Zubsolv - patient leaflet, side effects, dosage

Patient leaflet - Zubsolv

B. PACKAGE LEAFLET

Package leaflet: 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 all of this leaflet carefully before you start taking this medicine because it contains important information for you.

– Keep this leaflet. You may need to read it again.
– If you have any further questions, ask your doctor or pharmacist.
– This medicine has been prescribed for you only. Do not pass it on to others. It may harm

them, even if their signs of illness are the same as yours.

– If you get any side effects, talk to your doctor or pharmacist. This includes any possible

side effects not listed in this leaflet. See section 4.

What is in 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 Zubsolv is and what it is used for

Zubsolv contains the active substances buprenorphine and naloxone. Zubsolv 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. 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) dependence. It also contains naloxone which is used to deter intravenous abuse of the product.

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)
- have serious breathing problems
– have serious liver problems
– are intoxicated due to alcohol or have trembling, sweating, anxiety, confusion, or hallucinations caused by alcohol
– are taking naltrexone or nalmefene for the treatment of alcohol or opioid dependence

Warnings and precautions

Misuse, abuse and diversion

Serious cases of infections with potential fatal outcome may occur if Zubsolv is misused, by taking it intravenously.

This medicine can be a target for people who abuse prescription medicines, and should be kept in a safe place to protect it from theft. Do not give this medicine to anyone else. It can cause death or otherwise harm them.

Breathing problems (see also ‘Do not take Zubsolv’ above )

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

The product should be used with care in patients with pre-existing breathing problems

This medicine may cause severe, possibly fatal, respiratory depression (reduced ability to breathe) in children and non-opioid dependent people.

Drowsiness

This medicine can cause drowsiness, particularly when taken together with alcohol or other central nervous system depressants (such as tranquilisers, sedatives or hypnotics).

Dependence

This product can cause dependence.

Liver damage

Liver damage has been reported after taking buprenorphine/naloxone, 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 that can harm your liver. Regular blood tests may be conducted by your doctor to monitor the condition of your liver. Tell your doctor if you have any liver problems before you start treatment with Zubsolv.

Withdrawal symptoms

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

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

Blood pressure

This product may cause your blood pressure to drop suddenly, causing you to feel dizzy if you get up too quickly from sitting or lying down.

Sleep-related breathing disorders

Zubsolv 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.

Children and adolescents

You may be more closely monitored by your doctor if you are below the age of 18. This medicine should not be taken by those under 15 years of age.

Diagnosis of unrelated medical conditions

This medicine may mask pain symptoms that could assist in the diagnosis of some diseases. Do not forget to advise your doctor if you take this medicine.

Talk to your doctor before taking Zubsolv if you:

have a depression or other conditions that are treated with antidepressants.

The use of these medicines together with Zubsolv can lead to serotonin syndrome, a potentially life-threatening condition (see “Other medicines and Zubsolv”)

have kidney problems
have recently suffered a head injury or brain disease
have low blood pressure, enlarged prostate gland or difficulties passing water because of narrowing of the urethra
have under-active thyroid gland which can cause tiredness or weight gain
have poor adrenal gland function (e.g. Addison’s disease)
have problems with the biliary tract (e.g. gall bladder, 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 may increase the side effects of Zubsolv and may sometimes cause very serious reactions. Do not take any other medicines whilst taking Zubsolv without first talking to your doctor, especially:

anti-depressants such as moclobemide, tranylcypromine, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine, venlafaxine, amitriptyline, doxepine, or trimipramine. These medicines may interact with Zubsolv 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.
Naltrexone and nalmefene (drugs used to treat addictive disorders) as they may prevent the therapeutic effects of Zubsolv. They must not be taken at the same time as Zubsolv treatment because you may experience a sudden onset of prolonged and intense withdrawal.
Benzodiazepines (used to treat anxiety or sleep disorders) such as diazepam, temazepam, alprazolam. Your doctor will prescribe the correct dose for you. Taking the wrong dose of benzodiazepines may cause death due to respiratory failure (inability to breathe).
Other medicines that may make you feel sleepy which are used to treat illnesses such as anxiety, sleeplessness, convulsions/seizures, pain and other mental disorders. These types of medicines will reduce your alertness levels making it dangerous for you to drive and use machines. They may also cause central nervous system depression, which is very serious. Below is a list of examples of these types of medicines:
– other opioid containing medicines such as methadone, certain pain killers and cough suppressants
– some anti-depressants (used to treat depression) such as isocarboxazid, phenelzine, selegiline, tranylcypromine, valproate and monoamine oxidase inhibitors (MAOIs) may increase the effects of this medicine
– sedative Hi receptor antagonists (used to treat allergic reactions) such as diphenhydramine and chlorphenamine
– barbiturates (used to cause sleep or sedation) such as phenobarbital, secobarbital
– tranquilisers (used to cause sleep or sedation) such as chloral hydrate
– clonidine (used to treat high blood pressure) and related medicines may extend the effects of this medicine

anti-retrovirals (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 extend the effects of this medicine
some medicines may decrease 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, drink and alcohol

Alcohol may increase drowsiness and may increase the risk of respiratory failure if taken with Zubsolv. Do not take Zubsolv together with alcohol. Do not swallow or consume food or any drink until the tablet is completely dissolved.

