Appendix 1: Interactions

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1 Appendix 1: Interactions Two or more drugs given at the same time may interact with each other. The interaction may be potentiation or antagonism of one drug by another, or occasionally some other. Drug interactions may be pharmacodynamic or pharmacokinetic. Pharmacodynamic interactions occur between drugs which have similar or antagonistic pharmacological s or adverse s. They are usually predictable from a knowledge of the pharmacology of the interacting drugs and an interaction occurring with one drug is likely to occur with a related drug. Pharmacodynamic interactions may be due to competition at receptor sites drugs acting on the same physiological system Pharmacodynamic interactions occur to some extent in most patients who receive the interacting drugs. Pharmacokinetic interactions occur when one drug increases or reduces the amount of another drug available to produce its pharmacological action. They are not easily predicted and an interaction occurring with one drug cannot be assumed to occur with a related drug unless their pharmacokinetic properties are similar. Pharmacokinetic interactions may be due to interference with absorption changes in protein binding modification of drug metabolism interference with renal excretion Many pharmacokinetic interactions affect only a small proportion of patients taking the combination of drugs. Many drug interactions do not have serious consequences and many which are potentially harmful occur only in a small proportion of patients. A known interaction will not necessarily occur to the same extent in all patients. Drugs with a small therapeutic ratio (such as phenytoin) and drugs which require careful dose control (such as anticoagulants, antihypertensives or antidiabetics) are most often involved. Patients at increased risk from drug interactions include the elderly and those with impaired renal or liver function. In the following table the symbol * indicates a potentially hazardous interaction and the combined administration of the drugs involved should be avoided, or only taken with caution and appropriate monitoring. Interactions with no symbol do not usually have serious consequences. Acetazolamide Acetylsalicylic acid Reduced excretion of

2 acetazolamide (risk of toxicity) Acetazolamide Alcohol Enhanced hypotensive Acetazolamide Amitriptyline Increased risk of postural hypotension Acetazolamide Atenolol Enhanced hypotensive * Acetazolamide Carbamazepine Increased risk of hyponatraemia; acetazolamide increases plasmacarbamazepine Acetazolamide Chlorpromazine Enhanced hypotensive Acetazolamide Cisplatin Increased risk of nephrotoxicity and ototoxicity Acetazolamide Clomipramine Increased risk of postural hypotension Acetazolamide Clonazepam Enhanced hypotensive Acetazolamide Contraceptives, Oral Antagonism of diuretic Acetazolamide Dexamethasone Increased risk of hypokalaemia; antagonism of diuretic Acetazolamide Diazepam Enhanced hypotensive * Acetazolamide Digoxin Cardiac toxicity of digoxin increased if hypokalaemia occurs Acetazolamide Enalapril Enhanced hypotensive (can be extreme) Acetazolamide Ether, Anaesthetic Enhanced hypotensive Acetazolamide Fluphenazine Enhanced hypotensive Acetazolamide Furosemide Increased risk of hypokalaemia Acetazolamide Glyceryl trinitrate Enhanced hypotensive

3 Acetazolamide Halothane Enhanced hypotensive Acetazolamide Hydralazine Enhanced hypotensive Acetazolamide Hydrochlorothiazide Increased risk of hypokalaemia Acetazolamide Hydrocortisone Increased risk of hypokalaemia; antagonism of diuretic Acetazolamide Ibuprofen Risk of nephrotoxicity of ibuprofen increased; antagonism of diuretic Acetazolamide Isosorbide dinitrate Enhanced hypotensive Acetazolamide Ketamine Enhanced hypotensive Acetazolamide Levodopa Enhanced hypotensive * Acetazolamide Lidocaine Action of lidocaine antagonised by hypokalaemia * Acetazolamide Lithium Excretion of lithium increased Acetazolamide Methyldopa Enhanced hypotensive Acetazolamide Nifedipine Enhanced hypotensive Acetazolamide Nitrous oxide Enhanced hypotensive Acetazolamide Phenytoin Increased risk of osteomalacia Acetazolamide Prednisolone Increased risk of hypokalaemia; antagonism of diuretic Acetazolamide Propranolol Enhanced hypotensive * Acetazolamide Quinidine Cardiac toxicity of quinidine increased if hypokalaemia occurs; acetazolamide reduces

4 excretion of quinidine (occasionally increased plasma ) Acetazolamide Salbutamol Increased risk of hypokalaemia with high doses of salbutamol Acetazolamide Sodium nitroprusside Enhanced hypotensive Acetazolamide Theophylline Increased risk of hypokalaemia Acetazolamide Thiopental Enhanced hypotensive Acetazolamide Timolol Enhanced hypotensive Acetazolamide Verapamil Enhanced hypotensive Acetylsalicylic acid Acetazolamide Reduced excretion of acetazolamide (risk of toxicity) Acetylsalicylic acid Antacids (Aluminium hydroxide; Magnesium hydroxide) Excretion of acetylsalicylic acid increased in alkaline urine Acetylsalicylic acid Dexamethasone Increased risk of gastrointestinal bleeding and ulceration; dexamethasone reduces plasmasalicylate Acetylsalicylic acid Enalapril Antagonism of hypotensive ; increased risk of renal impairment * Acetylsalicylic acid Heparin Enhanced anticoagulant Acetylsalicylic acid Hydrocortisone Increased risk of gastrointestinal bleeding and ulceration; hydrocortisone reduces plasmasalicylate

5 * Acetylsalicylic acid Ibuprofen Avoid concurrent administration (increased adverse s, including gastrointestinal damage); antiplatelet of acetylsalicyclic acid possibly reduced * Acetylsalicylic acid Methotrexate Reduced excretion of methotrexate (increased toxicity) Acetylsalicylic acid Metoclopramide Enhanced of acetylsalicylic acid (increased rate of absorption) Acetylsalicylic acid Phenytoin Enhancement of of phenytoin Acetylsalicylic acid Prednisolone Increased risk of gastrointestinal bleeding and ulceration; prednisolone reduces plasma-salicylate Acetylsalicylic acid Spironolactone Antagonism of diuretic Acetylsalicylic acid Valproic acid Enhancement of of valproic acid * Acetylsalicylic acid Warfarin Increased risk of bleeding due to antiplatelet Albendazole Dexamethasone Plasma-albendazole possibly increased Albendazole Praziquantel Increased plasma of active metabolite of albendazole Alcohol Acetazolamide Enhanced hypotensive Alcohol Amiloride Enhanced hypotensive * Alcohol Amitriptyline Enhanced sedative

