The document discusses important drug-drug interactions, including their intensity, mechanism, and management. It defines drug-drug interactions as when taking two drugs together causes a change in one drug's effects on the body. Interactions can be pharmacodynamic, involving receptor-level or intracellular effects, or pharmacokinetic, altering a drug's absorption, distribution, metabolism, or excretion. The document provides examples of serious interactions to avoid or monitor closely, outlines approaches to minimizing interactions, and poses sample cases to identify and manage interactions.

1. UNDERSTANDING OF SOME IMPORTANT
DRUG-DRUG INTERACTIONS
Dr. Saeed Ahmad
(RPh, Pharm.D., MPhil)
Pharmacist
Sui Field Hospital
Pakistan Petroleum Limited

2. DRUG-DRUG INTERACTIONS
Definition:
A change in a drug’s effect on the body,
when the drug is taken together with a
second drug.

3. DRUG INTERACTIONS INVOLVE:
PHARMACODYNAMICS
PHARMACOKINETICS
• In pharmacodynamic interactions, one drug alters the sensitivity or
responsiveness of tissues to another drug by having the same (agonistic)
or a blocking (antagonistic) effect. These effects usually occur at the
receptor level but may occur intracellularly.
• In pharmacokinetic interactions, a drug usually alters absorption,
distribution, protein binding, metabolism, or excretion of another drug.
Thus, the amount and persistence of available drug at receptor sites
change. They are often predicted based on knowledge of the individual
drugs or detected by monitoring drug concentrations or clinical signs.

4. EFFECTS OF DRUG-DRUG
INTERACTIONS

5. Some important drug-drug interactions
(Intensity & Mechanism)

7. INTENSITY AND MECHANISM
Serious - Use Alternative
metronidazole + warfarin
metronidazole increases levels of warfarin by inhibiting hepatic enzyme CYP2C9/10 .
Avoid or Use Alternate Drug.

9. INTENSITY AND MECHANISM
Serious - Use Alternative
verapamil + propranolol
verapamil, propranolol. Either increases toxicity of the other by unspecified interaction
mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

11. INTENSITY AND MECHANISM
Monitor Closely
omeprazole + ferrous sulfate
• omeprazole will decrease the level or effect of ferrous sulfate by increasing gastric pH.
Applies only to oral form of both agents. Use Caution/Monitor.
Monitor Closely
famotidine + ferrous sulfate
• famotidine will decrease the level or effect of ferrous sulfate by increasing gastric pH.
Applies only to oral form of both agents. Use Caution/Monitor.

13. INTENSITY AND MECHANISM
Serious - Use Alternative
tetracycline + penicillin
tetracycline decreases effects of penicillin by pharmacodynamic antagonism. Avoid or
Use Alternate Drug.

15. INTENSITY AND MECHANISM
Monitor Closely
warfarin + diclofenac
warfarin and diclofenac both increase anticoagulation. Modify Therapy/Monitor Closely.

17. INTENSITY AND MECHANISM
Serious - Use Alternative
furosemide + gentamicin
furosemide, gentamicin. Either increases toxicity of the other by Mechanism:
pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of ototoxicity
and nephrotoxicity.
Monitor Closely
furosemide + gentamicin
• furosemide and gentamicin both decrease serum potassium. Use Caution/Monitor.

19. INTENSITY AND MECHANISM
Serious - Use Alternative
omeprazole + clopidogrel
omeprazole decreases effects of clopidogrel by affecting hepatic enzyme CYP2C19
metabolism. Avoid or Use Alternate Drug. Clopidogrel efficacy may be reduced by drugs
that inhibit CYP2C19.

21. INTENSITY AND MECHANISM
Contraindicated
gemfibrozil + atorvastatin
• gemfibrozil increases toxicity of atorvastatin by Other (see comment). Contraindicated.
may increase risk of myopathy.
Serious - Use Alternative
gemfibrozil + atorvastatin
• gemfibrozil, atorvastatin. Either increases effects of the other by pharmacodynamic
synergism. Avoid or Use Alternate Drug. Gemfibrozil may further increase risk for
rhabdomyolysis when added to optimal statin regimen to further decrease TG and
increase HDLs.

22. INTENSITY AND MECHANISM
Serious - Use Alternative
fenofibrate + atorvastatin
fenofibrate, atorvastatin. Either increases effects of the other by pharmacodynamic
synergism. Avoid or Use Alternate Drug. Fenofibrate may further increase risk for
rhabdomyolysis when added to optimal statin regimen to further decrease TG and
increase HDLs.

24. INTENSITY AND MECHANISM
Monitor Closely
omega 3 fatty acids + clopidogrel
omega 3 fatty acids, clopidogrel. Other (see comment). Use Caution/Monitor. Comment:
Patients taking omega-3-fatty acids and an anticoagulant or other drug affecting
coagulation should be monitored periodically due to potential increased risk of bleeding.
.

25. INTENSITY AND MECHANISM
Monitor Closely
omega 3 fatty acids + warfarin
omega 3 fatty acids, warfarin. Other (see comment). Use Caution/Monitor. Comment:
Patients taking omega-3-fatty acids and an anticoagulant or other drug affecting
coagulation should be monitored periodically due to potential increased risk of bleeding.
Monitor for changes in INR.

