Coumarins + Antidiabetics; Alpha-glucosidase

inhibitors

Miglitol and voglibose do not appear to alter the pharmacokinetics

or effects of warfarin. There are isolated cases of reduced or
increased INRs in patients given warfarin and acarbose.

Clinical evidence, mechanism, importance and management

(a) Acarbose
A 66-year-old man taking fosinopril, hydrochlorothiazide, diphenhydramine,
insulin, glipizide and warfarin started taking acarbose to improve
the control of his diabetes. Four days before starting acarbose his
INR was 3.09, but after 2 weeks (25 mg acarbose daily for week one and
then 50 mg daily for week 2) his INR had risen to 4.85. The warfarin was
temporarily stopped, then it was reintroduced at a lower dose, and finally
the acarbose was withdrawn, resulting in an INR of 2.84. No bleeding was
seen.1 In contrast, in 1997, the manufacturer had on record 2 other cases
of patients taking warfarin whose INRs were reduced when acarbose was
added. One of them stopped taking the acarbose, whereupon her INR returned to its previous
value. The other patient needed an increased warfarin
dose.2
These appear to be the only cases on record, and therefore the general
picture is that usually no interaction occurs, but in isolated cases some
changes in warfarin requirements occur. Bear this potential interaction in
mind if anticoagulant control alters in a patient taking acarbose.
(b) Miglitol
In a double-blind, randomised, placebo-controlled study, 24 healthy subjects
were given miglitol 100 mg three times daily for 7 days, with a single
25-mg oral dose of warfarin on day 4. Neither the pharmacokinetics nor
the pharmacodynamics of R- or S-warfarin were affected by the miglitol.3
No special precautions would therefore appear to be needed if these two
drugs are used concurrently.
(c) Voglibose
Twelve healthy male subjects were given individually adjusted doses of
warfarin to give Quick values of 30 to 40%, and then from day 11 to 15
they were also given voglibose 5 mg three times daily. It was found that
the voglibose had no effect on the pharmacokinetics of warfarin nor on
its anticoagulant effects.4 No special precautions would therefore appear
to be needed if these two drugs are used concurrently.

1. Morreale AP, Janetzky K. Probable interaction of warfarin and acarbose. Am J Health-Syst

Pharm (1997) 54, 1551–2.
2. Bayer. Personal communication, December 1997.
3. Schall R, Müller FO, Hundt HKL, Duursema L, Groenewoud G, Middle MV. Study of the
effect
of miglitol on the pharmacokinetics and pharmacodynamics of warfarin in healthy males.
Arzneimittelforschung (1996) 46, 41–6.
4. Fuder H, Kleist P, Birkel M, Ehrlich A, Emeklibas S, Maslak W, Stridde E, Wetzelsberger
N,
Wieckhorst G, Lücker PW. The 􀁄-glucosidase inhibitor voglibose (AO-128) does not change
pharmacodynamics or pharmacokinetics of warfarin. Eur J Clin Pharmacol (1997) 53, 153–
7.
Coumarin + Antidiabetics: Dipeptidylpeptidase-4 inhibitor

Linagliptin,sitagliptinand vidagliptin do not aappear to alter the pharmacokinetics or

anticoagulan effect ofwarfarin

Clinical evidence,mechanism,importance and management

a) Linagliptin

In a study in 18 healty subjects. Linagliptin 5 mg daily for 12 days had no effect on the
pharmacokinetics of R- and S-warfarin when a single 10-mg dose of warfarin was given on
day 6. Similarly, the anticoagulant effect of warfarin (prothrombin time and INR) was not
altered by linagliptin. No warfarin dosing adjustments would therefore be expected to be
necessary on concurrent use.

b) Sitagliptin

In a study in 11 healthy subjects, sitagliptin 200 mg for 11 days had no effect on the
pharmacokinetics or R- and S-warfarin when a single 30-mg dose of warfarin was given on
day 5. Similarly, the anticoagulant effect of warfarin (assessed by INR) was not altered by
sitagliptin. No warfarin dosing adjustments would therefore be expected to be necessary on
concurrent use.

c) vildagliptin

In controlled study in 15 healthy subjects, vildagliptin 100 mg daily for 6 days had no effect
on the pharmacokinetics of R- and S-warfarin when a single 25-mg dose of warfarin was
given on day 2. Similarly, the anticoagulant effect of warfarin (prothrombin time and INR)
was not altered by vildagliptin. No warfarin dosing adjustments would therefore be expected
to be necessary on concurrent use.

1. Graefe-Mody EU, Brand T,Ring A