BUPRENORPHINE/NALOXONE MYLAN

Treatment must be under the supervision of a physician experienced in the management of opiate dependence/addiction. e. long-or short-acting opioid), the time since last opioid use and the degree of opioid dependence. 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 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. 5 mg. 5 mg as a single dose, which can be repeated up to twice on day 1, to minimise undue withdrawal symptoms and retain the patient in treatment.

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. 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/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 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.

5 mg and 8 mg/2 mg allows for a downward titration of dose. 4 mg sublingual tablet may be used. Patients should be monitored following medical withdrawal because of the potential for relapse. 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 buprenorphine/naloxone sublingual tablets and buprenorphine/naloxone 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 buprenorphine/naloxone film compared to buprenorphine/naloxone 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. 2). If switching between buprenorphine/naloxone film and buprenorphine/naloxone 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 have 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 […]

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 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 available data).

4). 4). Drug dependence Repeated use of Buprenorphine/Naloxone Mylan can lead to drug dependence, even at therapeutic doses. 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Tolerance and opioid use disorder (abuse and dependence) Tolerance, physical and psychological dependence, and opioid use disorder (OUD) may develop upon repeated administration of opioids such as Buprenorphine/Naloxone Mylan. Abuse or intentional misuse of Buprenorphine/Naloxone Mylan may result in overdose and/or death.

g. major depression, anxiety and personality disorders). 2). g. too early requests for refills). This includes the review of concomitant opioids and psychoactive drugs (like benzodiazepines). For patients with signs and symptoms of OUD, consultation with an addiction specialist should be considered.

Combining buprenorphine with naloxone in buprenorphine/naloxone is intended to deter misuse and abuse of the buprenorphine. Intravenous or intranasal misuse of buprenorphine/naloxone is expected to be less likely than with buprenorphine alone since the naloxone in this medicinal product can precipitate withdrawal in individuals dependent on heroin, methadone, or other opioid agonists.

Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs: Concomitant use of buprenorphine/naloxone and sedative medicines such as benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death.

Because of these risks, concomitant prescribing with these sedative medicines 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 medicines, the lowest effective dose 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. 5). The risk for respiratory depression also exists when buprenorphine is 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. 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 medicinal product in front of children.

An emergency unit should be contacted immediately in case of accidental ingestion or suspicion of ingestion. 7). Dependence Buprenorphine is a partial agonist at the μ (mu)-opiate receptor and chronic administration produces dependence of the opioid type.

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 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 […]

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.