Appendix 6c:
Drug–Drug Interactions

Two or more drugs administred at the same time may interact with each other. The interactions may be potentiation or antagonism of one drug by another or occasionally some other effect. Drug interactions may be of pharmacokinetic or pharmacodynamic type. The pharmacokinetic interactions can be because of absorption mechanism, competition of two drugs at the protein binding sites, metabolizing enzyme system or excretion. When two or more drugs are concomitantly administered there is always a possibility of pharmacokinetic or pharmacodynamic interaction. The pharmacodynamic interactions can be at the receptor level for competition at same drug target (enzyme/receptor) acting synergistically or antagonizing the effect of each other. The drugs which have narrow therapeutic window have greater potential to cause unexpected adverse effect when their pharmacokinetics or pharmacodynamics is altered. In such situation, the following precautions are advisable:

1. Concomitant administration of drugs should possibly be avoided.
2. When unavoidable, care should be taken and TDM is recommended.
3. When TDM is not possible logistically, clinical symptomatology be done.
4. Careful dose titration (upward/downward) be done to get optimum dose modification.
The following drug categories are considered as drugs of narrow therapeutic window:

Antiepileptics, anticoagulants, anticancers, xanthenes, antide pressants, antiarrhythmics etc.

Some representative clinically relevant drug–drug interactions are listed below:

ABCIXIMAB

 

Anticoagulant

Increased risk of bleedin

 Antiplatelet agents

Increased risk of bleedin

ACETAZOLAMIDE

 

Carbamazepine

Increased risk of hyponatraemia; acetazolamide increases plasma–carbamazepine concentration

Digoxin

Cardiac toxicity of digoxin increased if hypokalaemia occurs

Furosemide

Increased risk of hypokalaemia

Nifedipine

Enhanced hypotensive effect

Phenytoin

Increased risk of osteomalacia

ACETYLSALICYLIC ACID

 

Corticosteroids

Increased risk of gastrointestinal bleeding and ulceration; corticosteroids reduce plasma–salicylate concentration

Heparin

Enhanced anticoagulant effect

 Methotrexate

Reduced excretion of methotrexate (increased toxicity)

Warfarin

Increased risk of bleeding due to antiplatelet effect

ALENDRONATE

 

Calcium supplements

Reduced absorption of alendronate

Antacids

Reduced absorption of alendronate

ALLOPURINOL

 

Azathioprine

Effects of azathioprine enhanced with increased toxicity; reduce dose when given with allopurinol

Mercaptopurine

Effects of 6-mercaptopurine enhanced with increased toxicity; reduce dose when given with allopurinol

ALTEPLASE

 

Prostacyclin, nitrates

Increased plasma–alteplase clearance

Abciximab

Additive effect

Nitroglycerin

Decreased thrombolytic effect of alteplase

Warfarin, Antiplatelet agents

Increased risk of bleeding

NSAIDs

Increased risk of GI bleeding

AMILORIDE

 

Artemether + Lumefantrine

Increased risk of ventricular arrhythmias if electrolyte disturbance occurs

Cisplatin

Increased risk of nephrotoxicity and ototoxicity

Cyclosporine

Increased risk of hyperkalaemia

Enalapril

Enhanced hypotensive effect; risk of severe hyperkalaemia

AMINOPHYLLINE

 

Febuxostat

Increased effect of aminophylline

Rifamycin

Decreased effect of aminophylline

AMITRIPTYLINE

 

Artemether + Lumefantrine

Increased risk of ventricular arrhythmias

Carbamazepine

Antagonism of anticonvulsant effect

Haloperidol

Increased plasma–amitriptyline concentration; increased risk of ventricular arrhythmias

Phenobarbital

Antagonism of anticonvulsant effect

Phenytoin

Antagonism of anticonvulsant effect

Valproic acid

Antagonism of anticonvulsant effect

AMOXYCILLIN

 

Methotrexate

Reduced excretion of methotrexate; increased risk of toxicity

AMOXYCILLIN + CLAVULANIC ACID

Probenecid

Increased concentrations of amoxycillin in serum and bile

Allopurinol

Occurrence of allergic cutaneous reactions

Digoxin

Increased absorption

Warfarin

Increased incidence of bleeding

AMPHOTERICIN B

 

Corticosteroids

Increased risk of hypokalaemia

Cyclosporine

Increased risk of nephrotoxicity

Digoxin

Increased digoxin toxicity if hypokalaemia occurs

Tacrolimus

Synergistic effect of amphotercin

AMPICILLIN

 

Methotrexate

Reduced excretion of methotrexate; increased risk of toxicity

Warfarin

Studies have failed to demonstrate an interaction, but common experience in anticoagulant clinics is that INR can be altered by a course of ampicillin

ANTACIDS (Aluminium Hydroxide; Magnesium Hydroxide)

Note: Antacids should preferably not be taken at the same time as other drugs since they may impair absorption

Ciprofloxacin

Reduced absorption of ciprofloxacin

Digoxin

Reduced absorption of digoxin

Isoniazid

Reduced absorption of isoniazid

Phenytoin

Reduced absorption of phenytoin

Rifampicin

Reduced absorption of rifampicin

ARTEMETHER + LUMEFANTRINE

Amitriptyline

Increased risk of ventricular arrhythmias

Azithromycin

Avoid concomitant use

Chloroquine

Increased risk of ventricular arrhythmias

Ciprofloxacin

Avoid concomitant use

Fluconazole

Avoid concomitant use

Furosemide

Increased risk of ventricular arrhythmias if electrolyte disturbance occurs

Mefloquine

Increased risk of ventricular arrhythmias

Ofloxacin

Avoid concomitant use

Pyrimethamine

Avoid concomitant use

Quinine

Increased risk of ventricular arrhythmias

Sulfadoxine + Pyrimethamine

Avoid concomitant use

ATENOLOL

 

Glibenclamide

Masking of warning signs of hypoglycaemia such as tremor

Insulins

Enhanced hypoglycaemic effect; masking of warning signs of hypoglycaemia such as tremor

Lidocaine

Increased risk of myocardial depression

Nifedipine

Severe hypotension and heart failure occasionally

Verapamil

Asystole, severe hypotension and heart failure

ATORVASTATIN

 

Ketoconazole

Increased plasma concentration of atorvastatin and risk of myotoxicity in frequent

Itraconazole

Increased plasma concentration of atorvastatin and risk of myotoxicity in frequent

Ritonavir

Increased plasma concentration of atorvastatin and risk of myotoxicity in frequent

Erythromycin

Increased plasma concentration of atorvastatin and risk of myotoxicity in frequent

Fibrates

Increased risk of rhabdomyolysis

AZATHIOPRINE

 

Allopurinol

Effects of azathioprine enhanced

Phenytoin

Reduced absorption of phenytoin

Rifampicin

Transplants rejected

Sulfamethoxazole + Trimethoprim

Increased risk of haematological toxicity

Vaccines, Live

Avoid use of live vaccines with azathioprine (impairment of immune response)

Warfarin

Reduced effect of anticoagulant

AZITHROMYCIN

 

Cyclosporine

Plasma concentration of cyclosporine increased

Digoxin

Effect of digoxin enhanced

Digoxin

Effect of digoxin enhanced

Warfarin

Enhanced anticoagulant effect of warfarin

BACLOFEN

 

Tricyclic antidepressents

Risk of muscle weakness

MAO inhibitors

Depression of brain function as well as low blood pressure

Antidiabetic drugs

Increased blood sugar level

BENZATHINE BENZYLPENICILLIN

Aminoglycosides

Reduced effect of aminoglycosides in patient with renal impairment

Methotrexate

Reduced excretion of methotrexate

BLEOMYCIN

 

Vaccines, Live

Avoid use of live vaccines with bleomycin (impairment of immune response)

Vinblastine

Increased risk of cardiovascular toxicity

BROMOCRIPTINE

 

Ergot derivatives

Additive dopamine agonistic activity

BUDESONIDE

 

Ketoconazole

Plasma concentration of orally administered budesonide increased

Itraconazole

Metabolism of budesonide inhibited

Clarithromycin

Metabolism of budesonide inhibited

Erythromycin

Metabolism of budesonide inhibited

BUPIVACAINE

 

