that control eye movement, agitation, hallucinations, coma, excessive sweating, tremor, increased muscle contraction, fever above 38 °C may occur. Contact your doctor if you experience these symptoms.
• Naltrexone and nalmefene(medicines used to treat addiction disorders) as these may counteract the therapeutic effects of Zubsolv. They should not be taken at the same time as Zubsolv as it may cause a sudden onset of prolonged and severe withdrawal.
• Benzodiazepines(used to treat anxiety or sleep disorders) such as diazepam, temazepam, alprazolam. The concomitant use of Zubsolv with sedative medicines, such as benzodiazepines 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 other treatment options are not possible. However, if Zubsolv is prescribed together with sedative medicines, the dose and duration of concomitant treatment must be limited by the doctor. Tell your doctor all the sedative medicines you are taking and carefully follow their recommendations regarding the dose. It may be helpful to inform friends or family members to pay attention to the signs and symptoms above. Contact your doctor if these symptoms occur.
• Gabapentin or pregabalin to treat epilepsy or pain caused by nerve problems (neuropathic pain).
• Othermedicines that can make you feel sleepythat are used to treat conditions such as anxiety, insomnia, seizures/epilepsy, pain and other mental disorders. These types of medicines will reduce levels of alertness making it dangerous for you to drive vehicles and operate machinery. They can also cause central nervous system depression, which is very serious. A list of examples of these types of medicines is provided below:
• other medicines containing opioids, such as methadone, certain painkillers and cough suppressants
• some antidepressants (used to treat depression) such as isocarboxazid, phenelzine, selegiline, tranylcypromine, valproate and MAO inhibitors may increase the effects of this medicine
• Antihistamine receptor HI antagonists (used to treat allergic reactions) such as diphenhydramine and chlorphenamine
• barbiturates (used to induce sleep or sedation) such as phenobarbital, secobarbital
• tranquilizers (used to induce sleep or sedation) such as chloral hydrate
• clonidine (used to treat high blood pressure) and related medicines may extend the effects of this medicine
• antiretroviral agents (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 some antibiotics, may amplify the effects of this drug
• Some medicines can reduce the effect of Zubsolv. These include medicines used to treat epilepsy (such as carbamazepine and phenytoin) and medicines used to treat tuberculosis (rifampicin)

Zubsolv with food, drinks and alcohol
Alcohol can increase drowsiness and the risk of respiratory failure if taken with Zubsolv.

Do not take Zubsolv with alcohol.Do not ingest or consume any food or drink until
the tablet has completely dissolved.

Pregnancy and breastfeeding
The risks associated with the use of Zubsolv in pregnant women are not known. Tell your doctor if you
are
pregnant or planning a pregnancy. The doctor will decide whether treatment should be
continued with an alternative medicine.
If taken during pregnancy, especially during late pregnancy, medicines such as
Zubsolv can cause withdrawal symptoms including breathing problems in your newborn.
These may appear several days after birth.
Do not breastfeed while taking this medicine, as Zubsolv passes into breast milk.
Ask your doctor or pharmacist before taking any medicine.

Driving and using machines
Zubsolv can cause drowsiness, dizziness or cause changes in thinking. This may occur
more often in the first weeks of treatment when your dose is changed, but can happen
even if you drink alcohol or take other sedative medicines when taking Zubsolv. Do not drive, use
tools or machinery, or perform dangerous activities until you know how this
medicine affects you.

Zubsolv contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, that is
essentially ‘sodium-free’.

3. How to take Zubsolv

Take this medicine exactly as your doctor or pharmacist has told you. If you have
any doubts, ask your doctor or pharmacist.
Your treatment has been prescribed and monitored by doctors experienced in the treatment of
drug dependence.
The doctor will determine the best dose for you. During treatment, the doctor may adjust the
dose, depending on your response.

Initial treatment
The recommended starting dose for adults and adolescents over 15 years of age is:

• one Zubsolv 1.4 mg/0.36 mg tablet daily, or
• one Zubsolv 2.9 mg/0.71 tablet daily

An additional Zubsolv 1.4 mg / 0.36 mg or 2.9 mg / 0.71 mg tablet may be
administered on day 1 as needed.
Other strengths are available and your doctor will decide the optimal treatment for you. This
may involve taking a combination of different strengths, however your daily dose should not exceed 17.2 mg of buprenorphine.
There must be clear signs of withdrawal before taking your first dose of Zubsolv. A
doctor’s assessment of your readiness for treatment will guide the timing of your first
Zubsolv dose.

