DESCRIPTION
NASOVAC (Influenza Vaccine(Human,Live Attenuated)) Pandemic (H1N1), freeze dried is a live monovalent vaccine for administration by intranasal spray. The influenza vaccine contains Influenza virus cultivated on embryonated eggs.

COMPOSITION
[Propagated in Embryonated hen eggs (SPF)]
Each single dose of 0.5 ml contains:
A/17/California/2009/38 > 10⁷EID50
Gelatin (Partially hydrolyzed) 2.5%, Sorbitol 5%, L-Alanine 0.1%, L-Histidine 0.21%, Tricine 0.3%, L-Arginine hydrochloride 1.6%, Lactalbumin hydrolysate 0.35%, Phosphate buffer saline Base
Reconstitute with Sterile Water for Inhalation USP. The vaccine contains no preservatives.
Dose: 0.5 ml intranasal (spray 0.25 ml per nostril). The tip attached to the sprayer is equipped with a nozzle that produces a fine mist that is primarily deposited in the nose and nasopharynx.

NASOVAC is supplied as a vial containing freeze-dried cake in USP type 1 glass vials. A ampoule/vial containing sterile water for inhalation as diluent, syringe (for reconstitution of multi dose vaccine vial), syringe (for administration) , needle free device and intranasal spray device are also supplied along with the vaccine.
The vaccine complies with the WHO recommendation and EU decision for the pandemic.

INDICATIONS
NASOVAC, Intranasal is indicated for the active immunization of individuals above 3 years of age against influenza disease caused by pandemic (H1N1) 2009 virus.
Prophylaxis of influenza in an officially declared pandemic situation (see sections Posology and method of administration and Pharmacodynamic properties).
Pandemic influenza vaccine should be used in accordance with official guidance.

POSOLOGY AND METHOD OF ADMINISTRATION
Each freeze-dried vaccine vial is reconstituted using the entire contents of sterile water for inhalation that is supplied along with the vaccine, using the supplied syringe and vial adapter.

A dose of 0.5 ml is administered as 0.25 ml per nostril using a 0.5/1.0 ml syringe and a spray device. The sprayer device creates a fine spray that primarily deposits the vaccine in the nose and nasopharynx. A single intranasal dose is recommended for people above 3 years of age.

Adults (18-49 years), elderly (≥ 50 years) and children and adolescents (3-17 years) of age: A single dose of 0. 5 ml by intranasal route. A second dose of vaccine could be given after an interval of at least 21 days.
There is no clinical experience in children below 3 years of age.
For further information, see (Pharmacodynamic properties).

If the vaccine is not used immediately then it should be stored at 2-8ºC for no longer than 6 hours. While storing the reconstituted vaccine, ensure that the administration syringe is locked on to the needle free transfer device and the combined unit is stored at 2 to 8ºC to ensure that the opening created by the device is blocked and the syringe is also stored in a manner which prevents the proliferation of bio-burden. Any opened container remaining at the end of a session (within six hours of reconstitution) should be discarded.

The diluent supplied is specially designed for use with the vaccine. Only this diluent must be used to reconstitute the vaccine. Do not use diluents from other types of vaccine or from other manufacturers. Using an incorrect diluent may result in damage to the vaccine and/or serious reactions to those receiving the vaccine. Diluent must not be frozen, but should be kept cool.
The diluent and reconstituted vaccine should be inspected visually for any foreign particulate matter and / or variation of physical aspects prior to administration. In the event of either being observed, discard the diluent or reconstituted vaccine.

CONTRAINDICATIONS
Hypersensitivity
NASOVAC is contraindicated in individuals with a history of hypersensitivity, especially anaphylactic reactions, to eggs, egg proteins, gentamicin, gelatin, or arginine or with life-threatening reactions to previous influenza vaccinations.

Concomitant Pediatric and Adolescent Aspirin Therapy and Reye's syndrome
NASOVAC is contraindicated in children and adolescents (3-17 years of age) receiving aspirin therapy or aspirin containing-therapy, because of the association of Reye's syndrome with aspirin and wild-type influenza infection.

WARNINGS AND PRECAUTIONS
Caution is needed when administrating this vaccine to persons with a known hypersensitivity (other than anaphylactic reaction) to the active substance(s), to any of the excipients, and to residues e.g. eggs, chicken proteins, etc.
As with all vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine.
Do not administer NASOVAC to children <36 months of age since there is no clinical data available.
NASOVAC should not be administered to any individuals with asthma or children < 5 years of age with recurrent wheezing because of the potential for increased risk of wheezing post vaccination unless the potential benefit outweighs the potential risk.
Do not administer NASOVAC to individuals with severe asthma or active wheezing because these individuals have not been studied in clinical trials.
If Guillain-Barré syndrome has occurred within 6 weeks of any prior influenza vaccination, the decision to give NASOVAC should be based on careful consideration of the potential benefits and potential risks.
If the pandemic situation allows, immunisation shall be postponed in patients with severe febrile illness or acute infection.
The vaccine can be given to people with minor illnesses (e.g., diarrhea or mild upper respiratory tract infection with or without fever). However, if nasal congestion is present that might limit delivery of the vaccine to the nasal lining, then delaying of vaccination until the nasal congestion is reduced should be considered.
People who are in contact with others with severely compromised immune systems, should not get NASOVAC.
NASOVAC should under no circumstances be injected.
Administration of NASOVAC, to immunocompromised persons should be based on careful consideration of potential benefits and risks. There is no clinical data available on the use of this vaccine in immunocompromised persons.
Antibody response in such patients may be insufficient.
The safety of NASOVAC in individuals with underlying medical conditions that may predispose them to complications following wild-type influenza infection has not been established. NASOVAC should not be administered unless the potential benefit outweighs the potential risk.