Lidocaine

Increased myocardial depression

Procainamide

Increased myocardial depression

Quinidine

Increased myocardial depression

BUSULPHAN

 

Itraconazole

Increased level of busulphan

Metronidazole

Increased level of busulphan

Nalidixic acid

Risk of gastrointestinal toxicity

Thioguanine

Risk of portal hypertension and espohageal varices

CALCIUM CARBONATE + VITAMIN D3

Quinolones

Risk of decreased absorption into the body

Tetracycline

Risk of decreased absorption into the body

Mycophenolate mofetil

Decreased effectiveness of mycophenolate mofetil

CALCIUM SALTS

 

Digoxin

Large intravenous doses of calcium can precipitate arrhythmias

Tetracyclines

Reduced absorption of tetracyclines

CAPREOMYCIN

 

BCG vaccine

May make the vaccine ineffective

Neuromuscular blocking agents

Increase in neuromuscular blocking effects

Typhoid vaccine

May make the vaccine ineffective

CARBAMAZEPINE

 

Acetazolamide

Increased risk of hyponatraemia; acetazolamide increases plasma–carbamazepine concentration

Amitriptyline

Antagonism (convulsive threshold lowered); accelerated metabolism of amitriptyline; reduced plasma concentration; reduced effect antidepressant

Chloroquine

Convulsive threshold occasionally lowered

Chlorpromazine

Antagonism of anticonvulsant effect (convulsive threshold lowered)

Corticosteroids

Accelerated metabolism of corticosteroids

Cyclosporine

Accelerated metabolism (reduced plasma–cyclosporine concentration)

Diltiazem

Increased carbamazepine level

Erythromycin

Increased plasma–carbamazepine concentration

Fluphenazine

Antagonism of anticonvulsant effect (convulsive threshold lowered)

Haloperidol

Antagonism of anticonvulsant effect

Isoniazid

Increased plasma–carbamazepine concentration (also isoniazid hepatotoxicity increased)

Lopinavir

Reduced plasma-lopinavir concentration

Progestins

Accelerated metabolism of progestins

Sulfamethoxazole + Trimethoprim

May be enhanced toxicity without corresponding increase in antiepileptic effect; plasma concentration of carbamazepine often lowered

Phenytoin

May be enhanced toxicity without corresponding increase in antiepileptic effect; plasma concentration of phenytoin often lowered

Ritonavir

Plasma concentration increased by ritonavir

Valproic acid

Plasma concentration of valproic acid often lowered; plasma concentration of active metabolite of carbamazepine often raised

Verapamil

Enhanced effect of carbamazepine

Warfarin

Accelerated metabolism of warfarin (reduced anticoagulant effect)

CEFAZOLIN

 

Oral anticoagulants

Increased hypoprothrombinemic effect of anticoagulant.

CEFIXIME

 

Carbamazepine

Elevated carbamazepine levels

Anticoagulants

Increased prothrombin time

CEFTAZIDIME

 

Furosemide

Nephrotoxicity of ceftazidime increased

Warfarin

Enhanced anticoagulant effect

CEFTRIAXONE

 

Warfarin

Enhanced anticoagulant effect

CHLORAMPHENICOL

 

Cyclosporine

Plasma concentration of cyclosporine increased

Iron

Avoid as can cause bone marrow depression which appears treatment of anaemia

Phenobarbital

Metabolism of chloramphenicol accelerated (reduced chloramphenicol concentration)

Phenytoin

Plasma–phenytoin concentration increased (risk of toxicity)

Vitamin B12

Avoid concomitant use, can cause bone marrow depression

CHLOROQUINE

 

Artemether + Lumefantrine

Increased risk of ventricular arrhythmias

Carbamazepine

Convulsive threshold occasionally lowered

Cyclosporine

Increased plasma–cyclosporine concentration (increased risk of toxicity)

Digoxin

Plasma–digoxin concentration increased

Mefloquine

Increased risk of convulsions

Phenytoin

Convulsive threshold occasionally lowered

Valproic acid

Convulsive threshold occasionally lowered

CHLORPROMAZINE

 

Amitriptyline

Increased antimuscarinic adverse effects; increased plasma-amitriptyline concentration; increased risk of ventricular arrhythmias

Artemether + Lumefantrine

Increased risk of ventricular arrhythmias

Clomipramine

Increased antimuscarinic adverse effects; increased plasma-clomipramine concentration; increased risk of ventricular arrhythmias

Ether, Anaesthetic

Enhanced hypotensive effect

Halothane

Enhanced hypotensive effect

Ketamine

Enhanced hypotensive effect

Nitrous oxide

Enhanced hypotensive effect

Phenobarbital

Antagonism of anticonvulsant effect (convulsive threshold lowered)

Phenytoin

Antagonism of anticonvulsant effect (convulsive threshold lowered)

Procainamide

Increased risk of ventricular arrhythmias

Propranolol

Concomitant administration may increase plasma concentration of both drugs; enhanced hypotensive effect

Quinidine

Increased risk of ventricular arrhythmias

Ritonavir

Plasma concentration increased by ritonavir

Thiopental

Enhanced hypotensive effect

Valproic acid

Antagonism of anticonvulsant effect (convulsive threshold lowered)

CINNARIZINE

 

CNS depressants (alcohol, barbiturates, hypnotics, narcotic analgesics, tricyclic antidepressants, sedatives and tranquillizers)

Additive sedation

Zolpidem

Additive toxicity

CIPROFLOXACIN

 

Artemether + Lumefantrine

Avoid concomitant use

Cyclosporine

Increased risk of nephrotoxicity

Glibenclamide

Enhanced effect of glibenclamide

Ibuprofen

Increased risk of convulsions

Warfarin

Enhanced anticoagulant effect

CISPLATIN

 

Aminoglycoside antibiotics

Increased risk of nephrotoxicity and ototoxicity

Furosemide

Increased risk of nephrotoxicity and ototoxicity

Hydrochlorothiazide

Increased risk of nephrotoxicity and ototoxicity

Vancomycin

Increased risk of nephrotoxicity and ototoxicity

CLARITHROMYCIN

 

Oral anticoagulants

Increased anticoagulant effect.

Carbamazepine

Increased serum concentration of carbamazepine.

Digoxin

Increased concentration of digoxin.

Lovastatin

Avoid concomitant use

Sildenafil

Dose reduction of sildenafil may be required.

Simvastatin

Avoid concomitant use

Sirolimus

Elevation in serum sirolimus level

Tacrolimus

Elevation in serum sirolimus level

Tadalafil

Dose reduction of tadalafil may be required.

CLINDAMYCIN

 

Erythromycin

Antagonist activity

Pancuronium

Neuromuscular blockade exaggerated

Kaoli-pectin

Reduced absorption rate

Gentamycin

Synergistic effect

CLOBAZAM

 

Cimetidine

Increased effect of clobazam

Barbiturates

Decreased serum level of clobazam

CLONAZEPAM

 

Carbamazepine

Decreased level of carbamazepine

Ketoconazole

Inhibition of metabolism of clonazepam

CLOPIDOGREL

 

Omeprazole

Plasma concentration of active metabolite of clopidogrel is decreased

NSAIDs

Increased risk of gastrointestinal bleeding

CLONIDINE

 

Beta blockers

Sinus bradycardia, monitor heart rate

Clomipramine

Risk of hypertensive crisis

CLONIDINE

 

Diazepam

Enhanced sedative effect

Ritonavir

Ritonavir increases plasma concentration of codeine

CORTICOSTEROIDS

 

Acetylsalicylic acid

Increased risk of gastrointestinal bleeding and ulceration; hydrocortisone reduces plasma-salicylate concentration

Amphotericin B

Increased risk of hypokalaemia

Atenolol

Antagonism of hypotensive effect

Carbamazepine

Accelerated metabolism of hydrocortisone (reduced effect)

