Patient leaflet - Buprenorphine/naloxone 8 mg / 2 mg sublingual tablets

1. What Buprenorphine/Naloxone Ethypharm is and what it is used for

Buprenorphine/Naloxone Ethypharm 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. Buprenorphine/Naloxone Ethypharm is used in adults and adolescents over 15 years of age, who are also receiving medical, social and psychological support.

2. What you need to know before you take Buprenorphine/Naloxone Ethypharm

Do not take Buprenorphine/Naloxone Ethypharm

if you are allergic to buprenorphine, naloxone or any of the other ingredients of this medicine (see section 6)
if you have serious breathing problems
if you have serious liver problems
if you are intoxicated due to alcohol or have trembling, sweating, anxiety, confusion, or hallucinations caused by alcohol.
if you are taking naltrexone or nalmefene for the treatment of alcohol or opioid dependence.
- 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) 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 medicines (used to treat fungal infections) such as ketoconazole, itraconazole, certain antibiotics, may extend the effects of this medicine.
- some medicines may decrease the effect of Buprenorphine/Naloxone Ethypharm. These include medicines used to treat epilepsy (such as carbamazepine and phenytoin), and medicines used to treat tuberculosis (rifampicin).
- naltrexone and nalmefene (medecines used to treat addictive disorders) may prevent the therapeutic effects of Buprenorphine/Naloxone Ethypharm. They should not be taken at the same time as Buprenorphine/Naloxone Ethypharm treatment because you may experience a sudden onset of prolonged and intense withdrawal.
- anti-depressants such as moclobemide, tranylcypromine, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine, venlafaxine, amitriptyline, doxepine, or trimipramine. These medicines may interact with Buprenorphine/Naloxone Ethypharm 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.

Warnings and precautions

Talk to your doctor before taking Buprenorphine/ Naloxone Ethypharm if you have:

asthma or other breathing problems
any liver disease such as hepatitis
low blood pressure
recently suffered a head injury or brain disease
a urinary disorder (especially linked to enlarged prostrate in men)
any kidney disease
thyroid problems
adrenocortical disorder (e.g. Addison’s disease)
depression or other conditions that are treated with antidepressants. The use of these medicines together with Buprenorphine/Naloxone Ethypharm can lead to serotonin syndrome, a potentially life-threatening condition (see “Other medicines and Buprenorphine/ Naloxone Ethypharm”).
Buprenorphine/Naloxone Ethypharm with food, drink and alcohol
Alcohol may increase drowsiness and may increase the risk of respiratory failure if taken with Buprenorphine/ Naloxone Ethypharm. Do not take Buprenorphine/ Naloxone Ethypharm together with alcohol. Do not swallow or consume food or any drink until the tablet is completely dissolved.
Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
The risks of using Buprenorphine/Naloxone Ethypharm 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.

Never open the blister in advance.

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

Important things to be aware of:

Additional monitoring
You may be more closely monitored by your doctor if you are below the age of 18 or over the age of 65. This medicine should not be taken by those under 15 years of age.
When taken during pregnancy, particularly late pregnancy, medicines like Buprenorphine/Naloxone Ethypharm 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 Buprenorphine/Naloxone Ethypharm passes into breast milk.
Misuse and abuse
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
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.
This medicine may cause severe, possibly fatal, respiratory depression (reduced ability to breathe) in children and non-dependent people who accidentally or deliberately take it.
Dependence
This product can cause dependence.
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.
Driving and using machines
Buprenorphine/Naloxone Ethypharm 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 Buprenorphine/Naloxone Ethypharm. Do not drive, use any tools or machines, or perform dangerous activities until you know how this medicine affects you.
The medicine can affect your ability to drive as it may make you sleepy or dizzy.
- Do not drive while taking this medicine until you know how it affects you.
- It is an offence to drive if this medicine affects your ability to drive.
- However, you would not be committing an offence if:
  o The medicine has been prescribed to treat a medical or dental problem and
  o You have taken it according to the instructions given by the prescriber or in the information provided with the medicine and
  o It was not affecting your ability to drive safely

Buprenorphine/Naloxone Ethypharm contains lactose

If you have been told by your doctor that you have intolerance to some sugars, contact your doctor before taking this medicine.

