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4.2 Posology and Method of Administration
Administration of Nalorex must not be started before a naloxone challenge test is performed and a negative result obtained
Naloxone test
- Intravenous: Administer 0.2 mg naloxone IV. If no adverse reactions appear after 30 seconds, administer another dose of 0.6 mg naloxone iv. Continue observing the patient over 20 minutes for signs of withdrawal.
- Subcutaneous: Administer 0.8 mg naloxone subcutaneously Observe the patient for 20 minutes for signs and symptoms of withdrawal.
Confirmation of the test: If there is any doubt that the patient is opioid-free, treatment with Nalorex should be delayed 24 hours. In this case, the test should be repeated with 1.6 mg naloxone.
If there is no evidence of a reaction, Nalorex administration may be initiated with 25 mg by mouth (half a tablet).
Nalorex treatment should be initiated in a drug addiction centre and supervised by suitably qualified physicians.
Before starting Nalorex treatment, this test must be confirmed by urine screening. Treatment must begin with low doses of naltrexone, according to the treatment induction schedule.
The initial dose of Nalorex should be 25 mg (half a tablet) followed by 50 mg (one tablet) daily.
A three-times-a-week dosing schedule may be considered if it is likely to result in better compliance e.g. 100 mg on Monday, 100 mg on Wednesday and 150 mg on Friday.
A dose of over 150 mg on any single day is not recommended, since this can lead to a higher incidence of side effects.
Treatment with Nalorex should be considered only in patients who have remained opioid-free for a minimum of 7-10 days.
NarcanÒ (Naloxone hydrochloride) challenge is recommended to minimise the chance of a prolonged withdrawal syndrome precipitated by Nalorex (see also Warnings).
As NALOREX is an adjunctive therapy and full recovery from opioid dependence is variable, no standard duration of treatment can be recommended; an initial period of three months should be considered. However, prolonged administration may be necessary.
.
4.3 Contraindications NALOREX is contraindicated in patients with renal failure
4.3 Contraindications
NALOREX is contraindicated in patients with renal failure
4.4 Special Warnings and Special Precautions for Use It is not uncommon for opioid abusing individuals to have impaired liver function. In addition, it is not unusual for alcohol abusers to have altered liver function. Changes in hepatic function tests have been described in obese elderly patients receiving naltrexone at doses higher than recommended (up to 300 mg/day) for the treatment of alcoholism. Liver function tests should be performed before starting treatment and periodically throughout treatment. 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. Since NALOREX is extensively metabolised by the liver and excreted predominantly in the urine, caution should be observed in administering the drug to patients with impaired hepatic or renal function. Liver function tests should be carried out both before and during treatment. A withdrawal syndrome may be precipitated by NALOREX in opioid dependent patients; signs and symptoms may develop within 5 minutes and last up to 48 hours. Treatment should be symptomatic and may include opioid administration. The naloxone-challenge test should neither be performed in patients with clinically significant withdrawal symptoms nor in patients tested positive for opioids in the urine. If there is no evidence of a reaction, Nalorex administration may be initiated with 25 mg by mouth (half a tablet). In an emergency situation in which the administration of opioid analgesics is required in patients receiving NALOREX a higher than usual dose of opioid analgesics may be administered to have the same therapeutic effect. The resulting respiratory depression may be deeper and more prolonged and non-receptor mediated effects may also appear (e.g. swelling of the face, pruritus, generalized erythema, diaphoresis, and other dermal and mucosal symptoms presumably due to histamine liberation). In these circumstances, the patient must be carefully monitored by trained personnel in a hospital center. The risk of suicide is known to increase in substance abusers, with or without concomitant depression. Treatment with Nalorex does not eliminate this risk. Lactose: Patients with the rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take NALOREX. 4.5 Interaction with Other Medicinal Products and Other Forms of Interaction Patients taking naltrexone may not benefit from opioid containing medicines, such as cough and cold preparations, antidiarrhoeal preparations, and opioid analgesics. Patients should be warned that attempts to overcome the blockade by administering large doses of opioids may result in acute opioid intoxication which may be life threatening. In an emergency requiring opioid analgesia an increased dose of opioid may be required to control pain. The patient should be closely monitored for evidence of respiratory depression or other adverse symptoms and signs. Presently, clinical experience and experimental data on the effect of naltrexone on the pharmacokinetics of other substances are limited. Concomitant treatment with naltrexone and other medicinal products should be conducted with caution and should be followed carefully. No interaction studies have been performed. In vitro studies have shown that neither naltrexone nor its main metabolite 6-ß-naltrexol is metabolised via human CYP450 enzymes. Therefore it is unlikely that the pharmacokinetics of naltrexone is affected by cytochrome P450 enzyme inhibiting drugs. Sedative products: opioid derivatives (analgesics, antitussives, substitution treatments), neuroleptics, barbiturates, benzodiazepins, anxiolytics others than benzodiazepins (i.e meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, trimipramine), sedative