Suboxone

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Suboxone 2 mg/0.5 mg sublingual tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each sublingual tablet contains 2 mg buprenorphine (as hydrochloride) and 0.5 mg naloxone (as 
hydrochloride dihydrate). 
Excipients with known effect:  
Each sublingual tablet contains 42 mg lactose (as monohydrate) 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Sublingual tablet 
White hexagonal biconvex tablets of 6.5 mm with “N2” debossed on one side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Substitution treatment for opioid drug dependence, within a framework of medical, social and 
psychological treatment. The intention of the naloxone component is to deter intravenous misuse. 
Treatment is intended for use in adults and adolescents over 15 years of age who have agreed to be 
treated for addiction. 
 
 
4.2 Posology and method of administration 
 
Treatment must be under the supervision of a physician experienced in the management of opiate 
dependence/addiction.  
 
Precautions to be taken before induction 
Prior to treatment initiation, consideration should be given to the type of opioid dependence (i.e. long- 
or short-acting opioid), the time since last opioid use and the degree of opioid dependence. To avoid 
precipitating withdrawal, induction with buprenorphine/naloxone or buprenorphine only should be 
undertaken when objective and clear signs of withdrawal are evident (demonstrated e.g. by a score 
indicating mild to moderate withdrawal on the validated Clinical Opioid Withdrawal Scale, COWS).  

o For patients dependent upon heroin or short-acting opioids, the first dose of 
buprenorphine/naloxone should be taken when signs of withdrawal appear, but not less than 
6 hours after the patient last used opioids. 

o For patients receiving methadone, the dose of methadone should be reduced to a maximum of 
30 mg/day before beginning buprenorphine/naloxone therapy. The long half life of methadone 
should be considered when starting buprenorphine/naloxone. The first dose of 
buprenorphine/naloxone should be taken only when signs of withdrawal appear, but not less 
than 24 hours after the patient last used methadone. Buprenorphine may precipitate symptoms 
of withdrawal in patients dependent upon methadone.  

 



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Posology 
 
Initiation therapy (induction) 
The recommended starting dose in adults and adolescents over 15 years of age is one to two Suboxone 
2 mg/0.5 mg.  An additional one to two Suboxone 2 mg/0.5 mg may be administered on day one 
depending on the individual patient’s requirement.  
During the initiation of treatment, daily supervision of dosing is recommended to ensure proper 
sublingual placement of the dose and to observe patient response to treatment as a guide to effective 
dose titration according to clinical effect.   
 
Dosage adjustment and maintenance therapy 
Following treatment induction on day one, the patient should be stabilised to a maintenance dose 
during the next few days by progressively adjusting the dose according to the clinical effect of the 
individual patient.  Dose titration in steps of 2-8 mg buprenorphine is guided by reassessment of the 
clinical and psychological status of the patient, and should not exceed a maximum single daily dose of 
24 mg buprenorphine.  
 
Less than daily dosing  
After a satisfactory stabilisation has been achieved the frequency of dosing may be decreased to 
dosing every other day at twice the individually titrated daily dose. For example, a patient stabilised to 
receive a daily dose of 8 mg buprenorphine may be given 16 mg buprenorphine on alternate days, with 
no dose on the intervening days. In some patients, after a satisfactory stabilisation has been achieved, 
the frequency of dosing may be decreased to 3 times a week (for example on Monday, Wednesday and 
Friday). The dose on Monday and Wednesday should be twice the individually titrated daily dose, and 
the dose on Friday should be three times the individually titrated daily dose, with no dose on the 
intervening days. However, the dose given on any one day should not exceed 24 mg buprenorphine. 
Patients requiring a titrated daily dose> 8 mg buprenorphine /day may not find this regimen adequate. 
 
Medical withdrawal  
After a satisfactory stabilisation has been achieved, if the patient agrees, the dosage may be reduced 
gradually to a lower maintenance dose; in some favourable cases, treatment may be discontinued. The 
availability of doses of 2 mg/0.5 mg and 8 mg/2 mg allows for a downward titration of dosage. For 
patients who may require a lower buprenorphine dose, buprenorphine 0.4 mg may be used. Patients 
should be monitored following medical withdrawal because of the potential for relapse. 
 
Special populations 
 
Elderly 
The safety and efficacy of buprenorphine/naloxone in elderly patients over 65 years of age have not 
been established. No recommendation on posology can be made. 
 
Hepatic impairment 
Baseline liver function tests and documentation of viral hepatitis status is recommended prior to 
commencing therapy. Patients who are positive for viral hepatitis, on concomitant medicinal products 
(see section 4.5) and/or have existing liver dysfunction are at risk of accelerated liver injury. Regular 
monitoring of liver function is recommended (see section 4.4).  
Both active substances of Suboxone, buprenorphine and naloxone, are extensively metabolized in the 
liver, and the plasma levels were found to be higher for both buprenorphine and naloxone in patients 
with moderate and severe hepatic impairment. Patients should be monitored for signs and symptoms 
of precipitated opioid withdrawal, toxicity or overdose caused by increased levels of naloxone and/or 
buprenorphine.  
As buprenorphine/naloxone pharmacokinetics may be altered in patients with hepatic impairment, 
lower initial doses and careful dose titration in patients with mild to moderate hepatic impairment are 
recommended. Buprenorphine/naloxone is contraindicated in patients with severe hepatic impairment. 
(see section 4.3 and 5.2).  
 
Renal impairment 



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Modification of the buprenorphine/naloxone dose is not required in patients with renal impairment. 
Caution is recommended when dosing patients with severe renal impairment (creatinine 
clearance < 30 ml/min) (see section 4.4 and 5.2). 
 
Paediatric population 
The safety and efficacy of buprenorphine/naloxone in children below the age of 15 years have not 
been established. No data are available. 
 
Method of administration 
Physicians must warn patients that the sublingual route is the only effective and safe route of 
administration for this medicinal product (see section 4.4). The tablet is to be placed under the tongue 
until completely dissolved. Patients should not swallow or consume food or drink until the tablet is 
completely dissolved.  
 
The dose is made up from multiple Suboxone tablets of different strengths, which may be taken all at 
the same time or in two divided portions; the second portion to be taken directly after the first portion 
has dissolved.  
 
 
4.3 Contraindications 
  
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. 
Severe respiratory insufficiency 
Severe hepatic impairment  
Acute alcoholism or delirium tremens. 
Concomitant administration of opioid antagonists (naltrexone, nalmefene) for the treatment of alcohol 
or opioid dependence. 
 
 
4.4 Special warnings and precautions for use 
 
Misuse, abuse and diversion 
Buprenorphine can be misused or abused in a manner similar to other opioids, legal or illicit. Some 
risks of misuse and abuse include overdose, spread of blood borne viral or localised and systemic 
infections, respiratory depression and hepatic injury. Buprenorphine misuse by someone other than the 
intended patient poses the additional risk of new drug dependent individuals using buprenorphine as 
the primary drug of abuse, and may occur if the medicine is distributed for illicit use directly by the 
intended patient or if the medicinal product is not safeguarded against theft.  
 
Sub-optimal treatment with buprenorphine/naloxone may prompt medicine misuse by the patient, 
leading to overdose or treatment dropout. A patient who is under-dosed with buprenorphine/naloxone 
may continue responding to uncontrolled withdrawal symptoms by self-medicating with opioids, 
alcohol or other sedative-hypnotics such as benzodiazepines. 
 
To minimize the risk of misuse, abuse and diversion, physicians should take appropriate precautions 
when prescribing and dispensing buprenorphine, such as to avoid prescribing multiple refills early in 
treatment, and to conduct patient follow-up visits with clinical monitoring that is appropriate to the 
patient's needs.  
 
Combining buprenorphine with naloxone in Suboxone is intended to deter misuse and abuse of the 
buprenorphine. Intravenous or intranasal misuse of Suboxone is expected to be less likely than 
buprenorphine alone since the naloxone in Suboxone can precipitate withdrawal in individuals 
dependent on heroin, methadone, or other opioid agonists.  
 
Respiratory depression 
A number of cases of death due to respiratory depression have been reported, particularly when 
buprenorphine was used in combination with benzodiazepines (see section 4.5) or when 



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buprenorphine was not used according to prescribing information.  Deaths have also been reported in 
association with concomitant administration of buprenorphine and other depressants such as alcohol or 
other opioids. If buprenorphine is administered to some non-opioid dependent individuals, who are not 
tolerant to the effects of opioids, potentially fatal respiratory depression may occur. 
 
This product should be used with care in patients with asthma or respiratory insufficiency (e.g. chronic 
obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, 
pre-existing respiratory depression or kyphoscoliosis (curvature of spine leading to potential shortness 
of breath)). 
 
Buprenorphine/naloxone may cause severe, possibly fatal, respiratory depression in children and non-
dependent persons in case of accidental or deliberate ingestion. Patients must be warned to store the 
blister safely, to never open the blister in advance, to keep them out of the reach of children and other 
household members, and not to take this medicine in front of children. An emergency unit should be 
contacted immediately in case of accidental ingestion or suspicion of ingestion. 
 
CNS depression 
Buprenorphine/naloxone may cause drowsiness, particularly when taken together with alcohol or 
central nervous system depressants (such as tranquilisers, sedatives or hypnotics) (see section 4.5). 
 
Dependence 
Buprenorphine is a partial agonist at the µ (mu)-opiate receptor and chronic administration produces 
dependence of the opioid type.  Studies in animals, as well as clinical experience, have demonstrated 
that buprenorphine may produce dependence, but at a lower level than a full agonist e.g. morphine.  
 
Abrupt discontinuation of treatment is not recommended as it may result in a withdrawal syndrome 
that may be delayed in onset. 
 
Hepatitis and hepatic events 
Cases of acute hepatic injury have been reported in opioid-dependent addicts both in clinical trials and 
in post marketing adverse reaction reports. The spectrum of abnormalities ranges from transient 
asymptomatic elevations in hepatic transaminases to case reports of hepatic failure, hepatic necrosis, 
hepatorenal syndrome, hepatic encephalopathy and death. In many cases the presence of pre-existing 
mitochondrial impairment (genetic disease, liver enzyme abnormalities, infection with hepatitis B or 
hepatitis C virus, alcohol abuse, anorexia, concomitant use of other potentially hepatotoxic medicines) 
and ongoing injecting drug use may have a causative or contributory role. These underlying factors 
must be taken into consideration before prescribing buprenorphine/naloxone and during treatment. 
When a hepatic event is suspected, further biological and etiological evaluation is required. Depending 
upon the findings, the medicinal product may be discontinued cautiously so as to prevent withdrawal 
symptoms and to prevent a return to illicit drug use. If the treatment is continued, hepatic function 
should be monitored closely. 
 
Precipitation of opioid withdrawal syndrome  
When initiating treatment with buprenorphine/naloxone, the physician must be aware of the partial 
agonist profile of buprenorphine and that it can precipitate withdrawal in opioid-dependent patients, 
particularly if administered less than 6 hours after the last use of heroin or other short-acting opioid, or 
if administered less than 24 hours after the last dose of methadone. Patients should be clearly 
monitored during the switching period from buprenorphine or methadone to buprenorphine/naloxone 
since withdrawal symptoms have been reported. To avoid precipitating withdrawal, induction with 
buprenorphine/naloxone should be undertaken when objective signs of withdrawal are evident (see 
section 4.2). 
 
Withdrawal symptoms may also be associated with sub-optimal dosing. 
 
Hepatic impairment 
The effect of hepatic impairment on the pharmacokinetics of buprenorphine and naloxone were 
evaluated in a post-marketing study.  Since both buprenorphine and naloxone are extensively 



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metabolized, plasma levels were found to be higher for both buprenorphine and naloxone in patients 
with moderate and severe hepatic impairment after single-dose administration.  Patients should be 
monitored for signs and symptoms of precipitated opioid withdrawal, toxicity or overdose caused by 
increased levels of naloxone and/or buprenorphine.  Suboxone sublingual tablets should be used with 
caution in patients with moderate hepatic impairment (See section 4.3 and 5.2). In patients with severe 
hepatic insufficiency the use of buprenorphine/naloxone is contraindicated. 
 
Renal impairment 
Renal elimination may be prolonged since 30 % of the administered dose is eliminated by the renal 
route. Metabolites of buprenorphine accumulate in patients with renal failure. Caution is 
recommended when dosing patients with severe renal impairment (creatinine clearance <30 ml/min) 
(see sections 4.2 and 5.2). 
 
Use in adolescents (Age 15-<18) 
Due to the lack of data in adolescents (age 15-<18), patients in this age group should be more closely 
monitored during treatment.  
 
CYP 3A inhibitors 
Medicines that inhibit the enzyme CYP3A4 may give rise to increased concentrations of 
buprenorphine. A reduction of the buprenorphine/naloxone dose may be needed. Patients already 
treated with CYP3A4 inhibitors should have their dose of buprenorphine/naloxone titrated carefully 
since a reduced dose may be sufficient in these patients (see section 4.5). 
 
General warnings relevant to the administration of opioids  
Opioids may produce orthostatic hypotension in ambulatory patients. 
 
Opioids may elevate cerebrospinal fluid pressure, which may cause seizures, so opioids should be used 
with caution in patients with head injury, intracranial lesions, other circumstances where cerebrospinal 
pressure may be increased, or history of seizure. 
 
Opioids should be used with caution in patients with hypotension, prostatic hypertrophy or urethral 
stenosis. 
 
Opioid-induced miosis, changes in the level of consciousness, or changes in the perception of pain as a 
symptom of disease may interfere with patient evaluation or obscure the diagnosis or clinical course of 
concomitant disease. 
 
Opioids should be used with caution in patients with myxoedema, hypothyroidism, or adrenal cortical 
insufficiency (e.g., Addison's disease). 
 
Opioids have been shown to increase intracholedochal pressure, and should be used with caution in 
patients with dysfunction of the biliary tract. 
 
Opioids should be administered with caution to elderly or debilitated patients. 
 
The concomitant use of monoamine oxidase inhibitors (MAOI) might produce an exaggeration of the 
effects of opioids, based on experience with morphine (see section 4.5). 
 
Suboxone contains lactose.  Patients with rare hereditary problems of galactose intolerance, should not 
take this medicine. 
 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Suboxone should not be taken together with: 
 



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 alcoholic drinks or medicines containing alcohol, as alcohol increases the sedative effect of 
buprenorphine (see section 4.7). 

 
Suboxone should be used cautiously when co-administered with: 
 

o  benzodiazepines: This combination may result in death due to respiratory depression of central 
origin. Therefore, dosages must be limited and this combination must be avoided in cases 
where there is a risk of misuse. Patients should be warned that it is extremely dangerous to 
self-administer non-prescribed benzodiazepines while taking this product, and should also be 
cautioned to use benzodiazepines concurrently with this product only as directed by their 
physician (see section 4.4). 

 
o other central nervous system depressants, other opioid derivatives (e.g. methadone, analgesics 

and antitussives), certain antidepressants, sedative H1-receptor antagonists, barbiturates, 
anxiolytics other than benzodiazepines, neuroleptics, clonidine and related substances: these 
combinations increase central nervous system depression. The reduced level of alertness can 
make driving and using machines hazardous. 

 
o  Furthermore, adequate analgesia may be difficult to achieve when administering a full opioid 

agonist in patients receiving buprenorphine/naloxone. Therefore the potential to overdose with 
a full agonist exists, especially when attempting to overcome buprenorphine partial agonist 
effects, or when buprenorphine plasma levels are declining.  

 
o naltrexone and nalmefene are opioid antagonists that can block the pharmacological effects of 

buprenorphine. Co-administration during buprenorphine/naloxone treatment is contraindicated 
due to the potentially dangerous interaction that may precipitate a sudden onset of prolonged 
and intense opioid withdrawal symptoms (see section 4.3). 

 
o CYP3A4 inhibitors: an interaction study of buprenorphine with ketoconazole (a potent 

inhibitor of CYP3A4) resulted in increased Cmax and AUC (area under the curve) of 
buprenorphine (approximately 50 % and 70 % respectively) and, to a lesser extent, of 
norbuprenorphine. Patients receiving Suboxone should be closely monitored, and may require 
dose-reduction if combined with potent CYP3A4 inhibitors (e.g. protease inhibitors like 
ritonavir, nelfinavir or indinavir or azole antifungals such as ketoconazole or itraconazole, 
macrolide antibiotics).  

 
o CYP3A4 inducers: Concomitant use of CYP3A4 inducers with buprenorphine may decrease 

buprenorphine plasma concentrations, potentially resulting in sub-optimal treatment of opioid 
dependence with buprenorphine. It is recommended that patients receiving 
buprenorphine/naloxone should be closely monitored if inducers (e.g. phenobarbital, 
carbamazepine, phenytoin, rifampicin) are co-administered. The dose of buprenorphine or the 
CYP3A4 inducer may need to be adjusted accordingly.  

 
o the concomitant use of monoamine oxidase inhibitors (MAOI) might produce exaggeration of 

the effects of opioids, based on experience with morphine. 
 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are no adequate data from the use of Suboxone in pregnant women.  Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. 
 
Towards the end of pregnancy buprenorphine may induce respiratory depression in the newborn infant 
even after a short period of administration. Long-term administration of buprenorphine during the last 
three months of pregnancy may cause a withdrawal syndrome in the neonate (e.g. hypertonia, neonatal 



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tremor, neonatal agitation, myoclonus or convulsions). The syndrome is generally delayed for several 
hours to several days after birth. 
 
Due to the long half-life of buprenorphine, neonatal monitoring for several days should be considered 
at the end of pregnancy, to prevent the risk of respiratory depression or withdrawal syndrome in 
neonates.  
 
Furthermore, the use of buprenorphine/naloxone during pregnancy should be assessed by the 
physician. Buprenorphine/naloxone should be used during pregnancy only if the potential benefit 
outweighs the potential risk to the foetus. 
 
Breast-feeding 
It is unknown whether naloxone is excreted in human breast milk. Buprenorphine and its metabolites 
are excreted in human breast milk. In rats buprenorphine has been found to inhibit lactation. 
Therefore, breastfeeding should be discontinued during treatment with Suboxone. 
 
Fertility 
Animal studies have shown a reduction in female fertility at high doses (systemic exposure > 2.4 times 
the human exposure at the maximum recommended dose of 24 mg buprenorphine, based on AUC). 
See section 5.3. 
 
 
4.7 Effects on ability to drive and use machines 
 
Buprenorphine/naloxone has minor to moderate influence on the ability to drive and use machines 
when administered to opioid dependent patients. This product may cause drowsiness, dizziness, or 
impaired thinking, especially during treatment induction and dose adjustment. If taken together with 
alcohol or central nervous system depressants, the effect is likely to be more pronounced (see sections 
4.4 and 4.5). 
 
Patients should be cautioned about driving or operating hazardous machinery in case 
buprenorphine/naloxone may affect their ability to engage in such activities. 
 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The most commonly reported treatment related adverse reactions reported during the pivotal clinical 
trials were constipation and symptoms commonly associated with drug withdrawal (i.e. insomnia, 
headache, nausea, hyperhidrosis and pain). Some reports of seizure, vomiting, diarrhoea, and elevated 
liver function tests were considered serious. 
 
Tabulated list of adverse reactions 
Table 1 summarises adverse reactions reported from pivotal clinical trials in which, 342 of 
472 patients (72.5 %) reported adverse reactions and adverse reactions reported during post-marketing 
surveillance.   
 
The frequency of possible side effects listed below is defined using the following convention:  
Very common (1/10), Common (1/100 to <1/10), Uncommon (1/1,000 to <1/100), Not known 
(cannot be estimated from available data). 
 
Table 1: Treatment-related adverse reactions reported in clinical trials and post-marketing 
surveillance of buprenorphine/naloxone 
 
System Organ 
Class 

Very common Common Uncommon Not Known 

Infections and  Influenza Urinary tract  



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infestations Infection 
Pharyngitis 
Rhinitis

infection 
Vaginal infection 

Blood and 
lymphatic system 
disorders 

  Anaemia 
Leukocytosis 
Leukopenia 
Lymphadenopathy 
Thrombocytopenia 

 

Immune system 
disorders 

  Hypersensitivity Anaphylactic 
shock 

Metabolism and 
nutrition 
disorders 

  Decreased appetite 
Hyperglycaemia 
Hyperlipidaemia 
Hypoglycaemia

 

Psychiatric 
disorders 

Insomnia 
 

Anxiety 
Depression 
Libido decreased 
Nervousness 
Thinking 
abnormal 

Abnormal dreams 
Agitation 
Apathy 
Depersonalisation 
Drug dependence 
Euphoric mood 
Hostility

Hallucination 

Nervous system 
disorders 

Headache Migraine 
Dizziness 
Hypertonia 
Paraesthesia 
Somnolence

Amnesia 
Hyperkinesia 
Seizure 
Speech disorder 
Tremor

Hepatic 
encephalopathy 
Syncope 

Eye disorders  Amblyopia 
Lacrimal disorder

Conjunctivitis 
Miosis

 

Ear and labyrinth 
disorders 

   Vertigo 

Cardiac disorders   Angina Pectoris 
Bradycardia 
Myocardial 
infarction 
Palpitations 
Tachycardia

 

Vascular 
disorders 

 Hypertension 
Vasodilatation

Hypotension Orthostatic 
hypotension

Respiratory, 
thoracic and 
mediastinal 
disorders 

 Cough Asthma 
Dyspnoea 
Yawning 

Bronchospasm 
Respiratory 
depression 

Gastrointestinal 
disorders 

Constipation 
Nausea 

Abdominal Pain 
Diarrhoea 
Dyspepsia 
Flatulence 
Vomiting

Mouth ulceration 
Tongue 
discolouration 

 

Hepatobiliary 
disorders 

   Hepatitis 
Hepatitis acute 
Jaundice 
Hepatic necrosis 
Hepatorenal 
syndrome 

Skin and 
subcutaneous 
tissue disorders 

Hyperhidrosis Pruritus 
Rash 
Urticaria 

Acne 
Alopecia 
Dermatitis 
exfoliative

Angioedema 



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Dry skin 
Skin mass

Musculoskeletal 
and connective 
tissue disorders 

 Back Pain 
Arthralgia 
Muscle spasms 
Myalgia

Arthritis  

Renal and urinary 
disorders 

 Urine 
Abnormality 
 

Albuminuria 
Dysuria 
Haematuria 
Nephrolithiasis 
Urinary retention 

 

Reproductive 
system and breast 
disorders 

 Erectile 
dysfunction 

Amenorrhoea 
Ejaculation 
disorder 
Menorrhagia 
Metrorrhagia

 

General disorders 
and 
administration 
site conditions 

Drug withdrawal 
syndrome 

Asthenia 
Chest Pain 
Chills 
Pyrexia 
Malaise 
Pain 
Oedema 
peripheral 

Hypothermia 
 

Drug withdrawal 
syndrome 
neonatal (see 
section 4.6) 

Investigations  Liver function test 
abnormal 
Weight decreased

Blood creatinine 
increased 

Transaminases 
increased 

Injury, poisoning 
and procedural 
complications 

 Injury Heat stroke  

 
Description of selected adverse reactions  
In cases of intravenous drug misuse, some adverse experiences are attributed to the act of misuse 
rather than the medicinal product and include local reactions, sometimes septic (abscess, cellulitis), 
and potentially serious acute hepatitis, and other acute infections such as pneumonia, endocarditis 
have been reported (see section 4.4). 
 
In patients presenting with marked drug dependence, initial administration of buprenorphine can 
produce a drug withdrawal syndrome similar to that associated with naloxone (see sections 4.2 and 
4.4). 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
 



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4.9 Overdose 
 
Symptoms 
Respiratory depression as a result of central nervous system depression is the primary symptom 
requiring intervention in the case of overdose because it may lead to respiratory arrest and death. Signs 
of overdose may also include somnolence, amblyopia, miosis, hypotension, nausea, vomiting and/or 
speech disorders. 
 
Management 
General supportive measures should be instituted, including close monitoring of respiratory and 
cardiac status of the patient.  Symptomatic treatment of respiratory depression, and standard intensive 
care measures, should be implemented. A patent airway and assisted or controlled ventilation must be 
assured. The patient should be transferred to an environment within which full resuscitation facilities 
are available. 
 
If the patient vomits, care must be taken to prevent aspiration of the vomitus. 
 
Use of an opioid antagonist (i.e., naloxone) is recommended, despite the modest effect it may have in 
reversing the respiratory symptoms of buprenorphine compared with its effects on full agonist opioid 
agents. 
 
If naloxone is used, the long duration of action of buprenorphine should be taken into consideration 
when determining the length of treatment and medical surveillance needed to reverse the effects of an 
overdose. Naloxone can be cleared more rapidly than buprenorphine, allowing for a return of 
previously controlled buprenorphine overdose symptoms, so a continuing infusion may be necessary. 
If infusion is not possible, repeated dosing with naloxone may be required.  Initial naloxone doses may 
range up to 2 mg and be repeated every 2-3 minutes until a satisfactory response is achieved, 
but should not exceed a 10 mg starting dose. Ongoing intravenous infusion rates should be titrated to 
patient response. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other nervous system drugs, drugs used in addictive disorders, ATC 
code: N07BC51. 
 
