Use in adults

Abernil treatment should be initiated and supervised by suitable qualified physicians.

The initial dose of Abernil hydrochloride should be 25 mg (half a tablet) for opioid-dependent patient followed by the usual dose of one tablet per day (= 50 mg Abernil hydrochloride)

A missed dose can be managed by providing 1 tablet per day each day till the next regular dosage-administration.

Abernil administered to opioid-dependent persons can cause life-threatening withdrawal symptoms. Patients suspected of using or being addicted to opioids must undergo a naloxone provocation test , unless it can be verified that the patient has not taken any opioids for 7-10 days (urine test) prior to the initiation of treatment with Abernil.

As Abernil is an adjunctive therapy and the full recovery process in opioid-dependent patients is individually variable, no standard duration of treatment can be stated; an initial period of three months should be considered. However, prolonged administration may be necessary.

The recommended dose for alcohol dependence to support abstinence is 50 mg per day (1 tablet). A dose of over 150 mg on any single day is not recommended, since this can lead to a higher incidence of side effects.

As Abernil hydrochloride is an adjunctive therapy and the full recovery process from alcohol dependence is individually variable, no standard duration of treatment can be stated; an initial period of three months should be considered. However, prolonged administration may be necessary

The dosage-regimen can be modified in order to improve compliance to a three-times-a-week dosing schedule as follows: administration of 2 tablets (=100 mg Abernil hydrochloride) on Monday and on Wednesday and 3 tablets (=150 mg Abernil hydrochloride) on Friday.

Paediatric population

Abernil should not be used in children and adolescents under 18 years of age, since clinical data in this age-group are lacking. Safe use in children has not been established.

Older people

There are insufficient data on the safety and efficacy of Abernil for this indication in elderly patients.

Use in adults

Naltrexone treatment should be initiated and supervised by suitable qualified physicians.

The initial dose of Abernil should be 25 mg (half a tablet) for opioid-dependent patient followed by the usual dose of one tablet per day (= 50 mg Abernil)

A missed dose can be managed by providing 1 tablet per day each day till the next regular dosage-administration.

Naltrexone administered to opioid-dependent persons can cause life-threatening withdrawal symptoms. Patients suspected of using or being addicted to opioids must undergo a naloxone provocation test , unless it can be verified that the patient has not taken any opioids for 7-10 days (urine test) prior to the initiation of treatment with naltrexone.

As Naltrexone is an adjunctive therapy and the full recovery process in opioid-dependent patients is individually variable, no standard duration of treatment can be stated; an initial period of three months should be considered. However, prolonged administration may be necessary.

The recommended dose for alcohol dependence to support abstinence is 50 mg per day (1 tablet). A dose of over 150 mg on any single day is not recommended, since this can lead to a higher incidence of side effects.

As Abernil is an adjunctive therapy and the full recovery process from alcohol dependence is individually variable, no standard duration of treatment can be stated; an initial period of three months should be considered. However, prolonged administration may be necessary

The dosage-regimen can be modified in order to improve compliance to a three-times-a-week dosing schedule as follows: administration of 2 tablets (=100 mg Abernil) on Monday and on Wednesday and 3 tablets (=150 mg Abernil) on Friday.

Paediatric population

Naltrexone should not be used in children and adolescents under 18 years of age, since clinical data in this age-group are lacking. Safe use in children has not been established.

Older people

There are insufficient data on the safety and efficacy of naltrexone for this indication in elderly patients.

In accordance to national guidance the therapy should be initiated and supervised by a physician experienced in treatment of opioid-addicted and alcohol-addicted patients

High dose opioid intake, concomitant with Abernil treatment, can lead to life-threatening opioid poisoning from respiratory and circulatory impairment.

Should Abernil be used in opioid-dependent patients a withdrawal syndrome may occur rapidly: the first symptoms can occur within 5 minutes, the last after 48 hours. The treatment of withdrawal symptoms is symptomatic.

It is not uncommon for alcohol abusing individuals to show signs of impaired hepatic function. Abnormal hepatic function test parameters have been reported in obese and elderly patients receiving Abernil in dosages higher than recommended (up to 300 mg/day). Hepatic function controls should be made before and during treatment. Special attention should be paid to patients with hepatic enzyme levels in serum exceeding three times the normal value and patients with renal impairment.

Liver function test abnormalities have been reported in obese and elderly patients taking Abernil who have no history of drug abuse. Liver function tests should be carried out both before and during treatment.

