- In section 4.2 Posology and method of administration
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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).
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.
A dose of over 150 mg on any single day is not recommended, since this can lead to a higher incidence of side effects.
Nalorex is not recommended in patients below 18 years old
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Nalorex treatment should be initiated in a drug addiction centre and supervised by suitably qualified physicians.
- In section 4.3 Contraindications
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Nalorex is contraindicated in any patient who has a positive screen for opioids or who has failed the Narcan Challenge.
..... naltrexone hydrochloride or any of the excipients
Nalorex is contraindicated in patients with severe renal failure
- In section 4.4 Special warnings and special precautions for use
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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.
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 naloxone challenge test is recommended to screen for presence of opioids use; a withdrawal syndrome precipitated by
naloxone hydrochloride will be of shorter duration than one precipitated by nalorex.
he naloxone-challenge test should neither be performed in patients with clinically significant withdrawal symptoms nor in patients tested positive for opioids in the urine.
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.
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.
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Narcan (Naloxone Hydrochloride) challenge is recommended to screen for presence of opioid use; a withdrawal syndrome precipitated by Narcan will be of shorter duration than one precipitated by Nalorex.
The recommended procedure is as follows:
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i.v. injection of 0.2 mg Narcan
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if after 30 seconds no adverse reactions occur, a further i.v. injection of 0.6 mg Narcan may be administered
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continue to observe the patient for withdrawal effects for a further 30 minutes.
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If doubt exists that the patient is opioid-free, the challenge may be repeated with a Narcan dose of 1.6 mg.
If there is no evidence of a reaction, Nalorex administration may be initiated with 25 mg by mouth (half a tablet).
- In section 4.5 Interaction with other medicinal products and other forms of interaction
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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.
- In section section 4.6 Pregnancy and lactation
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Pregnancy: 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 and 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).
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.
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Animal studies do not suggest a teratogenic effect. Because of absence of documented clinical experience Nalorex should only be given to pregnant or breast-feeding women when, in the judgement of the attending physician, the potential benefits outweigh the possible risks.
- In section 4.8 Undesirable effects
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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.
Blood and lymphatic system disorders
Uncommon: lymphadenopathy
Rare: idiopathic thrombocytopenic purpura
Psychiatric disorders
Very common: nervousness, anxiety, insomnia
Common: irritability, affective disorders
Uncommon: hallucination, confusional state, depression, paranoïa, disorientation, nightmare, agitation, libido disorder, abnormal dreams
Rare: suicidal ideation, attempted suicide
Nervous system disorders
Very common: headache, restlessness
Common: dizziness
Uncommon: tremor, somnolence, headache
Eye disorders
Common: lacrimation increased
Uncommon: vision-blurred, eye irritation, photophobia, eye swelling, eye pain or asthenopia
Cardiac disorders
Common: tachycardia, palpitations, electrocardiogram change
Uncommon: palpitation
Vascular disorders
Uncommon: blood pressure fluctuation, flushing
Respiratory disorders
Common: chest pain
Uncommon: nasal congestion, nasal discomfort, rhinorrhea, sneezing, oropharyngeal pain, sputum increased, sinus
disorder, dyspnoea, dysphonia, cough, yawning
Gastrointestinal disorders
Very common: abdominal pain, nausea and/ or vomiting
Common: diarrhoea, constipation
Uncommon: flatulence, haemorrhoids, ulcer, dry mouth
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.
Skin and subcutaneous tissue disorders
Common: rash
Uncommon: seborrhoea, pruritus, acne, alopecia
Musculoskeletal and connective tissue disorders
Very common: arthralgia and myalgia
Very rare: rhabdomyolysis
Uncommon: groin pain
Reproductive system and breast disorders
Common: ejaculation delayed, erectile dysfunction
Renal and urinary tract disorders
Uncommon: pollakiuria, dysuria
Ear and labyrinth disorders
Uncommon: ear discomfort, ear pain, tinnitus, vertigo
Infections and infestations
Uncommon: oral herpès, tinea pedis
Metabolism and nutrition disorders
Common: decreased appetite
General disorders
Very common: asthenia
Common: thirst, energy increased, chills, hyperhidrosis
Uncommon: increased appetite, weight loss, weight gain, pyrexia, pain, peripheral coldness, feeling hot
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The following adverse reactions have been reported before and during naltrexone medication:
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an incidence of more than 10% in detoxified opioid abusers:
difficulty sleeping, anxiety, nervousness, abdominal pain/cramps, nausea and/or vomiting, low energy, joint and muscle pain, and headache;
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an incidence of less than 10%:
loss of appetite, diarrhoea, constipation, increased thirst, increased energy, feeling down, irritability, dizziness, skin rash, delayed ejaculation, decreased potency, chills, chest pain, increased sweating and increased lacrimation.
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Occasional liver function abnormalities have also been reported. One case of reversible idiopathic thrombocytopenic purpura has occurred in a patient taking Nalorex.
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