Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: SELVITRAN 75  
Dosage form and strength: Capsules and 75 mg  
PROFESSIONAL INFORMATION FOR SELVITRAN 75 mg  
SCHEDULING STATUS  
S4  
1. NAME OF THE MEDICINE  
SELVITRAN 75 (capsules)  
2. QUALITATIVE AND QUANTITATIVE COMPOSITION  
Each capsule contains 75 mg oseltamivir phosphate.  
Sugar free  
For full list of excipients, see section 6.1  
3. PHARMACEUTICAL FORM  
Size 2 hard gelatin capsules with a light-yellow opaque cap and grey opaque body. ‘H’ is printed on the cap  
and ‘5’ is printed on the body with blue ink. The capsules are filled with a white to off-white granular powder.  
4. CLINICAL PARTICULARS  
4.1 Therapeutic indications  
Treatment:  
SELVITRAN 75 is indicated for the treatment of influenza in adults and children ≥1 year of age.  
Prophylaxis:  
SELVITRAN 75 is indicated for the prophylaxis of influenza in adults and children ≥ 1 year of age.  
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Product proprietary name: SELVITRAN 75  
Dosage form and strength: Capsules and 75 mg  
4.2 Posology and method of administration  
Posology  
Treatment of Influenza  
Adults and adolescents 13 years and over:  
Treatment should be initiated as soon as possible within the first two days of onset of symptoms of influenza.  
The recommended oral dose of SELVITRAN 75 capsules in adults and adolescents ≥ 13 years is a 75 mg  
capsule twice daily, for 5 days.  
Paediatric population:  
Children weighing > 40 kg or ≥ 8 years who are able to swallow capsules, may also receive treatment with  
a 75mg twice daily.  
Body  
Recommended dose for  
5 days  
Weight  
> 40 kg  
75 mg twice daily  
Children ≥ 1 year of age may receive weight appropriate doses of SELVITRAN for treatment by opening  
the capsule and mixing with 5 mL of water then drawing out the appropriate dose (see method of  
administration). The dosage to be given according to weight is detailed in the below:  
Body weight recommended dose for 5 days.  
≤15kg  
30 mg twice daily  
45 mg twice daily  
60 mg twice daily  
>15 kg to 23 kg  
>23 kg to 40 kg  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: SELVITRAN 75  
Dosage form and strength: Capsules and 75 mg  
The safety and efficacy of SELVITRAN 75 in children under 1 year has not been established. SELVITRAN  
75 should not be used in children under 1 year of age.  
Post -exposure prevention:  
The recommended oral dose for prevention of influenza following close contact with an infected individual  
is SELVITRAN 75 once daily for 10 days for adolescents (13 to 17 years of age) and adults.  
Therapy should begin as soon as possible within two days of exposure to an infected individual.  
Paediatric population  
Children weighing > 40 kg, who are able to swallow capsules, may also receive prophylaxis with a 75 mg  
capsule once daily for 10 days.  
Body weight  
Recommended dose for  
10 days  
>40 kg  
75 mg once daily  
Children ≥ 1 year of age may receive weight appropriate doses of [PN] for prophylaxis by opening the  
capsule and mixing with 5 mL of water then drawing out the appropriate dose (see method of  
administration). The dosage to be given according to weight is detailed in the below:  
Body weight  
≤15kg  
recommended dose for 10 days  
30mg once daily  
>15 kg to 23 kg  
>23 kg to 40 kg  
45mg once daily  
60mg twice daily  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: SELVITRAN 75  
Dosage form and strength: Capsules and 75 mg  
The safety and efficacy of SELVITRAN 75 in children under 1 year has not been established. SELVITRAN  
75 should not be used in children under 1 year of age.  
Prevention during an influenza epidemic in the community:  
The recommended dose for prevention of influenza during a community outbreak is 75 mg oseltamivir once  
daily for up to 6 weeks. The duration of protection lasts for as long as dosing is continued.  
