Menveo is a vaccine indicated for active immunization to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135. Menveo is approved for use in persons 2 through 55 years of age.
Menveo does not prevent N. meningitidis serogroup B infections.
Menveo Dosage and Administration
Reconstitution Instructions
Menveo is supplied in two vials that must be combined prior to administration. Menveo must be prepared for administration by reconstituting the MenA lyophilized conjugate vaccine component with the MenCYW-135 liquid conjugate vaccine component. Using a graduated syringe, withdraw the entire contents of the vial of MenCYW-135 liquid conjugate component and inject into the MenA lyophilized conjugate component vial. Invert the vial and shake well until the vaccine is dissolved and then withdraw 0.5 mL of reconstituted product.
Please note that it is normal for a small amount of liquid to remain in the vial following withdrawal of the dose.
Following reconstitution, the vaccine is a clear, colorless solution, free from visible foreign particles. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If any of these conditions exist, Menveo should not be administered.
The reconstituted vaccine should be used immediately, but may be held at or below 77°F (25°C) for up to 8 hours.
Administration
For intramuscular injection only. Do not administer Menveo intravenously, subcutaneously or intradermally.
Dose and Schedule
Menveo should be administered as a single 0.5mL intramuscular injection, preferably into the deltoid muscle (upper arm). For children 2 through 5 years of age at continued high risk of meningococcal disease a second dose may be administered 2 months after the first dose (sections 6.1, 14, 14.1). The duration of protection following immunization is not known.
Dosage Forms and Strengths
Menveo is a solution for intramuscular injection (0.5 mL dose) supplied as a lyophilized vaccine component that is combined through reconstitution with a liquid vaccine component, both in single dose vials [See Dosage and Administration (2), How Supplied/Storage and Handling (16)].
Contraindications
Severe allergic reaction (e.g. anaphylaxis) after a previous dose of Menveo, any component of this vaccine, or any other CRM197, diphtheria toxoid or meningococcal-containing vaccine is a contraindication to administration of Menveo. [See Description (11)].
Warnings and Precautions
Management of Acute Allergic Reactions
Appropriate medical treatment must be available should an acute allergic reaction, including an anaphylactic reaction, occur following administration of Menveo.
Syncope
Syncope, sometimes resulting in falling injury associated with seizure-like movements has been reported following vaccination with Menveo. Vaccinees should be observed for 15 minutes after vaccine administration to prevent and manage syncopal reactions.
Altered Immunocompetence
Safety and effectiveness of Menveo have not been evaluated in immunocompromised persons. If Menveo is administered to immunocompromised persons, including those receiving immunosuppressive therapy, the expected immune response may not be obtained.
Guillain-Barre Syndrome
Following vaccination with a U.S. licensed meningococcal quadrivalent polysaccharide conjugate vaccine, an evaluation of post-marketing adverse events suggested a potential for an increased risk of Guillain-Barré Syndrome (GBS)(1). Data are not available to evaluate the potential risk of GBS following administration of Menveo.
Bleeding Disorders
Menveo should not be administered to persons with any bleeding disorder, or persons receiving anticoagulant therapy, unless the potential benefit outweighs the risk of administration.
Adverse Reactions
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.
The safety of Menveo in children 2 through 10 years of age was evaluated in 4 clinical trials conducted in North America (66%), Latin America (28%) and Europe (6%) in which 3181 subjects received Menveo and 2116 subjects received comparator vaccines (either Meningococcal Polysaccharide Vaccine, Groups A, C, Y and W-135 Combined - Menomune®, Sanofi Pasteur [N=861], or Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine - Menactra®, Sanofi Pasteur [N=1255]). The subjects 2 through 10 years of age who received Menveo were Caucasian (69%), Hispanic (13%), African American (7%), and other racial/ethnic groups (6%), 51% male, with a mean age of 5.2 years. The safety of a second dose of Menveo administered 2 months following a first dose was studied in 351 children 2 through 5 years of age.
