Tetanus

Boostrix by GlaxoSmithKline (Tdap)

Captured 2022-12-07

Document Highlights

Initial U.S. Approval: 2005

BOOSTRIX is a vaccine indicated for:
– active booster immunization against tetanus, diphtheria, and pertussis in individuals aged 10 years and older,
– immunization during the third trimester of pregnancy to prevent pertussis in infants younger than 2 months of age.

The incidence of unsolicited adverse events reported in the 31 days after vaccination was… 25.4%… for BOOSTRIX…

Serious Adverse Events (SAEs)
In non-U.S. adolescent studies in which serious adverse events were monitored for up to 37 days, 1 subject was diagnosed with insulin-dependent diabetes 20 days following administration of BOOSTRIX…

In the U.S. adult (aged 19 to 64 years) study… serious adverse events were reported to occur during the entire study period (0-6 months) by 1.4%…

In the U.S. elderly (aged 65 years and older) study… Serious adverse events were reported to occur by 4.2%… during the 6-month period after vaccination.

Vaccination During Pregnancy*
In the randomized, controlled study… 687 pregnant individuals received the non-U.S. formulation of BOOSTRIX or placebo during the third trimester (341 non-U.S. formulation of BOOSTRIX, 346 placebo [saline]). The placebo recipients received the non-U.S. formulation of BOOSTRIX postpartum.

Postmarketing Experience
– Lymphadenitis, lymphadenopathy.
– Allergic reactions, including anaphylactic and anaphylactoid reactions.
– Myocarditis.
– Extensive swelling of the injected limb, injection site induration, injection site inflammation, injection site mass, injection site pruritus, injection site nodule, injection site warmth, injection site reaction.
– Arthralgia, back pain, myalgia.
– Convulsions (with and without fever), encephalitis, facial palsy, loss of consciousness, paresthesia, syncope.
– Angioedema, exanthem, Henoch-Schönlein purpura, rash, urticaria.

It is not known whether the vaccine components of BOOSTRIX are excreted in human milk.

Tetanus toxin is produced… in a… medium derived from bovine casein. The diphtheria toxin is produced… in… medium containing a bovine extract.

Each 0.5-mL dose contains aluminum hydroxide as adjuvant (formulated to contain 0.3 mg aluminum)… polysorbate 80…

BOOSTRIX has not been evaluated for carcinogenic or mutagenic potential, or for impairment of male fertility in animals.

Comments

*Regarding the one small clinical trial on vaccination during pregnancy (less than 750 participants total and less than 350 subjects initially received saline placebo):

Using an average time of delivery of 39 weeks, placebo and Boostrix were administered to all subjects, 3-12 weeks apart.

"...pregnant women... will receive a single dose of Boostrix at 27-36 weeks... of gestation... and will receive a dose of the placebo post-delivery (within 72 hours)... [or]... a single dose of placebo at 27-36 weeks... of gestation... and will receive a dose of Boostrix post-delivery (within 72 hours)."

Reference, here.

From the published study of this clinical trial:
"77 SAEs [severe adverse events] were reported for 52 infants (15.2%) in the Tdap group and 63 SAEs for 45 infants (13.0%) in the control group... one (respiratory distress in an infant in the Tdap group)... led to a withdrawal."

Participants were monitored for adverse events until 2 months post-delivery.

From the insert: "It is not known whether the vaccine components of BOOSTRIX are excreted in human milk."

From the supplementary material:
Women who were not in excellent health were excluded from the trial.
Exclusion criteria...
- Women with co-morbid medical or obstetric conditions that in the opinion of the investigator had the potential to complicate the pregnancy course and outcomes...
- Gestational diabetes as determined by glucose tolerance test conducted after 20 weeks of gestation...
- Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 6 months prior to the first vaccine. For corticosteroids, this meant prednisone ≥20 mg/day, or equivalent.
- Serious underlying medical condition, e.g., immunosuppressive disease or therapy, human immunodeficiency virus infection, collagen vascular disease, epilepsy, diabetes mellitus, chronic hypertension, moderate to severe asthma, lung/heart disease, liver/kidney disease, infections including TORCHES (toxoplasmosis, rubella, cytomegalovirus, herpes simplex, syphilis) infections.
- Significant mental illness (e.g., schizophrenia, psychosis and major depression).
- Family history (first degree relatives only) of congenital anomalies, recurrent pregnancy losses (2 or more consecutive losses) and unexplained neonatal death(s) in the woman.
- Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination...
- History of major congenital anomalies in previous pregnancies.
- History of early onset (<34 weeks of gestation) of eclampsia or pre-eclampsia in a previous pregnancy.

Reference, here.

Why placebo controlled trials are necessary.

Vaccine.Guide

Boostrix by GlaxoSmithKline (Tdap)