Phenoxymethylpenicillin potassium

Health surveillance data

Administrative data

Endpoint:

health surveillance data

Type of information:

other: Review

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2015

Materials and methods

Study type:

human medical data

Test guideline

Qualifier:

no guideline followed

Test material

Test material information

1

Reference substance name:

Phenoxymethylpenicillin potassium

EC Number:

205-086-5

EC Name:

Phenoxymethylpenicillin potassium

Cas Number:

132-98-9

Molecular formula:

C16H17KN2O5S

IUPAC Name:

potassium (2S,5R,6R)-3,3-dimethyl-7-oxo-6-[(2-phenoxyacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate

Test material form:

solid

Specific details on test material used for the study:

Beta-Lactams and Related Antibiotics - Penicillins

Method

Type of population:

other: Pregnants

Details on study design:

During pregnancy, untreated sexually transmitted or urinary tract infections are associated with significant morbidity, including low birth weight, preterm birth, and spontaneous abortion. Approximately one in four women will be prescribed an antibiotic during pregnancy, accounting for nearly 80% of prescription medications in pregnant women. Antibiotic exposures during pregnancy have been associated with both short-term (e.g., congenital abnormalities) and long-term effects (e.g., changes in gut microbiome, asthma, atopic dermatitis) in the newborn. However, it is estimated that only 10% of medications have sufficient data related to safe and effective use in pregnancy. Antibiotics such as beta-lactams, vancomycin, nitrofurantoin, metronidazole, clindamycin, and fosfomycin are generally
considered safe and effective in pregnancy. Physiologic changes in pregnancy lead to an increase in glomerular filtration rate, increase in total body volume, and enhanced cardiac output. These changes may lead to pharmacokinetic alterations in antibiotics that require dose adjustment or careful monitoring and assessment.

Results and discussion

Results:

Penicillins and their newer derivatives are the most widely prescribed antimicrobial class during pregnancy. Intravenous penicillin from the time of rupture of the placental membranes until delivery remains first-line prophylaxis if the patient is colonized with Group B Streptococcus, while ampicillin is recommended as a suitable alternative. Penicillins generally cross the placenta in high concentrations. Penicillins
with increased protein binding such as the anti-staphylococcal penicillins (except methicillin) produce lower fetal tissue concentrations compared with penicillins such as penicillin G or ampicillin that have low protein binding. Due to increased plasma volume and creatinine clearance in pregnant women, serum penicillin concentrations may be decreased by as much as 50%, which may require increased doses and/or
frequency.

Applicant's summary and conclusion

Conclusions:

Penicillins have a long track record of safety, with the parent compound penicillin and the aminopenicillins (ampicillin and amoxicillin) having the most robust safety data. All penicillins and their derivatives, as well as penicillin combinations with beta-lactamase inhibitors such as clavulanate or sulbactam, have been assigned a Pregnancy Category B rating.

Executive summary:

The use of antibiotics in pregnancy requires careful assessment and a discussion of risk versus benefit to mother and fetus, both short and long term. In general, many antibiotics are considered safe in pregnancy, especially beta-lactams: Penicillins have a long track record of safety, with the parent compound penicillin and the aminopenicillins (ampicillin and amoxicillin) having the most robust safety data. All penicillins and their derivatives, as well as penicillin combinations with beta-lactamase inhibitors such as clavulanate or sulbactam, have been assigned a Pregnancy Category B rating.