Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - sixmo

Document Subject

Generated Narrative: MedicinalProductDefinition mp257716587c0bc57c8b7f0da168f8cf11

identifier: http://ema.europa.eu/identifier/EU/1/19/1369/001

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: Sixmo 74.2 mg implant

type: Full name

part

part: nan

type: Invented name part

part

part: nan

type: Scientific name part

part

part: nan

type: Strength part

part

part: nan

type: Pharmaceutical dose form part

Usages

-	Country	Jurisdiction	Language
*	EU	EU	en

Document Content

Generated Narrative: Composition composition-en-257716587c0bc57c8b7f0da168f8cf11

identifier: http://ema.europa.eu/identifier/EU/1/19/1369/001

status: Final

type: Package Leaflet

category: Raw

date: 2022-02-16 13:28:17+0000

author: Organization ACME industry

title: TEST PURPOSES ONLY - sixmo

Attesters

What is in this leaflet

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

Sixmo contains the active substance buprenorphine, which is a type of opioid medicine. It is used to treat opioid dependence in adults who are also receiving medical, social and psychological support.

Do not use Sixmo if you:

• are allergic to buprenorphine or any of the other ingredients of this medicine (listed in section 6)
• have severe breathing problems
• have severly reduced liver function
• have acute alcoholism or alcohol delirium caused by withdrawal from alcohol
• are using naltrexone or nalmefene to treat alcohol or opioid dependence
• have had an increased formation of scare tissue

Patients who may not be investigated using a magnetic resonance imaging (MRI) scan must not be allowed to receive Sixmo.

Warnings and precautions

Talk to your doctor before using Sixmo if you have:

• asthma or other breathing problems
• mild or moderate liver problems
• reduced kidney function
• head injury or other circumstances where the pressure in the head may be increased
• a history of fits
• low blood pressure
• enlarged prostate or narrowed urethra
• underactive thyroid
• reduced adrenal gland function, such as Addison's disease
• abnormal function of the bile duct
• general weakness and poor health, or you are elderly
• a history of connective tissue disease such as scleroderma
• a history of recurrent methicillin-resistant Staphylococcus aureus infections (MRSA)
• depression or other conditions that are treated with antidepressants.
  The use of these medicines together with Sixmo can lead to serotonin syndrome, a potentially life-threatening condition (see Other medicines and Sixmo ).

Important aspects to consider during treatment:

• Drowsiness may occur especially in the first week after insertion. See Driving and using machines .
• Your doctor should examine the insertion site for infections and wound problems:

• one week after implant insertion and
• at least once a month thereafter

• Infection may occur at the site of the insertion or removal of the implant. Excessive touching of the implants or insertion site shortly after insertion may increase the chance of infection. Tell your doctor immediately if you have any signs of infection (such as redness or inflammation) at the site of insertion or removal.
• If an implant comes out after insertion, take the following steps:

• Schedule an appointment with the inserting doctor as soon as possible.
• Place the implant in a glass jar with a lid. Store it safely away from others, especially children. Bring it to the inserting doctor to determine whether the full implant has been expelled. Please note: Buprenorphine can cause severe, possibly fatal, breathing depression (shortness of breath or stops breathing) in children who are accidentally exposed to it.
• The doctor will monitor you until the implant is replaced to evaluate for withdrawal symptoms.

• Avoid moving implants around under the skin or gain a lot of weight after insertion of Sixmo as this may make it difficult to locate implants.
• Misuse and abuse: If buprenorphine is abused it can lead to overdose and death. This risk increases when additionally using alcohol or other substances.
• This medicine can cause dependence, but at a lower level than other substances such as morphine. If you stop Sixmo treatment your doctor will monitor you for withdrawal symptoms.
• A number of cases of death due to breathing depression have been reported while on buprenorphine. Particularly, this occurs when additionally using alcohol, other opioids or certain medicines which calm, induce sleep or relax muscles. Buprenorphine can cause fatal breathing problems in non-dependent people or children. Sixmo should be used with caution in patients with asthma or other breathing problems.
• Liver damage, including liver failure, has been reported when using buprenorphine. This may be related to existing reduced liver function and ongoing injecting drug use. If liver problems are suspected your doctor will carry out tests to decide if treatment should be stopped.
• While using Sixmo, situations may arise where you need acute pain treatment or anaesthesia. Ask your doctor or pharmacist for advice in these cases.
• Substances like buprenorphine may cause pinpoint pupils, change consciousness or the way you feel pain.
• Substances like buprenorphine may cause a sudden drop in blood pressure, causing dizziness when getting up quickly.

