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This page lists cases that relate to the monographs posted on the PharmAdept  page.
If you wish to share a case or comment on one of the cases please an e-mail to David Woods info@pharminfotech.co.nz

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Case 1 Drugs in Milk Calculation Case 2 Drugs in Milk-cyclosporin    
       

Case 1- Drugs in Milk Calculation

Question

Drug X has a M:P ratio of 0.15. The average steady state plasma concentration from a dose of 20 mg twice daily is 250 ng/mL. Estimate the infant exposure received via breast milk if the mother (weight 60 kg) is taking 20 mg twice daily. Assume that the oral bioavailability is 1

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Case 2- Drugs in Milk (cyclosporin)

Question
What is your advice regarding the use of cyclosporin in a breastfeeding woman ?
Many texts state that this is contraindicated due to the toxicity of cyclosporin. What is your advice ?
Search the resources that you have available. You can also do a Medline search.

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Case Answers

Case 1

Question

Drug X has a M:P ratio of 0.15. The average steady state plasma concentration from a dose of 20 mg twice daily is 250 ng/mL. Estimate the infant exposure received via breast milk if the mother (weight 60 kg) is taking 20 mg twice daily. Assume that the oral bioavailability is 1.

Answer
Maternal dose = 40 mg/60 kg = 0.66 mg/kg/day
Infant dose = 250 ng/mL x 0.15 x 150 mL/kg/day = 5625 ng/kg/day
5625 ng = 0.006 mg (approximately)
Therefore the infant dose relative to the maternal dose is:-
0.006/0.66 = 0.009 or approximately 1 %

NB it is important to ensure that units are the same on both sides of the equations.

There are several assumptions in this estimate.
If oral bioavailability was less than 1 then infant exposure would be lower. However with continuous dosing reduced infant clearance could lead to higher then predicted exposure.
We have also used an average steady state maternal plasma concentration. Nursing at times corresponding to the peak plasma concentration could lead to higher milk concentations and a correspondingly higher infant dose. Drug exposure can usually be minimised by avoiding feeding at peak plasma concentrations.

From the estimate, excretion of this drug in to breast milk is minimal. There is a large margin of safety in that the weight adjusted infant dose is only 1% of the maternal dose. Providing that the drug was not inherently toxic it would appear safe to use in a healthy full-term infant at normal maternal doses.

Another way to look at this would be to estimate the actual infant dose and compare this with the adult dose. In this case, if the infant weighs 6 kg the actual dose received would be 6 x 0.006 = 0.036 mg/day compared with the maternal dose of 40 mg per day.
For more details of drug excretion in to breast milk click here

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Case 2

Question
What is your advice regarding the use of cyclosporin in a breastfeeding woman ?
Many texts state that this is contraindicated due to the toxicity of cyclosporin. What is your advice ?
Search the resources that you have available. You can also do a Medline search.

Answer
Many texts advise against breastfeeding if the woman is taking cyclosporin. This advice is largely precautionary due to the potential toxicity of the drug. The results of at least three published studies provide some reassurance that cyclosporin is relatively safe in breastfeeding due to very low infant plasma concentrations. Breastfeeding infants have also been monitored for toxicity over several months. The results of these studies do not prove that cyclosporin is safe in breastfeeding but there are enough data to suggest that the risk of adverse effects in the infant is low. Ultimately, you as the practitioner need to provide informed advice that is more meaningful than some of the reference texts provide. With the exception of the article by Thiru et al, only abstracts are immediately available. Access to the complete paper would be recommended for critical appraisal of the study.

The studies are listed below. Click on the link for the PubMed citation or full text article.

Thiru Y et al :BMJ 1997 Aug 23;315(7106):463

Nyberg G et al
Transplantation 1998 Jan 27;65(2):253-5 Breast-feeding during treatment with cyclosporine.

Munoz-Flores-Thiagarajan KD et al.
Obstet Gynecol 2001 May;97(5 Pt 2):816-8 Breast-feeding by a cyclosporine-treated mother.

Note that using the correct search strategy is important in order to retrieve all the relevant articles:
In PubMed, compare:-

cyclosporin AND lactation                 Retrieves none of the above articles

cyclosporin AND milk                       Retrieves only two of the above articles     

cyclosporin AND breastfeeding          Retrieves all of the above articles

It is important to work out why these search results are different. This does not mean that "breastfeeding" is the best term to use in all similar searches. It is pure good fortune in this case. Often "milk" is the most comprehensive term, but a combination of terms should be used to achieve the best results. Refer to the search strategy in the Drugs in Breast Milk Chapter.

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