Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: H. Lundbeck A/S, Ottiliavej 9, DK-2500, Valby, Denmark
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Patients taking opioid agonists (such as opioid analgesics, opioids for substitution therapy with opioid agonists (e.g. methadone) or partial agonists (e.g. buprenorphine)) (see section 4.4).
Patients with current or recent opioid addiction.
Patients with acute symptoms of opioid withdrawal.
Patients for whom recent use of opioids is suspected.
Patients with severe hepatic impairment (Child-Pugh classification).
Patients with severe renal impairment (eGFR <30 ml/min per 1.73 m²).
Patients with a recent history of acute alcohol withdrawal syndrome (including hallucinations, seizures, and delirium tremens).
Selincro is not for patients for whom the treatment goal is immediate abstinence. Reduction of alcohol consumption is an intermediate goal on the way to abstinence.
In an emergency situation when opioids must be administered to a patient taking Selincro, the amount of opioid required to obtain the desired effect may be greater than usual. The patient should be closely monitored for symptoms of respiratory depression as a result of the opioid administration and for other adverse reactions.
If opioids are needed in an emergency, the dose must always be titrated individually. If unusually large doses are required, close observation is necessary.
Selincro should be temporarily discontinued for 1 week prior to the anticipated use of opioids, for example, if opioid analgesics might be used during elective surgery.
The prescriber should advise patients that it is important to inform their health care professional of last Selincro intake if opioid use becomes necessary.
Caution should be exercised when using medicinal products containing opioids (for example, cough medicines, opioid analgesics (see section 4.5)).
Psychiatric effects were reported in clinical studies (see section 4.8). If patients develop psychiatric symptoms that are not associated with treatment initiation with Selincro, and/or that are not transient, the prescriber should consider alternative causes of the symptoms and assess the need for continuing treatment with Selincro.
Selincro has not been investigated in patients with unstable psychiatric disease. Caution should be exercised if Selincro is prescribed to patients with current psychiatric comorbidity such as major depressive disorder.
The increased suicidal risk in alcohol and substances abusers, with or without accompanying depression, is not reduced by the intake of nalmefene.
There is limited experience in patients with a history of seizure disorders, including alcohol withdrawal seizures.
Caution is advised if treatment aimed at reduction of alcohol consumption is started in such patients.
Selincro is extensively metabolised by the liver and excreted predominantly in the urine. Therefore, caution should be exercised when prescribing Selincro to patients with mild or moderate hepatic or mild or moderate renal impairment, for example, by more frequent monitoring.
Caution should be exercised when prescribing Selincro to patients with elevated ALAT or ASAT (>3 times ULN) as these patients were excluded from the clinical development programme.
Limited clinical data are available on the use of Selincro in patients ≥65 years of age with alcohol dependence.
Caution should be exercised when prescribing Selincro to patients ≥65 years of age (see sections 4.2 and 5.2).
Caution is advised if Selincro is co-administered with a potent UGT2B7 inhibitor (see section 4.5).
Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.
No in vivo drug-drug interaction studies have been conducted.
Based on in vitro studies, no clinically relevant interactions between nalmefene, or its metabolites, and concomitantly administered medicinal products metabolised by the most common CYP450 and UGT enzymes or membrane transporters are anticipated. Co-administration with medicinal products that are potent inhibitors of the UGT2B7 enzyme (for example, diclofenac, fluconazole, medroxyprogesterone acetate, meclofenamic acid) may significantly increase the exposure to nalmefene. This is unlikely to present a problem with occasional use, but if long-term concurrent treatment with a potent UGT2B7 inhibitor is initiated, a potential for an increase in nalmefene exposure cannot be excluded (see section 4.4). Conversely, concomitant administration with a UGT inducer (for example, dexamethasone, phenobarbital, rifampicin, omeprazole) may potentially lead to subtherapeutic nalmefene plasma concentrations.
If Selincro is taken concomitantly with opioid agonists (for example, certain types of cough and cold medicinal products, certain antidiarrhoeal medicinal products, and opioid analgesics), the patient may not benefit from the opioid agonist.
There is no clinically relevant pharmacokinetic drug-drug interaction between nalmefene and alcohol. There seems to be a small impairment in cognitive and psychomotor performance after administration of nalmefene. However, the effect of nalmefene and alcohol in combination did not exceed the sum of the effects of each substance when taken alone.
Simultaneous intake of alcohol and Selincro does not prevent the intoxicating effects of alcohol.
There are no or limited data (fewer than 300 pregnancy outcomes) from the use of nalmefene in pregnant women.
Animal studies have shown reproductive toxicity (see section 5.3).
Selincro is not recommended during pregnancy.
Available pharmacodynamic/toxicological data in animals have shown excretion of nalmefene/metabolites in milk (see section 5.3). It is unknown whether nalmefene is excreted in human milk.
A risk to newborns/infants cannot be excluded.
A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Selincro therapy, taking into account the benefit of breast-feeding to the child and the benefit of therapy to the woman.
In fertility studies in rats, no effects were observed for nalmefene on fertility, mating, pregnancy, or sperm parameters.
Adverse reactions such as disturbance in attention, feeling abnormal, nausea, dizziness, somnolence, insomnia, and headache may occur following administration of nalmefene (see section 4.8). The majority of these reactions were mild or moderate, associated with treatment initiation, and of short duration.
Consequently, Selincro may have minor to moderate influence on the ability to drive and use machines and patients should exercise caution particular when starting treatment with Selincro.
The frequencies of the adverse reactions in Table 1 were calculated based on three randomised, double-blind, placebo-controlled studies in patients with alcohol dependence.
The most common adverse reactions were nausea, dizziness, insomnia, and headache. The majority of these reactions were mild or moderate, associated with treatment initiation, and of short duration.
Confusional state and, rarely, hallucinations and dissociation were reported in the clinical studies. The majority of these reactions were mild or moderate, associated with treatment initiation, and of short duration (a few hours to a few days). Most of these adverse reactions resolved during continued treatment and did not recur upon repeated administration. While these events were generally shortlasting, they could represent alcoholic psychosis, alcohol withdrawal syndrome, or comorbid psychiatric disease.
Frequencies are defined as: 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), or not known (cannot be estimated from the available data).
Table 1. Frequencies of adverse reactions:
Common: Decreased appetite
Very common: Insomnia
Common: Sleep disorder, Confusional state, Restlessness, Libido decreased (including loss of libido)
Not known: Hallucination (including hallucination auditory, hallucination tactile, hallucination visual, and somatic hallucination), Dissociation
Very Common: Dizziness, Headache
Common: Somnolence, Tremor, Disturbance in attention, Paraesthesia, Hypoaesthesia
Common: Tachycardia, Palpitations
Very Common: Nausea
Common: Vomiting, Dry mouth, Diarrhoea
Common: Hyperhidrosis
Unknown Angioedema, Urticaria, Pruritus, Rash, Erythema
Common: Muscle spasms
Unknown: Myalgia
Unknown: Priapism
Common: Fatigue, Asthenia, Malaise, Feeling abnormal
Common: Weight decreased
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 the national reporting system listed in Appendix V.
Not applicable.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