Mechanism of action 
Buprenorphine is an opioid partial agonist/antagonist which binds to the  and  (kappa) opioid 
receptors of the brain. Its activity in opioid maintenance treatment is attributed to its slowly reversible 
properties with the -opioid receptors which, over a prolonged period, might minimise the need of 
addicted patients for drugs. 
 
Opioid agonist ceiling effects were observed during clinical pharmacology studies in opioid-dependent 
persons. 
 
Naloxone is an antagonist at -opioid receptors. When administered orally or sublingually in usual 
doses to patients experiencing opioid withdrawal, naloxone exhibits little or no pharmacological effect 
because of its almost complete first pass metabolism. However, when administered intravenously to 
opioid-dependent persons, the presence of naloxone in Suboxone produces marked opioid antagonist 
effects and opioid withdrawal, thereby deterring intravenous abuse. 
 
Clinical efficacy 
Efficacy and safety data for buprenorphine/naloxone are primarily derived from a one-year clinical 
trial, comprising a 4-week randomised double blind comparison of buprenorphine/naloxone, 
buprenorphine and placebo followed by a 48 week safety study of buprenorphine/naloxone. In this 



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trial, 326 heroin-addicted subjects were randomly assigned to either buprenorphine/naloxone 16 mg 
per day, 16 mg buprenorphine per day or placebo. For subjects randomized to either active treatment, 
dosing began with 8 mg of buprenorphine on Day 1, followed by 16 mg (two 8 mg) of buprenorphine 
on Day 2. On Day 3, those randomized to receive buprenorphine/naloxone were switched to the 
combination tablet. Subjects were seen daily in the clinic (Monday through Friday) for dosing and 
efficacy assessments. Take-home doses were provided for weekends. The primary study comparison 
was to assess the efficacy of buprenorphine and buprenorphine/naloxone individually against placebo. 
The percentage of thrice-weekly urine samples that were negative for non-study opioids was 
statistically higher for both buprenorphine/naloxone versus placebo (p < 0.0001) and buprenorphine 
versus placebo (p < 0.0001). 
 
In a double-blind, double-dummy, parallel-group study comparing buprenorphine ethanolic solution to 
a full agonist active control, 162 subjects were randomized to receive the ethanolic sublingual solution 
of buprenorphine at 8 mg/day (a dose which is roughly comparable to a dose of 12 mg/day of 
buprenorphine/naloxone), or two relatively low doses of active control, one of which was low enough 
to serve as an alternative to placebo, during a 3 to10 day induction phase, a 16-week maintenance 
phase and a 7-week detoxification phase. Buprenorphine was titrated to maintenance dose by Day 3; 
active control doses were titrated more gradually. Based on retention in treatment and the percentage 
of thrice-weekly urine samples negative for non-study opioids, buprenorphine was more effective than 
the low dose of the control, in keeping heroin addicts in treatment and in reducing their use of opioids 
while in treatment. The effectiveness of buprenorphine, 8 mg per day was similar to that of the 
moderate active control dose, but equivalence was not demonstrated. 
 
 
5.2 Pharmacokinetic properties 
 
Buprenorphine 
 
Absorption 
Buprenorphine, when taken orally, undergoes first-pass metabolism with N-dealkylation and 
glucuroconjugation in the small intestine and the liver. The use of this medicinal product by the oral 
route is therefore inappropriate. 
 
Peak plasma concentrations are achieved 90 minutes after sublingual administration. Plasma levels of 
buprenorphine increased with the sublingual dose of buprenorphine/naloxone. Both Cmax and AUC of 
buprenorphine increased with the increase in dose (in the range of 4-16 mg), although the increase was 
less than dose-proportional.  
 
Pharmacokinetic Parameter 
 

Suboxone 4 mg Suboxone 8 mg Suboxone 16 mg 

Cmax ng/ml 
 

1.84 (39) 3.0 (51) 5.95 (38) 

AUC0-48   
hour ng/ml 

12.52 (35) 20.22 (43) 34.89 (33) 

 
Distribution 
The absorption of buprenorphine is followed by a rapid distribution phase (distribution half-life of 2 to 
5 hours). 
 
Biotransformation and elimination 
Buprenorphine is metabolised by 14-N-dealkylation and glucuroconjugation of the parent molecule 
and the dealkylated metabolite. Clinical data confirm that CYP3A4 is responsible for the N-
dealkylation of buprenorphine. N-dealkylbuprenorphine is a -opioid agonist with weak intrinsic 
activity. 
 
Elimination of buprenorphine is bi- or tri-exponential, and has a mean half-life from plasma of 
32 hours.  



13 

Buprenorphine is eliminated in the faeces by biliary excretion of the glucuroconjugated metabolites 
(70 %), the rest being eliminated in the urine. 
 
Naloxone 
 
Absorption and distribution  
Following intravenous administration, naloxone is rapidly distributed (distribution half-
life ~ 4 minutes). Following oral administration, naloxone is barely detectable in plasma; following 
sublingual administration of buprenorphine/naloxone, plasma naloxone concentrations are low and 
decline rapidly.  
 
Biotransformation  
The medicinal product is metabolized in the liver, primarily by glucuronide conjugation, and excreted 
in the urine. Naloxone has a mean half-life from plasma of 1.2 hours. 
 
Special populations 
 
Elderly 
No pharmacokinetic data in elderly patients are available. 
 
Renal impairment 
Renal elimination plays a relatively small role (~30 %) in the overall clearance of 
buprenorphine/naloxone. No dose modification based on renal function is required but caution is 
recommended when dosing subjects with severe renal impairment (see Section 4.3). 
 
Hepatic impairment 
The effect of hepatic impairment on the pharmacokinetics of buprenorphine and naloxone were 
evaluated in a post-marketing study.   
 
Table 3 summarizes the results from a clinical trial in which the exposure after single-dose 
administration of Suboxone 2.0/0.5mg (buprenorphine/naloxone) sublingual tablet was determined in 
healthy subjects, and in subjects with hepatic impairment. 
 

Table 3.  Effect of hepatic impairment on pharmacokinetic parameters of buprenorphine and 
naloxone following SUBOXONE administration (change relative to healthy subjects) 

PK Parameter 
Mild Hepatic Impairment 

(Child-Pugh Class A) 
(n=9) 

Moderate Hepatic 
Impairment 

(Child-Pugh Class B) 
(n=8) 

Severe Hepatic 
Impairment 

(Child-Pugh Class C) 
(n=8) 

Buprenorphine 

Cmax 1.2-fold increase 1.1-fold Increase 1.7-fold increase 

AUClast Similar to control 1.6-fold increase 2.8-fold increase 

 

Naloxone 

Cmax Similar to control 2.7-fold increase 11.3-fold increase 

AUClast  0.2-fold decrease 3.2-fold increase 14.0-fold increase 

 



14 

Overall, buprenorphine plasma exposure increased approximately 3-fold in patients with severely 
impaired hepatic function, while naloxone plasma exposure increased 14-fold with severely impaired 
hepatic function. 
 
 
5.3 Preclinical safety data 
 
The combination of buprenorphine and naloxone has been investigated in acute and repeated dose (up 
to 90 days in rats) toxicity studies in animals. No synergistic enhancement of toxicity has been 
observed. Undesirable effects were based on the known pharmacological activity of opioid agonistic 
and/or antagonistic substances.  
 
The combination (4:1) of buprenorphine hydrochloride and naloxone hydrochloride was not 
mutagenic in a bacterial mutation assay (Ames test), and was not clastogenic in an in vitro cytogenetic 
assay in human lymphocytes or in an intravenous micronucleus test in the rat. 
 
Reproduction studies by oral administration of buprenorphine: naloxone (ratio 1:1) indicated that 
embryolethality occurred in rats in the presence of maternal toxicity at all doses. The lowest dose 
studied represented exposure multiples of 1x for buprenorphine and 5x for naloxone at the maximum 
human therapeutic dose calculated on a mg/m² basis. No developmental toxicity was observed in 
rabbits at maternally toxic doses. Further, no teratogenicity has been observed in either rats or rabbits. 
A peri-postnatal study has not been conducted with buprenorphine/naloxone; however, maternal oral 
administration of buprenorphine at high doses during gestation and lactation resulted in difficult 
parturition (possible as a result of the sedative effect of buprenorphine), high neonatal mortality and a 
slight delay in the development of some neurological functions (surface righting reflex and startle 
response) in neonatal rats. 
 
Dietary administration of buprenorphine in the rat at dose levels of 500 ppm or greater produced a 
reduction in fertility demonstrated by reduced female conception rates. A dietary dose of 100 ppm 
(estimated exposure approximately 2.4x for buprenorphine at a human dose of 24 mg 
buprenorphine/naloxone based on AUC, plasma levels of naloxone were below the limit of detection 
in rats) had no adverse effect on fertility in females. 
 
A carcinogenicity study with buprenorphine/naloxone was conducted in rats at doses of 7, 30 and 
120 mg/kg/day, with estimated exposure multiples of 3 to 75 times, based on a human daily sublingual 
dose of 16 mg calculated on a mg/m² basis. Statistically significant increases in the incidence of 
benign testicular interstitial (Leydig's) cell adenomas were observed in all dosage groups.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Lactose monohydrate 
Mannitol 
Maize starch 
Povidone K 30 
Citric acid anhydrous 
Sodium citrate 
Magnesium stearate 
Acesulfame potassium 
Natural lemon and lime flavour 
 
 
6.2 Incompatibilities 
 
Not applicable. 



15 

 
 
6.3 Shelf life 
 
3 years. 
 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
 
6.5 Nature and contents of container 
 
7 tablets in blister packs Paper/Aluminium/Nylon/Aluminium/PVC. 
 
28 tablets in blister packs Paper/Aluminium/Nylon/Aluminium/PVC. 
 
Not all pack sizes may be marketed. 
 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Indivior Europe Limited  
27 Windsor Place 
Dublin 2 
Ireland 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/359/001 
EU/1/06/359/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 26 September 2006 
Date of latest renewal: 16 September 2011 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this product is available on the website of the European Medicines Agency 
http://www.ema.europa.eu/ 
 



16 

1. NAME OF THE MEDICINAL PRODUCT 
 
Suboxone 8 mg/2 mg sublingual tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each sublingual tablet contains 8 mg buprenorphine (as hydrochloride) and 2 mg naloxone (as 
hydrochloride dihydrate).  
 
Excipients with known effect:  
Each sublingual tablet contains 168 mg lactose (as monohydrate) 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Sublingual tablet 
White hexagonal biconvex tablets of 11 mm with “N8” debossed on one side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Substitution treatment for opioid drug dependence, within a framework of medical, social and 
psychological treatment. The intention of the naloxone component is to deter intravenous misuse. 
Treatment is intended for use in adults and adolescents over 15 years of age who have agreed to be 
treated for addiction. 
 
 
4.2 Posology and method of administration 
 
Treatment must be under the supervision of a physician experienced in the management of opiate 
dependence/addiction.  
 
Precautions to be taken before induction 
 
Prior to treatment initiation, consideration should be given to the type of opioid dependence (i.e. long- 
or short-acting opioid), the time since last opioid use and the degree of opioid dependence. To avoid 
precipitating withdrawal, induction with buprenorphine/naloxone or buprenorphine only should be 
undertaken when objective and clear signs of withdrawal are evident (demonstrated e.g. by a score 
indicating mild to moderate withdrawal on the validated Clinical Opioid Withdrawal Scale, COWS).  

o For patients dependent upon heroin or short-acting opioids, the first dose of 
buprenorphine/naloxone should be taken when signs of withdrawal appear, but not less than 
6 hours after the patient last used opioids. 

o For patients receiving methadone, the dose of methadone should be reduced to a maximum of 
30 mg/day before beginning buprenorphine/naloxone therapy. The long half life of methadone 
should be considered when starting buprenorphine/naloxone. The first dose of 
buprenorphine/naloxone should be taken only when signs of withdrawal appear, but not less 
than 24 hours after the patient last used methadone. Buprenorphine may precipitate symptoms 
of withdrawal in patients dependent upon methadone.  

 

Posology 



17 

 
Initiation therapy (induction) 
The recommended starting dose in adults and adolescents over 15 years of age is one to two Suboxone 
2 mg/0.5 mg.  An additional one to two Suboxone 2 mg/0.5 mg may be administered on day one 
depending on the individual patient’s requirement.  
During the initiation of treatment, daily supervision of dosing is recommended to ensure proper 
sublingual placement of the dose and to observe patient response to treatment as a guide to effective 
dose titration according to clinical effect.   
 
Dosage adjustment and maintenance therapy 
Following treatment induction on day one, the patient should be stabilised to a maintenance dose 
during the next few days by progressively adjusting the dose according to the clinical effect of the 
individual patient.  Dose titration in steps of 2-8 mg buprenorphine is guided by reassessment of the 
clinical and psychological status of the patient, and should not exceed a maximum single daily dose of 
24 mg buprenorphine.  
 
Less than daily dosing  
After a satisfactory stabilisation has been achieved the frequency of dosing may be decreased to 
dosing every other day at twice the individually titrated daily dose. For example, a patient stabilised to 
receive a daily dose of 8 mg buprenorphine may be given 16 mg buprenorphine on alternate days, with 
no dose on the intervening days. In some patients, after a satisfactory stabilisation has been achieved, 
the frequency of dosing may be decreased to 3 times a week (for example on Monday, Wednesday and 
Friday). The dose on Monday and Wednesday should be twice the individually titrated daily dose, and 
the dose on Friday should be three times the individually titrated daily dose, with no dose on the 
intervening days. However, the dose given on any one day should not exceed 24 mg buprenorphine. 
Patients requiring a titrated daily dose> 8 mg buprenorphine /day may not find this regimen adequate. 
 
Medical withdrawal  
After a satisfactory stabilisation has been achieved, if the patient agrees, the dosage may be reduced 
gradually to a lower maintenance dose; in some favourable cases, treatment may be discontinued. The 
availability of doses of 2 mg/0.5 mg and 8 mg/2 mg allows for a downward titration of dosage. For 
patients who may require a lower buprenorphine dose, buprenorphine 0.4 mg may be used. Patients 
should be monitored following medical withdrawal because of the potential for relapse. 
 
Special populations 
 
Elderly 
The safety and efficacy of buprenorphine/naloxone in elderly patients over 65 years of age have not 
been established. No recommendation on posology can be made. 
 
Hepatic impairment 
Baseline liver function tests and documentation of viral hepatitis status is recommended prior to 
commencing therapy. Patients who are positive for viral hepatitis, on concomitant medicinal products 
(see section 4.5) and/or have existing liver dysfunction are at risk of accelerated liver injury. Regular 
monitoring of liver function is recommended (see section 4.4).  
Both active substances of Suboxone, buprenorphine and naloxone, are extensively metabolized in the 
liver, and the plasma levels were found to be higher for both buprenorphine and naloxone in patients 
with moderate and severe hepatic impairment. Patients should be monitored for signs and symptoms 
of precipitated opioid withdrawal, toxicity or overdose caused by increased levels of naloxone and/or 
buprenorphine.  
As buprenorphine/naloxone pharmacokinetics may be altered in patients with hepatic impairment, 
lower initial doses and careful dose titration in patients with mild to moderate hepatic impairment are 
recommended. Buprenorphine/naloxone is contraindicated in patients with severe hepatic impairment. 
(see section 4.3 and 5.2).  
 
Renal impairment 



18 

Modification of the buprenorphine/naloxone dose is not required in patients with renal impairment. 
Caution is recommended when dosing patients with severe renal impairment (creatinine 
clearance < 30 ml/min) (see section 4.4 and 5.2). 
 
Paediatric population 
The safety and efficacy of buprenorphine/naloxone in children below the age of 15 years have not 
been established. No data are available. 
 
Method of administration 
Physicians must warn patients that the sublingual route is the only effective and safe route of 
administration for this medicinal product (see section 4.4). The tablet is to be placed under the tongue 
until completely dissolved. Patients should not swallow or consume food or drink until the tablet is 
completely dissolved.  
 
The dose is made up from multiple Suboxone tablets of different strengths, which may be taken all at 
the same time or in two divided portions; the second portion to be taken directly after the first portion 
has dissolved.  
 
 
4.3 Contraindications 
 
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. 
Severe respiratory insufficiency 
Severe hepatic impairment  
Acute alcoholism or delirium tremens. 
Concomitant administration of opioid antagonists (naltrexone, nalmefene) for the treatment of alcohol 
or opioid dependence. 
 
 
4.4 Special warnings and precautions for use 
 
Misuse, abuse and diversion 
Buprenorphine can be misused or abused in a manner similar to other opioids, legal or illicit. Some 
risks of misuse and abuse include overdose, spread of blood borne viral or localised and systemic 
infections, respiratory depression and hepatic injury. Buprenorphine misuse by someone other than the 
intended patient poses the additional risk of new drug dependent individuals using buprenorphine as 
the primary drug of abuse, and may occur if the medicine is distributed for illicit use directly by the 
intended patient or if the medicinal product is not safeguarded against theft.  
 
Sub-optimal treatment with buprenorphine/naloxone may prompt medicine misuse by the patient, 
leading to overdose or treatment dropout. A patient who is under-dosed with buprenorphine/naloxone 
may continue responding to uncontrolled withdrawal symptoms by self-medicating with opioids, 
alcohol or other sedative-hypnotics such as benzodiazepines. 
 
To minimize the risk of misuse, abuse and diversion, physicians should take appropriate precautions 
when prescribing and dispensing buprenorphine, such as to avoid prescribing multiple refills early in 
treatment, and to conduct patient follow-up visits with clinical monitoring that is appropriate to the 
patient's needs.  
 
Combining buprenorphine with naloxone in Suboxone is intended to deter misuse and abuse of the 
buprenorphine. Intravenous or intranasal misuse of Suboxone is expected to be less likely than 
buprenorphine alone since the naloxone in Suboxone can precipitate withdrawal in individuals 
dependent on heroin, methadone, or other opioid agonists.  
 
Respiratory depression 
A number of cases of death due to respiratory depression have been reported, particularly when 
buprenorphine was used in combination with benzodiazepines (see section 4.5) or when 



19 

buprenorphine was not used according to prescribing information.  Deaths have also been reported in 
association with concomitant administration of buprenorphine and other depressants such as alcohol or 
other opioids. If buprenorphine is administered to some non-opioid dependent individuals, who are not 
tolerant to the effects of opioids, potentially fatal respiratory depression may occur. 
 
This product should be used with care in patients with asthma or respiratory insufficiency (e.g. chronic 
obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, 
pre-existing respiratory depression or kyphoscoliosis (curvature of spine leading to potential shortness 
of breath)). 
 
Buprenorphine/naloxone may cause severe, possibly fatal, respiratory depression in children and non-
dependent persons in case of accidental or deliberate ingestion. Patients must be warned to store the 
blister safely, to never open the blister in advance, to keep them out of the reach of children and other 
household members, and not to take this medicine in front of children. An emergency unit should be 
contacted immediately in case of accidental ingestion or suspicion of ingestion. 
 
CNS depression 
Buprenorphine/naloxone may cause drowsiness, particularly when taken together with alcohol or 
central nervous system depressants (such as tranquilisers, sedatives or hypnotics) (see section 4.5). 
 
Dependence 
Buprenorphine is a partial agonist at the µ (mu)-opiate receptor and chronic administration produces 
dependence of the opioid type.  Studies in animals, as well as clinical experience, have demonstrated 
that buprenorphine may produce dependence, but at a lower level than a full agonist e.g. morphine.  
 
Abrupt discontinuation of treatment is not recommended as it may result in a withdrawal syndrome 
that may be delayed in onset. 
 
Hepatitis and hepatic events 
Cases of acute hepatic injury have been reported in opioid-dependent addicts both in clinical trials and 
in post marketing adverse reaction reports. The spectrum of abnormalities ranges from transient 
asymptomatic elevations in hepatic transaminases to case reports of hepatic failure, hepatic necrosis, 
hepatorenal syndrome, hepatic encephalopathy and death. In many cases the presence of pre-existing 
mitochondrial impairment (genetic disease, liver enzyme abnormalities, infection with hepatitis B or 
hepatitis C virus, alcohol abuse, anorexia concomitant use of other potentially hepatotoxic medicines) 
and ongoing injecting drug use may have a causative or contributory role. These underlying factors 
must be taken into consideration before prescribing buprenorphine/naloxone and during treatment. 
When a hepatic event is suspected, further biological and etiological evaluation is required. Depending 
upon the findings, the medicinal product may be discontinued cautiously so as to prevent withdrawal 
symptoms and to prevent a return to illicit drug use. If the treatment is continued, hepatic function 
should be monitored closely. 
 
Precipitation of opioid withdrawal syndrome  
When initiating treatment with buprenorphine/naloxone, the physician must be aware of the partial 
agonist profile of buprenorphine and that it can precipitate withdrawal in opioid-dependent patients, 
particularly if administered less than 6 hours after the last use of heroin or other short-acting opioid, or 
if administered less than 24 hours after the last dose of methadone. Patients should be clearly 
monitored during the switching period from buprenorphine or methadone to buprenorphine/naloxone 
since withdrawal symptoms have been reported. To avoid precipitating withdrawal, induction with 
buprenorphine/naloxone should be undertaken when objective signs of withdrawal are evident (see 
section 4.2). 
 
Withdrawal symptoms may also be associated with sub-optimal dosing. 
 
Hepatic impairment 
The effect of hepatic impairment on the pharmacokinetics of buprenorphine and naloxone were 
evaluated in a post-marketing study.  Since both buprenorphine and naloxone are extensively 



20 

metabolized, plasma levels were found to be higher for both buprenorphine and naloxone in patients 
with moderate and severe hepatic impairment after single-dose administration.  Patients should be 
monitored for signs and symptoms of precipitated opioid withdrawal, toxicity or overdose caused by 
increased levels of naloxone and/or buprenorphine.  Suboxone sublingual tablets should be used with 
caution in patients with moderate hepatic impairment (See section 4.3 and 5.2). In patients with severe 
hepatic insufficiency the use of buprenorphine/naloxone is contraindicated. 
 
Renal impairment 
Renal elimination may be prolonged since 30 % of the administered dose is eliminated by the renal 
route. Metabolites of buprenorphine accumulate in patients with renal failure. Caution is 
recommended when dosing patients with severe renal impairment (creatinine clearance <30 ml/min) 
(see sections 4.2 and 5.2). 
 
Use in adolescents (Age 15-<18) 
Due to the lack of data in adolescents (age 15-<18), patients in this age group should be more closely 
monitored during treatment.  
 
CYP 3A inhibitors 
Medicines that inhibit the enzyme CYP3A4 may give rise to increased concentrations of 
buprenorphine. A reduction of the buprenorphine/naloxone dose may be needed. Patients already 
treated with CYP3A4 inhibitors should have their dose of buprenorphine/naloxone titrated carefully 
since a reduced dose may be sufficient in these patients (see section 4.5). 
 
 
 
General warnings relevant to the administration of opioids  
Opioids may produce orthostatic hypotension in ambulatory patients. 
 
Opioids may elevate cerebrospinal fluid pressure, which may cause seizures, so opioids should be used 
with caution in patients with head injury, intracranial lesions, other circumstances where cerebrospinal 
pressure may be increased, or history of seizure. 
 
Opioids should be used with caution in patients with hypotension, prostatic hypertrophy or urethral 
stenosis. 
 
Opioid-induced miosis, changes in the level of consciousness, or changes in the perception of pain as a 
symptom of disease may interfere with patient evaluation or obscure the diagnosis or clinical course of 
concomitant disease. 
 
Opioids should be used with caution in patients with myxoedema, hypothyroidism, or adrenal cortical 
insufficiency (e.g., Addison's disease). 
 
Opioids have been shown to increase intracholedochal pressure, and should be used with caution in 
patients with dysfunction of the biliary tract. 
 
Opioids should be administered with caution to elderly or debilitated patients. 
 
The concomitant use of monoamine oxidase inhibitors (MAOI) might produce an exaggeration of the 
effects of opioids, based on experience with morphine (see section 4.5). 
 
Suboxone contains lactose.  Patients with rare hereditary problems of galactose intolerance, should not 
take this medicine. 
 
 



21 

4.5 Interaction with other medicinal products and other forms of interaction 
 
Suboxone should not be taken together with: 
 
 alcoholic drinks or medicines containing alcohol, as alcohol increases the sedative effect of 

buprenorphine (see section 4.7). 
 