antihistaminics H1, central antihypertensives, baclofen, thalidomide. Association not recommended: agonist opioid analgesics; agonist-antagonist opioids; opioids in substitution treatment Association to be taken into account: barbiturates; benzodiazepines Until now no interaction between cocaine and naltrexone hydrochloride has been described. Data from a safety and tolerability study of the co-administration of naltrexone with acamprosate in non-treatment seeking, alcohol dependent individuals showed that naltrexone administration significantly increased acamprosate plasma level. Interaction with other psychopharmacological agents (e.g. disulfirame, amitryptiline, doxepine, lithium, clozapine, benzodiazepines) have not been investigated. There are no known interactions between naltrexone and alcohol. There have been reports of cases of lethargy and somnolence following concomitant administration of naltrexone and thioridazine. 4.6 Pregnancy and Lactation 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. Animal studies do not suggest a teratogenic effect, but there is no experience of use during human pregnancy. The drug should only be used in pregnancy or lactation if considered essential by the physician. The use of naltrexone in pregnant alcoholic patients receiving long-term treatment with opiates or substitution treatment with opiates, or in pregnant patients who are opioid-dependent, creates a risk of acute withdrawal syndrome which could have serious consequences for the mother and the foetus (see section 4.4). Naltrexone administration must be suspended if opiate analgesics are prescribed (see section 4.5).Lactation: There are no clinical data on naltrexone HCl use in lactation. It is unknown whether naltrexone or 6-beta-naltrexol is excreted in human breast milk. Breast feeding is not recommended duing naltrexone treatment. 4.8 Undesirable Effects The following adverse reactions have been reported before and during naltrexone medication: Frequency is defined using the following convention: very common (>1/10); common (>1/100, <1/10); uncommon (>1/1,000, <1/100); rare (>1/10,000, <1,000); very rare (<1/10,000) The side effects observed with naltrexone appear to be similar in both alcoholics and patients dependent on opioids. Serious adverse reactions are unusual. Respiratory disorders Common: chest pain Uncommon: nasal congestion, itching, rhinorrhea, sneezing, sore throat, excess mucus or phlegm, sinus trouble, heavy breathing, hoarseness, cough, shortness of breath, yawning Cardiovascular disorders Common: tachycardia, palpitations, electrocardiogram change Uncommon: nose bleeds, phlebitis, edema, increased blood pressure Gastrointestinal disorders Very common: abdominal pain/cramps, nausea and/or vomiting Common: diarrhoea, constipation Uncommon: excessive gas, hemorrhoids, diarrhoea, ulcer, dry mouth Musculoskeletal disorders Very common: joint and muscle pain Uncommon: painful shoulders, legs or knees, tremors, twitching, groin pain Very rare: rhabdomyolysis Genitourinary disorders Common: delayed ejaculation, decreased potency Uncommon: increased frequency of or discomfort during urination, increased or decreased sexual interest Skin and subcutaneous disorders Common: skin rash Uncommon: oily skin, purities, acne, athlete’s foot, cold sores, alopecia. Psychiatric disorders Very common: Difficulty sleeping, anxiety, nervousness, head ache Common: feeling down, irritability, dizziness Uncommon: depression, paranoia, fatigue, restlessness, confusion, disorientation, hallucinations, nightmares, bad dreams Eye disorders Common: increased lacrimation. Uncommon: eyes-blurred, burning, light sensitive, swollen, aching or strained. Ear and labyrinth disorders Uncommon: ears- clogged, aching, tinnitus,vertigo Nervous system disorders Very common: headache, restlessness Common: dizziness Uncommon: tremor, somnolence, headache Renal and urinary tract disorders Uncommon: pollakiuria, dysuria Infections and infestations Uncommon: oral herpès, tinea pedis Metabolism and nutrition disorders Common: decreased appetite General disorders Very common: low energy Common: loss of appetite, increased thirst, increased energy, chills, increased sweating. Uncommon: increased appetite, weight loss, weight gain, yawning, somnolence, fever, dry mouth, head “pounding”, inguinal pain, swollen glands, side pains, cold feet, hot spells. Hepatobiliary disorders Uncommon: liver disorder, blood bilirubin increased, hepatitis (During treatment an increase of liver transaminases may occur. After discontinuation of Nalorex the transaminases decreased to baseline within several weeks.) Occasional liver function abnormalities have also been reported. One case of reversible idiopathic thrombocytopenic purpura has occurred in a patient taking Nalorex. DATE OF (PARTIAL) REVISION OF TEXT March 2011
4.4 Special Warnings and Special Precautions for Use
It is not uncommon for opioid abusing individuals to have impaired liver function.
In addition, it is not unusual for alcohol abusers to have altered liver function. Changes in hepatic function tests have been described in obese elderly patients receiving naltrexone at doses higher than recommended (up to 300 mg/day) for the treatment of alcoholism. Liver function tests should be performed before starting treatment and periodically throughout treatment.
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.
Since NALOREX is extensively metabolised by the liver and excreted predominantly in the urine, caution should be observed in administering the drug to patients with impaired hepatic or renal function. Liver function tests should be carried out both before and during treatment.
A withdrawal syndrome may be precipitated by NALOREX in opioid dependent patients; signs and symptoms may develop within 5 minutes and last up to 48 hours. Treatment should be symptomatic and may include opioid administration.
