What alternative influenza antiviral, chemically unrelated to oseltamivir, can be used in a patient who developed a rash to oseltamivir?

Alternative Influenza Antiviral for Oseltamivir Rash

Zanamivir (inhaled) is the recommended alternative influenza antiviral for patients who developed a rash to oseltamivir, as it is chemically unrelated (both are neuraminidase inhibitors but structurally distinct) and has a different side effect profile with minimal skin reactions reported. 1

Primary Alternative: Zanamivir

Mechanism and Structural Difference

• Zanamivir is a neuraminidase inhibitor like oseltamivir but is administered via inhalation rather than oral absorption, resulting in minimal systemic exposure and a distinctly different adverse event profile 1
• The inhaled route of delivery means zanamivir is deposited primarily in the oropharynx (70-87%) and lungs (7-21%), with only 4-17% absorbed systemically, compared to oseltamivir's 80% oral absorption 1
• Allergic reactions including oropharyngeal or facial edema have been reported with zanamivir during postmarketing surveillance, but skin rash is not a characteristic adverse event 1

Dosing and Administration

• Treatment dose: 10 mg (two inhalations) twice daily for 5 days 1
• Must be initiated within 48 hours of symptom onset for maximum clinical benefit 1
• The medication comes as a dry powder self-administered via a plastic inhalation device 1

Critical Contraindications and Precautions

• Do NOT use zanamivir in patients with underlying respiratory disease (asthma, COPD) due to risk of bronchospasm 1
• In one phase-I study, 1 of 13 asthmatic patients experienced bronchospasm after zanamivir administration 1
• Zanamivir is difficult to administer to critically ill patients because of the inhalation mechanism 1
• Not licensed for treatment in children <7 years of age 1

Safety Profile

• In clinical trials, adverse events were similar between zanamivir and placebo (inhaled lactose vehicle alone) 1
• Most common adverse events (each <5%): diarrhea, nausea, sinusitis, nasal symptoms, bronchitis, cough, headache, dizziness 1
• Notably, skin rash is not listed among the common or characteristic adverse events for zanamivir 1

Secondary Alternative: Peramivir

When to Consider

• Peramivir (intravenous neuraminidase inhibitor) can be considered for patients who cannot absorb oral oseltamivir, cannot tolerate oseltamivir, or cannot use inhaled zanamivir 1
• Available as an intravenous injection with comparable clinical outcomes to oseltamivir 1
• Limited data available on activity, particularly in immunocompromised patients 1

Third-Line Option: Baloxavir

Limited Role

• Baloxavir is a polymerase inhibitor (different mechanism from neuraminidase inhibitors) active against influenza A and B 1
• Small case studies showed limited efficacy in immunocompromised patients with oseltamivir- or peramivir-resistant influenza 1
• Not routinely recommended by the CDC due to limited data and emergence of resistant strains 1
• May be considered in specific cases of documented oseltamivir resistance 1

Practical Algorithm for Selection

Step 1: Assess respiratory status

• If patient has asthma, COPD, or chronic cardiopulmonary disease → Use peramivir IV (zanamivir contraindicated) 1
• If no respiratory disease → Proceed to Step 2

Step 2: Assess ability to use inhaler

• If patient can properly use dry powder inhaler and is ≥7 years old → Use zanamivir inhaled 1
• If critically ill, unable to use inhaler, or <7 years old → Use peramivir IV 1

Step 3: Timing consideration

• All alternatives must be initiated within 48 hours of symptom onset for treatment efficacy 1, 2
• Exception: Severely ill hospitalized or immunocompromised patients may benefit from treatment started >48 hours after onset 2

Common Pitfall to Avoid

• Do not assume cross-reactivity between oseltamivir and zanamivir for rash reactions - while both are neuraminidase inhibitors, their chemical structures, routes of administration, and systemic exposure profiles are sufficiently different that a rash to oseltamivir does not predict rash to zanamivir 1, 3
• Oseltamivir's most common adverse events are gastrointestinal (nausea, vomiting in 5-15%), while skin reactions including rash are listed as rare adverse events 1, 3
• The rash may have been coincidental or related to influenza illness itself rather than the medication 4