A Study of the Pharmacology of Tamiflu in Pregnancy

A Study of the Pharmacology of Oseltamivir (Tamiflu-Roche) in Pregnancy

The purpose of this study is to determine the pharmacokinetics (PK) of the anti-flu medication, Tamiflu during pregnancy and to determine to what extent pregnancy may affect the currently recommended dosage of this medication.

Study Overview

• Status: Completed
• Conditions: H1N1 Influenza Treatment During Pregnancy

Detailed Description

The emergence of the novel H1N1 influenza virus has raised concern among public health officials and the public alike. Although initial reports suggested that the risk of serious disease or death was less than initially feared, continued experience suggests that the disease will have a major impact on the public's health. To address this urgent public health challenge, the centers of the Obstetric-Fetal Pharmacology Research Units Network (OPRU) will recruit a total of 75 pregnant women (25 per trimester with singletons pregnancies) who are receiving oseltamivir for supposed influenza infection. When possible, we will recruit women with twin gestation to determine if fetal number affects the drugs pharmacokinetics. We do not anticipated a significant number of multi-fetal gestations (< 10) but even limited data might prove useful in this population given the tremendous change in renal drug clearance that is normally seen in this group of women. An additional 25 healthy non-pregnant women will be studied to define pregnancy- related changes in the PK of oseltamivir and the carboxylate.

We will study each woman once during therapy, performing steady state pharmacokinetic analyses. This study will be performed after 3 days of oral therapy to optimize the possibility that steady state concentrations have been achieved.

We will:

1. collect biological fluids (plasma and urine) to further characterize the pharmacology of the drug;
2. collect a check swab for DNA to allow study of the impact of single nucleotide polymorphisms on drug handing and disease expression;
3. develop an assay or partner with others to develop an assay for oseltamivir and the primary metabolite, oseltamivir carboxylate;
4. compare the pharmacokinetics of oseltamivir and its metabolite in each trimester of pregnancy to evaluate whether gestational age has an impact on the drug's pharmacokinetics;
5. assess the impact of fetal number on the drug's pharmacokinetics;
6. ask all participants about GI tolerance to the drug and any side effects they may be experiencing, especially related to mood and psychiatric well being; and
7. on all pregnant subjects studied, when possible, we will obtain at delivery maternal and umbilical cord blood to evaluate placental transport especially in those who deliver proximate (within 3 days) to drug treatment.

• Study Type: Observational
• Enrollment (Actual): 63

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Pregnant and non-pregnant women

Description

Inclusion Criteria:

1. Taking or about to start oral oseltamivir for presumed influenza viral infection or for prophylaxis
2. Able to give informed consent
3. Pregnant female with singleton or multifetal gestation or healthy non-pregnant female (ancillary study)

Exclusion Criteria:

1. Unable to take medication orally
2. Renal failure - creatinine > 1.5
3. Hct <28

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Tamiflu use during first trimester; This group will consist of twenty-five pregnant women who are being treated with Oseltamivir for clinical indications during the first trimester of their pregnancy.
Tamiflu use during second trimester; This group will consist of twenty-five pregnant women who are being treated with Oseltamivir for clinical indications during the second trimester of their pregnancy.
Tamiflu use during third trimester; This group will consist of twenty-five pregnant women who are being treated with Oseltamivir for clinical indications during the first trimester of their pregnancy.
Tamiflu use in non-pregnant women; This group will consist of twenty-five non-pregnant healthy female volunteers who are being treated with Oseltamivir.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Apparent oral clearance of oseltamivir in singletons	At the time of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Apparent oral clearance of oseltamivir in twins	At the time of treatment
Apparent renal clearance of oseltamivir carboxylate in non-pregnant women (ancillary study)	At the time of treatment
Concentration of oseltamivir carboxylate and oseltamivir at times 0 and 12h to ascertain steady state status	At the time of treatment
Plasma esterase activity. (ancillary study)	At the time of treatment
Maternal side effects -GI upset, pregnancy loss, neuropsychiatric disorder	At the time of treatment
Maternal and cord blood oseltamivir and oseltamivir carboxylate concentrations	At delivery

Collaborators and Investigators

• Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Richard Beigi, MD, University of Pittsburgh; Principal Investigator: Steve Caritis, MD, University of Pittsburgh; Principal Investigator: Raman Venkataramanan, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: September 15, 2010
• First Submitted That Met QC Criteria: September 15, 2010
• First Posted (Estimate): September 16, 2010

Study Record Updates

• Last Update Posted (Estimate): October 9, 2013
• Last Update Submitted That Met QC Criteria: October 8, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Pregnancy; Oseltamivir; H1N1 influenza; Swine flu; Tamiflu
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: OPRU Tamiflu