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Hypersensitivity to buprenorphine or any of the excipients - Children and adolescents less than 16 years of age - Severe respiratory insufficiency - Severe hepatic insufficiency - Acute alcoholism or delirium tremens - Breast feeding Special warnings and precautions for use Buprenorphine Sublingual Tablets are recommended only for the treatment of opioid drug dependence.

It is also recommended that that treatment is prescribed by a physician who ensures comprehensive management of the opioid-dependent patient(s) 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 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 medicine is not safeguarded against theft.

Sub-optimal treatment with buprenorphine may prompt medication misuse by the patient, leading to overdose or treatment dropout. A patient who is under- dosed with buprenorphine may continue responding to uncontrolled withdrawal symptoms by self-medicating with opioids, alcohol or other sedative-hypnotics such as benzodiazepines.

To minimise the risk of misuse, abuse and diversion, 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 level of stability.

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 nonopioid dependent individuals who are not tolerant to the effects of opioids, potentially fatal respiratory depression may occur.

g. chronic obstructive pulmonary disease, asthma, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, pre-existing respirator depression or kyphoscoliosis). Buprenorphine may cause severe, possibly fatal, respiratory depression in children and non-dependent persons who accidentally or deliberately ingest it.

Protect children and non-dependent persons against exposure. 7). Dependence Buprenorphine is a partial agonist at the 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.

Abrupt discontinuation of treatment is not recommended as it may result in a withdrawal that may be delayed in onset. Hepatitis and hepatic events Cases of acute hepatic injury have been reported in opioid-dependent patients both in clinical trials and in post-marketing adverse event reports.

The spectrum of abnormalities ranges from transient asymptomatic elevations in hepatic transaminases to case reports of cytolytic hepatitis, hepatic failure, hepatic necrosis, hepatorenal syndrome, hepatic encephalopathy and death.

In many cases, the presence of pre-existing liver enzyme abnormalities, genetic disease, infection with hepatitis B or hepatitis C virus, alcohol abuse, anorexia, concomitant use of other potentially hepatotoxic drugs and ongoing injecting drug use may have a causative or contributory role.

These underlying factors must be taken into consideration before prescribing buprenorphine and during treatment. When a hepatic event is suspected further biological and etiological evaluation is required. Depending on the findings, buprenorphine may be discontinued cautiously so as to prevent withdrawal symptoms and to prevent a return to illicit drug use.

If treatment is continued, hepatic function should be monitored closely. All patients should have liver function tests performed at regular intervals. Precipitation of opioid withdrawal syndrome When initiating treatment with buprenorphine, it is important to be aware of the partial agonist profile of buprenorphine.

Sublingually administered buprenorphine can precipitate withdrawal in opioid-dependent patients particularly if administered before the agonist effects resulting from recent opioid use or misuse have subsided. 2). Hepatic impairment The effects of hepatic impairment on the pharmacokinetics of buprenorphine were evaluated in a post-marketing study.

Buprenorphine is extensively metabolized in the liver, plasma levels were found to be higher for buprenorphine 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 buprenorphine.

2). In patients with severe hepatic insufficiency the use of buprenorphine is contraindicated. Renal impairment Renal elimination plays a relatively small role (approximately 30%) in the overall clearance of buprenorphine; […]