Zubsolv

1  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2  

1. NAME OF THE MEDICINAL PRODUCT 
 
Zubsolv 0.7 mg / 0.18 mg sublingual tablets 
Zubsolv 1.4 mg / 0.36 mg sublingual tablets 
Zubsolv 2.9 mg / 0.71 mg sublingual tablets 
Zubsolv 5.7 mg / 1.4 mg sublingual tablets 
Zubsolv 8.6 mg / 2.1 mg sublingual tablets 
Zubsolv 11.4 mg / 2.9 mg sublingual tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Zubsolv 0.7 mg / 0.18 mg sublingual tablets 
 
Each 0.7 mg / 0.18 mg sublingual tablet contains 0.7 mg buprenorphine (as hydrochloride) and 0.18 
mg naloxone (as hydrochloride dihydrate).  
 
Zubsolv 1.4 mg / 0.36 mg sublingual tablets 
 
Each 1.4 mg / 0.36 mg sublingual tablet contains 1.4 mg buprenorphine (as hydrochloride) and 0.36 
mg naloxone (as hydrochloride dihydrate).  
 
Zubsolv 2.9 mg / 0.71 mg sublingual tablets 
 
Each 2.9 mg / 0.71 mg sublingual tablet contains 2.9 mg buprenorphine (as hydrochloride) and 0.71 
mg naloxone (as hydrochloride dihydrate).  
 
Zubsolv 5.7 mg / 1.4 mg sublingual tablets 
 
Each 5.7 mg / 1.4 mg sublingual tablet contains 5.7 mg buprenorphine (as hydrochloride) and 1.4 mg 
naloxone (as hydrochloride dihydrate). 
 
Zubsolv 8.6 mg / 2.1 mg sublingual tablets 
 
Each 8.6 mg / 2.1 mg sublingual tablet contains 8.6 mg buprenorphine (as hydrochloride) and 2.1 mg 
naloxone (as hydrochloride dihydrate). 
 
Zubsolv 11.4 mg / 2.9 mg sublingual tablets 
 
Each 11.4 mg / 2.9 mg sublingual tablet contains 11.4 mg buprenorphine (as hydrochloride) and 2.9 
mg naloxone (as hydrochloride dihydrate).  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Sublingual tablet 
 
Zubsolv 0.7 mg / 0.18 mg sublingual tablets 
 
White, oval tablets, length 6.8 mm and width 4.0 mm, debossed with “.7” on one side.  
 
Zubsolv 1.4 mg / 0.36 mg sublingual tablets 
 
White, triangular tablets, base 7.2 mm and height 6.9 mm, debossed with “1.4” on one side. 



3  

 
Zubsolv 2.9 mg / 0.71 mg sublingual tablets 
 
White, D-shaped tablets, height 7.3 mm and width 5.65 mm, debossed with “2.9” on one side.  
 
Zubsolv 5.7 mg / 1.4 mg sublingual tablets 
 
White, round tablets, 7 mm in diameter, debossed with “5.7” on one side.  
 
Zubsolv 8.6 mg / 2.1 mg sublingual tablets 
 
White, diamond shaped tablets, length 9.5 mm and width 8.2 mm, debossed with “8.6” on one side.  
 
Zubsolv 11.4 mg / 2.9 mg sublingual tablets 
 
White, capsule shaped tablets, length 10.3 mm and width 8.2 mm, debossed with “11.4” 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 opioid 
dependence/addiction. 
 
Zubsolv is not interchangeable with other buprenorphine products, as different buprenorphine 
products have different bioavailability. Therefore the dose in mg can differ between products. Once 
the appropriate dose has been identified for a patient with a specific buprenorphine product, that 
product should not be exchanged with another product. 
 
If a patient is changed between buprenorphine or buprenorphine and naloxone containing 
products, dose adjustments may be necessary due to the potential differences in bioavailability 
(see sections 4.4 and 5.2). 
 
Use of multiples of the three lower dose presentations of Zubsolv to substitute for any of the three 
higher dose presentations (in for example cases where the higher dose presentations are 
temporarily not available) is not recommended (see section 5.2). 
 
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 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). 
• 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. 

• For patients receiving methadone, the dose of methadone should be reduced to a maximum of 



4  

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. 

 
Baseline liver function tests and documentation of viral hepatitis status are 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) 
 
Posology 
 
Initiation therapy 
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. 
 
Induction 
The recommended starting dose in adults and adolescents over 15 years of age is Zubsolv 
1.4 mg / 0.36 mg or 2.9 mg / 0.71 mg a day. An additional Zubsolv 1.4 mg / 0.36 mg or 
2.9 mg / 0.71 mg may be administered on day one depending on the individual patient’s requirement. 
 
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 on the 
individual patient. Patients should be monitored during dose titration. For steps of 1.4-5.7 mg 
buprenorphine this titration is guided by reassessment of the clinical and psychological status of the 
patient, and should not exceed a maximum single daily dose of 17.2 mg buprenorphine (e.g. given as 
11.4 + 5.7 mg, 2 x 8.6 mg or 3 x 5.7 mg). 
 
The 0.7mg / 0.18mg strength is intended to be used to fine tune the dose for patients especially 
during tapering of treatment or in case of tolerability issues during titration. 
 
