4.1. Therapeutic indications

Dectova is indicated for the treatment of complicated and potentially life-threatening influenza A or B virus infection in adult and paediatric patients (aged ≥6 months) when:

• The patient's influenza virus is known or suspected to be resistant to anti-influenza medicinal products other than zanamivir, and/or

• Other anti-viral medicinal products for treatment of influenza, including inhaled zanamivir, are not suitable for the individual patient.

Dectova should be used in accordance with official guidance.

4.2. Posology and method of administration

Posology

Treatment with Dectova should commence as soon as possible and usually within 6 days of the onset of symptoms of influenza (see section 5.1).

Adults

The recommended dose is 600 mg twice daily for 5 to 10 days given by intravenous infusion.

Paediatric population

Adolescents, children and infants should receive a weight-based dose regimen for 5 to 10 days (Table 1).

Table 1: Weight-based dose regimen by age for infants, children and adolescents with normal renal function

Age range

Weight-based dose regimen

6 months to < 6 years

14 mg/kg twice daily

≥ 6 years to < 18 years

12 mg/kg twice daily up to a maximum dose of 600 mg twice daily

The safety and efficacy of Dectova in children aged under 6 months have not been established. No data are available.

Elderly

No dose adjustment is required based on age.

Renal impairment

Adults and children (aged 6 years and over with a body weight of 50 kg or above) with creatinine clearance (CLcr) or clearance by continual renal replacement therapy (CLCRRT) < 80 mL/min should receive an initial 600 mg dose followed by twice-daily maintenance dosing according to their renal function (Table 2).

Table 2: Initial and maintenance dose regimens for adults and children (6 years and over with a body weight of 50 kg or above) with renal impairment

CLcr or CLCRRT

(mL/min or mL/min/1.73m2)*

Initial Dose

Maintenance Dose

Maintenance Dose Schedule

50 to <80

600 mg

400 mg twice daily

Begin maintenance dosing 12 hours after the initial dose

30 to <50

600 mg

250 mg twice daily

15 to <30

600 mg

150 mg twice daily

Begin maintenance dosing 24 hours after the initial dose

< 15

600 mg

60 mg twice daily

Begin maintenance dosing 48 hours after the initial dose

*CLcr or CLCRRT units in mL/min for adolescents 13 years to less than 18 years, or in mL/min/1.73m2 for children 6 years to less than 13 years.

Children and adolescents (6 years to less than 18 years with a body weight less than 50 kg), and infants and children (6 months to less than 6 years) with creatinine clearance (CLcr) or clearance by continual renal replacement therapy (CLCRRT) <80 mL/min should receive an initial dose followed by an appropriate twice‑daily maintenance dose as shown in Tables 3, 4 and 5.

Table 3: Initial and maintenance dose regimens for children and adolescents (6 years to less than 18 years, with a body weight less than 50 kg) with renal impairment

CLcr or CLCRRT)

(mL/min or mL/min/1.73m2)*

Initial dose

Maintenance Dose

Maintenance Dose Schedule

50 to <80

12 mg/kg

8 mg/kg twice daily

Begin twice daily maintenance dosing 12 hours after the initial dose

30 to <50

12 mg/kg

5 mg/kg twice daily

15 to <30

12 mg/kg

3 mg/kg twice daily

Begin twice daily maintenance dosing 24 hours after the initial dose

< 15

12 mg/kg

1.2 mg/kg twice daily

Begin twice daily maintenance dosing 48 hours after the initial dose

*CLcr or CLCRRT units in mL/min for adolescents 13 years to less than 18 years, or in mL/min/1.73m2 for children 6 years to less than 13 years.

Table 4: Initial and maintenance dose regimens for infants and children (6 months to less than 6 years, with a body weight of 42.8 kg or above) with renal impairment

CLcr or CLCRRT

(mL/min/1.73 m2)

Initial dose

Maintenance Dose

Maintenance Dose Schedule

50 to <80

600 mg

400 mg twice daily

Begin twice daily maintenance dosing 12 hours after the initial dose

30 to <50

600 mg

250 mg twice daily

15 to <30

600 mg

150 mg twice daily

Begin twice daily maintenance dosing 24 hours after the initial dose

< 15

600 mg

60 mg twice daily

Begin twice daily maintenance dosing 48 hours after the initial dose

Table 5: Initial and maintenance dose regimens for infants and children (6 months to less than 6 years, with a body weight less than 42.8 kg) with renal impairment

CLcr or CLCRRT

(mL/min/1.73 m2)

Initial dose

Maintenance Dose

Maintenance Dose Schedule

50 to <80

14 mg/kg

9.3 mg/kg twice daily

Begin twice daily maintenance dosing 12 hours after the initial dose

30 to <50

14 mg/kg

5.8 mg/kg twice daily

15 to <30

14 mg/kg

3.5 mg/kg twice daily

Begin twice daily maintenance dosing 24 hours after the initial dose

< 15

14 mg/kg

1.4 mg/kg twice daily

Begin twice daily maintenance dosing 48 hours after the initial dose

For patients on intermittent haemodialysis or intermittent peritoneal dialysis, the dose should be given after completion of the dialysis session.

For patients receiving continuous renal replacement therapy, the dose should be selected using the appropriate CRRT clearance (CLCRRT in mL/min).

Hepatic impairment

No dose modification is required (see section 5.2).

Method of administration

Intravenous use

Dectova is administered by intravenous infusion over 30 minutes.