Digoxin

Increased risk of hypokalaemia

Enalapril

Antagonism of hypotensive effect

Furosemide

Antagonism of diuretic effect; increased risk of hypokalaemia

Glibenclamide

Antagonism of hypoglycaemic effect

Hydrochlorothiazide

Antagonism of diuretic effect; increased risk of hypokalaemia

Insulins

Antagonism of hypoglycaemic effect

Levonorgestrel

Levonorgestrel increases plasma concentration of corticosteroids

Methotrexate

Increased risk of haematological toxicity

Nifedipine

Antagonism of hypotensive effect

Phenobarbital

Metabolism of hydrocortisone accelerated (reduced effect)

Phenytoin

Metabolism of hydrocortisone accelerated (reduced effect)

Rifampicin

Accelerated metabolism of corticosteroids (reduced effect)

Salbutamol

Increased risk of hypokalaemia if high doses of corticosteroids given with high doses of salbutamol

Warfarin

Anticoagulant effect altered

CYCLOPHOSPHAMIDE

 

Vaccines, Live

Avoid use of live vaccines with cyclophosphamide (impairment of immune response)

CYCLOSPORINE

 

Amphotericin B

Increased risk of nephrotoxicity

Ciprofloxacin

Increased risk of nephrotoxicity

Digoxin

Reduced clearance of digoxin (risk of toxicity)

Enalapril

Increased risk of hyperkalaemia

Erythromycin

Increased plasma-cyclosporine concentration

Methotrexate

Increased toxicity

Metoclopramide

Plasma-cyclosporine concentration increased

Ofloxacin

Increased risk of nephrotoxicity

Phenobarbital

Metabolism of cyclosporine accelerated

Phenytoin

Accelerated metabolism

Rifampicin

Accelerated metabolism (reduced plasma-cyclosporine concentration)

Ritonavir

Plasma concentration increased by ritonavir

Rosuvastatin

Marked rise in serum rosuvastatin level

Sulfonamides and Trimethoprim

Increased toxicity

Vaccines, Live

Avoid use of live vaccines with cyclosporine

Vancomycin

Increased risk of nephrotoxicity

DANAZOL

 

Anticoagulants (warfarin )

Danazol inhibits metabolism of coumarins

Cyclosporine

Danazol inhibits metabolism of cyclosporine

Lovastatin

Increased risk of myopathy

Simvastatin

Increased risk of myopathy

Tacrolimus

Danazol increases plasma concentration of tacrolimus

DAPSONE

 

Rifampicin

Reduced plasma-dapsone concentration

Sulfamethoxazole + Trimethoprim

Plasma concentration of both dapsone and trimethoprim increased with concomitant use

DESFERRIOXAMINE MESYLATE

Ascorbic acid

May worsen iron toxicity

DEXAMETHASONE

 

Acetazolamide

Increased risk of hypokalaemia; antagonism of diuretic effect

Acetylsalicylic acid

Increased risk of gastrointestinal bleeding and ulceration; dexamethasone reduces plasma-salicylate concentration

Albendazole

Plasma-albendazole concentration increased

Amiloride

Antagonism of diuretic effect

Amphotericin B

Increased risk of hypokalaemia (avoid concomitant use unless dexamethasone needed to control reactions)

Atenolol

Antagonism of hypotensive effect

Carbamazepine

Accelerated metabolism of dexamethasone (reduced effect)

Digoxin

Increased risk of hypokalaemia

Enalapril

Antagonism of hypotensive effect

Ephedrine

Metabolism of dexamethasone accelerated

Erythromycin

Erythromycin inhibits metabolism of dexamethasone

Furosemide

Antagonism of diuretic effect; increased risk of hypokalaemia

Glibenclamide

Antagonism of hypoglycaemic effect

Glyceryl trinitrate

Antagonism of hypotensive effect

Hydralazine

Antagonism of hypotensive effect

Hydrochlorothiazide

Antagonism of diuretic effect; increased risk of hypokalaemia

Ibuprofen

Increased risk of gastrointestinal bleeding and ulceration

Indinavir

Reduced plasma-indinavir concentration

Insulins

Antagonism of hypoglycaemic effect

Isosorbide dinitrate

Antagonism of hypotensive effect

Levonorgestrel

Levonorgestrel increases plasma concentration of dexamethasone

Lopinavir

Reduced plasma-lopinavir concentration

Medroxyprogesterone

Medroxyprogesterone increases plasma concentration of dexamethasone

Metformin

Antagonism of hypoglycaemic effect

Methotrexate

Increased risk of haematological toxicity

Methyldopa

Antagonism of hypotensive effect

Nifedipine

Antagonism of hypotensive effect

Norethisterone

Norethisterone increases plasma concentration of dexamethasone

Phenobarbital

Metabolism of dexamethasone accelerated (reduced effect)

Phenytoin

Metabolism of dexamethasone accelerated (reduced effect)

Praziquantel

Plasma-praziquantel concentration reduced

Propranolol

Antagonism of hypotensive effect

Rifampicin

Accelerated metabolism of dexamethasone (reduced effect)

Ritonavir

Increased plasma concentration by ritonavir

Salbutamol

Increased risk of hypokalaemia if high doses of dexamethasone given with high doses of salbutamol

Saquinavir

Reduced plasma-saquinavir concentration

Sodium nitroprusside

Antagonism of hypotensive effect

Spironolactone

Antagonism of diuretic effect

Theophylline

Increased risk of hypokalaemia

Vaccines, Live

High doses of dexamethasone impair immune response; avoid use of live vaccines

Verapamil

Antagonism of hypotensive effect

Warfarin

Anticoagulant effect altered

DEXTRAN 40

 

Abciximab

Additive effect

DEXTROMETHORPHAN

 

MAO Inhibitors

Risk of hypotension, hyperpyrexia, sedation etc.

Sibutramine

Risk of serotonin syndrome

DIAZEPAM

 

Atenolol

Enhanced hypotensive effect

Enalapril

Enhanced hypotensive effect

Furosemide

Enhanced hypotensive effect

Glyceryl trinitrate

Enhanced hypotensive effect

Ritonavir

Plasma concentration increased by ritonavir

DICLOFENAC

 

Cyclosporine

Decreased renal function

Methotrexate

Increased levels of methotrexate.

DICYCLOMINE

 

Antidepressants

Increased risk of antimuscarinic side effects

Antipsychotics

Antimuscarinics reduce effects of haloperidol; increased risk of antimuscarinic side-effects when antimuscarinics given with clozapine; antimuscarinics reduce plasma concentration of phenothiazines, but risk of antimuscarinic side effects increased

DIDANOSINE

 

Divalproex

Risk of additive toxicity

Ganciclovir

Increased didanosine concentration

Metronidazole

Risk of additive toxicity

Pentamidine

Risk of additive toxicity

Stavudine

Risk of additive toxicity

Vinblastine

Risk of additive toxicity

DIGOXIN

 

Acetazolamide

Cardiac toxicity of digoxin increased if hypokalaemia occurs

Amphotericin B

Increased digoxin toxicity if hypokalaemia occurs

Atenolol

Increased AV block and bradycardia

Corticosteroids

Increased risk of hypokalamia

Cyclosporine

Reduced clearance of digoxin (risk of toxicity)

Furosemide

Cardiac toxicity of digoxin increased if hypokalaemia occurs

Hydrochlorothiazide

Cardiac toxicity of digoxin increased if hypokalaemia occurs

Nifedipine

Increased plasma concentration of digoxin

Timolol

Increased AV block and bradycardia

Verapamil

Increased plasma concentration of digoxin; increased AV block and bradycardia

DIHYDROERGOTAMINE

 

Amiodarone

Increased cardiac depressant effects

Azoles antifungal

Increased level of alkoloid

Buspirone

Increased serum level of buspirone

Macrolide antibiotics

Increased plasma level of unchanged alkaloid and peripheral vasoconstriction

Protease inhibitors

Elevated levels of ergot alkaloids

Sumatriptan

Additive effect with dihydroergotamine

DILTIAZEM

 

Carbamazepine

Increased serum level of carbamazepine

Rifampin

Decreased diltiazem plasma concentration

DOBUTAMINE

 

Beta-blockers

Risk of peripheral resistance

DOMPERIDONE

 

