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Drug Interactions of Antidiabetics (Part 8): Interactions of DPP 4 Inhibitors

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Title: Drug Interactions of Antidiabetics (Part 8): Interactions of DPP 4 Inhibitors


1
Drug Interactions of antidiabetics (part 8)
  • Dr.P.Naina Mohamed
  • Pharmacologist

2
Oral 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.

3
DPP4 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.

4
DPP4 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.

5
DPP4 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.

6
DPP4 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.

7
DPP4 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.

8
DPP4 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.

9
DPP4 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.

10
DPP4 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.

11
Sitagliptin 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.

12
Sitagliptin 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.

13
Sitagliptin 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.

14
Sitagliptin 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

15
Saxagliptin 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.

16
Saxagliptin 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.

17
Saxagliptin 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.

18
Saxagliptin 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.

19
Saxagliptin 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.

20
Linagliptin 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.

21
Linagliptin 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.

22
Linagliptin 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.

23
Linagliptin 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.

24
Linagliptin 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.

25
Conclusion
  • 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.

26
References
  • 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

27
References
  • 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
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