Pregnancy and breast-feeding

The risks of using Zubsolv in pregnant women are not known. Tell your doctor if you are pregnant or intend to become pregnant. Your doctor will decide if your treatment should be continued with an alternative medicine.

When taken during pregnancy, particularly late pregnancy, medicines like Zubsolv may cause drug withdrawal symptoms including problems with breathing in your newborn baby. This may appear several days after birth.

Do not breast-feed whilst taking this medicine, since Zubsolv passes into breast milk. Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Zubsolv may cause drowsiness. This may happen more often in the first few weeks of treatment when your dose is being changed, but can also happen if you drink alcohol or take other sedative medicines when you take Zubsolv. Do not drive, use any tools or machines, or perform dangerous activities until you know how this medicine affects you.

3. How to take Zubsolv

Your treatment is prescribed and monitored by doctors who are experienced in the treatment of drug dependence.

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

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

Starting treatment

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

– one tablet of Zubsolv 1.4 mg / 0.36 mg each day, or
– one tablet of Zubsolv 2.9 mg / 0.71 mg each day

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

There are other strengths that are available to be used by your doctor who will decide what is the best treatment for you. This may involve taking a combination of different strengths, but your daily dose should not exceed 17.2mg of buprenorphine.

Clear signs of withdrawal should be evident 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.

Starting treatment of Zubsolv whilst dependent on heroin:

If you are dependent upon 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 you last used opioids

Starting treatment of Zubsolv whilst dependent on methadone:

If you have been taking methadone or a long acting opioid, the dose of methadone should ideally be reduced to below 30 mg/day before beginning Zubsolv therapy. The first dose of Zubsolv should be taken when signs of withdrawal appear, but not less than 24 hours after you last used methadone

Taking Zubsolv

Take the dose once a day or as advised by your doctor.
Remove the tablet as described below. Only open the blister immediately before taking the

dose. Never open in advance as the tablet is sensitive to moisture

Place the tablets under the tongue
Keep the tablets in place under the tongue until they have completely dissolved
Do not chew or swallow the tablets, as the medicine will not work and you may get

withdrawal symptoms

Do not consume any food or drink until the tablets have completely dissolved. Whilst you may notice that most of the table disintegrates within 40 seconds, it may take 5 to 10 minutes for the entire table to disappear from your mouth

How to remove the tablet from the blister

1. Do not push the tablet through the foil.
2. Remove just one section from the blister pack, tearing it along the perforated line.
3. Fold the packet along the dotted line.
4. Tear following the direction of the arrow. If the blister is damaged, discard the tablet.

Dosage adjustment and maintenance therapy

Your doctor may increase the dose of Zubsolv you take according to your needs. If you feel that 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 period of successful treatment, you may agree with your doctor to reduce the dose gradually to a lower maintenance dose.

Stopping treatment

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

Depending on your condition, the dose of Zubsolv may continue to be reduced under careful medical supervision, until eventually it may be stopped.

If you take more Zubsolv than you should

If you or someone else takes too much of this medicine, you must go or be taken immediately to an emergency centre or hospital for treatment as overdose with Zubsolv may cause serious and life-threatening breathing problems.

Symptoms of overdose may include breathing more slowly and weakly than normal, feeling more sleepy than normal, reduction in the size of the pupils, low blood pressure, feeling sick, vomit and/or slurred speech.

If you forget to take Zubsolv

Tell your doctor as soon as possible if you miss a dose.

If you stop taking Zubsolv

Do not change the treatment in any way or stop treatment without the agreement of the doctor who is treating you. Stopping treatment suddenly may cause withdrawal symptoms.