6 Alcohol Atenolol Enhanced hypotensive Alcohol Carbamazepine Possibly enhanced CNS adverse s of carbamazepine Alcohol Chlorphenamine Enhanced sedative Alcohol Chlorpromazine Enhanced sedative * Alcohol Clomipramine Enhanced sedative Alcohol Clonazepam Enhanced sedative Alcohol Codeine Enhanced sedative and hypotensive Alcohol Diazepam Enhanced sedative Alcohol Enalapril Enhanced hypotensive Alcohol Fluphenazine Enhanced sedative Alcohol Furosemide Enhanced hypotensive Alcohol Glibenclamide Enhanced hypoglycaemic Alcohol Glyceryl trinitrate Enhanced hypotensive Alcohol Haloperidol Enhanced sedative Alcohol Hydralazine Enhanced hypotensive Alcohol Hydrochlorothiazide Enhanced hypotensive Alcohol Insulins Enhanced hypoglycaemic Alcohol Isosorbide dinitrate Enhanced hypotensive Alcohol Levamisole Disulfiram-like reaction Alcohol Metformin Enhanced hypoglycaemic ; increased risk of lactic

7 acidosis Alcohol Methyldopa Enhanced hypotensive Alcohol Metronidazole Disulfiram-like reaction Alcohol Morphine Enhanced sedative and hypotensive Alcohol Nifedipine Enhanced hypotensive Alcohol Paracetamol Increased risk of liver damage with regular large amounts of alcohol Alcohol Phenobarbital Enhanced sedative Alcohol Phenytoin Plasma-phenytoin reduced with regular large amounts of alcohol Alcohol Procarbazine Disulfiram-like reaction Alcohol Promethazine Enhanced sedative Alcohol Propranolol Enhanced hypotensive Alcohol Sodium nitroprusside Enhanced hypotensive Alcohol Spironolactone Enhanced hypotensive Alcohol Timolol Enhanced hypotensive Alcohol Verapamil Enhanced hypotensive ; plasma of alcohol possibly increased by verapamil * Alcohol Warfarin Enhanced anticoagulant with large amounts of alcohol; major changes in alcohol consumption may affect anticoagulant control

8 Alcuronium Carbamazepine Antagonism of muscle relaxant (recovery from neuromuscular blockade accelerated) Alcuronium Clindamycin Enhanced muscle relaxant Alcuronium Ether, Anaesthetic Effects of alcuronium enhanced * Alcuronium Gentamicin Enhanced muscle relaxant Alcuronium Halothane Effects of alcuronium enhanced Alcuronium Lithium Enhanced muscle relaxant Alcuronium Magnesium (parenteral) Enhanced muscle relaxant Alcuronium Neostigmine Antagonism of muscle relaxant Alcuronium Nifedipine Enhanced muscle relaxant Alcuronium Phenytoin Antagonism of muscle relaxant (accelerated recovery from neuromuscular blockade) * Alcuronium Procainamide Enhanced muscle relaxant Alcuronium Propranolol Enhanced muscle relaxant Alcuronium Pyridostigmine Antagonism of muscle relaxant * Alcuronium Quinidine Enhanced muscle relaxant * Alcuronium Streptomycin Enhanced muscle relaxant Alcuronium Verapamil Enhanced muscle relaxant Allopurinol Amoxicillin Increased risk of rash Allopurinol Ampicillin Increased risk of rash * Allopurinol Azathioprine Effects of azathioprine enhanced with increased toxicity, reduce dose when

9 given with allopurinol Allopurinol Ciclosporin Plasma-ciclosporin possibly increased (risk of nephrotoxicity) * Allopurinol Mercaptopurine Effects of mercaptopurine enhanced with increased toxicity, reduce dose when given with allopurinol Allopurinol Theophylline Plasma-theophylline possibly increased Allopurinol Warfarin Anticoagulant possibly enhanced Aluminium hydroxide. see Antacids Amiloride Alcohol Enhanced hypotensive Amiloride Amitriptyline Increased risk of postural hypotension * Amiloride Artemether + Lumefantrine Increased risk of ventricular arrhythmias if electrolyte disturbance occurs Amiloride Atenolol Enhanced hypotensive Amiloride Carbamazepine Increased risk of hyponatraemia Amiloride Chlorpromazine Enhanced hypotensive * Amiloride Ciclosporin Increased risk of hyperkalaemia Amiloride Cisplatin Increased risk of nephrotoxicity and ototoxicity Amiloride Clomipramine Increased risk of postural hypotension Amiloride Clonazepam Enhanced hypotensive Amiloride Contraceptives, Oral Antagonism of diuretic Amiloride Dexamethasone Antagonism of

10 diuretic Amiloride Diazepam Enhanced hypotensive * Amiloride Enalapril Enhanced hypotensive (can be extreme); risk of severe hyperkalaemia Amiloride Ether, Anaesthetic Enhanced hypotensive Amiloride Fluphenazine Enhanced hypotensive Amiloride Glyceryl trinitrate Enhanced hypotensive Amiloride Halothane Enhanced hypotensive Amiloride Hydralazine Enhanced hypotensive Amiloride Hydrocortisone Antagonism of diuretic Amiloride Ibuprofen Risk of nephrotoxicity of ibuprofen increased; antagonism of diuretic ; possibly increased risk of hyperkalaemia Amiloride Isosorbide dinitrate Enhanced hypotensive Amiloride Ketamine Enhanced hypotensive Amiloride Levodopa Enhanced hypotensive * Amiloride Lithium Reduced lithium excretion (increased plasma-lithium and risk of toxicity) Amiloride Methyldopa Enhanced hypotensive Amiloride Nifedipine Enhanced hypotensive Amiloride Nitrous oxide Enhanced hypotensive * Amiloride Potassium salts Risk of hyperkalaemia Amiloride Prednisolone Antagonism of

11 diuretic Amiloride Propranolol Enhanced hypotensive Amiloride Sodium nitroprusside Enhanced hypotensive Amiloride Thiopental Enhanced hypotensive Amiloride Timolol Enhanced hypotensive Amiloride Verapamil Enhanced hypotensive Aminophylline. see Theophylline Amitriptyline Acetazolamide Increased risk of postural hypotension * Amitriptyline Alcohol Enhanced sedative Amitriptyline Amiloride Increased risk of postural hypotension * Amitriptyline Artemether + Lumefantrine Increased risk of ventricular arrhythmias (manufacturer of artemether with lumefantrine advises avoid concomitant use) Amitriptyline Atropine Increased antimuscarinic adverse s Amitriptyline Biperiden Increased antimuscarinic adverse s * Amitriptyline Carbamazepine Antagonism (convulsive threshold lowered); possibly accelerated amitriptyline (reduced plasma ; reduced antidepressant ) Amitriptyline Chlorphenamine Increased antimuscarinic and sedative s * Amitriptyline Chlorpromazine Increased