Physicians are encouraged to prescribe a single tablet once daily regimen where possible to minimise 
risk of diversion. 
 
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. 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 17.2 mg buprenorphine. Patients requiring a titrated daily dose > 5.7 
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 six different tablet strengths supports individual dose titration and tapering. 
Patients should be monitored following medical withdrawal because of the potential for relapse. 
 
Special populations 
 
Elderly 



5  

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, receiving 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 Zubsolv, 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 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 (see section 5.2). Buprenorphine/naloxone is contraindicated in patients with severe 
hepatic impairment (see sections 4.3 and 5.2). 
 
Renal impairment 
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 
 
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. 
 
Zubsolv disintegrates usually within 40 seconds, however it may take 5 to 10 minutes for the patient 
to feel complete tablet disappearance from the mouth. 
 
If more than one tablet is required, they may be taken all at the same time or in two divided portions; 
the second portion is 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 



6  

risks to opioid misusers and abusers 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 Zubsolv is intended to deter misuse and abuse of the 
buprenorphine. Intravenous or intranasal misuse of Zubsolv is expected to be less likely than 
buprenorphine alone since the naloxone in Zubsolv 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 
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 sight and 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. 
 
Serotonin syndrome 
 
Concomitant administration of Zubsolv and other serotonergic agents, such as MAO inhibitors, 
selective serotonin re-uptake inhibitors (SSRIs), serotonin norepinephrine re-uptake inhibitors 
(SNRIs) or tricyclic antidepressants may result in serotonin syndrome, a potentially life-threatening 
condition (see section 4.5). 
If concomitant treatment with other serotonergic agents is clinically warranted, careful observation 
of the patient is advised, particularly during treatment initiation and dose increases. 
 
Symptoms of serotonin syndrome may include mental-status changes, autonomic instability, 
neuromuscular abnormalities, and/or gastrointestinal symptoms. 
 



7  

If serotonin syndrome is suspected, a dose reduction or discontinuation of therapy should be 
considered depending on the severity of the symptoms. 
 
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 withdrawal syndrome 
with delayed 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 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. To avoid precipitating 
withdrawal, induction with buprenorphine/naloxone should be undertaken when objective signs of 
withdrawal are evident (see section 4.2). Patients should be closely monitored during the switching 
period from buprenorphine or methadone to buprenorphine/naloxone since withdrawal symptoms 
have been reported. 
 
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 
metabolized in liver, 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 opioid withdrawal, toxicity or overdose caused by 
increased levels of naloxone and/or buprenorphine. Zubsolv sublingual tablets should be used with 
caution in patients with moderate hepatic impairment (see sections 4.2 and 5.2). In patients with 
severe hepatic insufficiency the use of buprenorphine/naloxone is contraindicated (see section 4.3). 



8  

 
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 years) 
 
Due to the lack of data in adolescents (age 15 - <18 years), patients in this age group should be more 
closely monitored during treatment. 
 
Changing between buprenorphine containing products 
 
The dose in mg can differ between buprenorphine products and products are not directly 
interchangeable. Therefore, patients should be monitored when changing between different 
buprenorphine containing products as differences in bioavailability (see section 5.2) may be 
noticeable in some individual cases. Dosage adjustments may therefore be necessary. 
 
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 
opioid effects, based on experience with morphine (see section 4.5). 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Zubsolv must not be taken together with: 



9  

• 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) 

 
Zubsolv should not be taken together with: 
• alcoholic drinks or medicines containing alcohol, as alcohol increases the sedative effect 

of buprenorphine (see section 4.7) 
 
Zubsolv should be used cautiously when co-administered with: 
• 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) 

• serotonergic medicinal products, such as MAO inhibitors, selective serotonin re-uptake 
inhibitors (SSRIs), serotonin norepinephrine re-uptake inhibitors (SNRIs) or tricyclic 
antidepressants as the risk of serotonin syndrome, a potentially life-threatening condition, 
is increased (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 

• Full opioid agonist: 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 

• 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 Zubsolv should be closely monitored, and may require 
dose-reduction if combined with potent CYP3A4 inhibitors (e.g. protease inhibitors like 
ritonavir, nelfinavir or indinavir, azole antifungals such as ketoconazole, itraconazole or 
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 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 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 



10  

the last three months of pregnancy may cause withdrawal syndrome in the neonate (e.g. hypertonia, 
neonatal 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 
 
In rats buprenorphine has been found to inhibit lactation. Buprenorphine and its metabolites are 
excreted in human milk. It is unknown whether naloxone/metabolites are excreted in human milk. 
Therefore, breastfeeding should be discontinued during treatment with Zubsolv. 
 
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 17.2 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), Rare 
(≥/10,000 to <1/1,000), Very rare (<1/10,000), 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 



11  

 
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 
disorders 

   Hepatitis  
Hepatitis acute 
Jaundice  
Hepatic 



12  

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  

 
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. These include local reactions, sometimes septic (abscess, cellulitis), 
potentially serious acute hepatitis, and other acute infections such as pneumonia, endocarditis (see 
section 4.4). 
 
In patients 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. 
 



