Title: Drug Interactions of Antidiabetics (Part 8): Interactions of DPP 4 Inhibitors
1Drug Interactions of antidiabetics (part 8)
- Dr.P.Naina Mohamed
- Pharmacologist
2Oral Antidiabetic Drugs
- Dipeptidylpeptidase-4 inhibitors
- Sitagliptin (Januvia)
- Vildagliptin (Galvus)
- Saxagliptin (Onglyza)
- Linagliptin (Tradjenta)
- Inhibitors of dipeptidyl peptidase 4, also DPP-4
inhibitors or gliptins, block DPP-4 enzyme which
is responsible for the degradation of Glucagon
Like Peptide 1 (GLP 1). - Glucagon Like Peptide 1 (GLP 1) inhibit Glucagon
release which leads to increased insulin
secretion, decreased gastric emptying, and
decreased blood glucose levels.
3DPP4 inhibitors and Tocofersolan
- Dipeptidylpeptidase-4 inhibitors
- Tocofersolan
- Tocofersolan inhibits P-glycoprotein-mediated
efflux transport of DPP4 inhibitors - Increased exposure of Dipeptidylpeptidase-4
inhibitors - If concomitant use of DPP4 inhibitors and
Tocofersolan is required, monitoring and dose
adjustments are recommended.
4DPP4 inhibitors and Nilotinib
- Dipeptidylpeptidase-4 inhibitors
- Nilotinib
- Nilotinib inhibits P-glycoprotein-mediated efflux
transport of DPP4 inhibitors - Increased exposure of Dipeptidylpeptidase-4
inhibitors - Exercise caution if DPP4 inhibitors and Nilotinib
are administered concomitantly.
5DPP4 inhibitors and Lomitapide
- Dipeptidylpeptidase-4 inhibitors
- Lomitapide
- Lomitapide inhibits P-glycoprotein-mediated
efflux transport of DPP4 inhibitors - Increased exposure of Dipeptidylpeptidase-4
inhibitors - Consider reducing the dose of DPP4 inhbitors if
lomitapide is used concurrently.
6DPP4 inhibitors and Piperaquine
- Dipeptidylpeptidase-4 inhibitors
- Piperaquine
- Piperaquine inhibits CYP3A4 -mediated metabolism
of DPP4 inhibitors - Increased exposure of Dipeptidylpeptidase-4
inhibitors - Due to the long half-life of piperaquine, caution
is advised with administration of a DPP4
inhibitors for up to 3 months after
discontinuation of piperaquine therapy. - If concomitant administration is required, use
caution and monitor the patient closely.
7DPP4 inhibitors and Amiodarone
- Dipeptidylpeptidase-4 inhibitors
- Amiodarone
- Amiodarone inhibits CYP1A2, CYP2C9, CYP2D6,
CYP3A4, and of P-glycoprotein efflux transport - Increased exposure of DPP4 inhibitors
- As amiodarone has a variable and long half-life,
potential drug interaction may occur even after
amiodarone is discontinued. - If amiodarone is used concomitantly (or after
amiodarone is discontinued) with sitagliptin, use
with caution, monitor for increased adverse
effects, and consider dose adjustment as
appropriate.
8DPP4 inhibitors and Dabrafenib
- Dipeptidylpeptidase-4 inhibitors
- Dabrafenib
- Dabrafenib induces CYP3A4 -mediated metabolism of
DPP4 inhibitors - Decreased exposure of Dipeptidylpeptidase-4
inhibitors - If possible, substitute the use of CYP3A4
substrates during dabrafenib therapy. - If concomitant use cannot be avoided, monitor
patients for loss of efficacy.
9DPP4 inhibitors and Eslicarbazepine
- Dipeptidylpeptidase-4 inhibitors
- Eslicarbazepine
- Eslicarbazepine induces CYP3A4 -mediated
metabolism of DPP4 inhibitors - Decreased exposure of Dipeptidylpeptidase-4
inhibitors - If concomitant administration is required,
consider increasing the dose of the DPP4
inhibitors.
10DPP4 inhibitors and Primidone
- Dipeptidylpeptidase-4 inhibitors
- Primidone
- Primidone induces CYP3A4 -mediated metabolism of
DPP4 inhibitors - Decreased exposure of Dipeptidylpeptidase-4
inhibitors - Avoid concomitant use if clinically possible.
- If coadministration is required, use caution and
monitor the patient closely.
11Sitagliptin And Danazol
- Sitagliptin
- Danazol
- Danazol induces insulin resistance
- Increased blood glucose levels (Hyperglycemia)
- Use caution with the concomitant use of danazol
and antidiabetic medications. - Increased blood sugar monitoring and dose
adjustments of antidiabetic medications may be
warranted during coadministration and after
discontinuation of danazol.
12Sitagliptin And Sulfonylureas
- Sitagliptin
- Sulfonylureas
- Additive hypoglycemic effects
- Increased risk of hypoglycemia
- The dose of the sulfonylurea may need to be
reduced. - Monitor blood glucose concentrations closely when
sitagliptin and a sulfonylurea are used
concomitantly.
13Sitagliptin And Trandolapril
- Sitagliptin
- Trandolapril
- Increased blood glucose lowering effect
- Increased risk of hypoglycemia
- More frequent blood glucose monitoring and/or
observation for signs or symptoms of hypoglycemia
may be necessary.