Suboxone should be used cautiously when co-administered with: 
 

o benzodiazepines: This combination may result in death due to respiratory depression of central 
origin. Therefore, dosages must be limited and this combination must be avoided in cases 
where there is a risk of misuse. Patients should be warned that it is extremely dangerous to 
self-administer non-prescribed benzodiazepines while taking this product, and should also be 
cautioned to use benzodiazepines concurrently with this product only as directed by their 
physician (see section 4.4). 

 
o other central nervous system depressants, other opioid derivatives (e.g. methadone, analgesics 

and antitussives), certain antidepressants, sedative H1-receptor antagonists, barbiturates, 
anxiolytics other than benzodiazepines, neuroleptics, clonidine and related substances: these 
combinations increase central nervous system depression. The reduced level of alertness can 
make driving and using machines hazardous. 

 
o  Furthermore, adequate analgesia may be difficult to achieve when administering a full opioid 

agonist in patients receiving buprenorphine/naloxone. Therefore the potential to overdose with 
a full agonist exists, especially when attempting to overcome buprenorphine partial agonist 
effects, or when buprenorphine plasma levels are declining.  

 
o naltrexone and nalmefene are opioid antagonists that can block the pharmacological effects of 

buprenorphine. Co-administration during buprenorphine/naloxone treatment is contraindicated 
due to the potentially dangerous interaction that may precipitate a sudden onset of prolonged 
and intense opioid withdrawal symptoms (see section 4.3). 

 
o CYP3A4 inhibitors: an interaction study of buprenorphine with ketoconazole (a potent 

inhibitor of CYP3A4) resulted in increased Cmax and AUC (area under the curve) of 
buprenorphine (approximately 50 % and 70 % respectively) and, to a lesser extent, of 
norbuprenorphine. Patients receiving Suboxone should be closely monitored, and may require 
dose-reduction if combined with potent CYP3A4 inhibitors (e.g. protease inhibitors like 
ritonavir, nelfinavir or indinavir or azole antifungals such as ketoconazole or itraconazole, 
macrolide antibiotics). 

 
o CYP3A4 inducers: Concomitant use of CYP3A4 inducers with buprenorphine may decrease 

buprenorphine plasma concentrations, potentially resulting in sub-optimal treatment of opioid 
dependence with buprenorphine. It is recommended that patients receiving 
buprenorphine/naloxone should be closely monitored if inducers (e.g. phenobarbital, 
carbamazepine, phenytoin, rifampicin) are co-administered. The dose of buprenorphine or the 
CYP3A4 inducer may need to be adjusted accordingly.  

 
o the concomitant use of monoamine oxidase inhibitors (MAOI) might produce exaggeration of 

the effects of opioids, based on experience with morphine. 
 

 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are no adequate data from the use of Suboxone in pregnant women.  Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. 
 



22 

Towards the end of pregnancy buprenorphine may induce respiratory depression in the newborn infant 
even after a short period of administration. Long-term administration of buprenorphine during the last 
three months of pregnancy may cause a withdrawal syndrome in the neonate (e.g. hypertonia, neonatal 
tremor, neonatal agitation, myoclonus or convulsions). The syndrome is generally delayed from 
several hours to several days after birth. 
 
Due to the long half-life of buprenorphine, neonatal monitoring for several days should be considered 
at the end of pregnancy, to prevent the risk of respiratory depression or withdrawal syndrome in 
neonates. 
 
Furthermore, the use of buprenorphine/naloxone during pregnancy should be assessed by the 
physician. Buprenorphine/naloxone should be used during pregnancy only if the potential benefit 
outweighs the potential risk to the foetus. 
 
Breast-feeding 
It is unknown whether naloxone is excreted in human breast milk. Buprenorphine and its metabolites 
are excreted in human breast milk. In rats buprenorphine has been found to inhibit lactation. 
Therefore, breastfeeding should be discontinued during treatment with Suboxone. 
 
Fertility 
Animal studies have shown a reduction in female fertility at high doses (systemic exposure > 2.4 times 
the human exposure at the maximum recommended dose of 24 mg buprenorphine, based on AUC). 
See section 5.3. 
 
 
4.7 Effects on ability to drive and use machines 
 
Buprenorphine/naloxone has minor to moderate influence on the ability to drive and use machines 
when administered to opioid dependent patients. This product may cause drowsiness, dizziness, or 
impaired thinking, especially during treatment induction and dose adjustment. If taken together with 
alcohol or central nervous system depressants, the effect is likely to be more pronounced (see sections 
4.4 and 4.5). 
 
Patients should be cautioned about driving or operating hazardous machinery in case 
buprenorphine/naloxone may affect their ability to engage in such activities. 
 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The most commonly reported treatment related adverse reactions reported during the pivotal clinical 
trials were constipation and symptoms commonly associated with drug withdrawal (i.e. insomnia, 
headache, nausea, hyperhidrosis and pain). Some reports of seizure, vomiting, diarrhoea, and elevated 
liver function tests were considered serious. 
 
Tabulated list of adverse reactions 
Table 1 summarises adverse reactions reported from pivotal clinical trials in which, 342 of 
472 patients (72.5 %) reported adverse reactions and adverse reactions reported during post-marketing 
surveillance.   
 
The frequency of possible side effects listed below is defined using the following convention:  
Very common (1/10), Common (1/100 to <1/10), Uncommon (1/1,000 to <1/100), Not known 
(cannot be estimated from available data).  



23 

 
Table 1: Treatment-related adverse reactions reported in clinical trials and post-marketing 
surveillance of buprenorphine/naloxone 
 
System Organ 
Class 

Very common Common Uncommon Not Known 

Infections and 
infestations 

 Influenza 
Infection 
Pharyngitis 
Rhinitis

Urinary tract 
infection 
Vaginal infection 

 

Blood and 
lymphatic system 
disorders 

  Anaemia 
Leukocytosis 
Leukopenia 
Lymphadenopathy 
Thrombocytopenia

 

Immune system 
disorders 

  Hypersensitivity Anaphylactic shock 

Metabolism and 
nutrition disorders 

  Decreased appetite 
Hyperglycaemia 
Hyperlipidaemia 
Hypoglycaemia

 

Psychiatric 
disorders 

Insomnia Anxiety 
Depression 
Libido 
decreased 
Nervousness 
Thinking 
abnormal

Abnormal dreams 
Agitation 
Apathy 
Depersonalisation 
Drug dependence 
Euphoric mood 
Hostility

Hallucination 

Nervous system 
disorders 

Headache Migraine 
Dizziness 
Hypertonia 
Paraesthesia 
Somnolence

Amnesia 
Hyperkinesia 
Seizure 
Speech disorder 
Tremor

Hepatic 
encephalopathy 
Syncope 
 

Eye disorders  Amblyopia 
Lacrimal 
disorder

Conjunctivitis 
Miosis 

 

Ear and labyrinth 
disorders 

   Vertigo 

Cardiac disorders   Angina Pectoris 
Bradycardia 
Myocardial 
infarction 
Palpitations 
Tachycardia

 

Vascular disorders  Hypertension 
Vasodilatation

Hypotension Orthostatic 
hypotension 

Respiratory, 
thoracic and 
mediastinal 
disorders 

 Cough Asthma 
Dyspnoea 
Yawning 

Bronchospasm 
Respiratory 
depression 
 

Gastrointestinal 
disorders 

Constipation 
Nausea 

Abdominal 
Pain 
Diarrhoea 
Dyspepsia 
Flatulence 
Vomiting

Mouth ulceration 
Tongue 
discolouration 

 

Hepatobiliary  Hepatitis 



24 

disorders Hepatitis acute 
Jaundice 
Hepatic necrosis 
Hepatorenal 
syndrome 

Skin and 
subcutaneous tissue 
disorders 

Hyperhidrosis Pruritus 
Rash 
Urticaria 

Acne 
Alopecia 
Dermatitis 
exfoliative 
Dry skin 
Skin mass

Angioedema 

Musculoskeletal and 
connective tissue 
disorders 

 Back Pain 
Arthralgia 
Muscle spasms 
Myalgia

Arthritis  

Renal and urinary 
disorders 

 Urine 
Abnormality 
 

Albuminuria 
Dysuria 
Haematuria 
Nephrolithiasis 
Urinary retention

 

Reproductive system 
and breast disorders 

 Erectile 
dysfunction 

Amenorrhoea 
Ejaculation 
disorder 
Menorrhagia 
Metrorrhagia

 

General disorders 
and administration 
site conditions 

Drug 
withdrawal 
syndrome 

Asthenia 
Chest Pain 
Chills 
Pyrexia 
Malaise 
Pain 
Oedema 
peripheral 

Hypothermia Drug withdrawal 
syndrome neonatal 
(see section 4.6) 

Investigations  Liver function 
test abnormal 
Weight 
decreased

Blood creatinine 
increased 

Transaminases 
increased 

Injury, poisoning 
and procedural 
complications 

 Injury Heat stroke  

 
Description of selected adverse reactions  
In cases of intravenous drug misuse, some adverse experiences are attributed to the act of misuse 
rather than the medicinal product and include local reactions, sometimes septic (abscess, cellulitis), 
and potentially serious acute hepatitis and other acute infections such as pneumonia, endocarditis have 
been reported (see section 4.4). 
 
In patients presenting with marked drug dependence, initial administration of buprenorphine can 
produce a drug withdrawal syndrome similar to that associated with naloxone (see sections 4.2 and 
4.4). 
 



25 

Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
 
4.9 Overdose 
 
Symptoms 
Respiratory depression as a result of central nervous system depression is the primary symptom 
requiring intervention in the case of overdose because it may lead to respiratory arrest and death. Signs 
of overdose may also include somnolence, amblyopia, miosis, hypotension, nausea, vomiting and/or 
speech disorders. 
 
Management 
General supportive measures should be instituted, including close monitoring of respiratory and 
cardiac status of the patient.  Symptomatic treatment of respiratory depression, and standard intensive 
care measures, should be implemented. A patent airway and assisted or controlled ventilation must be 
assured. The patient should be transferred to an environment within which full resuscitation facilities 
are available. 
 
If the patient vomits, care must be taken to prevent aspiration of the vomitus. 
 
Use of an opioid antagonist (i.e., naloxone) is recommended, despite the modest effect it may have in 
reversing the respiratory symptoms of buprenorphine compared with its effects on full agonist opioid 
agents. 
 
If naloxone is used, the long duration of action of buprenorphine should be taken into consideration 
when determining the length of treatment and medical surveillance needed to reverse the effects of an 
overdose. Naloxone can be cleared more rapidly than buprenorphine, allowing for a return of 
previously controlled buprenorphine overdose symptoms, so a continuing infusion may be necessary. 
If infusion is not possible, repeated dosing with naloxone may be required.  Initial naloxone doses may 
range up to 2 mg and be repeated every 2-3 minutes until a satisfactory response is achieved, 
but should not exceed a 10 mg starting dose. Ongoing intravenous infusion rates should be titrated to 
patient response. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other nervous system drugs, drugs used in addictive disorders, ATC 
code: N07BC51. 
 
Mechanism of action 
Buprenorphine is an opioid partial agonist/antagonist which binds to the  and  (kappa) opioid 
receptors of the brain. Its activity in opioid maintenance treatment is attributed to its slowly reversible 
properties with the -opioid receptors which, over a prolonged period, might minimise the need of 
addicted patients for drugs. 
 
Opioid agonist ceiling effects were observed during clinical pharmacology studies in opioid-dependent 
persons. 
 
Naloxone is an antagonist at -opioid receptors. When administered orally or sublingually in usual 
doses to patients experiencing opioid withdrawal, naloxone exhibits little or no pharmacological effect 
because of its almost complete first pass metabolism. However, when administered intravenously to 



26 

opioid-dependent persons, the presence of naloxone in Suboxone produces marked opioid antagonist 
effects and opioid withdrawal, thereby deterring intravenous abuse. 
 
Clinical efficacy 
Efficacy and safety data for buprenorphine/naloxone are primarily derived from a one-year clinical 
trial, comprising a 4-week randomised double blind comparison of buprenorphine/naloxone, 
buprenorphine and placebo followed by a 48 week safety study of buprenorphine/naloxone. In this 
trial, 326 heroin-addicted subjects were randomly assigned to either buprenorphine/naloxone 16 mg 
per day, 16 mg buprenorphine per day or placebo. For subjects randomized to either active treatment, 
dosing began with 8 mg of buprenorphine on Day 1, followed by 16 mg (two 8 mg) of buprenorphine 
on Day 2. On Day 3, those randomized to receive buprenorphine/naloxone were switched to the 
combination tablet. Subjects were seen daily in the clinic (Monday through Friday) for dosing and 
efficacy assessments. Take-home doses were provided for weekends. The primary study comparison 
was to assess the efficacy of buprenorphine and buprenorphine/naloxone individually against placebo. 
The percentage of thrice-weekly urine samples that were negative for non-study opioids was 
statistically higher for both buprenorphine/naloxone versus placebo (p < 0.0001) and buprenorphine 
versus placebo (p < 0.0001). 
 
In a double-blind, double-dummy, parallel-group study comparing buprenorphine ethanolic solution to 
a full agonist active control, 162 subjects were randomized to receive the ethanolic sublingual solution 
of buprenorphine at 8 mg/day (a dose which is roughly comparable to a dose of 12 mg/day of 
buprenorphine/naloxone), or two relatively low doses of active control, one of which was low enough 
to serve as an alternative to placebo, during a 3 to10 day induction phase, a 16-week maintenance 
phase and a 7-week detoxification phase. Buprenorphine was titrated to maintenance dose by Day 3; 
active control doses were titrated more gradually. Based on retention in treatment and the percentage 
of thrice-weekly urine samples negative for non-study opioids, buprenorphine was more effective than 
the low dose of the control, in keeping heroin addicts in treatment and in reducing their use of opioids 
while in treatment. The effectiveness of buprenorphine, 8 mg per day was similar to that of the 
moderate active control dose, but equivalence was not demonstrated. 
 
 
5.2 Pharmacokinetic properties 
 
Buprenorphine 
 
Absorption 
Buprenorphine, when taken orally, undergoes first-pass metabolism with N-dealkylation and 
glucuroconjugation in the small intestine and the liver. The use of this medicinal product by the oral 
route is therefore inappropriate. 
 
Peak plasma concentrations are achieved 90 minutes after sublingual administration. Plasma levels of 
buprenorphine increased with the sublingual dose of buprenorphine/naloxone. Both Cmax and AUC of 
buprenorphine increased with the increase in dose (in the range of 4-16 mg), although the increase was 
less than dose-proportional.  
 
 
Pharmacokinetic Parameter 
 

Suboxone 4 mg Suboxone 8 mg Suboxone 16 mg 

Cmax ng/ml 
 

1.84 (39) 3.0 (51) 5.95 (38) 

AUC0-48   
hour ng/ml 

12.52 (35) 20.22 (43) 34.89 (33) 

 
Distribution 
The absorption of buprenorphine is followed by a rapid distribution phase (distribution half-life of 2 to 
5 hours). 
 



27 

Biotransformation and elimination 
Buprenorphine is metabolised by 14-N-dealkylation and glucuroconjugation of the parent molecule 
and the dealkylated metabolite. Clinical data confirm that CYP3A4 is responsible for the N-
dealkylation of buprenorphine. N-dealkylbuprenorphine is a -opioid agonist with weak intrinsic 
activity. 
 
Elimination of buprenorphine is bi- or tri-exponential, and has a mean half-life from plasma of 
32 hours.  
Buprenorphine is eliminated in the faeces by biliary excretion of the glucuroconjugated metabolites 
(70 %), the rest being eliminated in the urine. 
 
Naloxone 
 
Absorption and distribution:  
Following intravenous administration, naloxone is rapidly distributed (distribution half-
life ~ 4 minutes). Following oral administration, naloxone is barely detectable in plasma; following 
sublingual administration of buprenorphine/naloxone, plasma naloxone concentrations are low and 
decline rapidly.  
 
Biotransformation  
The medicinal product is metabolized in the liver, primarily by glucuronide conjugation, and excreted 
in the urine. Naloxone has a mean half-life from plasma of 1.2 hours. 
 
Special populations 
 
Elderly 
No pharmacokinetic data in elderly patients are available. 
 
Renal impairment 
Renal elimination plays a relatively small role (~30 %) in the overall clearance of 
buprenorphine/naloxone. No dose modification based on renal function is required but caution is 
recommended when dosing subjects with severe renal impairment (see Section 4.3). 
 
Hepatic impairment 
The effect of hepatic impairment on the pharmacokinetics of buprenorphine and naloxone were 
evaluated in a post-marketing study.   
 



28 

Table 3 summarizes the results from a clinical trial in which the exposure after single-dose 
administration of Suboxone 2.0/0.5mg (buprenorphine/naloxone) sublingual tablet was determined in 
healthy subjects, and in subjects with hepatic impairment. 
 

Table 3.  Effect of hepatic impairment on pharmacokinetic parameters of buprenorphine and 
naloxone following SUBOXONE administration (change relative to healthy subjects) 

PK Parameter 
Mild Hepatic Impairment 

(Child-Pugh Class A) 
(n=9) 

Moderate Hepatic 
Impairment 

(Child-Pugh Class B) 
(n=8) 

Severe Hepatic 
Impairment 

(Child-Pugh Class C) 
(n=8) 

Buprenorphine 

Cmax 1.2-fold increase 1.1-fold Increase 1.7-fold increase 

AUClast Similar to control 1.6-fold increase 2.8-fold increase 

 

Naloxone 

Cmax Similar to control 2.7-fold increase 11.3-fold increase 

AUClast  0.2-fold decrease 3.2-fold increase 14.0-fold increase 

 
Overall, buprenorphine plasma exposure increased approximately 3-fold in patients with severely 
impaired hepatic function, while naloxone plasma exposure increased 14-fold with severely impaired 
hepatic function. 
 
 
5.3 Preclinical safety data 
 
The combination of buprenorphine and naloxone has been investigated in acute and repeated dose (up 
to 90 days in rats) toxicity studies in animals. No synergistic enhancement of toxicity has been 
observed. Undesirable effects were based on the known pharmacological activity of opioid agonistic 
and/or antagonistic substances.  
 
The combination (4:1) of buprenorphine hydrochloride and naloxone hydrochloride was not 
mutagenic in a bacterial mutation assay (Ames test), and was not clastogenic in an in vitro cytogenetic 
assay in human lymphocytes or in an intravenous micronucleus test in the rat. 
 
Reproduction studies by oral administration of buprenorphine: naloxone (ratio 1:1) indicated that 
embryolethality occurred in rats in the presence of maternal toxicity at all doses. The lowest dose 
studied represented exposure multiples of 1x for buprenorphine and 5x for naloxone at the maximum 
human therapeutic dose calculated on a mg/m² basis. No developmental toxicity was observed in 
rabbits at maternally toxic doses. Further, no teratogenicity has been observed in either rats or rabbits. 
A peri-postnatal study has not been conducted with buprenorphine/naloxone; however, maternal oral 
administration of buprenorphine at high doses during gestation and lactation resulted in difficult 
parturition (possible as a result of the sedative effect of buprenorphine), high neonatal mortality and a 
slight delay in the development of some neurological functions (surface righting reflex and startle 
response) in neonatal rats. 
 
Dietary administration of buprenorphine in the rat at dose levels of 500 ppm or greater produced a 
reduction in fertility demonstrated by reduced female conception rates. A dietary dose of 100 ppm 
(estimated exposure approximately 2.4x for buprenorphine at a human dose of 24 mg 



29 

buprenorphine/naloxone based on AUC, plasma levels of naloxone were below the limit of detection 
in rats) had no adverse effect on fertility in females. 
 
A carcinogenicity study with buprenorphine/naloxone was conducted in rats at doses of 7, 30 and 
120 mg/kg/day, with estimated exposure multiples of 3 to 75 times, based on a human daily sublingual 
dose of 16 mg calculated on a mg/m² basis. Statistically significant increases in the incidence of 
benign testicular interstitial (Leydig's) cell adenomas were observed in all dosage groups.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Lactose monohydrate 
Mannitol 
Maize starch 
Povidone K 30 
Citric acid anhydrous 
Sodium citrate 
Magnesium stearate 
Acesulfame potassium 
Natural lemon and lime flavour 
 
 
6.2 Incompatibilities 
 
Not applicable. 
 
 
6.3 Shelf life 
 
3 years. 
 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
 
6.5 Nature and contents of container 
 
7 tablets in blister packs Paper/Aluminium/Nylon/Aluminium/PVC. 
 
28 tablets in blister packs Paper/Aluminium/Nylon/Aluminium/PVC. 
 
Not all pack sizes may be marketed. 
 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 



30 

7. MARKETING AUTHORISATION HOLDER 
 
Indivior Europe Limited  
27 Windsor Place 
Dublin 2 
Ireland 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/359/003 
EU/1/06/359/004 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 26 September 2006 
Date of latest renewal: 16 September 2011 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this product is available on the website of the European Medicines Agency 
http://www.ema.europa.eu/ 
 

 



31 

1. NAME OF THE MEDICINAL PRODUCT 
 
Suboxone 16 mg/4 mg sublingual tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each sublingual tablet contains 16 mg buprenorphine (as hydrochloride) and 4 mg naloxone (as 
hydrochloride dihydrate). 
 
Excipients with known effect:  
Each sublingual tablet contains 156.64 mg lactose (as monohydrate) 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Sublingual tablet 
White round biconvex tablets of 10.5 mm with “N16” debossed on one side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Substitution treatment for opioid drug dependence, within a framework of medical, social and 
psychological treatment. The intention of the naloxone component is to deter intravenous misuse. 
Treatment is intended for use in adults and adolescents over 15 years of age who have agreed to be 
treated for addiction. 
 
 
4.2 Posology and method of administration 
 
Treatment must be under the supervision of a physician experienced in the management of opiate 
dependence/addiction.  
 
Precautions to be taken before induction 
Prior to treatment initiation, consideration should be given to the type of opioid dependence (i.e. long- 
or short-acting opioid), the time since last opioid use and the degree of opioid dependence. To avoid 
precipitating withdrawal, induction with buprenorphine/naloxone or buprenorphine only should be 
undertaken when objective and clear signs of withdrawal are evident (demonstrated e.g. by a score 
indicating mild to moderate withdrawal on the validated Clinical Opioid Withdrawal Scale, COWS).  

o For patients dependent upon heroin or short-acting opioids, the first dose of 
buprenorphine/naloxone should be taken when signs of withdrawal appear, but not less than 
6 hours after the patient last used opioids. 

o For patients receiving methadone, the dose of methadone should be reduced to a maximum of 
30 mg/day before beginning buprenorphine/naloxone therapy. The long half life of methadone 
should be considered when starting buprenorphine/naloxone. The first dose of 
buprenorphine/naloxone should be taken only when signs of withdrawal appear, but not less 
than 24 hours after the patient last used methadone. Buprenorphine may precipitate symptoms 
of withdrawal in patients dependent upon methadone.  

 



32 

Posology 
 
Initiation therapy (induction) 
The recommended starting dose in adults and adolescents over 15 years of age is one to two Suboxone 
2 mg/0.5 mg.  An additional one to two Suboxone 2 mg/0.5 mg may be administered on day one 
depending on the individual patient’s requirement.  
During the initiation of treatment, daily supervision of dosing is recommended to ensure proper 
sublingual placement of the dose and to observe patient response to treatment as a guide to effective 
dose titration according to clinical effect.   
 
Dosage adjustment and maintenance therapy 
Following treatment induction on day one, the patient should be stabilised to a maintenance dose 
during the next few days by progressively adjusting the dose according to the clinical effect of the 
individual patient.  Dose titration in steps of 2-8 mg buprenorphine is guided by reassessment of the 
clinical and psychological status of the patient, and should not exceed a maximum single daily dose of 
24 mg buprenorphine.  
 
Less than daily dosing  
After a satisfactory stabilisation has been achieved the frequency of dosing may be decreased to 
dosing every other day at twice the individually titrated daily dose. For example, a patient stabilised to 
receive a daily dose of 8 mg buprenorphine may be given 16 mg buprenorphine on alternate days, with 
no dose on the intervening days. In some patients, after a satisfactory stabilisation has been achieved, 
the frequency of dosing may be decreased to 3 times a week (for example on Monday, Wednesday and 
Friday). The dose on Monday and Wednesday should be twice the individually titrated daily dose, and 
the dose on Friday should be three times the individually titrated daily dose, with no dose on the 
intervening days. However, the dose given on any one day should not exceed 24 mg buprenorphine. 
Patients requiring a titrated daily dose> 8 mg buprenorphine/day may not find this regimen adequate. 
 
Medical withdrawal  
After a satisfactory stabilisation has been achieved, if the patient agrees, the dosage may be reduced 
gradually to a lower maintenance dose; in some favourable cases, treatment may be discontinued. The 
availability of doses of 2 mg/0.5 mg and 8 mg/2 mg allows for a downward titration of dosage. For 
patients who may require a lower buprenorphine dose, buprenorphine 0.4 mg may be used. Patients 
should be monitored following medical withdrawal because of the potential for relapse. 
 
Special populations 
 
Elderly 
The safety and efficacy of buprenorphine/naloxone in elderly patients over 65 years of age have not 
been established. No recommendation on posology can be made. 
 
Hepatic impairment 
Baseline liver function tests and documentation of viral hepatitis status is recommended prior to 
commencing therapy. Patients who are positive for viral hepatitis, on concomitant medicinal products 
(see section 4.5) and/or have existing liver dysfunction are at risk of accelerated liver injury. Regular 
monitoring of liver function is recommended (see section 4.4).  
Both active substances of Suboxone, buprenorphine and naloxone, are extensively metabolized in the 
liver, and the plasma levels were found to be higher for both buprenorphine and naloxone  in patients 
with moderate and severe hepatic impairment. Patients should be monitored for signs and symptoms 
of precipitated opioid withdrawal, toxicity or overdose caused by increased levels of naloxone and/or 
buprenorphine.  
As buprenorphine/naloxone pharmacokinetics may be altered in patients with hepatic impairment, 
lower initial doses and careful dose titration in patients with mild to moderate hepatic impairment are 
recommended. Buprenorphine/naloxone is contraindicated in patients with severe hepatic impairment 
(see section 4.3 and 5.2). 
 
