Oseltamivir Capsules IP 75 mg
Oseltamivir Capsules IP
Each hard gelatin capsule contains:
Oseltamivir Phosphate IP eq. to Oseltamivir…75mg
Excipients…………………………………………………. q.s.
Approved colours used in empty hard gelatin capsule shells
Hard gelatin capsule, 75mg
Oseltamivir is indicated in adults and children including full term neonates who present symptoms typical of influenza, when influenza virus is circulating in the community.
Adults, and adolescents 13 years and over
Treatment of Influenza
The recommended oral dose is 75 mg oseltamivir twice daily for 5 days for adolescents (13 to 17 years of age) and adults.
| Body Weight | Recommended dose for 5 days | Recommended dose for 10 days Immunocompromised Patients |
|---|---|---|
| > 40 kg | 75 mg twice daily | 75 mg twice daily |
Treatment should be initiated as soon as possible within the first two days of onset of symptoms of influenza.
Post-exposure prevention
The recommended dose for prevention of influenza following close contact with an infected individual is 75 mg oseltamivir once daily for 10 days for adolescents (13 to 17 years of age) and adults.
| Body Weight | Recommended dose for 10 days | Recommended dose for 10 days Immunocompromised Patients |
|---|---|---|
| > 40 kg | 75 mg once daily | 75 mg once daily |
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 (or up to 12 weeks in immuno-compromised patients).
Paediatric population
Children 1 to 12 years of age
Treatment of Influenza
The following weight-adjusted dosing regimens are recommended for treatment of infants and children 1year of age or older:
| Body Weight | Recommended dose for 5 days | Recommended dose for 10 days Immunocompromised Patients |
|---|---|---|
| 10 Kg to 15 Kg | 30 mg twice daily | 30 mg twice daily |
| > 15 Kg to 23 Kg | 45 mg twice daily | 45 mg twice daily |
| > 23 Kg to 40 Kg | 60 mg twice daily | 60 mg twice daily |
| > 40 Kg | 75 mg twice daily | 75 mg twice daily |
Treatment should be initiated as soon as possible within the first two days of onset of symptoms of influenza.
Post-exposure prevention
The recommended post-exposure prevention dose of Oseltamivir is:
| Body Weight | Recommended dose for 10 days | Recommended dose for 10 days For Immunocompromised Patients |
|---|---|---|
| > 40 kg | 75 mg once daily | 75 mg once daily |
Prevention during an influenza epidemic in the community
Prevention during an influenza epidemic has not been studied in children below 12 years of age.
Infants 0 - 12 months of age
Treatment
The recommended treatment dose for infants 0 - 12 months of age is 3 mg/kg twice daily. This is based upon pharmacokinetic and safety data indicating that this dose in infants 0 - 12 months provides plasma concentrations of the pro-drug and active metabolite that are anticipated to be clinically efficacious with a safety profile comparable to that seen in older children and adults. The following dosing regimen is recommended for treatment of infants 0 - 12 months of age:
| Body Weight | Recommended dose for 5 days | Recommended dose for 10 days** Immunocompromised Patients |
|---|---|---|
| 3 Kg | 9 mg twice daily | 9 mg twice daily |
| 4 Kg | 12 mg twice daily | 12 mg twice daily |
| 5 Kg | 15 mg twice daily | 15 mg twice daily |
| 6 Kg | 18 mg twice daily | 18 mg twice daily |
| 7 Kg | 21 mg twice daily | 21 mg twice daily |
| 8 Kg | 24 mg twice daily | 24 mg twice daily |
| 9 Kg | 27 mg twice daily | 27 mg twice daily |
| 10 Kg | 30 mg twice daily | 30 mg twice daily |
** The recommended duration in immunocompromised infants (0-12 months old) is 10 days. Treatment should be initiated as soon as possible within the first two days of onset of symptoms of influenza. This dosing recommendation is not intended for premature infants, i.e. those with a post-conceptual age less than 36 weeks. Insufficient data are available for these patients, in whom different dosing may be required due to the immaturity of physiological functions.
Post-exposure prevention
The recommended prophylaxis dose for infants less than 1 year of age during a pandemic influenza outbreak is half of the daily treatment dose. This is based upon clinical data in infants and children 1 year of age or older and adults showing that a prophylaxis dose equivalent to half the daily treatment dose is clinically efficacious for the prevention of influenza.
Prevention during an influenza epidemic in the community
Prevention during an influenza epidemic has not been studied in children 0-12 months of age.
Special populations
Hepatic impairment: No dose adjustment is required either for treatment or for prevention in patients with hepatic dysfunction. No studies have been carried out in paediatric patients with hepatic disorder.
