Oseltamivir

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications: 

• Treatment and prophylaxis of influenza in adults and children ≥1 year
• Treatment of infants 6-12 months of age during a pandemic influenza outbreak only, and not for endemic (seasonal) influenza use

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Pregnancy
• Breastfeeding
• Moderate to severe renal impairment (CrCl<60ml/min)
• Renal impairment (paediatric population)
• Hepatic impairment (paediatric population)
• Infections caused by agents other than influenza
• Severe concomitant conditions at imminent risk of hospitalization
• Immunocompromised patients
• Chronic cardiac disease
• Chronic respiratory disease
• Premature children (<36 weeks conceptual age)
• Newborn babies (≤4 weeks) (sus)
• Hereditary fructose intolerance (sus)

Forms avail. in SA and covered in this monograph: cap, sus

Post-exposure prophylaxis of influenza 

• >40kg: Oral (cap, sus): 75mg, dly; Treatment duration: 10 days

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Therapy should begin as soon as possible within 48 hours of exposure to an infected individual

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See additional prescribing points

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Treatment of influenza

• >40kg: Oral (cap, sus): 75mg, 12hrly; Treatment duration: 5 days (or 10 days for immunocompromised patients)

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Should be started within 48 hours of onset of symptoms

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See additional prescribing points

Paed. forms avail. in SA and covered in this monograph: cap, sus

Post-exposure prophylaxis of influenza

Younger than 12 months

• Not established for use
• During a pandemic influenza outbreak: Oral (sus): 3mg/kg, dly; Treatment duration: 10 days

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This dosing recommendation is not intended for premature infants (those with a post-conceptual age less than 36 weeks)

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A 3ml oral dispenser (graduated in 0.1ml steps) should be used for dosing children below 1 year requiring 1-3 ml of 6mg/ml oral suspension. For higher doses the 10ml syringe should be used

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Between 1-12 years

• Oral (cap, sus): According to table below; Treatment duration: 10 days

Body weight	Recommended dose	Amount of 6mg/ml oral suspension
10-15kg	30mg, dly	5ml, dly
>15-23kg	45mg, dly	7.5ml, dly
>23-40kg	60mg, dly	10ml, dly
>40kg	75mg, dly	12.5ml, dly

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Children weighing >40 kg and who are able to swallow capsules may receive a 75mg capsule daily for 10 days as an alternative to the oseltamivir suspension

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Older than 13 years

• >40kg: See adult dosage

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Therapy should begin as soon as possible within 48 hours of exposure to an infected individual

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See additional prescribing points

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Treatment of influenza 

Younger than 12 months 

• Oral (sus): 3mg/kg, 12hrly; Treatment duration: 5 days (or 10 days for immunocompromised patients)

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This dosing recommendation is not intended for premature infants (those with a post-conceptual age less than 36
weeks)

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A 3ml oral dispenser (graduated in 0.1ml steps) should be used for dosing children below 1 year requiring 1-3 ml of 6mg/ml oral suspension. For higher doses the 10ml syringe should be used

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Older than 12 months

• Oral (cap, sus): According to table below; Treatment duration: 5 days (or 10 days for immunocompromised patients)

Body weight	Recommended dose	Amount of 6mg/ml oral suspension
10-15kg	30mg, 12hrly	5ml, 12hrly
>15-23kg	45mg, 12hrly	7.5ml, 12hrly
>23-40kg	60mg, 12hrly	10ml, 12hrly
>40kg	75mg, 12hrly	12.5ml, 12hrly

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Children weighing >40 kg and who are able to swallow capsules may receive a 75mg capsule daily for 10 days as an alternative to the oseltamivir suspension

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Older than 13 years

• >40kg: See adult dosage

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Should be started within 48 hours of onset of symptoms

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See additional prescribing points 

Pregnancy

• Caution
• Influenza is associated with adverse pregnancy and foetal outcomes, with a risk of major congenital malformations, including congenital heart defects. A large amount of data on oseltamivir exposure of pregnant women from post-marketing reports and observational studies (more than 1000 exposed outcomes during the first trimester) indicate no malformative nor feto/neonatal toxicity by oseltamivir
• However, in one observational study, while the overall malformation risk was not increased, the results for major congenital heart defects diagnosed within 12 months of birth were not conclusive. In this study, the rate of major congenital heart defects following oseltamivir exposure during the first trimester was 1.76% (7 infants out of 397 pregnancies) compared to 1.01% in unexposed pregnancies from the general population (Odds Ratio 1.75, 95% Confidence Interval 0.51 to 5.98). The clinical significance of this finding is not clear, as the study had limited power. Additionally, this study was too small to reliably assess individual types of major malformations; moreover, women exposed to oseltamivir and women unexposed could not be made fully comparable, in particular, whether or not they had influenza
• Animal studies do not indicate reproductive toxicity
• The use of oseltamivir may be considered during pregnancy if necessary and after considering the available safety and benefit information and the pathogenicity of the circulating influenza virus strain