12 antimuscarinic adverse s; increased plasma-amitriptyline ; possibly increased risk of ventricular arrhythmias Amitriptyline Clonazepam Enhanced sedative Amitriptyline Codeine Possibly increased sedation Amitriptyline Contraceptives, Oral Antagonism of antidepressant but adverse s possibly increased due to increased plasma of amitriptyline Amitriptyline Diazepam Enhanced sedative * Amitriptyline Epinephrine Hypertension and arrhythmias (but local anaesthetics with epinephrine appear to be safe) Amitriptyline Ether, Anaesthetic Increased risk of arrhythmias and hypotension * Amitriptyline Ethosuximide Antagonism (convulsive threshold lowered) * Amitriptyline Fluphenazine Increased antimuscarinic adverse s; increased plasma-amitriptyline ; possibly increased risk of ventricular arrhythmias Amitriptyline Furosemide Increased risk of postural hypotension Amitriptyline Glyceryl trinitrate Enhanced hypotensive ; reduced of sublingual glyceryl trinitrate (owing to dry mouth)

13 * Amitriptyline Haloperidol Increased plasmaamitriptyline ; possibly increased risk of ventricular arrhythmias Amitriptyline Halothane Increased risk of arrhythmias and hypotension Amitriptyline Hydralazine Enhanced hypotensive Amitriptyline Hydrochlorothiazide Increased risk of postural hypotension Amitriptyline Isosorbide dinitrate Enhanced hypotensive ; reduced of sublingual isosorbide dinitrate (owing to dry mouth) Amitriptyline Ketamine Increased risk of arrhythmias and hypotension Amitriptyline Methyldopa Enhanced hypotensive Amitriptyline Morphine Possibly increased sedation Amitriptyline Nitrous oxide Increased risk of arrhythmias and hypotension * Amitriptyline Phenobarbital Antagonism of anticonvulsant (convulsive threshold lowered); metabolism of amitriptyline possibly accelerated (reduced plasma ) * Amitriptyline Phenytoin Antagonism (convulsive threshold lowered); possibly reduced plasmaamitriptyline * Amitriptyline Procainamide Increased risk of ventricular arrhythmias Amitriptyline Promethazine Increased

14 antimuscarinic and sedative s * Amitriptyline Quinidine Increased risk of ventricular arrhythmias Amitriptyline Rifampicin Plasma of amitriptyline possibly reduced (reduced antidepressant ) * Amitriptyline Ritonavir Plasma possibly increased by ritonavir Amitriptyline Sodium nitroprusside Enhanced hypotensive Amitriptyline Spironolactone Increased risk of postural hypotension Amitriptyline Thiopental Increased risk of arrhythmias and hypotension * Amitriptyline Valproic acid Antagonism (convulsive threshold lowered) Amitriptyline Verapamil Possibly increased plasma of amitriptyline Amodiaquine Chlorpromazine Plasma of chlorpromazine increased (consider reducing chlorpromazine dose) Amoxicillin Allopurinol Increased risk of rash Amoxicillin Contraceptives, Oral Possibility of reduced contraceptive of estrogen-containing preparations Amoxicillin Methotrexate Reduced excretion of methotrexate (increased risk of toxicity) Amoxicillin Warfarin Studies have failed to demonstrate an interaction, but common experience in anticoagulant clinics is

15 Amoxicillin + Clavulanic acid Amphotericin B. see Amoxicillin that INR can be altered by a course of amoxicillin NOTE. Close monitoring required with concomitant administration of nephrotoxic drugs or cytotoxics * Amphotericin B Ciclosporin Increased risk of nephrotoxicity * Amphotericin B Dexamethasone Increased risk of hypokalaemia (avoid concomitant use unless dexamethasone needed to control reactions) * Amphotericin B Digoxin Increased digoxin toxicity if hypokalaemia occurs Amphotericin B Fluconazole Possible antagonism of of amphotericin B Amphotericin B Flucytosine Renal excretion of flucytosine decreased and cellular uptake increased (flucytosine toxicity possibly increased) Amphotericin B Furosemide Increased risk of hypokalaemia Amphotericin B Gentamicin Increased risk of nephrotoxicity Amphotericin B Hydrochlorothiazide Increased risk of hypokalaemia * Amphotericin B Hydrocortisone Increased risk of hypokalaemia (avoid concomitant use unless hydrocortisone needed to control reactions) * Amphotericin B Prednisolone Increased risk of hypokalaemia (avoid concomitant use unless prednisolone needed to control reactions)

16 Amphotericin B Streptomycin Increased risk of nephrotoxicity Ampicillin Allopurinol Increased risk of rash Ampicillin Contraceptives, Oral Possibility of reduced contraceptive of estrogen-containing preparations Ampicillin Methotrexate Reduced excretion of methotrexate (increased risk of toxicity) Ampicillin 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) Antacids (Aluminium hydroxide; Magnesium hydroxide) Antacids (Aluminium hydroxide; Magnesium hydroxide) Antacids (Aluminium hydroxide; Magnesium hydroxide) Antacids (Aluminium hydroxide; Magnesium hydroxide) Antacids (Aluminium hydroxide; Magnesium hydroxide) Antacids (Aluminium hydroxide; Magnesium hydroxide) Antacids (Aluminium hydroxide; Magnesium hydroxide) NOTE. Antacids should preferably not be taken at the same time as other drugs since they may impair absorption Acetylsalicylic acid Azithromycin Chloroquine Chlorpromazine Ciprofloxacin Digoxin Doxycycline Excretion of acetylsalicylic acid increased in alkaline urine Reduced absorption of azithromycin Reduced absorption of chloroquine Reduced absorption of chlorpromazine Reduced absorption of ciprofloxacin Possibly reduced absorption of digoxin Reduced absorption of doxycycline Antacids (Aluminium Enalapril Absorption of

17 hydroxide; Magnesium hydroxide) Antacids (Aluminium hydroxide; Magnesium hydroxide) Antacids (Aluminium hydroxide; Magnesium hydroxide) Antacids (Aluminium hydroxide; Magnesium hydroxide) Antacids (Aluminium hydroxide; Magnesium hydroxide) Antacids (Aluminium hydroxide; Magnesium hydroxide) Antacids (Aluminium hydroxide; Magnesium hydroxide) * Artemether + Lumefantrine * Artemether + Lumefantrine * Artemether + Lumefantrine * Artemether + Lumefantrine Isoniazid Ofloxacin Penicillamine Phenytoin Quinidine Rifampicin Amiloride Amitriptyline Azithromycin Chloroquine enalapril reduced Reduced absorption of isoniazid Reduced absorption of ofloxacin Reduced absorption of penicillamine Reduced absorption of phenytoin Reduced quinidine excretion in alkaline urine (plasmaquinidine occasionally increased) Reduced absorption of rifampicin Increased risk of ventricular arrhythmias if electrolyte disturbance occurs Increased risk of ventricular arrhythmias (manufacturer of artemether with lumefantrine advises avoid concomitant use) Avoid concomitant use Increased risk of ventricular arrhythmias (manufacturer of artemether with lumefantrine advises avoid concomitant