Patients must be warned against the concomitant use of opioids (e.g. opioids in cough medication, opioids in symptomatic medication for the treatment of common colds, or opioids contained in anti diarrhoeal agents, etc.) during Abernil treatment.

Abernil treatment must begin only when the opioid has been discontinued for a sufficiently long period (about 5 to 7 days for heroin and at least 10 days for methadone).

If the patient needs opioid treatment, e.g. opioid analgesia or anesthesia in emergency situations, the dose needed may be higher than normal. In these cases, the respiratory depression and circulatory effects will be more profound and longer lasting. Symptoms related to release of histamine (generalized erythema, diaphoresis, itching and other skin and mucocutaneous manifestations) can also be manifested more easily. The patient requires specific attention and care in these situations.

During treatment with Abernil, painful conditions should be treated with non-opioid analgesia only.

Patients should be warned that large doses of opioids to overcome the blockade may after the cessation of the Abernil result in an acute opioid overdose, with possible fatal outcome.

Patients might be more sensitive to opioid containing medicines after treatment with Abernil.

Patients suspected of using or being addicted to opioids must undergo a naloxone provocation test, unless it can be verified that the patient has not taken any opioids for 7-10 days (urine test) prior to the initiation of treatment with Abernil.

A withdrawal syndrome precipitated by naloxone will be of shorter duration than withdrawal precipitated by Abernil.

The recommended procedure is as follows:

Intravenous provocation

- Intravenous injection of 0.2 mg naloxone

- If after 30 seconds no adverse reactions occur, a further i.v. injection of 0.6 mg naloxone may be administered.

- The patient should be observed continuously for 30 minutes for any detectable sign of withdrawal symptoms.

If any symptoms of withdrawal occur Abernil-therapy must not be undertaken. If the test-result is negative the treatment can be initiated. If any doubt exists that the patient is opioid-free, the challenge may be repeated with the dosage of 1.6 mg. If no reaction occurs after this, 25 mg of Abernil hydrochloride can be administered to the patient.

A naloxone hydrochloride provocation test should not be made in patients with clinically prominent withdrawal symptoms nor in any case of a positive urine test for opioids.

Abernil is extensively metabolised by the liver and excreted predominantly in the urine. Therefore, caution should be observed in administering the medicinal product to patients with impaired hepatic or renal function. Liver function tests should be carried out both before and during treatment.

The risk of suicide is known to increase in substance abusers, with or without concomitant depression. Treatment with Abernil tablet does not eliminate this risk.

Lactose

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

In accordance to national guidance the therapy should be initiated and supervised by a physician experienced in treatment of opioid-addicted and alcohol-addicted patients

High dose opioid intake, concomitant with Naltrexone treatment, can lead to life-threatening opioid poisoning from respiratory and circulatory impairment.

Should naltrexone be used in opioid-dependent patients a withdrawal syndrome may occur rapidly: the first symptoms can occur within 5 minutes, the last after 48 hours. The treatment of withdrawal symptoms is symptomatic.

It is not uncommon for alcohol abusing individuals to show signs of impaired hepatic function. Abnormal hepatic function test parameters have been reported in obese and elderly patients receiving naltrexone in dosages higher than recommended (up to 300 mg/day). Hepatic function controls should be made before and during treatment. Special attention should be paid to patients with hepatic enzyme levels in serum exceeding three times the normal value and patients with renal impairment.

Liver function test abnormalities have been reported in obese and elderly patients taking naltrexone who have no history of drug abuse. Liver function tests should be carried out both before and during treatment.

Patients must be warned against the concomitant use of opioids (e.g. opioids in cough medication, opioids in symptomatic medication for the treatment of common colds, or opioids contained in anti diarrhoeal agents, etc.) during naltrexone treatment.

Naltrexone treatment must begin only when the opioid has been discontinued for a sufficiently long period (about 5 to 7 days for heroin and at least 10 days for methadone).

If the patient needs opioid treatment, e.g. opioid analgesia or anesthesia in emergency situations, the dose needed may be higher than normal. In these cases, the respiratory depression and circulatory effects will be more profound and longer lasting. Symptoms related to release of histamine (generalized erythema, diaphoresis, itching and other skin and mucocutaneous manifestations) can also be manifested more easily. The patient requires specific attention and care in these situations.

During treatment with naltrexone, painful conditions should be treated with non-opioid analgesia only.

Patients should be warned that large doses of opioids to overcome the blockade may after the cessation of the naltrexone result in an acute opioid overdose, with possible fatal outcome.

Patients might be more sensitive to opioid containing medicines after treatment with naltrexone.