Children and adolescents

Sixmo is not recommended for children under 18 years.

Patients over 65 years Sixmo is not recommended for patients over 65 years.

Other medicines and Sixmo

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

Especially, inform your doctor during Sixmo treatment before using:

• medicines which calm, induce sleep or relax muscles, with active substance names ending with azepam
  This combination may result in death due to breathing depression. Therefore, use these medicines during Sixmo treatment only on doctor s advice and at the prescribed dosage.
• other medicines that depress the brain or spinal cord, as these reduce alertness, making driving and using machines hazardous

• other opioid derivatives such as methadone, strong painkillers and cough suppressants
• certain medicines to treat depressions
• medicines called antihistamines used to treat allergic reactions, sleep disturbances, cold; or prevent and treat nausea and vomiting
• medicines to treat epilepsy or to sedate, with active substance names mostly ending with tal
• medicines to treat anxiety, other than those described in the first bullet point
• medicines to treat mental or anxiety disorders, with sedative effects, called neuroleptics
• clonidine: a medicine to treat high blood pressure and high eye pressure

• naltrexone, nalmefene, used to treat addiction They can block the effects of buprenorphine. Do not use these medicines during Sixmo treatment as they can cause a sudden onset of prolonged, intense withdrawal symptoms.
• medicines to treat HIV infections with active substance names ending in navir , such as ritonavir, nelfinavir, amprenavir, fosamprenavir
• medicines to treat fungal infections, like thrush, with active substance names ending in azole , such as ketoconazole, itraconazole, fluconazole
• clarithromycin, erythromycin, troleandomycin: medicines to treat bacterial infections
• nefazodone: a medicine to treat depression
• verapamil, diltiazem, amiodarone: medicines to treat high blood pressure and heart disorders
• aprepitant: a medicine to prevent nausea and vomiting
• phenobarbital, carbamazepine, phenytoin: medicines to treat epilepsy and other illnesses
• rifampicin: a medicine to treat tuberculosis or certain other infections
• certain medicines to treat depression or Parkinson s disease, called monoamine oxidase inhibitors, such as phenelzine, isocarboxazid, iproniazid and tranylcypromine
• anti-depressants such as moclobemide, tranylcypromine, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine, venlafaxine, amitriptyline, doxepine, or trimipramine. These medicines may interact with Sixmo 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.

Sixmo with food, drink and alcohol

Do not drink alcohol during Sixmo treatment, as it increases the sedative effect. Avoid grapefruit juice to prevent possible side effects.

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 for advice before using this medicine.

• pregnancy Sixmo is not recommended during pregnancy, nor in women of childbearing age not using contraception. When used during pregnancy, particularly late pregnancy, buprenorphine may cause withdrawal symptoms, including breathing problems, in the newborn baby. This may appear several days after birth.
• breast-feeding Do not breast-feed during Sixmo treatment, as buprenorphine passes into breast milk.

Driving and using machines

Buprenorphine may reduce the ability to drive and use machines; especially during the first 24 to 48 hours up to one week following implant insertion. You may fell dizzy, drowsy and less alert. Do not drive or perform dangerous activities until you are certain Sixmo does not reduce your ability in such activities.

Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not sure. Sixmo implants must be inserted, removed, and patients monitored by a healthcare professional familiar with the procedure, with experience in the management of opioid addiction.

Before administering Sixmo implants

You must be on a stable buprenorphine dose of between 2 to 8 mg per day, given under the tongue. This must be for at least 30 days and to be decided by your doctor.

Buprenorphine given under the tongue will be stopped 12 to 24 hours before insertion of Sixmo implants.

Treatment with Sixmo implants

Each dose consists of 4 implants.

Before inserting Sixmo, your doctor will give you a local anaesthetic to numb the area. The implants will then be inserted under the skin in the inner side of the upper arm.

After insertion of the implants, the doctor will apply a sterile gauze with a pressure bandage to minimize bruising. You may remove the pressure bandage after 24 hours and the adhesive bandage after five days. Apply an ice pack on the arm for 40 minutes every two hours for the first 24 hours, then as needed.

