Naltrexone Hydrochloride 50 mg film-coated tablets - Summary of Product Characteristics (SPC) (2023)

Film-coated tablet.

Beige, capsule-shaped, film-coated tablets scored on each side. The tablet can be divided into equal doses.

Treatment with naltrexone hydrochloride should be initiated and supervised by appropriately qualified physicians.

Naltrexone hydrochloride given to people addicted to opiates can cause life-threatening withdrawal symptoms. Administration of naltrexone hydrochloride should not be initiated until a naloxone challenge test has been performed and a negative result obtained (see section 4.4).

Treatment with naltrexone hydrochloride should only be considered in patients who have been opioid-free for at least 7 to 10 days.

Before starting treatment with naltrexone hydrochloride, this test must be confirmed by urinalysis.

Dosage

use in adults

Treatment should be started with low doses of naltrexone according to the treatment induction schedule.

The recommended starting dose of naltrexone hydrochloride is 25 mg (half a tablet) followed by 50 mg daily (one tablet).

The dosing regimen can be modified to improve adherence to a three-times-weekly dosing schedule as follows: administration of 2 tablets (= 100 mg naltrexone hydrochloride) on Monday and Wednesday and 3 tablets (= 150 mg naltrexone hydrochloride) on Friday.

A missed dose can be managed by giving 1 tablet daily until the next regular dose.

A dose greater than 150 mg in a single day is not recommended as this may lead to a higher incidence of side effects.

Used for children and young people

Naltrexone hydrochloride is not recommended for children and adolescents under 18 years of age. Safe use in children has not been established.

use in the elderly

Safe use in the treatment of opioid dependence in the elderly has not been established.

administration method

Naltrexone hydrochloride 50 mg film-coated tablets should be taken with liquid.

duration of administration

Since naltrexone hydrochloride is an adjunctive treatment and the process of full recovery in opiate-dependent patients is individually variable, it is not possible to establish a standard duration of treatment; an initial period of three months should be considered. However, long-term administration may be necessary.

Naltrexone hydrochloride is contraindicated:

- in patients who have shown hypersensitivity to naltrexone hydrochloride or to one or more of the excipients listed in section 6.1.

- in patients with acute hepatitis or liver failure

- in patients with severely reduced kidney function

- in patients currently dependent on opiates, as an acute withdrawal syndrome may occur.

- in any patient with a positive opioid test result or who has failed a naloxone test.

- for use with an opioid-containing medicinal product

- in combination with methadone (see section 4.5).

In accordance with national guidelines, treatment should be initiated and supervised by a physician experienced in the treatment of opioid and alcohol dependent patients.

Since naltrexone hydrochloride is extensively metabolized by the liver and predominantly excreted in the urine, caution should be exercised when administering the drug to patients with impaired hepatic or renal function. Liver function tests should be performed before and during treatment.

Liver function test abnormalities have been reported in obese and elderly patients taking naltrexone hydrochloride who have no history of substance abuse. Liver function tests should be performed before and during treatment.

It is not uncommon for people who abuse opioids to have impaired liver function. Furthermore, it is not uncommon for users who abuse alcohol to have altered liver function. Changes in liver function tests have been described in elderly obese patients receiving naltrexone hydrochloride at doses higher than recommended (up to 300 mg/day) for the treatment of alcoholism. Liver function tests should be performed before initiation of treatment and periodically during treatment.

A withdrawal syndrome may be precipitated by naltrexone hydrochloride in opioid-dependent patients; signs and symptoms can develop within 5 minutes and last up to 48 hours. Treatment should be symptomatic and may include administration of opioids.

In an emergency situation where administration of opioid analgesics is required in patients receiving Naltrexone, a higher dose of opioid analgesic than usual may be administered to achieve the same therapeutic effect. The resulting respiratory depression may be more profound and prolonged, and non-receptor-mediated effects may also occur (eg, facial swelling, pruritus, generalized erythema, diaphoresis, and other dermal and mucosal symptoms, presumably due to histamine release). In these circumstances, the patient must be closely monitored by trained personnel in a hospital center.

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

Patients should be advised that attempts to overcome the blockade by administration of large doses of opioids may result in acute opioid intoxication after naltrexone hydrochloride wears off, which may be fatal. Ingestion of high doses of opioids, concurrently with treatment with naltrexone hydrochloride, can lead to potentially fatal opioid intoxication due to respiratory and circulatory disturbance.

Patients should be warned against the concomitant use of opiates (e.g. opiates in cough medicines, opiates in symptomatic medicines for the treatment of the common cold or opiates contained in antidiarrheal agents, etc.) during treatment with naltrexone hydrochloride (see section 4.3).

A naloxone challenge test is recommended to screen for the presence of opioid use; a withdrawal syndrome precipitated by naloxone hydrochloride will be of shorter duration than one precipitated by naltrexone.

The naloxone hydrochloride challenge test should not be performed in patients with clinically significant withdrawal symptoms or in patients who test positive for opioids in the urine.

