Influenza H1N1 Vaccine

Dosage Form: injection
FULL PRESCRIBING INFORMATION

Indications and Usage

Influenza A (H1N1) 2009 Monovalent Vaccine is an inactivated influenza virus vaccine indicated for immunization of persons 4 years of age and older against influenza disease caused by pandemic (H1N1) 2009 virus.

Dosage and Administration

Preparation for Administration

Inspect Influenza A (H1N1) 2009 Monovalent Vaccine syringes and multidose vials visually for particulate matter and/or discoloration prior to administration. If either of these conditions exists, the vaccine should not be administered.

Shake the syringe vigorously before administering the vaccine and shake the multidose vial preparation each time before withdrawing a dose of vaccine.

Between uses, return the multidose vial to the recommended storage conditions between 2º and 8ºC (36º and 46ºF). Do not freeze. Discard if the vaccine has been frozen.

A separate syringe and needle or a sterile disposable unit should be used for each injection to prevent transmission of infectious agents from one person to another. Needles should be disposed of properly and not recapped.

It is recommended that small syringes (0.5-mL or 1-mL) should be used to minimize any product loss.

Recommended Dose and Schedule

Clinical studies are ongoing with Influenza A (H1N1) 2009 Monovalent Vaccine to determine the optimal dosage, number of doses and schedule.

Available data show that children 9 years of age and younger are largely serologically naïve to the pandemic (H1N1) 2009 virus (15.1). Based upon these data Influenza A (H1N1) 2009 Monovalent Vaccine should be administered as follows:

Children (4 to 17 years of age):

Children 4 through 9 years of age should receive two 0.5mL doses by intramuscular injection approximately 1 month apart.

Children 10 through 17 years of age should receive a single 0.5-mL intramuscular injection.

The needle size may range from 7/8 to 1¼ inches, depending on the size of the child’s deltoid muscle, and should be of sufficient length to penetrate the muscle tissue. The anterolateral thigh can be used, but the needle should be longer, usually 1 inch.

The vaccine should not be injected in the gluteal region or areas where there may be a major nerve trunk.

Adults (18 years of age and older):

Influenza A (H1N1) 2009 Monovalent Vaccine should be administered as a single 0.5-mL intramuscular injection preferably in the region of the deltoid muscle of the upper arm.

A needle of ≥1 inch is preferred because needles <1 inch might be of insufficient length to penetrate muscle tissue in certain adults.

The vaccine should not be injected in the gluteal region or areas where there may be a major nerve trunk.

Dosage Forms and Strengths

Influenza A (H1N1) 2009 Monovalent Vaccine is a sterile suspension for intramuscular injection. [see DESCRIPTION (11) for the complete list of ingredients]

Influenza A (H1N1) 2009 Monovalent Vaccine is available in two presentations:

1) Prefilled single dose syringe, 0.5-mL. Thimerosal, a mercury derivative used during manufacture, is removed by subsequent purification steps to a trace amount (≤ 1 mcg mercury per 0.5-mL dose).

2) Multidose vial, 5-mL. Contains thimerosal, a mercury derivative, added as a preservative. Each 0.5-mL dose from the multidose vial contains 25 mcg mercury.

Contraindications

Hypersensitivity

Influenza A (H1N1) 2009 Monovalent Vaccine should not be administered to anyone with known systemic hypersensitivity reactions to egg proteins (eggs or egg products), or to any component of Influenza A (H1N1) 2009 Monovalent Vaccine, or who has had a life-threatening reaction to previous influenza vaccinations [see DESCRIPTION (11)].

Warnings and Precautions

Guillain-Barré Syndrome

If Guillain-Barré syndrome has occurred within 6 weeks of receipt of prior influenza vaccine, the decision to give Influenza A (H1N1) 2009 Monovalent Vaccine should be based on careful consideration of the potential benefits and risks.

Altered Immunocompetence

If Influenza A (H1N1) 2009 Monovalent Vaccine is administered to immunocompromised persons, including individuals receiving immunosuppressive therapy, the expected immune response may not be obtained.

Preventing and Managing Allergic Reactions

Prior to administration of any dose of Influenza A (H1N1) 2009 Monovalent Vaccine, the healthcare provider should review the patient’s prior immunization history for possible adverse events, to determine the existence of any contraindication to immunization with Influenza A (H1N1) 2009 Monovalent Vaccine and to allow an assessment of benefits and risks. Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine.

Limitations of Vaccine Effectiveness

Vaccination with Influenza A (H1N1) 2009 Monovalent Vaccine may not protect all individuals.

Adverse Reactions

Novartis’ Influenza A (H1N1) 2009 Monovalent Vaccine and seasonal trivalent Influenza Virus Vaccine (FLUVIRIN®) are manufactured by the same process. The data in this section were obtained from clinical studies and postmarketing experience with FLUVIRIN.