Your doctor will also give you a Patient Alert Card that provides the

• insertion site and date
• latest date on which the implant must be removed Keep this card in a safe place, since the information on the card may make it easier to carry out removal.

Your doctor will examine the insertion site one week following implant insertion and at a minimum once-monthly thereafter for signs of:

• infection or any problems with wound healing
• evidence of implant coming out of the skin Please attend all of these necessary appointments. Inform your doctor immediately if you think you have an infection at the implant site or if the implant starts to come out.

If you feel the need for additional buprenorphine doses, contact your doctor straight away.

Removal of Sixmo implants

Sixmo implants are intended to be in place for 6 months and provide a continuous delivery of buprenorphine. They are removed by the doctor at the end of the sixth month.

The implants should only be removed by a doctor who is familiar with the procedure. If the implants cannot be located, the doctor may use ultrasound or a type of scan called magnetic resonance imaging (MRI).

After removal of the implant, the doctor will apply a sterile gauze with a pressure bandage to minimize bruising. You may remove the pressure bandage after 24 hours and the adhesive bandage after five days. Apply an ice pack on the arm for 40 minutes every two hours for the first 24 hours, then as needed.

Retreatment with Sixmo implants

When the first 6-month treatment period is up, a new set of Sixmo implants may be given after removal of the old implants, preferably on the same day. New implants will be inserted in the other arm.

If another set of implants is not inserted on the same day as the previous set is removed: A dose of between 2 and 8 mg buprenorphine daily, given under the tongue, is recommended until repeat treatment occurs. This should be stopped 12 to 24 hours before insertion of the next set of Sixmo implants.

If you have more Sixmo than you need

In some cases, the dose delivered by the implants might be more than the one you need. Overdose symptoms include:

• pinpoint pupils
• sedation
• low blood pressure
• breathing difficulties, breathing slowly In the worst case, it can result in breathing stopping, heart failure and death.

Inform your doctor immediately if the above symptoms occur, or go to the nearest hospital and bring this leaflet and your Patient Alert Card with you. Do not attempt to remove the implants by yourself as this could be very dangerous.

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

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

Side effects can occur with the following frequencies: Common, may affect up to 1 in 10 people

• constipation, nausea, vomiting, diarrhoea
• other stomach and bowel disorders, tooth disorder
• pain, such as abdominal pain, bone pain, muscle pain, chest pain, headache
• dizziness, drowsiness
• sleeplessness, anxiety, hostility, nervousness
• mental condition, chracterised by delusions and irrationality
• high blood pressure, feeling heartbeat
• fainting
• dilated pupils
• hot flush, bruising, dilation of blood vessels
• drug withdrawal syndrome, such as sweating, feeling hot and cold
• fatigue, chills, weakness, increased muscle tone
• infection, such as viral infection (e.g. flu)
• cough, breathlessness
• inflammation of the airways in the lungs, throat or inner lining of the nose
• increased sweating, feeling unwell
• decreased appetite
• increased level of a liver enzyme, alanine aminotransferase, in blood tests
• reactions at the implant site

• pain, itching
• procedural site reaction, such as pain during the insertion procedure
• bruising, skin reddening, scar
• bleeding

Uncommon, may affect up to 1 in 100 people

• dry mouth, wind, indigestion, bloody stool
• migraine, tremor
• excessive sleepiness
• abnormal sensation such as prickling, pins and needles , tingling and itchiness
• reduced consciousness
• sleep disorder, disinterest
• depression, euphoria
• decreased sexual desire, decreased orgasmic sensation
• restlessness, excitement, excitability, abnormal thoughts
• drug dependence
• reduced sense of touch or sensation
• fever, feeling cold, discomfort
• swelling, including tissue swelling in arms, legs or face caused by excess fluid
• muscle spasms, limb discomfort
• pain affecting muscles and skeleton, neck, limbs, joints
• pain and dysfunction of chewing muscles and joints called temporomandibular joint syndrome
• breathing depression, yawning
• cellulitis, skin infection, boil
• tonsil complications
• rash, rash pustular, skin lesion
• cold sweat, dry skin
• small bleeds beneath the skin
• changes in blood levels

