Nalmefene

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. Conversely, concomitant administration with a UGT inducer (for example, dexamethasone, phenobarbital, rifampicin, omeprazole) may potentially lead to subtherapeutic nalmefene plasma concentrations.

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. Nalmefene is not recommended during pregnancy.

Available pharmacodynamic/toxicological data in animals have shown excretion of nalmefene/metabolites in milk. 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 nalmefene therapy, taking into account the benefit of breast-feeding to the child and the benefit of therapy to the woman.

Fertility

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. The majority of these reactions were mild or moderate, associated with treatment initiation, and of short duration.

Consequently, nalmefene may have minor to moderate influence on the ability to drive and use machines and patients should exercise caution particular when starting treatment with nalmefene.

Summary of the safety profile

The frequencies of the adverse reactions 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.

list of adverse reactions

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).

Metabolism and nutrition disorders

Common: Decreased appetite

Psychiatric disorders

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

Nervous system disorders

Very Common: Dizziness, Headache

Common: Somnolence, Tremor, Disturbance in attention, Paraesthesia, Hypoaesthesia

Cardiac disorders

Common: Tachycardia, Palpitations

Gastrointestinal disorders

Very Common: Nausea

Common: Vomiting, Dry mouth, Diarrhoea

Skin and subcutaneous tissue disorders

Common: Hyperhidrosis

Unknown Angioedema, Urticaria, Pruritus, Rash, Erythema

Musculoskeletal and connective tissue disorders

Common: Muscle spasms

Unknown: Myalgia

Reproductive system and breast disorder

Unknown: Priapism

General disorders and administration site conditions

Common: Fatigue, Asthenia, Malaise, Feeling abnormal

Investigations

Common: Weight decreased