13  

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 initiated, 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 where 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 eliminated 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. Ongoing intravenous infusion rates should 
be titrated to patient response. The diagnosis of opioid-related toxicity should be reconsidered if 
there is still failure to respond after a total of 10 mg of naloxone has been administered. 
 
 
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 patients. 
 
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 because of its almost complete first pass metabolism. However, when administered 
intravenously to opioid-dependent patients the presence of naloxone in Zubsolv produces marked 
opioid antagonist effects, thereby deterring intravenous abuse. 
 
Clinical efficacy 



14  

 
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 randomised 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 randomised 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 randomised 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 
 
Zubsolv disintegrates usually within 40 seconds, however it may take 5 to 10 minutes for the patient 
to feel complete tablet disappearance from the mouth. 
 
Zubsolv sublingual tablets have a higher bioavailability than conventional sublingual tablets. 
Therefore the dose in mg can differ between products. Zubsolv is not interchangeable with other 
buprenorphine products. 
 
In comparative bioavailability studies Zubsolv 11.4/2.9 mg displayed equivalent buprenorphine 
exposure to 16/4mg (2 x 8/2mg) buprenorphine/naloxone administered as conventional sublingual 
tablets however Zubsolv 2 x 1.4/0.36 mg displayed 20% lower buprenorphine exposure to 2 x 
2/0.5 mg buprenorphine/naloxone administered as conventional sublingual tablets. Naloxone 
exposure was not higher from Zubsolv at any of the tested dose levels. 
 
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. 
 
There are small deviations in buprenorphine dose proportionality exposure parameters as well as 
deviations from strict compositional proportionality for the three lower strengths (2.9/0.71, 1.4/0.36, 
and 0.7/0.18 mg) compared to the three higher dose presentations. Therefore, multiples of the three 
lower dose presentations of Zubsolv should not be used to substitute for any of the three higher dose 
Zubsolv presentations. 
 
Peak plasma concentrations are achieved approximately 90 minutes after sublingual administration. 



15  

Plasma levels of buprenorphine increased with the sublingual dose of buprenorphine/naloxone. Both 
Cmax and AUC of buprenorphine increased with the increase in dose, although the increase was less 
than dose-proportional. 
 
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 μ-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 
Naloxone is metabolised 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 4.4). 
 
Hepatic impairment 
The effect of hepatic impairment on the pharmacokinetics of buprenorphine and naloxone were 
evaluated in a post-marketing study. 
 
Table 2 summarizes the results from a clinical trial in which the exposure after single-dose 
administration of buprenorphine/naloxone sublingual tablet was determined in healthy subjects, and 
in subjects with hepatic impairment. 
 



16  

Table 2: Effect of hepatic impairment on pharmacokinetic parameters of buprenorphine 
and naloxone following 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 5 x 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 2.4 x for buprenorphine at a human dose of 17.2 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 dose multiples of 3 to75 times, based on a Zubsolv equivalent human 
daily sublingual dose of 11.4 mg of buprenorphine calculated on a mg/m² basis. Statistically 
significant increases in the incidence of benign testicular interstitial (Leydig's) cell adenomas were 



17  

observed in all dosage groups. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Mannitol 
Citric acid anhydrous  
Sodium citrate  
Microcrystalline cellulose  
Croscarmellose sodium  
Sucralose 
Levomenthol 
Colloidal anhydrous silica  
Sodium stearyl fumarate 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
0.7 mg / 0.18 mg 
 
2 years 
 
1.4 mg / 0.36 mg 
 
4 years 
 
2.9 mg / 0.71 mg 
 
3 years 
 
5.7 mg / 1.4 mg 
 
4 years 
 
8.6 mg / 2.1 mg 
 
4 years 
 
11.4 mg / 2.9 mg 
 
4 years 
 
6.4 Special precautions for storage 
 
Store in the original package below 25°C in order to protect from moisture. 
 
6.5 Nature and contents of container 
 
PVC/OPA/Al/PVC // Al/PET/Paper child resistant blister cards.  
Pack-size of 7 (1 x 7) tablets. 
Pack-size of 28 (4 x 7) tablets. 



18  

Pack-size of 30 (3 x 10) tablets. 
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 
 
Orexo AB 
Box 303 
751 05 Uppsala 
Sweden 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/17/1233/001  
EU/1/17/1233/002  
EU/1/17/1233/003 
 EU/1/17/1233/004 
 EU/1/17/1233/005 
 EU/1/17/1233/006 
EU/1/17/1233/007 
EU/1/17/1233/008 
EU/1/17/1233/009 
EU/1/17/1233/010 
EU/1/17/1233/011 
EU/1/17/1233/012 
EU/1/17/1233/013 
EU/1/17/1233/014 
EU/1/17/1233/015 
EU/1/17/1233/016 
EU/1/17/1233/017 
EU/1/17/1233/018 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 10 November 2017 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
 

Detailed information on this medicinal product is available on the website of the European 
Medicines Agency http://www.ema.europa.eu. 



19  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 

 



20  

 
A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Orexo AB  
Virdings allé 32 A  
Uppsala 
751 05 
Sweden 
 
 
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 
 
The requirements for submission of periodic safety update reports 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. 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
 

• Risk Management Plan (RMP) 
 
The 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. 