Overall Adverse Reaction Profile

Serious allergic reactions, including anaphylactic shock, have been observed in individuals receiving FLUVIRIN during postmarketing surveillance.

Clinical Trial Experience

Adverse event information from clinical trials provides a basis for identifying adverse events that appear to be related to vaccine use and for approximating the rates of these events. However, because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine, and may not reflect rates observed in clinical practice.

Adult and Geriatric Subjects

Safety data were collected in a total of 2768 adult and geriatric subjects (18 years of age and older) who have received FLUVIRIN in 29 clinical studies since 1982.

In 9 clinical studies since 1997, among 1261 recipients of FLUVIRIN, 745 (59%) were women; 1211 (96%) were White, 23 (2%) Asian, 15 (1%) Black and 12 (1%) other; 370 (29%) of subjects were elderly (≥65 years of age). All studies have been conducted in the UK, apart from a study run in the US in 2005-2006 where FLUVIRIN was used as a comparator for an unlicensed vaccine.

After vaccination, the subjects were observed for 30 minutes for hypersensitivity or other immediate reactions. Subjects were instructed to complete a diary card for three days following immunization (i.e. Day 1 to 4) to collect local and systemic reactions (see Tables 1 and 2). All local and systemic adverse events were considered to be at least possibly related to the vaccine. Local and systemic reactions mostly began between day 1 and day 2. The overall adverse events reported in clinical trials since 1998 in at least 5% of the subjects are summarized in Table 3.

TABLE 1 Solicited Adverse Events in the First 72-96 Hours after Administration of FLUVIRIN in Adult (18-64 years of age) and Geriatric (≥65 years of age) Subjects.

	1998-1999*§		1999-2000*§		2000-2001*§
	18-64 yrs	≥ 65 yrs	18-64 yrs	≥ 65 yrs	18-64 yrs	≥ 65 yrs
	N = 66	N = 44	N = 76	N = 34	N = 75	N = 35
Results reported to the nearest whole percent; Fever defined as >38°C
– not reported
* Solicited adverse events in the first 72 hours after administration of FLUVIRIN
§ Solicited adverse events reported by COSTART preferred term
^ Solicited adverse events reported by MEDDRA preferred term
Local Adverse Events
Pain	16 (24%)	4 (9%)	16 (21%)	-	9 (12%)	-
Mass	7 (11%)	1 (2%)	4 (5%)	-	8 (11%)	1 (3%)
Inflammation	5 (8%)	2 (5%)	6 (8%)	-	7 (9%)	1 (3%)
Ecchymosis	4 (6%)	1 (2%)	3 (4%)	1 (3%)	4 (5%)	-
Edema	2 (3%)	1 (2%)	1 (1%)	2 (6%)	3 (4%)	1 (3%)
Reaction	2 (3%)	-	2 (3%)	-	4 (5%)	1 (3%)
Hemorrhage	-	-	1 (1%)	-	-	-
Systemic Adverse Events
Headache	7 (11%)	1 (2%)	17 (22%)	3 (9%)	4 (5%)	-
Fatigue	3 (5%)	2 (5%)	4 (5%)	1 (3%)	3 (4%)	-
Malaise	2 (3%)	1 (2%)	2 (3%)	1 (3%)	1 (1%)	-
Myalgia	1 (2%)	-	2 (3%)	-	-	-
Fever	1 (2%)	-	1 (1%)	-	-	-
Arthralgia	-	1 (2%)	-	1 (3%)	-	-
Sweating	-	-	3 (4%)	-	1 (1%)	1 (3%)
	2001-2002*^		2002-2003*^		2004-2005*^
	18-64 yrs	≥ 65 yrs	18-64 yrs	≥ 65 yrs	18-64 yrs	≥ 65 yrs
	N = 75	N = 35	N = 107	N = 88	N = 74	N = 61
Local Adverse Events
Pain	12 (16%)	1 (3%)	14 (13%)	7 (8%)	15 (20%)	9 (15%)
Mass	4 (5%)	1 (3%)	-	-	-	-
Ecchymosis	2 (3%)	-	3 (3%)	3 (3%)	2 (3%)	1 (2%)
Edema	2 (3%)	1 (3%)	6 (6%)	2 (2%)	-	-
Erythema	5 (7%)	-	11 (10%)	5 (6%)	16 (22%)	5 (8%)
Swelling	-	-	-	-	11 (15%)	4 (7%)
Reaction	-	-	2 (2%)	-	-	-
Induration	-	-	14 (13%)	3 (3%)	11 (15%)	1 (2%)
Pruritus	-	-	1 (1%)	-	-	-
Systemic Adverse Events
Headache	8 (11%)	1 (3%)	12 (11%)	9 (10%)	14 (19%)	3 (5%)
Fatigue	1 (1%)	1 (3%)	-	-	5 (7%)	2 (3%)
Malaise	3 (4%)	-	3 (3%)	4 (5%)	1 (1%)	1 (2%)
Myalgia	3 (4%)	-	5 (5%)	3 (3%)	8 (11%)	1 (2%)
Fever	-	-	-	1 (1%)	-	-
Arthralgia	-	-	2 (2%)	-	1 (1%)	-
Sweating	3 (4%)	1 (3%)	-	2 (2%)	-	-
Shivering	-	-	-	1 (1%)	-	-