The safety of Menveo in individuals 11 through 55 years of age was evaluated in 5 randomized controlled clinical trials in which 6185 participants received Menveo alone (5286 participants), Menveo concomitant with other vaccine(s) (899 participants), or a U.S. licensed comparator vaccine (1966 participants). In the concomitant trials Menveo was given with Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed (Boostrix®, GlaxoSmithKline Biologicals) or with Boostrix plus Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant (Gardasil®, Merck & Co., Inc.). The comparator vaccine was either Menomune (209 participants) or Menactra (1757 participants). The trials were conducted in North America (46%), Latin America (41%) and Europe (13%). In two of the studies, subjects received concomitant vaccination with Boostrix, or with Boostrix plus Gardasil. Overall, subjects were Caucasian (50%), followed by Hispanic (40%), African American (7%), and other racial/ethnic groups (3%). Among Menveo recipients, 61%, 17% and 22% were in the 11 through 18 year, 19 through 34 year and 35 through 55 year age groups, respectively, with a mean age of 23.5 years (SD 12.9 years). Among Menactra recipients, 31%, 32% and 37% were in the 11 through 18 year, 19 through 34 year and 35 through 55 year age groups, respectively, with a mean age of 29.2 years (SD 13.4 years). Among Menomune recipients, 100% were in the 11 through 18 year age group, and the mean age was 14.2 years (SD 1.8 years).
Solicited local reactions and systemic adverse events were monitored daily for 7 days following vaccination and recorded on a diary card. Participants were monitored for 28 days for unsolicited adverse events which included adverse events requiring a physician visit, Emergency Department visit or which led to a subject's withdrawal from the study. Medically significant adverse events and serious adverse events (SAE) were monitored for 6 months after vaccination.
Solicited Adverse Reactions
In clinical trials of children 2 through 10 years of age, the most frequently occurring adverse reactions (≥ 10%) among all subjects who received Menveo were injection site pain (31%), erythema (23%), irritability (18%), induration (16%), sleepiness (14%), malaise (12%), and headache (11%).Among subjects 11 through 55 years of age, the most frequently occurring adverse reactions (≥ 10%) among all subjects who received Menveo were pain at the injection site (41%), headache (30%), myalgia (18%), malaise (16%) and nausea (10%).
The rates of solicited adverse reactions reported for subjects 2 through 5 years and 6 through 10 years of age who received a single dose of Menveo or Menactra in a randomized controlled, multicenter study conducted in the U.S. and Canada are shown in Table 1. Following a second dose of Menveo administered to children 2 through 5 years of age, the most common solicited adverse reactions (≥ 10%) were pain at injection site (28%), erythema (22%), irritability (16%), induration (13%), and sleepiness (12%). The solicited adverse events from a separate randomized controlled multicenter study conducted in the U.S. in adolescents and adults are provided in Tables 2 and 3, respectively. In neither study were concomitant vaccines administered with the study vaccines.
