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

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Drug Interactions of antidiabetics(PART 4)

• Dr.P.Naina Mohamed
• Pharmacologist

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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)

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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

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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/
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