Drug Interactions of antidiabetics (Part 2)

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Drug Interactions of antidiabetics(part 2)

• Dr.P.Naina Mohamed
• Pharmacologist

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Antidiabetic Drugs

• PARENTERAL ANTIDIABETIC DRUGS
• Insulins
• Rapid acting insulins
• Regular insulin (Humulin R, Novolin R)
• Insulin lispro (Humalog)
• Insulin aspart (Novolog)
• Insulin glulisine (Apidra)
• Prompt insulin zinc (Semilente, Slightly slower
  acting)
• Intermediate acting insulins include
• Isophane insulin, neutral protamine Hagedorn
  (NPH) (Humulin N, Novolin N)
• Insulin zinc (Lente)
• Long acting insulins include
• Extended insulin zinc insulin (Ultralente)
• Insulin glargine (Lantus)
• Insulin detemir (Levemir)
• Incretin Mimetics (Glucagon-like peptide
  analogues)
• Exenatide (Exendin-4, Byetta) - First GLP-1
  agonist.
• Liraglutide (Victoza) - once-daily human
  analogue.
• Taspoglutide - Presently in Phase III clinical
  trials.

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Antidiabetic Drugs

• 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)
• Insulin sensitizers
• Biguanides
• Metformin (Glucophage)
• Thiazolidinediones (TZDs)
• Rosiglitazone (Avandia)
• Pioglitazone (Actos)

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Antidiabetic Drugs

• Alpha-glucosidase inhibitors
• Acarbose (Precose/Glucobay)
• Miglitol (Glyset)
• Voglibose
• Dipeptidylpeptidase-4 inhibitors
• Sitagliptin (Januvia)
• Vildagliptin (Galvus)
• Saxagliptin (Onglyza)
• Linagliptin (Tradjenta)
• Aldose reductase inhibitors
• Epalrestat
• Sodium-glucose co-transporter 2 inhibitors
• Dapagliflozin
• Canagliflozin

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Interactions of incretin mimetics amylin
analogue

• Interactions of Incretin Mimetics
• Exenatide Warfarin Interaction
• Exenatide Digoxin Interaction
• Exenatide Paracetamol Interaction
• Exenatide Antibacterials Interaction
• Exenatide Thyroid Hormones Interaction
• Exenatide Danazol Interaction
• Exenatide ACE Inhibtors Interaction
• Interactions of Amylin Analogue
• Pramlintide Alpha glucosidase inhibitors
  Interaction
• Pramlintide Danazol Interaction
• Pramlintide ACE Inhibitors Interaction
• Pramlintide Thyroid Hormones Interaction
• Pramlintide Paracetamol Interaction
• Pramlintide Antimuscarinics Interaction

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Exenatide warfarin

• Exenatide
• Warfarin
• May increase INR
• Increased bleeding risk
• Moderately severe interaction is possible between
  exenatide and warfarin.
• More frequent monitoring of prothrombin time or
  INR when initiating or changing exenatide therapy
  is recommended.

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Exenatide digoxin

• Exenatide
• Dgoxin
• Slowed gastric emptying by exenatide
• Decrease in digoxin plasma concentrations
• Moderate interaction may occur between Exenatide
  and digoxin.
• The patient should wait at least 1 hour after
  taking digoxin before using exenatide.
• Digoxin serum levels should be measured before
  initiating exenatide, and the dose of digoxin
  should be increased by approximately 20 to 40
  as necessary.
• Monitoring of digoxin levels and clinical
  efficacy is recommended during concomitant
  therapy.

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Exenatide paracetamol

• Exenatide
• Paracetamol
• Exenatide slows gastric emptying
• Delayed absorption of other drugs (Paracetamol)
• The manufacturers recommend that exenatide should
  be used with caution in patients receiving oral
  drugs that require rapid gastrointestinal
  absorption, for example, an analgesic for acute
  pain or fever.
• It may be prudent to give the drug at least one
  hour before exenatide, or delay exenatide until
  more than 2 hours after the drug.