DRUG INTERACTIONS
Do not administer NASOVAC to children or adolescents who are receiving aspirin therapy or aspirin-containing therapy (see Contraindications).
The concurrent use of NASOVAC with antiviral agents that are active against influenza A and/or B viruses has not been evaluated. However, based upon the potential for antiviral agents to reduce the effectiveness of NASOVAC, do not administer this vaccine until 48 hours after the cessation of antiviral therapy and antiviral agents should not be administered until two weeks after administration of this vaccine unless medically indicated. If antiviral agents and NASOVAC are administered concomitantly, revaccination should be considered when appropriate.
There are no data on co-administration of NASOVAC with other vaccines. However, if co-administration with another vaccine is indicated, immunisation may be carried. It should be noted that the adverse reactions may be intensified.
There are no data regarding co-administration of NASOVAC with other intranasal preparations. The immunological response may be diminished if the patient is undergoing immunosuppressant treatment.
Following influenza vaccination, false positive results in serology tests using the ELISA method to detect antibodies against HIV1, Hepatitis C and especially HTLV1 have been observed. The Western Blot technique may disprove the false positive results and confirm the true results. The transient false positive reactions could be due to the IgM response by the vaccine.

Pregnancy and lactation
Data from vaccinations with unadjuvanted interpandemic trivalent vaccines in pregnant women do not indicate that adverse foetal and maternal outcomes were attributable to the vaccine.
Animal teratogenicity studies are ongoing with NASOVAC. It is not known whether NASOVAC can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Healthcare providers need to assess the benefit and potential risks of administering the vaccine to pregnant women.
It is not known whether NASOVAC is excreted in human milk. Therefore, as some viruses are excreted in human milk and additionally, because of the possibility of shedding of vaccine virus and the close proximity of a nursing infant and mother, caution should be exercised if NASOVAC is administered to nursing mothers.

Effects on ability to drive and use machines
The vaccine is unlikely to produce an effect on the ability to drive and use machines.

ADVERSE REACTIONS
In clinical trials a few local and systemic reaction were observed. They were mild to moderate in severity and resolved
without any sequelae.
Local : Nasal discomfort, stuffy nose, sneezing, runny nose, loss of smell red eyes, lacrimation, facial swelling.
Systemic : Headache, fatigue, myalgia, arthralgia, irritability, loss of appetite, sore throat, cough, diarrhoea.
The incidence was similar in both the study groups.
There were a few unsolicited event reported in both the groups and none of them were causally related to study vaccines.

OVERDOSE
No case of overdose has been reported.

PHARMACOLOGICAL PROPERTIES
Pharmacodynamic properties
NASOVAC is a live monovalent vaccine for administration by intranasal spray. The influenza virus strain in NASOVAC is (a) cold-adapted (ca) (i.e., it replicates efficiently at 25ºC, a temperature that is restrictive for replication of many wild-type influenza viruses); (b) temperature-sensitive (ts) (i.e., it is restricted in replication at 39ºC, a temperature at which many wild-type influenza viruses grow efficiently); and (c) attenuated (att) (it does not produce classic influenza-like illness in the ferret model of human influenza infection). The cumulative effect of the antigenic properties and the ca, ts, and att phenotypes is that the attenuated vaccine virus replicates in the nasopharynx to induce protective immunity.
Immune mechanisms conferring protection against influenza following receipt of Intranasal Live attenuated influenza vaccines are not fully understood, though it is well-established that these vaccines provide clinical protection to the majority of the vaccinees. Likewise, naturally acquired immunity to wild-type influenza has not been completely elucidated. Serum antibodies and mucosal antibodies may play a role in prevention and recovery from infection.
However, it is well known that there are no correlates of protection for live attenuated influenza vaccines.
Pharmacokinetic properties
Not applicable.
Preclinical safety data
NASOVAC has undergone Single-dose and Repeated-dose toxicity studies in mice and rats when administered intranasally. In single-dose studies, higher than normal doses of the vaccine were given to animals and they were observed for 14 days for toxic effects. No vaccine-related untoward effects were found in animals receiving NASOVAC.
In repeated-dose toxicity studies, three doses of higher than normal doses of the vaccine were given intranasally to animals on day 0, 7 and 14 and were subsequently sacrificed. Necropsy was done to assess adverse effects on any organs. No vaccine-related adverse effects were found in the study animals receiving NASOVAC.

INCOMPATIBILITIES
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

INSTRUCTIONS FOR USE AND HANDLING AND DISPOSAL
The vaccine should be allowed to reach room temperature before use. Shake before use.
Once NASOVAC, Intranasal has been administered, the sprayer should be disposed of according to the standard procedures for medical waste (e.g., sharps container or biohazard container).

SHELF-LIFE
Do not exceed the expiry date printed on the outer box.

STORAGE
NASOVAC (Influenza Vaccine(Human,Live Attenuated)) Intranasal SHOULD BE STORED IN A REFRIGERATOR AT 2-8ºC (35-46ºF) UPON RECEIPT AND UNTIL USE. THE PRODUCT MUST BE USED BEFORE THE EXPIRATION DATE ON THE LABEL.
The cold chain (2 to 8ºC) must be maintained when transporting Influenza Vaccine(Human,Live Attenuated) Intranasal.

PRESENTATION
NASOVAC (Influenza Vaccine(Human,Live Attenuated)) Intranasal is available as:
1 dose vial plus diluent ( 0.5 ml)
5 dose vial plus diluent (2.5 ml)