Buprenorphine/Naloxone Ethypharm can also cause withdrawal symptoms if you stop taking it abruptly.

Liver damage
Liver damage has been reported after taking Buprenorphine/Naloxone Ethypharm, 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 with the ability to harm your liver (see section 4). 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 Buprenorphine/Naloxone Ethypharm.
Buprenorphine/Naloxone Ethypharm contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per sublingual tablet, that is to say essentially ‘sodium-free’.

3. How to take Buprenorphine/Naloxone Ethypharm

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.

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.
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
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.

Other medicines and Buprenorphine/Naloxone Ethypharm

Tell your doctor if you are taking, have recently taken or might take any other medicines.

Some medicines may increase the side effects of Buprenorphine/Naloxone Ethypharm and may sometimes cause very serious reactions. Do not take any other medicines whilst taking Buprenorphine/Naloxone Ethypharm without first talking to your doctor, especially:

The recommended starting dose for adults and adolescents over the age of 15 years is one to two tablets of Buprenorphine/Naloxone Ethypharm 2 mg/0.5 mg. An additional one to two tablets of the Buprenorphine/ Naloxone Ethypharm 2 mg/0.5 mg may be administered on day 1 depending on your needs.

Clear signs of withdrawal should be evident before taking your first dose of Buprenorphine/Naloxone Ethypharm. A doctor’s assessment of your readiness for treatment will guide the timing of your first Buprenorphine/Naloxone Ethypharm dose.

Starting treatment of Buprenorphine/Naloxone Ethypharm whilst dependent on heroin
Concomitant use of Buprenorphine/Naloxone Ethypharm and sedative medicines such as benzodiazepines or related medicines increases the risk of drowsiness, difficulties in breathing (respiratory depression), coma and may be life-threatening. Because of this, concomitant use should only be considered when other treatment options are not possible. However, if your doctor does prescribe Buprenorphine/Naloxone Ethypharm together with sedative medicines, the dose and duration of concomitant treatment should be limited by your doctor. Please tell your doctor about all sedative medicines you are taking, and follow your doctor’s dose recommendation closely. It could be helpful to inform friends or relatives to be aware of the signs and symptoms stated above. Contact your doctor when experiencing such symptoms.
Other medicines that may make you feel sleepy which are used to treat illnesses such as anxiety, sleeplessness, convulsions/seizures, pain. These types of medicines will reduce your alertness levels making it difficult 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.
anti-depressants (used to treat depression) such as isocarboxazide, phenelzine, selegiline, tranylcypromine and valproate may increase the effects of this medicine.
sedative Hı receptor antagonists (used to treat allergic reactions) such as diphenhydramine and chlorphenamine.
If you are dependent upon heroin or a short acting opioid, your first dose of Buprenorphine/Naloxone Ethypharm should be taken when signs of withdrawal appear, but not less than 6 hours after you last used opioids.
Starting treatment of Buprenorphine/Naloxone Ethypharm 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 Buprenorphine/ Naloxone Ethypharm therapy. The first dose of Buprenorphine/Naloxone Ethypharm should be taken when signs of withdrawal appear, but not less than 24 hours after you last used methadone.

Taking Buprenorphine/Naloxone Ethypharm

Take the dose once a day by placing the tablets under the tongue.
Keep the tablets in place under the tongue until they have completely dissolved. This may take 5-10 minutes.
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.

How to remove the tablet from the blister

1 - Do not push the tablet through the foil.

2 - Remove just one sec-tion from the blister pack, tearing it along the perfora-ted line.

3 - Starting from the edge where the seal is lifted, pull back the foil on the back to remove the tablets.

If the blister is damaged, discard the tablet.

Dosage adjustment and maintenance therapy:

During the days after you start treatment, your doctor may increase the dose of Buprenorphine/Naloxone Ethypharm you take according to your needs. If you have the impression that the effect of Buprenorphine/Naloxone Ethypharm is too strong or too weak, talk to your doctor or pharmacist. The maximum daily dose is 24 mg.

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

Stopping treatment

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

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

If you take more Buprenorphine/Naloxone Ethypharm 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 Buprenorphine/Naloxone Ethypharm may cause serious and lifethreatening breathing problems.

Symptoms of overdose may include feeling sleepy and uncoordinated with slowed reflexes, blurred vision, and/ or slurred speech. You may be unable to think clearly, and may breathe much slower than is normal for you.

