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Interactions of Thiazolidinediones

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Thiazolidinediones interact with Abiraterone, Pixantrone, Azole Antifungals, Fibrates, Teriflunomide, Dabrafenib and Rifampin. Pioglitazone also interacts with Calcium channel blockers (Nifedipine, Amlodipine), Cobicistat, Piperaquine, Ifosfamide, Tolvaptan, Midazolam, Tipranavir/Ritonavir, Macrolide antibiotics, Sulphonamides, Amiodarone, Topiramate, Oral contraceptives, Atorvastatin, Danazol and Trandolapril. – PowerPoint PPT presentation

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Title: Interactions of Thiazolidinediones


1
Drug Interactions of antidiabetics (part 6)
  • Dr.P.Naina Mohamed
  • Pharmacologist

2
ORAL Antidiabetic Drugs
  • Insulin sensitizers
  • Thiazolidinediones (TZDs)
  • Rosiglitazone (Avandia)
  • Pioglitazone (Actos)
  • The thiazolidinediones (TZDs) or 'glitazones'
    improve metabolic control in patients with type 2
    diabetes through the improvement of insulin
    sensitivity.
  • TZDs reduce insulin resistance in adipose tissue,
    muscle and the liver.

3
Thiazolidinediones AND Abiraterone
  • Thiazolidinediones
  • Abiraterone
  • Abiraterone inhibits CYP2C8- and CYP2C9
  • Blockade of metabolism of TZDs
  • Increased plasma concentrations of TZDs
  • If TZDs and abiraterone acetate are administered
    concurrently, patients should be monitored
    closely.
  • Changes to diabetes therapy may be needed,
    especially when abiraterone acetate is started or
    stopped during treatment with TZDs.

4
Thiazolidinediones AND Pixantrone
  • Thiazolidinediones
  • Pixantrone
  • Pixantrone inhibits CYP2C8
  • Inhibition of metabolism of TZDs
  • Enhanced plasma concentrations of TZDs
  • If concomitant use is required, careful
    monitoring for side effects associated with
    increased concentrations of the TZDs is
    recommended.

5
Thiazolidinediones AND Azole Antifungals
  • Thiazolidinediones
  • Azole Antifungals (Fluconazole, Ketoconazole,
    Itraconazole, Miconazole)
  • Inhibition of CYP enzymes (CYP2C9, CYP3A4,
    CYP2C8)
  • Blockade of metabolism of Thiazolidinediones
  • Accumulation of TZDs
  • Increased glucose lowering effects
  • Caution is advised if ketoconazole is used with
    pioglitazone.
  • Monitor blood glucose concentrations if
    ketoconazole is added to or withdrawn from a
    treatment regimen that includes pioglitazone.
  • Dose adjustments to pioglitazone may be
    necessary.

6
Thiazolidinediones AND Fibrates
  • Thiazolidinediones
  • Fibrates (Gemfibrozil, Fenofibrate)
  • Fibrates inhibit CYP2C8
  • Inhbition of metabolism of TZDs
  • Elevated Plasma levels of TZDs
  • Increased risk of hypoglycemia
  • If used in combination with gemfibrozil, the
    maximum recommended dose of pioglitazone is 15
    mg/day.
  • Blood glucose levels should be carefully
    monitored during coadministration.

7
Thiazolidinediones and Teriflunomide
  • Thiazolidinediones
  • Teriflunomide
  • Teriflunomide inhibit CYP2C8
  • Inhbition of metabolism of TZDs
  • Elevated Plasma levels of TZDs
  • Increased risk of hypoglycemia
  • If concomitant use is required, monitoring is
    recommended.
  • Pioglitazone dose adjustment may be necessary.

8
Thiazolidinediones and Dabrafenib
  • Thiazolidinediones
  • Dabrafenib
  • Dabrafenib induces CYP3A4 and possibly CYP2C8,
    CYP2C9, CYP2C19, and CYP2B6
  • Increased metabolism of TZDs
  • If possible, substitute the use of TZDs (multiple
    enzyme substrates) during dabrafenib therapy.
  • If concomitant use of dabrafenib and a TZD is
    required, monitor patients for loss of efficacy.

9
Thiazolidinediones and Rifampin
  • Thiazolidinediones
  • Rifampin
  • Rifampin induces CYP2C8
  • Induction of metabolism of TZDs
  • Decreased Plasma levels of TZDs
  • Increased risk of hyperglycemia
  • Caution is advised if these 2 agents are
    coadministered.
  • TZDs dosage should be adjusted based on clinical
    response.

10
Pioglitazone and CCBs
  • Pioglitazone
  • CCBs (Nifedipine , Amlodipine, Nimidipine)
  • Pioglitazole induce CYP3A4-mediated nifedipine
    metabolism
  • Decreased nifedipine exposure
  • Coadministration of Pioglitazone and CCBs
    (Nifedipine , Amlodipine, Nimidipine) may
    significantly reduce the effectiveness of CCBs.
  • Avoid concomitant use of CCBs and any known
    CYP3A4 inducer.
  • Alternate antihypertensive treatment should be
    considered.

11
Pioglitazone and Cobicistat
  • Pioglitazone
  • Cobicistat
  • Pioglitazole induce CYP3A4-mediated Cobicistat
    metabolism
  • Decreased plasma concentrations of Cobicistat
  • Loss of therapeutic efficacy of Cobicistat
  • Development of viral resistance
  • Caution is advised when using cobicistat together
    with a CYP3A inducer.
  • If concomitant use is required, consider
    monitoring HIV virologic response.