18 * Artemether + Lumefantrine * Artemether + Lumefantrine * Artemether + Lumefantrine * Artemether + Lumefantrine * Artemether + Lumefantrine * Artemether + Lumefantrine * Artemether + Lumefantrine * Artemether + Lumefantrine Chlorpromazine Ciprofloxacin Clomipramine Erythromycin Fluconazole Fluphenazine Furosemide Grapefruit Juice use) Increased risk of ventricular arrhythmias (manufacturer of artemether with lumefantrine advises avoid concomitant use) Manufacturer of artemether with lumefantrine advises avoid concomitant use Increased risk of ventricular arrhythmias (manufacturer of artemether with lumefantrine advises avoid concomitant use) Manufacturer of artemether with lumefantrine advises avoid concomitant use Manufacturer of artemether with lumefantrine advises avoid concomitant use Increased risk of ventricular arrhythmias (manufacturer of artemether with lumefantrine advises avoid concomitant use) Increased risk of ventricular arrhythmias if electrolyte disturbance occurs Metabolism of artemether and lumefantrine may be inhibited (avoid concomitant use)

19 * Artemether + Lumefantrine * Artemether + Lumefantrine * Artemether + Lumefantrine * Artemether + Lumefantrine * Artemether + Lumefantrine * Artemether + Lumefantrine * Artemether + Lumefantrine * Artemether + Lumefantrine Hydrochlorothiazide Mefloquine Nalidixic acid Ofloxacin Procainamide Pyrimethamine Quinidine Quinine Increased risk of ventricular arrhythmias if electrolyte disturbance occurs Increased risk of ventricular arrhythmias (manufacturer of artemether with lumefantrine advises avoid concomitant use) Manufacturer of artemether with lumefantrine advises avoid concomitant use Manufacturer of artemether with lumefantrine advises avoid concomitant use Increased risk of ventricular arrhythmias (manufacturer of artemether with lumefantrine advises avoid concomitant use) Manufacturer of artemether with lumefantrine advises avoid concomitant use Increased risk of ventricular arrhythmias (manufacturer of artemether with lumefantrine advises avoid concomitant use) Increased risk of ventricular arrhythmias (manufacturer of artemether with lumefantrine advises

20 * Artemether + Lumefantrine Artemether + Lumefantrine Spironolactone Sulfadoxine + Pyrimethamine avoid concomitant use) Increased risk of ventricular arrhythmias if electrolyte disturbance occurs Manufacturer of artemether with lumefantrine advises avoid concomitant use Asparaginase Vaccine, Live Avoid use of live vaccines with asparaginase (impairment of immune response) Atenolol Acetazolamide Enhanced hypotensive Atenolol Alcohol Enhanced hypotensive Atenolol Amiloride Enhanced hypotensive Atenolol Chlorpromazine Enhanced hypotensive Atenolol Clonazepam Enhanced hypotensive Atenolol Contraceptives, Oral Antagonism of hypotensive Atenolol Dexamethasone Antagonism of hypotensive Atenolol Diazepam Enhanced hypotensive Atenolol Digoxin Increased AV block and bradycardia Atenolol Enalapril Enhanced hypotensive * Atenolol Epinephrine Severe hypertension Atenolol Ergotamine Increased peripheral vasoconstriction Atenolol Ether, Anaesthetic Enhanced hypotensive Atenolol Fluphenazine Enhanced hypotensive Atenolol Furosemide Enhanced hypotensive

21 Atenolol Glibenclamide Masking of warning signs of hypoglycaemia such as tremor Atenolol Glyceryl trinitrate Enhanced hypotensive Atenolol Halothane Enhanced hypotensive Atenolol Hydralazine Enhanced hypotensive Atenolol Hydrochlorothiazide Enhanced hypotensive Atenolol Hydrocortisone Antagonism of hypotensive Atenolol Ibuprofen Antagonism of hypotensive Atenolol Insulins Enhanced hypoglycaemic ; masking of warning signs of hypoglycaemia such as tremor Atenolol Isosorbide dinitrate Enhanced hypotensive Atenolol Ketamine Enhanced hypotensive Atenolol Levodopa Enhanced hypotensive * Atenolol Lidocaine Increased risk of myocardial depression Atenolol Mefloquine Increased risk of bradycardia Atenolol Metformin Masking of warning signs of hypoglycaemia such as tremor Atenolol Methyldopa Enhanced hypotensive * Atenolol Nifedipine Severe hypotension and heart failure occasionally Atenolol Nitrous oxide Enhanced hypotensive

22 Atenolol Prednisolone Antagonism of hypotensive * Atenolol Procainamide Increased risk of myocardial depression * Atenolol Quinidine Increased risk of myocardial depression Atenolol Sodium nitroprusside Enhanced hypotensive Atenolol Spironolactone Enhanced hypotensive Atenolol Thiopental Enhanced hypotensive * Atenolol Verapamil Asystole, severe hypotension and heart failure Atropine Note. Many drugs have antimuscarinic s; concomitant use of 2 or more such drugs can increase adverse s such as dry mouth, urine retention, and constipation, and can also lead to confusion in the elderly Atropine Amitriptyline Increased antimuscarinic adverse s Atropine Chlorphenamine Increased antimuscarinic adverse s Atropine Chlorpromazine Increased antimuscarinic adverse s of chlorpromazine (but reduced plasma ) Atropine Clomipramine Increased antimuscarinic adverse s Atropine Fluphenazine Increased antimuscarinic adverse s of fluphenazine (but reduced plasma ) Atropine Glyceryl trinitrate Possibly reduced of sublingual nitrates (failure to dissolve under the tongue owing to dry mouth)

23 Atropine Isosorbide dinitrate Possibly reduced of sublingual nitrates (failure to dissolve under the tongue owing to dry mouth) Atropine Levodopa Absorption of levodopa possibly reduced Atropine Metoclopramide Antagonism of on gastrointestinal activity Atropine Neostigmine Antagonism of Atropine Promethazine Increased antimuscarinic adverse s Atropine Pyridostigmine Antagonism of * Azathioprine Allopurinol Effects of azathioprine enhanced with increased toxicity, reduce dose when given with allopurinol Azathioprine Phenytoin Reduced absorption of phenytoin * Azathioprine Rifampicin Manufacturer reports interaction (transplants possibly rejected) * Azathioprine Sulfamethoxazole + Trimethoprim Increased risk of haematological toxicity Azathioprine Sulfasalazine Possibly increased risk of leukopenia * Azathioprine Trimethoprim Increased risk of haematological toxicity * Azathioprine Vaccine, Live Avoid use of live vaccines with azathioprine (impairment of immune response) * Azathioprine Warfarin Anticoagulant possibly reduced Azithromycin Antacids Reduced absorption of azithromycin * Azithromycin Artemether with lumefantrine Avoid concomitant