Special populations  
Elderly population  
No dose adjustment is required for elderly patients in the treatment or prophylaxis of influenza.  
Renal impairment  
Treatment of influenza  
No dose adjustment is necessary for patients with creatinine clearance above 60 mL/min. In patients with a  
creatinine clearance of > 30- 60 mL/min, it is recommended that the treatment dose be reduced to 30 mg of  
SELVITRAN twice daily for 5 days. In patients with a creatinine clearance of 10- 30 mL/min, it is  
recommended that the dose be reduced to 30 mg of SELVITRAN once daily for 5 days. In patients  
undergoing routine haemodialysis an initial dose of 30 mg SELVITRAN can be administered prior to the  
start of dialysis if influenza symptoms develop during the 48 hours between dialysis sessions. To maintain  
plasma concentrations at a therapeutic level, a dose of 30 mg should be administered after every  
haemodialysis session. For peritoneal dialysis an initial dose of 30 mg of SELVITRAN administered prior to  
the start of dialysis followed by further 30 mg doses administered every 5 days is recommended for  
treatment. The pharmacokinetics of SELVITRAN have not been studies in patients with end-stage renal  
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Product proprietary name: SELVITRAN 75  
Dosage form and strength: Capsules and 75 mg  
disease (i.e., creatinine clearance < 10 mL/min) not undergoing dialysis. Hence, dosing recommendation  
cannot be provided for this group.  
Prevention of influenza:  
No dose adjustment is necessary for patients with creatinine clearance above 60 mL/min. In patients with a  
creatinine clearance of > 30- 60 mL/min, it is recommended that the treatment dose be reduced to 30 mg of  
SELVITRAN once daily. In patients with a creatinine clearance of 10- 30 mL/min receiving SELVITRAN, it  
is recommended that the dose be reduced to 30 mg of SELVITRAN every other day. In patients undergoing  
routine haemodialysis an initial dose of 30 mg SELVITRAN can be administered prior to the start of dialysis.  
To maintain plasma concentrations at a therapeutic level, a dose of 30 mg should be administered after  
every alternate haemodialysis session. For peritoneal dialysis an initial dose of 30 mg of SELVITRAN  
administered prior to the start of dialysis followed by further 30 mg doses administered every 7 days is  
recommended for prevention. The pharmacokinetics of SELVITRAN have not been studies in patients with  
end-stage renal disease (i.e., creatinine clearance < 10 mL/min) not undergoing dialysis. Hence, dosing  
recommendation cannot be provided for this group.  
Hepatic impairment:  
No dose adjustment is required either for treatment or prevention of influenza in patients with mild or  
moderate hepatic dysfunction, (see section 5.2, Special Populations). The safety and pharmacokinetics in  
patients with severe hepatic impairment have not been studies.  
Method of administration  
Oral use.  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: SELVITRAN 75  
Dosage form and strength: Capsules and 75 mg  
SELVITRAN 75 may be taken with or without food. However, SELVITRAN 75 taken with food may enhance  
tolerability in some patients.  
When adults, adolescents or children who are unable to swallow SELVITRAN 75 capsules:  
During situations when adults, adolescents or children who are unable to swallow capsules may receive  
appropriate doses of SELVITRAN 75 by opening capsules and pouring the contents of capsule into a  
suitable, small amount (1 teaspoon maximum) of sweetened food product such as regular or sugar-free  
chocolate syrup, honey, light brown or table sugar dissolved in water, dessert toppings, sweetened  
condensed milk, apple sauce or yoghurt to mask the bitter taste. The mixture should be stirred, and the  
entire contents given to the patient. The mixture must be swallowed immediately after its preparation.  
When using the 75 mg capsules: for patients requiring 30 – 60 mg doses, follow these instructions to ensure  
proper dosing:  
1. Hold one SELVITRAN 75 capsule over a small bowl, the capsule must be carefully pulled open, and  
the powder poured into the bowl.  
