Zubsolv

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. 2). 2). e. long- or short-acting opioid), the time since last opioid use and the degree of opioid dependence.

g. by 4 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.

71 mg a day. 71 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 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.

g. 7 mg). During maintenance therapy, it may be necessary to periodically restabilise the patient on a new maintenance dose in response to changing patient needs. 18 mg 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.

e. insomnia, headache, nausea, hyperhidrosis and pain). Some reports of seizure, vomiting, diarrhoea, and elevated liver function tests were considered serious. 5%) reported adverse reactions and adverse reactions reported during post-marketing surveillance.

The frequency of possible adverse reactions 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).

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.

Misuse, abuse and diversion Buprenorphine can be misused or abused in a manner similar to other opioids, legal or illicit. Some risks of 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 medicinal product 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 medicinal product 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- 6 medicating with opioids, alcohol or other sedative-hypnotics such as benzodiazepines.

To minimize the risk of misuse, abuse and diversion, appropriate precautions should be taken when prescribing and dispensing buprenorphine, such as to avoiding prescribing multiple refills early in treatment, and to conducting 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 with buprenorphine alone since the naloxone in Zubsolv can precipitate withdrawal in individual’s dependent on heroin, methadone, or other opioid agonists.

Sleep-related breathing disorders Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep- related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the total opioid dosage.

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.