Q&A 270.3
Can zanamivir be given to patients with renal impairment or patients on renal replacement therapies?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
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Date prepared: November 2013
Background
Zanamivir is a selective inhibitor of neuraminidase, the influenza virus surface enzyme (1). Zanamivir is licensed for the treatment and post-exposure prophylaxis of both influenza A and B in adults and children ( 5 years) (1).
The normal dose of zanamivir for the treatment of influenza, by inhalation of powder, is 10mg twice daily for 5 days (1-3). This treatment course may be extended for up to 10 days if resistance to oseltamivir is suspected, although this is an unlicensed duration (2,3). The normal dose of zanamivir for post-exposure prophylaxis of influenza is 10mg once daily for 10 days (1-3).For seasonal prophylaxis, the normal dose of zanamivir is 10mg once daily for up to 28 days (1-3).
Inhaled zanamivir results in approximately 10%-20% of the inhaled dose being absorbed. The poor absorption of the drug results in low systemic concentrations and therefore there is no significant systemic exposure to zanamivir after oral inhalation. Following inhalation, zanamivir is entirely excreted unchanged in the urine (1).
Answer
Renal Impairment
The manufacturer states that zanamivir does not require dose modification in patients with impaired renal function (1, 4).
There are no data on the pharmacokinetics of zanamivir after oral inhalation in patients with renal failure (5). It has been suggested that the safety and efficacy of zanamivir is not documented in the presence of severe renal impairment, but systemic exposure is limited after oral inhalation (6). The half life is prolonged in patients with renal impairment (4,6,7) and the potential for drug accumulation should be considered (6).
However, the manufacturer states that in the severe renal impairment group from the single IV zanamivir dose trial, subjects were sampled after a dose of 2 mg or twice to four times the expected exposure from inhalation. Using the normal dosing regimen (10mg twice daily), the predicted exposure at Day 5 is 40 fold lower than what was tolerated in healthy subjects after repeated IV administration. Given the importance of local concentrations, the low systemic exposure, and the previous tolerance of much higher exposures no dose adjustment is advised (1).
Renal Replacement Therapies
There is no information about the use of zanamivir in patients undergoing renal replacement therapies. However, because of the low systemic absorption achieved from oral inhalation, zanamivir is unlikely to be removed by haemodialysis to a significant extent (5). Although dialysability is unknown (8), references advise to dose as in normal renal function for all forms of dialysis (4, 7).
Summary
Inhaled zanamivir results in approximately 10%-20% of the inhaled dose being absorbed. Following inhalation, zanamivir is entirely excreted unchanged in the urine.
The half life of zanamivir is prolonged in patients with renal impairment.
Given the importance of local concentrations, the low systemic exposure, and the previous tolerance of much higher exposures, the manufacturers recommend that no dose adjustment is required in patients with renal impairment.
There are no published data about the use of zanamivir in patients undergoing renal replacement therapies, however for the above reasons, it has been suggested that the normal dose is used in these patients.
Limitations
There are very few data available for patients with renal impairment and patients undergoing renal replacement therapies receiving zanamivir. The information in this Q&A relates only to inhaled zanamivir, it is not applicable to the use of intravenous zanamivir.
References
1) GlaxoSmithKline UK. Summary of Product Characteristics for Relenza 5mg/dose inhalation powder. Date of revision of text 29/03/2011. Accessed via: on 29/11/13.
2) Martin J (editor). British National Formulary. Accessed online via: 28/11/13.
3) BNF for Children. Accessed via: 29/11/13.
4) Ashley, C. Currie, A. editors. Renal Drug Handbook 3rd Edition. Oxford, Radcliffe Medical Press Ltd; 2009 p.783.
5) Karie S, Launay-Vacher V, Janus N, et al. Pharmacokinetics and dosage adjustment of oseltamivir and zanamivir in patients with renal failure. Nephrology Dialysis Transplantation, 2006; 21(12); 3606-8.
6) American Society of Health-System Pharmacists. AHFS Drug Information. Accessed online via: 28/11/13.
7) Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure; Dosing Guidelines for Adults and Children 5th edition. Philadelphia, American College of Physicians; 2007 p.82.
8) Bailie GR, Mason NA. 2013 Dialysis of Drugs. Renal Pharmacy Consultants, LLC. Accessed via: 20/12/13.
Quality Assurance
Prepared by
Michèle Skipp, South West Medicines Information, Bristol
Date Prepared
09/01/2014
Checked by
Julia Kuczynska, South West Medicines Information, Bristol
Date of check
20/02/2014
Search strategy
Embase (*Zanamivir OR zanamivir) AND (exp *Kidney Failure OR exp *Renal Replacement Therapy).
Medline (Zanamivir OR zanamivir) AND (exp Renal Insufficiency OR exp Renal Replacement Therapy).
Manufacturer (GlaxoSmithKline UK, Personal Communication, email 09/01/2014).
Internet search ( term “zanamivir +renal”; “zanamivir +dialysis”.
Internet search (Google search term: “zanamivir renal”; “zanamivir dialysis”).
Internet search (Cochrane Library), search term “zanamivir AND renal”; “zanamivir AND dialysis”.
In-house database. Keywords - Zanamivir.
In-house renal files and texts.
The Renal Association website:
Clinical expert, Renal Pharmacist, Royal Devon & Exeter NHS Foundation Trust.
1
Available throughNICE Evidence Search at