The naloxone-challenge test should neither be performed in patients with clinically significant withdrawal symptoms nor in patients tested positive for opioids in the urine. If there is no evidence of a reaction, Nalorex administration may be initiated with 25 mg by mouth (half a tablet). In an emergency situation in which the administration of opioid analgesics is required in patients receiving NALOREX a higher than usual dose of opioid analgesics may be administered to have the same therapeutic effect. The resulting respiratory depression may be deeper and more prolonged and non-receptor mediated effects may also appear (e.g. swelling of the face, pruritus, generalized erythema, diaphoresis, and other dermal and mucosal symptoms presumably due to histamine liberation). In these circumstances, the patient must be carefully monitored by trained personnel in a hospital center. The risk of suicide is known to increase in substance abusers, with or without concomitant depression. Treatment with Nalorex does not eliminate this risk. Lactose: Patients with the rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take NALOREX. 4.5 Interaction with Other Medicinal Products and Other Forms of Interaction Patients taking naltrexone may not benefit from opioid containing medicines, such as cough and cold preparations, antidiarrhoeal preparations, and opioid analgesics. Patients should be warned that attempts to overcome the blockade by administering large doses of opioids may result in acute opioid intoxication which may be life threatening. In an emergency requiring opioid analgesia an increased dose of opioid may be required to control pain. The patient should be closely monitored for evidence of respiratory depression or other adverse symptoms and signs. Presently, clinical experience and experimental data on the effect of naltrexone on the pharmacokinetics of other substances are limited. Concomitant treatment with naltrexone and other medicinal products should be conducted with caution and should be followed carefully. No interaction studies have been performed. In vitro studies have shown that neither naltrexone nor its main metabolite 6-ß-naltrexol is metabolised via human CYP450 enzymes. Therefore it is unlikely that the pharmacokinetics of naltrexone is affected by cytochrome P450 enzyme inhibiting drugs. Sedative products: opioid derivatives (analgesics, antitussives, substitution treatments), neuroleptics, barbiturates, benzodiazepins, anxiolytics others than benzodiazepins (i.e meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, trimipramine), sedative antihistaminics H1, central antihypertensives, baclofen, thalidomide. Association not recommended: agonist opioid analgesics; agonist-antagonist opioids; opioids in substitution treatment Association to be taken into account: barbiturates; benzodiazepines Until now no interaction between cocaine and naltrexone hydrochloride has been described. Data from a safety and tolerability study of the co-administration of naltrexone with acamprosate in non-treatment seeking, alcohol dependent individuals showed that naltrexone administration significantly increased acamprosate plasma level. Interaction with other psychopharmacological agents (e.g. disulfirame, amitryptiline, doxepine, lithium, clozapine, benzodiazepines) have not been investigated. There are no known interactions between naltrexone and alcohol. There have been reports of cases of lethargy and somnolence following concomitant administration of naltrexone and thioridazine. 4.6 Pregnancy and Lactation 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. Animal studies do not suggest a teratogenic effect, but there is no experience of use during human pregnancy. The drug should only be used in pregnancy or lactation if considered essential by the physician. The use of naltrexone in pregnant alcoholic patients receiving long-term treatment with opiates or substitution treatment with opiates, or in pregnant patients who are opioid-dependent, creates a risk of acute withdrawal syndrome which could have serious consequences for the mother and the foetus (see section 4.4). Naltrexone administration must be suspended if opiate analgesics are prescribed (see section 4.5).Lactation: There are no clinical data on naltrexone HCl use in lactation. It is unknown whether naltrexone or 6-beta-naltrexol is excreted in human breast milk. Breast feeding is not recommended duing naltrexone treatment. 4.8 Undesirable Effects The following adverse reactions have been reported before and during naltrexone medication: Frequency is defined using the following convention: very common (>1/10); common (>1/100, <1/10); uncommon (>1/1,000, <1/100); rare (>1/10,000, <1,000); very rare (<1/10,000) The side effects observed with naltrexone appear to be similar in both alcoholics and patients dependent on opioids. Serious adverse reactions are unusual. Respiratory disorders Common: chest pain Uncommon: nasal congestion, itching, rhinorrhea, sneezing, sore throat, excess mucus or phlegm, sinus trouble, heavy breathing, hoarseness, cough, shortness of breath, yawning Cardiovascular disorders Common: tachycardia, palpitations, electrocardiogram change Uncommon: nose bleeds, phlebitis, edema, increased blood pressure Gastrointestinal disorders Very common: abdominal pain/cramps, nausea and/or vomiting Common: diarrhoea, constipation Uncommon: excessive gas, hemorrhoids, diarrhoea, ulcer, dry mouth Musculoskeletal disorders Very common: joint and muscle pain Uncommon: painful shoulders, legs or knees, tremors, twitching, groin pain Very rare: rhabdomyolysis Genitourinary disorders Common: delayed ejaculation, decreased potency Uncommon: increased frequency of or discomfort during urination, increased or decreased sexual interest Skin and subcutaneous disorders Common: skin rash Uncommon: oily skin, purities, acne, athlete’s foot, cold sores, alopecia. Psychiatric disorders Very common: Difficulty sleeping, anxiety, nervousness, head ache Common: feeling down, irritability, dizziness Uncommon: depression, paranoia, fatigue, restlessness, confusion, disorientation, hallucinations, nightmares, bad dreams Eye disorders Common: increased lacrimation. Uncommon: eyes-blurred, burning, light sensitive, swollen, aching or strained. Ear and labyrinth disorders Uncommon: ears- clogged, aching, tinnitus,vertigo Nervous system disorders Very common: headache, restlessness Common: dizziness Uncommon: tremor, somnolence, headache Renal and urinary tract disorders Uncommon: pollakiuria, dysuria Infections and infestations Uncommon: oral herpès, tinea pedis Metabolism and nutrition disorders Common: decreased appetite General disorders Very common: low energy Common: loss of appetite, increased thirst, increased energy, chills, increased sweating. Uncommon: increased appetite, weight loss, weight gain, yawning, somnolence, fever, dry mouth, head “pounding”, inguinal pain, swollen glands, side pains, cold feet, hot spells. Hepatobiliary disorders Uncommon: liver disorder, blood bilirubin increased, hepatitis (During treatment an increase of liver transaminases may occur. After discontinuation of Nalorex the transaminases decreased to baseline within several weeks.) Occasional liver function abnormalities have also been reported. One case of reversible idiopathic thrombocytopenic purpura has occurred in a patient taking Nalorex. DATE OF (PARTIAL) REVISION OF TEXT March 2011
In an emergency situation in which the administration of opioid analgesics is required in patients receiving NALOREX a higher than usual dose of opioid analgesics may be administered to have the same therapeutic effect. The resulting respiratory depression may be deeper and more prolonged and non-receptor mediated effects may also appear (e.g. swelling of the face, pruritus, generalized erythema, diaphoresis, and other dermal and mucosal symptoms presumably due to histamine liberation). In these circumstances, the patient must be carefully monitored by trained personnel in a hospital center.
The risk of suicide is known to increase in substance abusers, with or without concomitant depression. Treatment with Nalorex does not eliminate this risk.
Lactose: Patients with the rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take NALOREX.