 



21  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



22  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



23  

 
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
 
PACK OF 7, 28, and 30 TABLETS 0.7 mg / 0.18 mg STRENGTH 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zubsolv 0.7 mg / 0.18 mg sublingual tablets  
buprenorphine / naloxone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sublingual tablet contains 0.7 mg buprenorphine (as hydrochloride) and 0.18 mg naloxone (as 
hydrochloride dihydrate). 
 
 
3. LIST OF EXCIPIENTS 
 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
7 sublingual tablets 
28 sublingual tablets 
30 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 
 
Zubsolv is not interchangeable with other buprenorphine products. 
 
 
8. EXPIRY DATE 



24  

 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package below 25°C in order to protect from moisture. 
 
 
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 
 
Orexo AB 
Box 303 
751 05 Uppsala 
Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1233/001 
EU/1/17/1233/007 
EU/1/17/1233/008 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
ZUBSOLV 0.7 mg / 0.18 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 



25  

 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



26  

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
PACK OF 7, 28, and 30 TABLETS 0.7 mg / 0.18 mg STRENGTH 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zubsolv 0.7 mg / 0.18 mg sublingual tablets  
buprenorphine / naloxone 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Orexo AB 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Fold here  
Tear here 



27  

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
 
PACK OF 7, 28, and 30 TABLETS 1.4 mg / 0.36 mg STRENGTH 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zubsolv 1.4 mg / 0.36 mg sublingual tablets  
buprenorphine / naloxone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sublingual tablet contains 1.4 mg buprenorphine (as hydrochloride) and 0.36 mg naloxone (as 
hydrochloride dihydrate). 
 
 
3. LIST OF EXCIPIENTS 
 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
7 sublingual tablets 
28 sublingual tablets 
30 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 
 
Zubsolv is not interchangeable with other buprenorphine products. 
 
 
8. EXPIRY DATE 
 



28  

EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package below 25°C in order to protect from moisture. 
 
 
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 
 
Orexo AB 
Box 303 
751 05 Uppsala 
Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1233/002 
EU/1/17/1233/009 
EU/1/17/1233/010 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
ZUBSOLV 1.4 mg / 0.36 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



29  

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



30  

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
PACK OF 7, 28, and 30 TABLETS 1.4 mg / 0.36 mg STRENGTH 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zubsolv 1.4 mg / 0.36 mg sublingual tablets  
buprenorphine / naloxone 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Orexo AB 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Fold here  
Tear here 



31  

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
 
PACK OF 7, 28, and 30 TABLETS 2.9 mg / 0.71 mg STRENGTH 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zubsolv 2.9 mg / 0.71 mg sublingual tablets  
buprenorphine / naloxone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sublingual tablet contains 2.9 mg buprenorphine (as hydrochloride) and 0.71 mg naloxone (as 
hydrochloride dihydrate). 
 
 
3. LIST OF EXCIPIENTS 
 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
7 sublingual tablets 
28 sublingual tablets 
30 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 
 
Zubsolv is not interchangeable with other buprenorphine products. 
 
 
8. EXPIRY DATE 
 



32  

EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package below 25°C in order to protect from moisture. 
 
 
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 
 
Orexo AB 
Box 303 
751 05 Uppsala 
Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1233/003 
EU/1/17/1233/011 
EU/1/17/1233/012 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
ZUBSOLV 2.9mg / 0.71 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 



33  

 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 

PC: 
SN: 
NN: 



34  

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
PACK OF 7, 28, and 30 TABLETS 2.9 mg / 0.71 mg STRENGTH 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zubsolv 2.9 mg / 0.71 mg sublingual tablets  
buprenorphine / naloxone 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Orexo AB 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Fold here  
Tear here 



35  

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
 
PACK OF 7, 28, and 30 TABLETS 5.7 mg / 1.4 mg STRENGTH 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zubsolv 5.7 mg / 1.4 mg sublingual tablets  
buprenorphine / naloxone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sublingual tablet contains 5.7 mg buprenorphine (as hydrochloride) and 1.4 mg naloxone (as 
hydrochloride dihydrate). 
 
 
3. LIST OF EXCIPIENTS 
 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
7 sublingual tablets 
28 sublingual tablets 
30 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 
 
Zubsolv is not interchangeable with other buprenorphine products. 
 
 
8. EXPIRY DATE 
 



36  

EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package below 25°C in order to protect from moisture. 
 
 
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 
 
Orexo AB 
Box 303 
751 05 Uppsala 
Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1233/004 
EU/1/17/1233/013 
EU/1/17/1233/014 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
ZUBSOLV 5.7 mg / 1.4 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 



37  

 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 

PC: 
SN: 
NN: 



38  

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
PACK OF 7, 28, and 30 TABLETS 5.7 mg / 1.4 mg STRENGTH 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zubsolv 5.7 mg / 1.4 mg sublingual tablets  
buprenorphine / naloxone 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Orexo AB 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Fold here  
Tear here 



39  

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
 
PACK OF 7, 28, and 30 TABLETS 8.6 mg / 2.1 mg STRENGTH 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zubsolv 8.6 mg / 2.1 mg sublingual tablets  
buprenorphine / naloxone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sublingual tablet contains 8.6 mg buprenorphine (as hydrochloride) and 2.1 mg naloxone (as 
hydrochloride dihydrate). 
 