2. Add 5 mL water to the powder using a graduated syringe. Stir for approximately two minutes.  
3. Draw up into the syringe the correct amount of mixture from the bowl. See the table below to  
determine the correct amount of mixture. It is not necessary to draw up any undissolved white  
powder as this is inert material. Push down the plunger of the syringe to empty its entire contents  
into a second bowl. Discard any unused mixture.  
Recommended  
dose  
Required amount  
of SELVITRAN  
75 mixture for  
one dose  
30 mg  
45 mg  
2 mL  
3 mL  
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Product proprietary name: SELVITRAN 75  
Dosage form and strength: Capsules and 75 mg  
60 mg  
4 mL  
4.3 Contraindications  
Hypersensitivity to oseltamivir phosphate or to any of the excipients listed in section 6.1.  
4.4 Special warnings and precautions for use  
SELVITRAN 75 is effective only against illness caused by influenza viruses. There is no evidence for efficacy  
of SELVITRAN 75 in any illness caused by medicines other than influenza viruses types A and B (see  
section 5.1). SELVITRAN 75 is not a substitute for influenza vaccination. Use of SELVITRAN 75 must not  
affect the evaluation of individuals for annual influenza vaccination. The protection against influenza lasts  
only as long as SELVITRAN 75 is administered. SELVITRAN 75 should be used for the treatment and  
prevention of influenza only when reliable epidemiological data indicate that influenza virus is circulating in  
community.  
Susceptibility of circulating influenza virus strains to oseltamivir has been shown to be highly variable (see  
section 5.1). Therefore, prescribers should take into account the most recent information available on  
oseltamivir susceptibility patterns of the currently circulating viruses when deciding whether to use  
SELVITRAN 75. Resistance of influenza viruses to SELVITRAN 75 have been reported. The prevalence of  
virus resistance and virus strains on subtypes differs between countries and seasons. In South Africa where  
H1N1 viruses predominated among circulating strains, 100 % [225/ 225] of H1N1 viruses tested in 2008  
were resistant to oseltamivir phosphate. The resistance of the predominant virus to oseltamivir phosphate  
generally changes from season to season. Updated local surveillance data from the National Institute for  
Communicable Diseases (NICD) should be consulted for information on seasonal prevalence of medicine  
resistant viruses  
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Product proprietary name: SELVITRAN 75  
Dosage form and strength: Capsules and 75 mg  
Severe concomitant condition  
No information is available regarding the safety and efficacy ofoseltamivir in patients with any medical  
condition sufficiently severe or unstable to be considered at imminent risk of requiring hospitalisation.  
Immunocompromised patients  
The efficacy of oseltamivir in either treatment or prophylaxis of influenza in immunocompromised patients  
has not been firmly established (see section 5.1).  
Severe renal impairment  
Dose adjustment is recommended for patients with creatinine clearance of 10-30 mL/min for the treatment  
of influenza and the prophylaxis of influenza. No dosing recommendation is available for patients undergoing  
routine haemodialysis and continuous peritoneal dialysis with end stage renal disease and for patients with  
creatinine clearance of ≤ 10 mL/min (see sections 4.2 and 5.2).  
Neuropsychiatric events  
Neuropsychiatric events such as convulsions, abnormal and inappropriate behaviour, disturbances in  
consciousness, hallucinations and delirium have been reported during SELVITRAN 75 administration in  
patients with influenza, especially in children and adolescents. These events are also experienced by  
patients with influenza without oseltamivir administration. In some cases, the delirium resulted in accidental  
self-injury and death. These events occurred mostly within the first few days of taking SELVITRAN 75.  
Patients, and especially paediatric and adolescent patients, taking SELVITRAN 75 should be carefully  
monitored.  