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

4. Possible side effects

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

Tell your doctor immediately or seek urgent medical attention if you experience serious side effects, such as:

swelling of the face, lips, tongue or throat which may cause difficulty in swallowing or

breathing, severe hives/nettle rash. These may be signs of a life-threatening allergic reaction

feeling sleepy and uncoordinated, have blurred vision, have slurred speech, cannot think well or clearly, or your breathing gets much slower than is normal for you
severe tiredness, itching with yellowing of 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 one 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 painful swallowing, runny nose
anxiety, depression, decreased sexual drive, nervousness, abnormal thinking
migraines, dizziness, fainting, increase in muscle tension, tingling, drowsiness
increased tearing (watering eyes) or other tearing disorder
increased blood pressure, flushing
increased cough
abdominal pain, upset stomach or other stomach discomfort, diarrhoea, flatulence, vomiting
rash, itching, hives
back pain, joint pain, muscle pain, leg cramps (muscle spasm)
urine abnormality
difficulty in getting or keeping an erection
weakness, chest pain, chills, fever, feeling of general discomfort, pain, swelling (hands and feet)
abnormal liver function, weight loss
accidental injury caused by loss of alertness or co-ordination

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

abnormal blood tests swollen, glands (lymph nodes)
abnormal dreams, agitation, loss of interest, depersonalisation (not feeling like yourself), medicine dependence, exaggerated feeling of well-being, feelings of hostility
amnesia (memory disturbance), convulsion (fits), speech disorder, tremor
eye inflammation or infection, small pupil size
rapid or slow heartbeat, myocardial infarction (heart attack), palpitations, chest tightness
low blood pressure
asthma, shortness of breath, yawning
pain and sores in mouth, tongue discolouration
acne, hair loss, dry or scaling skin, skin nodule
inflammation of joints
protein in your urine, urinary tract infection, difficulty urinating, painful or difficult urination, blood in urine, kidney stone
menstrual or vaginal problems, abnormal ejaculation
sensitivity to heat or cold
heat stroke

Not known (frequency cannot be estimated from the available data):

deterioration of brain function that is a serious complication of liver disease
spinning sensation
drop in blood pressure on changing position from sitting or lying down to standing
sudden withdrawal syndrome caused by taking product too soon after use of illicit opioids,

5. How to store Zubsolv

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

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

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

Zubsolv can be a target for people who abuse prescription medicine. Keep this medicine in a safe place to protect it from theft.

Store the blister safely.

Never open the blister in advance.

Do not take this medicine in front of children.

An emergency unit should be contacted immediately in case of accidental ingestion or suspicion of ingestion.

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 to protect the environment.

6. Contents of the pack and other information

The active substances are buprenorphine and naloxone.

Each 0.7 mg / 0.18 mg sublingual tablet contains 0.7 mg buprenorphine (as hydrochloride) and

0.18 mg naloxone (as hydrochloride dihydrate).

Each 1.4 mg / 0.36 mg sublingual tablet contains 1.4 mg buprenorphine (as hydrochloride) and

0.36 mg naloxone (as hydrochloride dihydrate).

Each 2.9 mg / 0.71 mg sublingual tablet contains 2.9 mg buprenorphine (as hydrochloride) and

0.71 mg naloxone (as hydrochloride dihydrate).

Each 5.7 mg / 1.4 mg sublingual tablet contains 5.7 mg buprenorphine (as hydrochloride) and

1.4 mg naloxone (as hydrochloride dihydrate).

Each 8.6 mg / 2.1 mg sublingual tablet contains 8.6 mg buprenorphine (as hydrochloride) and

2.1 mg naloxone (as hydrochloride dihydrate).

Each 11.4 mg / 2.9 mg sublingual tablet contains 11.4 mg buprenorphine (as hydrochloride) and

2.9 mg naloxone (as hydrochloride dihydrate).

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

What Zubsolv looks like and contents of the pack

Zubsolv sublingual tablets are available in six different strengths, differentiated by shape and debossing:

Zubsolv tablet strength (buprenorphine/naloxone)	Zubsolv tablet description	Zubsolv tablet debossing	Appearance
0.7 mg / 0.18 mg	White, oval tablet, length 6.8 mm and width 4.0 mm	“.7” on one side
1.4 mg / 0.36 mg	White, triangular tablet, base 7.2 mm and height 6.9 mm	“1.4” on one side
2.9 mg / 0.71 mg	White, D-shaped tablet, height 7.3 mm and width 5.65 mm	“2.9” on one side	2
5.7 mg / 1.4 mg	White, round tablet, 7 mm in diameter	“5.7” on one side
8.6 mg / 2.1 mg	White, diamond shaped tablet, length 9.5 mm and width 8.2 mm	“8.6” on one side
11.4 mg / 2.9 mg	White, capsule shaped tablet, length 10.3 mm and width 8.2 mm	“11.4” on one side	jE)

All strengths will be available as packs of 7, 28, and 30 tablets presented in aluminium blisters. Not all strengths and 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 751 05

Sweden

This leaflet was last revised in.

Detailed information on this medicine is available on the European Medicines Agency web site:.