Amiodarone

Additive toxicity with amiodarone

DOPAMINE

 

Ergometrine

Increased risk of ergotism

Haloperidol

Antagonism of pressor action

DOXORUBICIN

 

Cyclosporine

Increased risk of neurotoxicity

Cyclophosphamide

Chances of exacerbation of cyclophosphamide-induced hemorrhagic cystitis

Digoxin

Decreased digoxin levels

Paclitaxel

Increased risk of cardiotoxicity

Progesterone

Increased risk of doxorubicin-induced neutropenia

Quinidine

Increases the levels of doxorubicin

Stavudine

Decreased level and effectiveness of stavudine

Vaccines, Live

Avoid use of live vaccines with doxorubicin

Zidovudine

Decreased effect of zidovudine

DOXYCYCLINE

 

Cyclosporine

Increased plasma-cyclosporine concentration

Ergotamine

Increased risk of ergotism

Warfarin

Anticoagulant effect enhanced

EFAVIRENZ

 

Ergot derivatives

Increased chance of ergotism

Itraconazole

Decreased plasma level of itraconazole

Lopinavir

Plasma concentration of lopinavir reduced

Ritonavir

Increased risk of toxicity

ENALAPRIL

 

Acetylsalicylic acid

Antagonism of hypotensive effect; increased risk of renal impairment

Antacids

Absorption of enalapril reduced

Cyclosporine

Increased risk of hyperkalaemia

Glibenclamide

Hypoglycaemic effect enhanced

Heparin

Increased risk of hyperkalaemia

Lithium

Increased plasma-lithium concentration

Spironolactone

Enhanced hypotensive effect, risk of severe hyperkalaemia

EPINEPHRINE (ADRENALINE)

Halothane

Risk of arrhythmias

ERYTHROMYCIN

 

Artemether + Lumefantrine

Avoid concomitant use

Carbamazepine

Increased plasma-carbamazepine concentration

Corticosteroids

Inhibits metabolism of corticosteroids

Cyclosporine

Increased plasma-cyclosporine concentration

Digoxin

Enhanced effect of digoxin

Warfarin

Enhanced anticoagulant effect

ERYTHROPOIETIN

 

Haematinics

Enhanced efficiency of erythropoietin

ESCITALOPRAM

 

Carbamazepine

Carbamazepine toxicity may be precipitated

ESMOLOL

 

Verapamil

Chances of cardiac arrest

ETHINYL ESTRADIOL

 

Hydantoin

Reduced effect of estrogen

ETOPOSIDE

 

Vaccines, Live

Avoid use of live vaccines with etoposide

EZETIMIBE

 

Bile Acid Sequestrants

Decreased levels and clinical effectiveness of ezetimibe

Fibrates

Elevated levels of ezetimibe leading to toxicity

Cyclosporine

Increased ezetimibe levels in patients with severe renal insufficiency

FACTOR IX

 

Acetylsalicylic acid

Risk of bleeding

FAMOTIDINE

 

Antacids

Reduced absorption of famotidine

Ketoconazole, itraconazole

Reduced absorption of ketoconazole and itraconazole

Ethanol

Gastric mucosal irritation may occur

FENOFIBRATE

 

Anticoagulants

Increased effect of anticoagulants

Statins

Increased risk of kidney and muscle problems

Cyclosporine

Increased risk of nephrotoxicity

IRON SALTS

 

Ciprofloxacin

Absorption of ciprofloxacin reduced by oral ferrous salts

Doxycycline

Reduced absorption of oral ferrous salts by doxycycline; reduced absorption of doxycycline by oral ferrous salts

Methyldopa

Reduced hypotensive effect of methyldopa

FEXOFENADINE

 

Antacids

Decreased absorption of fexofenadine

Erythromycin

Increased plasma concentration of fexofenadine

Ketoconazole

Increased plasma concentration of fexofenadine

FLUCONAZOLE

 

Artemether + Lumefantrine

Avoid concomitant use

Cyclosporine

Metabolism of cyclosporine inhibited

Glibenclamide

Plasma concentration of glibenclamide increased

Rifampicin

Accelerated metabolism of fluconazole

Warfarin

Enhanced anticoagulant effect

Zidovudine

Increased plasma concentration of zidovudine (increased risk of toxicity)

FLUCYTOSINE

 

Amphotericin B

Renal excretion of flucytosine decreased and cellular uptake increased (flucytosine toxicity increased)

5-FLUOROURACIL

 

Metronidazole

Metabolism of 5-fluorouracil inhibited

Phenytoin

Reduced absorption of phenytoin

Warfarin

Anticoagulant effect enhanced

FLUOXETINE

 

Benzodiazepines

Increased level of benzodiazepines

Clozapine

Increased levels of clozapine

Selected MAO inhibitors

Risk of serotonin syndrome

FLUPHENAZINE

 

Amitriptyline

Increased antimuscarinic adverse effects; increased plasma-amitriptyline concentration; increased risk of ventricular arrhythmias

Artemether + Lumefantrine

Increased risk of ventricular arrhythmias

Atenolol

Enhanced hypotensive effect

Carbamazepine

Antagonism of anticonvulsant effect

Enalapril

Enhanced hypotensive effect

Lithium

Increased risk of extrapyramidal effects and neurotoxicity

Methyldopa

Enhanced hypotensive effect; increased risk of extrapyramidal effects

Metoclopramide

Increased risk of extrapyramidal effects

Nifedipine

Enhanced hypotensive effect

Phenobarbital

Antagonism of anticonvulsant effect (convulsive threshold lowered)

Phenytoin

Antagonism of anticonvulsant effect (convulsive threshold lowered)

Valproic acid

Antagonism of anticonvulsant effect (convulsive threshold lowered)

FOLIC ACID AND FOLINIC ACID

Phenobarbital

Plasma concentration of phenobarbital reduced

Phenytoin

Plasma-phenytoin concentration reduced

FORMOTEROL + FLUTICASONE PROPIONATE

Ritonavir

Systemic corticosteroid effects including cushing syndrome and adrenal suppression

Ketoconazole

Increased plasma fluticasone propionate concentrations

MAO inhibitors

Increased risk of cardiovascular adverse effects

FOSPHENYTOIN

 

Albendazole

Efficacy is impaired by phenytoin

Antipsychotics

Efficacy is impaired by phenytoin

Furosemide

Efficacy is impaired by phenytoin

Quinidine

Efficacy is impaired by phenytoin

Theophylline

Efficacy is impaired by phenytoin

Vitamin D

Efficacy is impaired by phenytoin

FRAMYCETIN

 

Capreomycin

Additive toxicity with capreomycin

FURAZOLIDONE

 

SSRIs

Risk of serotonin syndrome

FUROSEMIDE

 

Amphotericin B

Increased risk of hypokalaemia

Artemether + Lumefantrine

Increased risk of ventricular arrhythmias if electrolyte disturbance occurs

Cisplatin

Increased risk of nephrotoxicity and ototoxicity

Digoxin

Cardiac toxicity of digoxin increased if hypokalaemia occurs

Enalapril

Enhanced hypotensive effect

Glibenclamide

Antagonism of hypoglycaemic effect

Corticosteroids

Antagonism of diuretic effect; increased risk of hypokalaemia

Lithium

Increased plasma-lithium concentration and risk of toxicity

Salbutamol

Increased risk of hypokalaemia with high doses of salbutamol

Streptomycin

Increased risk of ototoxicity

Vancomycin

Increased risk of ototoxicity

GEMCITABINE

 

Live vaccines

Serum antibody response may not be obtained

Zidovudine

Additive toxicity

GENTAMICIN

 

Cyclosporine

Increased risk of nephrotoxicity

Cisplatin

Increased risk of nephrotoxicity and ototoxicity

Suxamethonium

Enhanced muscle relaxant effect

Vancomycin

Increased risk of nephrotoxicity and ototoxicity

Vecuronium

Enhanced muscle relaxant effect

GLIBENCLAMIDE

 