 
3. LIST OF EXCIPIENTS 
 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
7 sublingual tablets 
28 sublingual tablets 
30 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 
 
Zubsolv is not interchangeable with other buprenorphine products. 
 
 
8. EXPIRY DATE 
 



40  

EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package below 25°C in order to protect from moisture. 
 
 
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 
 
Orexo AB 
Box 303 
751 05 Uppsala 
Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1233/005 
EU/1/17/1233/015 
EU/1/17/1233/016 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
ZUBSOLV 5.7 mg / 1.4 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 



41  

 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 

PC: 
SN: 
NN: 



42  

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
PACK OF 7, 28, and 30 TABLETS 8.6 mg / 2.1 mg STRENGTH 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zubsolv 8.6 mg / 2.1 mg sublingual tablets  
buprenorphine / naloxone 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Orexo AB 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Fold here  
Tear here 
 



43  

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
 
PACK OF 7, 28, and 30 TABLETS 11.4 mg / 2.9 mg STRENGTH 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zubsolv 11.4 mg / 2.9 mg sublingual tablets  
buprenorphine / naloxone 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each sublingual tablet contains 11.4 mg buprenorphine (as hydrochloride) and 2.9 mg naloxone (as 
hydrochloride dihydrate). 
 
 
3. LIST OF EXCIPIENTS 
 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
7 sublingual tablets 
28 sublingual tablets 
30 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 
 
Zubsolv is not interchangeable with other buprenorphine products. 
 
 
8. EXPIRY DATE 
 



44  

EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package below 25°C in order to protect from moisture. 
 
 
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 
 
Orexo AB 
Box 303 
751 05 Uppsala 
Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/17/1233/006 
EU/1/17/1233/017 
EU/1/17/1233/018 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
ZUBSOLV 11.4 mg / 2.9 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 



45  

 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



46  

 
MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
 
PACK OF 7, 28, and 30 TABLETS 11.4 mg / 2.9 mg STRENGTH 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zubsolv 11.4 mg / 2.9 mg sublingual tablets  
buprenorphine / naloxone 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Orexo AB 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
Fold here  
Tear here 
 



47  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



48  

Package leaflet: Information for the patient 
 

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

 
buprenorphine / naloxone 

 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm 

them, even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
 
What is in this leaflet 
 
1. What Zubsolv is and what it is used for 
2. What you need to know before you take Zubsolv 
3. How to take Zubsolv 
4. Possible side effects 
5. How to store Zubsolv 
6. Contents of the pack and other information 
 
 
1. What Zubsolv is and what it is used for 
 
Zubsolv contains the active substances buprenorphine and naloxone. Zubsolv is used to treat 
dependence on opioid (narcotic) drugs such as heroin or morphine in drug addicts who have agreed 
to be treated for their addiction. Zubsolv is used in adults and adolescents over 15 years of age, 
who are also receiving medical, social and psychological support. 
 
How Zubsolv works 
The tablet contains buprenorphine which is responsible for the treatment of opioid (narcotic) 
dependence. It also contains naloxone which is used to deter intravenous abuse of the product. 
 
 
2. What you need to know before you take Zubsolv 
 
Do not take Zubsolv if you: 
- are allergic to buprenorphine, naloxone or any of the other ingredients of this medicine 

(listed in section 6) 
- have serious breathing problems 
- have serious liver problems 
- are intoxicated due to alcohol or have trembling, sweating, anxiety, confusion, or 

hallucinations caused by alcohol 
- are taking naltrexone or nalmefene for the treatment of alcohol or opioid dependence 
 
Warnings and precautions 



49  

 
• Misuse, abuse and diversion 
Serious cases of infections with potential fatal outcome may occur if Zubsolv is misused, by taking 
it intravenously. 
 
This medicine can be a target for people who abuse prescription medicines, and should be kept in a 
safe place to protect it from theft. Do not give this medicine to anyone else. It can cause death or 
otherwise harm them. 
 
• Breathing problems (see also ‘Do not take Zubsolv’ above ) 
Some people have died from respiratory failure (inability to breathe) because they misused this 
medicine or took it in combination with other central nervous system depressants, such as alcohol, 
benzodiazepines (tranquilisers), or other opioids. 
 
The product should be used with care in patients with pre-existing breathing problems 
 
This medicine may cause severe, possibly fatal, respiratory depression (reduced ability to breathe) 
in children and non-opioid dependent people. 
 
• Drowsiness 
This medicine can cause drowsiness, particularly when taken together with alcohol or other central 
nervous system depressants (such as tranquilisers, sedatives or hypnotics). 
 
• Dependence 
This product can cause dependence. 
 
• Liver damage 
Liver damage has been reported after taking buprenorphine/naloxone, especially when the medicine 
is misused. This could also be due to viral infections (chronic hepatitis C), alcohol abuse, anorexia 
or use of other medicines that can harm your liver. Regular blood tests may be conducted by your 
doctor to monitor the condition of your liver. Tell your doctor if you have any liver problems 
before you start treatment with Zubsolv. 
 