4.5 Interaction with Other Medicinal Products and Other Forms of Interaction Patients taking naltrexone may not benefit from opioid containing medicines, such as cough and cold preparations, antidiarrhoeal preparations, and opioid analgesics. Patients should be warned that attempts to overcome the blockade by administering large doses of opioids may result in acute opioid intoxication which may be life threatening. In an emergency requiring opioid analgesia an increased dose of opioid may be required to control pain. The patient should be closely monitored for evidence of respiratory depression or other adverse symptoms and signs. Presently, clinical experience and experimental data on the effect of naltrexone on the pharmacokinetics of other substances are limited. Concomitant treatment with naltrexone and other medicinal products should be conducted with caution and should be followed carefully. No interaction studies have been performed. In vitro studies have shown that neither naltrexone nor its main metabolite 6-ß-naltrexol is metabolised via human CYP450 enzymes. Therefore it is unlikely that the pharmacokinetics of naltrexone is affected by cytochrome P450 enzyme inhibiting drugs. Sedative products: opioid derivatives (analgesics, antitussives, substitution treatments), neuroleptics, barbiturates, benzodiazepins, anxiolytics others than benzodiazepins (i.e meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, trimipramine), sedative antihistaminics H1, central antihypertensives, baclofen, thalidomide. Association not recommended: agonist opioid analgesics; agonist-antagonist opioids; opioids in substitution treatment Association to be taken into account: barbiturates; benzodiazepines Until now no interaction between cocaine and naltrexone hydrochloride has been described. Data from a safety and tolerability study of the co-administration of naltrexone with acamprosate in non-treatment seeking, alcohol dependent individuals showed that naltrexone administration significantly increased acamprosate plasma level. Interaction with other psychopharmacological agents (e.g. disulfirame, amitryptiline, doxepine, lithium, clozapine, benzodiazepines) have not been investigated. There are no known interactions between naltrexone and alcohol. There have been reports of cases of lethargy and somnolence following concomitant administration of naltrexone and thioridazine. 4.6 Pregnancy and Lactation 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. Animal studies do not suggest a teratogenic effect, but there is no experience of use during human pregnancy. The drug should only be used in pregnancy or lactation if considered essential by the physician. The use of naltrexone in pregnant alcoholic patients receiving long-term treatment with opiates or substitution treatment with opiates, or in pregnant patients who are opioid-dependent, creates a risk of acute withdrawal syndrome which could have serious consequences for the mother and the foetus (see section 4.4). Naltrexone administration must be suspended if opiate analgesics are prescribed (see section 4.5).Lactation: There are no clinical data on naltrexone HCl use in lactation. It is unknown whether naltrexone or 6-beta-naltrexol is excreted in human breast milk. Breast feeding is not recommended duing naltrexone treatment. 4.8 Undesirable Effects The following adverse reactions have been reported before and during naltrexone medication: Frequency is defined using the following convention: very common (>1/10); common (>1/100, <1/10); uncommon (>1/1,000, <1/100); rare (>1/10,000, <1,000); very rare (<1/10,000) The side effects observed with naltrexone appear to be similar in both alcoholics and patients dependent on opioids. Serious adverse reactions are unusual. Respiratory disorders Common: chest pain Uncommon: nasal congestion, itching, rhinorrhea, sneezing, sore throat, excess mucus or phlegm, sinus trouble, heavy breathing, hoarseness, cough, shortness of breath, yawning Cardiovascular disorders Common: tachycardia, palpitations, electrocardiogram change Uncommon: nose bleeds, phlebitis, edema, increased blood pressure Gastrointestinal disorders Very common: abdominal pain/cramps, nausea and/or vomiting Common: diarrhoea, constipation Uncommon: excessive gas, hemorrhoids, diarrhoea, ulcer, dry mouth Musculoskeletal disorders Very common: joint and muscle pain Uncommon: painful shoulders, legs or knees, tremors, twitching, groin pain Very rare: rhabdomyolysis Genitourinary disorders Common: delayed ejaculation, decreased potency Uncommon: increased frequency of or discomfort during urination, increased or decreased sexual interest Skin and subcutaneous disorders Common: skin rash Uncommon: oily skin, purities, acne, athlete’s foot, cold sores, alopecia. Psychiatric disorders Very common: Difficulty sleeping, anxiety, nervousness, head ache Common: feeling down, irritability, dizziness Uncommon: depression, paranoia, fatigue, restlessness, confusion, disorientation, hallucinations, nightmares, bad dreams Eye disorders Common: increased lacrimation. Uncommon: eyes-blurred, burning, light sensitive, swollen, aching or strained. Ear and labyrinth disorders Uncommon: ears- clogged, aching, tinnitus,vertigo Nervous system disorders Very common: headache, restlessness Common: dizziness Uncommon: tremor, somnolence, headache Renal and urinary tract disorders Uncommon: pollakiuria, dysuria Infections and infestations Uncommon: oral herpès, tinea pedis Metabolism and nutrition disorders Common: decreased appetite General disorders Very common: low energy Common: loss of appetite, increased thirst, increased energy, chills, increased sweating. Uncommon: increased appetite, weight loss, weight gain, yawning, somnolence, fever, dry mouth, head “pounding”, inguinal pain, swollen glands, side pains, cold feet, hot spells. Hepatobiliary disorders Uncommon: liver disorder, blood bilirubin increased, hepatitis (During treatment an increase of liver transaminases may occur. After discontinuation of Nalorex the transaminases decreased to baseline within several weeks.) Occasional liver function abnormalities have also been reported. One case of reversible idiopathic thrombocytopenic purpura has occurred in a patient taking Nalorex. DATE OF (PARTIAL) REVISION OF TEXT March 2011
4.5 Interaction with Other Medicinal Products and Other Forms of Interaction