Ciprofloxacin

Enhanced effect of glibenclamide

Corticosteroids

Antagonism of hypoglycaemic effect

Enalapril

Hypoglycaemic effect enhanced

Fluconazole

Plasma concentration of glibenclamide increased

Hydrochlorothiazide

Antagonism of hypoglycaemic effect

Levonorgestrel

Antagonism of hypoglycaemic effect

Sulfadoxine + Pyrimethamine

Effect of glibenclamide may be enhanced

Sulfamethoxazole + Trimethoprim

Effect of glibenclamide may be enhanced

Warfarin

Enhanced hypoglycaemic effects and changes to anticoagulant effect

GLICLAZIDE

 

Acetylsalicylic acid

Effect of gliclazide is potentiated

Clofibrate

Effect of gliclazide is potentiated

Sulphonamides

Effect of gliclazide is potentiated

Oral anticoagulants

Effect of gliclazide is potentiated

MAO inhibitors

Effect of gliclazide is potentiated

Rifampicin

Effect of gliclazide is antagonized

Barbiturates

Effect of gliclazide is antagonized

Diuretics

Effect of gliclazide is antagonized

Diazoxide

Effect of gliclazide is antagonized

Glucocorticoids

Effect of gliclazide is antagonized

Sympathomimetics

Effect of gliclazide is antagonized

GLIMEPIRIDE

 

Corticosteroids

Reduced hypoglycaemic action

Phenytoin

Reduced hypoglycaemic action

Thiazides

Reduced hypoglycaemic action

GLUCAGON

 

Anticoagulants

Excess hypoprothrombinemia and bleeding complications

GLYCERYL TRINITRATE

 

Atenolol

Enhanced hypotensive effect

Corticosteroids

Antagonism of hypotensive effect

GRISEOFULVIN

 

Levonorgestrel

Accelerated metabolism of levonorgestrel (reduced contraceptive effect)

Warfarin

Metabolism of warfarin accelerated (reduced anticoagulant effect)

HALOPERIDOL

 

Amitriptyline

Increased plasma-amitriptyline concentration; increased risk of ventricular arrhythmias

Carbamazepine

Antagonism of anticonvulsant effect; metabolism of haloperidol accelerated

Lithium

Increased risk of extrapyramidal effects and neurotoxicity

Metoclopramide

Increased risk of extrapyramidal effects

Phenobarbital

Antagonism of anticonvulsant effect; metabolism of haloperidol accelerated

Phenytoin

Antagonism of anticonvulsant effect (convulsive threshold lowered)

Rifampicin

Accelerated metabolism of haloperidol (reduced plasma-haloperidol concentration)

Valproic acid

Antagonism of anticonvulsant effect (convulsive threshold lowered)

HALOTHANE

 

Amitriptyline

Increased risk of arrhythmias and hypotension

Atenolol

Enhanced hypotensive effect

Diazepam

Enhanced sedative effect

Levodopa

Risk of arrhythmias

Vancomycin

Hypersensitivity-like reactions can occur with concomitant intravenous vancomycin

Verapamil

Enhanced hypotensive effect and AV delay

HEPARIN

 

Acetylsalicylic acid

Enhanced anticoagulant effect

Enalapril

Increased risk of hyperkalaemia

HYDRALAZINE

 

Corticosteroids

Antagonism of hypotensive effect

HYDROCHLOROTHIAZIDE

 

Amitriptyline

Increased risk of postural hypotension

Amphotericin B

Increased risk of hypokalaemia

Artemether + Lumefantrine

Increased risk of ventricular arrhythmias if electrolyte disturbance occurs

Carbamazepine

Increased risk of hyponatraemia

Cisplatin

Increased risk of nephrotoxicity and ototoxicity

Digoxin

Cardiac toxicity of digoxin increased if hypokalaemia occurs

Glibenclamide

Antagonism of hypoglycaemic effect

Ibuprofen

Risk of nephrotoxicity of ibuprofen increased; antagonism of diuretic effect

Insulins

Antagonism of hypoglycaemic effect

Lithium

Reduced lithium excretion (increased plasma-lithium concentration and risk of toxicity); furosemide safer than hydrochlorothiazide

Salbutamol

Increased risk of hypokalaemia with high doses of salbutamol

IBUPROFEN

 

Acetylsalicylic acid

Avoid concurrent administration (increased adverse effects including gastrointestinal damage); antiplatelet effect of acetylsalicylic acid reduced

Atenolol

Antagonism of hypotensive effect

Cyclosporine

Increased risk of nephrotoxicity

Ciprofloxacin

Increased risk of convulsions

Corticosteroids

Increased risk of gastrointestinal bleeding and ulceration

Digoxin

Exacerbation of heart failure, reduced GFR, and increased plasma-digoxin concentration

Enalapril

Antagonism of hypotensive effect, increased risk of renal impairment

Glibenclamide

Enhanced effect of glibenclamide

Hydrochlorothiazide

Risk of nephrotoxicity of ibuprofen increased; antagonism of diuretic effect

Lithium

Reduced excretion of lithium

Methotrexate

Excretion of methotrexate reduced

Nifedipine

Antagonism of hypotensive effect

Warfarin

Anticoagulant effect enhanced

Zidovudine

Increased risk of haematological toxicity

IMATINIB

 

Rifampin

Increased clearance of imatinib

Warfarin

Imatinib may inhibit metabolism of warfarin

IMIPENEM + CILASTATIN

 

Ganciclovir

May result in generalised seizures

INDINAVIR

 

Carbamazepine

Reduced plasma concentration of indinavir

Efavirenz

Reduced plasma concentration of indinavir

Ergotamine

Increased risk of ergotism (avoid concomitant use)

Nelfinavir

Combination may lead to increased plasma concentration of either drug (or both)

Nevirapine

Reduced plasma concentration of indinavir

Phenobarbital

Reduced plasma concentration of indinavir

Rifampicin

Metabolism enhanced by rifampicin

INSULINS

 

Atenolol

Enhanced hypoglycaemic effect; masking of warning signs of hypoglycaemia such as tremor

Corticosteroids

Antagonism of hypoglycaemic effect

Enalapril

Hypoglycaemic effect enhanced

Furosemide

Antagonism of hypoglycaemic effect

Hydrochlorothiazide

Antagonism of hypoglycaemic effect

Levonorgestrel

Antagonism of hypoglycaemic effect

Nifedipine

Occasionally impaired glucose tolerance

IODINE

 

Lithium

Synergistic toxicity

IOPANOIC ACID

 

Atenolol

Iopanoic acid toxicity may occur

Methotrexate

Methotrexate toxicity may occur

ISONIAZID

 

Carbamazepine

Increased plasma-carbamazepine concentration

Diazepam

Metabolism of diazepam inhibited

Phenytoin

Metabolism of phenytoin inhibited

ISOSORBIDE DINITRATE

 

Sildenafil

Serious hypotension; MI may be precipitated

ISOTRETINOIN

 

Vitamin A

Additive toxicity

Progesterone

Decreased efficacy of microdosed progesterone

Corticosteroids, phenytoin

Increased risk of osteoporosis

Carbamazepine

Decreased plasma levels of carbamazepine

Tetracyclines

Increased risk of pseudotumor cerebri

ISPAGHULA

 

Lithium

decreased effect of lithium

IVERMECTIN

 

Vitamin K Antagonists (e.g., warfarin)

Enhanced anticoagulant effect

KETOCONAZOLE

 

Amphotericin B

Increased adverse effect

Cyclosporine

Increased level of cyclosporine

Tolbutamide

Reduces blood glucose level

LAMIVUDINE

 

Foscarnet

Concurrent use not recommended

LATANOPROST

 

Thiomersal

Risk of precipitate formation

LEFLUNOMIDE

 

Acenocoumarol

Increased anticoagulant effect

Warfarin

Increased anticoagulant effect

Methotrexate

Increased risk of hepatotoxicity

Cholestyramine

Enhanced leflunomide excretion and increased total clearance by approximately 50%

LEVOCETIRIZINE

 

Alcohol or CNS depressants

Additive sedation

Theophylline

Increases the levels of levocetirizine in blood

LEVODOPA

 