For instructions on dilution of the medicinal product before administration, see section 6.6.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4. Special warnings and precautions for use

Renal impairment

Zanamivir is eliminated by renal clearance, therefore the dose of Dectova when administered intravenously must be reduced in patients with renal impairment (see section 4.2). All patients must have their renal function assessed before and regularly during treatment.

Serious hypersensitivity reactions

Anaphylactic reactions and serious skin reactions (including erythema multiforme, toxic epidermal necrolysis and Stevens-Johnson syndrome) have been reported with zanamivir (see section 4.8). If any hypersensitivity reaction occurs during infusion of Dectova, the infusion must be stopped immediately and appropriate management should be instituted.

Neuropsychiatric events

Influenza can be associated with a variety of neurological and behavioural symptoms. Neuropsychiatric events, including seizures, delirium, hallucination and abnormal behaviour, have been reported during administration of zanamivir in patients with influenza, especially in children and adolescents. Therefore, patients should be closely monitored for behavioural changes and the benefits and risks of continuing treatment should be carefully evaluated for each patient (see section 4.8).

Resistance in immunocompromised patients

Treatment emergent resistance is rare with zanamivir (see section 5.1). Selection of influenza resistant viruses is more likely to occur following treatment with antiviral medicinal products in immunocompromised patients, including treatment with Dectova; it is, therefore, important to monitor for resistance and consider switching to alternative therapies where appropriate.

Limitations of the clinical data

The efficacy of Dectova for the treatment of complicated influenza A or B virus infection in adults and children aged from 6 months has been inferred from:

• the in vitro activity of zanamivir;

• clinical and virological activity of zanamivir compared to placebo in a human influenza challenge study;

• levels of zanamivir in broncho-epithelial lining fluid and serum zanamivir from a broncho-alveolar lavage study;

• serum zanamivir levels from patients with complicated influenza (see section 5.1).

Risk of bacterial infections

Dectova has not been shown to reduce the risk of bacterial complications associated with influenza infection.

Excipients

This medicinal product contains 70.8 mg sodium per vial, equivalent to 3.54% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

4.5. Interaction with other medicinal products and other forms of interaction

The potential for interactions with other medicines is low, based on the known elimination pathway of zanamivir.

Zanamivir is not a substrate, inhibitor or inducer of cytochrome P450 isoenzymes nor a substrate or inhibitor of renal and hepatic transporters at clinically relevant concentrations (see section 5.2).

There was no evidence of interaction with oral oseltamivir in a clinical study.

4.6. Fertility, pregnancy and lactation

Pregnancy

There are limited data from the use of zanamivir in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

Reproductive studies performed in rats and rabbits indicated that placental transfer of zanamivir occurs and there was no evidence of teratogenicity. Results from a rat peri- and postnatal study showed no clinically meaningful impairment of offspring development. However, there is no information on placental transfer in humans.

As experience is limited, the use of Dectova in pregnancy should only be considered if the possible benefit to the patient is thought to outweigh any possible risk to the foetus.

Breast-feeding

It is unknown whether zanamivir is excreted in human milk. In rats, zanamivir has been shown to be secreted in low amounts into milk.

As experience is limited, the use of zanamivir in breast-feeding mothers should be considered only if the possible benefit to the mother is thought to outweigh any possible risk to the child.

Fertility

Animal studies indicate no clinically meaningful effects of zanamivir on male or female fertility.

4.7. Effects on ability to drive and use machines

Dectova has no or negligible influence on the ability to drive and use machines.

4.8. Undesirable effects

Summary of the safety profile

The safety profile of Dectova is based primarily on data from a single Phase II and a single Phase III study, with support from Phase I studies, a compassionate use programme, and adverse drug reactions reported for inhaled zanamivir. The frequency of adverse reactions is based on the number of reports in the adult population receiving zanamivir 600 mg twice daily intravenously in the Phase II and Phase III studies. Adverse reactions are listed by MedDRA system organ class.

The most commonly reported adverse reactions considered possibly or probably related to Dectova are alanine aminotransferase increased (2%), aspartate aminotransferase increased (1%), hepatocellular injury (1%), diarrhoea (1%) and rash (1%). The most important serious adverse reaction was hepatocellular injury, observed in two patients (<1%).

Tabulated list of adverse reactions

The frequency of adverse reactions is defined using the following convention: 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) and not known (cannot be estimated from available data).

System Organ Class

Adverse reactions

Frequency

Immune system disorders

oropharyngeal oedema

facial oedema

anaphylactic/anaphylactoid reactions

not known

Psychiatric disorders

abnormal behaviour

hallucinations

delirium

not known

Nervous system disorders

convulsions

depressed level of consciousness

not known

Gastrointestinal disorders

diarrhoea

common

Hepatobiliary disorders

alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) increased

hepatocellular injury

common

alkaline phosphatase increased

uncommon

Skin and subcutaneous tissue disorders

rash

common

urticaria

uncommon

erythema multiforme

Stevens-Johnson syndrome

toxic epidermal necrolysis

not known

Paediatric population

The adverse reaction profile in the paediatric population is based on 71 patients aged ≥6 months to <18 years in the Phase II study. Overall, the safety profile in paediatric patients was similar to that observed in adults in the clinical studies.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows

continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked

to report any suspected adverse reactions via the Yellow Card Scheme Website: http://www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

There is limited experience of overdose from administration of Dectova. There is no specific antidote to treat an overdose of this medicine. Treatment of an overdose should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. Zanamivir is cleared by renal excretion and is expected to be removed by haemodialysis.