Renal impairment 



33 

Modification of the buprenorphine/naloxone dose is not required in patients with renal impairment. 
Caution is recommended when dosing patients with severe renal impairment (creatinine 
clearance < 30 ml/min) (see section 4.4 and 5.2). 
 
Paediatric population 
The safety and efficacy of buprenorphine/naloxone in children below the age of 15 years have not 
been established. No data are available. 
 
Method of administration 
Physicians must warn patients that the sublingual route is the only effective and safe route of 
administration for this medicinal product (see section 4.4). The tablet is to be placed under the tongue 
until completely dissolved. Patients should not swallow or consume food or drink until the tablet is 
completely dissolved.  
 
The dose can be made up from  multiple Suboxone tablets of different strengths, which may be taken 
all at the same time or in two divided portions; the second portion to be taken directly after the first 
portion has dissolved. 
  
 
4.3 Contraindications 
  
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1. 
Severe respiratory insufficiency 
Severe hepatic impairment  
Acute alcoholism or delirium tremens. 
Concomitant administration of opioid antagonists (naltrexone, nalmefene) for the treatment of alcohol 
or opioid dependence. 
 
 
4.4 Special warnings and precautions for use 
 
Misuse, abuse and diversion 
Buprenorphine can be misused or abused in a manner similar to other opioids, legal or illicit. Some 
risks of misuse and abuse include overdose, spread of blood borne viral or localised and systemic 
infections, respiratory depression and hepatic injury. Buprenorphine misuse by someone other than the 
intended patient poses the additional risk of new drug dependent individuals using buprenorphine as 
the primary drug of abuse, and may occur if the medicine is distributed for illicit use directly by the 
intended patient or if the medicinal product is not safeguarded against theft.  
 
Sub-optimal treatment with buprenorphine/naloxone may prompt medicine misuse by the patient, 
leading to overdose or treatment dropout. A patient who is under-dosed with buprenorphine/naloxone 
may continue responding to uncontrolled withdrawal symptoms by self-medicating with opioids, 
alcohol or other sedative-hypnotics such as benzodiazepines. 
 
To minimize the risk of misuse, abuse and diversion, physicians should take appropriate precautions 
when prescribing and dispensing buprenorphine, such as to avoid prescribing multiple refills early in 
treatment, and to conduct patient follow-up visits with clinical monitoring that is appropriate to the 
patient's needs.  
 
Combining buprenorphine with naloxone in Suboxone is intended to deter misuse and abuse of the 
buprenorphine. Intravenous or intranasal misuse of Suboxone is expected to be less likely than 
buprenorphine alone since the naloxone in Suboxone can precipitate withdrawal in individuals 
dependent on heroin, methadone, or other opioid agonists.  
 
Respiratory depression 
A number of cases of death due to respiratory depression have been reported, particularly when 
buprenorphine was used in combination with benzodiazepines (see section 4.5) or when 



34 

buprenorphine was not used according to prescribing information.  Deaths have also been reported in 
association with concomitant administration of buprenorphine and other depressants such as alcohol or 
other opioids. If buprenorphine is administered to some non-opioid dependent individuals, who are not 
tolerant to the effects of opioids, potentially fatal respiratory depression may occur. 
 
This product should be used with care in patients with asthma or respiratory insufficiency (e.g. chronic 
obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, 
pre-existing respiratory depression or kyphoscoliosis (curvature of spine leading to potential shortness 
of breath)). 
 
Buprenorphine/naloxone may cause severe, possibly fatal, respiratory depression in children and non-
dependent persons in case of accidental or deliberate ingestion. Patients must be warned to store the 
blister safely, to never open the blister in advance, to keep them out of the reach of children and other 
household members, and not to take this medicine in front of children. An emergency unit should be 
contacted immediately in case of accidental ingestion or suspicion of ingestion. 
 
CNS depression 
Buprenorphine/naloxone may cause drowsiness, particularly when taken together with alcohol or 
central nervous system depressants (such as tranquilisers, sedatives or hypnotics) (see section 4.5). 
 
Dependence 
Buprenorphine is a partial agonist at the µ (mu)-opiate receptor and chronic administration produces 
dependence of the opioid type.  Studies in animals, as well as clinical experience, have demonstrated 
that buprenorphine may produce dependence, but at a lower level than a full agonist e.g. morphine.  
 
Abrupt discontinuation of treatment is not recommended as it may result in a withdrawal syndrome 
that may be delayed in onset. 
 
Hepatitis and hepatic events 
Cases of acute hepatic injury have been reported in opioid-dependent addicts both in clinical trials and 
in post marketing adverse reaction reports. The spectrum of abnormalities ranges from transient 
asymptomatic elevations in hepatic transaminases to case reports of hepatic failure, hepatic necrosis, 
hepatorenal syndrome, hepatic encephalopathy and death. In many cases the presence of pre-existing 
mitochondrial impairment (genetic disease, liver enzyme abnormalities, infection with hepatitis B or 
hepatitis C virus, alcohol abuse, anorexia, concomitant use of other potentially hepatotoxic medicines) 
and ongoing injecting drug use may have a causative or contributory role. These underlying factors 
must be taken into consideration before prescribing buprenorphine/naloxone and during treatment. 
When a hepatic event is suspected, further biological and etiological evaluation is required. Depending 
upon the findings, the medicinal product may be discontinued cautiously so as to prevent withdrawal 
symptoms and to prevent a return to illicit drug use. If the treatment is continued, hepatic function 
should be monitored closely. 
 
Precipitation of opioid withdrawal syndrome  
When initiating treatment with buprenorphine/naloxone, the physician must be aware of the partial 
agonist profile of buprenorphine and that it can precipitate withdrawal in opioid-dependent patients, 
particularly if administered less than 6 hours after the last use of heroin or other short-acting opioid, or 
if administered less than 24 hours after the last dose of methadone. Patients should be clearly 
monitored during the switching period from buprenorphine or methadone to buprenorphine/naloxone 
since withdrawal symptoms have been reported. To avoid precipitating withdrawal, induction with 
buprenorphine/naloxone should be undertaken when objective signs of withdrawal are evident (see 
section 4.2). 
 
Withdrawal symptoms may also be associated with sub-optimal dosing. 
 
Hepatic impairment 
The effect of hepatic impairment on the pharmacokinetics of buprenorphine and naloxone were 
evaluated in a post-marketing study.  Since both buprenorphine and naloxone are extensively 



35 

metabolized, plasma levels were found to be higher for both buprenorphine and naloxone in patients 
with moderate and severe hepatic impairment after single-dose administration.  Patients should be 
monitored for signs and symptoms of precipitated opioid withdrawal, toxicity or overdose caused by 
increased levels of naloxone and/or buprenorphine.  Suboxone sublingual tablets should be used with 
caution in patients with moderate hepatic impairment (See section 4.3 and 5.2). In patients with severe 
hepatic insufficiency the use of buprenorphine/naloxone is contraindicated. 
 
Renal impairment 
Renal elimination may be prolonged since 30 % of the administered dose is eliminated by the renal 
route. Metabolites of buprenorphine accumulate in patients with renal failure. Caution is 
recommended when dosing patients with severe renal impairment (creatinine clearance <30 ml/min) 
(see sections 4.2 and 5.2). 
 
Use in adolescents (Age 15-<18) 
Due to the lack of data in adolescents (age 15-<18), patients in this age group should be more closely 
monitored during treatment.  
 
CYP 3A inhibitors 
Medicines that inhibit the enzyme CYP3A4 may give rise to increased concentrations of 
buprenorphine. A reduction of the buprenorphine/naloxone dose may be needed. Patients already 
treated with CYP3A4 inhibitors should have their dose of buprenorphine/naloxone titrated carefully 
since a reduced dose may be sufficient in these patients (see section 4.5). 
 
General warnings relevant to the administration of opioids  
Opioids may produce orthostatic hypotension in ambulatory patients. 
 
Opioids may elevate cerebrospinal fluid pressure, which may cause seizures, so opioids should be used 
with caution in patients with head injury, intracranial lesions, other circumstances where cerebrospinal 
pressure may be increased, or history of seizure. 
 
Opioids should be used with caution in patients with hypotension, prostatic hypertrophy or urethral 
stenosis. 
 
Opioid-induced miosis, changes in the level of consciousness, or changes in the perception of pain as a 
symptom of disease may interfere with patient evaluation or obscure the diagnosis or clinical course of 
concomitant disease. 
 
Opioids should be used with caution in patients with myxoedema, hypothyroidism, or adrenal cortical 
insufficiency (e.g., Addison's disease). 
 
Opioids have been shown to increase intracholedochal pressure, and should be used with caution in 
patients with dysfunction of the biliary tract. 
 
Opioids should be administered with caution to elderly or debilitated patients. 
 
The concomitant use of monoamine oxidase inhibitors (MAOI) might produce an exaggeration of the 
effects of opioids, based on experience with morphine (see section 4.5). 
 
Suboxone contains lactose.  Patients with rare hereditary problems of galactose intolerance, should not 
take this medicine. 
 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Suboxone should not be taken together with: 
 



36 

 alcoholic drinks or medicines containing alcohol, as alcohol increases the sedative effect of 
buprenorphine (see section 4.7). 

 
Suboxone should be used cautiously when co-administered with: 
 

o  benzodiazepines: This combination may result in death due to respiratory depression of central 
origin. Therefore, dosages must be limited and this combination must be avoided in cases 
where there is a risk of misuse. Patients should be warned that it is extremely dangerous to 
self-administer non-prescribed benzodiazepines while taking this product, and should also be 
cautioned to use benzodiazepines concurrently with this product only as directed by their 
physician (see section 4.4). 

 
o other central nervous system depressants, other opioid derivatives (e.g. methadone, analgesics 

and antitussives), certain antidepressants, sedative H1-receptor antagonists, barbiturates, 
anxiolytics other than benzodiazepines, neuroleptics, clonidine and related substances: these 
combinations increase central nervous system depression. The reduced level of alertness can 
make driving and using machines hazardous. 

 
o  Furthermore, adequate analgesia may be difficult to achieve when administering a full opioid 

agonist in patients receiving buprenorphine/naloxone. Therefore the potential to overdose with 
a full agonist exists, especially when attempting to overcome buprenorphine partial agonist 
effects, or when buprenorphine plasma levels are declining.  

 
o naltrexone and nalmefene are opioid antagonists that can block the pharmacological effects of 

buprenorphine. Co-administration during buprenorphine/naloxone treatment is contraindicated 
due to the potentially dangerous interaction that may precipitate a sudden onset of prolonged 
and intense opioid withdrawal symptoms (see section 4.3). 

 
o CYP3A4 inhibitors: an interaction study of buprenorphine with ketoconazole (a potent 

inhibitor of CYP3A4) resulted in increased Cmax and AUC (area under the curve) of 
buprenorphine (approximately 50 % and 70 % respectively) and, to a lesser extent, of 
norbuprenorphine. Patients receiving Suboxone should be closely monitored, and may require 
dose-reduction if combined with potent CYP3A4 inhibitors (e.g. protease inhibitors like 
ritonavir, nelfinavir or indinavir or azole antifungals such as ketoconazole or itraconazole, 
macrolide antibiotics).  

 
o CYP3A4 inducers: Concomitant use of CYP3A4 inducers with buprenorphine may decrease 

buprenorphine plasma concentrations, potentially resulting in sub-optimal treatment of opioid 
dependence with buprenorphine. It is recommended that patients receiving 
buprenorphine/naloxone should be closely monitored if inducers (e.g. phenobarbital, 
carbamazepine, phenytoin, rifampicin) are co-administered. The dose of buprenorphine or the 
CYP3A4 inducer may need to be adjusted accordingly.  

 
o the concomitant use of monoamine oxidase inhibitors (MAOI) might produce exaggeration of 

the effects of opioids, based on experience with morphine. 
 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are no adequate data from the use of Suboxone in pregnant women.  Studies in animals have 
shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. 
 
Towards the end of pregnancy buprenorphine may induce respiratory depression in the newborn infant 
even after a short period of administration. Long-term administration of buprenorphine during the last 
three months of pregnancy may cause a withdrawal syndrome in the neonate (e.g. hypertonia, neonatal 



37 

tremor, neonatal agitation, myoclonus or convulsions). The syndrome is generally delayed for several 
hours to several days after birth. 
 
Due to the long half-life of buprenorphine, neonatal monitoring for several days should be considered 
at the end of pregnancy, to prevent the risk of respiratory depression or withdrawal syndrome in 
neonates.  
 
Furthermore, the use of buprenorphine/naloxone during pregnancy should be assessed by the 
physician. Buprenorphine/naloxone should be used during pregnancy only if the potential benefit 
outweighs the potential risk to the foetus. 
 
Breast-feeding 
It is unknown whether naloxone is excreted in human breast milk. Buprenorphine and its metabolites 
are excreted in human breast milk. In rats buprenorphine has been found to inhibit lactation. 
Therefore, breastfeeding should be discontinued during treatment with Suboxone. 
 
Fertility 
Animal studies have shown a reduction in female fertility at high doses (systemic exposure > 2.4 times 
the human exposure at the maximum recommended dose of 24 mg buprenorphine, based on AUC). 
See section 5.3. 
 
 
4.7 Effects on ability to drive and use machines 
 
Buprenorphine/naloxone has minor to moderate influence on the ability to drive and use machines 
when administered to opioid dependent patients. This product may cause drowsiness, dizziness, or 
impaired thinking, especially during treatment induction and dose adjustment. If taken together with 
alcohol or central nervous system depressants, the effect is likely to be more pronounced (see sections 
4.4 and 4.5). 
 
Patients should be cautioned about driving or operating hazardous machinery in case 
buprenorphine/naloxone may affect their ability to engage in such activities. 
 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The most commonly reported treatment related adverse reactions reported during the pivotal clinical 
trials were constipation and symptoms commonly associated with drug withdrawal (i.e. insomnia, 
headache, nausea, hyperhidrosis and pain). Some reports of seizure, vomiting, diarrhoea, and elevated 
liver function tests were considered serious. 
 
Tabulated list of adverse reactions 
Table 1 summarises adverse reactions reported from pivotal clinical trials in which, 342 of 
472 patients (72.5 %) reported adverse reactions and adverse reactions reported during post-marketing 
surveillance.   
 
The frequency of possible side effects listed below is defined using the following convention:  
Very common (1/10), Common (1/100 to <1/10), Uncommon (1/1,000 to <1/100), Not known 
(cannot be estimated from available data). 



38 

 
Table 1: Treatment-related adverse reactions reported in clinical trials and post- marketing 
surveillance of buprenorphine/naloxone 
 
System Organ 
Class 

Very common Common Uncommon Not known 

Infections and 
infestations 

 Influenza 
Infection 
Pharyngitis 
Rhinitis

Urinary tract 
infection 
Vaginal infection 

 

Blood and 
lymphatic system 
disorders 

  Anaemia 
Leukocytosis 
Leukopenia 
Lymphadenopathy 
Thrombocytopenia 

 

Immune system 
disorders 

  Hypersensitivity Anaphylactic 
shock 

Metabolism and 
nutrition 
disorders 

  Decreased appetite 
Hyperglycaemia 
Hyperlipidaemia 
Hypoglycaemia

 

Psychiatric 
disorders 

Insomnia 
 

Anxiety 
Depression 
Libido decreased 
Nervousness 
Thinking 
abnormal 

Abnormal dreams 
Agitation 
Apathy 
Depersonalisation 
Drug dependence 
Euphoric mood 
Hostility

Hallucination 

Nervous system 
disorders 

Headache Migraine 
Dizziness 
Hypertonia 
Paraesthesia 
Somnolence

Amnesia 
Hyperkinesia 
Sezuire 
Speech disorder 
Tremor

Hepatic 
encepalopathy 
Syncope 

Eye disorders  Amblyopia 
Lacrimal disorder

Conjunctivitis 
Miosis

 

Ear and labyrinth 
disorders 

   Vertigo 

Cardiac disorders   Angina Pectoris 
Bradycardia 
Myocardial 
infarction 
Palpitations 
Tachycardia

 

Vascular 
disorders 

 Hypertension 
Vasodilatation

Hypotension Orthostatic 
hypotension

Respiratory, 
thoracic and 
mediastinal 
disorders 

 Cough Asthma 
Dyspnoea 
Yawning 

Bronchospasm 
Respiratory 
depression 

Gastrointestinal 
disorders 

Constipation 
Nausea 

Abdominal Pain 
Diarrhoea 
Dyspepsia 
Flatulence 
Vomiting

Mouth ulceration 
Tongue 
discolouration 

 

Hepatobiliary 
disorders 

   Hepatitis  
Hepatitis acute 
Jaundice 



39 

Hepatic necrosis 
Hepatorenal 
syndrome 

Skin and 
subcutaneous 
tissue disorders 

Hyperhidrosis Pruritus 
Rash 
Urticaria 

Acne 
Alopecia 
Dermatitis 
exfoliative 
Dry skin 
Skin mass

Angioedema 

Musculoskeletal 
and connective 
tissue disorders 

 Back Pain 
Arthralgia 
Muscle spasms 
Myalgia

Arthritis  

Renal and urinary 
disorders 

 Urine 
Abnormality 
 

Albuminuria 
Dysuria 
Haematuria 
Nephrolithiasis 
Urinary retention 

 

Reproductive 
system and breast 
disorders 

 Erectile 
dysfunction 

Amenorrhoea 
Ejaculation 
disorder 
Menorrhagia 
Metrorrhagia

 

General disorders 
and 
administration 
site conditions 

Drug withdrawal 
syndrome 

Asthenia 
Chest Pain 
Chills 
Pyrexia 
Malaise 
Pain 
Oedema 
peripheral 

Hypothermia 
 

Drug withdrawal 
syndrome 
neonatal (see 
section 4.6) 

Investigations  Liver function test 
abnormal 
Weight decreased

Blood creatinine 
increased 

Transaminases 
increased 

Injury, poisoning 
and procedural 
complications 

 Injury Heat stroke  

 
Description of selected adverse reactions  
 
In cases of intravenous drug misuse, some adverse experiences are attributed to the act of misuse 
rather than the medicinal product and include local reactions, sometimes septic (abscess, cellulitis), 
and potentially serious acute hepatitis, and other acute infections such as pneumonia, endocarditis 
have been reported (see section 4.4). 
 
In patients presenting with marked drug dependence, initial administration of buprenorphine can 
produce a drug withdrawal syndrome similar to that associated with naloxone (see sections 4.2 and 
4.4). 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 



40 

 
4.9 Overdose 
 
Symptoms 
Respiratory depression as a result of central nervous system depression is the primary symptom 
requiring intervention in the case of overdose because it may lead to respiratory arrest and death. Signs 
of overdose may also include somnolence, amblyopia, miosis, hypotension, nausea, vomiting and/or 
speech disorders. 
 
Management 
General supportive measures should be instituted, including close monitoring of respiratory and 
cardiac status of the patient.  Symptomatic treatment of respiratory depression, and standard intensive 
care measures, should be implemented. A patent airway and assisted or controlled ventilation must be 
assured. The patient should be transferred to an environment within which full resuscitation facilities 
are available. 
 
If the patient vomits, care must be taken to prevent aspiration of the vomitus. 
 
Use of an opioid antagonist (i.e., naloxone) is recommended, despite the modest effect it may have in 
reversing the respiratory symptoms of buprenorphine compared with its effects on full agonist opioid 
agents. 
 
If naloxone is used, the long duration of action of buprenorphine should be taken into consideration 
when determining the length of treatment and medical surveillance needed to reverse the effects of an 
overdose. Naloxone can be cleared more rapidly than buprenorphine, allowing for a return of 
previously controlled buprenorphine overdose symptoms, so a continuing infusion may be necessary. 
If infusion is not possible, repeated dosing with naloxone may be required.  Initial naloxone doses may 
range up to 2 mg and be repeated every 2-3 minutes until a satisfactory response is achieved, 
but should not exceed a 10 mg starting dose. Ongoing intravenous infusion rates should be titrated to 
patient response. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other nervous system drugs, drugs used in addictive disorders, ATC 
code: N07BC51. 
 
Mechanism of action 
Buprenorphine is an opioid partial agonist/antagonist which binds to the  and  (kappa) opioid 
receptors of the brain. Its activity in opioid maintenance treatment is attributed to its slowly reversible 
properties with the -opioid receptors which, over a prolonged period, might minimise the need of 
addicted patients for drugs. 
 
Opioid agonist ceiling effects were observed during clinical pharmacology studies in opioid-dependent 
persons. 
 
Naloxone is an antagonist at -opioid receptors. When administered orally or sublingually in usual 
doses to patients experiencing opioid withdrawal, naloxone exhibits little or no pharmacological effect 
because of its almost complete first pass metabolism. However, when administered intravenously to 
opioid-dependent persons, the presence of naloxone in Suboxone produces marked opioid antagonist 
effects and opioid withdrawal, thereby deterring intravenous abuse. 
 
Clinical efficacy 
Efficacy and safety data for buprenorphine/naloxone are primarily derived from a one-year clinical 
trial, comprising a 4-week randomised double blind comparison of buprenorphine/naloxone, 



41 

buprenorphine and placebo followed by a 48 week safety study of buprenorphine/naloxone. In this 
trial, 326 heroin-addicted subjects were randomly assigned to either buprenorphine/naloxone 16 mg 
per day, 16 mg buprenorphine per day or placebo. For subjects randomized to either active treatment, 
dosing began with 8 mg of buprenorphine on Day 1, followed by 16 mg (two 8 mg) of buprenorphine 
on Day 2. On Day 3, those randomized to receive buprenorphine/naloxone were switched to the 
combination tablet. Subjects were seen daily in the clinic (Monday through Friday) for dosing and 
efficacy assessments. Take-home doses were provided for weekends. The primary study comparison 
was to assess the efficacy of buprenorphine and buprenorphine/naloxone individually against placebo. 
The percentage of thrice-weekly urine samples that were negative for non-study opioids was 
statistically higher for both buprenorphine/naloxone versus placebo (p < 0.0001) and buprenorphine 
versus placebo (p < 0.0001). 
 
In a double-blind, double-dummy, parallel-group study comparing buprenorphine ethanolic solution to 
a full agonist active control, 162 subjects were randomized to receive the ethanolic sublingual solution 
of buprenorphine at 8 mg/day (a dose which is roughly comparable to a dose of 12 mg/day of 
buprenorphine/naloxone), or two relatively low doses of active control, one of which was low enough 
to serve as an alternative to placebo, during a 3 to10 day induction phase, a 16-week maintenance 
phase and a 7-week detoxification phase. Buprenorphine was titrated to maintenance dose by Day 3; 
active control doses were titrated more gradually. Based on retention in treatment and the percentage 
of thrice-weekly urine samples negative for non-study opioids, buprenorphine was more effective than 
the low dose of the control, in keeping heroin addicts in treatment and in reducing their use of opioids 
while in treatment. The effectiveness of buprenorphine, 8 mg per day was similar to that of the 
moderate active control dose, but equivalence was not demonstrated. 
 
 
5.2 Pharmacokinetic properties 
 
Buprenorphine 
 
Absorption 
Buprenorphine, when taken orally, undergoes first-pass metabolism with N-dealkylation and 
glucuroconjugation in the small intestine and the liver. The use of this medicinal product by the oral 
route is therefore inappropriate. 
 
Peak plasma concentrations are achieved 90 minutes after sublingual administration. Plasma levels of 
buprenorphine increased with the sublingual dose of buprenorphine/naloxone. Both Cmax and AUC of 
buprenorphine increased with the increase in dose (in the range of 4-16 mg), although the increase was 
less than dose-proportional.  
 
Pharmacokinetic Parameter 
 

Suboxone 4 mg Suboxone 8 mg Suboxone 16 mg 

Cmax ng/ml 
 

1.84 (39) 3.0 (51) 5.95 (38) 

AUC0-48   
hour ng/ml 

12.52 (35) 20.22 (43) 34.89 (33) 

 
Distribution 
The absorption of buprenorphine is followed by a rapid distribution phase (distribution half-life of 2 to 
5 hours). 
 
Biotransformation and elimination 
Buprenorphine is metabolised by 14-N-dealkylation and glucuroconjugation of the parent molecule 
and the dealkylated metabolite. Clinical data confirm that CYP3A4 is responsible for the N-
dealkylation of buprenorphine. N-dealkylbuprenorphine is a -opioid agonist with weak intrinsic 
activity. 
 



42 

Elimination of buprenorphine is bi- or tri-exponential, and has a mean half-life from plasma of 
32 hours.  
Buprenorphine is eliminated in the faeces by biliary excretion of the glucuroconjugated metabolites 
(70 %), the rest being eliminated in the urine. 
 
Naloxone 
 
Absorption and distribution  
Following intravenous administration, naloxone is rapidly distributed (distribution half-
life ~ 4 minutes). Following oral administration, naloxone is barely detectable in plasma; following 
sublingual administration of buprenorphine/naloxone, plasma naloxone concentrations are low and 
decline rapidly.  
 
Biotransformation  
The medicinal product is metabolized in the liver, primarily by glucuronide conjugation, and excreted 
in the urine. Naloxone has a mean half-life from plasma of 1.2 hours. 
 
Special populations 
 
Elderly 
No pharmacokinetic data in elderly patients are available. 
 