24 * Azithromycin Ciclosporin Plasma of ciclosporin possibly increased use Azithromycin Digoxin Effect of digoxin possibly enhanced * Azithromycin Ergotamine Increased risk of ergotism avoid concomitant use Azithromycin Ritonavir Plasma of azithromycin possibly increased * Azithromycin Warfarin Possibly enhanced anticoagulant of warfarin Benzathine benzylpenicillin. see Benzylpenicillin Benzylpenicillin Methotrexate Reduced excretion of methotrexate (increased risk of toxicity) BCG vaccine Biperiden. see Vaccine, live Note. Many drugs have antimuscarinic s; concomitant use of 2 or more such drugs can increase adverse s such as dry mouth, urine retention, and constipation, and can also lead to confusion in the elderly Biperiden Amitriptyline Increased antimuscarinic adverse s Biperiden Chlorphenamine Increased antimuscarinic adverse s Biperiden Chlorpromazine Increased antimuscarinic adverse s of chlorpromazine (but reduced plasma ) Biperiden Clomipramine Increased antimuscarinic adverse s Biperiden Fluphenazine Increased antimuscarinic adverse s of fluphenazine (but reduced plasma

25 ) Biperiden Glyceryl trinitrate Possibly reduced of sublingual nitrates (failure to dissolve under the tongue owing to dry mouth) Biperiden Isosorbide dinitrate Possibly reduced of sublingual nitrates (failure to dissolve under the tongue owing to dry mouth) Biperiden Levodopa Absorption of levodopa possibly reduced Biperiden Metoclopramide Antagonism of on gastrointestinal activity Biperiden Neostigmine Antagonism of Biperiden Promethazine Increased antimuscarinic adverse s Biperiden Pyridostigmine Antagonism of * Bleomycin Oxygen Increased risk of pulmonary toxicity Bleomycin Vaccine, Live Avoid use of live vaccines with bleomycin (impairment of immune response) * Bleomycin Vinblastine Increased risk of cardiovascular toxicity Bupivacaine Lidocaine Increased myocardial depression Bupivacaine Procainamide Increased myocardial depression * Bupivacaine Propranolol Increased risk of bupivacaine toxicity Bupivacaine Quinidine Increased myocardial depression Calcium folinate Calcium gluconate. see Folic acid and Folinic acid. see Calcium salts Calcium salts Digoxin Large intravenous

26 doses of calcium can precipitate arrhythmias Calcium salts Hydrochlorothiazide Increased risk of hypercalcaemia * Carbamazepine Acetazolamide Increased risk of hyponatraemia; acetazolamide increases plasmacarbamazepine Carbamazepine Alcohol Possibly enhanced CNS adverse s of carbamazepine Carbamazepine Alcuronium Antagonism of muscle relaxant (recovery from neuromuscular blockade accelerated) Carbamazepine Amiloride Increased risk of hyponatraemia * Carbamazepine Amitriptyline Antagonism (convulsive threshold lowered); possibly accelerated amitriptyline (reduced plasma ; reduced antidepressant ) * Carbamazepine Chloroquine Convulsive threshold occasionally lowered * Carbamazepine Chlorpromazine Antagonism of anticonvulsant (convulsive threshold lowered) * Carbamazepine Ciclosporin Accelerated metabolism (reduced plasma-ciclosporin ) * Carbamazepine Clomipramine Antagonism (convulsive threshold lowered); possibly accelerated clomipramine

27 (reduced plasma ; reduced antidepressant ) * Carbamazepine Clonazepam May be enhanced toxicity without corresponding increase in antiepileptic ; plasma of clonazepam often lowered * Carbamazepine Contraceptives, Oral Accelerated metabolism (reduced contraceptive ) * Carbamazepine Dexamethasone Accelerated dexamethasone (reduced ) Carbamazepine Doxycycline Accelerated doxycycline metabolism (reduced ) Carbamazepine Ergocalciferol Ergocalciferol requirements possibly increased * Carbamazepine Erythromycin Increased plasmacarbamazepine * Carbamazepine Ethosuximide May be enhanced toxicity without corresponding increase in antiepileptic ; plasma of ethosuximide sometimes lowered * Carbamazepine Fluphenazine Antagonism of anticonvulsant (convulsive threshold lowered) Carbamazepine Furosemide Increased risk of hyponatraemia * Carbamazepine Haloperidol Antagonism of anticonvulsant (convulsive threshold lowered); metabolism

28 of haloperidol accelerated (reduced plasma ) Carbamazepine Hydrochlorothiazide Increased risk of hyponatraemia * Carbamazepine Hydrocortisone Accelerated hydrocortisone (reduced ) Carbamazepine Indinavir Possibly reduced plasma-indinavir * Carbamazepine Isoniazid Increased plasmacarbamazepine (also isoniazid hepatotoxicity possibly increased) * Carbamazepine Levonorgestrel Accelerated levonorgestrel (reduced contraceptive ) Carbamazepine Levothyroxine Accelerated levothyroxine (may increase levothyroxine requirements in hypothyroidism) Carbamazepine Lithium Neurotoxicity may occur without increased plasmalithium * Carbamazepine Lopinavir Possibly reduced plasma-lopinavir Carbamazepine Mebendazole Reduced plasmamebendazole (possibly increase mebendazole dose for tissue infection) * Carbamazepine Medroxyprogesterone Accelerated medroxyprogesterone (does not apply to

29 injectable medroxyprogesterone acetate for contraception) * Carbamazepine Mefloquine Antagonism of anticonvulsant Carbamazepine Nelfinavir Possibly reduced plasma-nelfinavir Carbamazepine Nifedipine Probably reduced of nifedipine * Carbamazepine Norethisterone Accelerated norethisterone (reduced contraceptive ) does not apply to injectable norethisterone enantate for contraception * Carbamazepine Phenobarbital May be enhanced toxicity without corresponding increase in antiepileptic ; plasma of carbamazepine often lowered * Carbamazepine Phenytoin May be enhanced toxicity without corresponding increase in antiepileptic ; plasma of phenytoin often lowered but may be raised; plasma of carbamazepine often lowered Carbamazepine Praziquantel Plasma-praziquantel reduced * Carbamazepine Prednisolone Accelerated prednisolone (reduced ) * Carbamazepine Ritonavir Plasma

30 possibly increased by ritonavir Carbamazepine Saquinavir Possibly reduced plasma-saquinavir Carbamazepine Spironolactone Increased risk of hyponatraemia Carbamazepine Theophylline Accelerated theophylline (reduced ) * Carbamazepine Valproic acid May be enhanced toxicity without corresponding increase in antiepileptic ; plasma of valproic acid often lowered; plasma of active metabolite of carbamazepine often raised Carbamazepine Vecuronium Antagonism of muscle relaxant (recovery from neuromuscular blockade accelerated) * Carbamazepine Verapamil Enhanced of carbamazepine * Carbamazepine Warfarin Accelerated warfarin (reduced anticoagulant ) Ceftazidime Contraceptives, Oral Possibility of reduced contraceptive of estrogen-containing preparations Ceftazidime Furosemide Nephrotoxicity of ceftazidime possibly increased * Ceftazidime Warfarin Possibly enhanced anticoagulant Ceftriaxone Contraceptives, Oral Possibility of reduced contraceptive of estrogen-containing