12
Pioglitazone and Piperaquine
  • Pioglitazone
  • Piperaquine
  • Pioglitazole induce CYP3A4-mediated Piperaquine
  • metabolism
  • Decreased plasma concentrations of Piperaquine
  • Loss of therapeutic efficacy of Piperaquine
  • The concomitant use of piperaquine (a CYP3A4
    substrate) with a CYP3A4 inducer may decrease
    piperaquine exposure and is not recommended.

13
Pioglitazone and Ifosfamide
  • Pioglitazone
  • Ifosfamide
  • Pioglitazole induce CYP3A4-mediated Ifosfamide
  • Metabolism
  • Increased formation of active alkylating
    metabolites of Ifosfamide
  • Increased risk of neurotoxic and nephrotoxic side
    effects of ifosfamide
  • Patients taking ifosfamide and CYP3A4 inducers,
    such as pioglitazone, should be carefully
    monitored for toxicity.
  • Ifosfamide dose adjustment may be required.

14
Pioglitazone and Tolvaptan
  • Pioglitazone
  • Tolvaptan
  • Pioglitazone induce CYP3A-mediated tolvaptan
    metabolism
  • Decreased tolvaptan plasma concentrations
  • Concomitant use of pioglitazone and tolvaptan
    should be avoided due to a risk of reduced plasma
    concentrations of tolvaptan.
  • If concomitant use is required, the dose of
    tolvaptan may need to be increased to achieve the
    same clinical effect.

15
Pioglitazone and Midazolam
  • Pioglitazone
  • Midazolam
  • Pioglitazone induce CYP3A4-mediated metabolism of
    midazolam
  • Decreased plasma concentrations of midazolam
  • The concomitant administration of midazolam and
    pioglitazone should be approached with caution.
  • Dosage adjustments of midazolam may be necessary
    when pioglitazone is added to or withdrawn from
    the therapy regimen.

16
Pioglitazone and Tipranavir/Ritonavir
  • Pioglitazone
  • Tipranavir/Ritonavir
  • Inhibition of CYP3A enzymes by Tipranavir/Ritonavi
    r
  • Altered pioglitazone plasma concentrations
  • Coadministration of tipranavir/ritonavir and
    pioglitazone may result in altered (increased or
    decreased) pioglitazone levels.
  • Monitor glucose levels when pioglitazone is
    administered concurrently with tipranavir/ritonavi
    r.

17
Pioglitazone and Macrolide antibiotics
  • Pioglitazone
  • Macrolide antibiotics (Clarithromycin)
  • Clarithromycin inhibits CYP3A4
  • Reduced metabolism of Pioglitazone
  • Increased plasma concentrations of pioglitazone
  • May cause hypoglycemia
  • Caution is advised if clarithromycin and
    pioglitazone are coadministered.
  • If concomitant use is necessary, advise the
    patient to carefully monitor blood glucose
    concentrations.

18
Pioglitazone and Sulphonamides
  • Pioglitazone
  • Sulphonamides (Trimethoprim, Sulphamethoxazole)
  • Trimethoprim inhibits CYP2C8
  • Reduced metabolism of pioglitazone
  • Increased pioglitazone exposure
  • Potentiation of hypoglycemic effects
  • Use caution with the coadministration of
    pioglitazone and trimethoprim.
  • If concomitant use is required, monitor blood
    glucose as clinically indicated.

19
Pioglitazone and Amiodarone
  • Pioglitazone
  • Amiodarone
  • Amiodarone induces CYP3A4
  • Increased metabolism of Pioglitazone
  • Decreased plasma concentrations of pioglitazone
  • Loss of efficacy
  • Additional monitoring and amiodarone dose
    adjustment may be warranted.

20
Pioglitazone and Topiramate
  • Pioglitazone
  • Topiramate
  • Decreased pioglitazone exposure
  • Loss of Therapeutic efficacy
  • If topiramate and pioglitazone are administered
    concurrently, routinely monitor patients for
    adequate control of their diabetes.

21
Pioglitazone and Oral Contraceptives
  • Pioglitazone
  • Oral Contraceptives
  • Loss of contraceptive efficacy
  • During administration of pioglitazone, the use of
    contraceptives containing ethinyl estradiol or
    norethindrone may not be effective.
  • Additional caution regarding contraceptive use
    and alternative methods of contraception should
    be considered.

22
Pioglitazone and Atorvastatin
  • Pioglitazone
  • Atorvastatin
  • Decreased pioglitazone serum concentrations
  • Loss of therapeutic efficacy
  • Caution is advised if atorvastatin is used with
    pioglitazone.
  • Monitor blood glucose concentrations if
    atorvastatin is added to or withdrawn from a
    treatment regimen that includes pioglitazone.
  • Dose adjustments to pioglitazone may be
    necessary.

23
Pioglitazone and Danazol
  • Pioglitazone
  • Danazol
  • Danazol can cause insulin resistance
  • Increased blood glucose levels
  • Use caution with the concomitant use of danazol
    and antidiabetic medications, such as
    pioglitazone.
  • Increased blood sugar monitoring and dose
    adjustments of antidiabetic medications may be
    warranted during coadministration and after
    discontinuation of danazol.

24
Pioglitazone and Trandolapril
  • Pioglitazone
  • Trandolapril
  • Increased blood glucose lowering effect
  • Elevated risk of hypoglycemia
  • More frequent blood glucose monitoring and/or
    observation for signs or symptoms of hypoglycemia
    may be necessary.

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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