Renal impairment 
Renal elimination plays a relatively small role (~30 %) in the overall clearance of 
buprenorphine/naloxone. No dose modification based on renal function is required but caution is 
recommended when dosing subjects with severe renal impairment (see Section 4.3). 
 
Hepatic impairment 
The effect of hepatic impairment on the pharmacokinetics of buprenorphine and naloxone were 
evaluated in a post-marketing study.   
 
Table 3 summarizes the results from a clinical trial in which the exposure after single-dose 
administration of Suboxone 2.0/0.5mg (buprenorphine/naloxone) sublingual tablet was determined in 
healthy subjects, and in subjects with hepatic impairment. 
 

Table 3.  Effect of hepatic impairment on pharmacokinetic parameters of buprenorphine and 
naloxone following SUBOXONE administration (change relative to healthy subjects) 

PK Parameter 
Mild Hepatic Impairment 

(Child-Pugh Class A) 
(n=9) 

Moderate Hepatic 
Impairment 

(Child-Pugh Class B) 
(n=8) 

Severe Hepatic 
Impairment 

(Child-Pugh Class C) 
(n=8) 

Buprenorphine 

Cmax 1.2-fold increase 1.1-fold Increase 1.7-fold increase 

AUClast Similar to control 1.6-fold increase 2.8-fold increase 

 

Naloxone 

Cmax Similar to control 2.7-fold increase 11.3-fold increase 

AUClast  0.2-fold decrease 3.2-fold increase 14.0-fold increase 

 



43 

Overall, buprenorphine plasma exposure increased approximately 3-fold in patients with severely 
impaired hepatic function, while naloxone plasma exposure increased 14-fold with severely impaired 
hepatic function. 
 
 
5.3 Preclinical safety data 
 
The combination of buprenorphine and naloxone has been investigated in acute and repeated dose (up 
to 90 days in rats) toxicity studies in animals. No synergistic enhancement of toxicity has been 
observed. Undesirable effects were based on the known pharmacological activity of opioid agonistic 
and/or antagonistic substances.  
 
The combination (4:1) of buprenorphine hydrochloride and naloxone hydrochloride was not 
mutagenic in a bacterial mutation assay (Ames test), and was not clastogenic in an in vitro cytogenetic 
assay in human lymphocytes or in an intravenous micronucleus test in the rat. 
 
Reproduction studies by oral administration of buprenorphine: naloxone (ratio 1:1) indicated that 
embryolethality occurred in rats in the presence of maternal toxicity at all doses. The lowest dose 
studied represented exposure multiples of 1x for buprenorphine and 5x for naloxone at the maximum 
human therapeutic dose calculated on a mg/m² basis. No developmental toxicity was observed in 
rabbits at maternally toxic doses. Further, no teratogenicity has been observed in either rats or rabbits. 
A peri-postnatal study has not been conducted with buprenorphine/naloxone; however, maternal oral 
administration of buprenorphine at high doses during gestation and lactation resulted in difficult 
parturition (possible as a result of the sedative effect of buprenorphine), high neonatal mortality and a 
slight delay in the development of some neurological functions (surface righting reflex and startle 
response) in neonatal rats. 
 
Dietary administration of buprenorphine in the rat at dose levels of 500 ppm or greater produced a 
reduction in fertility demonstrated by reduced female conception rates. A dietary dose of 100 ppm 
(estimated exposure approximately 2.4x for buprenorphine at a human dose of 24 mg 
buprenorphine/naloxone based on AUC, plasma levels of naloxone were below the limit of detection 
in rats) had no adverse effect on fertility in females. 
 
A carcinogenicity study with buprenorphine/naloxone was conducted in rats at doses of 7, 30 and 
120 mg/kg/day, with estimated exposure multiples of 3 to 75 times, based on a human daily sublingual 
dose of 16 mg calculated on a mg/m² basis. Statistically significant increases in the incidence of 
benign testicular interstitial (Leydig's) cell adenomas were observed in all dosage groups.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Lactose monohydrate 
Mannitol 
Maize starch 
Povidone K 30 
Citric acid anhydrous 
Sodium citrate 
Magnesium stearate 
Acesulfame potassium 
Natural lemon and lime flavour 
 
 



44 

6.2 Incompatibilities 
 
Not applicable. 
 
 
6.3 Shelf life 
 
3 years. 
 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
 
6.5 Nature and contents of container 
 
7 tablets in blister packs Paper/Aluminium/Nylon/Aluminium/PVC. 
 
28 tablets in blister packs Paper/Aluminium/Nylon/Aluminium/PVC. 
 
Not all pack sizes may be marketed. 
 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Indivior Europe Limited  
27 Windsor Place 
Dublin 2 
Ireland 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/06/359/005 
EU/1/06/359/006 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 26 September 2006 
Date of latest renewal: 16 September 2011 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this product is available on the website of the European Medicines Agency 
http://www.ema.europa.eu/ 
 



45 

1. NAME OF THE MEDICINAL PRODUCT 
 
Suboxone 2 mg/0.5 mg sublingual film 
Suboxone 4 mg/1 mg sublingual film 
Suboxone 8 mg/2 mg sublingual film 
Suboxone 12 mg/3 mg sublingual film 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Suboxone 2 mg/0.5 mg sublingual film 
Each film contains 2 mg buprenorphine (as hydrochloride) and 0.5 mg naloxone (as hydrochloride 
dihydrate). 
Excipients with known effect 
Each film contains 5.87 mg maltitol liquid and 0.01 mg sunset yellow (E 110). 
 
Suboxone 4 mg/1 mg sublingual film 
Each film contains 4 mg buprenorphine (as hydrochloride) and 1 mg naloxone (as hydrochloride 
dihydrate). 
Excipients with known effect 
Each film contains 11.74 mg maltitol liquid and 0.02 mg sunset yellow (E 110). 
 
Suboxone 8 mg/2 mg sublingual film 
Each film contains 8 mg buprenorphine (as hydrochloride) and 2 mg naloxone (as hydrochloride 
dihydrate). 
Excipients with known effect 
Each film contains 6.02 mg maltitol liquid and 0.02 mg sunset yellow (E 110). 
 
Suboxone 12 mg/3 mg sublingual film 
Each film contains 12 mg buprenorphine (as hydrochloride) and 3 mg naloxone (as hydrochloride 
dihydrate). 
Excipients with known effect 
Each film contains 9.03 mg maltitol liquid and 0.02 mg sunset yellow (E 110). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Sublingual film 
 
Suboxone 2 mg/0.5 mg sublingual film 
2 mg/0.5 mg orange rectangular film of nominal dimensions 22.0 mm × 12.8 mm, with ‘N2’ imprinted 
in white ink. 
 
Suboxone 4 mg/1 mg sublingual film 
4 mg/1 mg orange rectangular film of nominal dimensions 22.0 mm × 25.6 mm, with ‘N4’ imprinted 
in white ink. 
 
Suboxone 8 mg/2 mg sublingual film 
8 mg/2 mg orange rectangular film of nominal dimensions 22.0 mm × 12.8 mm, with ‘N8’ imprinted 
in white ink. 
 
Suboxone 12 mg/3 mg sublingual film 
12 mg/3 mg orange rectangular film of nominal dimensions 22.0 mm × 19.2 mm, with ‘N12’ 
imprinted in white ink. 
 



46 

 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Substitution treatment for opioid drug dependence, within a framework of medical, social and 
psychological treatment. The intention of the naloxone component is to deter intravenous misuse. 
Suboxone is indicated in adults and adolescents over 15 years of age who have agreed to be treated for 
addiction. 
 
4.2 Posology and method of administration 
 
Treatment must be under the supervision of a physician experienced in the management of opiate 
dependence/addiction. 
 
Precautions to be taken before induction 
Prior to treatment initiation, consideration should be given to the type of opioid dependence (i.e. long- 
or short-acting opioid), the time since last opioid use and the degree of opioid dependence. To avoid 
precipitating withdrawal, induction with buprenorphine/naloxone or buprenorphine only should be 
undertaken when objective and clear signs of withdrawal are evident (demonstrated by a score 
indicating mild to moderate withdrawal on the validated Clinical Opioid Withdrawal Scale, COWS). 
- For patients dependent upon heroin or short-acting opioids, the first dose of 

buprenorphine/naloxone must be taken when signs of withdrawal appear, but not less than 
6 hours after the patient last used opioids. 

- For patients receiving methadone, the dose of methadone must be reduced to a maximum of 
30 mg/day before beginning buprenorphine/naloxone therapy. The long half-life of methadone 
should be considered when starting buprenorphine/naloxone. The first dose of 
buprenorphine/naloxone should be taken only when signs of withdrawal appear, but not less 
than 24 hours after the patient last used methadone. Buprenorphine may precipitate symptoms 
of withdrawal in patients dependent upon methadone. 

 
Posology 
 
Initiation therapy (induction) 
The recommended starting dose in adults and adolescents over 15 years of age is two Suboxone 
2 mg/0.5 mg sublingual films or one Suboxone 4 mg/1 mg sublingual film. This may be achieved using 
two Suboxone 2 mg/0.5 mg sublingual films as a single dose or one Suboxone 4 mg/1 mg sublingual film, 
which can be repeated up to twice on day 1, to minimise undue withdrawal symptoms and retain the 
patient in treatment. 
 
Due to naloxone exposure being somewhat higher following buccal administration than sublingual 
administration, it is recommended that the sublingual site of administration be used during induction to 
minimise naloxone exposure and to reduce the risk of precipitated withdrawal. 
 
During the initiation of treatment, daily supervision of dosing is recommended to ensure proper sublingual 
placement of the dose and to observe patient response to treatment as a guide to effective dose titration 
according to clinical effect. 
 
Dosage stabilisation and maintenance therapy 
Following treatment induction on day 1, the patient must be rapidly stabilised on an adequate 
maintenance dose by titrating to achieve a dose that holds the patient in treatment and suppresses 
opioid withdrawal effects and is guided by reassessment of the clinical and psychological status of the 
patient. The maximum single daily dose should not exceed 24 mg buprenorphine. 
 
During maintenance therapy, it may be necessary to periodically restabilise the patient on a new 
maintenance dose in response to changing patient needs. 
 



47 

Less than daily dosing 
After a satisfactory stabilisation has been achieved the frequency of Suboxone dosing may be 
decreased to dosing every other day at twice the individually titrated daily dose. For example, a patient 
stabilised to receive a daily dose of 8 mg/2 mg may be given 16 mg/4 mg on alternate days, with no 
dose on the intervening days. In some patients, after a satisfactory stabilisation has been achieved, the 
frequency of Suboxone dosing may be decreased to 3 times a week (for example on Monday, 
Wednesday and Friday). The dose on Monday and Wednesday should be twice the individually 
titrated daily dose, and the dose on Friday should be three times the individually titrated daily dose, 
with no dose on the intervening days. However, the dose given on any one day should not exceed 
24 mg. Patients requiring a titrated daily dose > 8 mg/day may not find this regimen adequate. 
 
Medical withdrawal 
After a satisfactory stabilisation has been achieved, if the patient agrees, the dose may be reduced 
gradually to a lower maintenance dose, in some favourable cases, treatment may be discontinued. The 
availability of the sublingual film in doses of 2 mg/0.5 mg, 4 mg/1 mg and 8 mg/2 mg allows for a 
downward titration of dose. For patients who may require a lower buprenorphine dose, buprenorphine 
0.4 mg sublingual tablets may be used. Patients should be monitored following medical withdrawal 
because of the potential for relapse. 
 
Switching between sublingual and buccal sites of administration 
The systemic exposure of buprenorphine between buccal and sublingual administration of Suboxone 
film is approximately similar (see section 5.2). Therefore, once induction is complete, patients can 
switch between buccal and sublingual administration without significant risk of under- or overdosing. 
 
Switching between buprenorphine and buprenorphine/naloxone 
When used sublingually, buprenorphine/naloxone and buprenorphine have similar clinical effects and 
are interchangeable; however, before switching between buprenorphine/naloxone and buprenorphine, 
the prescriber and patient should agree to the change, and the patient should be monitored in case a 
need to readjust the dose occurs. 
 
Switching between sublingual tablet and film (where applicable) 
Patients being switched between Suboxone sublingual tablets and Suboxone film should be started on 
the same dose as the previously administered medicinal product. However, dose adjustments may be 
necessary when switching between medicinal products. Due to the potentially greater relative 
bioavailability of Suboxone film compared to Suboxone sublingual tablets, patients switching from 
sublingual tablets to film should be monitored for overdose. Those switching from film to sublingual 
tablets should be monitored for withdrawal or other indications of underdosing. In clinical studies, the 
pharmacokinetics of Suboxone film were not consistently shown to be similar to the respective dosage 
strengths of Suboxone sublingual tablets, as well as to the combinations (see section 5.2). If switching 
between Suboxone film and Suboxone sublingual tablets, the patient should be monitored in case a 
need to readjust the dose occurs. Combining different formulations or alternating between film and 
sublingual tablet formulations is not advised. 
 
Special populations 
 
Elderly 
The safety and efficacy of buprenorphine/naloxone in elderly patients over 65 years of age has not 
been established. No recommendation on posology can be made. 
 
Hepatic impairment 
As buprenorphine/naloxone pharmacokinetics may be altered in patients with hepatic impairment 
lower initial doses and careful dose titration in patients with mild to moderate hepatic impairment are 
recommended. Buprenorphine/naloxone is contraindicated in patients with severe hepatic impairment. 
(see sections 4.3 and 5.2). 
 
Renal impairment 



48 

Modification of the buprenorphine/naloxone dose is not required in patients with renal impairment. 
Caution is recommended when dosing patients with severe renal impairment (creatinine 
clearance < 30 mL/min) (see sections 4.4 and 5.2). 
Paediatric population 
The safety and efficacy of buprenorphine/naloxone in children below the age of 15 years have not 
been established. No data are available. 
 
Method of administration 
 
Sublingual use and/or buccal use only.  
 
For induction buprenorphine/naloxone should be administered sublingually. For maintenance therapy, 
Suboxone film may be administered buccally and/or sublingually.  
 
The film is not to be swallowed. The film is to be placed under the tongue or inside either cheek until 
completely dissolved. It is advised that patients moisten their mouths prior to dosing. Patients should 
not swallow or consume food or drink until the film is completely dissolved. The film should not be 
moved after placement, and proper administration technique should be demonstrated to the patient.  
 
For buccal use one film should be placed on the inside of the right or left cheek. If an additional film is 
necessary to achieve the prescribed dose, an additional film should be placed on the opposite side.  
The film must be kept on the inside of the cheek until completely dissolved. If a third film is necessary 
to achieve the prescribed dose, it should be placed on the inside of the right or left cheek after the first 
two films have dissolved.  
 
For sublingual use one film should be placed under the tongue. If an additional film is necessary to 
achieve the prescribed dose, an additional film should be placed under the tongue on the opposite side. 
The film must be kept under the tongue until completely dissolved. If a third film is necessary to 
achieve the prescribed dose, it should be placed under the tongue after the first two films have 
dissolved.  
 
A daily dose can be made up from multiple Suboxone films of different strengths.  This may be taken 
all at the same time or in two divided portions.  The second portion should be placed sublingually 
and/or buccally directly after the first portion has dissolved.  
 
No more than two films should be administered at the same time. It should be ensured that the films do 
not overlap.  
 
The film is not designed to be split or subdivided into smaller doses.  
 
 
4.3 Contraindications 
 
• Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 
• Severe respiratory insufficiency 
• Severe hepatic impairment 
• Acute alcoholism or delirium tremens 
• Concomitant administration of opioid antagonists (naltrexone, nalmefene) for the treatment of 

alcohol or opioid dependence 
 
4.4 Special warnings and precautions for use 
 
Misuse, abuse and diversion 
 
Buprenorphine can be misused or abused in a manner similar to other opioids, legal or illicit. Some 
risks of misuse and abuse include overdose, spread of blood-borne viral or localised and systemic 
infections, respiratory depression and hepatic injury. Buprenorphine misuse by someone other than the 



49 

intended patient poses the additional risk of new drug-dependent individuals using buprenorphine as 
the primary drug of abuse and may occur if the medicinal product is distributed for illicit use directly 
by the intended patient or if it is not safeguarded against theft. 
 
Suboptimal treatment with buprenorphine/naloxone may prompt misuse by the patient, leading to 
overdose or treatment dropout. A patient who is underdosed with buprenorphine/naloxone may 
continue responding to uncontrolled withdrawal symptoms by self-medicating with opioids, alcohol or 
other sedative-hypnotics such as benzodiazepines. 
 
To minimise the risk of misuse, abuse and diversion, appropriate precautions should be taken when 
prescribing and dispensing buprenorphine, such as avoiding prescribing multiple refills early in 
treatment, and conducting patient follow-up visits with clinical monitoring that is appropriate for the 
patient’s needs. 
 
Combining buprenorphine with naloxone in Suboxone is intended to deter misuse and abuse of the 
buprenorphine. Intravenous or intranasal misuse of Suboxone is expected to be less likely than with 
buprenorphine alone since the naloxone in this medicinal product can precipitate withdrawal in 
individual’s dependent on heroin, methadone, or other opioid agonists. 
 
Respiratory depression 
 
A number of cases of death due to respiratory depression have been reported, particularly when 
buprenorphine was used in combination with benzodiazepines (see section 4.5) or when 
buprenorphine was not used according to the prescribing information. Deaths have also been reported 
in association with concomitant administration of buprenorphine and other depressants such as alcohol 
or other opioids. If buprenorphine is administered to some non-opioid dependent individuals, who are 
not tolerant to the effects of opioids, potentially fatal respiratory depression may occur. 
 
This medicinal product should be used with care in patients with asthma or respiratory insufficiency 
(e.g. chronic obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve, hypoxia, 
hypercapnia, pre-existing respiratory depression or kyphoscoliosis (curvature of spine leading to 
potential shortness of breath)). 
 
Buprenorphine/naloxone may cause severe, possibly fatal, respiratory depression in children and non-
dependent persons in case of accidental or deliberate ingestion. Patients must be warned to store the 
sachet safely, to never open the sachet in advance, to keep them out of the reach of children and other 
household members, and not to use this medicinal product in front of children. An emergency unit 
should be contacted immediately in case of accidental ingestion or suspicion of ingestion. 
 
CNS depression 
 
Buprenorphine/naloxone may cause drowsiness, particularly when taken together with alcohol or 
central nervous system depressants (such as benzodiazepines, tranquilisers, sedatives or hypnotics; see 
sections 4.5 and 4.7). 
 
Risk from concomitant use of sedative medicinal products such as benzodiazepines or related 
medicinal products 
 
Concomitant use of buprenorphine/naloxone and sedative medicinal products such as benzodiazepines 
or related medicinal products may result in sedation, respiratory depression, coma and death. Because 
of these risks, concomitant prescribing with these sedative medicinal products should be reserved for 
patients for whom alternative treatment options are not possible. If a decision is made to prescribe 
buprenorphine/naloxone concomitantly with sedative  medicinal products, the lowest effective dose of 
the sedative medicines should be used, and the duration of treatment should be as short as possible. 
The patients should be followed closely for signs and symptoms of respiratory depression and 
sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware 
of these symptoms (see section 4.5). 



50 

 
Dependence 
 
Buprenorphine is a partial agonist at the µ (mu)-opiate receptor and chronic administration produces 
dependence of the opioid type. Studies in animals, as well as clinical experience, have demonstrated 
that buprenorphine may produce dependence, but at a lower level than a full agonist, e.g. morphine. 
 
Abrupt discontinuation of treatment is not recommended as it may result in a withdrawal syndrome 
that may be delayed in onset. 
 
Hepatitis and hepatic events 
Cases of acute hepatic injury have been reported in opioid-dependent addicts both in clinical trials and 
in post-marketing adverse reaction reports. The spectrum of abnormalities ranges from transient 
asymptomatic elevations in hepatic transaminases to case reports of hepatic failure, hepatic necrosis, 
hepatorenal syndrome, hepatic encephalopathy and death. In many cases the presence of pre-existing 
mitochondrial impairment (genetic disease, liver enzyme abnormalities, infection with hepatitis B or 
hepatitis C virus, alcohol abuse, anorexia, concomitant use of other potentially hepatotoxic medicinal 
products) and ongoing injecting drug use may have a causative or contributory role. These underlying 
factors must be taken into consideration before prescribing buprenorphine/naloxone and during 
treatment. When a hepatic event is suspected, further biological and aetiological evaluation is required. 
Depending upon the findings, the medicinal product may be discontinued cautiously so as to prevent 
withdrawal symptoms and to prevent a return to illicit drug use. If the treatment is continued, hepatic 
function should be monitored closely. 
 
Precipitation of opioid withdrawal syndrome 
 
When initiating treatment with buprenorphine/naloxone, the physician must be aware of the partial 
agonist profile of buprenorphine and that it can precipitate withdrawal in opioid-dependent patients, 
particularly if administered less than 6 hours after the last use of heroin or other short-acting opioid, or 
if administered less than 24 hours after the last dose of methadone. Patients should be  monitored 
during the switching period from buprenorphine or methadone to buprenorphine/naloxone since 
withdrawal symptoms have been reported. To avoid precipitating withdrawal, induction with 
buprenorphine/naloxone should be undertaken when objective signs of withdrawal are evident (see 
section 4.2). 
 
Withdrawal symptoms may also be associated with sub-optimal dosing. 
 
Hepatic impairment 
 
The effects of hepatic impairment on the pharmacokinetics of buprenorphine and naloxone were 
evaluated in a post-marketing study. Both buprenorphine and naloxone are extensively metabolised in 
the liver, and plasma levels were found to be higher for both buprenorphine and naloxone in patients 
with moderate and severe hepatic impairment compared with healthy subjects. Patients should be 
monitored for signs and symptoms of precipitated opioid withdrawal, toxicity or overdose caused by 
increased levels of naloxone and/or buprenorphine. 
 
Baseline liver function tests and documentation of viral hepatitis status is recommended prior to 
commencing therapy. Patients who are positive for viral hepatitis, on concomitant medicinal products 
(see section 4.5) and/or have existing liver dysfunction are at greater risk of liver injury. Regular 
monitoring of liver function is recommended (see section 4.4). 
 
Buprenorphine/naloxone should be used with caution in patients with moderate hepatic impairment 
(see sections 4.3 and 5.2). In patients with severe hepatic insufficiency the use of 
buprenorphine/naloxone is contraindicated. 
 
Renal impairment 
 



51 

Renal elimination may be prolonged since 30 % of the administered dose is eliminated by the renal 
route. Metabolites of buprenorphine accumulate in patients with renal failure. Caution is 
recommended when dosing patients with severe renal impairment (creatinine clearance < 30 ml/min) 
(see sections 4.2 and 5.2). 
 
CYP3 A inhibitors 
 
Medicinal products that inhibit the enzyme CYP3A4 may give rise to increased concentrations of 
buprenorphine. A reduction of the buprenorphine/naloxone dose may be needed. Patients already 
treated with CYP3A4 inhibitors should have their dose of buprenorphine/naloxone titrated carefully 
since a reduced dose may be sufficient in these patients (see section 4.5). 
 
Class effects 
 
Opioids may produce orthostatic hypotension in ambulatory patients. 
 
Opioids may elevate cerebrospinal fluid pressure, which may cause seizures, so opioids should be used 
with caution in patients with head injury, intracranial lesions, in other circumstances where 
cerebrospinal pressure may be increased, or in patients with a history of seizure. 
 
Opioids should be used with caution in patients with hypotension, prostatic hypertrophy or urethral 
stenosis. 
 
Opioid-induced miosis, changes in the level of consciousness, or changes in the perception of pain as a 
symptom of disease may interfere with patient evaluation or obscure the diagnosis or clinical course of 
concomitant disease. 
 
Opioids should be used with caution in patients with myxoedema, hypothyroidism, or adrenal cortical 
insufficiency (e.g., Addison's disease). 
 
Opioids have been shown to increase intracholedochal pressure and should be used with caution in 
patients with dysfunction of the biliary tract. 
 
Opioids should be administered with caution to elderly or debilitated patients. 
 
The concomitant use of monoamine oxidase inhibitors (MAOI) might produce an exaggeration of the 
effects of opioids, based on experience with morphine (see section 4.5). 
 
Excipients 
 
This medicinal product contains maltitol liquid. Patients with rare hereditary problems of fructose 
intolerance should not take this medicinal product. 
This medicinal product contains sunset yellow (E 110). Sunset yellow may cause allergic reactions. 
This medicinal product contains less than 1 mmol sodium (23 mg) per film i.e. essentially “sodium 
free”. 
 
Paediatric population 
 
Use in adolescents (age 15 - <18) 
Due to the lack of data in adolescents (age 15 - <18), patients in this age group should be more closely 
monitored during treatment. 
 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Buprenorphine/naloxone should not be taken together with: 
 



52 

• Alcoholic drinks or medicinal products containing alcohol, as alcohol increases the sedative 
effect of buprenorphine (see section 4.7). 

 
Buprenorphine/naloxone should be used cautiously when co-administered with: 
• Sedatives such as benzodiazepines or related medicinal products 
 The concomitant use of opioids with sedative medicinal products such as benzodiazepines or 

related medicinal products increases the risk of sedation, respiratory depression, coma and death 
because of additive CNS depressant effect. The dose and duration of concomitant use of 
sedative medicinal products should be limited (see section 4.4). Patients should be warned that 
it is extremely dangerous to self-administer non-prescribed benzodiazepines while taking this 
medicinal product and should also be cautioned to use benzodiazepines concurrently with this 
medicinal product only as directed by their physician (see section 4.4). 