31 preparations Ceftriaxone Furosemide Nephrotoxicity of ceftriaxone possibly increased * Ceftriaxone Warfarin Possibly enhanced anticoagulant Chlorambucil Vaccine, Live Avoid use of live vaccines with chlorambucil (impairment of immune response) * Chloramphenicol Ciclosporin Plasma of ciclosporin possibly increased * Chloramphenicol Glibenclamide Enhanced of glibenclamide * Chloramphenicol Phenobarbital Metabolism of chloramphenicol accelerated (reduced chloramphenicol ) * Chloramphenicol Phenytoin Plasma-phenytoin increased (risk of toxicity) Chloramphenicol Rifampicin Accelerated chloramphenicol (reduced plasmachloramphenicol ) * Chloramphenicol Warfarin Enhanced anticoagulant Chlormethine Vaccine, Live Avoid use of live vaccines with chlormethine (impairment of immune response) Chloroquine Antacids (Aluminium hydroxide; Magnesium hydroxide) Reduced absorption of chloroquine * Chloroquine Artemether + Lumefantrine Increased risk of ventricular arrhythmias (manufacturer of artemether with lumefantrine advises

32 avoid concomitant use) * Chloroquine Carbamazepine Convulsive threshold occasionally lowered * Chloroquine Ciclosporin Increased plasmaciclosporin (increased risk of toxicity) * Chloroquine Digoxin Plasma-digoxin possibly increased * Chloroquine Ethosuximide Convulsive threshold occasionally lowered * Chloroquine Mefloquine Increased risk of convulsions Chloroquine Neostigmine Chloroquine has potential to increase symptoms of myasthenia gravis and thus diminish of neostigmine * Chloroquine Phenytoin Convulsive threshold occasionally lowered Chloroquine Praziquantel Plasma-praziquantel possibly reduced Chloroquine Pyridostigmine Chloroquine has potential to increase symptoms of myasthenia gravis and thus diminish of pyridostigmine Chloroquine Quinidine Increased risk of ventricular arrhythmias Chloroquine Quinine Increased risk of ventricular arrhythmias * Chloroquine Valproic acid Convulsive threshold occasionally lowered Chlorphenamine Alcohol Enhanced sedative Chlorphenamine Amitriptyline Increased antimuscarinic and

33 sedative s Chlorphenamine Atropine Increased antimuscarinic adverse s Chlorphenamine Biperiden Increased antimuscarinic adverse s Chlorphenamine Clomipramine Increased antimuscarinic and sedative s Chlorphenamine Clonazepam Enhanced sedative Chlorphenamine Diazepam Enhanced sedative Chlorpromazine Acetazolamide Enhanced hypotensive Chlorpromazine Alcohol Enhanced sedative Chlorpromazine Amiloride Enhanced hypotensive * Chlorpromazine Amitriptyline Increased antimuscarinic adverse s; increased plasma-amitriptyline ; possibly increased risk of ventricular arrhythmias Chlorpromazine Amodiaquine Plasma of chlorpromazine increased (consider reducing chlorpromazine dose) Chlorpromazine Antacids (Aluminium hydroxide; Magnesium hydroxide) Reduced absorption of chlorpromazine * Chlorpromazine Artemether + Lumefantrine Increased risk of ventricular arrhythmias (manufacturer of artemether with lumefantrine advises avoid concomitant use) Chlorpromazine Atenolol Enhanced hypotensive

34 Chlorpromazine Atropine Increased antimuscarinic adverse s of chlorpromazine (but reduced plasma ) Chlorpromazine Biperiden Increased antimuscarinic adverse s of chlorpromazine (but reduced plasma ) * Chlorpromazine Carbamazepine Antagonism of anticonvulsant (convulsive threshold lowered) * Chlorpromazine Clomipramine Increased antimuscarinic adverse s; increased plasma-clomipramine ; possibly increased risk of ventricular arrhythmias Chlorpromazine Clonazepam Enhanced sedative Chlorpromazine Codeine Enhanced sedative and hypotensive Chlorpromazine Diazepam Enhanced sedative Chlorpromazine Dopamine Antagonism of pressor action Chlorpromazine Enalapril Enhanced hypotensive Chlorpromazine Ephedrine Antagonism of pressor action Chlorpromazine Epinephrine Antagonism of pressor action * Chlorpromazine Ether, Anaesthetic Enhanced hypotensive * Chlorpromazine Ethosuximide Antagonism (convulsive threshold lowered) Chlorpromazine Furosemide Enhanced hypotensive

35 Chlorpromazine Glibenclamide Possible antagonism of hypoglycaemic Chlorpromazine Glyceryl trinitrate Enhanced hypotensive * Chlorpromazine Halothane Enhanced hypotensive Chlorpromazine Hydralazine Enhanced hypotensive Chlorpromazine Hydrochlorothiazide Enhanced hypotensive Chlorpromazine Isoprenaline Antagonism of pressor action Chlorpromazine Isosorbide dinitrate Enhanced hypotensive * Chlorpromazine Ketamine Enhanced hypotensive Chlorpromazine Levodopa Antagonism of s of levodopa Chlorpromazine Lithium Increased risk of extrapyramidal s and possibility of neurotoxicity Chlorpromazine Methyldopa Enhanced hypotensive ; increased risk of extrapyramidal s Chlorpromazine Metoclopramide Increased risk of extrapyramidal s Chlorpromazine Morphine Enhanced sedative and hypotensive Chlorpromazine Nifedipine Enhanced hypotensive * Chlorpromazine Nitrous oxide Enhanced hypotensive * Chlorpromazine Phenobarbital Antagonism of anticonvulsant (convulsive threshold lowered) * Chlorpromazine Phenytoin Antagonism of anticonvulsant (convulsive threshold lowered) * Chlorpromazine Procainamide Increased risk of

36 ventricular arrhythmias * Chlorpromazine Propranolol Concomitant administration may increase plasma of both drugs; enhanced hypotensive * Chlorpromazine Quinidine Increased risk of ventricular arrhythmias * Chlorpromazine Ritonavir Plasma possibly increased by ritonavir Chlorpromazine Sodium nitroprusside Enhanced hypotensive Chlorpromazine Spironolactone Enhanced hypotensive * Chlorpromazine Thiopental Enhanced hypotensive Chlorpromazine Timolol Enhanced hypotensive * Chlorpromazine Valproic acid Antagonism of anticonvulsant (convulsive threshold lowered) Chlorpromazine Verapamil Enhanced hypotensive Ciclosporin Allopurinol Plasma-ciclosporin possibly increased (risk of nephrotoxicity) * Ciclosporin Amiloride Increased risk of hyperkalaemia * Ciclosporin Amphotericin B Increased risk of nephrotoxicity * Ciclosporin Azithromycin Plasma of ciclosporin possibly increased * Ciclosporin Carbamazepine Accelerated metabolism (reduced plasma-ciclosporin ) * Ciclosporin Chloramphenicol Plasma of ciclosporin possibly

