Amoxicillin for Pregnancy

Overseen By Jodie Dionne-Odom, MD MSPH

Age: < 65

Sex: Female

Trial Phase: Phase 1

Sponsor: University of Alabama at Birmingham

Must not be taking: Allopurinol, Methotrexate, Tetracyclines, others

Disqualifiers: Renal impairment, Amoxicillin allergy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1-8 hours per administration

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The study design is a prospective phase I pharmacokinetic study focused on dosing of 500 mg oral amoxicillin administration in pregnant women in the 2nd and 3rd trimester.

Will I have to stop taking my current medications?

You may need to stop taking certain medications that interact with amoxicillin, such as allopurinol, methotrexate, and warfarin. It's important to discuss your current medications with the trial team to see if any changes are needed.

Is amoxicillin safe to use during pregnancy?

Amoxicillin is commonly used during pregnancy and is generally considered safe, but studies show mixed results about its effects on the fetus. Some research suggests no significant risk of birth defects or other adverse outcomes, but findings are not entirely consistent. ^{1 2 3 4 5}

How is the drug amoxicillin unique for use during pregnancy?

Amoxicillin is unique for use during pregnancy because it is a broad-spectrum antibiotic with low toxicity, making it commonly used in obstetrics. It is also recommended for anthrax prevention in pregnancy, and studies have evaluated its pharmacokinetics to optimize dosage strategies for pregnant women. ^{2 4 6 7 8}

What data supports the effectiveness of the drug amoxicillin for use during pregnancy?

Amoxicillin is commonly used in pregnancy due to its low toxicity and is recommended for anthrax prevention. It is a broad-spectrum antibiotic, meaning it can treat a wide range of bacterial infections, and studies have shown it is often used during pregnancy without significant adverse effects. ^{2 4 7 9 10}

Who Is on the Research Team?

Jodie Dionne, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for pregnant women in their 2nd or 3rd trimester who are under prenatal care and can speak English. They must not have taken amoxicillin recently, be allergic to it or similar antibiotics, have high creatinine levels indicating kidney issues, or be on certain drugs that don't mix well with amoxicillin.

Inclusion Criteria

Able to provide informed consent

Pregnant, engaged in prenatal care with a medical provider (at least one visit)

English speaking

Exclusion Criteria

My kidney function is impaired with a creatinine level of 1.2 mg/dL or higher.

I haven't taken amoxicillin in the last week.

Known hypersensitivity or intolerance of amoxicillin, penicillin, other beta lactam or cephalosporin antibiotics

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 500 mg oral amoxicillin during the 2nd and 3rd trimester of pregnancy

1-8 hours per administration

Multiple visits for pharmacokinetic sampling

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Amoxicillin
• Probenecid

Trial Overview The study is testing how the body processes a dose of 500 mg oral amoxicillin when given to pregnant women. It's a phase I trial which means it's early in the testing process and focuses on understanding how the drug moves through and affects pregnant bodies.

How Is the Trial Designed?

Group I: Amox 500 mg Experimental Treatment 1 Intervention

Amoxicillin 500 mg PO

Amoxicillin is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Amoxicillin for:

• Bacterial infections
• Respiratory tract infections
• Urinary tract infections
• Skin and soft tissue infections
• Ear, nose and throat infections

Approved in United States as Amoxicillin for:

• Infections of the ear, nose, throat, genitourinary tract, skin and skin structure, and lower respiratory tract

Approved in Canada as Amoxicillin for:

• Bacterial infections
• Respiratory tract infections
• Urinary tract infections
• Skin and soft tissue infections

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

Amoxicillin clearance rates are significantly higher during pregnancy compared to postpartum, indicating that pregnant women may process the drug differently, which could affect its effectiveness.

Simulations suggest that achieving adequate amoxicillin concentrations to prevent anthrax may be challenging during pregnancy and postpartum, raising concerns about its suitability for anthrax exposure prophylaxis in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amoxicillin pharmacokinetics in pregnant women: modeling and simulations of dosage strategies. Andrew, MA., Easterling, TR., Carr, DB., et al.[2022]

A study of 4055 pregnant women in Finland found that penicillin, erythromycin, and pivmecillinam were the most commonly prescribed antibiotics, accounting for 65.4% of all antibiotic use during pregnancy.

The second trimester had the highest rates of antibiotic use and treated infections, suggesting that healthcare providers may need to consider individualized dosing and potentially shorter treatment durations for urinary tract infections to enhance safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotics in pregnancy--a prospective cohort study on the policy of antibiotic prescription. Heikkilä, AM.[2019]

In a study of 30 full-term pregnant women, amoxicillin levels were significantly higher in maternal serum (2.18 µg/g) compared to amniotic fluid (0.67 µg/g), umbilical blood (1.00 µg/g), and placenta (1.00 µg/g) two hours after oral administration, indicating limited penetration to fetal tissues.

To effectively treat infections in pregnant patients, especially targeting the fetus and placenta, a higher dose of amoxicillin may be necessary, and intravenous administration should be considered to ensure adequate drug levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the amoxicillin concentrations in amniotic fluid, placenta, umbilical cord blood and maternal serum two hours after oral administration. Zareba-Szczudlik, J., Romejko-Wolniewicz, E., Lewandowski, Z., et al.[2018]

A systematic review of four studies involving 260,491 pregnant mothers found that while most research did not link amoxicillin use to major congenital anomalies, one case-control study suggested a potential increased risk for cleft palate.