§ Moderate: Some limitation in normal daily activity, Severe: Unable to perform normal daily activity. | ||||||
| Participants 2 through 5 Years of Age | ||||||
| Menveo N = 693 % | Menactra N = 684 % | |||||
| Any | Moderate | Severe | Any | Moderate | Severe | |
Local | ||||||
| Injection site pain§ | 33 | 6 | 1 | 35 | 8 | 0.4 |
| Erythema¥ | 27 | 5 | 1 | 25 | 3 | 0.3 |
| Induration¥ | 18 | 2 | 0.4 | 18 | 2 | 0.3 |
Systemic ‡ | ||||||
| Irritability§ | 21 | 6 | 1 | 22 | 7 | 1 |
| Sleepiness§ | 16 | 3 | 1 | 18 | 5 | 1 |
| Change in eating§ | 9 | 2 | 1 | 10 | 2 | 0.3 |
| Diarrhea§ | 7 | 1 | 0.1 | 8 | 1 | 0 |
| Headache§ | 5 | 1 | 0 | 6 | 1 | 0.3 |
| Rash* | 4 | - | - | 5 | - | - |
| Arthralgia§ | 3 | 1 | 0.1 | 4 | 1 | 0 |
| Vomiting§ | 3 | 1 | 0.1 | 3 | 1 | 0 |
| Fever† | 2 | 0.4 | 0 | 2 | 0.3 | 0 |
Participants 6 through 10 Years of Age | ||||||
| Menveo N = 582 % | Menactra N = 571 % | |||||
| Any | Moderate | Severe | Any | Moderate | Severe | |
Local | ||||||
| Injection site pain§ | 39 | 8 | 1 | 45 | 10 | 2 |
| Erythema¥ | 28 | 5 | 1 | 22 | 2 | 0.2 |
| Induration¥ | 17 | 2 | 0.3 | 13 | 2 | 0 |
Systemic ‡ | ||||||
| Headache§ | 18 | 3 | 1 | 13 | 2 | 1 |
| Malaise§ | 14 | 3 | 1 | 11 | 3 | 1 |
| Myalgia§ | 10 | 2 | 1 | 10 | 2 | 1 |
| Nausea§ | 8 | 2 | 1 | 6 | 2 | 0.4 |
| Arthralgia§ | 6 | 1 | 0 | 4 | 1 | 0.4 |
| Chills§ | 5 | 1 | 0 | 5 | 1 | 0.4 |
| Rash* | 5 | - | - | 3 | - | - |
| Fever† | 2 | 1 | 0 | 2 | 0 | 0.4 |
§ Moderate: Some limitation in normal daily activity, Severe: Unable to perform normal daily activity. | ||||||
| Menveo N = 1631 % | Menactra N=539 % | |||||
| Reaction | Any | Moderate | Severe | Any | Moderate | Severe |
| Local | ||||||
| Injection site pain§ | 44 | 9 | 1 | 53 | 11 | 1 |
| Erythema¥ | 15 | 2 | 0.4 | 16 | 1 | 0 |
| Induration¥ | 12 | 2 | 0.2 | 11 | 1 | 0 |
Systemic | ||||||
| Headache§ | 29 | 8 | 2 | 28 | 7 | 1 |
| Myalgia§ | 19 | 4 | 1 | 18 | 5 | 0.4 |
| Nausea§ | 12 | 3 | 1 | 9 | 2 | 1 |
| Malaise§ | 11 | 3 | 1 | 12 | 5 | 1 |
| Chills§ | 8 | 2 | 1 | 7 | 1 | 0.2 |
| Arthralgia§ | 8 | 2 | 0.4 | 6 | 1 | 0 |
| Rash* | 3 | - | - | 3 | - | - |
| Fever† | 1 | 0.4 | 0 | 1 | 0 | 0 |
§ Moderate: Some limitation in normal daily activity, Severe: Unable to perform normal daily activity. | ||||||
| Menveo N=1018 % | Menactra N= 336 % | |||||
| Reaction | Any | Moderate | Severe | Any | Moderate | Severe |
| Local | ||||||
| Injection site pain§ | 38 | 7 | 0.3 | 41 | 6 | 0 |
| Erythema¥ | 16 | 2 | 1 | 12 | 1 | 0 |
| Induration¥ | 13 | 1 | 0.4 | 9 | 0.3 | 0 |
| Systemic | ||||||
| Headache§ | 25 | 7 | 2 | 25 | 7 | 1 |
| Myalgia§ | 14 | 4 | 0.5 | 15 | 3 | 1 |
| Malaise§ | 10 | 3 | 1 | 10 | 2 | 1 |
| Nausea§ | 7 | 2 | 0.4 | 5 | 1 | 0.3 |
| Arthralgia§ | 6 | 2 | 0.4 | 6 | 1 | 1 |
| Chills§ | 4 | 1 | 0.1 | 4 | 1 | 0 |
| Rash* | 2 | - | - | 1 | - | - |
| Fever† | 1 | 0.3 | 0 | 1 | 0.3 | 0 |
Solicited Adverse Reactions following concomitant vaccine administration
The safety of Menveo administered concomitantly with Boostrix and Gardasil was evaluated in a single center study conducted in Costa Rica. Solicited local and systemic adverse reactions were recorded and reported as noted above. In this study, subjects 11 through 18 years of age received Menveo concomitantly with Boostrix and Gardasil (N=540), or Menveo followed one month later by Boostrix and then one month later by Gardasil (N=541), or Boostrix followed one month later by Menveo and then one month later by Gardasil (N=539). Some solicited systemic adverse reactions were more frequently reported in the group that received Menveo, Boostrix and Gardasil concomitantly, (headache 40%, malaise 25%, myalgia 27%, and arthralgia 17%) compared to the group that first received Menveo alone (headache 36%, malaise 20%, myalgia 19%, and arthralgia 11%). Among subjects administered Menveo alone (one month prior to Boostrix), 36% reported headache, 20% malaise, and 16% myalgia. Among subjects administered Menveo one month after Boostrix, 27% reported headache, 18% malaise, and 16% myalgia.