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Product proprietary name: SELVITRAN 75  
Dosage form and strength: Capsules and 75 mg  
4.5 Interaction with other medicines and other forms of interaction  
Pharmacokinetic properties of oseltamivir, such as low protein binding and metabolism independent of the  
CYP450 and glucuronidase systems suggest that clinically significant medicine interactions are unlikely.  
SELVITRAN 75 is extensively converted to the active compound by esterases, located predominantly in the  
liver. Interactions involving competition for esterases have not been extensively reported in the literature.  
Low protein binding of SELVITRAN 75 and the active metabolite do not suggest the probability of medicine  
displacement interactions. In vitro studies demonstrated that neither oseltamivir nor the active metabolite is  
a good substrate for P450 mixed-function oxidases or for glucuronyl transferases, see section 5.2.  
There is no mechanistic basis for an interaction with oral contraceptives.  
Probenecid  
No dose adjustment is required when co-administering with probenecid in patients with normal renal  
function. Co-administration of probenecid, a potent inhibitor of the anionic pathway of renal tubular secretion,  
results in an approximate 2- fold increase in exposure to the active metabolite of oseltamivir.  
Amoxicillin  
Oseltamivir has no kinetic interaction with amoxicillin, which is eliminated via the same pathway, suggesting  
that oseltamivir interaction with this pathway is weak.  
Renal elimination  
Clinically important medicine interactions involving competition for renal tubular secretion are unlikely, due  
to the known safety margin for most of these medicines, the elimination characteristics of the active  
metabolite (glomerular filtration and anionic tubular secretion) and the excretion capacity of these pathways.  
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Product proprietary name: SELVITRAN 75  
Dosage form and strength: Capsules and 75 mg  
However, care should be taken when prescribing oseltamivir in patients when taking co-excreted medicines  
with a narrow therapeutic margin (e.g., chlorpropamide, methothrexate, phenylbutazone).  
Cimetidine, a non-specific inhibitor of cytochrome P450 isoforms and competitor for renal tubular secretion  
of basic or cationic medicines have no effect on plasma levels of SELVITRAN 75 or its active metabolite.  
Co-administration with paracetamol does not alter plasma levels of SELVITRAN 75, its active metabolite, or  
paracetamol.  
Additional information  
No pharmacokinetic interactions between oseltamivir or its major metabolite have been observed when co-  
administering SELVITRAN 75 with paracetamol, acetyl-salicylic acid, cimetidine or with antacids  
(magnesium and aluminium hydroxides and calcium carbonates).  
In phase III treatment and prophylaxis clinical studies, oseltamivir has been administered with commonly  
used medicines such as ACE inhibitors (enalapril,captopril), thiazide diuretics (bendrofluazide), antibiotics  
(penicillin, cephalosporin, azithromycin, erythromycin and doxycycline), H2-receptor blockers (ranitidine,  
cimetidine), beta-blockers (propranolol), xanthines (theophylline), sympathomimetics (pseudoephedrine),  
opioids (codeine), corticosteroids, inhaled bronchodilators, and analgesic medicines (aspirin, ibuprofen and  
paracetamol). No change in adverse event profile or frequency has been observed as a result of co  
administration of SELVITRAN 75 with these compounds.  
4.6 Fertility, pregnancy and lactation  
Pregnancy  
Safety and efficacy have not been established.  
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Product proprietary name: SELVITRAN 75  
Dosage form and strength: Capsules and 75 mg  
While no controlled clinical trials have been conducted on the use of oseltamivir in pregnant women, there  
are limited data available from post marketing and retrospective observational surveillance reports where  
pregnant women have used oseltamivir; the data are insufficient to evaluate the potential risk for  
SELVITRAN 75 to cause foetal malformations or foetal toxicity, or to make a recommendation regarding its  
use during pregnancy.  