Given the mixed findings, it is recommended that amoxicillin be used cautiously during pregnancy until more definitive evidence about its safety is available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship Between Amoxicillin Use in Pregnancy and Congenital Anomalies: A Systematic Review. Bahri, N., Dashti, S., Mohammadzadeh, A., et al.[2023]

In a study involving 108 pregnant women treated with amoxicillin for bacterial vaginosis, there were no significant differences in treatment outcomes compared to a placebo group.

The research concluded that amoxicillin is not an effective treatment for bacterial vaginosis during pregnancy, as it did not improve clinical or microbiologic measures or reduce obstetric complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amoxicillin treatment of bacterial vaginosis during pregnancy. Duff, P., Lee, ML., Hillier, SL., et al.[2013]

In a study of 401 primiparous women who took amoxicillin during pregnancy, their babies had a higher average birth weight (57 g more) compared to 10,237 women who did not take the antibiotic, suggesting a potential positive effect on fetal growth.

The research found no increased risk of adverse pregnancy outcomes such as low birth weight, preterm delivery, congenital malformations, or spontaneous abortion associated with amoxicillin use, indicating it may be safe during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A population-based study of maternal use of amoxicillin and pregnancy outcome in Denmark. Jepsen, P., Skriver, MV., Floyd, A., et al.[2019]

A study involving 191 pregnant women exposed to amoxycillin/clavulanic acid during the first trimester found no significant increase in major malformations compared to a control group, suggesting its safety during pregnancy.

The rates of major malformations were 1.9% in the amoxycillin/clavulanic acid group and 3% in the control group, indicating that the risk remains within the expected baseline for the general population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-trimester exposure to amoxycillin/clavulanic acid: a prospective, controlled study. Berkovitch, M., Diav-Citrin, O., Greenberg, R., et al.[2018]

A cohort study involving 414 pregnant women who used pivmecillinam showed no significant increase in the risk of congenital abnormalities compared to a reference group of 7472 women not prescribed any drugs, suggesting that pivmecillinam may be safe during pregnancy.

The study found no significant risks associated with pre-term delivery, low birth weight, low Apgar scores, or neonatal hypoglycaemia in infants exposed to pivmecillinam, indicating that concerns about carnitine depletion affecting pregnancy outcomes may not be warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Birth outcome and risk of neonatal hypoglycaemia following in utero exposure to pivmecillinam: a population-based cohort study with 414 exposed pregnancies. Larsen, H., Nielsen, GL., Møller, M., et al.[2019]

In a study involving 27 women undergoing termination of pregnancy due to beta-thalassemia major, antibiotics were administered to assess their effectiveness against maternal-fetal infections, showing successful amniotic fluid levels that were effective against pathogens after at least 3 hours post-administration.

The pharmacokinetics revealed that while cefoxitin levels in maternal serum were similar to those in nonpregnant women, moxalactam and ceftazidime had significantly lower serum levels, indicating altered drug absorption during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A study of cefoxitin, moxalactam, and ceftazidime kinetics in pregnancy. Giamarellou, H., Gazis, J., Petrikkos, G., et al.[2019]

Cefixime demonstrated the highest transplacental passage rate among the antibiotics studied, with 37.55%, suggesting it may be the most effective choice for treating infections during pregnancy that involve the membranes and placenta.

Moxifloxacin and levofloxacin showed significantly lower passage rates into amniotic fluid (7.83% and 15.67%, respectively), indicating that their effectiveness as therapeutic agents in pregnant women may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maternal blood and amniotic fluid levels of moxifloxacin, levofloxacin and cefixime. Ozyüncü, O., Beksac, MS., Nemutlu, E., et al.[2018]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Amoxicillin pharmacokinetics in pregnant women: modeling and simulations of dosage strategies. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Antibiotics in pregnancy--a prospective cohort study on the policy of antibiotic prescription. [2019]

3. Sweden pubmed.ncbi.nlm.nih.gov

Evaluation of the amoxicillin concentrations in amniotic fluid, placenta, umbilical cord blood and maternal serum two hours after oral administration. [2018]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Relationship Between Amoxicillin Use in Pregnancy and Congenital Anomalies: A Systematic Review. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Amoxicillin treatment of bacterial vaginosis during pregnancy. [2013]

6. England pubmed.ncbi.nlm.nih.gov

A population-based study of maternal use of amoxicillin and pregnancy outcome in Denmark. [2019]

7. England pubmed.ncbi.nlm.nih.gov

First-trimester exposure to amoxycillin/clavulanic acid: a prospective, controlled study. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Birth outcome and risk of neonatal hypoglycaemia following in utero exposure to pivmecillinam: a population-based cohort study with 414 exposed pregnancies. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

A study of cefoxitin, moxalactam, and ceftazidime kinetics in pregnancy. [2019]

10. Australia pubmed.ncbi.nlm.nih.gov

Maternal blood and amniotic fluid levels of moxifloxacin, levofloxacin and cefixime. [2018]