Breastfeeding

• Caution
• In lactating rats, oseltamivir and the active metabolite are excreted in milk. Very limited information is available on children breastfed by mothers taking oseltamivir and on excretion of oseltamivir in breast milk. Limited data demonstrated that oseltamivir and the active metabolite were detected in breast milk, however, the levels were low, which would result in a subtherapeutic dose to the infant. Considering this information, the pathogenicity of the circulating influenza virus strain and the underlying condition of the breastfeeding woman, administration of oseltamivir may be considered, where there are clear potential benefits to breastfeeding mothers

Fertility

• Based on preclinical data, there is no evidence that oseltamivir has an effect on male or female fertility

Renal Impairment

• CrCl>60m/min: No dose adjustment recommended
• CrCl 11-60ml/min: Caution; dose adjustment recommended 
• CrCl≤10ml/min: Use not recommended
• Paediatric population: ≤12 years: Caution; no information available

Treatment of influenza

CrCl (ml/min)	Dose
>60	No dose adjustment necessary
>30-60	30mg, 12hrly; Treatment duration: 5 days
>10-30	30mg, dly; Treatment duration: 5 days
≤10	Use not recommended
Haemodialysis patients	30 mg after each haemodialysis session
Peritoneal dialysis patients	30mg single dose

Prevention of influenza

CrCl (ml/min)	Dose
>60	No dose adjustment necessary
>30-60	30mg, dly
>10-30	30mg, on alternate days
≤10	Not recommended
Haemodialysis patients	30 mg after every alternate haemodialysis session
Peritoneal dialysis patients	30 mg, weekly

Hepatic Impairment

• No dose adjustment recommended 
• Paediatric population: Caution; no information available

Elderly

• No dose adjustment recommended

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Insomnia
• Altered level of consciousness
• Convulsion
• Agitation  
• Abnormal behaviour  
• Anxiety
• Confusion
• Delusions
• Delirium
• Hallucination
• Nightmares
• Self-injury
• Dizziness
• Fatigue

Cardiovascular Disorders

• Cardiac arrhythmia

Respiratory Disorders

• Cough  
• Sore throat
• Rhinorrhea
• Bronchitis
• Nasopharyngitis
• Upper respiratory tract infections  
• Sinusitis
• Nasal congestion (children)

Gastrointestinal Disorders

• Nausea and vomiting
• Abdominal pain  
• Dyspepsia
• Gastrointestinal bleedings  
• Haemorrhagic colitis

Hepatobiliary Disorders

• Elevated hepatic enzymes
• Hepatitis
• Hepatic failure

Musculoskeletal Disorders

• Limb pain

Skin and Subcutaneous Tissue Disorders

• Eczema
• Dermatitis
• Rash
• Urticaria
• Angioneurotic oedema
• Erythema multiforme
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis

Immune, Blood and Lymphatic System Disorders

• Thrombocytopenia  
• Hypersensitivity reaction
• Anaphylactic/anaphylactoid reactions
• Herpes simplex
• Fatigue

Sensory Disorders

• Visual disturbance
• Vertigo
• Otitis media (children)
• Conjunctivitis (children)
• Earache (children)
• Tympanic membrane disorder

Others

• Pain

• Probenecid
• Agents with a narrow therapeutic margin
• Chlorpropamide
• Methotrexate
• Phenylbutazone

• Mental status

None routine. Some cases may require

• Viral replication

Considerations for use

• Oseltamivir is not a substitute for influenza vaccination. Use of oseltamivir must not affect the evaluation of individuals for annual influenza vaccination. The protection against influenza lasts only as long as oseltamivir is administered
• Oseltamivir should be used for the treatment and prevention of influenza only when reliable epidemiological data indicate that influenza virus is circulating in the community. Susceptibility of circulating influenza virus strains to oseltamivir has been shown to be highly variable
• Prescribers should take into account the most recent information available on oseltamivir susceptibility patterns of the currently circulating viruses when deciding whether to use oseltamivir
• The use of antivirals for the treatment and prevention of influenza should be determined on the basis of official recommendations