TABLE 2 Solicited Adverse Events in the First 72 Hours after Administration of FLUVIRIN in Adult Subjects (18-49 years of age).

	2005-2006 US Trial
	FLUVIRIN
	N = 304
Results reported to the nearest whole percent
– not reported
Local Adverse Events
Pain	168 (55%)
Erythema	48 (16%)
Ecchymosis	22 (7%)
Induration	19 (6%)
Swelling	16 (5%)
Systemic Adverse Events
Headache	91 (30%)
Myalgia	64 (21%)
Malaise	58 (19%)
Fatigue	56 (18%)
Sore throat	23 (8%)
Chills	22 (7%)
Nausea	21 (7%)
Arthralgia	20 (7%)
Sweating	17 (6%)
Cough	18 (6%)
Wheezing	4 (1%)
Chest tightness	4 (1%)
Other difficulties breathing	3 (1%)
Facial edema	-

TABLE 3 Adverse Events Reported by at least 5% of Subjects in Clinical Trials since 1998

	1998-1999§			1999-2000§			2000-2001§
	18-64 yrs	≥ 65 yrs		18-64 yrs	≥ 65 yrs		18-64 yrs	≥ 65 yrs
	N = 66	N = 44		N = 76	N = 34		N = 75	N = 35
Results reported to the nearest whole percent; Fever defined as >38°C
– not reaching the cut-off of 5%
§ Solicited adverse events reported by COSTART preferred term
^ Solicited adverse events reported by MEDDRA preferred term
Adverse Events
Fatigue	8 (12%)	2 (5%)		8 (11%)	2 (6%)		5 (7%)	-
Back pain	4 (6%)	3 (7%)		-	-		-	-
Cough increased	2 (3%)	2 (5%)		-	-		-	-
Ecchymosis	4 (6%)	1 (2%)		4 (5%)	1 (3%)		5 (7%)	-
Fever	3 (5%)	-		-	-		-	-
Headache	12 (18%)	5 (11%)		22 (29%)	5 (15%)		14 (19%)	2 (6%)
Infection	3 (5%)	2 (5%)		-	-		-	-
Malaise	4 (6%)	4 (9%)		4 (5%)	1 (3%)		-	-
Migraine	4 (6%)	1 (2%)		-	-		-	-
Myalgia	4 (6%)	1 (2%)		-	-		-	-
Sweating	5 (8%)	1 (2%)		-	-		-	-
Rhinitis	3 (5%)	1 (2%)		-	-		5 (7%)	2 (6%)
Pharingitis	6 (9%)	1 (2%)		10 (13%)	-		6 (8%)	-
Arthralgia	-	-		-	2 (6%)		-	-
Injection site pain	16 (24%)	4 (9%)		16 (21%)	-		9 (12%)	-
Injection site ecchymosis	4 (6%)	1 (2%)		-	-		4 (5%)	-
Injection site mass	7 (11%)	1 (2%)		4 (5%)	-		8 (11%)	1 (3%)
Injection site edema	-	-		1 (1%)	2 (6%)		-	-
Injection site inflammation	5 (8%)	2 (5%)		6 (8%)	-		7 (9%)	1 (3%)
Injection site reaction	-	-		-	-		4 (5%)	1 (3%)
	2001-2002^			2002-2003^			2004-2005^
	18-64 yrs		≥ 65 yrs	18-64 yrs		≥ 65 yrs	18-64 yrs	≥ 65 yrs
	N = 75		N = 35	N = 107		N = 88	N = 74	N = 61
Adverse Events
Fatigue	5 (7%)		4 (11%)	11 (10%)		8 (9%)	4 (5%)	2 (3%)
Hypertension	-		-	1 (1%)		4 (5%)	-	-
Rinorrhea	-		-	2 (2%)		5 (6%)	-	-
Headache	20 (27%)		2 (6%)	35 (33%)		18 (20%)	12 (16%)	1 (2%)
Malaise	6 (8%)		1 (3%)	13 (12%)		8 (9%)	-	-
Myalgia	4 (5%)		1 (3%)	10 (9%)		4 (5%)