If you forget to take Buprenorphine/Naloxone Ethypharm

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

If you stop taking Buprenorphine/Naloxone Ethypharm

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 medicine, 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 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.

Also tell your doctor immediately if you experience side effects such as:

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).

Side effects reported with Buprenorphine/Naloxone Ethypharm

Very common (may affect more than one in 10 people):

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

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

weight loss,
swelling (hands and
feet),
drowsiness,
anxiety,
nervousness,
tingling,
depression,
decreased sexual drive,
increase in muscle ten-
sion,
abnormal thinking,
increased tearing (wate-
ring eyes) or other tea-
ring disorder,
blurred vision,
flushing,
increased blood pres-
sure,
migraines,
runny nose,
sore throat and painful
swallowing,
increased cough,
upset stomach or other
stomach discomfort,
diarrhoea,
abnormal liver function,
- flatulence,
- vomiting,
- rash,
- itching,
- hives,
- pain,
- joint pain,
- muscle pain,
- leg cramps (muscle spasm),
- difficulty in getting or keeping an erection,
- urine abnormality,
- abdominal pain,
- back pain,
- weakness,
- infection,
- chills,
- chest pain,
- fever,
- flu-like symptoms,
- feeling of general dis-comfort,
- accidental injury caused by loss of alertness or co-ordination,
- faintness and dizziness.

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

swollen glands (lymph
nodes),
agitation, tremor,
abnormal dream,
excessive muscle acti-
vity,
depersonalisation (not
feeling like yourself),
medicine dependence,
amnesia (memory distur-
bance),
loss of interest,
exaggerated feeling of
well being,
convulsion (fits),
speech disorder,
small pupil size,
difficulty urinating,
eye inflammation or
infection,
rapid or slow heart beat,
low blood pressure,
palpitations,
myocardial infarction
(heart attack),
chest tightness,
- shortness of breath,
- asthma,
- yawning,
- pain and sores in mouth,
- tongue discolouration,
- acne,
- skin nodule,
- hair loss,
- dry or scaling skin,
- inflammation of joints,
- urinary tract infection,
- abnormal blood tests,
- blood in urine,
- abnormal ejaculation,
- menstrual or vaginal problems,
- kidney stone,
- protein in your urine,
- painful or difficult urina-tion,
- 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/Naloxone Ethypharm too soon after use of illicit opioids, drug withdrawal syndrome in newborn.
Slow or difficult breathing, liver injury with or without jaundice, hallucinations, swelling of face and throat or life threatening allergic reactions, drop in blood pressure on changing position from sitting or lying down to standing.
- Misusing this medicine by injecting it can cause withdrawal symptoms, infections, other skin reactions and potentially serious liver problems (see Warnings and precautions).

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at www.mhra.gov.uk/ yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Buprenorphine/Naloxone Ethypharm

Keep out of the sight and reach of children and other household members.

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

Do not store above 30°C.

Store in the original package, in order to protect from light. However, Buprenorphine/Naloxone Ethypharm can be a target for people who abuse prescription medicine. Keep this medicine in a safe place to protect it from theft.

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. Content of the pack and other information

What Buprenorphine/Naloxone Ethypharm contains

The active substances are buprenorphine and naloxone. Each 8 mg/2 mg tablet contains 8mg of buprenorphine (as hydrochloride), and 2 mg of naloxone (as hydrochloride dihydrate).
The other ingredients are lactose monohydrate, maize starch, mannitol (E421), povidone K30, citric acid anhydrous, sodium citrate, lime flavour, lemon flavor, acesulfame potassium and sodium stearyl fumarate.

What Buprenorphine/Naloxone Ethypharm looks like and contents of the pack

Buprenorphine/Naloxone Ethypharm 8 mg/2 mg sublingual tablets are white to off-white, round biconvex, uncoated tablets, of 10.5 mm in diameter with “N8” engraved on one side and a logo “↑” on the other side.

Packed in child resistant, peelable unit-dose blisters of 7 x 1 tablets and 28 x 1 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Ethypharm

194, Bureaux de la Colline, Bâtiment D

92213 Saint-Cloud cedex

France

Manufacturer

Ethypharm

Chemin de la Poudrière

76120 Le Grand Quevilly