Administration directions

Preparation of 6mg/ml oral suspension:

1. Tap the closed bottle gently several times to loosen powder

2. Measure 55mL of water by filling a measuring cup to the indicated level

3. Add all 55mL of water to the bottle and shake well for 15 seconds. The suspension will appear opaque and white to light yellow after reconstitution

4. Remove the cap and push the bottle adapter into the neck of the bottle. Close the bottle tightly with the cap (on the top of the bottle adapter

It is recommended that the oral suspension be reconstituted by the pharmacist prior to being dispensed

When suspension is not available: Using 30mg and 45mg capsules:

1. Check the required number of capsules according to the table below

Body weight	Required number of capsule(s) needed to obtain the recommended doses for  5 days treatment	Required number of capsule(s) needed to obtain the recommended doses for prevention (10 days)
≤15kg	1 capsule of 30mg, 12hrly	1 capsule of 30mg, dly
>15-23kg	1 capsule of 45mg, 12hrly	1 capsule of 45mg, dly
>23-40kg	2 capsules of 30mg, 12hrly	2 capsules of 30mg, dly

Children weighing >40kg, may receive the adult dose of 75mg, 12hrly for 5 days for treatment or 75mg once daily for 10 days for prophylaxis

2. Hold the capsule (s) over a small bowl, carefully pull the capsule(s) open and pour the powder into the bowl

3. Add a suitable, small amount (1 teaspoon (5ml) maximum) of sweetened food product to the bowl (to mask the bitter taste) and mix well

4. Stir the mixture and give the entire contents of the bowl to the patient. This mixture must be swallowed immediately after its preparation. If there is some mixture left inside the bowl, rinse the bowl with a small amount of water and have the patient drink this mixture

5. Repeat this procedure every time this medicine is taken

When suspension is not available: Using 75mg capsules for patients requiring 30-60mg doses: 

1. Hold one 75mg capsule over the small bowl, carefully pull the capsule open and pour the powder into the bowl

2. Add 5ml water to the powder using a graduated syringe. Stir for approximately 2 mins

3. Draw up into the syringe the correct amount of mixture from the bowl as per the table below and push down the plunger of the syringe to empty its entire contents into a second bowl

Body weight	Recommended dose	Required amount of Oseltamivir mixture for one dose
≤15kg	30mg	2ml
>15-23kg	45mg	3ml
>23-40kg	60mg	4ml

The recommended dose is 30mg, 45mg or 60mg, 12hrly for 5 days for treatment or 30mg, 45mg or 60mg once daily for 10 days for prophylaxis

4. In the second bowl, add a suitable, small amount (1 teaspoon (5ml) maximum) of sweetened food product and mix well

5. Stir the mixture and give the entire contents of the bowl to the patient. This mixture must be swallowed immediately after its preparation. If there is some mixture left inside the bowl, rinse the bowl with a small amount of water and have the patient drink this mixture

6. Repeat this procedure every time this medicine is taken

When suspension is not available: Using 75mg capsules for patients requiring a 75mg dose:

1. Hold one 75mg capsule over the small bowl, carefully pull the capsule open and pour the powder into the bowl

2. Add a suitable, small amount (1 teaspoon (5ml) maximum) of sweetened food product and mix well

3. Stir the mixture and give the entire contents of the bowl to the patient. This mixture must be swallowed immediately after its preparation. If there is some mixture left inside the bowl, rinse the bowl with a small amount of water and have the patient drink this mixture

4. Repeat this procedure every time this medicine is taken

Oseltamivir carboxylate is a selective inhibitor of influenza virus neuraminidase enzymes, which are glycoproteins found on the virion surface. Viral neuraminidase enzyme activity is important both for viral entry into uninfected cells and for the release of recently formed virus particles from infected cells, and for the further spread of infectious virus in the body.

Spectrum of activity: Influenza virus Type A and B

Capsule 30mg

• Oseltamivir Adco 30mg (Adcock Ingram Limited)
• Tamiflu (Roche) originator

Capsule 45mg

• Oseltamivir Adco 45mg (Adcock Ingram Limited)
• Tamiflu (Roche) originator

Capsule 75mg

• Cipla oseltamivir (Cipla Medpro)
• Oselflu (Strides Pharma SA)
• Oseltamivir Adco 75mg (Adcock Ingram Limited)
• Tamiflu (Roche) originator
• Tamygen (Mylan)

Powder for oral suspension (per 1ml) 6mg

• Tamiflu (Roche) originator