Drug Interaction
Amikacin and Furosemide
Type of interaction: It is a Pharmacodynamic interaction.
• Furosemide is a high celling/ loop diuretic
• Amikacin is an aminoglycoside anti microbial agent.
Result of interaction: Renal failure, Hearing loss, vertigo, tinnitus,
Mechanism:
• Furosemide cause increased salt content of the endolymph and a direct toxic action on the hair cells in
internal ear. This results in ototoxicity. Furosemide also causes nephrotoxicity by excreting salt and water
resulting in fluid and electrolyte imbalance.
• On the other hand, Amikacin also produces ototoxicity by degeneration of hair cell and neurons of cochlea
resulting in irreversible, b/l, high frequency hearing loss. It also produces nephrotoxicity causing reduced
GFR, proteinuria and hyalin and granular cast formation.
• Additive ototoxicity and nephrotoxicity seen when this two drugs are combined
Remarks:
• Use of amikacin in combination with loop diuretics should be avoided.
• If used together renal function tests, vestibular, and audiometric tests should be performed before and
during therapy.
Cefoperazone and Warfarin
Type of interaction: It is a pharmacodynamic drug interaction.
• Cefoperazone is a third-generation cephalosporin.
• Warfarin is an oral anticoagulant.
Result of interaction: Increased risk of bleeding.
Mechanism:
• Warfarin inhibits the enzyme vit K epoxide reductase (VKOR) and there by interfere with the
synthesis of vit K dependent clotting factors in liver. Plasma level of prothrombin and factors VII, IX
and X decrease resulting in increased risk of bleeding.
• Cefoperazone also cause hypoprothrombinaemia by same mechanism as warfarin. Together they
will have additive action and increase risk of bleeding.
Remarks:
• Avoid use of two drugs together.
• Macrolides, oral penicillins or quinolones can be used in place of Cefoperazone.
• If used together closely monitor INR and adjust the dose of warfarin accordingly.
Clopidogrel and Omeprazole
Type of interaction: It is a Pharmacokinetic drug interaction.
• Clopidogrel is an antiplatelet drug.
• Omeprazole is a proton pump inhibitor
Result of interaction:
• Decreased antiplatelet action of clopidogrel. Progression of atherosclerosis may occur with increased chance
of Acute Coronary Syndrome.
Mechanism:
• Clopidogrel is a prodrug & activated by CYP2C19 isoenzyme. Active drug then irreversibly block P2Y 12
purinergic receptor on the surface of platelet. There by it prevent ADP induced platelet aggregation by
inhibiting generation of cAMP.
• Omeprazole inhibits CYP2C19 and prevents activation of clopidogrel. So, its antiplatelet action inhibited.
Remarks:
• Concomitant use of two drugs should be avoided.
• Use drugs which do not suppress CYP2C19 like H2 blocker or Pantoprazole can be used as acid suppressing
agent.
Rifampicin and OCP
Type of interaction: Pharmacokinetic interaction at the level of metabolism.
• Rifampicin is a bactericidal agent effective against mycobacterial infection.
• Oral Contraceptive Pill (OCP) is fixed dose combination of estrogen and progestin derivative
for preventing conception.
Result of interaction:
• Failure of contraception, menstrual irregularities like breakthrough bleeding, spotting etc.
Mechanism:
• Rifampicin is a hepatic microsomal enzyme inducer so metabolism of both estrogen and
progestin component is increased. Hence the effectiveness of OCP is decreased.
Remarks:
• Rifabutin, a second line anti TB drug, related to rifampicin can be used in place of rifampicin
as it has less enzyme inducing property. Use another contraceptive method like barrier
method for contraception for entire duration of rifampicin therapy
Thank you