Serious Adverse Events in all safety studies
The information regarding serious adverse events in subjects 2 through 10 years of age was derived from 3 randomized, controlled clinical trials. Safety follow-up ranged from 6 through 12 months and included 2883 subjects administered Menveo. Serious adverse events reported during the safety follow-up periods occurred in 21/2883 (0.7%) of Menveo subjects, in 7/1255 (0.6%) of Menactra subjects, and 2/861 (0.2%) of Menomune subjects. In the subjects receiving either one or two doses of Menveo, there were 6 subjects with pneumonia, 3 subjects with appendicitis and 2 subjects with dehydration; all other events were reported to occur in one subject. Among 1255 subjects administered a single dose of Menactra and 861 subjects administered Menomune, there were no events reported to occur in more than one subject. The serious adverse events occurring within the first 30 days after receipt of each vaccine were as follows: Menveo (6/2883 [0.2%]) – appendicitis, pneumonia, staphylococcal infection, dehydration, febrile convulsion, and tonic convulsion; Menactra (1/1255 [0.1%]) – inguinal hernia; Menomune (2/861 [0.2%]) – abdominal pain, lobar pneumonia. In a supportive study, 298 subjects received one or two doses of Menveo and 22 (7%) had serious adverse events over a 13 month follow-up period including 13 subjects with varicella and 2 subjects with laryngitis. All other events were reported to occur in one subject. During the 30 days post vaccination in this study, one limb injury and one case of varicella were reported.
The information regarding serious adverse events in subjects 11 through 55 years of age was derived from 5 randomized, controlled clinical trials. Serious adverse events reported within 6 months of vaccination occurred in 40/6185 (0.6%) of Menveo subjects, 13/1757 (0.7%) of Menactra subjects, and 5/209 (2.4%) of Menomune subjects. During the 6 months following immunization, serious adverse events reported by more than one subject were as follows: Menveo - appendicitis (3 subjects), road traffic accident (3 subjects), and suicide attempt (5 subjects); Menactra - intervertebral disc protrusion (2 subjects); Menomune - none. Serious adverse events that occurred within 30 days of vaccination were reported by 7 of 6185 (0.1%) subjects in the Menveo group, 4 of 1757 (0.2%) subjects in the Menactra group, and by none of 209 subjects in the Menomune group. The events that occurred during the first 30 days post immunization with Menveo were: vitello-intestinal duct remnant; Cushing's syndrome; viral hepatitis; pelvic inflammatory disease; intentional multiple drug overdose; simple partial seizure; and suicidal depression. The events that occurred during the first 30 days post immunization with Menactra were: herpes zoster; fall; intervertebral disc protrusion; and angioedema.
Postmarketing Experience
In addition to reports in clinical trials, worldwide voluntary reports of adverse events received for Menveo in persons 11 through 55 years of age since market introduction of this vaccine are listed below. This list includes serious events or events which have plausible causal connection to Menveo. Because these events are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to the vaccine.