Patients taking naltrexone may not benefit from opioid containing medicines, such as cough and cold preparations, antidiarrhoeal preparations, and opioid analgesics. Patients should be warned that attempts to overcome the blockade by administering large doses of opioids may result in acute opioid intoxication which may be life threatening. In an emergency requiring opioid analgesia an increased dose of opioid may be required to control pain. The patient should be closely monitored for evidence of respiratory depression or other adverse symptoms and signs. Presently, clinical experience and experimental data on the effect of naltrexone on the pharmacokinetics of other substances are limited. Concomitant treatment with naltrexone and other medicinal products should be conducted with caution and should be followed carefully. No interaction studies have been performed. In vitro studies have shown that neither naltrexone nor its main metabolite 6-ß-naltrexol is metabolised via human CYP450 enzymes. Therefore it is unlikely that the pharmacokinetics of naltrexone is affected by cytochrome P450 enzyme inhibiting drugs. Sedative products: opioid derivatives (analgesics, antitussives, substitution treatments), neuroleptics, barbiturates, benzodiazepins, anxiolytics others than benzodiazepins (i.e meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, trimipramine), sedative antihistaminics H1, central antihypertensives, baclofen, thalidomide. Association not recommended: agonist opioid analgesics; agonist-antagonist opioids; opioids in substitution treatment Association to be taken into account: barbiturates; benzodiazepines Until now no interaction between cocaine and naltrexone hydrochloride has been described. Data from a safety and tolerability study of the co-administration of naltrexone with acamprosate in non-treatment seeking, alcohol dependent individuals showed that naltrexone administration significantly increased acamprosate plasma level. Interaction with other psychopharmacological agents (e.g. disulfirame, amitryptiline, doxepine, lithium, clozapine, benzodiazepines) have not been investigated. There are no known interactions between naltrexone and alcohol. There have been reports of cases of lethargy and somnolence following concomitant administration of naltrexone and thioridazine. 4.6 Pregnancy and Lactation 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. Animal studies do not suggest a teratogenic effect, but there is no experience of use during human pregnancy. The drug should only be used in pregnancy or lactation if considered essential by the physician. The use of naltrexone in pregnant alcoholic patients receiving long-term treatment with opiates or substitution treatment with opiates, or in pregnant patients who are opioid-dependent, creates a risk of acute withdrawal syndrome which could have serious consequences for the mother and the foetus (see section 4.4). Naltrexone administration must be suspended if opiate analgesics are prescribed (see section 4.5).Lactation: There are no clinical data on naltrexone HCl use in lactation. It is unknown whether naltrexone or 6-beta-naltrexol is excreted in human breast milk. Breast feeding is not recommended duing naltrexone treatment. 4.8 Undesirable Effects The following adverse reactions have been reported before and during naltrexone medication: Frequency is defined using the following convention: very common (>1/10); common (>1/100, <1/10); uncommon (>1/1,000, <1/100); rare (>1/10,000, <1,000); very rare (<1/10,000) The side effects observed with naltrexone appear to be similar in both alcoholics and patients dependent on opioids. Serious adverse reactions are unusual. Respiratory disorders Common: chest pain Uncommon: nasal congestion, itching, rhinorrhea, sneezing, sore throat, excess mucus or phlegm, sinus trouble, heavy breathing, hoarseness, cough, shortness of breath, yawning Cardiovascular disorders Common: tachycardia, palpitations, electrocardiogram change Uncommon: nose bleeds, phlebitis, edema, increased blood pressure Gastrointestinal disorders Very common: abdominal pain/cramps, nausea and/or vomiting Common: diarrhoea, constipation Uncommon: excessive gas, hemorrhoids, diarrhoea, ulcer, dry mouth Musculoskeletal disorders Very common: joint and muscle pain Uncommon: painful shoulders, legs or knees, tremors, twitching, groin pain Very rare: rhabdomyolysis Genitourinary disorders Common: delayed ejaculation, decreased potency Uncommon: increased frequency of or discomfort during urination, increased or decreased sexual interest Skin and subcutaneous disorders Common: skin rash Uncommon: oily skin, purities, acne, athlete’s foot, cold sores, alopecia. Psychiatric disorders Very common: Difficulty sleeping, anxiety, nervousness, head ache Common: feeling down, irritability, dizziness Uncommon: depression, paranoia, fatigue, restlessness, confusion, disorientation, hallucinations, nightmares, bad dreams Eye disorders Common: increased lacrimation. Uncommon: eyes-blurred, burning, light sensitive, swollen, aching or strained. Ear and labyrinth disorders Uncommon: ears- clogged, aching, tinnitus,vertigo Nervous system disorders Very common: headache, restlessness Common: dizziness Uncommon: tremor, somnolence, headache Renal and urinary tract disorders Uncommon: pollakiuria, dysuria Infections and infestations Uncommon: oral herpès, tinea pedis Metabolism and nutrition disorders Common: decreased appetite General disorders Very common: low energy Common: loss of appetite, increased thirst, increased energy, chills, increased sweating. Uncommon: increased appetite, weight loss, weight gain, yawning, somnolence, fever, dry mouth, head “pounding”, inguinal pain, swollen glands, side pains, cold feet, hot spells. Hepatobiliary disorders Uncommon: liver disorder, blood bilirubin increased, hepatitis (During treatment an increase of liver transaminases may occur. After discontinuation of Nalorex the transaminases decreased to baseline within several weeks.) Occasional liver function abnormalities have also been reported. One case of reversible idiopathic thrombocytopenic purpura has occurred in a patient taking Nalorex. DATE OF (PARTIAL) REVISION OF TEXT March 2011
Patients taking naltrexone may not benefit from opioid containing medicines, such as cough and cold preparations, antidiarrhoeal preparations, and opioid analgesics.
Patients should be warned that attempts to overcome the blockade by administering large doses of opioids may result in acute opioid intoxication which may be life threatening. In an emergency requiring opioid analgesia an increased dose of opioid may be required to control pain. The patient should be closely monitored for evidence of respiratory depression or other adverse symptoms and signs.
Presently, clinical experience and experimental data on the effect of naltrexone on the pharmacokinetics of other substances are limited. Concomitant treatment with naltrexone and other medicinal products should be conducted with caution and should be followed carefully. No interaction studies have been performed.