Renal impairment
Treatment of influenza: Dose adjustment is recommended for adults and adolescents (13 to 17 years of age) with moderate or severe renal impairment. Recommended doses are detailed in the table below:
| Creatinine clearance | Recommended dose for treatment |
|---|---|
| > 60 (ml/min) | 75 mg twice daily |
| > 30 to 60 (ml/min) | 30 mg twice daily |
| > 10 to 30 (ml/min) | 30 mg once daily |
| ≤ 10 (ml/min) | Not recommended (no data available) |
| Haemodialysis patients | 30 mg after each haemodialysis session |
| Peritoneal dialysis patients | 30 mg single dose |
* Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients; the clearance of oseltamivir carboxylate is expected to be higher when automated peritoneal dialysis (APD) mode is used. Treatment mode can be switched from APD to CAPD if considered necessary by a nephrologist.
Prevention of influenza: Dose adjustment is recommended for adults and adolescents (13 to 17 years of age) with moderate or severe renal impairment as detailed in the table below:
| Creatinine clearance | Recommended dose for prevention |
|---|---|
| > 60 (ml/min) | 75 mg once daily |
| > 30 to 60 (ml/min) | 30 mg once daily |
| > 10 to 30 (ml/min) | 30 mg every second day |
| ≤ 10 (ml/min) | Not recommended (no data available) |
| Haemodialysis patients | 30 mg after every second haemodialysis session |
| Peritoneal dialysis patients | 30 mg once weekly |
* Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients; the clearance of oseltamivir carboxylate is expected to be higher when automated peritoneal dialysis (APD) mode is used. Treatment mode can be switched from APD to CAPD if considered necessary by a nephrologist.
There is insufficient clinical data available in infants and children (12 years of age and younger) with renal impairment to be able to make any dosing recommendation.
Elderly
No dose adjustment is required, unless there is evidence of moderate or severe renal impairment.
Immunocompromised patients
Treatment: For treatment of influenza, the recommended duration for immunocompromised patients is 10 days. No dose adjustment is necessary. Treatment should be initiated as soon as possible within the first two days of onset of symptoms of influenza.
Seasonal prophylaxis: Longer duration of seasonal prophylaxis up to 12 weeks has been evaluated in immuno-compromised patients.
Oseltamivir is contraindicated in patients with known serious hypersensitivity to oseltamivir or any component of the product. Severe allergic reactions have included anaphylaxis and serious skin reactions including toxic epidermal necrolysis, Stevens‐Johnson Syndrome, and erythema multiforme.
Oseltamivir is effective only against illness caused by influenza viruses. There is no evidence for efficacy of oseltamivir in any illness caused by agents other than influenza viruses.
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. 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.
Severe concomitant condition
No information is available regarding the safety and efficacy of oseltamivir 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.
Cardiac / respiratory disease
Efficacy of oseltamivir in the treatment of subjects with chronic cardiac disease and/or respiratory disease has not been established. No difference in the incidence of complications was observed between the treatment and placebo groups in this population.
Paediatric population
No data allowing a dose recommendation for premature children (<36 weeks post-conceptual age) are currently available.
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. 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.
Neuropsychiatric events
Neuropsychiatric events have been reported during administration of Oseltamivir in patients with influenza, especially in children and adolescents. These events are also experienced by patients with influenza without oseltamivir administration. Patients should be closely monitored for behavioural changes, and the benefits and risks of continuing treatment should be carefully evaluated for each patient.
Pharmacokinetic properties of oseltamivir, such as low protein binding and metabolism independent of the CYP450 and glucuronidase systems, suggest that clinically significant drug interactions via these mechanisms are unlikely.
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 drug 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 in subjects when taking co-excreted agents with a narrow therapeutic margin (e.g. chlorpropamide, methotrexate, phenylbutazone).
Additional information
No pharmacokinetic interactions between oseltamivir or its major metabolite have been observed when co-administering oseltamivir with paracetamol, acetylsalicylic acid, cimetidine, antacids (magnesium and aluminium hydroxides and calcium carbonates), rimantadine or warfarin (in subjects stable on warfarin and without influenza).
Pregnancy
Influenza is associated with adverse pregnancy and fetal 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 397pregnancies) 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
In lactating rats, oseltamivir and the active metabolite are excreted in milk. Very limited information is available on children breast-fed 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
There is no evidence that Oseltamivir has an effect on male or female fertility.