Breastfeeding  
In lactating rats, oseltamivir and the active metabolite are excreted in the milk. Limited information is  
available on infants breastfed by mothers taking SELVITRAN 75 and on excretion of SELVITRAN 75 in  
breast milk. Limited data demonstrated that low levels of oseltamivir and the active metabolite were detected  
in breast milk. Mothers on treatment with SELVITRAN 75 should not breastfeed their infants.  
Fertility  
Based on preclinical data, there is no evidence that SELVITRAN 75 has an effect on male or female fertility.  
4.7 Effects on ability to drive and use machines  
SELVITRAN 75 may cause side effects such as confusion, delusions, delirium, hallucinations, visual  
disturbances, dizziness and fatigue which may impact on a patient’s ability to drive and use machines.  
4.8 Undesirable effects  
a) Summary of the safety profiles  
In adults/ adolescents, the most frequently reported adverse reactions (ARs) were nausea and vomiting.  
The following serious adverse reactions have been reported anaphylactic and anaphylactoid reactions,  
hepatic disorders (fulminant hepatitis, hepatic function disorder and jaundice),  
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Product proprietary name: SELVITRAN 75  
Dosage form and strength: Capsules and 75 mg  
angioedema, Stevens-Johnson syndrome and toxic epidermal necrolysis, gastrointestinal bleeding and  
neuropsychiatric disorders. (Regarding neuropsychiatric disorders, see section 4.4)  
b. Tabulated summary of adverse reactions  
Table 1 Adverse reactions of SELVITRAN 75 for treatment and prevention of influenza in adults  
Infections and infestations  
Frequent:  
Bronchitis, acute bronchitis, Herpes simplex,  
Nasopharyngitis, Upper respiratory tract infections, Sinusitis  
Blood and lymphatic system disorders  
Less frequent:  
Thrombocytopenia  
Frequency unknown:  
Immune system disorders  
Less frequent:  
Anemia,  
Hypersensitivity reaction, anaphylactic reactions,  
anaphylactoid reactions  
Psychiatric disorders  
Less frequent:  
Agitation, abnormal behaviour, anxiety, confusion, delusions,  
delirium, hallucination, nightmares, self-injury  
Nervous system disorders  
Frequent:  
Headache, vertigo, insomnia  
Less frequent:  
Eye disorders  
Altered level of consciousness, convulsion  
Less frequent  
Visual disturbance  
Cardiac disorders  
Less frequent:  
Cardiac dysrhythmia  
Respiratory, thoracic and mediastinal disorders  
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Dosage form and strength: Capsules and 75 mg  
Frequent:  
Cough, sore throat, rhinorrhea,  
Nasal congestion, epistaxis  
Frequency unknown  
Gastrointestinal disorders  
Frequent:  
Asthma (including aggravated)  
Nausea, vomiting, abdominal pain (including upper  
abdominal pain), dyspepsia, diarrhoea  
Less frequent:  
Gastrointestinal bleedings, haemorrhagic colitis  
Hepato-biliary disorders  
Less frequent:  
Elevated liver enzymes, fulminant hepatitis, hepatic  
failure,hepatitis  
Skin and subcutaneous tissue disorders  
Less frequent: Eczema, dermatitis, rash, urticaria, angioedema, erythema  
multiforme, Stevens-Johnson syndrome, toxic epidermal  
necrolysis  
General disorders and administration site conditions  
Frequent: Pain, dizziness (including vertigo), fatigue, pyrexia, pain in  
limb  
Table 2 Adverse reactions of SELVITRAN 75 for treatment and prevention of influenza in children  
Infections and infestations  
Frequent:  
Otitis media, pneumonia, sinusitis, bronchitis,  
Blood and lymphatic system disorders  
Frequent:  
Lymphadenopathy  
Nervous system disorders  
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Dosage form and strength: Capsules and 75 mg  
Frequent:  
Headache  
Eye disorders  
Frequent:  
Conjunctivitis (including red eyes, eye discharge and eye  
pain)  
Ear and labyrinth disorders  
Frequent:  
Ear disorder  
Less frequent:  
Tympanic membrane disorder  
Respiratory, thoracic and mediastinal disorders  
Frequent:  
Cough, nasal congestion,asthma (including aggravated),  
epistaxis, rhinorrhoea  
Gastrointestinal disorders  
Frequent:  
Vomiting, diarrhoea, abdominal pain (including upper  
abdominal pain), nausea,dyspepsia  
Skin and subcutaneous tissue disorders  
Less frequent:  
Dermatitis (including allergic and atopic dermatitis)  
General disorders and administration site conditions  
Less frequent  
Dizziness, fatigue  
c. Description of selected adverse reactions  
Psychiatric disorders and nervous system disorders influenza can be associated with a variety of neurologic  
and behavioural symptoms which can include events such as hallucinations, delirium, and abnormal  
behaviour, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis  
or encephalopathy but can occur without obvious severe disease.  