14Sitagliptin And Digoxin
- Sitagliptin
- Digoxin
- Increased digoxin exposure and plasma
concentration - Use caution if these agents are coadministered
and monitor patients appropriately. - No dosage adjustment of digoxin is recommended
15Saxagliptin And Cobicistat
- Saxagliptin
- Cobicistat
- Cobicistat inhibits CYP3A4
- Increased plasma concentrations of saxagliptin
- Caution is advised when using saxagliptin
together with a strong CYP3A4 inhibitor such as
cobicistat. - If concomitant use is required, a dose adjustment
of saxagliptin to 2.5 mg/day is recommended.
16Saxagliptin And Azole antifungals
- Saxagliptin
- Azole antifungals (Posaconazole, Itraconazole
Ketoconazole) - Azole antifungals inhibit CYP3A4
- Increased plasma concentrations of saxagliptin
- Use caution if these agents are coadministered.
- Dose adjustment of saxagliptin 2.5 mg/day is
recommended when used with Posaconazole,
Itraconazole Ketoconazole.
17Saxagliptin And Antivirals (Protease
inhibitors)
- Saxagliptin
- Indinavir, Nelfinavir, Saquinavir Ritonavir
- Indinavir inhibits CYP3A4
- Increased plasma levels of saxagliptin
- Use caution when prescribing these antivirals in
patients taking saxagliptin, particularly in
patients with compromised renal function. - Dose adjustment of saxagliptin 2.5 mg/day is
recommended when used with these antivirals.
18Saxagliptin And Macrolide antibiotics
- Saxagliptin
- Macrolide antibiotics (Telithromycin and
Clarithromycin) - Inhibition of CYP3A4 by Macrolide antibiotics
- Increased plasma concentrations of saxagliptin
- Use caution if these agents are coadministered.
- Dose adjustment of saxagliptin 2.5 mg/day is
recommended when used with Macrolide antibiotics.
19Saxagliptin And Deferasirox
- Saxagliptin
- Deferasirox
- Induction of CYP3A4 by deferasirox
- Reduced plasma concentrations of saxagliptin
- Caution is advised when deferasirox and
saxagliptin are coadministered. - If concomitant use is required, monitor patients
for reduced effectiveness.
20Linagliptin And Rifampin
- Linagliptin
- Rifampin Rifabutin
- Induction of CYP3A4-mediated metabolism and
P-glycoprotein-mediated efflux of linagliptin by
rifampin - Decreased linagliptin exposure
- Selection of an alternative to rifampin, with no
or minimal enzyme induction potential, is
strongly recommended.
21Linagliptin And Phenytoin
- Linagliptin
- Phenytoin
- Induction of CYP3A4-mediated metabolism of
linagliptin by phenytoin - Decreased linagliptin exposure
- Selection of an alternative to phenytoin, with no
or minimal enzyme induction potential, is
strongly recommended.
22Linagliptin And Phenobarbital
- Linagliptin
- Phenobarbital
- Induction of CYP3A4-mediated metabolism of
linagliptin by phenobarbital - Decreased linagliptin exposure
- Selection of an alternative to phenobarbital,
with no or minimal enzyme induction potential, is
strongly recommended.
23Linagliptin And Carbamazepine
- Linagliptin
- Carbamazepine
- Induction of CYP3A4-mediated metabolism of
linagliptin by carbamazepine - Decreased linagliptin exposure
- Selection of an alternative to carbamazepine,
with no or minimal enzyme induction potential, is
strongly recommended.
24Linagliptin And St Johns Wort
- Linagliptin
- St Johns Wort
- Induction of P-glycoprotein-mediated efflux of
linagliptin by St John's wort - Decreased linagliptin plasma concentrations and
exposure - Selection of an alternative to St John's wort is
strongly recommended.
25Conclusion
- The diabetics should consult their physician and
pharmacist. - The diabetics should bring a list of all of the
drugs they are taking (or simply bring the drugs
themselves), including prescription drugs,
over-the-counter drugs, and any supplements,
herbal or otherwise, during their visit to the
doctor or pharmacist. - They are encouraged to ask their doctor or
pharmacist to look over their list for any
potentially dangerous combinations. - It is recommended that people fill all their
prescriptions at one pharmacy, if possible. In
addition, they should maintain a list of all of
their medicines and update it when one is added
or removed. - They should review their list with their doctor
or pharmacist regularly, particularly when they
begin to take a new medicine.
26References
- Stockleys Drug Interactions, 9e
- Karen Baxter
- British National Formulary
- June 2013
- Basic Clinical Pharmacology, 12e Bertram
G. Katzung, Susan B. Masters, Anthony J. Trevor - Goodman Gilman's The Pharmacological Basis of
Therapeutics, 12e Laurence L. Brunton, Bruce
A. Chabner, Björn C. Knollmann -
27References
- http//www.micromedexsolutions.com
- http//www.ncbi.nlm.nih.gov/pmc/articles/PMC301938
7/ - http//spectrum.diabetesjournals.org/content/19/4/
202.full.pdfhtml - http//www.fda.gov/cder/consumerinfo/druginteracti
ons.htm - http//medicine.iupui.edu/clinpharm/ddis/
- http//www.australianprescriber.com/magazine/24/4/
83/5