Oseltamivir Zydus 30 mg, 45 mg and 75 mg Hard capsule

TREATMENT
OSELTAMIVIR ZYDUS is indicated for the treatment of influenza in adults and children u2265 1 year of age (see section 4.4 and Special dosage instructions).

PANDEMIC USE
OSELTAMIVIR ZYDUS is indicated for the treatment of infants 6 u2013 12 months of age during a pandemic influenza outbreak only, and not for endemic (seasonal) influenza use (see section 4.4 and Pharmacokinetics in special populations).

PROPHYLAXIS
OSELTAMIVIR ZYDUS is indicated for the prophylaxis of influenza in adults and children u2265 1 year of age.

Posology
Standard dosage
Treatment of influenza
Treatment should begin within the first or second day of onset of symptoms of influenza.
Adults and adolescents: The recommended oral dose of OSELTAMIVIR ZYDUS capsules in adults and adolescents u2265 13 years is a 75 mg capsule twice daily, for 5 days.
Children: Children weighing > 40 kg who are able to swallow capsules, may also receive treatment with a 75 mg capsule twice daily or one 30 mg capsule plus one 45 mg capsule twice a day.

Prophylaxis of influenza
Adults and adolescents
The recommended oral dose of OSELTAMIVIR ZYDUS for prophylaxis of influenza following close contact with an infected individual is 75 mg once daily for at least 10 days. Therapy should begin within two days of exposure. The recommended dose for prophylaxis during a community outbreak of influenza is 75 mg once daily. Safety and efficacy have been demonstrated for up to six weeks. The duration of protection lasts for as long as dosing is continued.
Children u2265 1 year of age
Children weighing > 40 kg, who are able to swallow capsules, may also receive prophylaxis with a 75 mg capsule once daily or one 30 mg capsule plus one 45 mg capsule once a day, for 10 days.

Special dosage instructions
Patients with 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 u2013 60 mL/min, it is recommended that the treatment dose be reduced to 30 mg of OSELTAMIVIR ZYDUS twice daily for 5 days. In patients with a creatinine clearance of 10 u2013 30 mL/min, it is recommended that the dose be reduced to 30 mg of OSELTAMIVIR ZYDUS once daily for 5 days. In patients undergoing routine haemodialysis an initial dose of 30 mg OSELTAMIVIR ZYDUS 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 ZYDUS administered prior to the start of dialysis followed by further 30 mg doses administered every 5 days is recommended for treatment (see section 4.4). The pharmacokinetics of OSELTAMIVIR ZYDUS have not been studied 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 u2013 60 mL/min, it is recommended that the dose be reduced to 30 mg of OSELTAMIVIR ZYDUS once daily. In patients with a creatinine clearance between 10 and 30 mL/min receiving OSELTAMIVIR ZYDUS, it is recommended that the dose be reduced to 30 mg of OSELTAMIVIR ZYDUS every other day. In patients undergoing routine haemodialysis an initial dose of 30 mg of OSELTAMIVIR ZYDUS 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 ZYDUS administered prior to the start of dialysis followed by further 30 mg doses administered every 7 days is recommended for prophylaxis (see Pharmacokinetics in special populations and section 4.4). The pharmacokinetics of OSELTAMIVIR ZYDUS have not been studied 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.
Patients with hepatic impairment
No dose adjustment is required for patients with mild or moderate hepatic dysfunction in the treatment or prophylaxis of influenza (see Pharmacokinetics in special populations). The safety and pharmacokinetics in patients with severe hepatic impairment have not been studied.
Immunocompromised patients
Seasonal prophylaxis in immunocompromised patients 1 year of age and older is recommended for 12 weeks. No dose adjustment is necessary.
Elderly patients
No dose adjustment is required for elderly patients in the treatment or prophylaxis of influenza (see Pharmacokinetics in special populations).
Children
The safety and efficacy of OSELTAMIVIR ZYDUS in children under 1 year have not been established (see Pharmacokinetics in special populations). OSELTAMIVIR ZYDUS should not be used in children under 1 year of age, other than during a pandemic influenza outbreak.