37 increased * Ciclosporin Chloroquine Increased plasmaciclosporin (increased risk of toxicity) * Ciclosporin Ciprofloxacin Increased risk of nephrotoxicity * Ciclosporin Colchicine Possibly increased risk of nephrotoxicity and myotoxicity (increased plasma-ciclosporin ) * Ciclosporin Contraceptives, Oral Increased plasmaciclosporin * Ciclosporin Digoxin Reduced clearance of digoxin (risk of toxicity) * Ciclosporin Doxorubicin Increased risk of neurotoxicity * Ciclosporin Doxycycline Possibly increased plasma-ciclosporin * Ciclosporin Enalapril Increased risk of hyperkalaemia * Ciclosporin Erythromycin Increased plasmaciclosporin (inhibition of metabolism) * Ciclosporin Fluconazole Metabolism of ciclosporin inhibited (increased plasma ) * Ciclosporin Gentamicin Increased risk of nephrotoxicity * Ciclosporin Grapefruit Juice Increased plasmaciclosporin (risk of toxicity) Ciclosporin Griseofulvin Plasma-ciclosporin possibly reduced * Ciclosporin Ibuprofen Increased risk of

38 nephrotoxicity * Ciclosporin Levonorgestrel Inhibition of ciclosporin metabolism (increased plasma-ciclosporin ) * Ciclosporin Medroxyprogesterone Inhibition of ciclosporin metabolism (increased plasma-ciclosporin ) * Ciclosporin Methotrexate Increased toxicity * Ciclosporin Metoclopramide Plasma-ciclosporin increased * Ciclosporin Nalidixic acid Increased risk of nephrotoxicity Ciclosporin Nelfinavir Possibly increased plasma-ciclosporin Ciclosporin Nifedipine Possibly increased plasma-nifedipine (increased risk of adverse s such as gingival hyperplasia) * Ciclosporin Norethisterone Inhibition of ciclosporin metabolism (increased plasma-ciclosporin ) * Ciclosporin Ofloxacin Increased risk of nephrotoxicity * Ciclosporin Phenobarbital Metabolism of ciclosporin accelerated (reduced ) * Ciclosporin Phenytoin Accelerated metabolism (reduced plasma-ciclosporin ) * Ciclosporin Potassium salts Increased risk of hyperkalaemia Ciclosporin Prednisolone Increased plasma of prednisolone

39 * Ciclosporin Rifampicin Accelerated metabolism (reduced plasma-ciclosporin ) * Ciclosporin Ritonavir Plasma possibly increased by ritonavir * Ciclosporin Spironolactone Increased risk of hyperkalaemia * Ciclosporin Streptomycin Increased risk of nephrotoxicity * Ciclosporin Sulfadiazine Plasma-ciclosporin possibly reduced; increased risk of nephrotoxicity * Ciclosporin Sulfadoxine + Pyrimethamine Increased risk of nephrotoxicity * Ciclosporin Sulfamethoxazole + Trimethoprim Increased risk of nephrotoxicity; plasma-ciclosporin possibly reduced by intravenous trimethoprim * Ciclosporin Trimethoprim Increased risk of nephrotoxicity; plasma-ciclosporin possibly reduced by intravenous trimethoprim * Ciclosporin Vaccine, Live Avoid use of live vaccines with ciclosporin (impairment of immune response) * Ciclosporin Vancomycin Increased risk of nephrotoxicity * Ciclosporin Verapamil Increased plasmaciclosporin Ciprofloxacin Antacids (Aluminium hydroxide; Magnesium hydroxide) Reduced absorption of ciprofloxacin * Ciprofloxacin Artemether + Lumefantrine Manufacturer of artemether with lumefantrine advises

40 avoid concomitant use * Ciprofloxacin Ciclosporin Increased risk of nephrotoxicity Ciprofloxacin Ferrous salts Absorption of ciprofloxacin reduced by oral ferrous salts Ciprofloxacin Glibenclamide Possibly enhanced of glibenclamide * Ciprofloxacin Ibuprofen Possibly increased risk of convulsions Ciprofloxacin Morphine Manufacturer of ciprofloxacin advises avoid premedication with morphine (reduced plasmaciprofloxacin ) Ciprofloxacin Phenytoin Plasma-phenytoin possibly altered by ciprofloxacin * Ciprofloxacin Theophylline Increased plasmatheophylline ; possible increased risk of convulsions * Ciprofloxacin Warfarin Enhanced anticoagulant Cisplatin Acetazolamide Increased risk of nephrotoxicity and ototoxicity Cisplatin Amiloride Increased risk of nephrotoxicity and ototoxicity Cisplatin Furosemide Increased risk of nephrotoxicity and ototoxicity * Cisplatin Gentamicin Increased risk of nephrotoxicity and possibly of ototoxicity Cisplatin Hydrochlorothiazide Increased risk of nephrotoxicity and ototoxicity Cisplatin Phenytoin Reduced absorption of

41 phenytoin Cisplatin Spironolactone Increased risk of nephrotoxicity and ototoxicity * Cisplatin Streptomycin Increased risk of nephrotoxicity and possibly of ototoxicity Cisplatin Vaccine, Live Avoid use of live vaccines with cisplatin (impairment of immune response) Cisplatin Vancomycin Increased risk of nephrotoxicity and possibly of ototoxicity Clindamycin Alcuronium Enhanced muscle relaxant Clindamycin Neostigmine Antagonism of s of neostigmine Clindamycin Pyridostigmine Antagonism of s of pyridostigmine Clindamycin Vecuronium Enhanced muscle relaxant Clomipramine Acetazolamide Increased risk of postural hypotension * Clomipramine Alcohol Enhanced sedative Clomipramine Amiloride Increased risk of postural hypotension * Clomipramine Artemether + Lumefantrine Increased risk of ventricular arrhythmias (manufacturer of artemether with lumefantrine advises avoid concomitant use) Clomipramine Atropine Increased antimuscarinic adverse s Clomipramine Biperiden Increased antimuscarinic adverse s * Clomipramine Carbamazepine Antagonism (convulsive threshold lowered); possibly

42 accelerated clomipramine (reduced plasma ; reduced antidepressant ) Clomipramine Chlorphenamine Increased antimuscarinic and sedative s * Clomipramine Chlorpromazine Increased antimuscarinic adverse s; increased plasma-clomipramine ; possibly increased risk of ventricular arrhythmias Clomipramine Clonazepam Enhanced sedative Clomipramine Codeine Possibly increased sedation Clomipramine Contraceptives, Oral Antagonism of antidepressant but adverse s possibly increased due to increased plasma of clomipramine Clomipramine Diazepam Enhanced sedative * Clomipramine Epinephrine Hypertension and arrhythmias (but local anaesthetics with epinephrine appear to be safe) Clomipramine Ether, Anaesthetic Increased risk of arrhythmias and hypotension * Clomipramine Ethosuximide Antagonism (convulsive threshold lowered) * Clomipramine Fluphenazine Increased antimuscarinic adverse s; increased plasma-clomipramine ;

