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Drug Interactions of Metformin, Metformin and cationic drugs, Metformin and Carbonic anhydrase inhibitors, Metformin and

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Metformin interacts with Cationic drugs, Carbonic anhydrase inhibitors, Injection of iodinated contrast materials, phenprocoumon, dofetilide, rifampin, colesevelam, enalapril, trandolapril, guar gum and glycopyrrolate. – PowerPoint PPT presentation

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Title: Drug Interactions of Metformin, Metformin and cationic drugs, Metformin and Carbonic anhydrase inhibitors, Metformin and


1
Drug Interactions of antidiabetics (part 5)
  • Dr.P.Naina Mohamed
  • Pharmacologist

2
Oral Antidiabetic Drugs
  • Insulin sensitizers
  • Biguanides
  • Metformin (Glucophage)
  • Metformin is the first-line drug of choice for
    the treatment of type 2 diabetes.
  • It is particularly useful in overweight and obese
    people and those with normal kidney function.
  • It is also used in the treatment of polycystic
    ovary syndrome (PCOS).

3
Metformin and cationic drugs
  • Metformin
  • Cationic drugs (Cimetidine, Ranitidine,
    Procainamide, Digoxin, Quinidine, Quinine,
    Morphine, Triamterene, Amiloride, Dolutegravir,
    Cephalexin, Trimethoprim, and vancomycin)
  • Metformin is a cationic (positively charged)
    molecule and may compete for organic cation
    transporters in the kidneys with other cationic
    drugs for renal secretion
  • Inhibition of renal organic cation transporters
  • Inhibition of tubular secretion of metformin
  • Increase in metformin plasma concentrations
  • Increased risk of metformin-associated lactic
    acidosis (MALA)
  • If coadministration is required, closely monitor
    patient when starting or stopping combination
    therapy.
  • Dose adjustments of metformin may be warranted.

4
Metformin and Carbonic anhydrase inhibitors
  • Metformin
  • Carbonic anhydrase inhibitors (Topiramate,
    Acetazolamide, Zonisamide and Dichlorphenamide)
  • Carbonic anhydrase inhibitors may decrease sodium
    bicarbonate levels
  • Additive risk of metabolic acidosis
  • Concomitant use of metformin and topiramate is
    contraindicated.

5
Metformin and Injection of iodinated contrast
materials
  • Metformin
  • Injection of iodinated contrast materials
    (Iocetamic acid, Iopronic acid, Ioxitalamic acid,
    Iodoxamic acid, Acetrizoic acid, Metrizoic acid,
    Ioglycemic acid, Iopanoic acid, Iodohippuric
    acid, Ioseric acid, Iobenzamic acid, Ioglycic
    acid, Iocarmic acid, Iotroxic acid, Iobitridol,
    Iodamide, Ipodate, Iodixanol, Iodopyralet,
    Iosimide, Ethiodized oil, Metrizamide, Tyroponate
    sodium, Iopentol, Iodipamide, Iotasul, Iotrolan,
    Ioxaglate, Diatrizoate, Iothalamate, Iohexol,
    Iopromide, Iopamidol, Iophendylate, Ioversol and
    Iomeprol)
  • Lactic acidosis and acute renal failure
  • Concurrent use of metformin is contraindicated in
    patients receiving intravascular iodinated
    contrast media.
  • Withhold metformin prior to or at the time of the
    procedure and for 48 hours following the
    procedure.
  • Restart metformin only after kidney function has
    been re-evaluated and found to be normal.

6
Metformin and dofetilide
  • Metformin
  • Dofetilide
  • Metformin may compete with dofetilide for
    secretion via the renal cation transport system
  • Elimination of dofetilide may be decreased
  • Increased dofetilide plasma concentrations
  • Increased risk of cardiotoxicity (QT
    prolongation, torsades de pointes, cardiac
    arrest)
  • Metformin should be cautiously used in
    combination with dofetilide.
  • Monitor the patient for increased dofetilide
    plasma levels, and for signs of ventricular
    arrhythmias, including faintness, dizziness, and
    tachycardia.

7
Metformin and rifampin
  • Metformin
  • Rifampin
  • Increased organic cation transporter (OCT1)
    expression and hepatic uptake of metformin
  • Increased metformin plasma concentrations
  • Enhanced glucose lowering effects of metformin
  • Use caution when prescribing rifampin to patients
    who are taking metformin.
  • Closely monitor blood glucose levels and for
    signs and symptoms of hypoglycemia in patients
    taking metformin and rifampin concurrently.

8
Metformin and phenprocoumon
  • Metformin
  • Phenprocoumon
  • Metformin altering blood flow to the liver and
    interfering with enterohepatic circulation
  • Reduces efficacy of phenprocoumon
  • There is some evidence that a small increase in
    the dose of phenprocoumon may be necessary if
    metformin is given.
  • This can be managed with routine anticoagulant
    monitoring.

9
Metformin and colesevelam
  • Extended-release Metformin
  • Colesevelam
  • Increased exposure to extended-release metformin
  • If concurrent therapy with colesevelam and
    extended-release metformin is necessary, monitor
    patients for appropriate clinical response to
    metformin.

10
Metformin and enalapril
  • Metformin
  • Enalapril
  • Hyperkalemic lactic acidosis
  • Avoid metformin and enalapril in patients with
    renal insufficiency.

11
Metformin and trandolapril
  • Metformin
  • 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.

12
Metformin and danazol
  • Metformin
  • Danazol
  • Danazol cause insulin resistance
  • Raised blood glucose levels
  • Use caution with the concomitant use of danazol
    and antidiabetic medications, such as metformin.
  • Increased blood sugar monitoring and dose
    adjustments of antidiabetic medications may be
    warranted during coadministration and after
    discontinuation of danazol.

13
Metformin and guar gum
  • Metformin
  • Guar gum
  • Guar gum, acting as a gel, delays gastric
    emptying
  • Delayed delivery of metformin to its site of
    absorption
  • Reduced rate and extent of absorption of
    metformin
  • Decreased effectiveness of metformin
  • Administer guar gum at least 6 hours after
    metformin to retain maximal effectiveness of
    metformin , as metformin is absorbed within 6
    hours of administration.
  • Guar gum may also delay absorption of glucose
    from meals, leading to less postprandial
    hyperglycemia.
  • Closely monitor blood glucose levels and signs
    and symptoms of hypoglycemia when both agents are
    used together.

14
Metformin and glycopyrrolate
  • Metformin
  • Glycopyrrolate
  • Increased plasma concentrations of metformin
  • Caution is warranted if metformin is to be
    coadministered with glycopyrrolate.
  • Concurrent administration of glycopyrrolate with
    metformin requires monitoring of metformin
    activity.
  • Consider metformin dose adjustment as necessary.

15
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.

16
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

17
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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