The recommended procedure is as follows:

naloxon test

- Intravenous:

Administer 0.2 mg of naloxone intravenously. If no side effects occur after 30 seconds, another dose of 0.6 mg naloxone is administered intravenously. Continue to observe the patient for another 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.

If withdrawal symptoms occur, naltrexone treatment should not be undertaken. If the test result is negative, treatment can begin.

Test Confirmation: If there is any doubt that the patient is opioid-free, treatment with naltrexone hydrochloride should be delayed for 24 hours. In this case, the test must be repeated with 1.6 mg of naloxone.

If no reaction occurs thereafter, 25 mg of naltrexone hydrochloride can be given to the patient.

Treatment with naltrexone hydrochloride should not be initiated until the opioid has been discontinued for a sufficiently long period (approximately 5 to 7 days for heroin and at least 10 days for methadone).

It is known that the risk of suicide increases in drug users, with or without concurrent depression. Treatment with naltrexone hydrochloride does not eliminate this risk.

Patients may be more sensitive to opioid-containing medications after treatment with naltrexone hydrochloride.

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

Currently, clinical experience and experimental data on the effect of naltrexone hydrochloride on the pharmacokinetics of other substances are limited. Concomitant treatment with naltrexone hydrochloride and other drugs should be done with caution and carefully monitored.

Interaction studies have not been performed.

In vitro studies have shown that neither naltrexone hydrochloride nor its major metabolite 6-ß-naltrexol is metabolised via human CYP450 enzymes. Therefore, the pharmacokinetics of naltrexone hydrochloride are unlikely to be affected by cytochrome P450 enzyme inhibitors.

Association is not recommended: opioid derivatives (analgesics, antitussives, replacement treatments), central antihypertensives (alpha-methyldopa).

Concomitant administration of naltrexone hydrochloride and an opioid-containing medicinal product should be avoided.

Methadone in substitution treatment. There is a risk of withdrawal syndrome.

Association to consider: barbiturates; benzodiazepines, non-benzodiazepine anxiolytics (ie, meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin, mianserin, trimipramine), sedative H1 antihistamines, neuroleptics (droperidol).

There have been cases of lethargy and drowsiness following concomitant administration of naltrexone hydrochloride and thioridazine.

So far, no interaction between cocaine and naltrexone hydrochloride has been described.

Data from a study of the safety and tolerability of the simultaneous administration of naltrexone hydrochloride and acamprosate in non-treatment-seeking alcohol-dependent subjects showed that the administration of naltrexone hydrochloride significantly increased the plasma level of acamprosate.

Interaction with other psychopharmacological agents (eg, disulfiram, amitriptyline, doxepin, lithium, clozapine, benzodiazepines) has not been studied.

There are no known interactions between naltrexone hydrochloride and alcohol.

Simultaneous use with opiate-containing medicinal products is contraindicated (see sections 4.3 and 4.4).

Pregnancy:

There are no clinical data on the use of naltrexone hydrochloride during pregnancy. Data from animal experiments have shown reproductive toxicity (see section 5.3). Data are insufficient to establish clinical relevance. The potential risk to humans is unknown. Naltrexone hydrochloride should be given to pregnant women only when, in the opinion of the attending physician, the potential benefits outweigh the possible risks.

Use of naltrexone hydrochloride in alcoholic pregnant patients receiving long-term opioid therapy or opioid substitution therapy, or in opioid-dependent pregnant patients, creates a risk of acute withdrawal syndrome, which may have serious consequences for the mother and fetus. (see section 4.4). Administration of naltrexone hydrochloride should be stopped if opioid analgesics are prescribed (see section 4.5).

Breastfeeding:

There are no clinical data on the use of naltrexone hydrochloride during breastfeeding. It is not known whether naltrexone hydrochloride or 6-beta-naltrexol is excreted in human milk. Breast-feeding is not recommended during treatment with naltrexone hydrochloride.

The following side effects are classified by system organ class and their frequency:

Very common (≥ 1/10)

Common (≥1/100 to <1/10)

Uncommon (≥1/1000 to <1/100)

Rare (≥1/10,000 to <1/1,000)

Very rare (< 1/10,000)

Unknown (cannot be estimated from known data)

Side effects seen with naltrexone hydrochloride appear to be similar in both alcoholic and opioid-dependent patients. Serious side effects are not common.