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Hepato-biliary disorders  
Hepato-biliary system disorders, including hepatitis and elevated liver enzymes in patients with influenza-  
like illness. These cases include fatal fulminant hepatitis/hepatic failure.  
Reporting of suspected adverse effects  
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued  
monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any  
suspected adverse to report to SAHPRA via the “6.04 Adverse Drug Reactions Reporting Form”, found  
online under SAHPRA’s publications: https://www.sahpra.org.za/publications/Index/8 or to the Holder of  
certificate of registration through the mail: pvg.cdma@heterogroups.com.  
4.9 Overdose  
Anticipated manifestations of acute overdose would be nausea, with or without accompanying emesis.  
Treatment for overdose is symptomatic.  
5 Pharmacological properties  
5.1 Pharmacodynamic properties  
Pharmacotherapeutic group: Antivirals for systemic use, neuraminidase inhibitors ATC code: J05AH02  
Oseltamivir phosphate is a pro-drug of the active metabolite (oseltamivir carboxylate). The active metabolite  
is a selective inhibitor of influenza virus neuraminidase enzymes, which are glycoproteins found on the virion  
surface. Viral neuraminidase is essential for both 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.  
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Oseltamivir carboxylate inhibits influenza A and B neuraminidases in vitro. Oseltamivir phosphate inhibits  
influenza virus infection and replication in vitro. Oseltamivir given orally inhibits influenza A and B virus  
replication and pathogenicity in vivo in animal models of influenza infection at antiviral exposures similar to  
that achieved in man with 75 mg twice daily. The active metabolite reduces shedding of both influenza A  
and B virus by inhibiting the release of infectious virus from the infected cells.  
5.2 Pharmacokinetic properties  
Absorption:  
Oseltamivir is readily absorbed from the gastrointestinal tract after oral administration of oseltamivir  
phosphate (pro-drug) and is extensively converted predominantly by hepatic esterases to the active  
metabolite (oseltamivir carboxylate). Plasma concentrations of the active metabolite are measurable within  
30 minutes, reach near maximal levels in 2 to 3 hours post dose, and substantially exceed (> 20-fold) those  
of the pro-drug.  
At least 75 % of an oral dose reaches the systemic circulation as the active metabolite. Exposure to thepro-  
drug is less than 5 % relative to the the active metabolite. Plasma concentrations of both pro-drug and active  
metabolite are proportional to dose and are unaffected by co-administration with food (see section 4.2).  
Distribution  
The mean volume of distribution (Vss) of the active metabolite is approximately 23 litres in humans, a  
volume equivalent to extracellular body fluid. The active moiety reaches all key sites of influenza infection  
as shown by studies in the ferret, rat and rabbit.  
In these studies, antiviral concentrations of the active metabolite were seen in the lung, bronchoalveolar  
lavage, nasal mucosa, middle ear and trachea following oral administration of doses of oseltamivir  
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phosphate. The binding of the active metabolite to human plasma protein is negligible (approximately 3 %).  