In vitro studies have shown that neither naltrexone nor its main metabolite 6-ß-naltrexol is metabolised via human CYP450 enzymes. Therefore it is unlikely that the pharmacokinetics of naltrexone is affected by cytochrome P450 enzyme inhibiting drugs.
Sedative products: opioid derivatives (analgesics, antitussives, substitution treatments), neuroleptics, barbiturates, benzodiazepins, anxiolytics others than benzodiazepins (i.e meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, trimipramine), sedative antihistaminics H1, central antihypertensives, baclofen, thalidomide.
Association not recommended: agonist opioid analgesics; agonist-antagonist opioids; opioids in substitution treatment
Association to be taken into account: barbiturates; benzodiazepines
Until now no interaction between cocaine and naltrexone hydrochloride has been described.
Data from a safety and tolerability study of the co-administration of naltrexone with acamprosate in non-treatment seeking, alcohol dependent individuals showed that naltrexone administration significantly increased acamprosate plasma level. Interaction with other psychopharmacological agents (e.g. disulfirame, amitryptiline, doxepine, lithium, clozapine, benzodiazepines) have not been investigated.
There are no known interactions between naltrexone and alcohol.
There have been reports of cases of lethargy and somnolence following concomitant administration of naltrexone and thioridazine. 4.6 Pregnancy and Lactation 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. Animal studies do not suggest a teratogenic effect, but there is no experience of use during human pregnancy. The drug should only be used in pregnancy or lactation if considered essential by the physician. The use of naltrexone in pregnant alcoholic patients receiving long-term treatment with opiates or substitution treatment with opiates, or in pregnant patients who are opioid-dependent, creates a risk of acute withdrawal syndrome which could have serious consequences for the mother and the foetus (see section 4.4). Naltrexone administration must be suspended if opiate analgesics are prescribed (see section 4.5).Lactation: There are no clinical data on naltrexone HCl use in lactation. It is unknown whether naltrexone or 6-beta-naltrexol is excreted in human breast milk. Breast feeding is not recommended duing naltrexone treatment. 4.8 Undesirable Effects The following adverse reactions have been reported before and during naltrexone medication: Frequency is defined using the following convention: very common (>1/10); common (>1/100, <1/10); uncommon (>1/1,000, <1/100); rare (>1/10,000, <1,000); very rare (<1/10,000) The side effects observed with naltrexone appear to be similar in both alcoholics and patients dependent on opioids. Serious adverse reactions are unusual. Respiratory disorders Common: chest pain Uncommon: nasal congestion, itching, rhinorrhea, sneezing, sore throat, excess mucus or phlegm, sinus trouble, heavy breathing, hoarseness, cough, shortness of breath, yawning Cardiovascular disorders Common: tachycardia, palpitations, electrocardiogram change Uncommon: nose bleeds, phlebitis, edema, increased blood pressure Gastrointestinal disorders Very common: abdominal pain/cramps, nausea and/or vomiting Common: diarrhoea, constipation Uncommon: excessive gas, hemorrhoids, diarrhoea, ulcer, dry mouth Musculoskeletal disorders Very common: joint and muscle pain Uncommon: painful shoulders, legs or knees, tremors, twitching, groin pain Very rare: rhabdomyolysis Genitourinary disorders Common: delayed ejaculation, decreased potency Uncommon: increased frequency of or discomfort during urination, increased or decreased sexual interest Skin and subcutaneous disorders Common: skin rash Uncommon: oily skin, purities, acne, athlete’s foot, cold sores, alopecia. Psychiatric disorders Very common: Difficulty sleeping, anxiety, nervousness, head ache Common: feeling down, irritability, dizziness Uncommon: depression, paranoia, fatigue, restlessness, confusion, disorientation, hallucinations, nightmares, bad dreams Eye disorders Common: increased lacrimation. Uncommon: eyes-blurred, burning, light sensitive, swollen, aching or strained. Ear and labyrinth disorders Uncommon: ears- clogged, aching, tinnitus,vertigo Nervous system disorders Very common: headache, restlessness Common: dizziness Uncommon: tremor, somnolence, headache Renal and urinary tract disorders Uncommon: pollakiuria, dysuria Infections and infestations Uncommon: oral herpès, tinea pedis Metabolism and nutrition disorders Common: decreased appetite General disorders Very common: low energy Common: loss of appetite, increased thirst, increased energy, chills, increased sweating. Uncommon: increased appetite, weight loss, weight gain, yawning, somnolence, fever, dry mouth, head “pounding”, inguinal pain, swollen glands, side pains, cold feet, hot spells. Hepatobiliary disorders Uncommon: liver disorder, blood bilirubin increased, hepatitis (During treatment an increase of liver transaminases may occur. After discontinuation of Nalorex the transaminases decreased to baseline within several weeks.) Occasional liver function abnormalities have also been reported. One case of reversible idiopathic thrombocytopenic purpura has occurred in a patient taking Nalorex. DATE OF (PARTIAL) REVISION OF TEXT March 2011
4.6 Pregnancy and Lactation 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. Animal studies do not suggest a teratogenic effect, but there is no experience of use during human pregnancy. The drug should only be used in pregnancy or lactation if considered essential by the physician. The use of naltrexone in pregnant alcoholic patients receiving long-term treatment with opiates or substitution treatment with opiates, or in pregnant patients who are opioid-dependent, creates a risk of acute withdrawal syndrome which could have serious consequences for the mother and the foetus (see section 4.4). Naltrexone administration must be suspended if opiate analgesics are prescribed (see section 4.5).Lactation: There are no clinical data on naltrexone HCl use in lactation. It is unknown whether naltrexone or 6-beta-naltrexol is excreted in human breast milk. Breast feeding is not recommended duing naltrexone treatment. 