Disorders of the blood and lymphatic system

Uncommon: lymphadenopathy

Rare: idiopathic thrombocytopenic purpura

psychiatric disorders

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, suicide attempt

Disorders of the nervous system

Very common: headache, restlessness

Common: dizziness

Uncommon: tremor, drowsiness

eye disorders

Common: increased lacrimation

Uncommon: blurred vision, eye irritation, photophobia, eye swelling, eye pain or asthenopia

heart diseases

Common: tachycardia, palpitations, abnormal electrocardiogram

vascular disorders

Uncommon: fluctuations in blood pressure, flushing

respiratory disorders

Common: chest pain

Uncommon: nasal congestion, nasal discomfort, rhinorrhea, sneezing, oropharyngeal pain, increased expectoration, sinus disorders, dyspnoea, dysphonia, cough, yawning

gastrointestinal problems

Very common: abdominal pain, nausea and/or vomiting

Common: diarrhoea, constipation

Uncommon: flatulence, haemorrhoids, ulcers, dry mouth

Liver and biliary tract disorders

Uncommon: liver disease, increased blood bilirubin, hepatitis (an increase in liver transaminases may occur during treatment. After discontinuation of naltrexone hydrochloride, transaminases decreased to baseline values ​​within several weeks).

Disorders of the skin and subcutaneous tissue

Common: rash

Uncommon: seborrhea, pruritus, acne, alopecia

Muscle and connective tissue disorders

Very common: arthralgia and myalgia

Uncommon: groin pain

Very rare: rhabdomyolysis

Reproductive system and breast disorders

Common: delayed ejaculation, erectile dysfunction

Kidney and urinary tract disorders

Uncommon: pollakiuria, dysuria

Ear and labyrinth disorders

Uncommon: ear discomfort, ear pain, tinnitus, vertigo

Infections and infestations

Uncommon: oral herpes, tinea pedis

Disturbances in metabolism and nutrition

Common: decreased appetite

general disorders

Very common: asthenia

Common: thirst, increased energy, chills, hyperhidrosis

Uncommon: increased appetite, weight loss, weight gain, pyrexia, pain, peripheral cold, feeling hot

Notification of suspected side effects

It is important to report suspected side effects after approval of the drug. Allows for continuous monitoring of the benefit/risk ratio of the drug. Healthcare personnel are asked to report all suspected side effects via the yellow card system

Website: www.mhra.gov.uk/yellowcard or search MHRA Yellow Card on Google Play or Apple App Store

Symptoms

Clinical experience with naltrexone hydrochloride overdose in patients is limited. There was no evidence of toxicity in volunteers given 800 mg/day for seven days.

Treatment

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

Pharmacotherapeutic classification: Drugs for alcohol dependence

ATC-kode: N07BB04

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

Treatment with naltrexone hydrochloride does not cause physical or mental dependence. Tolerance to the antagonizing effect of opioids has not been observed.

Naltrexone Hydrochloride 50 mg film-coated tablet reduces the risk of relapse and supports opioid withdrawal.

Naltrexone hydrochloride 50 mg film-coated tablet is a non-aversive treatment and does not cause reactions after taking opioids. Therefore, it does not cause a disulfiram-type reaction.

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

It undergoes a first-pass effect in the liver, and maximum plasma concentrations are reached after approx. one hour.

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

The plasma half-life of naltrexone hydrochloride is approx. 4 hours, the mean blood level is 8.55 ng/ml and the plasma protein binding is 21%. The plasma half-life of 6-bethanaltrexol is 13 hours.

The drug is mainly excreted via the kidneys. Approx. 60% of the oral dose is excreted within 48 hours as glucuronidated 6-beta-naltrexol and naltrexone hydrochloride.

Preclinical data reveal no special hazard for humans based on conventional studies of safety, pharmacology, repeated dose toxicity, genotoxicity, carcinogenicity and toxicity to reproduction. However, there is evidence of hepatotoxicity with increasing dose, as reversible increases in liver enzymes have been found in humans at therapeutic and higher doses (see sections 4.4 and 4.8).

Naltrexone hydrochloride (100 mg/kg, approximately 140 times the human therapeutic dose) caused a significant increase in pseudopregnancy in rats. There was also a decrease in the pregnancy rate of mated rats. The relevance of these observations to human fertility is not known.

Naltrexone hydrochloride has been shown to have an embryocidal effect in rats and rabbits when administered in doses of approx. 140 times the human therapeutic dose. This effect was demonstrated in rats given 100 mg/kg naltrexone hydrochloride before and during pregnancy and in rabbits treated with 60 mg/kg naltrexone hydrochloride during the period of organogenesis.

Núcleo til tablets

lactose monohydrate

cellulose pulver

Microcrystalline cellulose

anhydrous colloidal silica

Crosprovidona

Magnesiumstearat

Film: Opadry 31 F 27245 Bege

lactose monohydrate

Hypromellose

Titanium Dioxide (E171)

Macrogol 4000

Black iron oxide (E172)

Red iron oxide (E172)

Yellow iron oxide (E172)

Do not store above 25°C.

Store in the original packaging to protect from moisture.

Pack size: 7, 14, 28, 30 and 56 tablets in aluminum PCV/PVDC blister.

Not all pack sizes can be marketed.

AOP Orphan Pharmaceuticals GmbH

Leopold-Ungar-Platz 2

1190 in

Austria

Date of first approval: 14.08.2006

Date of last renewal: 13.7.2010