Metoclopramide

Antagonism of effects of levodopa

Ether, Anaesthetic

Risk of arrhythmias

Ferrous salts

Absorption of levodopa may be reduced

Halothane

Risk of arrhythmias

Methyldopa

Enhanced hypotensive effect; antagonism of antiparkinsonian effect

Nifedipine

Enhanced hypotensive effect

Propranolol

Enhanced hypotensive effect

Pyridoxine

Antagonism of levodopa unless carbidopa also given

LEVOTHYROXINE

 

Phenobarbital

Metabolism of levothyroxine accelerated (may increase levothyroxine requirements in hypothyroidism)

Theophylline

Metabolism of theophylline is increased; larger doses are required

Warfarin

Enhanced anticoagulant effect

LIDOCAINE

 

Acetazolamide

Action of lidocaine antagonised by hypokalaemia

Atenolol

Increased risk of myocardial depression

Bupivacaine

Increased myocardial depression

Furosemide

Action of lidocaine antagonised by hypokalaemia

Hydrochlorothiazide

Action of lidocaine antagonised by hypokalaemia

Procainamide

Increased myocardial depression

Propranolol

Increased risk of myocardial depression; increased risk of lidocaine toxicity

Quinidine

Increased myocardial depression

Timolol

Increased risk of myocardial depression

Verapamil

Increased risk of myocardial depression

LITHIUM

 

Acetazolamide

Excretion of lithium increased

Amiloride

Reduced lithium excretion (increased plasma-lithium concentration and risk of toxicity)

Enalapril

Enalapril reduces excretion of lithium (increased plasma-lithium concentration)

Furosemide

Reduced lithium excretion (increased plasma-lithium concentration and risk of toxicity); furosemide safer than hydrochlorothiazide

Haloperidol

Increased risk of extrapyramidal effects and possibility of neurotoxicity

Hydrochlorothiazide

Reduced lithium excretion (increased plasma-lithium concentration and risk of toxicity); furosemide safer than hydrochlorothiazide

Ibuprofen

Reduced excretion of lithium (risk of toxicity)

Methyldopa

Neurotoxicity may occur without increased plasma-lithium concentration

Spironolactone

Reduced lithium excretion (increased plasma-lithium concentration and risk of toxicity)

Suxamethonium

Enhanced muscle relaxant effect

LOPERAMIDE

 

Quinidine

Increased CNS level of loperamide

MEBENDAZOLE

 

Carbamazepine

Reduced plasma-mebendazole concentration (increase mebendazole dose for tissue infection)

Phenytoin

Reduced plasma-mebendazole concentration (increase mebendazole dose for tissue infection)

MEFENAMIC ACID

 

Warfarin

Risk of serious GI bleeding higher than users of either drug alone.

Lithium

Reduced renal clearance and increased risk of lithium toxicity.

Methotrexate

Reduced excretion of methotrexate and possible increased risk of toxicity

Phenobarbital

Reduced plasma-mebendazole concentration (increase mebendazole dose for tissue infection)

6-MERCAPTOPURINE

 

Allopurinol

Effects of 6-mercaptopurine enhanced with increased toxicity, reduce dose when given with allopurinol

Phenytoin

Reduced absorption of phenytoin

Sulfamethoxazole + Trimethoprim

Increased risk of haematological toxicity

Sulfasalazine

Increased risk of leukopenia

Trimethoprim

Increased risk of haematological toxicity

Vaccines, Live

Avoid use of live vaccines with 6-mercaptopurine (impairment of immune response)

Warfarin

Anticoagulant effect reduced

MEROPENEM

 

Probenecid

Renal excretion of meropenem is inhibited

Valproic acid

Serum valproic acid concentration is decreased

METFORMIN

 

Atenolol

Masking of warning signs of hypoglycaemia such as tremor

Corticosteroids

Antagonism of hypoglycaemic effect

Enalapril

Hypoglycaemic effect enhanced

Levonorgestrel

Antagonism of hypoglycaemic effect

Lithium

May occasionally impair glucose tolerance

Medroxyprogesterone

Antagonism of hypoglycaemic effect

Norethisterone

Antagonism of hypoglycaemic effect

METHADONE

 

Cimetidine

Effect of methadone may be increased

MAO Inhibitors

Risk of hypotension, hyperexia etc.

METHOTREXATE

 

Acetylsalicylic acid

Reduced excretion of methotrexate (increased toxicity)

Amoxycillin

Reduced excretion of methotrexate (increased risk of toxicity)

Cyclosporine

Increased toxicity

Ibuprofen

Excretion of methotrexate reduced (increased risk of toxicity)

Nitrous oxide

Increased antifolate effect (avoid concomitant use)

Phenytoin

Reduced absorption of phenytoin; antifolate effect of methotrexate increased

Pyrimethamine

Antifolate effect of methotrexate increased

Sulfadoxine + Pyrimethamine

Antifolate effect of methotrexate increased; risk of methotrexate toxicity increased

Sulfamethoxazole + Trimethoprim

Antifolate effect of methotrexate increased (avoid concomitant use); risk of methotrexate toxicity increased

Trimethoprim

Antifolate effect of methotrexate increased (avoid concomitant use)

Vaccines, Live

Avoid use of live vaccines with methotrexate (impairment of immune response)

METHYLDOPA

 

Ferrous salts

Reduced hypotensive effect of methyldopa

Propranolol

Enhanced hypontensive effect

METHYL PREDNISOLONE

 

Amphotericin B

Chances of potentiation of K+ concentration

Cyclosporine

Levels increased upto 2 fold

METRONIDAZOLE

 

Phenytoin

Metabolism of phenytoin inhibited (increased plasma-phenytoin concentration)

Warfarin

Enhanced anticoagulant effect

MMR vaccine

See vaccines, live

MIDAZOLAM

 

Ketoconazole

Increased levels of midazolam

Verapamil

Increased levels of midazolam

MIFEPRISTONE

 

Dexamethasone

Decreased serum levels of mifepristone

MOMETASONE

 

Anticoagulants

Increased or decreased effects of anticoagulants

Bupropion

Increased risk of seizures

Quinolones

Increased risk of tendonitis and/or tendon rupture

Quetiapine

Decreased levels of quetiapine

MORPHINE

 

Ciprofloxacin

Avoid premedication with morphine (reduced plasma-ciprofloxacin concentration)

Quinidine

Decreased analgesic effect

Ritonavir

Ritonavir increases plasma concentration of morphine

MYCOPHENOLATE

 

Bile acid sequestrants

Decreased level and clinical effect of mycophenolate

Antacids

Decreased effect

NALIDIXIC ACID

 

Cyclosporine

Increased risk of nephrotoxicity

Ibuprofen

Increased risk of convulsions

Theophylline

Increased risk of convulsions

Warfarin

Enhanced anticoagulant effect

NELFINAVIR

 

Ergotamine

Increased risk of ergotism (avoid concomitant use)

Phenobarbital

Plasma concentration of nelfinavir reduced

Quinidine

Increased risk of ventricular arrhythmias (avoid concomitant use)

Rifampicin

Plasma concentration of nelfinavir significantly reduced (avoid concomitant use)

NEOSTIGMINE

 

Gentamicin

Antagonism of effect of neostigmine

Streptomycin

Antagonism of effect of neostigmine

NEVIRAPINE

 

Lopinavir

Plasma concentration of lopinavir reduced

Rifampicin

Reduced plasma concentration of nevirapine (avoid concomitant use)

Saquinavir

Plasma concentration of saquinavir reduced (avoid concomitant use)

NICOTINIC ACID

 

Ganglionic blocking agents and vasoactive drugs

Potentiates the effects of ganglionic blocking agents and vasoactive drugs resulting in postural hypotension

Bile acid sequest (for example, cholestyramine)

Bind and prevent absorption of niacin; should be separated by 4 to 6 h.