43 possibly increased risk of ventricular arrhythmias Clomipramine Furosemide Increased risk of postural hypotension Clomipramine Glyceryl trinitrate Enhanced hypotensive ; reduced of sublingual glyceryl trinitrate (owing to dry mouth) * Clomipramine Haloperidol Increased plasmaclomipramine ; possibly increased risk of ventricular arrhythmias Clomipramine Halothane Increased risk of arrhythmias and hypotension Clomipramine Hydralazine Enhanced hypotensive Clomipramine Hydrochlorothiazide Increased risk of postural hypotension Clomipramine Isosorbide dinitrate Enhanced hypotensive ; reduced of sublingual isosorbide dinitrate (owing to dry mouth) Clomipramine Ketamine Increased risk of arrhythmias and hypotension Clomipramine Methyldopa Enhanced hypotensive Clomipramine Morphine Possibly increased sedation Clomipramine Nitrous oxide Increased risk of arrhythmias and hypotension * Clomipramine Phenobarbital Antagonism of anticonvulsant (convulsive threshold lowered); metabolism of clomipramine possibly accelerated (reduced plasma )

44 * Clomipramine Phenytoin Antagonism (convulsive threshold lowered); possibly reduced plasmaclomipramine * Clomipramine Procainamide Increased risk of ventricular arrhythmias Clomipramine Promethazine Increased antimuscarinic and sedative s * Clomipramine Quinidine Increased risk of ventricular arrhythmias Clomipramine Rifampicin Plasma of clomipramine possibly reduced (reduced antidepressant ) * Clomipramine Ritonavir Plasma possibly increased by ritonavir Clomipramine Sodium nitroprusside Enhanced hypotensive Clomipramine Spironolactone Increased risk of postural hypotension Clomipramine Thiopental Increased risk of arrhythmias and hypotension * Clomipramine Valproic acid Antagonism (convulsive threshold lowered) Clomipramine Verapamil Possibly increased plasma of clomipramine Clonazepam Acetazolamide Enhanced hypotensive Clonazepam Alcohol Enhanced sedative Clonazepam Amiloride Enhanced hypotensive Clonazepam Amitriptyline Enhanced sedative Clonazepam Atenolol Enhanced hypotensive

45 * Clonazepam Carbamazepine May be enhanced toxicity without corresponding increase in antiepileptic ; plasma of clonazepam often lowered Clonazepam Chlorphenamine Enhanced sedative Clonazepam Chlorpromazine Enhanced sedative Clonazepam Clomipramine Enhanced sedative Clonazepam Codeine Enhanced sedative Clonazepam Enalapril Enhanced hypotensive Clonazepam Ether, Anaesthetic Enhanced sedative Clonazepam Fluphenazine Enhanced sedative Clonazepam Furosemide Enhanced hypotensive Clonazepam Glyceryl trinitrate Enhanced hypotensive Clonazepam Haloperidol Enhanced sedative Clonazepam Halothane Enhanced sedative Clonazepam Hydralazine Enhanced hypotensive Clonazepam Hydrochlorothiazide Enhanced hypotensive Clonazepam Isosorbide dinitrate Enhanced hypotensive Clonazepam Ketamine Enhanced sedative Clonazepam Levodopa Possibly occasional antagonism of levodopa s Clonazepam Methyldopa Enhanced hypotensive

46 Clonazepam Morphine Enhanced sedative Clonazepam Nifedipine Enhanced hypotensive Clonazepam Nitrous oxide Enhanced sedative * Clonazepam Phenobarbital May be enhanced toxicity without corresponding increase in antiepileptic ; plasma of clonazepam often lowered * Clonazepam Phenytoin May be enhanced toxicity without corresponding increase in antiepileptic ; plasma of clonazepam often lowered Clonazepam Promethazine Enhanced sedative Clonazepam Propranolol Enhanced hypotensive Clonazepam Rifampicin Metabolism of clonazepam possibly accelerated (possibly reduced plasma ) * Clonazepam Ritonavir Plasma possibly increased by ritonavir Clonazepam Sodium nitroprusside Enhanced hypotensive Clonazepam Spironolactone Enhanced hypotensive Clonazepam Thiopental Enhanced sedative Clonazepam Timolol Enhanced hypotensive Clonazepam Verapamil Enhanced hypotensive Cloxacillin. see Benzylpenicillin

47 Codeine Alcohol Enhanced sedative and hypotensive Codeine Amitriptyline Possibly increased sedation Codeine Chlorpromazine Enhanced sedative and hypotensive Codeine Clomipramine Possibly increased sedation Codeine Clonazepam Enhanced sedative Codeine Diazepam Enhanced sedative Codeine Fluphenazine Enhanced sedative and hypotensive Codeine Haloperidol Enhanced sedative and hypotensive Codeine Metoclopramide Antagonism of of metoclopramide on gastrointestinal activity * Codeine Ritonavir Ritonavir possibly increases plasma of codeine * Colchicine Ciclosporin Possibly increased risk of nephrotoxicity and myotoxicity (increased plasma-ciclosporin ) Contraceptives, Oral NOTE. Interactions also apply to ethinylestradiol taken alone. In hormone replacement therapy low dose unlikely to induce interactions Contraceptives, Oral Acetazolamide Antagonism of diuretic Contraceptives, Oral Amiloride Antagonism of diuretic Contraceptives, Oral Amitriptyline Antagonism of antidepressant but adverse s possibly increased due to increased plasma of amitriptyline Contraceptives, Oral Amoxicillin Possibility of reduced contraceptive of

48 estrogen-containing preparations Contraceptives, Oral Ampicillin Possibility of reduced contraceptive of estrogen-containing preparations Contraceptives, Oral Atenolol Antagonism of hypotensive * Contraceptives, Oral Carbamazepine Accelerated metabolism (reduced contraceptive ) Contraceptives, Oral Ceftazidime Possibility of reduced contraceptive of estrogen-containing preparations Contraceptives, Oral Ceftriaxone Possibility of reduced contraceptive of estrogen-containing preparations * Contraceptives, Oral Ciclosporin Increased plasmaciclosporin Contraceptives, Oral Clomipramine Antagonism of antidepressant but adverse s possibly increased due to increased plasma of clomipramine Contraceptives, Oral Dexamethasone Oral contraceptives increase plasma of dexamethasone Contraceptives, Oral Doxycycline Possibility of reduced contraceptive of estrogen-containing preparations Contraceptives, Oral Efavirenz Efficacy of oral contraceptives possibly reduced Contraceptives, Oral Enalapril Antagonism of hypotensive Contraceptives, Oral Fluconazole Anecdotal reports of contraceptive failure Contraceptives, Oral Furosemide Antagonism of

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