• Withdrawal symptoms 
This product can cause withdrawal symptoms if you take it less than six hours after you use a 
short-acting opioid (e.g. morphine, heroin) or less than 24 hours after you use a long-acting 
opioid such as methadone. 
 
Zubsolv can also cause withdrawal symptoms if you stop taking it abruptly. 
 
• Blood pressure 
This product may cause your blood pressure to drop suddenly, causing you to feel dizzy if you get 
up too quickly from sitting or lying down. 
 
• Children and adolescents 
You may be more closely monitored by your doctor if you are below the age of 18. This medicine 
should not be taken by those under 15 years of age. 
 
• Diagnosis of unrelated medical conditions 
This medicine may mask pain symptoms that could assist in the diagnosis of some diseases. Do not 
forget to advise your doctor if you take this medicine. 
 
Talk to your doctor before taking Zubsolv if you: 
• have a depression or other conditions that are treated with antidepressants. 

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



50  

• have kidney problems 
• have recently suffered a head injury or brain disease 
• have low blood pressure, enlarged prostate gland or difficulties passing water because 

of narrowing of the urethra 
• have under-active thyroid gland which can cause tiredness or weight gain 
• have poor adrenal gland function (e.g. Addison’s disease) 
• have problems with the biliary tract (e.g. gall bladder, bile duct) 
• are elderly 
• are debilitated 
 
Other medicines and Zubsolv 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
Some medicines may increase the side effects of Zubsolv and may sometimes cause very serious 
reactions. Do not take any other medicines whilst taking Zubsolv without first talking to your 
doctor, especially: 
• anti-depressants such as moclobemide, tranylcypromine, citalopram, escitalopram, 

fluoxetine, fluvoxamine, paroxetine, sertraline, duloxetine, venlafaxine, amitriptyline, 
doxepine, or trimipramine. These medicines may interact with Zubsolv and you may 
experience symptoms such as involuntary, rhythmic contractions of muscles, including the 
muscles that control movement of the eye, agitation, hallucinations, coma, excessive 
sweating, tremor, exaggeration of reflexes, increased muscle tension, body temperature 
above 38°C. Contact your doctor when experiencing such symptoms. 

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

• Benzodiazepines (used to treat anxiety or sleep disorders) such as diazepam, 
temazepam, alprazolam. Your doctor will prescribe the correct dose for you. Taking the 
wrong dose of benzodiazepines may cause death due to respiratory failure (inability 
to breathe). 

• Other medicines that may make you feel sleepy which are used to treat illnesses such 
as anxiety, sleeplessness, convulsions/seizures, pain and other mental disorders. These 
types of medicines will reduce your alertness levels making it dangerous for you to drive 
and use machines. They may also cause central nervous system depression, which is very 
serious. Below is a list of examples of these types of medicines: 
- other opioid containing medicines such as methadone, certain pain killers and 

cough suppressants 
- some anti-depressants (used to treat depression) such as isocarboxazid, phenelzine, 

selegiline, tranylcypromine, valproate and monoamine oxidase inhibitors (MAOIs) may 
increase the effects of this medicine 

- sedative 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) and related medicines may extend the 

effects of this medicine 
• anti-retrovirals (used to treat HIV) such as ritonavir, nelfinavir, indinavir may increase 

the effects of this medicine 
• some antifungal agents (used to treat fungal infections) such as ketoconazole, itraconazole 

and certain antibiotics, may extend the effects of this medicine 
• some medicines may decrease the effect of Zubsolv. These include medicines used to 

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

 
Zubsolv with food, drink and alcohol 



51  

Alcohol may increase drowsiness and may increase the risk of respiratory failure if taken with 
Zubsolv. Do not take Zubsolv together with alcohol. Do not swallow or consume food or any 
drink until the tablet is completely dissolved. 
 
Pregnancy and breast-feeding 
The risks of using Zubsolv in pregnant women are not known. Tell your doctor if you are pregnant or 
intend to become pregnant. Your doctor will decide if your treatment should be continued with an 
alternative medicine. 
When taken during pregnancy, particularly late pregnancy, medicines like Zubsolv may cause drug 
withdrawal symptoms including problems with breathing in your newborn baby. This may appear 
several days after birth. 
 
Do not breast-feed whilst taking this medicine, since Zubsolv passes into breast milk. Ask your 
doctor or pharmacist for advice before taking any medicine. 
 
Driving and using machines 
Zubsolv may cause drowsiness. This may happen more often in the first few weeks of treatment 
when your dose is being changed, but can also happen if you drink alcohol or take other sedative 
medicines when you take Zubsolv. Do not drive, use any tools or machines, or perform dangerous 
activities until you know how this medicine affects you. 
 
 
3. How to take Zubsolv 
 
Your treatment is prescribed and monitored by doctors who are experienced in the treatment of drug 
dependence. 
 
Your doctor will determine the best dose for you. During your treatment, the doctor may adjust the 
dose, depending upon your response. 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your 
doctor or pharmacist if you are not sure. 
 
Starting treatment 
The recommended starting dose for adults and adolescents over the age of 15 years is: 
 

- one tablet of Zubsolv 1.4 mg / 0.36 mg each day, or 
 

- one tablet of Zubsolv 2.9 mg / 0.71 mg each day 
 
An additional tablet of the Zubsolv 1.4 mg / 0.36 mg or 2.9 mg / 0.71 mg may be administered on 
Day 1 depending on your needs. 
 