NIFEDIPINE

 

Atenolol

Severe hypotension and heart failure occasionally

Cyclosporine

Increased plasma-nifedipine concentration (increased risk of adverse effects such as gingival hyperplasia)

Digoxin

Increased plasma concentration of digoxin

Magnesium (parenteral)

Profound hypotension reported with nifedipine and intravenous magnesium sulphate in pre-eclampsia

Phenobarbital

Effect of nifedipine reduced

Phenytoin

Reduced effect of nifedipine

Propranolol

Severe hypotension and heart failure occasionally

Ritonavir

Plasma concentration increased by ritonavir

Rifampicin

Accelerated metabolism of nifedipine (plasma concentration significantly reduced)

Theophylline

Enhanced theophylline effect (increased plasma-theophylline concentration)

Timolol

Severe hypotension and heart failure occasionally

NITROUS OXIDE

 

Chlorpromazine

Enhanced hypotensive effect

Fluphenazine

Enhanced hypotensive effect

Haloperidol

Enhanced hypotensive effect

Methotrexate

Increased antifolate effect (avoid concomitant use)

Verapamil

Enhanced hypotensive effect and AV delay

NORADRENALINE

 

Guanethidine + methyldopa + reserpine + tricyclic antidepressants

Pressor response to norepinephrine may be increased

Cocaine

Increased risk of arrhythmias

MAOIs

Hypertensive crisis occurs

Nonselective β-blockers

Increased hypertensive effects

OMEPRAZOLE

 

Cilostazol

Increased levels of cilastazole

Nelfinavir

Decreased level of nelfinavir

Raltegravir

Increased levels of raltigavir

ONDANSETRON

 

Tramadol

Decreased effectiveness of tramadol

OXCARBAMAZEPINE

 

Lamotrigine

Decreased levels of lamotrigine

OXYTETRACYCLINE

 

Calcium and Iron dextran

Formation of non-absorbable complexes

Penicillins

Antagonism of effect of oxytetracycline

Etritenate and isotretinoin

Associated with increased risk of intracranial hypertension

Oral contraceptives

May decrease the effect of oral contraceptives

PHENOBARBITONE

 

Amitriptyline

Antagonism of anticonvulsant effect (convulsive threshold lowered); metabolism of amitriptyline accelerated (reduced plasma concentration)

Carbamazepine

Enhanced toxicity without corresponding increase in antiepileptic effect; plasma concentration of carbamazepine often lowered

Cyclosporine

Metabolism of cyclosporine accelerated (reduced effect)

Haloperidol

Antagonism of anticonvulsant effect (convulsive threshold lowered); metabolism of haloperidol accelerated (reduced plasma concentration)

Nifedipine

Effect of nifedipine reduced

Phenytoin

Enhanced toxicity without corresponding increase in antiepileptic effect; plasma concentration of phenytoin often lowered but may be raised; plasma concentration of phenobarbital often raised

Valproic acid

Enhanced toxicity without corresponding increase in antiepileptic effect; plasma concentration of valproic acid often lowered; phenobarbital concentration often raised

Warfarin

Metabolism of warfarin accelerated (reduced anticoagulant effect)

PHENOXYMETHYL PENICILLIN

Methotrexate

Reduced excretion of methotrexate (increased risk of toxicity)

PHENYTOIN

 

Amitriptyline

Antagonism (convulsive threshold lowered); reduced plasma-amitriptyline concentration

Carbamazepine

Enhanced toxicity without corresponding increase in antiepileptic effect; plasma concentration of phenytoin often lowered but may be raised; plasma concentration of carbamazepine often lowered

Chloramphenicol

Plasma-phenytoin concentration increased (risk of toxicity)

Chloroquine

Convulsive threshold occasionally lowered

Cyclosporine

Accelerated metabolism (reduced plasma-cyclosporine concentration)

Clonazepam

Enhanced toxicity without corresponding increase in antiepileptic effect; plasma concentration of clonazepam often lowered

Fluconazole

Effect of phenytoin enhanced; plasma concentration increased

Haloperidol

Antagonism of anticonvulsant effect (convulsive threshold lowered)

Isoniazid

Metabolism of phenytoin inhibited (enhanced effect)

Mefloquine

Antagonism of anticonvulsant effect

Metronidazole

Metabolism of phenytoin inhibited (increased plasma-phenytoin concentration)

Nifedipine

Reduced effect of nifedipine

Pyrimethamine

Antagonism of anticonvulsant effect; increased antifolate effect

Rifampicin

Accelerated metabolism of phenytoin (reduced plasma concentration)

Sulfadoxine + Pyrimethamine

Plasma-phenytoin concentration increased; increased antifolate effect

Sulfamethoxazole + Trimethoprim

Antifolate effect and plasma-phenytoin concentration increased

Valproic acid

Enhanced toxicity without corresponding increase in antiepileptic effect; plasma concentration of valproic acid often lowered; plasma concentration of phenytoin often raised (but may also be lowered)

Warfarin

Accelerated metabolism of warfarin (reduced anticoagulant effect, but enhancement also reported)

PIOGLITAZONE

 

NSAID

Increased risk of fluid retention

Rifampicin

Decreased plasma concentration.

Ketoconazole

Increased plasma concentration.

PIPERACILLIN + TAZOBACTAM

Aminoglycosides

Inactivation of aminoglycosides

Methotrexate

Reduced clearance of methotrexate

PREDNISOLONE

 

Amphotericin B

Increased risk of hypokalaemia (avoid concomitant use unless prednisolone needed to control reactions)

Carbamazepine

Accelerated metabolism of prednisolone (reduced effect)

Phenobarbital

Metabolism of prednisolone accelerated (reduced effect)

Phenytoin

Metabolism of prednisolone accelerated (reduced effect)

Rifampicin

Accelerated metabolism of prednisolone (reduced effect)

Vaccines, Live

High doses of prednisolone impair immune response; avoid use of live vaccines

Warfarin

Anticoagulant effect altered

PROPOFOL

 

Fentanyl

Concomitant use in paediatric patients may result in serious bradycardia

CNS depressants

Increased sedative, anaesthetic and cardiorespiratory effects

PYRIDOXINE

 

Levodopa

Antagonism of levodopa unless carbidopa also given

PYRIMETHAMINE

 

Artemether + Lumefantrine

Avoid concomitant use

Methotrexate

Antifolate effect of methotrexate increased

Phenytoin

Antagonism of anticonvulsant effect; increased antifolate effect

Sulfonamides + Trimethoprim

Increased antifolate effect

RALOXIFENE

 

Estrogen

Increased risk of adverse effects

RAMIPRIL

 

Diuretics

Excessive reduction of blood pressure

Potassium supplements/Potassium sparing diuretics

Increased risk of hyperkalemia

Lithium

Increased serum lithium levels and lithium toxicity

RIFAMPICIN

 

Azathioprine

Transplants rejected

Cyclosporine

Accelerated metabolism (reduced plasma-cyclosporine concentration)

Dapsone

Reduced plasma-dapsone concentration

Fluconazole

Accelerated metabolism of fluconazole (reduced plasma concentration)

Glibenclamide

Accelerated metabolism (reduced effect) of glibenclamide

Haloperidol

Accelerated metabolism of haloperidol (reduced plasma-haloperidol concentration)

Nifedipine

Accelerated metabolism of nifedipine (plasma concentration significantly reduced)

Phenytoin

Accelerated metabolism of phenytoin (reduced plasma concentration)

Corticosteroids

Accelerated metabolism of corticosteroids

Verapamil

Accelerated metabolism of verapamil (plasma concentration significantly reduced)

Warfarin

Accelerated metabolism of warfarin (reduced anticoagulant effect)

RITONAVIR

 

Carbamazepine

Plasma concentration increased by ritonavir

Cyclosporine

Plasma concentration increased by ritonavir

Diazepam

Plasma concentration increased by ritonavir (risk of extreme sedation and respiratory depression-avoid concomitant use)

Fluconazole

Plasma concentration increased by ritonavir

Verapamil

Plasma concentration increased by ritonavir

Warfarin

Plasma concentration increased by ritonavir

SALBUTAMOL

 

Methyldopa

Acute hypotension reported with salbutamol infusion

SILDENAFIL

 

Protease inhibitors

Sildenafil metabolism is inhibited

Alpha blockers

Avoid concomitant use (may lead to low blood pressure)

Ketoconazole

Increased action of sildenafil

Erythromycin

Increased action of sildenafil

Verapamil

Increased action of sildenafil

Nitrates

Vasoconstrictor activity of nitrates is potentiated

STREPTOMYCIN

 

Amphotericin B

Increased risk of nephrotoxicity

Cyclosporine

Increased risk of nephrotoxicity

Cisplatin

Increased risk of nephrotoxicity and ototoxicity

Furosemide

Increased risk of ototoxicity

Neostigmine

Antagonism of effect of neostigmine

Suxamethonium

Enhanced muscle relaxant effect

STRONTIUM RENELATE

 

Calcium products

Reduced biovailability of strontium ranelate.

