Risk Summary
Vitamin K1 Injection contains benzyl alcohol, which has been associated with gasping syndrome in neonates. The preservative benzyl alcohol can cause serious adverse events and death when administered intravenously to neonates and infants. If Vitamin K1 Injection is needed during pregnancy, consider using a benzyl alcohol-free phytonadione formulation [see Warnings and Precautions (5.2), Use in Specific Populations (8.4)].
Published studies with the use of phytonadione during pregnancy have not reported a clear association with phytonadione and adverse developmental outcomes [see Data]. There are maternal and fetal risks associated with vitamin K deficiency during pregnancy [see Clinical Considerations]. Animal reproduction studies have not been conducted with phytonadione.
The estimated background risk for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Disease-associated Maternal and/or Embryo/Fetal Risk
Pregnant women with vitamin K deficiency hypoprothrombinemia may be at an increased risk for bleeding diatheses during pregnancy and hemorrhagic events at delivery. Subclinical maternal vitamin K deficiency during pregnancy has been implicated in rare cases of fetal intracranial hemorrhage.
Human Data
Phytonadione has been measured in cord blood of infants whose mothers were treated with phytonadione during pregnancy in concentrations lower than seen in maternal plasma. Administration of vitamin K1 to pregnant women shortly before delivery increased both maternal and cord blood concentrations. Published data do not report a clear association with phytonadione and adverse maternal or fetal outcomes when used during pregnancy. However, these studies cannot definitively establish the absence of any risk because of methodologic limitations including small sample size and lack of blinding.
Animal Data
In pregnant rats receiving vitamin K1 orally, fetal plasma and liver concentrations increased following administration, supporting placental transfer.
Risk Summary
Vitamin K1 Injection contains benzyl alcohol. If available, a preservative-free phytonadione formulation is recommended when Vitamin K1 Injection is needed during lactation [see Warnings and Precautions (5.2), Use in Specific Populations (8.4)].
Phytonadione is present in breastmilk. There are no data on the effects of Vitamin K1 Injection on the breastfed child or on milk production. The developmental and health benefits of breastfeeding should be considered along with the clinical need for Vitamin K1 Injection and any potential adverse effects on the breastfed child from Vitamin K1 Injection or from the underlying maternal condition.
The safety and effectiveness of Vitamin K1 Injection for prophylaxis and treatment of vitamin K deficiency have been established in neonates. Use of phytonadione injection for prophylaxis and treatment of vitamin K deficiency is based on published clinical studies.
Serious adverse reactions including fatal reactions and the “gasping syndrome” occurred in premature neonates and infants in the intensive care unit who received drugs containing benzyl alcohol as a preservative. In these cases, benzyl alcohol dosages of 99 to 234 mg/kg/day produced high levels of benzyl alcohol and its metabolites in the blood and urine (blood levels of benzyl alcohol were 0.61 to 1.378 mmol/L). Additional adverse reactions included gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Preterm, low birth weight infants may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol.
When prescribing Vitamin K1 Injection in infants consider the combined daily metabolic load of benzyl alcohol from all sources including Vitamin K1 Injection (Vitamin K1 Injection contains 9 mg of benzyl alcohol per mL) and other drugs containing benzyl alcohol. The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known [see Warnings and Precautions (5.2)].
Whenever possible, use preservative-free phytonadione formulations in neonates. The preservative benzyl alcohol has been associated with serious adverse events and death in pediatric patients. Premature and low birth weight infants may be more likely to develop toxicity.
{{section_name_patient}}
{{section_body_html_patient}}
Additional Resources
Chat online with Pfizer Medical Information regarding your inquiry on a Pfizer medicine or vaccine.
Speak with a Pfizer Medical Information Professional regarding your Pfizer medicine or vaccine inquiry.
Available 9AM-5PM ET Monday to Friday; excluding holidays.
Submit a medical question for a Pfizer medicine or a vaccine.
The submission will be reviewed during our standard business hours.
To report an adverse event related to a Pfizer product and you are not part of a clinical trial* for this medication, click the link below to submit your information:
Pfizer Safety Reporting Site
*If you are involved in a clinical trial for either product, adverse events should be reported to your coordinating study site.
If you cannot use the above website to report an adverse event related to a Pfizer medication, please call (800) 438-1985.
You may also contact the U.S. Food and Drug Administration (FDA) directly to report adverse events or product quality concerns either online at www.fda.gov/medwatch or by calling (800) 332-1088.