There are other strengths that are available to be used by your doctor who will decide what is the 
best treatment for you. This may involve taking a combination of different strengths, but your daily 
dose should not exceed 17.2mg of buprenorphine. 
 
Clear signs of withdrawal should be evident before taking your first dose of Zubsolv. A doctor’s 
assessment of your readiness for treatment will guide the timing of your first Zubsolv dose. 
 
• Starting treatment of Zubsolv whilst dependent on heroin: 
If you are dependent upon heroin or a short acting opioid, your first dose of Zubsolv should be 
taken when signs of withdrawal appear, but not less than 6 hours after you last used opioids 
 
• Starting treatment of Zubsolv whilst dependent on methadone: 
If you have been taking methadone or a long acting opioid, the dose of methadone should ideally be 



52  

reduced to below 30 mg/day before beginning Zubsolv therapy. The first dose of Zubsolv should be 
taken when signs of withdrawal appear, but not less than 24 hours after you last used methadone 
 
Taking Zubsolv 
• Take the dose once a day or as advised by your doctor. 
 
• Remove the tablet as described below. Only open the blister immediately before taking the 

dose.  Never open in advance as the tablet is sensitive to moisture 
 
• Place the tablets under the tongue 
 
• Keep the tablets in place under the tongue until they have completely dissolved 
 
• Do not chew or swallow the tablets, as the medicine will not work and you may get 

withdrawal symptoms 
 
• Do not consume any food or drink until the tablets have completely dissolved. Whilst you 

may notice that most of the table disintegrates within 40 seconds, it may take 5 to 10 minutes 
for the entire table to disappear from your mouth 

 
How to remove the tablet from the blister 

 
 
 
 

1. Do not push the tablet through the foil. 
 
 
 
 
 
 
 

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

 
 
 
 
 

3. Fold the packet along the dotted line.  
 
 
 
 
 
 
 
 
 

4. Tear following the direction of the arrow. If the blister is 
damaged, discard the tablet. 

 



53  

 
 
 
Dosage adjustment and maintenance therapy 
Your doctor may increase the dose of Zubsolv you take according to your needs. If you feel that 
the effect of Zubsolv is too strong or too weak, talk to your doctor or pharmacist. The maximum 
daily dose is 17.2 mg. 
 
After a period of successful treatment, you may agree with your doctor to reduce the dose gradually 
to a lower maintenance dose. 
 
Stopping treatment 
Do not change the treatment in any way or stop treatment without the agreement of the doctor who 
is treating you. 
 
Depending on your condition, the dose of Zubsolv may continue to be reduced under careful 
medical supervision, until eventually it may be stopped. 
 
If you take more Zubsolv than you should 
If you or someone else takes too much of this medicine, you must go or be taken immediately to an 
emergency centre or hospital for treatment as overdose with Zubsolv may cause serious and 
life-threatening breathing problems. 
 
Symptoms of overdose may include breathing more slowly and weakly than normal, feeling more 
sleepy than normal, reduction in the size of the pupils, low blood pressure, feeling sick, vomit 
and/or slurred speech. 
 
If you forget to take Zubsolv 
Tell your doctor as soon as possible if you miss a dose. 
 
If you stop taking Zubsolv 
Do not change the treatment in any way or stop treatment without the agreement of the doctor who is 
treating you. Stopping treatment suddenly may cause withdrawal symptoms. 
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Tell your doctor immediately or seek urgent medical attention if you experience serious side 
effects, such as: 
• swelling of the face, lips, tongue or throat which may cause difficulty in swallowing or 

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

• feeling sleepy and uncoordinated, have blurred vision, have slurred speech, cannot think well 
or clearly, or your breathing gets much slower than is normal for you 

• severe tiredness, itching with yellowing of skin or eyes. These may be symptoms of 
liver damage 

• seeing or hearing things that are not there (hallucinations) 
 
Other side effects 
Very common side effects (may affect more than one in 10 people): 
• insomnia (inability to sleep) 
• headache 



54  

• constipation, nausea 
• excessive sweating 
• drug withdrawal syndrome 
 
Common side effects (may affect up to 1 in 10 people): 
• flu-like symptoms, infection, sore throat and painful swallowing, runny nose 
• anxiety, depression, decreased sexual drive, nervousness, abnormal thinking 
• migraines, dizziness, fainting, increase in muscle tension, tingling, drowsiness 
• increased tearing (watering eyes) or other tearing disorder 
• increased blood pressure, flushing 
• increased cough 
• abdominal pain, upset stomach or other stomach discomfort, diarrhoea, flatulence, vomiting 
• rash, itching, hives 
• back pain, joint pain, muscle pain, leg cramps (muscle spasm) 
• urine abnormality 
• difficulty in getting or keeping an erection 
• weakness, chest pain, chills, fever, feeling of general discomfort, pain, swelling (hands and 

feet) 
• abnormal liver function, weight loss 
• accidental injury caused by loss of alertness or co-ordination 
 