Ear and Labyrinth Disorders: Hearing impaired, ear pain, vertigo, vestibular disorder.
Eye Disorders: Eyelid ptosis.
General Disorders and Administration Site Conditions: Injection site pruritus, pain, erythema, inflammation and swelling, fatigue, malaise, pyrexia.
Immune System Disorders: Hypersensitivity.
Infections and Infestations: Vaccination site cellulitis.
Injury, Poisoning and Procedural Complications: Fall, head injury.
Investigation: Alanine aminotransferase increased, body temperature increased.
Musculoskeletal and Connective Tissue Disorders: Arthralgia, bone pain.
Nervous System Disorders: Dizziness, syncope, tonic convulsion, headache, facial paresis, balance disorder.
Respiratory, Thoracic and Mediastinal Disorders: Oropharyngeal pain.
Skin and Subcutaneous Tissue Disorders: Skin exfoliation.
Drug Interactions
Concomitant Administration with Other Vaccines
Do not mix Menveo or any of its components with any other vaccine or diluent in the same syringe or vial.
For children 2 through 10 years of age, no data are available to evaluate safety and immunogenicity of other childhood vaccines when administered concomitantly with Menveo.
In a clinical trial in adolescents, Menveo was given concomitantly with Boostrix and Gardasil, no interference was observed in meningococcal immune responses when compared to Menveo given alone. Lower geometric mean antibody concentrations (GMCs) for antibodies to the pertussis antigens filamentous hemagglutinin (FHA) and pertactin were observed when Menveo was administered concomitantly with Boostrix and Gardasil as compared with Boostrix alone. [Immunogenicity of Concomitantly Administered Vaccines, 14.4]
Immunosuppressive Treatments
Immunosuppressive therapies, such as irradiation, antimetabolite medications, alkylating agents, cytotoxic drugs, and corticosteroids (when used in greater than physiologic doses) may reduce the immune response to Menveo [See Warnings and Precautions (5.3)]. The immunogenicity of Menveo has not been evaluated in persons receiving such therapies.
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category B
Reproduction studies have been performed in female rabbits at a dose of approximately 20 times the human dose (on a mg/kg basis) and have revealed no evidence of impaired fertility or harm to the fetus due to Menveo. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Menveo should be given to a pregnant woman only if clearly needed.
Nonclinical Studies
The effect of Menveo on embryo-fetal and post-natal development was evaluated in pregnant rabbits. Animals were administered Menveo 3 times prior to gestation, during the period of organogenesis (gestation day 7) and later in pregnancy (gestation day 20), 0.5 ml/rabbit/occasion (approximately 20-fold excess relative to the projected human dose on a body weight basis) by intramuscular injections. There were no adverse effects attributable to the vaccine on mating, female fertility, pregnancy, or embryo-fetal development. There were no vaccine related fetal malformations or other evidence of teratogenesis noted in this study.
Clinical Studies
To date, no clinical trials have been specifically designed to evaluate the use of Menveo in pregnant or lactating women.
Among the 5065 women in the adolescent and adult populations enrolled in the studies, 43 women were found to be pregnant during the 6-month follow-up period after vaccination. Of these, 37 pregnancies occurred among 3952 Menveo recipients (7 spontaneous abortions, no congenital anomalies). Six pregnancies occurred among 1113 Menactra recipients (no spontaneous abortions, one congenital anomaly (hydrocephalus)).
Among the seven subjects with adverse pregnancy outcomes who had received Menveo, the estimated dates of conception were 5 days prior to vaccination (1 subject), 6 to 17 weeks post vaccination (5 subjects), and 6 months post vaccination (1 subject). In the subject who had received Menactra the estimated date of conception was approximately 15 weeks post immunization.
Safety and effectiveness of Menveo have not been established in pregnant women.
Pregnancy Registry for Menveo
Novartis Vaccines and Diagnostics Inc. maintains a pregnancy registry to monitor the fetal outcomes of pregnant women exposed to Menveo. To enroll in th
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