BUPRENORPHINE/NALOXONE

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).

o For patients dependent upon heroin or short-acting opioids, the first dose of buprenorphine/naloxone should be taken when signs of withdrawal appear, but not less than 6 hours after the patient last used opioids. o For patients receiving methadone, the dose of methadone should be reduced to a maximum of 30 mg/day before beginning buprenorphine/naloxone therapy.

The long half life of methadone should be considered when starting buprenorphine/naloxone. The first dose of buprenorphine/naloxone should be taken only when signs of withdrawal appear, but not less than 24 hours after the patient last used methadone.

Buprenorphine may precipitate symptoms of withdrawal in patients dependent upon methadone. 5 mg. 5 mg may be administered on day one depending on the individual patient’s requirement. During the initiation of treatment, daily supervision of dosing is recommended to ensure proper sublingual placement of the dose and to observe patient response to treatment as a guide to effective dose titration according to clinical effect.

Dosage adjustment and maintenance therapy Following treatment induction on day one, the patient should be stabilised to a maintenance dose during the next few days by progressively adjusting the dose according to the clinical effect of the individual patient.

Dose titration in steps of 2-8 mg buprenorphine is guided by reassessment of the clinical and psychological status of the patient, and should not exceed a maximum single daily dose of 24 mg buprenorphine. Less than daily dosing After a satisfactory stabilisation has been achieved the frequency of dosing may be decreased to dosing every other day at twice the individually titrated daily dose.

For example, a patient stabilised to receive a daily dose of 8 mg buprenorphine may be given 16 mg buprenorphine on alternate days, with no dose on the intervening days. In some patients, after a satisfactory stabilisation has been achieved, the frequency of dosing may be decreased to 3 times a week (for example on Monday, Wednesday and Friday).

The dose on Monday and Wednesday should be twice the individually titrated daily dose, and the dose on Friday should be three times the individually titrated daily dose, with no dose on the intervening days. However, the dose given on any one day should not exceed 24 mg buprenorphine.

Patients requiring a titrated daily dose> 8 mg buprenorphine /day may not find this regimen adequate. Medical withdrawal After a satisfactory stabilisation has been achieved, if the patient agrees, the dosage may be reduced gradually to a lower maintenance dose; in some favourable cases, treatment may be discontinued.

5 mg and 8 mg/2 mg allows for a downward titration of dosage. 4 mg may be used. Patients should be monitored following medical withdrawal because of the potential for relapse. Special populations Elderly The safety and efficacy of buprenorphine/naloxone in elderly patients over 65 years of age have not been established.

No recommendation on posology can be made. Hepatic impairment Baseline liver function tests and documentation of viral hepatitis status is recommended prior to commencing therapy. 5) and/or have existing liver dysfunction are at risk of accelerated liver injury.

4). Both active substances of Buprenorphine/Naloxone Ethypharm, buprenorphine and naloxone, are extensively metabolized in the liver, and the plasma levels were found to be higher for both buprenorphine and naloxone in patients with moderate and severe hepatic impairment.

Patients should be monitored for signs and symptoms of precipitated opioid withdrawal, toxicity or overdose caused by increased levels of naloxone and/or buprenorphine. As buprenorphine/naloxone pharmacokinetics may be altered in patients with hepatic impairment, lower initial doses and careful dose titration in patients with mild to moderate hepatic impairment are recommended.

Buprenorphine/naloxone is contraindicated in patients with severe hepatic impairment. 2). Renal impairment Modification of the buprenorphine/naloxone dose is not required in patients with renal impairment. 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. 4). The tablet is to be placed under the tongue until completely dissolved. Patients should not swallow or consume food or drink until the tablet is completely dissolved. The dose is made up from multiple Buprenorphine/Naloxone Ethypharm […]

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 side effects listed below is defined using the following convention: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Not known (cannot be estimated from available data). 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. uk/yellowcard.

Misuse, abuse and diversion Buprenorphine can be misused or abused in a manner similar to other opioids, legal or illicit. Some risks of misuse and abuse include overdose, spread of blood borne viral or localised and systemic infections, respiratory depression and hepatic injury.

Buprenorphine misuse by someone other than the intended patient poses the additional risk of new drug dependent individuals using buprenorphine as the primary drug of abuse, and may occur if the 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-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 Buprenorphine/Naloxone Ethypharm is intended to deter misuse and abuse of the buprenorphine. Intravenous or intranasal misuse of Buprenorphine/Naloxone Ethypharm is expected to be less likely than buprenorphine alone since the naloxone in Buprenorphine/Naloxone Ethypharm can precipitate withdrawal in individuals dependent on heroin, methadone, or other opioid agonists.

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.

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 nondependent 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.

5). Risk from concomitant use of sedative medicinal products such as benzodiazepines or related active substances Concomitant use of buprenorphine/naloxone and sedative medicinal products such as benzodiazepines or related active substances may result in sedation, respiratory depression, coma and death.

Because of these risks, concomitant prescribing with these sedative medicinal products should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe Buprenorphine/Naloxone Ethypharm concomitantly with sedative medicinal products, 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). 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 […]

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.