Oseltamivir has no influence on the ability to drive and use machines
Tabulated list of adverse reactions
| System Organ Class (SOC) | Very common | common | Uncommon | Rare |
|---|---|---|---|---|
| Infections and infestations | Bronchitis, Herpes simplex, Nasopharyngitis, Upper respiratory tract infections, Sinusitis | |||
| Blood and lymphatic system disorders | Thrombocytopenia | |||
| Immune system disorders | Hypersensitivity reaction | Anaphylactic reactions, Anaphylactoid reactions | ||
| Psychiatric disorders | Agitation, Abnormal behavior, Anxiety, Confusion, Delusions, Delirium, Hallucination, Nightmares, Self-injury | |||
| Nervous system disorders | Headache | Insomnia | Altered level of consciousness, Convulsion | |
| Eye disorders | Visual disturbance | |||
| Cardiac disorders | Cardiac arrhythmia | |||
| Respiratory, thoracic and mediastinal disorders | Cough, Sore throat, Rhinorrhea | |||
| Gastrointestinal disorders | Nausea | Vomiting, Abdominal pain (incl. upper abdominal pain), Dyspepsia | Gastrointestinal bleedings, Hemorrhagic colitis | |
| Hepatobiliary disorders | Elevated liver enzymes | Fulminant hepatitis, Hepatic failure, Hepatitis | ||
| Skin and subcutaneous tissue disorders | Eczema, Dermatitis, Rash, Urticaria | Angioneurotic oedema, Erythema multiforme, Stevens-Johnson syndrome, Toxic epidermal necrolysis | ||
| General disorders and administration site conditions | Pain, Dizziness (incl. vertigo), Fatigue, Pyrexia, Pain in limb |
Reporting of Suspected Adverse Reactions
Reporting suspected adverse reactions after authorization 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 email to: medico@zorvia.com
By reporting side effects, you can help provide more information on the safety of this medicine.
Reports of overdoses with oseltamivir have been received from clinical trials and during post-marketing experience. In the majority of cases reporting overdose, no adverse events were reported. Adverse events reported following overdose were similar in nature and distribution to those observed with therapeutic doses of oseltamivir. No specific antidote is known.
Paediatric population
Pediatric population overdose has been reported more frequently for children than adults and adolescents. Caution should be exercised when preparing and when administering oseltamivir products to children.
Mechanism of Action
Oseltamivir phosphate is an ethyl ester prodrug requiring ester hydrolysis for conversion to the active form, oseltamivir carboxylate. Oseltamivir carboxylate is an inhibitor of influenza virus neuraminidase affecting release of viral particles. The median IC50 values of oseltamivir against influenza A/H1N1, influenza A/H3N2, and influenza B clinical isolates were 2.5 nM (range 0.93‐4.16 nM, N=74), 0.96 nM (range 0.13‐7.95 nM, N=774), and 60 nM (20‐285 nM, N=256), respectively, in a neuraminidase assay with a fluorescently labelled MUNA substrate.
Antiviral Activity
The antiviral activity of oseltamivir carboxylate against laboratory strains and clinical isolates of influenza virus was determined in cell culture. The concentrations of oseltamivir carboxylate required for inhibition of influenza virus in cell culture were highly variable depending on the assay method used and the virus tested. The 50% and 90% effective concentrations (EC50 and EC90) were in the range of 0.0008 micromolar to greater than 35 micromolar and 0.004 micromolar to greater than 100 micromolar, respectively (1 micromolar=0.284 microgram per mL). The relationship between the antiviral activities in cell culture, inhibitory activity in the neuraminidase assay, and the inhibition of influenza virus replication in humans has not been established.
Resistance
Cell culture studies: Influenza virus isolates with reduced susceptibility to oseltamivir carboxylate have been recovered by serial passage of virus in cell culture in the presence of increasing concentrations of oseltamivir carboxylate. Reduced susceptibility of influenza virus to inhibition by oseltamivir carboxylate may be conferred by amino acid substitutions in the viral neuraminidase and/or hemagglutinin proteins.
Pharmacodynamics
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 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.
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 invivo in animal models of influenza infection at antiviral exposures similar to that achieved in man with 75 mg twice daily.
Antiviral activity of oseltamivir was supported for influenza A and B by experimental challenge studies in healthy volunteers.
Neuraminidase enzyme IC50 values for oseltamivir for clinically isolated influenza A ranged from 0.1 nM to 1.3 nM, and for influenza B was 2.6 nM. Higher IC50 values for influenza B, up to a median of 8.5 nM, have been observed in published studies.
Absorption
Oseltamivir is readily absorbed from the gastrointestinal tract after oral administration of oseltamivir phosphate (pro-drug) and is extensively converted by predominantly hepatic esterases to the active metabolite (oseltamivir carboxylate). At least 75 % of an oral dose reaches the systemic circulation as the active metabolite. Exposure to the pro-drug is less than 5 % relative to the active metabolite. Plasma concentrations of both pro-drug and active metabolite are proportional to dose and are unaffected by co-administration with food.