• Initial Zubsolv treatment during heroin dependence: If you are dependent on heroin or a short-acting opioid, your first dose of Zubsolv should be taken when withdrawal symptoms appear, but no less than 6 hours after your last opioid use
• Initial Zubsolv treatment during methadone dependence: If you have been taking methadone or a long-acting opioid, the methadone dose should ideally be reduced to less than 30 mg/day before starting Zubsolv therapy. The first dose of Zubsolv should be taken when withdrawal symptoms appear, but no less than 24 hours after the last dose of methadone

Taking Zubsolv

• Take the dose once a day or as recommended by your doctor.
• Remove the tablet as described below. Only open the blister immediately before taking the dose. Never remove the tablet from the blister in advance as the tablet is sensitive to moisture
• Place the tablets under the tongue
• Keep the tablets under the tongue until they have completely dissolved.
• Do not chew or swallow the tablets, as the medicine will not work and you may develop withdrawal symptoms.
• Do not consume any food or beverage until the tablets have completely dissolved. Although you may notice that most of the tablet dissolves within 40 seconds, it may take 5 to 10 minutes for the tablet to dissolve in the mouth.

How to remove the tablet from the blister

• 1. Do not press the tablet through the aluminum foil

• 2. Remove only one section from the blister pack by cutting along the dotted line.

• 3. Fold the pack along the dotted line.
• 4. Cut along the direction of the arrow. If the blister is damaged, discard the tablet.

Dosage adjustment and maintenance therapy
The doctor may increase the dose of Zubsolv you take as needed. If you feel that
the effect of Zubsolv is too strong or too weak, contact your doctor or pharmacist. The maximum
daily dose is 17.2 mg.
After a period of effective treatment, you may agree with your doctor to gradually reduce the dose to
a lower maintenance dose.

Stopping treatment
Do not change the treatment in any way or stop the treatment without your doctor’s consent.
Depending on your condition, the dose of Zubsolv may continue to be reduced under close
medical supervision, until it can be stopped.

If you take more Zubsolv than you should
If you or someone else takes an excessive amount of this medicine, you should go to or be
taken to a casualty department immediately for treatment, as
an overdose with Zubsolv can cause serious and potentially life-threatening breathing problems.

Symptoms of overdose may include slower and shallower breathing than normal, feeling
more sleepy than usual, reduced pupil size, low blood pressure, feeling unwell, vomiting and/or speech problems.

If you forget to take Zubsolv
Inform your doctor immediately as soon as possible if you miss a dose.

If you stop taking Zubsolv
Do not change the treatment in any way or stop the treatment without the consent of your treating
doctor. Sudden discontinuation of treatment may cause withdrawal symptoms.
If you have any questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Immediately inform your doctor or seek urgent medical attentionif you experience serious side effects, such as:

• swelling of the face, lips, tongue or throat that can cause difficulty swallowing or breathing, severe hives/rash. These may be signs of a serious allergic reaction
• drowsiness and lack of coordination, blurred vision, slurred speech, inability to think properly or clearly, or breathing that becomes much slower than normal.
• severe fatigue, 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 side effects (may affect more than 1 in 10 people):

• insomnia (inability to sleep)
• headache
• constipation, nausea
• excessive sweating
• drug withdrawal syndrome

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

• flu-like symptoms, infection, sore throat and pain when swallowing, runny nose
• anxiety, depression, decreased sexual desire, nervousness, abnormal thinking
• migraine, dizziness, fainting, increased muscle tension, tingling, drowsiness
• increased tearing (eye hydration) or other tearing disorder, blurred vision
• increased blood pressure, hot flashes
• increased cough
• abdominal pain, stomach problems or other stomach disorders, diarrhea, flatulence, vomiting
• skin rash, itching, hives
• back pain, joint pain, muscle pain, leg cramps (muscle spasm)
• urine abnormality
• difficulty achieving or maintaining an erection
• weakness, chest pain, chills, fever, general feeling of discomfort, pain, swelling (hands and feet)
• abnormal liver function, weight loss
• accidental injuries caused by loss of vigilance or coordination

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

• abnormal results in blood tests, swollen adrenal glands (lymph nodes)
• abnormal dreams, agitation, loss of interest, depersonalization (not feeling like yourself), drug dependence, exaggerated feeling of well-being, feelings of hostility
• amnesia (memory disorders), seizures (convulsions), speech disorders, tremors
• eye inflammation or infection, decreased pupil size
• fast or slow heartbeat, myocardial infarction (heart attack), palpitations, feeling of tightness in the chest
• low blood pressure
• asthma, shortness of breath, yawning
• pain and sores in the mouth, discoloration of the tongue
• acne, hair loss, dry or flaky skin, skin nodule
• 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
• stroke
• excessive muscle activity
• loss of appetite

Not known(frequency cannot be estimated based on available data):

• slow or difficult breathing
• liver damage with or without jaundice
• Dental caries
• hallucinations
• swelling of the face and throat or life-threatening allergic reactions
• low blood pressure when moving from a sitting or lying position to an upright position
• sudden withdrawal syndrome caused by taking the product too soon after using illegal opioids,
• drug withdrawal syndrome in newborns

Improper use of this medicine, through injection, can cause withdrawal symptoms,
infections, other skin reactions and potentially serious liver problems (see section 2,
Warnings and precautions).