Patients suspected of using or being addicted to opioids must undergo a naloxone provocation test, unless it can be verified that the patient has not taken any opioids for 7-10 days (urine test) prior to the initiation of treatment with naltrexone.

A withdrawal syndrome precipitated by naloxone will be of shorter duration than withdrawal precipitated by naltrexone.

The recommended procedure is as follows:

Intravenous provocation

- Intravenous injection of 0.2 mg naloxone

- If after 30 seconds no adverse reactions occur, a further i.v. injection of 0.6 mg naloxone may be administered.

- The patient should be observed continuously for 30 minutes for any detectable sign of withdrawal symptoms.

If any symptoms of withdrawal occur naltrexone-therapy must not be undertaken. If the test-result is negative the treatment can be initiated. If any doubt exists that the patient is opioid-free, the challenge may be repeated with the dosage of 1.6 mg. If no reaction occurs after this, 25 mg of Abernil can be administered to the patient.

A naloxone hydrochloride provocation test should not be made in patients with clinically prominent withdrawal symptoms nor in any case of a positive urine test for opioids.

Naltrexone is extensively metabolised by the liver and excreted predominantly in the urine. Therefore, caution should be observed in administering the medicinal product to patients with impaired hepatic or renal function. Liver function tests should be carried out both before and during treatment.

The risk of suicide is known to increase in substance abusers, with or without concomitant depression. Treatment with Naltrexone tablet does not eliminate this risk.

Lactose

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Abernil may impair the mental and/or physical abilities required for performance of potentially hazardous tasks such as driving a car or operating machinery.

Naltrexone may impair the mental and/or physical abilities required for performance of potentially hazardous tasks such as driving a car or operating machinery.

The following undesirable effects are ranked according to system organ class and to their frequency:

Very common (> 1/10)

Common (>1/100 to < 1/10)

Uncommon (>1/1,000 to < 1/100)

Rare (> 1/10,000 to < 1/1,000)

Very rare (< 1/10,000)

not known (cannot be estimated from the available data)

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 (To be completed nationally).

The following undesirable effects are ranked according to system organ class and to their frequency:

Very common (> 1/10)

Common (>1/100 to < 1/10)

Uncommon (>1/1,000 to < 1/100)

Rare (> 1/10,000 to < 1/1,000)

Very rare (< 1/10,000)

not known (cannot be estimated from the available data)

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 (To be completed nationally).

Symptoms

- There is limited clinical experience with Abernil overdose in patients.

- There was no evidence of toxicity in volunteers receiving 800 mg/day for seven days.

Treatment

- In case of overdose, patients should be monitored and treated symptomatically in a closely supervised environment.

Symptoms

- There is limited clinical experience with naltrexone overdose in patients.

- There was no evidence of toxicity in volunteers receiving 800 mg/day for seven days.

Treatment

- In case of overdose, patients should be monitored and treated symptomatically in a closely supervised environment.

Pharmacotherapeutic group: other nervous system drugs; drugs used in addictive disorders, ATC code: N07BB04

Abernil is a specific opioid antagonist with only minimal agonistic activity. It acts by stereospecific competition with receptors which are mainly located in the central and peripheral nervous system. Abernil competitively binds to these receptors and blocks the access for exogenously administered opioids.

Abernil treatment does not lead to physical or mental dependence. No tolerance for the opioid antagonising effect is seen.

Abernil Hydrochloride 50 mg film-coated tablets reduces the risk of relapse and supports abstinence from opioids.

Abernil Hydrochloride 50 mg film-coated tablets is a non-aversive therapy and does not cause reactions after opioid intake. Therefore it does not cause a disulfiram-type reaction.

The mechanism of action of Abernil in alcoholism is not completely elucidated, however an interaction with the endogenous opioid system is suspected to play an important role. Alcohol consumption in humans has been hypothesised to be reinforcing through an alcohol-induced stimulation of the endogenous opioid system.

Abernil is not an aversive therapy and does not cause a disulfiram-like negative reaction when alcohol is ingested.

The prominent effect of Abernil treatment of alcohol-addicted patients seems to be a reduction of the risk of a full relapse with uncontrolled binge-drinking after having consumed a limited amount of alcohol.

This gives the patient a “second chance” to escape the otherwise mutually reinforcing mechanisms of a full relapse with complete loss of control. Abernil also seems to have an effect on the primary craving as it is non-reinforcing on isolated consumption of limited amounts of alcohol.