4.8 Undesirable Effects The following adverse reactions have been reported before and during naltrexone medication: Frequency is defined using the following convention: very common (>1/10); common (>1/100, <1/10); uncommon (>1/1,000, <1/100); rare (>1/10,000, <1,000); very rare (<1/10,000) The side effects observed with naltrexone appear to be similar in both alcoholics and patients dependent on opioids. Serious adverse reactions are unusual. Respiratory disorders Common: chest pain Uncommon: nasal congestion, itching, rhinorrhea, sneezing, sore throat, excess mucus or phlegm, sinus trouble, heavy breathing, hoarseness, cough, shortness of breath, yawning Cardiovascular disorders Common: tachycardia, palpitations, electrocardiogram change Uncommon: nose bleeds, phlebitis, edema, increased blood pressure Gastrointestinal disorders Very common: abdominal pain/cramps, nausea and/or vomiting Common: diarrhoea, constipation Uncommon: excessive gas, hemorrhoids, diarrhoea, ulcer, dry mouth Musculoskeletal disorders Very common: joint and muscle pain Uncommon: painful shoulders, legs or knees, tremors, twitching, groin pain Very rare: rhabdomyolysis Genitourinary disorders Common: delayed ejaculation, decreased potency Uncommon: increased frequency of or discomfort during urination, increased or decreased sexual interest Skin and subcutaneous disorders Common: skin rash Uncommon: oily skin, purities, acne, athlete’s foot, cold sores, alopecia. Psychiatric disorders Very common: Difficulty sleeping, anxiety, nervousness, head ache Common: feeling down, irritability, dizziness Uncommon: depression, paranoia, fatigue, restlessness, confusion, disorientation, hallucinations, nightmares, bad dreams Eye disorders Common: increased lacrimation. Uncommon: eyes-blurred, burning, light sensitive, swollen, aching or strained. Ear and labyrinth disorders Uncommon: ears- clogged, aching, tinnitus,vertigo Nervous system disorders Very common: headache, restlessness Common: dizziness Uncommon: tremor, somnolence, headache Renal and urinary tract disorders Uncommon: pollakiuria, dysuria Infections and infestations Uncommon: oral herpès, tinea pedis Metabolism and nutrition disorders Common: decreased appetite General disorders Very common: low energy Common: loss of appetite, increased thirst, increased energy, chills, increased sweating. Uncommon: increased appetite, weight loss, weight gain, yawning, somnolence, fever, dry mouth, head “pounding”, inguinal pain, swollen glands, side pains, cold feet, hot spells. Hepatobiliary disorders Uncommon: liver disorder, blood bilirubin increased, hepatitis (During treatment an increase of liver transaminases may occur. After discontinuation of Nalorex the transaminases decreased to baseline within several weeks.) Occasional liver function abnormalities have also been reported. One case of reversible idiopathic thrombocytopenic purpura has occurred in a patient taking Nalorex. DATE OF (PARTIAL) REVISION OF TEXT March 2011
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.
Animal studies do not suggest a teratogenic effect, but there is no experience of use during human pregnancy. The drug should only be used in pregnancy or lactation if considered essential by the physician.
The use of naltrexone in pregnant alcoholic patients receiving long-term treatment with opiates or substitution treatment with opiates, or in pregnant patients who are opioid-dependent, creates a risk of acute withdrawal syndrome which could have serious consequences for the mother and the foetus (see section 4.4). Naltrexone administration must be suspended if opiate analgesics are prescribed (see section 4.5).Lactation: There are no clinical data on naltrexone HCl use in lactation. It is unknown whether naltrexone or 6-beta-naltrexol is excreted in human breast milk. Breast feeding is not recommended duing naltrexone treatment.
4.8 Undesirable Effects The following adverse reactions have been reported before and during naltrexone medication: Frequency is defined using the following convention: very common (>1/10); common (>1/100, <1/10); uncommon (>1/1,000, <1/100); rare (>1/10,000, <1,000); very rare (<1/10,000) The side effects observed with naltrexone appear to be similar in both alcoholics and patients dependent on opioids. Serious adverse reactions are unusual. Respiratory disorders Common: chest pain Uncommon: nasal congestion, itching, rhinorrhea, sneezing, sore throat, excess mucus or phlegm, sinus trouble, heavy breathing, hoarseness, cough, shortness of breath, yawning Cardiovascular disorders Common: tachycardia, palpitations, electrocardiogram change Uncommon: nose bleeds, phlebitis, edema, increased blood pressure Gastrointestinal disorders Very common: abdominal pain/cramps, nausea and/or vomiting Common: diarrhoea, constipation Uncommon: excessive gas, hemorrhoids, diarrhoea, ulcer, dry mouth Musculoskeletal disorders Very common: joint and muscle pain Uncommon: painful shoulders, legs or knees, tremors, twitching, groin pain Very rare: rhabdomyolysis Genitourinary disorders Common: delayed ejaculation, decreased potency Uncommon: increased frequency of or discomfort during urination, increased or decreased sexual interest Skin and subcutaneous disorders Common: skin rash Uncommon: oily skin, purities, acne, athlete’s foot, cold sores, alopecia. Psychiatric disorders Very common: Difficulty sleeping, anxiety, nervousness, head ache Common: feeling down, irritability, dizziness Uncommon: depression, paranoia, fatigue, restlessness, confusion, disorientation, hallucinations, nightmares, bad dreams Eye disorders Common: increased lacrimation. Uncommon: eyes-blurred, burning, light sensitive, swollen, aching or strained. Ear and labyrinth disorders Uncommon: ears- clogged, aching, tinnitus,vertigo Nervous system disorders Very common: headache, restlessness Common: dizziness Uncommon: tremor, somnolence, headache Renal and urinary tract disorders Uncommon: pollakiuria, dysuria Infections and infestations Uncommon: oral herpès, tinea pedis Metabolism and nutrition disorders Common: decreased appetite General disorders Very common: low energy Common: loss of appetite, increased thirst, increased energy, chills, increased sweating. Uncommon: increased appetite, weight loss, weight gain, yawning, somnolence, fever, dry mouth, head “pounding”, inguinal pain, swollen glands, side pains, cold feet, hot spells. Hepatobiliary disorders Uncommon: liver disorder, blood bilirubin increased, hepatitis (During treatment an increase of liver transaminases may occur. After discontinuation of Nalorex the transaminases decreased to baseline within several weeks.) Occasional liver function abnormalities have also been reported. One case of reversible idiopathic thrombocytopenic purpura has occurred in a patient taking Nalorex. DATE OF (PARTIAL) REVISION OF TEXT March 2011
4.8 Undesirable Effects
The following adverse reactions have been reported before and during naltrexone medication:
Frequency is defined using the following convention: very common (>1/10); common (>1/100, <1/10); uncommon (>1/1,000, <1/100); rare (>1/10,000, <1,000); very rare (<1/10,000)
The side effects observed with naltrexone appear to be similar in both alcoholics and patients dependent on opioids. Serious adverse reactions are unusual.
