Products
Neuraminidase inhibitors are commercially available in the form of capsules, powder for oral suspension, powder inhalers, and injectables. The first agents to be approved were zanamivir (Relenza) in 1999, followed by oseltamivir (Tamiflu). Laninamivir (Inavir) was released in Japan in 2010 and Peramivir (Rapivab) in the USA in 2014. The public is most familiar with Tamiflu.
Structure and properties
The neuraminidase inhibitors are derived from -acetylneuraminic acid (Neu5Ac, sialic acid), the catalytic product of the enzyme neuraminidase (see below). They are transition-state analogues. Oseltamivir is a prodrug that is biotransformed in the body by esterases to the active metabolite oseltamivir carboxylate. Laninamiviroctanoate is the prodrug of laninamivir. Zanamivir is polar and therefore not orally bioavailable (bioavailability approximately 2%).
Effects
Neuraminidase inhibitors (ATC J05AH) have antiviral properties against influenza viruses. The effects are due to inhibition of the viral enzyme neuraminidase (sialidase). This enzyme and glycoprotein is located on the surface of the influenza virus along with hemagglutinin. It is essential for the release of newly formed viruses from infected cells and thus for the further spread of infectious viruses in the organism. Neuraminidase cuts off the terminal sialic acid to which the virus is bound after replication to the host cell surface. See also our descriptive animation on the topic: Tamiflu animation.
Indications
For the prevention and treatment of influenza (influenza, influenza A, and influenza B).
Dosage
According to the SmPC. Treatment should be started as early as possible, ideally within 36 hours of the onset of symptoms (1st or 2nd day after the first symptoms appear). Neuraminidase inhibitors are administered perorally, inhalationally (powder inhalation), and parenterally (intravenous infusion). For laninamivir, a single dose is sufficient because it is long-acting. It is one of the so-called LANIs (long-acting neuraminidase inhibitors).
Active Ingredients
- Oseltamivir (Tamiflu) – oral
- Zanamivir (Relenza) – inhalation
Not commercially available in many countries:
- Laninamivir (Inavir, Japan) – inhaled.
- Peramivir (Rapivab, Alpivab) – parenterally
Contraindications
Neuraminidase inhibitors are contraindicated in the presence of hypersensitivity. Refer to the drug label for complete precautions.
Interactions
Oseltamivir is excreted and secreted by the kidney in the form of the active metabolite oseltamivir carboxylate. Zanamivir is also eliminated primarily renally. Clinically relevant interactions are considered unlikely. Caution should be exercised with organic anions with a narrow therapeutic range such as methotrexate, which, like the neuraminidase inhibitors, are subject to active tubular secretion.
Adverse effects
The most common potential adverse effects of oseltamivir include nausea, vomiting, pain, and headache. Adverse reactions reported with zanamivir in clinical trials were comparable to placebo in type and frequency.
