Drug-Drug Interactions (DDIs)
1. Pharmacokinetic Interactions
These affect the movement of drugs through the body—
Absorption, Distribution, Metabolism, and Excretion
(ADME).
1. Absorption
- Tetracycline (Antibiotic) + Antacids (Calcium/Magnesium salts)
-> Chelation reduces absorption.
- Levothyroxine (Thyroid hormone) + Iron supplements (Mineral)
-> Binding reduces absorption.
- Digoxin (Cardiac glycoside) + Cholestyramine (Bile acid
sequestrant) -> Reduced absorption.
1. Distribution
- Warfarin (Anticoagulant) + Valproic acid (Antiepileptic) ->
Displacement from protein binding -> Increased bleeding
risk.
- Phenytoin (Antiepileptic) + Aspirin (NSAID) -> Displacement -
> Phenytoin toxicity.
1. Metabolism (CYP enzymes)
- Ketoconazole (Antifungal) + Cyclosporine (Immunosuppressant) -> CYP3A4
inhibition -> Increased cyclosporine levels.
- Rifampin (Antibiotic) + Warfarin (Anticoagulant) -> CYP induction -> Decreased
warfarin effect.
- Fluconazole (Antifungal) + Warfarin (Anticoagulant) -> CYP2C9 inhibition ->
Increased INR.
1. Excretion
- Probenecid (Uricosuric agent) + Penicillin (Antibiotic) -> Decreased renal clearance ->
Increased penicillin level.
- NSAIDs (e.g., Ibuprofen) + Lithium (Mood stabilizer) -> Decreased lithium clearance -
> Toxicity.
- Thiazide diuretics (e.g., Hydrochlorothiazide) + Lithium (Mood stabilizer) ->
Increased reabsorption -> Toxicity.
Pharmacodynamic Interactions
1. Additive
-Aspirin (NSAID) + Warfarin (Anticoagulant) -> Increased
bleeding risk.
-Benzodiazepines (e.g., Diazepam) + Opioids (e.g.,
Morphine) -> Increased CNS depression
Synergistic
- Trimethoprim (Antibiotic) + Sulfamethoxazole (Antibiotic) ->
Enhanced bacterial inhibition.
- Carbidopa (DOPA decarboxylase inhibitor) + Levodopa
(Dopamine precursor) -> Increased levodopa bioavailability.
1. Antagonistic
- Naloxone (Opioid antagonist) + Morphine (Opioid analgesic) ->
Reverses opioid effect.
- NSAIDs (e.g., Ibuprofen) + Antihypertensives (e.g., ACE
inhibitors) -> Blunts blood pressure control.
Special Interactions
- Serotonin Syndrome: SSRI (e.g., Fluoxetine, Antidepressant) +
MAOI (e.g., Selegiline, Antidepressant) -> Increased serotonin ->
Agitation, seizures.
- QT Prolongation: Azithromycin (Macrolide antibiotic) + Haloperidol
(Antipsychotic) -> Risk of Torsades de Pointes.
1. Antihypertensives
ACE Inhibitors (e.g., Enalapril, Lisinopril)
• Interaction: + Potassium-sparing diuretics (e.g., Spironolactone)
o Reason: Both increase potassium levels → Hyperkalemia
o Class: ACE Inhibitor + Potassium-sparing diuretic
• Interaction: + NSAIDs (e.g., Ibuprofen)
o Reason: NSAIDs reduce prostaglandin-mediated vasodilation → ↓
antihypertensive effect
o Class: ACE Inhibitor + NSAID
2. Beta-Blockers (e.g., Metoprolol, Propranolol)
• Interaction: + Non-dihydropyridine CCBs (calcium channel blockers) (e.g.,
Verapamil, Diltiazem)
o Reason: Additive bradycardia and AV block due to nodal conduction
suppression
o Class: Beta-blocker + Calcium channel blocker
• Interaction: + Clonidine
o Reason: Sudden clonidine withdrawal while on beta-blocker → Rebound
hypertension
o Class: Beta-blocker + Centrally acting alpha-agonist
3. Calcium Channel Blockers (CCBs)
Non-Dihydropyridines (e.g., Verapamil, Diltiazem)
• Interaction: + Beta-blockers
o Reason: Both decrease AV node conduction → Severe bradycardia
or AV block
o Class: CCB + Beta-blocker
• Interaction: + Statins (e.g., Simvastatin)
o Reason: Verapamil/Diltiazem inhibit CYP3A4 → ↑ statin levels →
Myopathy risk
o Class: CCB + HMG-CoA reductase inhibitor
4. Diuretics
Loop/Thiazide Diuretics (e.g., Furosemide, Hydrochlorothiazide)
• Interaction: + Digoxin
o Reason: Hypokalemia from diuretic use ↑ digoxin toxicity
o Class: Diuretic + Cardiac glycoside
• Interaction: + Lithium
o Reason: Diuretics reduce lithium excretion → Lithium toxicity
o Class: Diuretic + Mood stabilizer
5. Nitrates (e.g., Nitroglycerin, Isosorbide dinitrate)
• Interaction: + PDE-5 inhibitors (e.g., Sildenafil)
o Reason: Profound vasodilation → Severe hypotension
o Class: Vasodilator + Erectile dysfunction medication
6. Anticoagulants
Warfarin (Vitamin K antagonist)
• Interaction: + Antibiotics (e.g., Metronidazole)
o Reason: Antibiotics alter gut flora → ↓ vitamin K → ↑ INR →
Bleeding
o Class: Anticoagulant + Antibiotic
• Interaction: + NSAIDs
o Reason: Both impair clotting and damage GI mucosa → GI bleeding
o Class: Anticoagulant + NSAID
7. Antiplatelets
Aspirin + Clopidogrel
• Interaction: Combined use
o Reason: Additive platelet inhibition → Increased
bleeding risk
o Class: NSAID + P2Y12 inhibitor
• Interaction: + Proton pump inhibitors (e.g., Omeprazole)
Reason: Omeprazole inhibits CYP2C19 → ↓ activation of clopidogrel
Class: Antiplatelet + GI protective agent
8. Statins (e.g., Simvastatin, Atorvastatin)
• Interaction: + Macrolide antibiotics (e.g., Clarithromycin)
o Reason: CYP3A4 inhibition → ↑ statin levels →
Myopathy or rhabdomyolysis
o Class: Statin + Antibiotic
• Interaction: + Grapefruit juice
o Reason: Inhibits intestinal CYP3A4 → ↑ statin absorption
o Class: Statin + Dietary component
