Source: Health Products Regulatory Authority (IE) Revision Year: 2022 Publisher: AOP Orphan Pharmaceuticals Gmbh, Leopold-Ungar-Platz 2, A-1190 Vienna, Austria
Ethylex is contraindicated:
In accordance to national guidance the therapy should be initiated and supervised by a physician experienced in treatment of alcohol-addicted patients.
Since Ethylex 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.
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.
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.
A withdrawal syndrome may be precipitated by Ethylex 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.
In an emergency situation in which the administration of opioid analgesics is required in patients receiving Ethylex, 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.
During the treatment with Ethylex, painful conditions should be treated with non-opioid analgesia only.
Patients should be warned that attempts to overcome the blockade by administering large doses of opioids may result in acute opioid intoxication after the end of the naltrexone effect which may be possibly life threatening. High dose opioid intake, concomitant with naltrexone treatment, can lead to life-threatening opioid poisoning from respiratory and circulatory impairment.
Patients must be cautioned about the concomitant use of opioids (e.g. opioids in cough preparations, opioids for symptomatic treatment of colds or opioids in antidiarrhoeal preparations etc.) during treatment with naltrexone.
A naloxone provocation is recommended to screen for presence of opioid use; a withdrawal syndrome precipitated by naloxone will be of shorter duration than a withdrawal precipitated by Ethylex.
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.
The recommended procedure is as follows:
Intravenous provocation
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 naltrexone hydrochloride can be administered to the patient.
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).
The risk of suicide is known to increase in substance abusers, with or without concomitant depression. Treatment with INVENTED NAME does not eliminate this risk.
Lactose: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
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 active metabolite 6-beta-naltrexol is metabolised by human cytochrom P450 enzymes. Therefore it is unlikely that the pharmacokinetics of naltrexone hydrochloride is affected by cytochrom P450 enzyme inhibiting drugs.
Association contraindicated: opioid derivates (analgesics, antitussives, substitution treatments). Concomitant administration of naltrexone with an opioid-containing medication is contraindicated.
Methadone in substitution treatment: There is a risk of onset of withdrawal syndrome.
Association not recommended: central antihypertensives (alpha-methyldopa).
Association to be taken into account: barbiturates; benzodiazepines; anxiolytics others than benzodiazepines (i.e. meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, trimipramine), sedative antihistaminics H1, neuroleptics (droperidol).
Until now no interaction between cocaine and naltrexone hydrochloride has been described.
Data from a safety and tolerability study of co-administration of naltrexone with acamprosate in non-treatment seeking, alcohol dependent individuals showed that naltrexone administration significantly increased acamprosate plasma level. Interactions 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.
Concomitant use with opioid containing medicines is contraindicated (see section 4.3).
There are no clinical data on naltrexone hydrochloride use in pregnancy. Data from animal studies have shown reproductive toxicity (see section 5.3). The data are insufficient to establish clinical relevance. The potential risk for humans is unknown. Naltrexone should only be given to pregnant women when, in the judgment of the attending physician, the potential benefits outweigh the possible risk.
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).
There are no clinical data on naltrexone hydrochloride use in lactation. It is unknown whether naltrexone or 6-beta-naltrexol is excreted in human breast milk. Breast feeding is not recommended during naltrexone treatment.
Ethylex 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 adverse reactions have been reported before and during naltrexone medication:
Frequency is defined using the following convention: 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).
The side effects observed with naltrexone appear to be similar in both alcoholics and patients dependent on opioids. Serious adverse reactions are unusual.
Uncommon: lymphadenopathy
Rare: idiopathic thrombocytopenic purpura
Very common: nervousness, anxiety, insomnia
Common: irritability, affective disorders
Uncommon: hallucination, confusional state, depression, paranoia, disorientation, nightmare, agitation, libido disorder, abnormal dreams
Rare: suicidal ideation, attempted suicide
Very common: headache, restlessness
Common: dizziness
Uncommon: tremor, somnolence
Common: lacrimation increased
Uncommon: vision-blurred, eye irritation, photophobia, eye swelling, eye pain or asthenopia
Common: tachycardia, palpitations, electrocardiogram change
Uncommon: blood pressure fluctuation, flushing
Common: chest pain
Uncommon: nasal congestion, nasal discomfort, rhinorrhea, sneezing, oropharyngeal pain, sputum increased, sinus disorder, dyspnoea, dysphonia, cough, yawning
Very common: abdominal pain, nausea and/ or vomiting
Common: diarrhoea, constipation
Uncommon: flatulence, haemorrhoids, ulcer, dry mouth
Uncommon: liver disorder, blood bilirubin increased, hepatitis (During treatment an increase of liver transaminases may occur.
After discontinuation of Ethylex the transaminases decreased to baseline within several weeks.)
Common: rash
Uncommon: seborrhoea, pruritus, acne, alopecia
Very common: arthralgia and myalgia
Uncommon: groin pain
Very rare: rhabdomyolysis
Common: ejaculation delayed, erectile dysfunction
Uncommon: pollakiuria, dysuria
Uncommon: ear discomfort, ear pain, tinnitus, vertigo
Uncommon: oral herpes, tinea pedis
Common: decreased appetite
Very common: asthenia
Common: thirst, energy increased, chills, hyperhidrosis
Uncommon: increased appetite, weight loss, weight gain, pyrexia, pain, peripheral coldness, feeling hot
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 HPRA Pharmacovigilance, Website: www.hpra.ie.
Not applicable.
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