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Exenatide antibacterials

• Exenatide
• Antibacterials
• Exenatide slows gastric emptying
• Delayed absorption of other drugs
  (Antibacterials)
• The manufacturers also suggest that exenatide
  should be used with caution in patients receiving
  oral drugs that are dependent on threshold
  concentrations for efficacy, for example
  antibacterials.
• They recommend that antibacterials should be
  taken at least one hour before exenatide.

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Exenatide thyroid hormones

• Exenatide
• Thyroid hormones (Liothyronine, dextrothyroxine,
  levothyroxine, thyroglobulin)
• Decreased effectiveness of the antidiabetic agent
• Increased dose of exenatide may be required
• Moderate interaction may occur between Exenatide
  and Thyroid hormones.
• Carefully monitor diabetic control, especially
  when a thyroid hormone agent is initiated,
  changed or discontinued.

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Exenatide danazol

• Exenatide
• Danazol
• Danazol associated insulin resistance
• Increased blood glucose levels
• Moderate interaction may occur between Exenatide
  and Danazol.
• Use caution with the concomitant use of danazol
  and exenatide.
• Increased blood sugar monitoring and dose
  adjustments of antidiabetic medications may be
  warranted during coadministration and after
  discontinuation of danazol.

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Exenatide trandolapril

• Exenatide
• Trandolapril
• Increased glucose utilisation
• increased insulin sensitivity
• Increased risk of hypoglycemia
• Moderate interaction may occur between exenatide
  and trandalopril.
• More frequent blood glucose monitoring and/or
  observation for signs or symptoms of hypoglycemia
  may be necessary.

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Pramlintide alpha glucosidase inhibitors

• Pramlintide
• Alpha glucosidase inhibitors
• Pramlintide slows gastric emptying
• Clinical study is needed
• The manufacturer of pramlintide suggests that it
  should not be used in patients taking drugs that
  slow the intestinal absorption of nutrients, such
  as the alpha-glucosidase inhibitors.
• Clinical study is needed to see if there is any
  important effect if the drugs are used together.
• Patients taking alpha-glucosidase inhibitors
  should not be given pramlintide until the
  combination has been studied clinically.

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Pramlintide danazol

• Pramlintide
• Danazol
• Danazol-associated insulin resistance
• Increased blood glucose levels
• Moderate interaction may occur between
  pramlintide and danazol.
• Use caution with the concomitant use of danazol
  and pramlintide.
• Increased blood sugar monitoring and dose
  adjustments of antidiabetic medications may be
  warranted during coadministration and after
  discontinuation of danazol.

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Pramlintide trandolapril

• Pramlintide
• Trandolapril
• Increased glucose utilisation
• increased insulin sensitivity
• Increased risk of hypoglycemia
• Moderate interaction may occur between
  pramlintide and trandolapril.
• Close monitoring and dose adjustments may be
  required.

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Pramlintide thyroid hormones

• Pramlintide
• Thyroid hormones (liothyronine, dextrothyroxine,
  levothyroxine, thyroglobulin)
• Reduced efficacy of the antidiabetic agent
• Increased dosage requirement of pramlintide
• Moderate interaction may occur between
  pramlintide and thyroid hormones.
• Carefully monitor diabetic control, especially
  when a thyroid hormone agent is initiated,
  changed or discontinued.

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Pramlintide paracetamol

• Pramlintide
• Paracetamol
• Pramlintide modestly slows gastric emptying
• Delayed absorption of other drugs (Paracetamol)
• The manufacturer recommends that if a rapid onset
  of action is required (for example when giving an
  oral analgesic), the drug should be given at
  least one hour before or 2 hours after
  pramlintide.

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Pramlintide antimuscarinics

• Pramlintide
• Antimuscarinics
• Pramlintide modestly slows gastric emptying
• Further delay of gastric emptying
• The manufacturer recommends that pramlintide
  should not be used in patients taking other drugs
  that alter gastrointestinal motility such as
  antimuscarinics (Atropine) which delay gastric
  emptying.

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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.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
• www.micromedexsolutions.com