 
• Other central nervous system depressants, other opioid derivatives (e.g. methadone, analgesics 

and antitussives), certain antidepressants, sedative H1-receptor antagonists, barbiturates, 
anxiolytics other than benzodiazepines, neuroleptics, clonidine and related substances: these 
combinations increase central nervous system depression. The reduced level of alertness can 
make driving and using machines hazardous. 

 
• Furthermore, adequate analgesia may be difficult to achieve when administering a full opioid 

agonist in patients receiving buprenorphine/naloxone. Therefore, the potential to overdose with 
a full agonist exists, especially when attempting to overcome buprenorphine partial agonist 
effects, or when buprenorphine plasma levels are declining. 

 
• Naltrexone and nalmefene are opioid antagonists that can block the pharmacological effects of 

buprenorphine. Co-administration during buprenorphine/naloxone treatment is contraindicated 
due to the potentially dangerous interaction that may precipitate a sudden onset of prolonged 
and intense opioid withdrawal symptoms (see section 4.3). 

 
• CYP3A4 inhibitors: an interaction study of buprenorphine with ketoconazole (a potent inhibitor 

of CYP3A4) resulted in increased Cmax and AUC (area under the curve) of buprenorphine 
(approximately 50 % and 70 % respectively) and, to a lesser extent, of norbuprenorphine. 
Patients receiving Suboxone should be closely monitored and may require dose reduction if 
combined with potent CYP3A4 inhibitors (e.g. protease inhibitors like ritonavir, nelfinavir or 
indinavir or azole antifungals such as ketoconazole or itraconazole, macrolide antibiotics). 

 
• CYP3A4 inducers: Concomitant use of CYP3A4 inducers with buprenorphine may decrease 

buprenorphine plasma concentrations, potentially resulting in sub-optimal treatment of opioid 
dependence with buprenorphine. It is recommended that patients receiving 
buprenorphine/naloxone should be closely monitored if inducers (e.g. phenobarbital, 
carbamazepine, phenytoin, rifampicin) are co-administered. The dose of buprenorphine or the 
CYP3A4 inducer may need to be adjusted accordingly. 

 
• The concomitant use of MAOI might produce exaggeration of the effects of opioids, based on 

experience with morphine. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited amount of data from the use of buprenorphine/naloxone in pregnant women. 
Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is 
unknown. 
 
Towards the end of pregnancy buprenorphine may induce respiratory depression in the newborn infant 
even after a short period of administration. Long-term administration of buprenorphine during the last 
three months of pregnancy may cause a withdrawal syndrome in the neonate (e.g. hypertonia, neonatal 



53 

tremor, neonatal agitation, myoclonus or convulsions). The syndrome is generally delayed from 
several hours to several days after birth. 
 
Due to the long half-life of buprenorphine, neonatal monitoring for several days should be considered 
at the end of pregnancy, to prevent the risk of respiratory depression or withdrawal syndrome in 
neonates. 
 
Furthermore, the use of buprenorphine/naloxone during pregnancy should be assessed by the 
physician. Buprenorphine/naloxone should be used during pregnancy only if the potential benefit 
outweighs the potential risk to the fetus. 
 
Breast-feeding 
 
It is unknown whether naloxone is excreted in human milk. Buprenorphine and its metabolites are 
excreted in human milk. In rat’s buprenorphine has been found to inhibit lactation. Therefore, 
breastfeeding should be discontinued during treatment with Suboxone. 
 
Fertility 
 
Animal studies have shown a reduction in female fertility at high doses (systemic exposure > 2.4 times 
the human exposure at the maximum recommended dose of 24 mg buprenorphine, based on AUC; see 
section 5.3). 
 
 
4.7 Effects on ability to drive and use machines 
 
Buprenorphine/naloxone has minor to moderate influence on the ability to drive and use machines 
when administered to opioid-dependent patients. This medicinal product may cause drowsiness, 
dizziness, or impaired thinking, especially during treatment induction and dose adjustment. If taken 
together with alcohol or central nervous system depressants, the effect is likely to be more pronounced 
(see sections 4.4 and 4.5). 
 
Patients should be cautioned about driving or operating hazardous machinery in case 
buprenorphine/naloxone may adversely affect their ability to engage in such activities. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The most commonly reported treatment-related adverse reactions reported during the pivotal clinical 
studies were constipation and symptoms commonly associated with drug withdrawal (i.e. insomnia, 
headache, nausea, hyperhidrosis and pain). Some reports of seizure, vomiting, diarrhoea, and elevated 
liver function tests were considered serious. 
 
The most commonly reported treatment-related adverse reactions associated with the sublingual or 
buccal administration of buprenorphine/naloxone were oral hypoesthesia and oral mucosal erythema, 
respectively. Other treatment-related adverse reactions reported by more than one patient were 
constipation, glossodynia and vomiting. 
 
Tabulated list of adverse reactions 
 
Adverse reactions reported during post-marketing surveillance are also included. 
 
The frequency of possible undesirable effects listed below is defined using the following convention: 
Very common (≥ 1/10), Common (≥ 1/100 to < 1/10), Uncommon (≥ 1/1,000 to < 1/100), Not known 
(cannot be estimated from the available data). 
 



54 

Table 1: Treatment-related adverse reactions reported in clinical trials and post-marketing 
surveillance of buprenorphine/naloxone 
 
System Organ 
Class 

Very common 
 

Common Uncommon Not Known 

Infections and 
infestations 

 Influenza, 
Infection, 
Pharyngitis, 
Rhinitis

Urinary tract 
infection, 
Vaginal infection 

 

Blood and 
lymphatic system 
disorders 

  Anaemia, 
Leukocytosis, 
Leukopenia, 
Lymphadenopathy, 
Thrombocytopenia 

 

Immune system 
disorders 

  Hypersensitivity Anaphylactic 
shock 

Metabolism and 
nutrition 
disorders 

  Decreased appetite, 
Hyperglycaemia, 
Hyperlipidaemia, 
Hypoglycaemia

 

Psychiatric 
disorders 

Insomnia Anxiety, 
Depression, 
Libido decreased, 
Nervousness, 
Thinking 
abnormal 

Abnormal dreams, 
Agitation, 
Apathy, 
Depersonalisation, 
Drug dependence, 
Euphoric mood, 
Hostility

Hallucination 

Nervous system 
disorders 

Headache Migraine, 
Dizziness, 
Hypertonia, 
Paraesthesia, 
Somnolence 

Amnesia, 
Disturbance in 
attention, 
Hyperkinesia, 
Seizure, 
Speech disorder, 
Tremor

Hepatic 
encephalopathy, 
Syncope 

Eye disorders  Amblyopia, 
Lacrimal disorder 

Conjunctivitis, 
Miosis, 
Vision blurred

 

Ear and labyrinth 
disorders 

   Vertigo 

Cardiac disorders   Angina pectoris, 
Bradycardia, 
Myocardial 
infarction, 
Palpitations, 
Tachycardia

 

Vascular 
disorders 

 Hypertension, 
Vasodilatation

Hypotension Orthostatic 
hypotension

Respiratory, 
thoracic and 
mediastinal 
disorders 

 Cough Asthma, 
Dyspnoea, 
Yawning 

Bronchospasm, 
Respiratory 
depression 

Gastrointestinal 
disorders 

Constipation, 
Nausea 

Abdominal pain, 
Diarrhoea, 
Dyspepsia, 
Flatulence, 
Oral mucosal 
erythema,

Hypoaesthesia oral, 
Glossodynia, 
Mouth ulceration, 
Oedema mouth, 
Oral pain, 
Paraesthesia oral, 

Glossitis, 
Stomatitis 



55 

System Organ 
Class 

Very common 
 

Common Uncommon Not Known 

Vomiting Tongue 
discolouration

Hepatobiliary 
disorders 

 Hepatic function 
abnormal 

 Hepatitis, 
Hepatitis acute, 
Jaundice, 
Hepatic necrosis, 
Hepatorenal 
syndrome 

Skin and 
subcutaneous 
tissue disorders 

Hyperhidrosis Pruritus, 
Rash, 
Urticaria 

Acne, 
Alopecia, 
Dermatitis 
exfoliative, 
Dry skin, 
Skin mass

Angioedema 

Musculoskeletal 
and connective 
tissue disorders 

 Back pain, 
Arthralgia, 
Muscle spasms, 
Myalgia

Arthritis  

Renal and urinary 
disorders 

 Urine abnormality Albuminuria, 
Dysuria, 
Haematuria, 
Nephrolithiasis, 
Urinary retention 

 

Reproductive 
system and breast 
disorders 

 Erectile 
dysfunction 

Amenorrhoea, 
Ejaculation 
disorder, 
Menorrhagia, 
Metrorrhagia

 

General disorders 
and 
administration 
site conditions 

Drug withdrawal 
syndrome 

Asthenia, 
Chest pain, 
Chills, 
Pyrexia, 
Malaise, 
Pain, 
Oedema 
peripheral 

Hypothermia Drug withdrawal 
syndrome 
neonatal 

Investigations  Liver function test 
abnormal, 
Weight decreased

Blood creatinine 
increased 

Transaminases 
increased 

Injury, poisoning 
and procedural 
complications 

 Injury Heat stroke, 
Poisoning 
(Intoxication)

 

 
Description of selected adverse reactions 
 
In cases of intravenous drug misuse, some adverse reactions are attributed to the act of misuse rather 
than the medicinal product and include local reactions, sometimes septic (abscess, cellulitis), and 
potentially serious acute hepatitis, and other infections such as pneumonia, endocarditis have been 
reported (see section 4.4). 
 
In patients presenting with marked drug dependence, initial administration of buprenorphine can 
produce a drug withdrawal syndrome similar to that associated with naloxone (see sections 4.2 and 
4.4). 
 



56 

Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Symptoms 
 
Respiratory depression as a result of central nervous system depression is the primary symptom 
requiring intervention in the case of overdose because it may lead to respiratory arrest and death. Signs 
of overdose may also include somnolence, amblyopia, miosis, hypotension, nausea, vomiting and/or 
speech disorders. 
 
Management 
 
General supportive measures should be instituted, including close monitoring of respiratory and 
cardiac status of the patient. Symptomatic treatment of respiratory depression and standard intensive 
care measures should be implemented. A patent airway and assisted or controlled ventilation must be 
assured. The patient should be transferred to an environment within which full resuscitation facilities 
are available. 
 
If the patient vomits, care must be taken to prevent aspiration of the vomitus. 
 
Use of an opioid antagonist (i.e., naloxone) is recommended, despite the modest effect it may have in 
reversing the respiratory symptoms of buprenorphine compared with its effects on full agonist opioid 
agents. 
 
If naloxone is used, the long duration of action of buprenorphine should be taken into consideration 
when determining the length of treatment and medical surveillance needed to reverse the effects of an 
overdose. Naloxone can be cleared more rapidly than buprenorphine, allowing for a return of 
previously controlled buprenorphine overdose symptoms, so a continuing infusion may be necessary. 
If infusion is not possible, repeated dosing with naloxone may be required. Ongoing intravenous 
infusion rates should be titrated to patient response. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other nervous system drugs, drugs used in addictive disorders, ATC 
code: N07BC51. 
 
Mechanism of action 
 
Buprenorphine is an opioid partial agonist/antagonist which binds to the μ and κ (kappa) opioid 
receptors of the brain. Its activity in opioid maintenance treatment is attributed to its slowly reversible 
properties with the μ-opioid receptors which, over a prolonged period, might minimise the need of 
addicted patients for drugs. 
 
Opioid agonist ceiling effects were observed during clinical pharmacology studies in opioid-dependent 
persons. 
 
Naloxone is an antagonist at μ-opioid receptors. When administered orally or sublingually in usual 
doses to patients experiencing opioid withdrawal, naloxone exhibits little or no pharmacological effect 



57 

because of its almost complete first pass metabolism. However, when administered intravenously to 
opioid-dependent persons, the presence of naloxone in Suboxone produces marked opioid antagonist 
effects and opioid withdrawal, thereby deterring intravenous abuse. 
 
Clinical efficacy and safety 
 
Efficacy and safety data for buprenorphine/naloxone are primarily derived from a one-year clinical 
trial, comprising a 4-week randomised double blind comparison of buprenorphine/naloxone, 
buprenorphine and placebo followed by a 48-week safety study of buprenorphine/naloxone. In this 
trial, 326 heroin-addicted subjects were randomly assigned to either buprenorphine/naloxone 16 mg 
per day, 16 mg buprenorphine per day or placebo. For subjects randomized to either active treatment, 
dosing began with 8 mg of buprenorphine on Day 1, followed by 16 mg (two 8 mg) of buprenorphine 
on Day 2. On Day 3, those randomized to receive buprenorphine/naloxone were switched to the 
combination tablet. Subjects were seen daily in the clinic (Monday through Friday) for dosing and 
efficacy assessments. Take-home doses were provided for weekends. The primary study comparison 
was to assess the efficacy of buprenorphine and buprenorphine/naloxone individually against placebo. 
The percentage of thrice-weekly urine samples that were negative for non-study opioids was 
statistically higher for both buprenorphine/naloxone versus placebo (p < 0.0001) and buprenorphine 
versus placebo (p < 0.0001). 
 
In a double-blind, double-dummy, parallel-group study comparing buprenorphine ethanolic solution 
versus a full agonist active control, 162 subjects were randomized to receive the ethanolic sublingual 
solution of buprenorphine at 8 mg/day (a dose which is roughly comparable to a dose of 12 mg/day of 
buprenorphine/naloxone), or two relatively low doses of active control, one of which was low enough 
to serve as an alternative to placebo, during a 3 to10 day induction phase, a 16-week maintenance 
phase and a 7-week detoxification phase. Buprenorphine was titrated to maintenance dose by Day 3; 
active control doses were titrated more gradually. Based on retention in treatment and the percentage 
of thrice-weekly urine samples negative for non-study opioids, buprenorphine was more effective than 
the low dose of the control in keeping heroin addicts in treatment and in reducing their use of opioids 
while in treatment. The effectiveness of buprenorphine, 8 mg per day was similar to that of the 
moderate active control dose, but equivalence was not demonstrated. 
 
In a multicentre RCT study, 92 patients received either Suboxone film or Suboxone sublingual tablets 
following a 7-day run-in period with Suboxone sublingual tablets. It took 4 minutes on average for the 
sublingual tablets to visibly dissolve and 3 minutes on average for the sublingual film to dissolve. As 
concerns removability of sublingually applied films it was demonstrated that after 30 seconds of the 
application of a single film, none of the study participants could remove some or all the film. 
However, when 2 or more films were administered the participants were more likely to be able to 
remove some or all the film after 30 seconds. No more than 2 films should be administered at the same 
time (see section 4.2). 
 
5.2 Pharmacokinetic properties 
 
Buprenorphine 
 
Absorption 
Buprenorphine, when taken orally, undergoes first-pass metabolism with N-dealkylation and 
glucuroconjugation in the small intestine and the liver. The use of this medicinal product by the oral 
route is therefore inappropriate. 
 
Plasma levels of buprenorphine increased with increasing sublingual dose of buprenorphine/naloxone. 
There was wide inter-patient variability in buprenorphine plasma levels, but within subjects the 
variability was low. 
 



58 

Table 2. Pharmacokinetic parameters (Mean ± SD) of buprenorphine and naloxone following 
sublingual administration of Suboxone film  
 
PK Parameter Suboxone film dose (mg) 

2 mg/0.5 mg 4 mg / 1 mg* 8 mg / 2 mg 12 mg / 3 mg
Buprenorphine 
Cmax (ng/mL) 0.947 ± 0.374 1.40 ± 0.687 3.37 ± 1.80 4.55 ± 2.50 
Tmax (h) Median, (min-max) 1.53 (0.75 - 4.0) 1.50 (0.5, 3.0) 1.25 (0.75 - 4.0) 1.50 (0.5, 3.0) 
AUCinf (ng.hr/mL) 8.654 ± 2.854 13.71 ± 5.875 30.45 ± 13.03 42.06 ± 14.64 
t1/2 (hr) 33.41 ± 13.01 24.30 ± 11.03 32.82 ± 9.81 34.66 ± 9.16 
Norbuprenorphine 
Cmax (ng/mL) 0.312 ±0.140 0.617 ±0.311 1.40 ±1.08 2.37 ±1.87 
Tmax (h) Median, (min-max) 1.38 (0.5 - 8.0) 1.25 (0.5, 48.0) 1.25 (0.75 - 12.0) 1.25 (0.75, 8.0) 

AUCinf (ng.hr/mL) 14.52 ±5.776 23.73 ±10.60 54.91 ±36.01 71.77 ±29.38 
t1/2 (hr) 56.09 ±31.14 45.96 ±40.13 41.96 ±17.92 34.36 ±7.92 
Naloxone 
Cmax (ng/mL) 0.054 ± 0.023 0.0698 ± 0.0378 0.193 ± 0.091 0.238 ± 0.144 
Tmax (h) Median, (min-max) 0.75 (0.5 - 2.0) 0.75 (0.5, 1.5) 0.75 (0.5 - 1.25) 0.75 (0.50, 1.25) 
AUCinf (ng.hr/mL) 0.137 ± 0.043 0.204 ± 0.108 0.481 ± 0.201 0.653 ± 0.309 
t1/2 (hr) 5.00 ± 5.52 3.91 ± 3.37 6.25 ± 3.14 11.91 ± 13.80 
*There are no data for the 4 mg/1 mg strength film; it is compositionally proportional to 2 mg/0.5 mg 
strength film and has the same size of 2 × 2 mg/0.5 mg film strength. 
 
Table 3. Changes in pharmacokinetic parameters for Suboxone film administered sublingually 
or buccally in comparison to Suboxone sublingual tablet 
 
 
Dosage PK 

Parameter 
Increase in Buprenorphine PK 

Parameter 
Increase in Naloxone 

Film 
Sublingual 
Compared 
to Tablet 
Sublingual 

Film 
Buccal 
Compared 
to Tablet 
Sublingual

Film 
Buccal 
Compared 
to Film 
Sublingual

Film 
Sublingual 
Compared 
to Tablet 
Sublingual 

Film 
Buccal 
Compared 
to Tablet 
Sublingual

Film 
Buccal 
Compared 
to Film 
Sublingual

1 × 
2 mg/0.5 mg 

Cmax 22 % 25 % - Cmax - - -
AUC0-last - 19 % - AUC0-last - - -

2 × 
2 mg/0.5 mg 

Cmax - 21 % 21 % Cmax - 17 % 21 %
AUC0-last - 23 % 16 % AUC0-last - 22 % 24 %

1 × 
8 mg/2 mg 

Cmax 28 % 34 % - Cmax 41 % 54 % -
AUC0-last 20 % 25 % - AUC0-last 30 % 43 % -

1 × 
12 mg/3 mg 

Cmax 37 % 47 % - Cmax 57 % 72 % 9 %
AUC0-last 21 % 29 % - AUC0-last 45 % 57 % -

1 × 
8 mg/2 mg 
plus 
2 × 
2 mg/0.5 mg 

Cmax - 27 % 13 % Cmax 17 % 38 % 19 %
AUC0-last - 23 % - AUC0-last - 30 % 19 % 

Note 1. ‘– ‘represents no change when the 90 % confidence intervals for the geometric mean ratios of 
the Cmax and AUC0-last values are within the 80 % to 125 % limit. 
Note 2. There are no data for the 4 mg/1 mg strength film; it is compositionally proportional to the 
2 mg/0.5 mg strength film and has the same size as the 2 × 2 mg/0.5 mg film strength. 
 
Distribution 



59 

The absorption of buprenorphine is followed by a rapid distribution phase (distribution half-life of 2 to 
5 hours). 
 
Buprenorphine is highly lipophilic, which leads to rapid penetration of the blood-brain barrier. 
Buprenorphine is approximately 96 % protein bound, primarily to alpha and beta globulin. 
 
Biotransformation 
Buprenorphine is primarily metabolised through N-dealkylation by liver microsomal CYP3A4. The 
parent molecule and the primary dealkylated metabolite, norbuprenorphine, undergo subsequent 
glucuronidation. Norbuprenorphine binds to opioid receptors in vitro; however, it is not known 
whether norbuprenorphine contributes to the overall effect of buprenorphine/naloxone. 
 
Elimination 
Elimination of buprenorphine is bi- or tri-exponential, and the mean terminal elimination half-life 
from plasma is reported in Table 2. 
Buprenorphine is excreted in the faeces (~70 %) by biliary excretion of the glucuroconjugated 
metabolites, the rest (~30 %) being excreted in the urine. 
 
Linearity/non-linearity 
Buprenorphine Cmax and AUC increased in a linear fashion with the increasing dose (in the range of 4 
to 16 mg), although the increase was not directly dose-proportional. 
 
Naloxone 
 
Absorption 
Naloxone mean peak plasma concentrations were too low to assess dose-proportionality, and in seven 
of eight subjects tested who had naloxone plasma levels above the limit of quantification 
(0.05 ng/mL), naloxone was not detected beyond 2 hours post-dose. 
Naloxone has not been found to affect the pharmacokinetics of buprenorphine, and both 
buprenorphine sublingual tablets and buprenorphine/naloxone sublingual film deliver similar plasma 
concentrations of buprenorphine. 
 
Distribution 
Naloxone is approximately 45 % protein bound, primarily to albumin. 
 
Biotransformation 
Naloxone is metabolized in the liver, primarily by glucuronide conjugation, and excreted in the urine. 
Naloxone undergoes direct glucuronidation to naloxone 3-glucuronide, as well as N-dealkylation and 
reduction of the 6-oxo group. 
 
Elimination 
Naloxone is excreted in the urine, with a mean half-life of elimination from plasma ranging from 2 to 
12 hours. 
 
Special populations 
 
Elderly 
No pharmacokinetic data in elderly patients are available. 
 
Renal impairment 
Renal elimination plays a relatively small role (~30 %) in the overall clearance of 
buprenorphine/naloxone. No dose modification based on renal function is required but caution is 
recommended when dosing subjects with severe renal impairment (see section 4.3). 
 
Hepatic impairment 
The effect of hepatic impairment on the pharmacokinetics of buprenorphine were evaluated in a post-
marketing study. Table 4 summarises the results from a clinical trial in which the exposure of 



60 

buprenorphine and naloxone was determined after administering a buprenorphine/naloxone 2.0/0.5 mg 
sublingual tablet in healthy subjects, and in subjects with varied degrees of hepatic impairment. 
 
Table 4. Effect of hepatic impairment on pharmacokinetic parameters of buprenorphine and 
naloxone following Suboxone administration (change relative to healthy subjects) 
 

PK 
Parameter 

Mild Hepatic 
Impairment 
(Child-Pugh Class A) 
(n = 9) 

Moderate Hepatic 
Impairment 
(Child-Pugh Class B) 
(n = 8) 

Severe Hepatic 
Impairment 
(Child-Pugh Class C) 
(n = 8) 

Buprenorphine 
Cmax 1.2-fold increase 1.1-fold Increase 1.7-fold increase 
AUClast Similar to control 1.6-fold increase 2.8-fold increase 
 
Naloxone 
Cmax Similar to control 2.7-fold increase 11.3-fold increase 
AUClast 0.2-fold decrease 3.2-fold increase 14.0-fold increase 

 
Overall, buprenorphine plasma exposure increased approximately 3-fold in patients with severely 
impaired hepatic function, while naloxone plasma exposure increased 14-fold with severely impaired 
hepatic function. 
 
5.3 Preclinical safety data 
 
The combination of buprenorphine and naloxone has been investigated in acute and repeated dose (up 
to 90 days in rats) toxicity studies in animals. No synergistic enhancement of toxicity has been 
observed. Undesirable effects were based on the known pharmacological activity of opioid agonist 
and/or antagonistic substances. 
 
The combination (4:1) of buprenorphine hydrochloride and naloxone hydrochloride was not 
mutagenic in a bacterial mutation assay (Ames test) and was not clastogenic in an in vitro cytogenetic 
assay in human lymphocytes or in an intravenous micronucleus test in the rat. 
 
Reproduction studies by oral administration of buprenorphine: naloxone (ratio 1:1) indicated that 
embryolethality occurred in rats in the presence of maternal toxicity at all doses. The lowest dose 
studied represented exposure multiples of 1 × for buprenorphine and 5 × for naloxone at the maximum 
human therapeutic dose calculated on a mg/m2 basis. No developmental toxicity was observed in 
rabbits at maternally toxic doses. Further, no teratogenicity has been observed in either rats or rabbits. 
A peri-postnatal study has not been conducted with buprenorphine/naloxone; however, maternal oral 
administration of buprenorphine at high doses during gestation and lactation resulted in difficult 
parturition (possible as a result of the sedative effect of buprenorphine), high neonatal mortality and a 
slight delay in the development of some neurological functions (surface righting reflex and startle 
response) in neonatal rats. 
 