Method of administration
OSELTAMIVIR ZYDUS may be taken with or without food (see section 5.2). However, OSELTAMIVIR ZYDUS taken with food may enhance tolerability in some patients.
Adults, adolescents or children unable to swallow capsules
Adults, adolescents or children who are unable to swallow capsules may receive appropriate doses of OSELTAMIVIR ZYDUS by opening capsules and pouring the contents of capsules into a suitable, small amount (1 teaspoon [5 mL] maximum) of sweetened food product, such as regular or sugar-free chocolate syrup, honey (only for children two years or older), 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.

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

OSELTAMIVIR ZYDUS is effective only against illness caused by influenza viruses. There is no evidence for efficacy of OSELTAMIVIR ZYDUS in any illness caused by agents other than influenza viruses (see section 5.1).
OSELTAMIVIR ZYDUS is not a substitute for influenza vaccination. The use of OSELTAMIVIR ZYDUS must not affect the evaluation of individuals for annual influenza vaccination. The protection against influenza lasts only as long as OSELTAMIVIR ZYDUS is administered. OSELTAMIVIR ZYDUS 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 (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 OSELTAMIVIR ZYDUS.
Severe concomitant condition
No information is available regarding the safety and efficacy of OSELTAMIVIR ZYDUS 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 ZYDUS in either treatment or prophylaxis of influenza in immunocompromised patients has not been firmly established (see section 5.1).
Cardiac/respiratory disease
Efficacy of OSELTAMIVIR ZYDUS in the treatment of subjects with chronic cardiac disease and/or respiratory disease has not been established.
Severe renal impairment
Dose adjustment is recommended for both treatment and prevention in adolescents (13 to 17 years of age) and adults with severe renal impairment. No dosing recommendation is available for patients with end-stage renal disease and for patients with creatinine clearance of u2264 10 mL/min (see section 4.2). There is insufficient clinical data available in infants and children (1 year of age or older) with renal impairment to be able to make any dosing recommendation (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 oseltamivir administration in patients with influenza, especially in children and adolescents. In some cases, the delirium resulted in accidental self-injury and death. More events were reported in males than in females. These events are also experienced by patients with influenza without oseltamivir administration. Patients, and especially paediatric and adolescent patients, taking OSELTAMIVIR ZYDUS should be closely monitored for behavioural changes.
Paediatric population
No data allowing a dose recommendation for premature children (< 36 weeks post-conceptual age) are currently available. Based on limited pharmacokinetic and safety data, OSELTAMIVIR ZYDUS may only be used in infants 6 u2013 12 months of age for treatment during a pandemic influenza outbreak.

Pharmacokinetic properties of oseltamivir, such as low protein binding and metabolism independent of the CYP450 and glucuronidase systems (see section 5.2), suggest that clinically significant medicine interactions via these mechanisms are unlikely.
Oral contraceptives
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 substances, the elimination characteristics of the active metabolite (glomerular filtration and anionic tubular secretion) and the excretion capacity of these pathways. However, care should be taken when prescribing OSELTAMIVIR ZYDUS in subjects when taking co-excreted medicines with a narrow therapeutic margin (e.g. chlorpropamide, methotrexate, phenylbutazone).
Additional information
No pharmacokinetic interactions between OSELTAMIVIR ZYDUS or its major metabolite have been observed when co-administering OSELTAMIVIR ZYDUS with paracetamol, acetylsalicylic acid, cimetidine, antacids (magnesium and aluminium hydroxides and calcium carbonates), rimantadine, amantadine or warfarin (in subjects stable on warfarin and without influenza). In treatment and prophylaxis clinical studies, oseltamivir as in OSELTAMIVIR ZYDUS 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 the adverse event profile or frequency has been observed as a result of co-administration of oseltamivir with these compounds.