The binding of the pro-drug to human plasma protein is 42 %. These levels are insufficient to cause  
significant medicine interactions.  
Biotransformation  
Oseltamivir phosphate is extensively converted to the active metabolite by esterases located predominantly  
in the liver. Neither oseltamivir nor the active metabolite is substrates for or inhibitors of cytochrome P450  
isoforms, (see section 4.5).  
Elimination  
Absorbed oseltamivir is primarily (> 90 %) eliminated by conversion to the active metabolite. The active  
metabolite is not further metabolised and is eliminated in the urine. Peak plasma concentrations of the active  
metabolite decline, with a half-life of 6- 10 hours in most subjects. The active drug is eliminated entirely (>  
99 %) by renal excretion. Renal clearance (18,8 L/h) exceeds glomerular filtration rate (7,5 L/h) indicating  
that tubular secretion in addition to glomerular filtration occurs. Less than 20 % of an oral radio-labelled dose  
is eliminated in faeces.  
Pharmacokinetics in special population  
Patients with renal impairment:  
Administration of 100 mg of oseltamivir twice daily for five days to patients with various degrees of renal  
impairment showed that exposure to the active metabolite is inversely proportional to declining renal  
function.  
Treatment of influenza:  
No dose adjustment is necessary for patients with creatinine clearance above 60 mL/min. In patients with a  
creatinine clearance of > 30- 60 mL/min, it is recommended that the treatment dose be reduced to 30 mg of  
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oseltamivir twice daily for 5 days. In patients with a creatinine clearance of 10- 30 mL/min, it is recommended  
that the dose be reduced to 30 mg of oseltamivir once daily for 5 days. In patients undergoing routine  
haemodialysis an initial dose of 30 mg oseltamivir can be administered prior to the start of dialysis if influenza  
symptoms develop during the 48 hours between dialysis sessions. To maintain plasma concentrations at a  
therapeutic level, a dose of 30 mg should be administered after every haemodialysis session. For peritoneal  
dialysis an initial dose of 30 mg of oseltamivir administered prior to the start of dialysis followed by further  
30 mg doses administered every 5 days is recommended for treatment. The pharmacokinetics of oseltamivir  
have not been studies in patients with end-stage renal disease (i.e., creatinine clearance < 10 mL/min) not  
undergoing dialysis. Hence, dosing recommendation cannot be provided for this group.  
Prophylaxis of influenza:  
No dose adjustment is necessary for patients with creatinine clearance above 60 mL/min. In patients with a  
creatinine clearance of > 30- 60 mL/min, it is recommended that the treatment dose be reduced to 30 mg of  
oseltamivir once daily. In patients with a creatinine clearance of 10- 30 mL/min receiving oseltamivir, it is  
recommended that the dose be reduced to 30 mg of oseltamivir every other day. In patients undergoing  
routine haemodialysis an initial dose of 30 mg oseltamivir can be administered prior to the start of dialysis.  
To maintain plasma concentrations at a therapeutic level, a dose of 30 mg should be administered after  
every alternate haemodialysis session. For peritoneal dialysis an initial dose of 30 mg of oseltamivir  
administered prior to the start of dialysis followed by further 30 mg doses administered every 7 days is  
recommended for prevention. The pharmacokinetics of oseltamivir have not been studies in patients with  
end-stage renal disease (i.e., creatinine clearance < 10 mL/min) not undergoing dialysis. Hence, dosing  
recommendation cannot be provided for this group.  
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Dosage form and strength: Capsules and 75 mg  
Patients with hepatic impairment:  
In-vitro studies have shown that exposure to oseltamivir is not expected to be increased significantly nor is  
exposure to the active metabolite expected to be significantly decreased in patients with hepatic impairment  
(see section 4.2). The safety and pharmacokinetics in patients with severe hepatic impairment have not  
been studied.  