Distribution
The mean volume of distribution at steady state of the oseltamivir carboxylate is approximately 23 litres in humans, a volume equivalent to extracellular body fluid. Since neuraminidase activity is extracellular, oseltamivir carboxylate distributes to all sites of influenza virus spread. The binding of the oseltamivir carboxylate to human plasma protein is negligible (approximately 3 %).
Biotransformation
Oseltamivir is extensively converted to oseltamivir carboxylate by esterases located predominantly in the liver. In vitro studies demonstrated that neither oseltamivir nor the active metabolite is a substrate for, or an inhibitor of, the major cytochrome P450 isoforms. No phase 2 conjugates of either compound have been identified in vivo.
Elimination
Absorbed oseltamivir is primarily (> 90 %) eliminated by conversion to oseltamivir carboxylate. It is not further metabolised and is eliminated in the urine. Peak plasma concentrations of oseltamivir carboxylate decline with a half-life of 6 to 10 hours in most subjects. The active metabolite is eliminated entirely by renal excretion. Renal clearance (18.8l/h) exceeds glomerular filtration rate (7.5 l/h) indicating that tubular secretion occurs in addition to glomerular filtration. Less than 20 % of an oral radiolabelled dose is eliminated in faeces.
Special populations
Patients with renal impairment
Dose adjustment is recommended for adults and adolescents (13 to 17 years of age) with moderate or severe renal impairment. Administration of 100 mg oseltamivir phosphate twice daily for 5 days to patients with various degrees of renal impairment showed that exposure to oseltamivir carboxylate is inversely proportional to declining renal function.
Patients with hepatic impairment
In vitro studies have concluded 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. No dose adjustment is required either for treatment or for prevention in patients with hepatic dysfunction.
Elderly
Exposure to the active metabolite at steady state was 25 to 35% higher in older people (age 65 to 78 years) compared to adults less than 65 years of age given comparable doses of oseltamivir. Half-lives observed in older people were similar to those seen in young adults. On the basis of drug exposure and tolerability, dosage adjustments are not required for older people unless there is evidence of moderate or severe renal impairment (creatinine clearance below 60 ml/min).
Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated-dose toxicity and genotoxicity. Results of the conventional rodent carcinogenicity studies showed a trend towards a dose-dependent increase in the incidence of some tumours that are typical for the rodent strains used. Considering the margins of exposure in relation to the expected exposure in the human use, these findings do not change the benefit-risk of oseltamivir in its adopted therapeutic indications.
Teratology studies have been conducted in rats and rabbits at doses of up to 1,500 mg/kg/day and 500 mg/kg/day, respectively. No effects on foetal development were observed. A rat fertility study up to a dose of 1,500 mg/kg/day demonstrated no adverse reactions on either sex. In pre- and post-natal rat studies, prolonged parturition was noted at 1,500 mg/kg/day: the safety margin between human exposure and the highest no-effect dose (500 mg/kg/day) in rats is480-fold for oseltamivir and 44-fold for the active metabolite, respectively. Foetal exposure in the rats and rabbits was approximately 15 to 20 % of that of the mother.
In lactating rats, oseltamivir and the active metabolite are excreted in the milk. Limited data indicate that oseltamivir and the active metabolite are excreted in human milk. Extrapolation of the animal data provides estimates of 0.01 mg/day and 0.3 mg/day for the respective compounds.
A potential for skin sensitisation to oseltamivir was observed in a "maximisation" test in guinea pigs. Approximately 50 % of the animals treated with the unformulated active substance showed erythema after challenging the induced animals. Reversible irritancy of rabbits' eyes was detected.
Whereas very high oral single doses of oseltamivir phosphate salt, up to the highest dose tested (1,310 mg/kg), had no adverse reactions in adult rats, such doses resulted in toxicity in juvenile 7-day-old rat pups, including death. These reactions were seen at doses of 657 mg/kg and higher. At 500 mg/kg, no adverse reactions were seen, including upon chronic treatment (500 mg/kg/day administered from 7 to 21 days post-partum).
TamibidTM-75 (oseltamivir phosphate) is an influenza neuraminidase inhibitor (NAI), which is available as Capsules containing 75 mg of oseltamivir for oral use, in the form of oseltamivir phosphate.
Chemical name: (3R,4R,5S) ‐4‐acetylamino‐5‐amino‐3(1 ethylpropoxy) ‐1‐cyclohexene‐1‐carboxylic acid, ethyl ester, phosphate (1:1).
Molecular formula: C16H28N2O4 (free base).
Molecular weight: 312.4 for oseltamivir free base and 410.4 for oseltamivir phosphate salt
None.
Refer on pack.
As per carton.
Store below 25°C, protect from light & moisture.
Keep out of reach of children
Ruby Organics Pvt. Ltd. D-79, T.T.C., MIDC, Turbhe, Navi Mumbai-400705.
KD/37
28-04-2026