Safety in pregnancy and lactation has not been established. In animal reproductive studies in rats and rabbits, no teratogenic effect was observed.
Pregnancy
Influenza is associated with adverse pregnancy and fetal outcomes, with a risk of major congenital malformations, including congenital heart defects. No controlled clinical trials have been conducted on the use of OSELTAMIVIR ZYDUS in pregnant women. Safety in pregnancy has not been established.
Lactation
In lactating rats, oseltamivir and the active metabolite are excreted in milk. Very limited information is available on children breastfed by mothers taking OSELTAMIVIR ZYDUS and on excretion of OSELTAMIVIR ZYDUS in breast milk. Limited data demonstrated that oseltamivir and the active metabolite were detected in breast milk. Safety in humans has not been demonstrated in children of breastfeeding women using OSELTAMIVIR ZYDUS. Mothers on treatment with OSELTAMIVIR ZYDUS should not breastfeed their infants.
Fertility
There is no evidence that OSELTAMIVIR ZYDUS has an effect on male or female fertility.

OSELTAMIVIR ZYDUS causes side effects, such as dizziness, fatigue and delirium, which may affect the ability to drive and use machinery. Caution is advised before driving a vehicle or operating machinery until the effects of OSELTAMIVIR ZYDUS are known.

Treatment and prevention of influenza in adults and adolescents
Infections and infestations: Frequent: bronchitis, herpes simplex, nasopharyngitis, upper respiratory tract infections, sinusitis
Blood and lymphatic system disorders: Less frequent: thrombocytopenia
Immune system disorders: Less frequent: hypersensitivity reaction, anaphylactic reactions, angioedema, anaphylactoid reactions
Psychiatric disorders: Less frequent: agitation, abnormal behaviour, anxiety, confusion, delusions, delirium, hallucination, nightmares, self-injury (accidental)
Nervous system disorders: Frequent: headache, insomnia Less frequent: altered level of consciousness, convulsions
Eye disorders: Less frequent: visual disturbance
Cardiac disorders: Less frequent: cardiac dysrhythmia
Respiratory, thoracic and mediastinal disorders: Frequent: cough, sore throat, rhinorrhoea
Gastrointestinal disorders: Frequent: nausea, vomiting, abdominal pain (incl. upper abdominal pain), dyspepsia Less frequent: gastrointestinal bleedings, haemorrhagic colitis
Hepatobiliary disorders: Less frequent: elevated liver enzymes, fulminant hepatitis, hepatic failure, hepatitis
Skin and subcutaneous tissue disorders: Less frequent: eczema, dermatitis, rash, urticaria, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis
General disorders and administration site conditions: Frequent: pain, dizziness (incl. vertigo), fatigue, pyrexia, pain in limb
Treatment and prevention of influenza in children
Infections and infestations: Frequent: otitis media, bronchitis, pneumonia, sinusitis
Nervous system disorders: Frequent: headache
Eye disorders: Frequent: conjunctivitis (including red eyes, eye discharge and eye pain)
Ear and labyrinth disorders: Frequent: earache Less frequent: tympanic membrane disorder
Respiratory, thoracic and mediastinal disorders: Frequent: cough, nasal congestion, rhinorrhoea, asthma (including aggravated asthma), epistaxis
Gastrointestinal disorders: Frequent: vomiting, abdominal pain (incl. upper abdominal pain), dyspepsia, nausea, diarrhoea
Skin and subcutaneous tissue disorders: Frequent: dermatitis (including allergic and atopic dermatitis)
Post-marketing experience
Immune system disorders: Less frequent: face oedema.
Other special populations
Paediatric population (infants less than one year of age) Safety information available on oseltamivir administered for treatment of influenza in infants less than one year of age suggests that the safety profile in infants less than one year of age is similar to the established safety profile of children aged one year and older.
Older people and patients with chronic cardiac and/or respiratory disease The safety profile in older people and patients with chronic cardiac or respiratory disease is qualitatively similar to that in otherwise healthy adults/adolescents.
Children with pre-existing bronchial asthma In general, the adverse reaction profile in children with pre-existing bronchial asthma is qualitatively similar to that of otherwise healthy children.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of OSELTAMIVIR ZYDUS is important. It allows continued monitoring of the benefit/risk balance of OSELTAMIVIR ZYDUS. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

In overdose, symptoms may be the exacerbation or exaggeration of side effects. Treatment is supportive and symptomatic.