Drug Interactions of antidiabetics (PART 4): Interactions of MEGLITINIDES - PowerPoint PPT Presentation

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Drug Interactions of antidiabetics (PART 4): Interactions of MEGLITINIDES

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¢ Drug interactions of Meglitinides (Repaglinide & Nateglinide) are dealt in this presentation. ¢ Repaglinide is metabolized by the CYP3A4 and CYP2C8 and hence it interacts with Gemfibrozil, Azole antifungals, Dabrafenib, Montelukast, Macrolide antibiotics and Rifampicin. ¢ Nateglinide is metabolized by CYP2C9 (70%) and CYP3A4 (30%) and it interacts with Amiodarone and Macrolide antibiotics. It also interacts with NSAIDs, MAOIs, Trandolapril, Non selective beta blockers Thiazide diuretics, Corticosteroids, Danazol, Sympathomimetics, Phenytoin and St.John’s wort. – PowerPoint PPT presentation

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Title: Drug Interactions of antidiabetics (PART 4): Interactions of MEGLITINIDES


1
Drug Interactions of antidiabetics(PART 4)
  • Dr.P.Naina Mohamed
  • Pharmacologist

2
ORAL Antidiabetic Drugs
  • Secretagogues
  • Sulfonylureas
  • First-generation agents
  • Tolbutamide (Orinase), Acetohexamide (Dymelor),
    Tolazamide (Tolinase), Chlorpropamide (Diabinese)
  • Second-generation agents
  • Glipizide (Glucotrol), Glyburide or Glibenclamide
    (Diabeta, Micronase, Glynase), Glimepiride
    (Amaryl), Gliclazide (Diamicron), Glycopyramide,
    Gliquidone.
  • Meglitinides
  • Repaglinide (Prandin)
  • Nateglinide (Starlix)

3
Repaglinide and gemfibrozil
  • Repaglinide
  • Gemfibrozil
  • Gemfibrozil inhibits CYP2C8
  • Inhibition of metabolism of repaglinide
  • Increased plasma concentrations of repaglinide
  • Hypoglycemic Complications
  • Concomitant use of repaglinide and gemfibrozil is
    not recommended.
  • If the combination is considered clinically
    necessary, repaglinide dose should be reduced and
    blood glucose concentrations carefully monitored.

4
Repaglinide and Azole Antifungals
  • Repaglinide
  • Azole Antifungals (Itraconazole)
  • Itraconazole inhibits CYP3A4
  • Inhibition of metabolism of repaglinide
  • Increased plasma concentrations of repaglinide
  • Hypoglycemic Complications
  • Concomitant use of repaglinide and itraconazole
    is not recommended.
  • If the combination is considered clinically
    necessary, repaglinide dose should be reduced and
    blood glucose concentrations carefully monitored.

5
Repaglinide and dabrafenib
  • Repaglinide
  • Dabrafenib
  • Dabrafenib induces CYP3A4, CYP2C8 CYP2C9
  • Decrease the exposure of the Repaglinide
  • Loss of Efficacy
  • If concomitant use of dabrafenib and a multiple
    enzyme substrate is required, monitor patients
    for loss of efficacy.

6
Repaglinide and montelukast
  • Repaglinide
  • Montelukast
  • Montelukast inhibit CYP2C8
  • Increased repaglinide plasma concentrations
  • Use caution if montelukast and repaglinide are
    coadministered.
  • Dosage adjustments to repaglinide may be
    necessary and blood glucose concentrations should
    be carefully monitored.

7
Meglitinides and macrolides
  • Meglitinides
  • Macrolide Antibiotics (Clarithromycin)
  • Clarithromycin inhibits CYP3A4
  • Increased exposure to nateglinide
  • Hypoglycemia
  • Caution is advised if clarithromycin and
    nateglinide are coadministered.
  • Blood glucose concentrations should be carefully
    monitored.

8
Nateglinide and amiodarone
  • Nateglinide
  • Amiodarone
  • Amiodarone inhibits CYP2C9
  • Inhibition of metabolism of Nateglinide
  • Increased risk of hypoglycemia
  • In patients receiving amiodarone and nateglinide,
    monitor for changes in glycemic control during
    both administration and treatment withdrawal.

9
Meglitinides and rifampicin
  • Repaglinide or Nateglinide
  • Rifampicin (Rifampin)
  • Rifampin induces CYP2C8 CYP2C9
  • Increased metabolism of meglitinides
  • Loss of efficacy
  • The information regarding nateglinide and
    repaglinide is limited.
  • Increase in blood glucose monitoring would be
    prudent.

10
Nateglinide and nsaid
  • Nateglinide
  • NSAIDs
  • NSAIDS Potentiate the hypoglycemic action of
    Nateglinide
  • Increased risk of hypoglycemia
  • Use caution and monitor the patient for changes
    in glycemic control when an NSAID and nateglinide
    are coadministered.