• increased enzyme levels: aspartate aminotransferase, gamma-glutamyltransferase, blood lactate dehydrogenase, lipase, amylase
• decreased enzyme levels: alkaline phosphatase
• increased bicarbonate level
• increased bilirubin level - a yellow breakdown substance of the blood pigment
• increased glucose level
• decreased cholesterol level
• decreased haematocrit - the percentage of blood cells on the blood volume
• decreased haemoglobin - the red blood cell pigment, increased mean cell haemoglobin
• increase in certain white blood cell count: monocyte, neutrophils
• decreased cell count: platelets, red blood cells, lymphocytes

• abnormal mean cell volume
• increased or decreased weight, including abnormal weight gain
• dehydration, increased appetite
• painful period, erectile dysfunction
• eye discharge, blurred vision, lacrimal disorder
• slow heartbeat, abnormal heart rhythm that starts in the atrial chambers of the heart
• urinary hesitation, urge to urinate, urinating more frequently with little urinary output
• urinary tract infection
• vulvovaginal fungal infection
• lymph node disease
• lack of a white blood cell type called neutrophils
• complication after the procedure
• migration of implant(s), device breakage or expulsion
• reopening of a closed wound
• reactions at the implant site

• infection, including wound infection
• rash, scaring
• reduced healing
• swollen area containing pus

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 national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

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 label and carton after EXP. The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

What Sixmo contains

• The active substance is buprenorphine. Each implant contains buprenorphine hydrochloride equivalent to 74.2 mg of buprenorphine.
• The other ingredient is ethylene vinyl acetate copolymer.

What Sixmo looks like and contents of the pack

Sixmo is a white/off-white to pale yellow rod-shaped implant, 26.5 mm long and 2.4 mm in diameter.

Sixmo is provided in a carton. It consists of four implants individually packaged into laminated foil sachets and one individually packaged sterile disposable applicator.

Marketing Authorisation Holder and Manufacturer

L. Molteni & C. dei F.lli Alitti Soc.Es.S.p.A, Strada Statale 67, 50018 Scandicci (Firenze), Italy

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgi /Belgique/Belgien Accord Healthcare bv T l/Tel: +32 51 79 40 Lietuva Accord Healthcare AB Tel: +46 8 624 00
Accord Healthcare Polska Sp. z o.o. Te .: +48 22 577 28 Luxembourg/Luxemburg Accord Healthcare bv T l/Tel: +32 51 79 40 esk republika Accord Healthcare Polska Sp. z o.o. Tel: +48 22 577 28 Magyarorsz g Accord Healthcare Polska Sp. z o.o. Tel.: +48 22 577 28 Danmark Accord Healthcare AB Tlf: + 46 8 624 00 Malta Accord Healthcare Ireland Ltd Tel: +44 (0) 208 901 3Deutschland Accord Healthcare GmbH Tel: +49 89 700 9951 0

Nederland Accord Healthcare B.V. Tel: +31 30 850 6Eesti Accord Healthcare AB Tel: +46 8 624 00 Norge Accord Healthcare AB Tlf: + 46 8 624 00
Accord Healthcare Italia Srl : +39 02 943 23 sterreich Accord Healthcare GmbH Tel: +43 (0)662 424899-0

Espa a Accord Healthcare S.L.U. Tel: +34 93 301 00 Polska Molteni Farmaceutici Polska Sp. z o.o. Tel.: +48 (12) 653 15 France Accord Healthcare France SAS T l: +33 (0)320 401 Portugal Accord Healthcare, Unipessoal Lda Tel: +351 214 697 Hrvatska
Accord Healthcare Polska Sp. z o.o. Tel: +48 22 577 28 Rom nia Accord Healthcare Polska Sp. z o.o. Tel: +48 22 577 28 Ireland Accord Healthcare Ireland Ltd Tel: +353 (0) 21 461 9Slovenija Accord Healthcare Polska Sp. z o.o. Tel: +48 22 577 28 sland Accord Healthcare AB S mi: + 46 8 624 00 Slovensk republika Accord Healthcare Polska Sp. z o.o. Tel: +48 22 577 28 Italia L.Molteni & C. dei F.lli Alitti Soc.Es.S.p.A Tel: +39 055 73Suomi/Finland Accord Healthcare Oy Puh/Tel. +358 10 231 4
Accord Healthcare S.L.U. Tel: +34 93 301 00 Sverige Accord Healthcare AB Tel: + 46 (0)8 624 00 Latvija Accord Healthcare AB Tel: +46 8 624 00 United Kingdom (Northern Ireland) Accord-UK Ltd Tel: +44 (0)1271 385This leaflet was last revised in

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