Appendix 6a:

Drug-Alcohol Interactions

Mixing alcohol with medications can cause a variety of symptoms like nausea, vomiting, headache, drowsiness, fainting, or loss of coordination. By virtue of its effects on the CNS consumption of alcohol, even in small quantities, puts the patient at a high risk. There are medicines which should never be taken with alcohol (Table 1). However, there are many other medicines which should be used with high level of caution while the patient is on alcohol (Table 2).

Table 1: Drugs not to be used with alcohol

Acetylsalicylic Acid Alprazolam Amitriptyline Atorvastatin Benazepril
Butalbital + Codeine Carisoprodol Cefoperazone Chlordiazepoxide Clomipramine Clonazepam Clonidine Cyclobenzaprine Desipramine Diazepam Diphenhydramine Doxazosin Doxylamine
Enalapril Eszopiclone Fluoxetine Griseofulvin
Herbal Preparations Hydrochlorothiazide Ibuprofen
Isoniazid Isosorbide Ketoconazole Leflunomide Lorazepam
Losartan Lovastatin Lovastatin+ Niacin Meperidine Metronidazole Naproxen
Nicotinic acid Nitrazepam Nitrofurantoin Nitroglycerin Paracetamol Paroxetine Phenobarbital Phenytoin Pravastatin
Pravastatin + Acetylsalicylic acid
Prazosin
Propoxyphene
Quinapril
Ramipril
Rosuvastatin
Simvastatin
Simvastatin + Ezetimibe
Temazepam
Terazosin
Tinidazole
Vitamin D
Warfarin
Zolpidem

Table 2: Drugs to be avoided with alcohol

Abacavir Amobarabital Atenolol Atropine Bromocriptine
Brompheniramine Cetirizine Chlorpheniramine Chlorpromazine Cimetidine Dextromethorphan Diclofenac Dimenhydrinate Diphenhydramine Doxycycline Fexofenadine Fluphenazine Furazolidone Glyburide
Guaifenesin + Codeine Haloperidol Imipramine
Insulin
Loratadine
Metformin Methadone Methotrexate Metoclopramide Midazolam Morphine Nizatidine Oxytocin Pentazocine Prazosin Procarbazine Prochlorperazine Promethazine Propranolol Ranitidine
Sodium Valproate Tamsulosin Thiopental Tolbutamide Trifluoperazine Trihexyphenidyl