Pharmacotherapeutic group: other nervous system drugs; drugs used in addictive disorders, ATC code: N07BB04

Naltrexone is a specific opioid antagonist with only minimal agonistic activity. It acts by stereospecific competition with receptors which are mainly located in the central and peripheral nervous system. Naltrexone competitively binds to these receptors and blocks the access for exogenously administered opioids.

Naltrexone treatment does not lead to physical or mental dependence. No tolerance for the opioid antagonising effect is seen.

Abernil 50 mg film-coated tablets reduces the risk of relapse and supports abstinence from opioids.

Abernil 50 mg film-coated tablets is a non-aversive therapy and does not cause reactions after opioid intake. Therefore it does not cause a disulfiram-type reaction.

The mechanism of action of naltrexone in alcoholism is not completely elucidated, however an interaction with the endogenous opioid system is suspected to play an important role. Alcohol consumption in humans has been hypothesised to be reinforcing through an alcohol-induced stimulation of the endogenous opioid system.

Naltrexone is not an aversive therapy and does not cause a disulfiram-like negative reaction when alcohol is ingested.

The prominent effect of naltrexone treatment of alcohol-addicted patients seems to be a reduction of the risk of a full relapse with uncontrolled binge-drinking after having consumed a limited amount of alcohol.

This gives the patient a “second chance” to escape the otherwise mutually reinforcing mechanisms of a full relapse with complete loss of control. Naltrexone also seems to have an effect on the primary craving as it is non-reinforcing on isolated consumption of limited amounts of alcohol.

Absorption

Abernil is rapidly and almost completely absorbed from the gastrointestinal tract after oral administration.

Biotransformation

It undergoes a liver first-pass effect and peak plasma concentration is reached within approximately one hour.

Abernil is hydroxylated in the liver basically to the main active metabolite 6-beta-naltrexol and, to a lesser extent, to 2-hydroxy-3-methoxy-6-beta-naltrexol.

The plasma-half-life of Abernil is approximately 4 hours, the average blood level is 8.55 mg/ml, and plasmaprotein-binding is 21%. The plasma-half-life of 6-beta-naltrexol is 13 hours.

Elimination

The medicinal product is excreted primarily renal. About 60% of the peroral dose is excreted within 48 hours as glucuronidised 6-beta-naltrexol and Abernil.

Absorption

Naltrexone is rapidly and almost completely absorbed from the gastrointestinal tract after oral administration.

Biotransformation

It undergoes a liver first-pass effect and peak plasma concentration is reached within approximately one hour.

Naltrexone is hydroxylated in the liver basically to the main active metabolite 6-beta-naltrexol and, to a lesser extent, to 2-hydroxy-3-methoxy-6-beta-naltrexol.

The plasma-half-life of naltrexone is approximately 4 hours, the average blood level is 8.55 mg/ml, and plasmaprotein-binding is 21%. The plasma-half-life of 6-beta-naltrexol is 13 hours.

Elimination

The medicinal product is excreted primarily renal. About 60% of the peroral dose is excreted within 48 hours as glucuronidised 6-beta-naltrexol and naltrexone.

Preclinical data revealed no special hazard for humans based on conventional studies of safety, pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential. However, there is some evidence on hepatotoxicity with increasing dose, since reversible increases of liver enzymes has been found in humans with therapeutic and higher doses.

Abernil (100 mg/kg, approximately 140 times the human therapeutic dose) caused a significant increase in pseudo-pregnancy in the rat. A decrease in the pregnancy rate of mated female rats also occurred. The relevance of these observations to human fertility is not known.

Abernil has been shown to have an embryocidal effect in the rat and rabbit when given in doses approximately 140 times the human therapeutic dose. This effect was demonstrated in rats dosed with 100 mg/kg of Abernil prior to and throughout gestation, and rabbits treated with 60 mg/kg of Abernil during the period of organogenesis.

Preclinical data revealed no special hazard for humans based on conventional studies of safety, pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential. However, there is some evidence on hepatotoxicity with increasing dose, since reversible increases of liver enzymes has been found in humans with therapeutic and higher doses.

Naltrexone (100 mg/kg, approximately 140 times the human therapeutic dose) caused a significant increase in pseudo-pregnancy in the rat. A decrease in the pregnancy rate of mated female rats also occurred. The relevance of these observations to human fertility is not known.

Naltrexone has been shown to have an embryocidal effect in the rat and rabbit when given in doses approximately 140 times the human therapeutic dose. This effect was demonstrated in rats dosed with 100 mg/kg of naltrexone prior to and throughout gestation, and rabbits treated with 60 mg/kg of naltrexone during the period of organogenesis.