Respiratory disorders
Common: chest pain
Uncommon: nasal congestion, itching, rhinorrhea, sneezing, sore throat, excess mucus or phlegm, sinus trouble, heavy breathing, hoarseness, cough, shortness of breath, yawning
Cardiovascular disorders
Common: tachycardia, palpitations, electrocardiogram change
Uncommon: nose bleeds, phlebitis, edema, increased blood pressure
Gastrointestinal disorders
Very common: abdominal pain/cramps, nausea and/or vomiting
Common: diarrhoea, constipation
Uncommon: excessive gas, hemorrhoids, diarrhoea, ulcer, dry mouth
Musculoskeletal disorders
Very common: joint and muscle pain
Uncommon: painful shoulders, legs or knees, tremors, twitching, groin pain
Very rare: rhabdomyolysis
Genitourinary disorders
Common: delayed ejaculation, decreased potency
Uncommon: increased frequency of or discomfort during urination, increased or decreased sexual interest
Skin and subcutaneous disorders
Common: skin rash
Uncommon: oily skin, purities, acne, athlete’s foot, cold sores, alopecia.
Psychiatric disorders
Very common: Difficulty sleeping, anxiety, nervousness, head ache
Common: feeling down, irritability, dizziness
Uncommon: depression, paranoia, fatigue, restlessness, confusion, disorientation, hallucinations, nightmares, bad dreams
Eye disorders
Common: increased lacrimation.
Uncommon: eyes-blurred, burning, light sensitive, swollen, aching or strained.
Ear and labyrinth disorders
Uncommon: ears- clogged, aching, tinnitus,vertigo
Nervous system disorders
Very common: headache, restlessness
Common: dizziness
Uncommon: tremor, somnolence, headache
Renal and urinary tract disorders
Uncommon: pollakiuria, dysuria
Infections and infestations
Uncommon: oral herpès, tinea pedis
Metabolism and nutrition disorders
Common: decreased appetite
General disorders
Very common: low energy
Common: loss of appetite, increased thirst, increased energy, chills, increased sweating.
Uncommon: increased appetite, weight loss, weight gain, yawning, somnolence, fever, dry mouth, head “pounding”, inguinal pain, swollen glands, side pains, cold feet, hot spells.
Hepatobiliary disorders
Uncommon: liver disorder, blood bilirubin increased, hepatitis (During treatment an increase of liver transaminases may occur. After discontinuation of Nalorex the transaminases decreased to baseline within several weeks.)
Occasional liver function abnormalities have also been reported. One case of reversible idiopathic thrombocytopenic purpura has occurred in a patient taking Nalorex. DATE OF (PARTIAL) REVISION OF TEXT March 2011
DATE OF (PARTIAL) REVISION OF TEXT
March 2011
4.2 Posology and method of administration
Use in Children and Adolescents
Safe use in children has not been established.
Nalorex is not recommended in patients below 18 years old.
Safe use in children has not been extablished
NALOREX is contraindicated in patients with acute hepatitis or liver failure.
NALOREX is contraindicated in patients currently dependent on opioids since an acute withdrawal syndrome may ensue.
NALOREX is contraindicated in patients in acute opiod withdrawal
NALOREX is contraindicated for use in conjunction with an opioid-containing medication.
NALOREX is contraindicated in any patient who has a positive screen for opioids or who has failed the Narcan Challenge.
NALOREX is contraindicated in patients who have demonstrated hypersensitivity to Nalorex or any of the excipients.
4.8 Undesirable effects
Frequency is defined using the following convention: very common (>1/10); common
(>1/100, <1/10); uncommon (>1/1,000, <1/100); rare (>1/10,000, <1,000); very rare
(<1/10,000)
Uncommon: nasal congestion, itching, rhinorrhea, sneezing, sore throat, excess mucus or
phlegm, sinus trouble, heavy breathing, hoarseness, cough, shortness of breath.
Uncommon: nose bleeds, phlebitis, edema, increased blood pressure, non-specific ECG
changes palpitations, tachycardia.
Uncommon: excessive gas, hemorrhoids, diarrhoea, ulcer
Uncommon: painful shoulders, legs or knees, tremors, twitching
Uncommon: increased frequency of or discomfort during urination, increased or decreased
sexual interest
Uncommon: depression, paranoia, fatigue, restlessness, confusion, disorientation,
hallucinations, nightmares, bad dreams
Uncommon: ears- clogged, aching, tinnitus
Uncommon: increased appetite, weight loss, weight gain, yawning, somnolence, fever, dry
mouth, head “pounding”, inguinal pain, swollen glands, side pains, cold feet, hot spells.
6.4 Special precautions for storage
Do not store above 30°C. Store in the original package.
White opaque PVC/PE/Aclar blister with aluminium foil in packs of 28 tablets.