Uncommon side effects (may affect up to 1 in 100 people): 
• abnormal blood tests swollen, glands (lymph nodes) 
• abnormal dreams, agitation, loss of interest, depersonalisation (not feeling like 

yourself), medicine dependence, exaggerated feeling of well-being, feelings of 
hostility 

• amnesia (memory disturbance), convulsion (fits), speech disorder, tremor 
• eye inflammation or infection, small pupil size 
• rapid or slow heartbeat, myocardial infarction (heart attack), palpitations, chest tightness 
• low blood pressure 
• asthma, shortness of breath, yawning 
• pain and sores in mouth, tongue discolouration 
• acne, hair loss, dry or scaling skin, skin nodule 
• inflammation of joints 
• protein in your urine, urinary tract infection, difficulty urinating, painful or difficult 

urination, blood in urine, kidney stone 
• menstrual or vaginal problems, abnormal ejaculation 
• sensitivity to heat or cold 
• heat stroke 
 
Not known (frequency cannot be estimated from the available data): 
• deterioration of brain function that is a serious complication of liver disease 
• spinning sensation 
• drop in blood pressure on changing position from sitting or lying down to standing 
• sudden withdrawal syndrome caused by taking product too soon after use of illicit opioids, 

drug withdrawal syndrome in newborn 
 
Misusing this medicine by injecting it can cause withdrawal symptoms, infections, other skin 
reactions and potentially serious liver problems (see section 2, Warnings and precautions). 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety 



55  

of this medicine. 
 
 
5. How to store Zubsolv 
 
Keep this medicine out of the sight and reach of children. 
Do not use this medicine after the expiry date which is stated on the carton and blister after EXP. The 
expiry date refers to the last day of that month. 
 
Store in the original package below 25°C in order to protect from moisture. 
 
Zubsolv can be a target for people who abuse prescription medicine. Keep this medicine in a safe 
place to protect it from theft. 
 
Store the blister safely. 
 
Never open the blister in advance. 
 
Do not take this medicine in front of children. 
 
An emergency unit should be contacted immediately in case of accidental ingestion or suspicion of 
ingestion. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
The active substances are buprenorphine and naloxone. 
 
Each 0.7 mg / 0.18 mg sublingual tablet contains 0.7 mg buprenorphine (as hydrochloride) and 
0.18 mg naloxone (as hydrochloride dihydrate). 
 
Each 1.4 mg / 0.36 mg sublingual tablet contains 1.4 mg buprenorphine (as hydrochloride) and 
0.36 mg naloxone (as hydrochloride dihydrate). 
 
Each 2.9 mg / 0.71 mg sublingual tablet contains 2.9 mg buprenorphine (as hydrochloride) and 
0.71 mg naloxone (as hydrochloride dihydrate). 
 
Each 5.7 mg / 1.4 mg sublingual tablet contains 5.7 mg buprenorphine (as hydrochloride) and 
1.4 mg naloxone (as hydrochloride dihydrate). 
 
Each 8.6 mg / 2.1 mg sublingual tablet contains 8.6 mg buprenorphine (as hydrochloride) and 
2.1 mg naloxone (as hydrochloride dihydrate). 
 
Each 11.4 mg / 2.9 mg sublingual tablet contains 11.4 mg buprenorphine (as hydrochloride) and 
2.9 mg naloxone (as hydrochloride dihydrate). 
 
The other ingredients are mannitol, citric acid anhydrous, sodium citrate, microcrystalline cellulose, 
croscarmellose sodium, sucralose, levomenthol, colloidal anhydrous silica and sodium stearyl 
fumarate. 
 
What Zubsolv looks like and contents of the pack 
 
Zubsolv sublingual tablets are available in six different strengths, differentiated by shape and 



56  

debossing: 
 

Zubsolv tablet strength 
(buprenorphine/naloxone) 

Zubsolv tablet description Zubsolv tablet 
debossing 

Appearance 

0.7 mg / 0.18 mg White, oval tablet, length 
6.8 mm and width 4.0 mm 

“.7” on one side 

 1.4 mg / 0.36 mg White, triangular tablet, 
base 7.2 mm and height 6.9 
mm 

“1.4” on one side 

 

2.9 mg / 0.71 mg White, D-shaped tablet, 
height 7.3 mm and width 
5.65 mm 

“2.9” on one side  

 

5.7 mg / 1.4 mg White, round tablet, 7 mm 
in diameter 

“5.7” on one side  

 
8.6 mg / 2.1 mg White, diamond shaped 

tablet, length 9.5 mm and 
width 8.2 mm 

“8.6” on one side 

 

11.4 mg / 2.9 mg White, capsule shaped 
tablet, length 10.3 mm and 
width 8.2 mm 

“11.4” on one side 

 
 

 
 
All strengths will be available as packs of 7, 28, and 30 tablets presented in 
aluminium blisters. Not all strengths and pack-sizes may be marketed. 
 
Marketing Authorisation Holder  
Orexo AB 
Box 303 
751 05 Uppsala 
Sweden 
 
Manufacturer  
Orexo AB  
Virdings allé 32 A  
Uppsala 751 05  
Sweden 
 
 
This leaflet was last revised in. 
 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER 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
	A. LABELLING
	B. PACKAGE LEAFLET