Elderly:  
Exposure to the active metabolite at steady state was 25- 35 % higher in elderly (age range 65-78) compared  
to young adults who were given comparable doses of oseltamivir. Half-lives observed in the elderly were  
similar to those seen in young adults. On the basis of medicine exposure and tolerability, dosage  
adjustments are not required for elderly patients for either the treatment or prophylaxis of influenza unless  
there is evidence of moderate or severe renal impairment (creatinine clearance below 60 ml/min) (see  
section 4.2).  
Immunocompromised Patients.  
Population pharmacokinetic analyses indicate that treatment of adult and paediatric (< 18 years old)  
immunocompromised patients with oseltamivir results in an increased predicted exposure (from  
approximately 5 % up to 50 %) to the active metabolite when compared to non-immunocompromised  
patients with comparable creatinine clearance. Due to the wide safe margin of the active metabolite, no  
dose adjustments are required in patients due to their immunocompromised status.  
Pharmacokinetic and pharmacodynamic analyses from two studies in immunocompromised patients  
indicated that there was no meaningful additional benefit in exposures higher than those achieved after the  
administration of the standard dose.  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: SELVITRAN 75  
Dosage form and strength: Capsules and 75 mg  
Paediatric population  
Children ≥ 1 year of age:  
The pharmacokinetics of oseltamivir has been evaluated in single dose pharmacokinetic studies in children  
aged 1 to 16 years. Multiple dose pharmacokinetics was studied in a small number of children aged 3-12  
years enrolled in a clinical trial. The rate of clearance of the active metabolite, corrected for bodyweight, was  
faster in children than in adults, resulting in lower exposure in these children for a given mg/kg dose. The  
rate of clearance of the active metabolite increased with decreasing age over the age range 3 to 16 years.  
Doses of 2 mg/kg yield oseltamivir carboxylate exposures comparable to those achieved in adults receiving  
a single 75 mg capsule dose (approximately 1 mg/kg). The pharmacokinetics of oseltamivir in children over  
12 years of age are similar to those in adults.  
6. Pharmaceutical particulars  
6.1 List of excipients  
Oseltamivir phosphate  
Croscarmellose sodium  
Dehydrated alcohol  
Povidone  
Pregelatinised starch  
Talc  
Sodium stearyl fumarate.  
Hard gelatin capsule shells  
Printing ink  
6.2 Incompatibilities  
Not applicable  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: SELVITRAN 75  
Dosage form and strength: Capsules and 75 mg  
6.3 Shelf life  
24 months  
6.4 Special precautions for storage  
Store at or below 25 °C. Protect from light and moisture.  
Keep the blisters in the outer carton until required for use.  
KEEP OUT OF REACH OF CHILDREN.  
6.5 Nature and contents of container  
Blister strips consisting of clear triplex film (PVC/PE/PVdC) and plain peelable lidding foil.  
Pack sizes: 10 x 10 Peelable blister pack  
1 x 10 Peelable blister pack  
6.6 Special precautions for disposal and other handling  
No special requirements required.  
7 HOLDER OF CERTIFICATE OF REGISTRATION  
Hetero Drugs South Africa (Pty) Ltd.,  
Waterfall Corporate Campus,  
Building No.2, First Floor, 74 Waterfall Drive  
Midrand, 2066  
Telephone: 012 644 1220  
Fax number: 012 644 1564  
e-mail address: nokuthula.n@heterodrugs.com  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: SELVITRAN 75  
Dosage form and strength: Capsules and 75 mg  
8 REGISTRATION NUMBER (S)  
52/20.2.8/0847  
9 DATE OF FIRST AUTHORISATION/  
04 October 2022  
10 DATE OF REVISION OF THE TEXT  
28/05/2024  
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Applicant/PHRC: Hetero Drugs South Africa (Pty) Ltd.  
Product proprietary name: SELVITRAN 75  
Dosage form and strength: Capsules and 75 mg  
May 2024  
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