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, tell
your doctor or pharmacist. You can also report side effects directly through the
national reporting system at the national reporting system address
in Appendix V. By reporting side effects, you can help provide more
information on the safety of this medicine.

5. How to store Zubsolv

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

It can cause serious harm and be fatal to people who may take this
medicine accidentally or intentionally when it has not been prescribed to them.
Do not use this medicine after the expiry date which is stated on the box and blister after
Exp. The expiry date refers to the last day of that month.
Store at a temperature below 25°C.
Store in the original package, to protect the medicine from moisture.
Zubsolv may be a target for people who abuse prescription drugs.
Keep this medicine in a safe place, to protect it from theft.
Store the blister securely.
Do not open the blister early.
Do not take this medicine in front of children.
An emergency unit must be contacted immediately in case of accidental ingestion or
suspicion.
Do not dispose of any medicine in the wastewater and 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 Zubsolv contains
The active ingredients are buprenorphine and naloxone.
Each sublingual tablet of 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 of 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 of 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 of 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 of 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 of 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 excipients are mannitol, citric acid, sodium citrate, microcrystalline cellulose, sodium
croscarmellose, sucralose, levomenthol, colloidal silicon dioxide and sodium stearyl fumarate (see section 2”
Zubsolv contains sodium”).

Description of the appearance of Zubsolv and contents of the pack
Zubsolv is available in six different dosages, differing in shape and embossed mark:

Concentration of the Zubsolv tablet (buprenorphine/naloxone)	Description of the Zubsolv tablet	Embossed mark on the Zubsolv tablet	Appearance
A 0.7 mg/0.18 mg	tablet from white to whitish, oval, length 6.8 mm and	“.7” on one side
1.4 mg/0.36 mg	tablet from white to whitish, triangular, base 7.2 mm and height 6.9	“1.4” on one side

2.9 mg/0.71 mg	tablet from white to whitish, D-shaped, height 7.3 mm and	“2.9” on one side
5.7 mg / 1.4 mg	tablet from white to whitish, round, diameter 7 mm	“5.7” on one side	o
8.6 mg / 2.1 mg	Tablet from white to whitish, diamond-shaped, length 9.5 mm and width	“8.6” on one side	a c
11.4 mg/2.9 mg	Tablet from white to whitish, capsule-shaped, length 10.3 mm and width	“11.4” on one side r	m

Zubsolv is available in blisters of 7, 28, or 30 tablets, sublingual tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona s/n
Edifici Est, 6a planta
08039 Barcelona
Spain

Manufacturer
Orexo AB
Virdings allé 32 A
Uppsala 754 50
Sweden
More detailed information on this medicine is available on the website of the European
Medicines Agency, http://www.ema.europa.eu.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND MOTIVATIONS FOR THE
VARIATION OF THE TERMS OF THE MARKETING
AUTHORISATIONS
Scientific conclusions
In light of the assessment by the Pharmacovigilance and Risk Assessment Committee (PRAC) of the
Periodic Safety Update Reports (PSUR) for buprenorphine/naloxone, the PRAC’s scientific conclusions are as follows:
In light of the available data on the interaction between opioids and gabapentinoids from the
literature, in light of a plausible mechanism of action and taking into account the
existing warnings reported in the product information regarding other opioid-containing medicines, the PRAC considers that a causal relationship between buprenorphine/naloxone and
an interaction with gabapentinoids is at least a reasonable possibility. The PRAC has
concluded that the product information regarding medicines containing
buprenorphine/naloxone should be amended accordingly.
In light of the available data on dental caries from the literature and spontaneous reports including, in some cases, a close temporal relationship and in light of a
plausible mechanism of action, the PRAC considers that a causal relationship between
buprenorphine/naloxone and dental caries is at least a reasonable possibility. The PRAC has
concluded that the product information regarding medicines containing
buprenorphine/naloxone should be amended accordingly.
In light of the available data on paediatric intoxication and fatal outcomes from the
literature and spontaneous reports and in light of a plausible mechanism of action,
the PRAC considers that a causal relationship between buprenorphine/naloxone and paediatric intoxication
and fatal outcomes is at least a reasonable possibility. The PRAC concluded that the
consequence.
Having examined the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the related
overall conclusions and with the rationale for the recommendation.

Motivations for the variation of the terms of the marketing
authorisations
Based on the scientific conclusions on buprenorphine/naloxone, the CHMP considers that the
benefit/risk ratio of medicines containing buprenorphine/naloxone remains unchanged
subject to the proposed changes to the product information.
The CHMP recommends the variation of the terms of the marketing
authorisations.