Appendix 6b: Drug–Contraceptive Interactions

CONTRACEPTIVES, ORAL

Acetazolamide Antagonism of diuretic effect Amiloride Antagonism of diuretic effect Amitriptyline Antagonism of antidepressant effect
but adverse effects increased due to
increased plasma concentration of
amitriptyline
Amoxycillin Reduced contraceptive effect of estrogen- containing preparations
Ampicillin Reduced contraceptive effect of estrogen- containing preparations
Atenolol Antagonism of hypotensive effect
Carbamazepine Accelerated metabolism of medroxyprogesterone (does not apply to injectable medroxyprogesterone acetate for contraception); reduced contraceptive effect (does not apply to injectable norethisterone enantate for contraception)
Ceftazidime Reduced contraceptive effect of estrogen- containing preparations
Ceftriaxone Reduced contraceptive effect of estrogen- containing preparations
Cefuroxime Reduced effect of contraceptives
Corticosteroids Oral contraceptives increase plasma concentration of corticosteroids
Clomipramine Antagonism of antidepressant effect but adverse effects increased due to increased plasma concentration of clomipramine
Cyclosporine Inhibition of cyclosporine metabolism (increased plasma–cyclosporine concentration)
Doxycycline Reduced contraceptive effect of estrogen- containing preparations
Efavirenz Efficacy of oral contraceptives reduced Enalapril Antagonism of hypotensive effect Fluconazole Anecdotal reports of contraceptive failure
Fosphenytoin Reduced contraceptive effect Furosemide Antagonism of diuretic effect Glibenclamide Antagonism of hypoglycaemic effect Glimepiride Reduced hypoglycaemic action Glucagon Antagonism of hypotensive effect Glyceryl trinitrate Antagonism of hypotensive effect
Griseofulvin Reduced contraceptive effect of levonorgestrel, accelerated metabolism of medroxyprogesterone (does not apply to injectable medroxyprogesterone acetate for contraception); does not apply to injectable norethisterone enantate for contraception
Hydralazine Antagonism of hypotensive effect
Hydrochlorothiazide Antagonism of diuretic effect
Insulins Antagonism of hypoglycaemic effect Isosorbide dinitrate Antagonism of hypotensive effect Metformin Antagonism of hypoglycaemic effect Methyldopa Antagonism of hypotensive effect Nelfinavir Accelerated metabolism of
levonorgestrel, medroxyprogesterone
and norethisterone (reduced
contraceptive effect); does not apply to
injectable medroxyprogestrone acetate
for contraception
Nevirapine Accelerated metabolism of levonorgestrel, medroxyprogesterone and norethisterone (reduced contraceptive effect); does not apply to injectable medroxyprogestrone acetate for contraception
Nifedipine Antagonism of hypotensive effect
Phenobarbital Metabolism accelerated (reduced contraceptive effect); does not apply to injectable medroxyprogestrone acetate for contraception; does not apply to injectable norethisterone enantate for contraception
Phenytoin Accelerated metabolism of levonorgestrel, norethisterone (reduced contraceptive effect); does not apply to injectable medroxyprogestrone acetate for contraception; does not apply to injectable norethisterone enantate for contraception
Propranolol Antagonism of hypotensive effect
Rifampicin Accelerated metabolism of levonorgestrol and medroxyprogesterone (reduced contraceptive effect); does not apply to injectable medroxyprogestrone acetate
for contraception; does not apply to injectable norethisterone enantate for contraception
Ritonavir Accelerated metabolism of levonorgestrol and norethisterone (reduced contraceptive effect); does not apply to injectable medroxyprogestrone acetate
for contraception; does not apply to injectable norethisterone enantate for contraception
Sodium nitroprusside Antagonism of hypotensive effect Spironolactone Antagonism of diuretic effect Topiramate Failure of contraceptive effect Theophylline Delayed excretion of theophylline;
increased plasma concentration
Verapamil Antagonism of hypotensive effect
Warfarin Antagonism of anticoagulant effect

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 phar- macodynamic 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 symptoma- tology 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:

leeding
leeding
yponatraemia; reases plasma– ncentration
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
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

CODEINE

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

DESFERRIOXAMINE MESYLATE

Plasma concentration of both dapsone and trimethoprim increased with concomitant use
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
Bile acid sequestrants
(for example, cholestyramine)

NIFEDIPINE

Potentiates the effects of ganglionic blocking agents and vasoactive drugs resulting in postural hypotension
Bind and prevent absorption of niacin; should be separated by
4 to 6 h.
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 RANELATE

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

Appendix 6d:

Drug – Food Interactions

Several drugs when given orally can interact with food consumed by the patients. Table 1 shows the medications which should be taken on an empty stomach.

Table 1: Medications which should be taken on an EMPTY STOMACH

Drug

Food interactions and effect

Ampicillin

Reduced absorption

Alendronate

Decreased bioavailability

Azithromycin

Reduced absorption

Bisacodyl

Dissolves enteric coating

Didanosine

Decreased absorption

Indinavir

Reduced absorption with fat,

proteins

Isoniazid

Reduced absorption

Isosorbide dinitrate

Delayed absorption

Levothyroxine

Reduced absorption; anionic exchange resins reduce absorption

Melphalan

Reduced absorption

Methotrexate

Reduced absorption

Mycophenolate

Enhanced absorption

Omeprazole

Delayed absorption

Oxytetracycline

Reduced absorption when taken with dairy products.

Rifampin

Delayed absorption

Roxithromycin

Reduced absorption

Sulfadiazine

Formation of crystalluria on consumption with vitamin C or acidifying agents

Tacrolimus

Reduced absorption

Tetracycline

Reduced absorption, especially when taken with antacids or dairy products

Thyroid

Reduced absorption

Typhoid vaccine (oral)

Reduced absorption

Zidovudine

Enhanced absorption

Food can also impact the effectiveness of a drug due to the way it is consumed. Generally, medicine is to be taken almost at the same time the food is eaten. This is because the medicine may upset the stomach, if the stomach is empty. Certain medications are recommended to be taken with food (Table 2).