26. INTENSITY AND MECHANISM
Monitor Closely
omega 3 fatty acids + aspirin
omega 3 fatty acids, aspirin. Other (see comment). Use Caution/Monitor. Comment:
Patients taking omega-3-fatty acids and an anticoagulant or other drug affecting
coagulation should be monitored periodically due to potential increased risk of bleeding.

28. INTENSITY AND MECHANISM
Monitor Closely
lisinopril + spironolactone
lisinopril, spironolactone. Mechanism: pharmacodynamic synergism. Use
Caution/Monitor. Risk of hyperkalemia.

30. INTENSITY AND MECHANISM
Contraindicated
nitroglycerin PO + sildenafil
Nitroglycerin PO, sildenafil. Mechanism: additive vasodilation. Contraindicated.
Potentially fatal hypotension.

32. INTENSITY AND MECHANISM
Serious - Use Alternative
ciprofloxacin + theophylline
ciprofloxacin will increase the level or effect of theophylline by affecting hepatic enzymes
CYP1A2 & CYP3A4 metabolism. Avoid or Use Alternate Drug. Concomitant use of
theophylline and ciprofloxacin has decreased theophylline clearance and increased
plasma levels and symptoms of toxicity. Serious and fatal reactions have included cardiac
arrest, seizure, status epilepticus, and respiratory failure. If concomitant use cannot be
avoided, monitor theophylline levels and adjust dosage as needed.

33. INTENSITY AND MECHANISM
Serious - Use Alternative
erythromycin stearate + theophylline
Erythromycin stearate will increase the level or effect of theophylline by affecting
hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

34. INTENSITY AND MECHANISM
Serious - Use Alternative
clarithromycin + theophylline
clarithromycin will increase the level or effect of theophylline by affecting
hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

35. INTENSITY AND MECHANISM
Serious - Use Alternative
fluvoxamine + theophylline
fluvoxamine will increase the level or effect of theophylline by affecting hepatic and
intestinal enzymes CYP1A2 & CYP3A4 metabolism. Avoid or Use Alternate Drug.

36. INTENSITY AND MECHANISM
Serious - Use Alternative
cimetidine + theophylline
Cimetidine will increase the level or effect of theophylline by affecting hepatic/intestinal
enzyme CYP3A4 & CYP1A2 metabolism. Avoid or Use Alternate Drug.

37. MINIMIZING DRUG INTERACTIONS
Clinicians should know all of their patients’ current drugs, including:
• Drugs prescribed by other clinicians
• Over-the-counter drugs
• Herbal products
• Nutritional supplements
• Asking patients relevant questions about diet and alcohol consumption is recommended.
• The effects, desired and undesired, of all drugs taken should be determined because these effects usually
include the spectrum of drug interactions.
• If possible, drugs with a wide safety margin should be used so that any unforeseen interactions do not cause
toxicity.
• Patients should be observed and monitored for adverse effects, particularly after a change in treatment;
some interactions (eg, effects that are influenced by enzyme induction) may take ≥ 1 week to appear.
• Drug interactions should be considered as a possible cause of any unexpected problems.
• When unexpected clinical responses occur, prescribers should determine serum concentrations of selected
drugs being taken, consult the literature or an expert in drug interactions, and adjust the dosage until the
desired effect is produced.
• If dosage adjustment is ineffective, the drug should be replaced by one that does not interact with other
drugs being taken.

38. QUIZ & GROUP DISCUSSION
Patient presented with dental pain and slight gum bleeding. On examination the dentist
found that there is pus in the gum as well. The patient was also febrile. He advised the
following medications. The patient was also having coagulation dysfunction and was already
on Warfarin.
Cap. Amoxil 500mg TDS
Tab. Flagyl 400mg TDS
Tab. Voren 50mg BD
Chlorhexidine mouth wash
Find the interaction & manage accordingly??

39. Hypertensive patient visited a GP clinic with increased BP upto 240/110 mmHg. The
patient complaint of head ache and generalized body aches. The patient was taking Tab.
Calan SR 240mg OD. The doctor prescribed the following medication.
Tab. Byscard 5mg BD
Tab. Artifen 50mg BD
Inj: Voltral stat
Find interaction & manage accordingly

40. Patient was suffering from acne vulgaris and was using Cap. Vibramycin 100mg OD. The
patient was also given the following medication for rheumatic fever.
Tab. Prednisolone
Tab. Panadol
Inj. Benzibiotic
Find interaction and manage accordingly.

41. Few days ago a patient was suffering from some severe urinary tract infection and was
already using Gentamycin parentally, per the C/S report. Now patient presented with
severe hypertension and Lasix injection was administered to controlled his BP. The
patient left hospital with the prescription of:
Tab. Lasix 40mg
Tab. Eziday 50mg
Tab. Norvasc 5mg
Find Interaction and manage accordingly.

42. Patient presented with epigastric pain in ER. Upon investigation H.Pylori was positive. All
other alarming symptom of peptic ulcer were present. The patient was already using Tab.
Ferrous sulphat, as previously diagnosed with iron deficiency anemia. The doctor
prescribed:
Tab. Losec 20mg BD.
Tab. Klaricid 500mg BD
Cap Amoxil 500 mg 2BD
Find the interaction and manage accordingly.

43. Patient is using the following chronic medications:
Tab. Lowplat plus
Tab. Lipiget 20mg
Cap. Risek 20mg
Tab. Treviamet 50/500 mg
Find interaction and manage accordingly

44. CONCLUSION
The fewest drugs in the lowest
effective doses for the shortest
possible time should be prescribed

45. Thank You