ADEPEND

4). Treatment with naltrexone should according to national guidelines only be initiated and monitored by physicians experienced with the treatment of alcohol-addicted patients. 4). The treatment should be initiated with low doses of naltrexone according to the treatment induction schedule.

Higher doses than 150 mg even for only one day may result in an increase in side effects and are therefore not recommended. Use in adults The recommended dose of naltrexone hydrochloride in adults is 50 mg per day (1 tablet per day).

Use in children and adolescents (<18 years) Adepend 50 mg film-coated tablets are not recommended for use in children and adolsecents below 18 in this indication due to a lack of data on safety and efficacy. Use in elderly Safe use for the treatment of opiate dependence in the elderly has not been established.

Use in patients with liver and/or kidney diseases Adepend 50 mg film-coated tablets are contraindicated for patients with severe liver and/or kidney diseases. 4). 2). Method of administration Adepend 50 mg film-coated tablets should be taken with a liquid.

Duration of administration A common duration of administration cannot be specified as Adepend 50 mg film- coated tablets are used as concomitant therapy and recovery is individually different for patients addicted to alcohol, even if they are psychologically attended.

A treatment duration of at least 3 months is recommended whereas a prolongation might be necessary. Efficacy is proven by controlled studies over a period up to 12 months. Naltrexone hydrochloride neither causes psychical nor physic addiction.

There is no decrease of antagonistic effects during long term treatments.

000) Not known (cannot be estimated from the known data) The side effects observed with naltrexone appear to be similar in both alcoholics and patients dependent on opioids. Serious adverse reactions are unusual. Infections and infestations Uncommon: oral herpes, tinea pedis Blood and lymphatic system disorders Uncommon: lymphadenopathy Rare: idiopathic thrombocytopenic purpura Metabolism and nutrition disorders Common: decrease of appetite Psychiatric disorders Very common: nervousness, anxiety, insomnia Common: irritability, affective disorder Uncommon: hallucination, confusion, despondency, depression, paranoia, disorientation, nightmares, agitation, libido disorder, abnormal dreams Rare: suicidal ideation, attempted suicide Nervous system disorders Very common: headache, restlessness, Common: dizziness Uncommon: tremor, somnolence Eye disorders Common: increased lacrimation Uncommon: blurred vision, irritation and swelling of the eye, photophobia, eye pain or tiredness, colour asthenopia Ear and labyrinth disorders Uncommon: ear discomfort, ear pain, tinnitus, vertigo Cardiac disorders Common: tachycardia, heart palpitation, anomalies in the ECG Vascular disorders Uncommon: blood pressure changes, flushing Respiratory, thoracic and mediastinal disorders Common: pain in the chest Uncommon: nasal congestion, nasal discomfort, rhinorrhoea, sneezing, oropharyngeal disorders, increased sputum, sinus disorders, dyspnoea, dysphonia, coughing, yawning Gastrointestinal disorders Very common: abdominal pain, nausea, emesis Common: diarrhoea, constipation Uncommon: flatulence, haemorrhoids, ulcus, mouth dryness Hepatobiliary disorders Uncommon: hepatic disorders, increased bilirubin levels, hepatitis (During treatment, increase of transaminases is possible.

) Skin and subcutaneous tissue disorders Common: rash Uncommon: seborrhea, pruritus, acne, alopecia Musculoskeletal and connective tissue disorders Very common: arthralgia and myalgia Uncommon: groin pain Very rare: rhabdomyolysis Renal and urinary disorders Uncommon: pollakisuria, dysuria Reproductive system and breast disorders Common: delayed ejaculation, erectile dysfunction, libido disorders General disorders and administration site conditions Very common: asthenia Common: thirst, increased energy, chills, hyperhidrosis Uncommon: increased appetite, weight loss, weight gain, fever, pain, sensation of cold in extremities, hot flushes Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard.

In accordance with national guidance the therapy should be initiated and supervised by a physician experienced in the treatment of alcohol-addicted patients. During the treatment, painful conditions should be treated with non-opioid analgesia only.

In opioid-dependent patients, withdrawal symptoms may be caused by Adepend 50 mg film-coated tablets. These may manifest after 5 minutes and least up to 48 hours. The treatment should be symptomatic and may include administration of opioids.

Liver function test Due to its hepatotoxic effect, special caution should be taken with the administration of Adepend in patients with acute liver disease or liver impairment. Naltrexone hydrochloride is metabolised mainly by the liver and mainly eliminated by urine.

3). Liver function tests should be conducted before and during therapy. It is not uncommon that the liver function of alcohol addicts is impaired. In elderly, obese alcohol addicted patients, liver function tests have demonstrated abnormal results after administration of higher doses of naltrexone (up to 300 mg/day).

Liver function tests should be carried out both before and during treatment. Screen for presence of opioid use In case of the suspicion of opioid dependence it is recommended to screen for the presence of opioid use: • Urine test: If the suspicion of opioid use is aroused despite a negative urine test result and the lack of visible clinical withdrawal symptoms, it is recommended to confirm the result of the urine test with a naloxone challenge test.

• Naloxone challenge test: Withdrawal symptoms caused by naloxone hydrochloride are of shorter duration than those precipitated by Adepend 50 mg film-coated tablets. A 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 withdrawal symptoms should occur during this test the treatment with Adepend 50 mg film-coated tablets must not be initiated. The treatment may be initiated following a negative test result. 2 mg naloxone iv. 6 mg naloxone iv. Continue observing the patient over 30 minutes for signs of withdrawal.

8 mg naloxone sc. Observe the patient for 30 minutes for signs of withdrawal.

Confirmation of the test:

If there is any doubt that the patient is opioid-free, treatment with Adepend 50 mg film-coated tablets should be delayed 24 hours. 6 mg naloxone. Naltrexone treatment must begin only when the opioid has been discontinued for sufficiently long period (about 5 to 7 days for heroin and at least 10 days for methadone).

Patients must be warned against the use of high doses of opioids to neutralize the blockade as this might result in acute and possibly fatal opioid intoxication as soon as the effect of naltrexone has ceased. High-dose opioid intake, concomitant with naltrexone treatment, can lead to life-threatening opioid poisoning from respiratory and circulatory impairment.

Patients might be more sensitive to opioid containing medicines after treatment with Adepend 50 mg film-coated tablets. Naltrexone may cause a transient increase in the diastolic blood pressure followed by decrease in body temperature and heart rate.

g. ) during treatment with Adepend 50 mg film-coated tablets. g. opioid analgesia or anesthesia in emergency situations, the dose needed may be higher than normal to reach the same therapeutic effect. In these cases, respiratory depression and circulatory disturbance will be more profound and longer lasting.

g. face swelling, itching, erythema, diaphoresis and other skin and mucocutaneous manifestations) can occur more easily. The patient requires specific attention and supervision by health care personnel in a medical unit. The increased suicidal risk in drug addicts with or without accompanying depression is not reduced by the intake of Adepend 50 mg film-coated tablets.

Special attention should be paid to patients with hepatic enzyme levels in serum exceeding three times the normal value and patients with renal impairment.

Lactose:

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

5) - Opioid-addicted patients as acute opioid withdrawal symptoms may occur - Patients with withdrawal symptoms after administering naloxon hydrochloride (positive result of the naloxone provocation test) - Positive urine test for opioids