Table 2: Medications which should be taken WITH FOOD

Drug

Food interactions and effect

Acetylsalicylic Acid

Reduced side effects.

Allopurinol

Reduced side effects; reduced clearance of active metabolite with protein-poor diet

Amiodarone

Enhances both the rate and

extent of absorption.

Amoxycillin/clavulanic acid

Reduced side effects

Azathioprine

Reduced side effects

Baclofen

Reduced side effects

Bromocriptine

Reduced side effects

Carbamazepine

Increased absorption

Cefuroxime

Increased absorption

Chloroquine

Reduced side effects

Clofazimine

Increased drug absorption

Conjugated estrogens

Reduced side effects

Diclofenac

Reduced peak concentration but not extent of absorption; reduced side effects

Doxycycline

Reduced side effects; reduced absorption with milk

Ethinyl estradiol

Reduced side effects

Ferrous salts

Take between meals, if gastrointestinal upset occurs take with food

Griseofulvin

Increased rate or extent of absorption with fats; reduced side effects

Hydroxychloroquine

Reduced bowel side effects;

masks the bitter taste of drug

Hydrocortisone

Slows rate of absorption; reduced peak levels; reduced side effects

Ibuprofen

Reduced side effects

Iron preparations

See iron salts

Levocetirizine

May be taken with or without food

Lithium

Reduced side effects

Mebendazole

Increased absorption

Methadone

Reduced side effects

Methylprednisolone

Reduced side effects

Metronidazole

Reduced side effects

Mexiletine

Reduced side effects; slows rate of absorption; reduces rate of caffeine clearance

Morphine

Increased absorption

Nelfinavir

Greatly increases absorption

and AUC

Niacin

Reduced absorption; decreases side effects

Nitrofurantoin

Increased absorption

Pioglitazone

Food slightly delays absorption rate but extent of absorption is not affected

Potassium salts

Reduced side effects

Prednisolone

Reduced side effects

Prednisone

Reduced stomach irritation

Procainamide

Reduced side effects; increased absorption with fat

Propranolol

Slows rate but increases extent of absorption

Quinine

Reduced side effects

Ritonavir

Increased absorption

Salsalate

Reduced stomach irritation

Saquinavir

Increased absorption

Appendix 6d: Drug – Food Interactions

Sodium chloride

Reduced side effects

Spironolactone

Increased absorption; reduced side effects

Sulfasalazine

Reduced side effects

Sodium valproate

Reduced side effects

Table 3: Selected herbal or food products resulting in adverse effects

Herb/Food

Drug

Adverse Effects/Reported Drug Interactions/ Remark

Licorice

Digoxin

Spironolactone

Elevates serum digoxin levels 4-fold, arrhythmias Hypokalemia and muscle weakness

Foods high in vitamin K (broccoli, sprouts, turnip greens, spinach, cauliflower, legumes, mayonnaise, soybean oils and fish

Anticoagulants

(warfarin)

Such foods may reduce the effectiveness of anticoagulants, increasing the risk of clotting. Intake of such foods should be limited, and the amount consumed daily should remain constant.

Foods high in sodium (like licorice, processed meats, canned foods)

Amlodipine

Such foods decrease the effectiveness of the drug

Calcium or foods containing calcium (milk and other dairy products)

Tetracycline

These foods can reduce the absorption of tetracycline, which should be taken 1 h before or 2 h after eating

Foods high in tyramine, (includes cheese, yoghurt, sour cream, cured meats, liver, dried fish, bananas, yeast extracts, raisins, soya sauce, red wine, certain beers)

MAO - inhibitors (such as phenelzine and tranylcypromine)

Severe headache and a potentially fatal increase in BP (hypertensive

crisis) can occur if people taking MAO - inhibitors consume these foods. These foods must be avoided.