11
Nateglinide and mao inhibitors
  • Nateglinide
  • MAO Inhbitors
  • MAOIs may potentiate the actions of nateglinide
  • Additive reduction of blood sugar
  • Increased risk of hypoglycemia
  • Use caution when prescribing an MAOI such as
    phenelzine, tranylcypromine, or selegiline to
    patients who take nateglinide and monitor the
    patient for changes in glycemic control during
    both administration and treatment withdrawal.

12
Nateglinide and trandolapril
  • Nateglinide
  • 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.

13
Nateglinide and beta blockers
  • Nateglinide
  • Nonselective beta blockers
  • Nonselective beta blockers may potentiate the
    hypoglycemic action of nateglinide
  • Increased risk of hypoglycemia
  • Use caution when prescribing a non-selective
    beta-blocker such as propranolol, sotalol, or
    timolol to patients who take nateglinide and
    monitor the patient for changes in glycemic
    control during both administration and treatment
    withdrawal.

14
Nateglinide and thiazides
  • Nateglinide
  • Thiazide diuretics
  • Reduced hypoglycemic action of nateglinide
  • Use caution when prescribing a thiazide diuretic
    such as hydrochlorothiazide or metolazone to
    patients who take nateglinide and monitor the
    patient for changes in glycemic control during
    both administration and treatment withdrawal.

15
Nateglinide and corticosteroids
  • Nateglinide
  • Corticosteroid
  • Reduced hypoglycemic action of nateglinide
  • Use caution when prescribing a corticosteroid
    such as dexamethasone, hydrocortisone, or
    prednisone to patients who take nateglinide and
    monitor the patient for changes in glycemic
    control during both administration and treatment
    withdrawal.

16
Nateglinide and danazol
  • Nateglinide
  • Danazol
  • Danazol can cause insulin resistance
  • Increased blood glucose levels
  • Use caution with the concomitant use of danazol
    and antidiabetic medications, such as
    nateglinide.
  • Increased blood sugar monitoring and dose
    adjustments of antidiabetic medications may be
    warranted during coadministration and after
    discontinuation of danazol.

17
Nateglinide and sympathomimetics
  • Nateglinide
  • Sympathomimetic (Pseudoephedrine or
    Phenylephrine)
  • Reduced hypoglycemic action of nateglinide
  • Use caution when prescribing a sympathomimetic,
    such as pseudoephedrine or phenylephrine to
    patients who take nateglinide.
  • Monitor the patient for changes in glycemic
    control during both administration and treatment
    withdrawal.

18
Nateglinide and phenytoin
  • Nateglinide
  • Phenytoin
  • Phenytoin inhibits insulin release
  • Reduced hypoglycemic action of nateglinide
  • Use caution when prescribing phenytoin to
    patients who take nateglinide.
  • In patients receiving concomitant treatment with
    nateglinide and phenytoin, monitoring for changes
    in glycemic control during both administration
    and treatment withdrawal is recommended.

19
Nateglinide and st johns wort
  • Nateglinide
  • St Johns Wort
  • Reduction in the hypoglycemic action of
    nateglinide
  • Use caution when prescribing St. John's wort to
    patients who take nateglinide.
  • Monitor the changes in glycemic control during
    administration of Nateglinide and treatment
    withdrawal.

20
Antidiabetics and thyroid hormones
  • Antidiabetic
  • Thyroid hormone
  • Reduced efficacy of antidiabetic
  • If concurrent use of a thyroid hormone
    (levothyroxine or liothyronine) and an
    antidiabetic agent (glyburide, nateglinide, or
    insulin) is required, an increase in the
    antidiabetic agent dose may be necessary.
  • Careful monitoring of diabetic control is
    recommended, particularly when a thyroid hormone
    agent is initiated, changed, or stopped.

21
Antidiabetics and bitter melon
  • Antidiabetic
  • Bitter melon
  • Bitter melon increases hepatic or peripheral
    glucose disposal
  • Additive reductions in blood glucose
  • Increased risk of hypoglycemia
  • If bitter melon and an antidiabetic agent are
    used together, blood glucose levels should be
    monitored regularly.

22
Antidiabetics and glucomannan
  • Antidiabetic
  • Glucomannan
  • Glucomannan may slow gastric emptying, increase
    the viscosity of gastrointestinal contents, and
    act as a barrier to diffusion
  • Slowed absorption of hypoglycemic agents and
    glucose
  • Increased risk of hypoglycemia
  • Blood glucose should be monitored closely in
    patients taking glucomannan concomitantly with
    antidiabetic agents.

23
Antidiabetics and gymnema
  • Antidiabetic
  • Gymnema extracts
  • Increased risk of hypoglycemia
  • If patients choose to take gymnema with an
    antidiabetic agent, monitor blood glucose levels
    and signs symptoms of hypoglycemia.

24
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.

25
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

26
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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