Appendix

Dosage adjustment in pregnancy

General considerations

Some of the physiological changes occurring in pregnancy may affect the pharmacokinetics of drugs taken during the gestational period and postpartum. Depending on the clinical significance of these changes, adjustment of the dose and/or dosing interval may warrant consideration. Below are some examples of altered drug distribution and elimination in pregnancy.

• Increased maternal plasma volume may increase the volume of distribution of some drugs, which may require a dose increase.
• Decreased plasma protein concentration, specifically albumin, may increase the free fraction of highly protein bound drugs, which may require a dose reduction.
• Increased renal blood flow and glomerular filtration rate may increase the elimination of drugs that are excreted primarily in the urine. This may require use of an increased dose and/or a shorter dosing interval.
• Alterations in the activity of hepatic drug metabolizing enzymes may require dosage adjustment as follows.
  • Decreased activity (e.g., CYP1A2 and CYP2C19). For drugs that are dependent on these enzymes for elimination, a dose reduction may be required. For drugs that require these enzymes for conversion to their active form, a dose increase may be appropriate.
  • Increased activity (e.g., CYP3A, CYP2D6 and CYP2C9). For drugs that are dependent on these enzymes for elimination, a dose increase may be required. For drugs that require these enzymes for conversion to their active form, a dose reduction may be required.

Note: there is a lack of pharmacokinetic data on which to base dosage adjustment of anti-infective agents in pregnancy, and there is a lack of evidence demonstrating benefit. Accordingly, routine dosage adjustment is not practiced at Sunnybrook.