Gardasil 9 Use In Pregnancy & Lactation

Pregnancy: Studies in Female Rats: Reproduction studies have been performed in female rats at a dose approximately 240 times the human dose (mg/kg basis) and have revealed no evidence of impaired female fertility or harm to the fetus due to GARDASIL 9.
An evaluation of the effect of GARDASIL 9 on embryo-fetal, pre- and postweaning development was conducted in studies using rats. No adverse effects on mating, fertility, pregnancy, parturition, lactation, embryo-fetal or pre- and postweaning development were observed. There were no vaccine-related fetal malformations or other evidence of teratogenesis noted. In addition, there were no treatment-related effects on developmental signs, behavior, reproductive performance, or fertility of the offspring. GARDASIL 9 induced a specific antibody response against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in pregnant rats following one or multiple intramuscular injections. Antibodies against all 9 HPV types were transferred to the offspring during the period of gestation and lactation.
Clinical Studies in Humans: There are no adequate and well-controlled studies in pregnant women. Data from more than 1,000 pregnancy exposures to GARDASIL 9 in clinical studies and post-marketing experience do not demonstrate vaccine-associated increase in risk of major birth defects and miscarriages when GARDASIL 9 is administered during pregnancy. These pregnancies occurred in women who were pregnant at time of vaccination or became pregnant during the follow-up period in clinical studies. As a precautionary measure, the administration of GARDASIL 9 during pregnancy should be avoided. Women who become or plan to become pregnant during the vaccination series should be advised to interrupt or postpone the vaccination regimen until completion of pregnancy.
In clinical studies, women underwent serum or urine pregnancy testing prior to administration of GARDASIL 9. Women who were found to be pregnant before completion of a 3-dose regimen of GARDASIL 9 were instructed to defer completion of their vaccination regimen until resolution of the pregnancy.
The overall proportion of pregnancies occurring at any time during the studies that resulted in an adverse outcome defined as the combined numbers of spontaneous abortion, late fetal death and congenital anomaly cases out of the total number of pregnancy outcomes for which an outcome was known (and excluding elective terminations), was 12.9% (174/1,353) in women who received GARDASIL 9 and 14.4% (187/1,303) in women who received GARDASIL. The proportions of adverse outcomes observed were consistent with pregnancy outcomes observed in the general population.
Further sub-analyses were conducted to evaluate pregnancies with estimated onset within 30 days or more than 30 days from administration of a dose of GARDASIL 9 or GARDASIL. For pregnancies with estimated onset within 30 days of vaccination, no cases of congenital anomaly were observed in women who have received GARDASIL 9 or GARDASIL. In pregnancies with onset more than 30 days following vaccination, 30 and 23 cases of congenital anomaly were observed in women who have received GARDASIL 9 and GARDASIL, respectively. The types of anomalies observed were consistent (regardless of when pregnancy occurred in relation to vaccination) with those generally observed in pregnancies in the general population.
Post-marketing Experience: A six-year pregnancy registry for GARDASIL 9 enrolled 185 women who were inadvertently exposed to GARDASIL 9 within one month prior to the last menstrual period (LMP) or at any time during pregnancy, 180 of whom were prospectively followed. After excluding elective terminations (n=1), ectopic pregnancies (n=0) and those lost to follow-up (n=110), there were 69 pregnancies with known outcomes. Frequencies of miscarriage and major birth defects were 4.3% of pregnancies (3/69) and4.5% of live born infants (3/67), respectively. These frequencies of the assessed outcomes in the prospective population were consistent with estimated background frequencies.
Data for adverse pregnancy outcomes for GARDASIL are included as follow as they are relevant to GARDASIL 9 since the vaccines are similar in composition and contain HPV L1 proteins of 4 of the same HPV types.
A five-year pregnancy registry for GARDASIL enrolled 2,942 women who were inadvertently exposed to GARDASIL within one month prior to the LMP or at any time during pregnancy, 2,566 of whom were prospectively followed. After excluding elective terminations (n=107), ectopic pregnancies (n=5) and those lost to follow-up (n=814), there were 1,640 pregnancies with known outcomes. Frequencies of miscarriage and major birth defects were 6.8% of pregnancies (111/1,640) and 2.4% of live born infants (37/1,527), respectively. These frequencies of the assessed outcomes in the prospective population were consistent with estimated background frequencies.
In two post-marketing studies of GARDASIL (one conducted in the U.S., and the other in Nordic countries), pregnancy outcomes among subjects who received GARDASIL within one month prior to the LMP or at any time during pregnancy were evaluated retrospectively. In the U.S. study database, 2,678 pregnancies were assessed for adverse pregnancy outcomes. After excluding elective terminations (n=442), and pregnancies with unknown outcomes (n=938), there were 1,298 pregnancies with known outcomes. Frequencies of confirmed miscarriages and major birth defects were 0.7% of pregnancies (9/1,298) and 3.6% of live born infants (24/665), respectively. In the Nordic registry study, 499 live born infants were assessed for major birth defects. The frequency of major birth defects was 5.4% (27/499). In both studies, frequencies of the assessed outcomes did not suggest an increased risk with the administration of GARDASIL within one month prior to the LMP or at any time during pregnancy.
Thus, there is no evidence to suggest that administration of GARDASIL 9 adversely affects fertility, pregnancy, or infant outcomes.
Nursing Mothers: GARDASIL 9 may be administered to lactating women.
It is not known whether vaccine antigens or antibodies induced by the vaccine are excreted in human milk.
A total of 92 women were breast feeding during the vaccination period of the clinical studies for GARDASIL 9 in women aged 16 to 26 years. In these studies, vaccine immunogenicity was comparable between nursing women and women who did not nurse. In addition, the adverse experience profile for nursing women was comparable to that of the women in the overall safety population. There were no vaccine-related serious adverse experiences reported in infants who were nursing during the vaccination period.