Tetracycline

Reduced absorption of oral tetracycline

Quinolone antibiotics

Reduced absorption of quinolone antibiotics

Almunium and Magnesium Hydroxides

Decreased absorption of strontium ranelate

SULFADOXINE + PYRIMETHAMINE

Artemether + Lumefantrine

Avoid concomitant use

Cyclosporine

Increased risk of nephrotoxicity

Glibenclamide

Effect of glibenclamide rarely, enhanced

Methotrexate

Antifolate effect of methotrexate increased; risk of methotrexate toxicity increased

Phenytoin

Plasma-phenytoin concentration increased; increased antifolate effect

Warfarin

Enhanced anticoagulant effect

SULFASALAZINE

 

Azathioprine

Increased risk of leukopenia

Mercaptopurine

Increased risk of leukopenia

TACROLIMUS

 

Aminoglycosides

Increased risk of renal dysfunction

Carbamazepine

Decreased tacrolimus blood concentration

Cisplatin

Increased risk of renal dysfunction

Clarithromycin

Increased tacrolimus blood concentration

Chloramphenicol

Increased tacrolimus blood concentration

Clotrimazole

Increased tacrolimus blood concentration

Phenytoin

Decreased tacrolimus blood concentration

Rifampin

Decreased tacrolimus blood concentration

Diltiazem

Increased tacrolimus blood concentration

Nifedipine

Increased tacrolimus blood concentration

Verapamil

Increased tacrolimus blood concentration

TELMISARTAN

 

Lithium

Increased in serum lithium concentration and toxicity

THALIDOMIDE

 

Barbiturates

Enhanced sedative activity

Alcohol

Enhanced sedative activity

Chlorpromazine

Enhanced sedative activity

Reserpine

Enhanced sedative activity

Vincristine

Potential to cause peripheral neuropathy

Bortezomib

Potential to cause peripheral neuropathy

THEOPHYLLINE

 

Ciprofloxacin

Increased plasma-theophylline concentration; increased risk of convulsions

Erythromycin

Inhibition of theophylline metabolism (increased plasma-theophylline concentration resulting in theophylline toxicity)

Fluconazole

Plasma-theophylline concentration increased

TIMOLOL

 

Epinephrine

Severe hypertension

Verapamil

Asystole, severe hypotension and heart failure

Note: Systemic absorption may follow topical application of timolol to the eye

TOPIRAMATE

 

Carbamazepine

Reduced plasma level of topiramate

Phenytoin

Reduced plasma level of topiramate

Rifampin

Reduced plasma level of topiramate

TRANEXAMIC ACID

 

Clotting factor complexes

Increased risk of thrombotic complications

Hormonal contraception

Exacerbate the increased thrombotic risk associated with combination hormonal contraceptives

all-trans Retinoic acid

Concomitant use in women with acute promyelocytic leukemia taking all-trans retinoic acid for remission induction may cause exacerbation of the procoagulant effect of all-trans retinoic acid

TRIMETHOPRIM

 

Mercaptopurine

Increased risk of haematological toxicity

Methotrexate

Antifolate effect of methotrexate increased (avoid concomitant use)

Phenytoin

Antifolate effect and plasma-phenytoin concentration increased

Pyrimethamine

Increased antifolate effect

Sulfadoxine + Pyrimethamine

Increased antifolate effect

VALPROIC ACID

 

Carbamazepine

Enhanced toxicity without corresponding increase in antiepileptic effect; plasma concentration of valproic acid often lowered; plasma concentration of active metabolite of carbamazepine often raised

Chloroquine

Convulsive threshold occasionally lowered

Mefloquine

Antagonism of anticonvulsant effect

Phenobarbital

Enhanced toxicity without corresponding increase in antiepileptic effect; plasma concentration of valproic acid often lowered; phenobarbital concentration often raised

Phenytoin

Enhanced toxicity without corresponding increase in antiepileptic effect; plasma concentration of valproic acid often lowered; plasma concentration of phenytoin often raised (but may also be lowered)

VANCOMYCIN

 

Cyclosporine

Increased risk of nephrotoxicity

Furosemide

Increased risk of ototoxicity

VARICELLA VACCINE

 

Salicylates

Increased risk of Reye’s syndrome

VERAPAMIL

 

Atenolol

Asystole, severe hypotension and heart failure

Carbamazepine

Enhanced effect of carbamazepine

Digoxin

Increased plasma concentration of digoxin; increased AV block and bradycardia

Halothane

Enhanced hypotensive effect and AV delay

Ketamine

Enhanced hypotensive effect and AV delay

Lidocaine

Increased risk of myocardial depression

Rifampicin

Accelerated metabolism of verapamil (plasma concentration significantly reduced)

VINBLASTINE

 

Bleomycin

Increased risk of cardiovascular toxicity

WARFARIN

 

Acetylsalicylic acid

Increased risk of bleeding due to antiplatelet effect

Azathioprine

Anticoagulant effect reduced

Azithromycin

Enhanced anticoagulant effect of warfarin

Carbamazepine

Accelerated metabolism of warfarin (reduced anticoagulant effect)

Ceftazidime

Enhanced anticoagulant effect

Ceftriaxone

Enhanced anticoagulant effect

Chloramphenicol

Enhanced anticoagulant effect

Ciprofloxacin

Enhanced anticoagulant effect

Corticosteroids

Anticoagulant effect altered

Doxycycline

Anticoagulant effect enhanced

Erythromycin

Enhanced anticoagulant effect

Fluconazole

Enhanced anticoagulant effect

5-Fluorouracil

Anticoagulant effect enhanced

Glibenclamide

Enhanced hypoglycaemic effects and changes to anticoagulant effect

Griseofulvin

Metabolism of warfarin accelerated (reduced anticoagulant effect)

Ibuprofen

Anticoagulant effect enhanced

Levamisole

Anticoagulant effect enhanced

Levonorgestrel

Antagonism of anticoagulant effect

Levothyroxine

Enhanced anticoagulant effect

Medroxyprogesterone

Antagonism of anticoagulant effect

Mercaptopurine

Anticoagulant effect reduced

Metronidazole

Enhanced anticoagulant effect

Nalidixic acid

Enhanced anticoagulant effect

Norethisterone

Antagonism of anticoagulant effect

Ofloxacin

Enhanced anticoagulant effect

Phenobarbital

Metabolism of warfarin accelerated (reduced anticoagulant effect)

Phenytoin

Accelerated metabolism of warfarin (reduced anticoagulant effect, but enhancement also reported)

Phytomenadione

Antagonism of anticoagulant effect by phytomenadione

Proguanil

Isolated reports of enhanced anticoagulant effect

Quinidine

Anticoagulant effect may be enhanced

Rifampicin

Accelerated metabolism of warfarin (reduced anticoagulant effect)

Ritonavir

Plasma concentration increased by ritonavir

Sulfadiazine

Enhanced anticoagulant effect

Sulfadoxine + Pyrimethamine

Enhanced anticoagulant effect

Sulfamethoxazole + Trimethoprim

Enhanced anticoagulant effect

Tamoxifen

Enhanced anticoagulant effect

ZIDOVUDINE

 

Fluconazole

Increased plasma concentration of zidovudine (increased risk of toxicity)

Stavudine

May inhibit effect of stavudine (avoid concomitant use)

ZOLPIDEM

 

Rifampin

Pharmacodynamic effects of zolpidem are decreased

Ketoconazole

Pharmacodynamic effects of zolpidem are increased