Dietary administration of buprenorphine/naloxone in the rat at dose levels of 500 ppm or greater 
produced a reduction in fertility demonstrated by reduced female conception rates. A dietary dose of 
100 ppm (estimated exposure approximately 2.4 × for buprenorphine at a human dose of 24 mg 
buprenorphine/naloxone based on AUC, plasma levels of naloxone were below the limit of detection 
in rats) had no adverse effect on fertility in females. 
 
A carcinogenicity study with buprenorphine/naloxone was conducted in rats at doses of 7 mg/kg/day, 
30 mg/kg/day and 120 mg/kg/day, with estimated exposure multiples of 3 times to 75 times, based on 
a human daily sublingual dose of 16 mg calculated on a mg/m2 basis. Statistically significant increases 
in the incidence of benign testicular interstitial (Leydig's) cell adenomas were observed in all dosage 
groups. 
 



61 

 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Macrogol  
Maltitol liquid 
Natural lime flavour 
Hypromellose 
Citric acid 
Acesulfame potassium 
Sodium citrate 
Sunset yellow (E 110) 
 
Printing ink 
Propylene Glycol (E1520) 
 
6.2 Incompatibilities 
 
Not applicable 
 
 
 
6.3 Shelf life 
 
18 months 
 
6.4 Special precautions for storage 
 
Store below 25 °C. 
 
6.5 Nature and contents of container 
 
The films are packed in child-resistant individual sachets consisting of four composite layers of 
polyethylene terephthalate (PET), Low Density Polyethylene (LDPE), aluminium foil and Low-
Density Polyethylene (LDPE), which are heat sealed at the edges. 
 
Pack sizes: 7 × 1, 14 × 1 and 28 × 1 sublingual films. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Indivior Europe Limited 
27 Windsor Place 
Dublin 2 
Ireland 
 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 



62 

 
Suboxone 2 mg/0.5 mg sublingual film 
EU/1/06/359/007 7 × 1 sublingual film  
EU/1/06/359/008 14 × 1 sublingual film  
EU/1/06/359/009 28 × 1 sublingual film  
 
Suboxone 4 mg/1 mg sublingual film 
EU/1/06/359/010 7 × 1 sublingual film 
EU/1/06/359/011 14 × 1 sublingual film 
EU/1/06/359/012 28 × 1 sublingual film 
 
Suboxone 8 mg/2 mg sublingual film 
EU/1/06/359/013 7 × 1 sublingual film  
EU/1/06/359/014 14 × 1 sublingual film  
EU/1/06/359/015 28 × 1 sublingual film  
 
Suboxone 12 mg/3 mg sublingual film 
EU/1/06/359/016 7 × 1 sublingual film  
EU/1/06/359/017 14 × 1 sublingual film  
EU/1/06/359/018 28 × 1 sublingual film  
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 26 September 2006 
Date of latest renewal: 16 September 2011 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the web-site of the European Medicines 
Agency http://www.ema.europa.eu/ 



63 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR 
BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS 

REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS 

OF THE MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH 

REGARD TO THE SAFE AND EFFECTIVE 
USE OF THE MEDICINAL PRODUCT 

 
 



64 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Sublingual tablet 
 
Reckitt Benckiser Healthcare (UK) Ltd  
Dansom Lane 
Hull, East Yorkshire 
HU8 7DS 
United Kingdom 
 
Or 
 
Indivior Europe Limited 
27 Windsor Place 
Dublin 2 
Ireland 
 
Sublingual film 
 
Almac Pharma Services Limited 
Seagoe Industrial Estate 
Portadown, Craigavon 
BT63 5UA, United Kingdom 
 
Or 
 
Almac Pharma Services (Ireland) Limited 
Finnabair Industrial Estate 
Dundalk, Co. Louth 
A91 P9KD, Ireland 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to special and restricted medical prescription (see Annex I: Summary of 
Product Characteristics, section 4.2). 
 
 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
 Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c (7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 
 
 
 
 



65 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT   
 
 Risk Management Plan (RMP) 

 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 
Marketing Authorisation and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 



66 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 



67 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



68 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
PACK OF 7 and 28 TABLETS 2 mg STRENGTH 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Suboxone 2 mg/0.5 mg sublingual tablets 
buprenorphine/naloxone  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sublingual tablet contains 2 mg buprenorphine (as hydrochloride) and 0.5 mg naloxone (as 
hydrochloride dihydrate).  
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
7 sublingual tablets 
28 sublingual tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Sublingual use 
Do not swallow. 
Keep the tablet under your tongue until it dissolves. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



69 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Indivior Europe Limited  
27 Windsor Place 
Dublin 2 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/359/001  2 mg sublingual tablets 7 
EU/1/06/359/002  2 mg sublingual tablets 28 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Suboxone 2 mg/0.5 mg sublingual tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:   
NN:   
 



70 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
PACK OF 7 and 28 TABLETS 2 mg STRENGTH 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Suboxone 2 mg/0.5 mg sublingual tablets 
buprenorphine / naloxone  
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Indivior Europe Limited  
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



71 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
PACK OF 7 and 28 TABLETS 8 mg STRENGTH 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Suboxone 8 mg/2 mg sublingual tablets 
buprenorphine/naloxone  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sublingual tablet contains 8 mg buprenorphine as buprenorphine hydrochloride and 2 mg 
naloxone as naloxone hydrochloride dihydrate.  
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
7 sublingual tablets 
28 sublingual tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Sublingual use 
Do not swallow. 
Keep the tablet under your tongue until it dissolves. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



72 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Indivior Europe Limited  
27 Windsor Place 
Dublin 2 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/359/003  8 mg sublingual tablets 7 
EU/1/06/359/004  8 mg sublingual tablets 28 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Suboxone 8 mg/2 mg sublingual tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:   
NN:   
 



73 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
PACK OF 7 and 28 TABLETS 8 mg STRENGTH 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Suboxone 8 mg/2 mg sublingual tablets 
buprenorphine / naloxone  
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Indivior Europe Limited  
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 



74 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
PACK OF 7 and 28 TABLETS 16 mg STRENGTH 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Suboxone 16 mg/4 mg sublingual tablets 
buprenorphine/naloxone  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sublingual tablet contains 16 mg buprenorphine (as hydrochloride) and 4 mg naloxone (as 
hydrochloride dihydrate).  
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose monohydrate. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
7 sublingual tablets 
28 sublingual tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Sublingual use 
Do not swallow. 
Keep the tablet under your tongue until it dissolves. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 



75 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Indivior Europe Limited  
27 Windsor Place 
Dublin 2 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/359/005  16 mg sublingual tablets 7 
EU/1/06/359/006  16 mg sublingual tablets 28 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Suboxone 16 mg/4 mg sublingual tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:   
NN:   
 
 



76 

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
PACK OF 7 and 28 TABLETS 16 mg STRENGTH 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Suboxone 16 mg/4 mg sublingual tablets 
buprenorphine / naloxone  
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Indivior Europe Limited  
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 



77 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Suboxone 2 mg/0.5 mg sublingual film 
buprenorphine/naloxone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film contains 2 mg buprenorphine (as hydrochloride) and 0.5 mg naloxone (as hydrochloride 
dihydrate). 
 
 
3. LIST OF EXCIPIENTS 
 
Contains maltitol liquid and sunset yellow (E110) 
See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Sublingual film 
 
7 × 1 sublingual film 
14 × 1 sublingual film 
28 × 1 sublingual film 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For sublingual use and/or buccal use only. 
Do not swallow or chew. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



78 

Store below 25 °C 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Indivior Europe Limited 
27 Windsor Place 
Dublin 2 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/359/007 (7 × 1 film) 
EU/1/06/359/008 (14 × 1 film) 
EU/1/06/359/009 (28 × 1 film) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Suboxone 2 mg/0.5 mg sublingual film 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18.  UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



79 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SACHET 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Suboxone 2 mg/0.5 mg sublingual film 
buprenorphine/naloxone 
 
2. METHOD OF ADMINISTRATION 
 
sublingual use and/or buccal use 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 sublingual film 
 
6. OTHER 
 
INSTRUCTIONS FOR USE 
To open, tear down at the slit or cut along the arrow. 
Read the package leaflet before use. 
Store below 25 °C. 
Keep out of the sight and reach of children. 
 



80 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Suboxone 4 mg/1 mg sublingual film 
buprenorphine/naloxone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film contains 4 mg buprenorphine (as hydrochloride) and 1 mg naloxone (as  hydrochloride 
dihydrate). 
 
 
3. LIST OF EXCIPIENTS 
 
Contains maltitol liquid and sunset yellow (E110) 
See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Sublingual film 
 
7 × 1 sublingual film 
14 × 1 sublingual film 
28 × 1 sublingual film 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For sublingual use and/or buccal use only. 
Do not swallow or chew. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 



81 

 
Store below 25 °C 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Indivior Europe Limited 
27 Windsor Place 
Dublin 2 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/359/010 (7 × 1 film) 
EU/1/06/359/011 (14 × 1 film) 
EU/1/06/359/012 (28 × 1 film) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Suboxone 4 mg/1 mg sublingual film 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 



82 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SACHET 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Suboxone 4 mg/1 mg sublingual film 
buprenorphine/naloxone 
 
 
2. METHOD OF ADMINISTRATION 
 
sublingual use and/or buccal use 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 sublingual film 
 
6. OTHER 
 
INSTRUCTIONS FOR USE 
To open, tear down at the slit or cut along the arrow. 
Read the package leaflet before use. 
Store below 25 °C. 
Keep out of the sight and reach of children. 
 



83 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Suboxone 8 mg/2 mg sublingual film 
buprenorphine/naloxone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film contains 8 mg buprenorphine (as hydrochloride) and 2 mg naloxone (as hydrochloride 
dihydrate). 
 
 
3. LIST OF EXCIPIENTS 
 
Contains maltitol liquid and sunset yellow (E 110) 
See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Sublingual film 
 
7 × 1 sublingual film 
14 × 1 sublingual film 
28 × 1 sublingual film 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For sublingual use and/or buccal use only. 
Do not swallow or chew. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 



84 

 
Store below 25 °C 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Indivior Europe Limited 
27 Windsor Place 
Dublin 2 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/359/013 (7 × 1 film) 
EU/1/06/359/014 (14 × 1 film) 
EU/1/06/359/015 (28 × 1 film) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Suboxone 8 mg/2 mg sublingual film 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



85 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SACHET 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Suboxone 8 mg/2 mg sublingual film 
buprenorphine/naloxone 
 
 
2. METHOD OF ADMINISTRATION 
 
sublingual use and/or buccal use 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 sublingual film 
 
6. OTHER 
 
INSTRUCTIONS FOR USE 
To open, tear down at the slit or cut along the arrow. 
Read the package leaflet before use. 
Store below 25 °C. 
Keep out of the sight and reach of children. 
 



86 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Suboxone 12 mg/3 mg sublingual film 
buprenorphine/naloxone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film contains 12 mg buprenorphine (as hydrochloride) and 3 mg naloxone (as hydrochloride 
dihydrate). 
 
 
3. LIST OF EXCIPIENTS 
 
Contains maltitol liquid and sunset yellow (E 110) 
See leaflet for further information 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Sublingual film 
 
7 × 1 sublingual film 
14 × 1 sublingual film 
28 × 1 sublingual film 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For sublingual use and/or buccal use only. 
Do not swallow or chew. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 



87 

 
Store below 25 °C 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Indivior Europe Limited 
27 Windsor Place 
Dublin 2 
Ireland 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/06/359/016 (7 × 1 film) 
EU/1/06/359/017 (14 × 1 film) 
EU/1/06/359/018 (28 × 1 film) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Suboxone 12 mg/3 mg sublingual film 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



88 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SACHET 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Suboxone 12 mg/3 mg sublingual film 
buprenorphine/naloxone 
 
 
2. METHOD OF ADMINISTRATION 
 
sublingual use and/or buccal use 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 sublingual film 
 
6. OTHER 
 
INSTRUCTIONS FOR USE 
To open, tear down at the slit or cut along the arrow. 
Read the package leaflet before use. 
Store below 25 °C. 
Keep out of the sight and reach of children. 

 
 
 



89 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



90 

PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Suboxone 2 mg/0.5 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  Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
 If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. See section 4. 
 
What is in this leaflet 
1. What Suboxone is and what it is used for 
2. What you need to know before you take Suboxone 
3. How to take Suboxone 
4. Possible side effects 
5 How to store Suboxone 
6. Contents of the pack and other information 
 
 
1. What Suboxone is and what it is used for 
 
Suboxone 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. Suboxone 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 Suboxone 
 
Do not take Suboxone 
 if you are allergic (hypersensitive) 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. 

 
 
Warnings and precautions  
 
Talk to your doctor before taking Suboxone 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) 
 



91 

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. 
 

 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. 

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

 
 Liver damage 

Liver damage has been reported after taking Suboxone, 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 Suboxone. 

 
 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. 

 
 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 Suboxone 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
 
Some medicines may increase the side effects of Suboxone and may sometimes cause very serious 
reactions. Do not take any other medicines whilst taking Suboxone without first talking to your doctor, 
especially: 
 
 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).  

 



92 

 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 isocarboxazid, 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. 
‐ 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 agents (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 Suboxone. These include medicines used to treat 

epilepsy (such as carbamazepine and phenytoin), and medicines used to treat tuberculosis 
(rifampicin). 

 Naltrexone and nalmefene (drugs used to treat addictive disorders) may prevent the therapeutic 
effects of Suboxone. They should not be taken at the same time as Suboxone treatment because 
you may experience a sudden onset of prolonged and intense withdrawal. 

 
Suboxone with food, drink and alcohol 
Alcohol may increase drowsiness and may increase the risk of respiratory failure if taken with 
Suboxone. Do not take Suboxone 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 Suboxone 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 Suboxone 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 Suboxone passes into breast milk. 
 
Ask your doctor or pharmacist for advice before taking any medicine. 
 
Driving and using machines 
Suboxone 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 Suboxone. Do not drive, use any tools or machines, or perform dangerous 
activities until you know how this medicine affects you.  
 
Suboxone contains lactose 
If you have been told by your doctor that you have intolerance to some sugars, contact your doctor 
before taking this medicine. 
 
3. How to take Suboxone 
 



93 

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 to two 
tablets of Suboxone 2 mg/0.5 mg. An additional one to two tablets of the Suboxone 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 Suboxone. A doctor’s 
assessment of your readiness for treatment will guide the timing of your first Suboxone dose.  
 
 Starting treatment of Suboxone whilst dependent on heroin 

 
If you are dependent upon heroin or a short acting opioid, your first dose of Suboxone should be 
taken when signs of withdrawal appear, but not less than 6 hours after you last used opioids. 

 
 Starting treatment of Suboxone 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 Suboxone therapy. The first dose of 
Suboxone should be taken when signs of withdrawal appear, but not less than 24 hours after you 
last used methadone.  

 
Taking Suboxone 
 
 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. 
 
 



94 

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 – Starting from the edge where the seal is lifted, pull back the foil on the back to 
remove the tablet 

 
 
 
 
 
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 Suboxone you take 
according to your needs. If you have the impression that the effect of Suboxone 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 Suboxone 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 Suboxone 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 Suboxone may cause serious and life-
threatening 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. 
 
 

1 

2 

3 



95 

If you forget to take Suboxone 
Tell your doctor as soon as possible if you miss a dose. 
 
If you stop taking Suboxone 
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, Suboxone 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 Suboxone 

Very common side effects (may effect more than one in 10 people): 
Insomnia (inability to sleep), constipation, nausea, excessive sweating, headache, drug 
withdrawal syndrome 

Common side effects (may effect up to 1 in 10 people): 
Weight loss, swelling (hands and feet), drowsiness, anxiety, nervousness, tingling, depression, 
decreased sexual drive, increase in muscle tension, abnormal thinking, increased tearing 
(watering eyes) or other tearing disorder, blurred vision, flushing, increased blood pressure, 
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 discomfort, accidental injury caused by 
loss of alertness or co-ordination, faintness and dizziness.

Uncommon side effects (may effect up to 1 in 100 people): 
Swollen glands (lymph nodes), agitation, tremor, abnormal dream, excessive muscle activity, 
depersonalisation (not feeling like yourself), medicine dependence, amnesia (memory 
disturbance), 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 urination, 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 Suboxone 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 

 



96 

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. 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. 
 
 
5. How to store Suboxone 
 
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 carton. The expiry date refers to 
the last day of that month  
 
This medicinal product does not require any special storage conditions. However, Suboxone 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. Content of the pack and other Information  
 
What Suboxone contains 
 
- The active substances are buprenorphine and naloxone.  

Each 2 mg/0.5 mg sublingual tablet contains 2 mg buprenorphine (as hydrochloride) and 0.5 mg 
naloxone (as hydrochloride dihydrate).  

- The other ingredients are lactose monohydrate, mannitol, maize starch, povidone K30, citric 
acid anhydrous, sodium citrate, magnesium stearate, acesulfame potassium and natural lemon 
and lime flavour. 

 
What Suboxone looks like and contents of the pack 
 
Suboxone 2 mg/0.5 mg sublingual tablets are white hexagonal biconvex tablets of 6.5 mm with “N2” 
debossed on one side. 
Packed in packs of 7 and 28 tablets. 
Not all pack sizes may be marketed. 
 
 
Marketing Authorisation Holder 
 
Indivior Europe Limited  
27 Windsor Place 
Dublin 2 
Ireland 
 



97 

 
Manufacturer 
Reckitt Benckiser Healthcare (UK) Ltd,  
Dansom Lane,  
Hull,  
East Yorkshire HU8 7DS,  
United Kingdom. 
 
Or 
 
Indivior Europe Limited 
27 Windsor Place 
Dublin 2 
Ireland 
 
For any information about this medicine, please contact the Marketing Authorisation Holder: 
 
België/Belgique/Belgien, България, Česká republika, Danmark, Deutschland, Eesti, Ελλάδα, España, 
Hrvatska, Ireland, Ísland, Italia, Κύπρος, Latvija, Lietuva, Luxembourg/Luxemburg, Magyarország, 
Malta, Nederland, Norge, Österreich, Polska, Portugal, România, Slovenija, Slovenská republika, 
Suomi/Finland, Sverige, United Kingdom.  
 
United Kingdom  
Indivior Europe Limited 
Telephone 0808 234 9243 
Email: PatientSafetyRoW@indivior.com 
 
 
This leaflet was last revised in  
 
Detailed information on this medicine is available on the website of the European Medicines Agency 
http://www.ema.europa.eu/ 



98 

Package leaflet: Information for the user 
 

Suboxone 8 mg/2 mg sublingual tablets 
buprenorphine / naloxone 

 
 

Read all of this leaflet carefully before you start taking this 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. Do not pass it on to others. It may harm them, even 

if their symptoms are the same as yours. 
 If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. See section 4. 
 
What is in this leaflet 
1. What Suboxone is and what it is used for 
2. What do you need to know before you take Suboxone 
3. How to take Suboxone 
4. Possible side effects 
5 How to store Suboxone 
6. Content of the pack and other information 
 
 
1. What Suboxone is and what it is used for 
 
Suboxone 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. Suboxone is used in adults and adolescents 
over 15 years of age, who are also receiving medical, social and psychological support. 
 
 
2. What do you need to know before you take Suboxone 
 
Do not take Suboxone 
 if you are allergic (hypersensitive) 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. 

 
 
Warnings and precautions 
 
Talk to your doctor before taking Suboxone 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 enlarge prostrate in men) 
 any kidney disease. 
 thyroid problems 
 adrenocortical disorder (e.g. Addison’s disease) 
 



99 

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. 
 

 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. 

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

 
 Liver damage 

Liver damage has been reported after taking Suboxone, 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 Suboxone.  

 
 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. 

 
 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 Suboxone 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
 
Some medicines may increase the side effects of Suboxone and may sometimes cause very serious 
reactions. Do not take any other medicines whilst taking Suboxone without first talking to your doctor 
especially: 
 
 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). 

 



100 

 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. 
‐ 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 agents (used to treat fungal infections) such as ketoconzaole, itraconazole, 

certain antibiotics may extend the effects of this medicine. 
 some medicines may decrease the effect of Suboxone. These include medicines used to treat 

epilepsy (such as carbamazepine and phenytoin), and medicines used to treat tuberculosis 
(rifampicin). 

 naltrexone and nalmefene (drugs used to treat addictive disorders) may prevent the therapeutic 
effects of Suboxone. They should not be taken at the same time as Suboxone treatment because 
you may experience a sudden onset of prolonged and intense withdrawal.  

 
Suboxone with food, drink and alcohol 
Alcohol may increase drowsiness and may increase the risk of respiratory failure if taken with 
Suboxone. Do not take Suboxone 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 Suboxone 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 Suboxone 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 Suboxone passes into breast milk. 
 
Ask your doctor or pharmacist for advice before taking any medicine. 
 
Driving and using machines 
Suboxone 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 Suboxone.  Do not drive, use any tools or machines, or perform dangerous 
activities until you know how this medicine affects you.  
 
Suboxone contains lactose 
If you have been told by your doctor that you have intolerance to some sugars, contact your doctor 
before taking this medicine. 
 



101 

3. How to take Suboxone 
 
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 to two 
tablets of Suboxone 2 mg/0.5 mg. An additional one to two tablets of the Suboxone 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 Suboxone. A doctor’s 
assessment of your readiness for treatment will guide the timing of your first Suboxone dose.  
 
 Starting treatment of Suboxone whilst dependent on heroin 

 
If you are dependent upon heroin or a short acting opioid, your first dose of Suboxone should be 
taken when signs of withdrawal appear, but not less than 6 hours after you last used opioids. 
 

 Starting treatment of Suboxone 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 Suboxone therapy. The first dose of 
Suboxone should be taken when signs of withdrawal appear, but not less than 24 hours after you 
last used methadone.  
 

Taking Suboxone 
 
 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. 
 
 
 
 

 

1 



102 

 
 

2 - Remove just one section from the blister pack, tearing it along the perforated 
line. 

 
 
 
 
 

 
3 – Starting from the edge where the seal is lifted, pull back the foil on the back to 
remove the tablet 

 
 
 
 
 
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 Suboxone you take 
according to your needs. If you have the impression that the effect of Suboxone is too strong or too 
weak, talk to your doctor or pharmacist. The maximum daily dose is 24 .  
 
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 Suboxone 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 Suboxone 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 Suboxone may cause serious and life-
threatening 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 Suboxone 
Tell your doctor as soon as possible if you miss a dose. 
 
If you stop taking Suboxone 
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, Suboxone can cause side effects, although not everybody gets them. 
 

2 

3 

 



103 

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 Suboxone 

Very common side effects(may effect more than one in 10 people): 
Insomnia (inability to sleep), constipation, nausea, excessive sweating, headache, drug 
withdrawal syndrome 

Common side effects (may effect up to 1 in 10 people): 
Weight loss, swelling (hands and feet), drowsiness, anxiety, nervousness, tingling, depression, 
decreased sexual drive, increase in muscle tension, abnormal thinking, increased tearing 
(watering eyes) or other tearing disorder, blurred vision, flushing, increased blood pressure, 
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 discomfort, accidental injury caused by 
loss of alertness or co-ordination, faintness and dizziness.

Uncommon side effects (may effect up to 1 in 100 people): 
Swollen glands (lymph nodes), agitation, tremor, abnormal dream, excessive muscle activity, 
depersonalisation (not feeling like yourself), medicine dependence, amnesia (memory 
disturbance), 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 urination, 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 Suboxone 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. 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. 
 
 
5. How to store Suboxone 
 
Keep out of the sight and reach of children and other household members. 
 



104 

Do not use this medicine after the expiry date which is stated on the carton. The expiry date refers to 
the last day of that month  
 
This medicinal product does not require any special storage conditions. However, Suboxone 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. Content of the pack and other Information 
 
What Suboxone contains 
 
- The active substances are buprenorphine and naloxone.  

Each 8 mg/2 mg tablet contains 8 mg buprenorphine (as hydrochloride) and 2 mg naloxone (as 
hydrochloride dihydrate). 

- The other ingredients are lactose monohydrate, mannitol, maize starch, povidone K30, citric 
acid anhydrous, sodium citrate, magnesium stearate, acesulfame potassium and natural lemon 
and lime flavour. 

 
What Suboxone looks like and contents of the pack 
 
Suboxone 8 mg/2 mg sublingual tablets are white hexagonal biconvex tablets of 11 mm with “N8” 
debossed on one side. 
Packed in packs of 7 and 28 tablets. 
Not all pack sizes may be marketed. 
 
 
Marketing Authorisation Holder 
 
Indivior Europe Limited  
27 Windsor Place 
Dublin 2 
Ireland 
 
Manufacturer 
Reckitt Benckiser Healthcare (UK) Ltd,  
Dansom Lane,  
Hull,  
East Yorkshire HU8 7DS,  
United Kingdom. 
 
Or 
 
Indivior Europe Limited 
27 Windsor Place 
Dublin 2 
Ireland 
 



105 

For any information about this medicine, please contact the Marketing Authorisation Holder: 
 
België/Belgique/Belgien, България, Česká republika, Danmark, Deutschland, Eesti, Ελλάδα, España, 
Hrvatska, Ireland, Ísland, Italia, Κύπρος, Latvija, Lietuva, Luxembourg/Luxemburg, Magyarország, 
Malta, Nederland, Norge, Österreich, Polska, Portugal, România, Slovenija, Slovenská republika, 
Suomi/Finland, Sverige, United Kingdom.  
 
