rimantadine
Sources réglementaires consultées
Indications approuvées
- Prophylaxie et traitement de la grippe A chez l’adulte ; prophylaxie chez l’enfant à partir de 1 an selon l’étiquette.
Contre-indications
Absolues
- Hypersensibilité à la rimantadine, à l’amantadine ou aux autres adamantanes.
Mises en garde cliniques
- Mise en garde majeure · Il peut provoquer vertiges, insomnie, nervosité et autres effets du SNC ; surveiller surtout chez les personnes âgées, en cas d’épilepsie ou d’insuffisance rénale. — DailyMed, set_id 49f7d69a-820b-4c75-a31d-b2104c019c12
- Mise en garde majeure · Une résistance virale peut apparaître pendant le traitement ; ne pas extrapoler l’activité à la grippe B. — DailyMed, set_id 49f7d69a-820b-4c75-a31d-b2104c019c12
Interactions médicamenteuses
- ModéréeParacétamol ou acide acétylsalicylique
Mécanisme: Ils peuvent réduire modestement l’exposition à la rimantadine.
Recommandation: Un ajustement n’est généralement pas nécessaire ; surveiller la réponse clinique.
DailyMed, set_id 49f7d69a-820b-4c75-a31d-b2104c019c12
- SévèreVaccin antigrippal vivant attenue intranasal
Mécanisme: Les antiviraux contre la grippe peuvent réduire la replication et l’efficacité du vaccin vivant.
Recommandation: Eviter le vaccin jusqu’à 48 h après l’arret de la rimantadine et eviter la rimantadine pendant les 2 semaines suivant la vaccination, sauf indication medicale.
DailyMed, set_id 49f7d69a-820b-4c75-a31d-b2104c019c12
Effets indésirables
Communs (≥1%)
Nausées, insomnie, vertiges et nervosité
Rares mais graves
Convulsions et confusion sévère
Grossesse et allaitement
Utiliser pendant la grossesse uniquement si le bénéfice justifie le risque ; décider entre allaitement et traitement selon l’étiquette.
Bibliographie récente (PubMed)
Antiviral post-exposure prophylaxis with neuraminidase inhibitors can reduce the incidence of influenza and the risk of symptomatic influenza, but the efficacy of the other classes of antiviral remains unclear. To support an update of WHO influenza guidelines, this systematic review and network meta-analysis evaluated antiviral drugs for post-exposure prophylaxis of influenza. We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Global Health, Epistemonikos, and ClinicalTrials.gov for randomised controlled trials published up to Sept 20, 2023 that evaluated the efficacy and safety of antivirals compared with another antiviral or placebo or standard care for prevention of influenza. Pairs of reviewers independently screened studies, extracted data, and assessed the risk of bias. We performed network meta-analyses with frequentist random effects model and assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. The outcomes of interest were symptomatic or asymptomatic infection, admission to hospital, all-cause mortality, adverse events related to antivirals, and serious adverse events. This study is registered with PROSPERO, CRD42023466450. Of 11 845 records identified by our search, 33 trials of six antivirals (zanamivir, oseltamivir, laninamivir, baloxavir, amantadine, and rimantadine) that enrolled 19 096 individuals (mean age 6·75-81·15 years) were included in this systematic review and network meta-analysis. Most of the studies were rated as having a low risk of bias. Zanamivir, oseltamivir, laninamivir, and baloxavir probably achieve important reductions in symptomatic influenza in individuals at high risk of severe disease (zanamivir: risk ratio 0·35, 95% CI 0·25-0·50; oseltamivir: 0·40, 0·26-0·62; laninamivir: 0·43, 0·30-0·63; baloxavir: 0·43, 0·23-0·79; moderate certainty) when given promptly
Influenza A and B viruses are among the most prominent human respiratory pathogens. About 3-5 million severe cases of influenza are associated with 300 000-650 000 deaths per year globally. Antivirals effective at reducing morbidity and mortality are part of the first line of defense against influenza. FDA-approved antiviral drugs currently include adamantanes (rimantadine and amantadine), neuraminidase inhibitors (NAI; peramivir, zanamivir, and oseltamivir), and the PA endonuclease inhibitor (baloxavir). Mutations associated with antiviral resistance are common and highlight the need for further improvement and development of novel anti-influenza drugs. A summary is provided for the current knowledge of the approved influenza antivirals and antivirals strategies under evaluation in clinical trials. Preclinical evaluations of novel compounds effective against influenza in different animal models are also discussed.
Viroporins are ion channels found in many viruses, where they contribute to virus life cycle and thereby pathogenesis. Viroporin targeting is a known, yet largely unexplored, therapeutic strategy so far only used in Influenza A with the drugs amantadine and rimantadine. In this review, we seek to utilize the inhibition by amantadine of the viroporin Protein E in SARS-CoV-2 in an attempt to treat COVID-19 in its early stages. We are executing a double-blinded placebo-controlled trial based on promising in vivo and in vitro work as a stepping-stone for establishing a therapeutic antiviral regime: blocking of viroporins.
Advent of the acute respiratory coronavirus SARS-CoV-2 has resulted in the search for novel antiviral agents and in the repurposing of existing agents with demonstrated efficacy against other known coronaviruses in the search for an agent with antiviral activity for use during the COVID-19 pandemic. Adamantanes including amantadine, rimantadine, and memantine have well-established benefit in the treatment of neurodegenerative diseases including Parkinson's disease (PD), Alzheimer's disease (AD) and fatigue related to Multiple sclerosis (MS) all of which are known comorbidities related to COVID-19 Moreover, results of basic pharmacological studies both in vitro and in vivo reveal that amantadine has the potential to inhibit SARS-CoV-2 via down-regulation of host-cell proteases resulting in impaired viral genome release into the host cell and via amantadine's property as an NMDA receptor antagonist resulting in the prevention of the acute lung injury and respiratory distress that is characteristic of COVID-19. Cases suggestive of COVID-19 prophylaxis have been reported in patients with PD or MS or severe cognitive impairment treated in all cases for several months with an adamantane [amantadine or memantine] who were subsequently infected with SARS-CoV-2 confirmed by RT-PCR, and, in all cases, no signs of infectious disease were encountered. Amantadine is effective for the treatment of fatigue in MS and for the neurological complications of Traumatic Brain Injury (TBI).
In recent decades, the world has gained experience of the dangerous effects of pandemic events caused by emerging respiratory viruses. In particular, annual epidemics of influenza are responsible for severe illness and deaths. Even if conventional influenza vaccines represent the most effective tool for preventing virus infections, they are not completely effective in patients with severe chronic disease and immunocompromised and new small molecules have emerged to prevent and control the influenza viruses. Thus, the attention of chemists is continuously focused on the synthesis of new antiviral drugs able to interact with the different molecular targets involved in the virus replication cycle. To date, different classes of influenza viruses inhibitors able to target neuraminidase enzyme, hemagglutinin protein, Matrix-2 (M2) protein ion channel, nucleoprotein or RNAdependent RNA polymerase have been synthesized using several synthetic strategies comprising the chemical modification of currently used drugs. The best results, in terms of inhibitory activity, are in the nanomolar range and have been obtained from the chemical modification of clinically used drugs such as Peramivir, Zanamivir, Oseltamir, Rimantadine, as well as sialylated molecules, and hydroxypyridinone derivatives. The aim of this review is to report, covering the period 2016-2022, the most recent routes related to the synthesis of effective influenza virus inhibitors.