United Kingdom  
Indivior Europe Limited 
Telephone 0808 234 9243 
Email: PatientSafetyRoW@indivior.com 
 
This leaflet was last revised in  
 
Detailed information on this medicine is available on the website of the European Medicines Agency 
http://www.ema.europa.eu/ 
 



106 

 Package leaflet: Information for the user 
 

Suboxone 16 mg/4 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 any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. See section 4. 
 
What is in this leaflet 
1. What Suboxone is and what it is used for 
2. What you need to know before you take Suboxone 
3. How to take Suboxone 
4. Possible side effects 
5 How to store Suboxone 
6. Content of the pack and other information 
 
 
1. What Suboxone is and what it is used for 
 
Suboxone 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. Suboxone 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 Suboxone 
 
Do not take Suboxone 
 if you are allergic (hypersensitive) 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. 
 
 
Warnings and precautions  
 
Talk to your doctor before taking Suboxone 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) 
 

 



107 

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. 
 

 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. 

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

 
 Liver damage 

Liver damage has been reported after taking Suboxone, 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 Suboxone. 

 
 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. 

 
 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 Suboxone 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
 
Some medicines may increase the side effects of Suboxone and may sometimes cause very serious 
reactions. Do not take any other medicines whilst taking Suboxone without first talking to your doctor, 
especially: 
 
 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).  

 



108 

 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 you 
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 isocarboxazid, 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. 
‐ 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 agents (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 Suboxone. These include medicines used to treat 

epilepsy (such as carbamazepine and phenytoin), and medicines used to treat tuberculosis 
(rifampicin). 

 naltrexone and nalmefene (drugs used to treat addiction disorders) may prevent the therapeutic 
effects of Suboxone. They should not be taken at the same time as Suboxone treatment because 
you may experience a sudden onset of prolonged and intense withdrawal. 

 
 
Suboxone with food, drink and alcohol 
Alcohol may increase drowsiness and may increase the risk of respiratory failure if taken with 
Suboxone. Do not take Suboxone 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 Suboxone 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 Suboxone 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 Suboxone passes into breast milk. 
 
Ask your doctor or pharmacist for advice before taking any medicine. 
 
Driving and using machines 
Suboxone 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 Suboxone. Do not drive, use any tools or machines, or perform dangerous 
activities until you know how this medicine affects you.  
 
Suboxone contains lactose 
If you have been told by your doctor that you have intolerance to some sugars, contact your doctor 
before taking this medicine. 
 
 



109 

3. How to take Suboxone 
 
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 to two 
tablets of Suboxone 2 mg/0.5 mg. An additional one to two tablets of the Suboxone 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 Suboxone. A doctor’s 
assessment of your readiness for treatment will guide the timing of your first Suboxone dose.  
 
 Starting treatment of Suboxone whilst dependent on heroin 

 
If you are dependent upon heroin or a short acting opioid, your first dose of Suboxone should be 
taken when signs of withdrawal appear, but not less than 6 hours after you last used opioids. 

 
 Starting treatment of Suboxone 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 Suboxone therapy. The first dose of 
Suboxone should be taken when signs of withdrawal appear, but not less than 24 hours after you 
last used methadone.  

 
Taking Suboxone 
 
 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. 
1 



110 

 
 
 
 
 
 
 
   2 - Remove just one section from the blister pack, tearing it along the perforated  
    line. 
 
 
 
 

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

 
 
 
 
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 Suboxone you take 
according to your needs. If you have the impression that the effect of Suboxone 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 Suboxone 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 Suboxone 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 Suboxone may cause serious and life-
threatening 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 Suboxone 
Tell your doctor as soon as possible if you miss a dose. 
 

2 

3 



111 

If you stop taking Suboxone 
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, Suboxone 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 Suboxone 

Very common side effects (may effect more than one in 10 people): 
Insomnia (inability to sleep), constipation, nausea, excessive sweating, headache, drug 
withdrawal syndrome 

Common side effects (may effect up to 1 in 10 people): 
Weight loss, swelling (hands and feet), drowsiness, anxiety, nervousness, tingling, depression, 
decreased sexual drive, increase in muscle tension, abnormal thinking, increased tearing 
(watering eyes) or other tearing disorder, blurred vision, flushing, increased blood pressure, 
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 discomfort, accidental injury caused by 
loss of alertness or co-ordination, faintness and dizziness.

Uncommon side effects (may effect up to 1 in 100 people): 
Swollen glands (lymph nodes), agitation, tremor, abnormal dream, excessive muscle activity, 
depersonalisation (not feeling like yourself), medicine dependence, amnesia (memory 
disturbance), loss of interest, exaggerated feeling of well-being, convulsion (fits), speech 
disorder, small pupil size, difficulty urinating, eye inflammation or infection, rapid or slow 
heartbeat, 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 urination, 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 Suboxone 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).  

 



112 

Reporting of side effects 
If you get any side effects, talk to your doctor. 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. 
 
 
5. How to store Suboxone 
 
Keep out of the sight and reach of children and other household members. 
 
Do not use the medicine after the expiry date which is stated on the carton. The expiry date refers to 
the last day of that month  
 
This medicinal product does not require any special storage conditions. However, Suboxone 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. Content of the pack and other Information  
 
What Suboxone contains 
 
- The active substances are buprenorphine and naloxone.  

Each 16 mg/4 mg sublingual tablet contains 16 mg buprenorphine (as hydrochloride) and 4 mg 
naloxone (as hydrochloride dihydrate).  

- The other ingredients are lactose monohydrate, mannitol, maize starch, povidone K30, citric 
acid anhydrous, sodium citrate, magnesium stearate, acesulfame potassium and natural lemon 
and lime flavour. 

 
What Suboxone looks like and contents of the pack 
 
Suboxone 16 mg/4 mg sublingual tablets are white round biconvex tablets of 10.5 mm with  “N16” 
debossed on one side. 
Packed in packs of 7 and 28 tablets. 
Not all pack sizes may be marketed. 
 
 
Marketing Authorisation Holder 
Indivior Europe Limited  
27 Windsor Place 
Dublin 2 
Ireland 
 



113 

Manufacturer 
Reckitt Benckiser Healthcare (UK) Ltd,  
Dansom Lane,  
Hull,  
East Yorkshire HU8 7DS,  
United Kingdom. 
 
Or 
 
Indivior Europe Limited 
27 Windsor Place 
Dublin 2 
Ireland 
 
For any information about this medicine, please contact the Marketing Authorisation Holder: 
 
België/Belgique/Belgien, България, Česká republika, Danmark, Deutschland, Eesti, Ελλάδα, España, 
Hrvatska, Ireland, Ísland, Italia, Κύπρος, Latvija, Lietuva, Luxembourg/Luxemburg, Magyarország, 
Malta, Nederland, Norge, Österreich, Polska, Portugal, România, Slovenija, Slovenská republika, 
Suomi/Finland, Sverige, United Kingdom.  
 
United Kingdom  
Indivior Europe Limited 
Telephone 0808 234 9243 
Email: PatientSafetyRoW@indivior.com 
 
 
This leaflet was last revised in  
 
Detailed information on this medicine is available on the website of the European Medicines Agency 
http://www.ema.europa.eu/ 



114 

Package leaflet: Information for the user 
 

Suboxone 2 mg/0.5 mg sublingual film 
Suboxone 4 mg/1 mg sublingual film 
Suboxone 8 mg/2 mg sublingual film 
Suboxone 12 mg/3 mg sublingual film 

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 symptoms 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 Suboxone is and what it is used for 
2. What you need to know before you take Suboxone 
3. How to take Suboxone 
4. Possible side effects 
5 How to store Suboxone 
6. Contents of the pack and other information 
 
 
1. What Suboxone is and what it is used for 
 
Suboxone is used to treat dependence to opioid (narcotic) drugs such as heroin or morphine in 
patients who have agreed to be treated for their addiction. 
 
Suboxone 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 Suboxone 
 
Do not take Suboxone: 
• if you are allergic to buprenorphine, naloxone or any of the other ingredients of this medicine 

listed in section 6); 
• if you have serious breathing problems; 
• if you have serious problems with your liver; 
• 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. 
 
Warnings and precautions 
 
Talk to your doctor before taking Suboxone if you have: 
• asthma or other breathing problems 
• problems with your liver 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 



115 

• thyroid problems 
• adrenocortical disorder (e.g. Addison’s disease) 
 
Important things to be aware of: 
•  An emergency unit should be contacted immediately in case of accidental ingestion or 

suspicion of ingestion. 
 
• Additional monitoring 

You may be more closely monitored by your doctor if you are over the age of 65. . 
 
• 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 (see section 5). 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 
buprenorphine or have taken 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 medicine can cause dependence. 
 
• Withdrawal symptoms 

This medicine can cause opioid withdrawal symptoms if you take it too soon after taking 
opioids. You should leave at least 6 hours after you use a short-acting opioid (e.g. morphine, 
heroin) or at least 24 hours after you use a long-acting opioid such as methadone. 

 
This medicine can also cause withdrawal symptoms if you stop taking it abruptly. See section 3 
‘stopping treatment’. 

 
• Liver damage 

Liver damage has been reported after taking Suboxone, especially when the medicine is 
misused. This could also be due to viral infections (e.g. 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 Suboxone. 

 
• Blood pressure 

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

 
• Diagnosis of unrelated medical conditions 
 

This medicine may mask pain symptoms that could assist in the diagnosis of some diseases. 
You must tell your doctor that you take this medicine. 

 
Children and adolescents 
Do not give this medicine to children under the age of 15. If you are between 15 and 18 years old 
your doctor may monitor you more closely during treatment, because of the lack of data in this age 
group. 
 
Other medicines and Suboxone 



116 

Tell your doctor if you are taking, have recently taken or might take any other medicines. 
 
Some medicines may increase the side effects of Suboxone, and these can be serious. Do not take any 
other medicines whilst taking Suboxone without first talking to your doctor, especially: 
 
• Benzodiazepines (used to treat anxiety or sleep disorders) such as diazepam, temazepam, or 

alprazolam. Concomitant use of Suboxone 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 Suboxone 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 may 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 painkillers and cough 

suppressants. 
- Antidepressants (used to treat depression) such as isocarboxazid, phenelzine, selegiline, 

tranylcypromine and valproate may increase the effects of this medicine. 
- Sedative H1 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) may extend the effects of this medicine. 
• Antiretrovirals (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, 

certain antibiotics, may extend the effects of this medicine. Some medicines may decrease the 
effect of Suboxone. These include medicines used to treat epilepsy (such as carbamazepine and 
phenytoin), and medicines used to treat tuberculosis (rifampicin). 

• Naltrexone and nalmefene (medicines used to treat addictive disorders) may prevent the 
therapeutic effects of Suboxone. They should not be taken at the same time as Suboxone 
treatment because you may experience a sudden onset of prolonged and intense withdrawal. 

 
Suboxone with food, drink and alcohol 
Do not have alcohol whilst being treated with this medicine. Alcohol may increase drowsiness and 
may increase the risk of respiratory failure if taken with Suboxone. Do not swallow or consume food 
or any drink until the film is completely dissolved. 
 
Pregnancy, breast-feeding and fertility 
Tell your doctor if you are pregnant, think you may be pregnant or are planning to have a baby. The 
risks of using Suboxone in pregnant women are not known. Your doctor will decide if your treatment 
should be continued with an alternative medicine. 
 
When taken during pregnancy, particularly late pregnancy, medicines like Suboxone 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, as buprenorphine passes into breast milk. 



117 

 
Ask your doctor or pharmacist for advice before taking any medicine. 
 
Driving and using machines 
Do not drive, cycle, use any tools or machines, or perform dangerous activities until you know how 
this medicine affects you. Suboxone may cause drowsiness, dizziness or impair your thinking. This 
may happen more often in the first few weeks of treatment when your dose is being changed, but it can 
also happen if you drink alcohol or take other sedative medicines at the same time as when you take 
Suboxone. 
 
Suboxone contains maltitol, sunset yellow (E110) and sodium. 
Suboxone contains maltitol liquid. If you have been told by your doctor that you have intolerance to 
some sugars, contact your doctor before taking this medicine. 
 
Suboxone contains sunset yellow (E110), which may cause allergic reactions. 
 
This medicine contains less than 1 mmol sodium (23 mg) per film, that is to say essentially ‘sodium 
free’. 
 
 
3. How to take Suboxone 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. 
 
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 to treatment. 
 
 
Starting treatment 
The recommended starting dose for adults and adolescents over the age of 15 years is usually two 
Suboxone 2 mg/0.5 mg sublingual films, or one Suboxone 4 mg/1 mg sublingual film. 
 
This dose may be repeated up to twice on day 1 depending on your needs. 
 
You should be aware of the clear signs of withdrawal before taking your first dose of Suboxone. Your 
doctor will tell you when to take your first dose. 
 
• Starting treatment of Suboxone whilst dependent on heroin 
 

If you are dependent upon heroin or a short-acting opioid, your first dose should be taken when 
signs of withdrawal appear, at least 6 hours after you last used opioids. 

 
• Starting treatment of Suboxone 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 Suboxone therapy. The first dose of 
Suboxone should be taken when signs of withdrawal appear, and at least 24 hours after you 
last used methadone. 

 
Dose adjustment and maintenance therapy: During the days after you start treatment, your doctor 
may increase the dose of Suboxone you take according to your needs. If you think that the effect of 
Suboxone is too strong or too weak, talk to your doctor or pharmacist. The maximum daily dose is 
24 mg buprenorphine. 



118 

 
After a time of successful treatment, you may agree with your doctor to reduce the dose gradually to a 
lower maintenance dose. 
 
Taking Suboxone 
• Take the dose once a day, at approximately the same time. 
• It is advisable to moisten your mouth before taking the film. 
• Place the sublingual film under the tongue (sublingual use) or on the inside of the cheek (buccal 

use) as advised by your doctor. Ensure the films do not overlap. 
• Keep the films in place under the tongue, or inside of the cheek, until they have completely 

dissolved. 
• Do not chew or swallow the film, as the medicine will not work, and you may get withdrawal 

symptoms. 
• Do not consume any food or drink until the film has completely dissolved. 
• Do not split the film or subdivide into smaller doses. 
 
How to remove the film from the sachet 
 
Each Suboxone film comes in a sealed child‐resistant sachet. Do not open the sachet until you are 
ready to use it. 
 
To open the sachet, find the dotted line that runs along the top edge of the sachet and fold the edge of 
the sachet along the dotted line (see Figure 1). 
 

 
Figure 1 
 
• Folding the sachet along the dotted line exposes a slit through the folded edge of the sachet that 

can then be torn in the direction of the arrow. 
 
• Alternatively, the sachet may be cut with scissors along the arrow (see Figure 2). 
 

 
Figure 2 
 
If the sachet is damaged, discard the film. 



119 

 
How to place a film under your tongue (sublingual use): 
Drink water to moisten your mouth first. This helps the film dissolve more easily. Then, hold a film 
between two fingers by the outside edges, and place the film under your tongue, close to the base 
either to the left or right (see Figure 3). 
 

 
Figure 3 
 
If your doctor tells you to take two films at a time, place the second film under your tongue on the 
opposite side. Ensure the films do not overlap 
If your doctor tells you to take a third film, place it under your tongue on either side after the first two 
films have dissolved. 
 
How to place a film on the inside of your cheek (buccal use): 
Drink water to moisten your mouth. Hold the film between two fingers by the outside edges and place 
one film on the inside of your right or left cheek (see Figure 4). 
 
 

 
 
Figure 4 
 
If your doctor tells you to take two films at a time, place the other film on the inside of the opposite 
cheek: and this will ensure that the films do not overlap. If your doctor tells you to take a third film, 
place it on the inside of your right or left cheek after the first two films have dissolved. 
 



120 

If you take more Suboxone than you should 
Seek urgent medical attention if you or someone else takes too much of this medicine. 
Overdose with Suboxone may cause serious and life-threatening 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 Suboxone 
Tell your doctor as soon as possible if you miss a dose. 
 
If you stop taking Suboxone 
Stopping treatment suddenly may cause withdrawal symptoms. Depending on your condition, the 
dose of Suboxone 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 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 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). 
 
Very common side effects (may affect more than one in 10 people): 
- Insomnia (inability to sleep),  
- constipation,  
- nausea,  
- excessive sweating,  
- headache,  
- drug withdrawal syndrome. 
 
Common side effects (may affect up to 1 in 10 people): 
- Weight loss,  
- swelling of the hands and feet,  
- drowsiness, anxiety,  
- nervousness,  
- tingling,  
- depression,  
- decreased sexual drive,  
- increase in muscle tension,  
- abnormal thinking,  
- increased tearing (watering eyes) or other tearing disorders,  
- flushing,  
- increased blood pressure,  
- migraines,  



121 

- runny nose,  
- sore throat and painful swallowing,  
- increased cough,  
- upset stomach or other stomach discomfort,  
- diarrhoea,  
- mouth redness,  
- 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 discomfort,  
- accidental injury caused by loss of alertness or co-ordination,  
- faintness, 
- dizziness. 
 
Uncommon side effects (may affect up to 1 in 100 people): 
- Swollen glands (lymph nodes),  
- agitation,  
- tremor,  
- abnormal dreams,  
- excessive muscle activity,  
- depersonalisation (not feeling like yourself),  
- medicine dependence,  
- amnesia (memory disturbance),  
- loss of interest,  
- disturbance in attention,  
- exaggerated feeling of wellbeing,  
- convulsion (fits),  
- speech disorder,  
- small pupil size,  
- difficulty urinating,  
- blurred vision,  
- eye inflammation or infection,  
- rapid or slow heartbeat,  
- low blood pressure,  
- palpitations,  
- heart attack,  
- chest tightness,  
- shortness of breath,  
- asthma,  
- yawning,  



122 

- mouth problems (sores, blisters, numbness, tingling, swelling, or pain),  
- tongue discolouration or pain,  
- 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 urination,  
- sensitivity to heat or cold,  
- heat stroke,  
- allergic reaction,  
- loss of appetite,  
- feelings of hostility,  
- intoxication. 
 
Not known (frequency cannot be estimated from the available data): 
- sudden withdrawal syndrome caused by taking Suboxone too soon after use of illicit opioids, 
- drug withdrawal syndrome in new-born babies.  
- 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, causing 

dizziness, 
- irritation or inflammation inside the mouth, including under the tongue. 
 
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 national reporting system 
listed in Appendix V. By reporting side affects you can help provide more information on the safety of 
this medicine. 
 
 
6. How to store Suboxone 
 
Keep this medicine 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 carton and the sachet. The expiry 
date refers to the last day of that month. 
Store below 25 °C. 
Suboxone can be a target for people who abuse prescription medicine. Keep this medicine in a safe 
place to protect it from theft. 
Store the sachet safely. 
Never open the sachet in advance. 
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. 
 
 



123 

6. Contents of the pack and other information 
 
What Suboxone contains 
 
- The active substances are buprenorphine and naloxone. 

Each 2 mg/0.5 mg film contains 2 mg buprenorphine (as hydrochloride) and 0.5 mg naloxone 
(as hydrochloride dihydrate). 
Each 4 mg/1 mg film contains 4 mg buprenorphine (as hydrochloride) and 1 mg naloxone (as 
hydrochloride dihydrate). 
Each 8 mg/2 mg film contains 8 mg buprenorphine (as hydrochloride) and 2 mg naloxone (as 
hydrochloride dihydrate). 
Each 12 mg/3 mg film contains 12 mg buprenorphine (as hydrochloride) and 3 mg naloxone (as 
hydrochloride dihydrate). 

 
- The other ingredients are macrogol, maltitol liquid, natural lime flavour, hypromellose, citric 

acid, acesulfame potassium, sodium citrate, sunset yellow (E110) and white ink. 
 
What Suboxone looks like and contents of the pack 
 
Suboxone 2 mg/0.5 mg sublingual films are orange rectangular films of nominal dimensions 22.0 mm 
× 12.8 mm, with ‘N2’ imprinted in white ink. 
 
Suboxone 4 mg/1 mg sublingual films are orange rectangular films of nominal dimensions 22.0 mm × 
25.6 mm, with ‘N4’ imprinted in white ink. 
 
Suboxone 8 mg/2 mg sublingual films are orange rectangular films of nominal dimensions 22.0 mm × 
12.8 mm, with ‘N8’ imprinted in white ink. 
 
Suboxone 12 mg/3 mg sublingual films are orange rectangular films of nominal dimensions 22.0 mm 
× 19.2 mm, with ‘N12’ imprinted in white ink. 
 
The films are packed in individual sachets. 
Pack sizes: cartons containing 7 × 1, 14 × 1 and 28 × 1 films. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Indivior Europe Limited 
27 Windsor Place 
Dublin 2 
Ireland 
 
Manufacturer 
Almac Pharma Services Limited 
Seagoe Industrial Estate, Portadown 
Craigavon BT63 5UA 
United Kingdom 
 
Almac Pharma Services (Ireland) Limited 
Finnabair Industrial Estate, Dundalk 
Co. Louth A91 P9KD 
Ireland 
 
 
 
 



124 

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

België/Belgique/Belgien 
Indivior Europe Limited 
Tél/Tel: 0800 780 41 
e-mail: PatientSafetyRow@indivior.com 
 

Lietuva 
Indivior Europe Limited 
Tel: 880030793 
e-mail: PatientSafetyRoW@indivior.com 
 

България 
Indivior Europe Limited 
Teл.: 00800 110 4104 
e-mail: PatientSafetyRoW@indivior.com 
 

Luxembourg/Luxemburg 
Indivior Europe Limited 
Tél/Tel: 800 245 43 
e-mail: PatientSafetyRow@indivior.com 

Česká republika 
Indivior Europe Limited 
Tel: 800 143 737 
e-mail: PatientSafetyRoW@indivior.com 
 

Magyarország 
Indivior Europe Limited 
Tel.: 6800 19301 
e-mail: PatientSafetyRoW@indivior.com 

Danmark 
Indivior Europe Limited 
Tlf: 80826653 
e-mail: PatientSafetyRoW@indivior.com 
 

Malta 
Indivior Europe Limited 
Tel: 80062185 
e-mail: PatientSafetyRoW@indivior.com 

Deutschland 
Indivior Europe Limited 
Tel: 800 181 3799 
e-mail: PatientSafetyRoW@indivior.com 
 

Nederland 
Indivior Europe Limited 
Tel: 0800 022 87 83 
e-mail: PatientSafetyRow@indivior.com 

Eesti 
Indivior Europe Limited 
Tel: 8000041004 
e-mail: PatientSafetyRoW@indivior.com 
 

Norge 
Indivior Europe Limited 
Tlf: 80016773 
e-mail: PatientSafetyRoW@indivior.com 

Ελλάδα 
Indivior Europe Limited 
Τηλ: 800 270 81 901   
e-mail: PatientSafetyRoW@indivior.com 
 

Österreich 
Indivior Europe Limited 
Tel: 800 296551 
e-mail: PatientSafetyRoW@indivior.com 

España 
Indivior Europe Limited 
Tel: 900 994 121 
e-mail: PatientSafetyRoW@indivior.com 
 

Polska 
Indivior Europe Limited 
Tel.: 0800 4111237 
e-mail: PatientSafetyRoW@indivior.com 

France 
Indivior Europe Limited 
Tél: 0800 909 972 
e-mail: PatientSafetyFrance@indivior.com 

Portugal 
Indivior Europe Limited 
Tel: 800 841 042 
e-mail: PatientSafetyRoW@indivior.com 

Hrvatska 
Indivior Europe Limited 
Tel: + +0800 222 899 
e-mail: PatientSafetyRoW@indivior.com 
 

România 
Indivior Europe Limited 
Tel: 800 477 029 
e-mail: PatientSafetyRoW@indivior.com 
 

Ireland 
Indivior Europe Limited 
Tel: 1800554156 
e-mail: PatientSafetyRoW@indivior.com

Slovenija 
Indivior Europe Limited 
Tel: 080080715 
e-mail: PatientSafetyRoW@indivior.com 



125 

 
Ísland 
Indivior Europe Limited 
Sími: 8009875 
Netfang: PatientSafetyRoW@indivior.com 
 

Slovenská republika 
Indivior Europe Limited 
Tel: 800110286 
e-mail: PatientSafetyRoW@indivior.com 
 

Italia 
Indivior Europe Limited 
Tel: 800 789 822 
e-mail: PatientSafetyRoW@indivior.com 
 

Suomi/Finland 
Indivior Europe Limited 
Puh/Tel: 0800417489 
e-mail: PatientSafetyRoW@indivior.com 

Κύπρος 
Indivior Europe Limited 
Τηλ: 800 270 81 901 
e-mail: PatientSafetyRoW@indivior.com 
 

Sverige 
Indivior Europe Limited 
Tel: 020791680 
e-mail: PatientSafetyRoW@indivior.com 
 

Latvija 
Indivior Europe Limited 
Tel: 800 05612   
e-mail: PatientSafetyRoW@indivior.com 
 

United Kingdom 
Indivior Europe Limited 
Tel: 0808 234 9243 
e-mail: PatientSafetyRoW@indivior.com 

This leaflet was last revised in  
 
Detailed information on this medicine is available on the website of the European Medicines Agency 
http://www.ema.europa.eu/ 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETINGAUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE ANDEFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET