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WHO Model List of Essential Drugs (EDL) with rational and evidence where available 11th edition (Nov. 1999) By Therapeutic Group 18. HORMONES, OTHER ENDOCRINE DRUGS AND CONTRACEPTIVES 18.1 Adrenal hormones and synthetic substitutes *dexamethasone tablet 500 micrograms, 4 mg; injection 4 mg dexamethasone phosphate (as disodium salt) in 1-ml ampoule Potent corticosteroid. Suppression of inflammatory and allergic disorders, shock and variety of other uses hydrocortisone powder for injection, 100 mg (as sodium succinate) in vial Corticosteroid For adrenocortical insufficiency *prednisolone tablet 1 mg, 5 mg Potent corticosteroid. Suppression of inflammatory and allergic disorders (C) tablet, 100 micrograms (acetate) For adrenocortical insufficiency Cochrane Library: No reviews but RCTs exist (C) (2) injection, 200 mg (enantate) in 1-ml ampoule Replacement therapy Cochrane Library: No reviews but RCTs exist *ethinylestradiol + *levonorgestrel tablet, 30 micrograms + 150 micrograms Oral contraceptive Cochrane Library: Several reviews on oral contraceptives *ethinylestradiol + *levonorgestrel tablet, 50 micrograms + 250 micrograms (pack of four) Emergency contraception Cochrane Library: Several reviews on oral contraceptives *ethinylestradiol + tablet, 35 micrograms + 1.0 mg EDL2 Oral contraceptive Cochrane Library: Several reviews on Complementary drug fludrocortisone 18.2 Androgens Complementary drug testosterone 18.3 Contraceptives 18.3.1 Hormonal contraceptives Section 3 Page 1 of 14 WHO Model List of Essential Drugs (EDL) with rational and evidence where available 11th edition (Nov. 1999) By Therapeutic Group *norethisterone oral contraceptives levonorgestrel tablets, 750 micrograms (pack of two) EDL11 added for emergency contraception Cochrane Library: Several reviews on oral contraceptives Complementary drugs *levonorgestrel (B) tablets, 30 micrograms EDL9 Replaces norethisterone, safer for lactating mothers Cochrane Library: Several reviews on oral contraceptives medroxyprogesterone acetate (B) (7, 8) depot injection, 150 mg/ml in 1-ml vial Provides contraception for 12 weeks. Cochrane Library: Several reviews on oral contraceptives norethisterone enantate (B) (7, 8) oily solution, 200 mg/ml in 1-ml ampoule Provides contraception for 8 weeks Cochrane Library: Several reviews on oral contraceptives Contraceptive device Cochrane Library: one review 18.3.2 Intrauterine devices copper-containing device 18.3.3 Barrier methods condoms with or without spermicide (nonoxinol) Contraceptive devices diaphragms with spermicide (nonoxinol) Contraceptive devices Cochrane Library: one review 18.4 Estrogens *ethinylestradiol tablet, 10 micrograms, 50 micrograms Hormone replacement sometimetimes used for menopausal symptoms tablets, 2.5 mg, 5 mg EDL10 Restored: recognised as more suitable prototype drug than 18.5 Insulins and other antidiabetic agents *glibenclamide Section 3 Page 2 of 14 CE6 intensive treatment reduces complications for Type 1 and type 2 WHO Model List of Essential Drugs (EDL) with rational and evidence where available 11th edition (Nov. 1999) By Therapeutic Group tolbutamide. Sulphonylurea. diabetes insulin (soluble) injection, 40 IU/ml in 10-ml vial, 100 IU/ml in 10-ml vial Replacement hormone for diabetes See glibenclamide intermediate-acting insulin injection, 40 IU/ml in 10 ml vial; 100 IU/ml in 10 ml vial (as compound insulin zinc suspension or isophane insulin) Replacement hormone for diabetes See glibenclamide metformin tablet, 500 mg (hydrochloride) EDL10 To complete the range of oral antidiabetic drugs. Different mode of action from sulphonylureas See glibenclamide tablet, 50 mg (citrate) EDL2 Female infertility due to oligomenorrhoea or secondary amenorrhoea CE6 One SR found clomiphene increases likelihood of pregnancy in women who ovulate infrequently. Little evidence that prolonged use increases risk of ovarian cancer tablet, 5 mg EDL2 Added as progesterone only contraceptive tablet, 5 mg Mild to moderate endometriosis CE6 SRs have shown that pain is reduced but no evidence that fertility was improved. For hypothyroidism Cochrane Library: No reviews but RCTs exist 18.6 Ovulation inducers *clomifene (2, 8) 18.7 Progestogens norethisterone Complementary drug medroxyprogesterone acetate (B) 18.8 Thyroid hormones and antithyroid drugs levothyroxine tablet, 50 micrograms, 100 micrograms (sodium salt) Section 3 Page 3 of 14 WHO Model List of Essential Drugs (EDL) with rational and evidence where available 11th edition (Nov. 1999) By Therapeutic Group potassium iodide tablet, 60 mg Prophylaxis and treatment of iodine deficiency and pre-operative management of hyperthyroidism *propylthiouracil tablet, 50 mg For hyperthyroidism Cochrane Library: No reviews but RCTs exist 19. IMMUNOLOGICALS 19.1 Diagnostic agents All tuberculins should comply with the WHO Requirements for Tuberculins (Revised 1985). WHO Expert Committee on Biological Standardization Thirty sixth report, WHO Technical Report Series, No. 745, 1987, Annex 1.. tuberculin, purified protein derivative (PPD) injection Intra dermal injection as diagnostic test for hypersensitivity to tubercular protein. Used prior to BCG vaccination Cochrane Library: One review 19.2 Sera and immunoglobulins All plasma fractions should comply with the WHO Requirements for the Collection, Processing and Quality Control of Blood, Blood Components and Plasma Derivatives (Revised 1992). WHO Expert Committee on Biological Standardization Forty-third report, WHO Technical Report Series, No. 840, 1994, Annex 2.. anti-D immunoglobulin (human) injection, 250 micrograms in single-dose vial To prevent rhesus negative mother from forming antibodies to fetal rhesus positive cells. Cochrane Library: No reviews or RCTs found *antitetanus immunoglobulin (human) injection, 500 IU in vial For the management of tetanus prone wounds and for established tetanus alongside other interventions. Cochrane Library: No reviews or RCTs found antivenom serum injection Range of specific sera for use following snake bite Cochrane Library: one review on preventing reactions to antivenoms diphtheria antitoxin injection, 10,000 IU, 20,000 IU in vial For active immunisation against diphtheria or when an individual has Cochrane Library: No reviews or RCTs found Section 3 Page 4 of 14 WHO Model List of Essential Drugs (EDL) with rational and evidence where available 11th edition (Nov. 1999) By Therapeutic Group come into contact with the disease or is travelling to an endemic area. immunoglobulin, human normal (2) intramuscular injection For protection against Hepatitis A, measles and to a lesser extent rubella. Cochrane Library: No reviews or RCTs found immunoglobulin, human normal (2, 8) intravenous injection Used in a variety of conditions as replacement therapy for patients who are immune deficient Cochrane Library: No reviews or RCTs found injection, 150 IU/ml Used following exposure of a unimmunised victim in or from a high risk country. Injected at the site of the bite and intramuscularly. Cochrane Library: No reviews or RCTs found BCG For immunisation against tuberculosis in those who have no natural immunity Cochrane Library: a number of reviews on immunisation diphtheria Routine childhood vaccine often combined with pertussis and tetanus hepatitis B Vaccine for health care workers and other groups at risk measles Routine childhood vaccine pertussis Routine childhood vaccine poliomyelitis Routine childhood vaccine tetanus Routine childhood vaccine or after *rabies immunoglobulin 19.3 Vaccines All vaccines should comply with the WHO Requirements for Biological Substances.. 19.3.1 For universal immunization Section 3 Page 5 of 14 CE6 Five doses probably confer life WHO Model List of Essential Drugs (EDL) with rational and evidence where available 11th edition (Nov. 1999) By Therapeutic Group injury long immunity 19.3.2 For specific groups of individuals influenza For at risk individuals meningitis For travellers to endemic areas or on the Hadj annual pilgrimage rabies For those at risk from rabid animals or treating rabies patients rubella Routine childhood vaccine for girls typhoid For travellers to endemic areas yellow fever For travellers to endemic areas 20. MUSCLE RELAXANTS (PERIPHERALLY ACTING) AND CHOLINESTERASE INHIBITORS *alcuronium chloride (2) *neostigmine injection, 5 mg/ml in 2-ml ampoule EDL8 Muscle relaxant for surgery. Replaces gallamine. Cochrane Library: No reviews but RCTs exist tablet, 15 mg (bromide); injection, 500 micrograms in 1-ml ampoule; 2.5 mg (metilsulfate) in 1-ml ampoule Reverses the effect of non depolarising muscle relaxants Tablets used in myasthenia gravis Cochrane Library: No reviews but RCTs exist pyridostigmine bromide (2, 8) tablet, 60 mg; injection, 1 mg in 1-ml ampoule Reverses the effect of non depolarising muscle relaxants Tablets used in myasthenia gravis Cochrane Library: No reviews but RCTs exist suxamethonium chloride (2) injection, 50 mg/ml in 2-ml ampoule; powder for injection Rapid onset short duration muscle relaxant for surgery Not heat stable Complementary drug Section 3 Page 6 of 14 Cochrane Library: No reviews but RCTs exist WHO Model List of Essential Drugs (EDL) with rational and evidence where available 11th edition (Nov. 1999) By Therapeutic Group vecuronium bromide (C) powder for injection, 10 mg in vial EDL7 Muscle relaxant for surgery Short duration of action and lack of vagolytic activity. Cochrane Library: No reviews but RCTs exist Broad spectrum antibiotic CE6 RCTs suggest that no significant differences between different agents 21. OPHTHALMOLOGICAL PREPARATIONS 21.1 Anti-infective agents *gentamicin solution (eye drops), 0.3% (sulfate) Has chloramphenicol been excluded ? *idoxuridine solution (eye drops), 0.1%; eye ointment, 0.2% EDL5 Of value as a specific antiviral agent in herpes keratitis CE6 one small RCT shows significant benefit silver nitrate solution (eye drops), 1% Used as prophylaxis against neonatal conjunctivitis (gonococcus) *tetracycline eye ointment, 1% (hydrochloride) For eye infections due to sensitive organisms Cochrane Library: 2 reviews exist eye drops, 0.5% (sodium phosphate) Local treatment of inflammation CE6 little evidence of effect solution (eye drops), 0.5% (hydrochloride) Local anaesthetic for minor surgery Cochrane Library: No reviews but RCTs exist acetazolamide tablet, 250 mg Oral treatment to reduce intra-ocular pressure. Not for prolonged use. Cochrane Library: No reviews but RCTs exist *pilocarpine solution (eye drops), 2%, 4% (hydrochloride To reduce intra-ocular pressure Cochrane Library: No reviews but 21.2 Anti-inflammatory agents *prednisolone 21.3 Local anaesthetics *tetracaine 21.4 Miotics and antiglaucoma drugs Section 3 Page 7 of 14 WHO Model List of Essential Drugs (EDL) with rational and evidence where available 11th edition (Nov. 1999) By Therapeutic Group or nitrate) *timolol RCTs exist solution (eye drops), 0.25%, 0.5% (as maleate) EDL4 reduces intra-ocular pressure in chronic simple glaucoma. Cochrane Library: No reviews but RCTs exist Solution (eye drops), 0.1%; solution 0.5%, 1% (sulfate) Used to dilate pupil in a variety of conditions Cochrane Library: No reviews but RCTs exist solution (eye drops), 2% (as hydrochloride) To reduce intra-ocular pressure Cochrane Library: No reviews or RCTs found 21.5 Mydriatics atropine Complementary drug epinephrine (adrenaline) (A) EDL11 committee asked for a systematic review of this section and on drugs for menorrhagia 22. OXYTOCICS AND ANTIOXYTOCICS 22.1 Oxytocics *ergometrine tablet, 200 micrograms (hydrogen maleate); injection, 200 micrograms (hydrogen maleate) in 1-ml ampoule For treatment of post partum haemorrhage Cochrane Library: Several reviews exist. oxytocin injection, 10 IU in 1-ml ampoule To induce or augment labour and treatment of post partum haemorrhage Cochrane Library: Several reviews exist. tablet, 4 mg (as sulfate); injection, 50 micrograms (as sulfate)/ml in 5-ml ampoule EDL5 new subsection. To inhibit uncomplicated premature labour Cochrane Library: No reviews but RCTs exist To maintain fluid and electrolyte balance in patients with acute or chronic renal failure Cochrane Library: No reviews but RCTs exist 22.2 Antioxytocics *salbutamol (2) 23. PERITONEAL DIALYSIS SOLUTION intraperitoneal dialysis solution (of appropriate composition) parenteral solution Section 3 Page 8 of 14 WHO Model List of Essential Drugs (EDL) with rational and evidence where available 11th edition (Nov. 1999) By Therapeutic Group ED11 Committee asked for a review of drugs to treat mental illness 24. PSYCHOTHERAPEUTIC DRUGS 24.1 Drugs used in psychotic disorders *chlorpromazine *fluphenazine decanoate (5) *haloperidol tablet, 100 mg (hydrochloride); syrup, 25 mg (hydrochloride)/5ml; injection, 25 mg (hydrochloride)/ml in 2-ml ampoule For schizophrenia and other psychoses injection, 25 mg (decanoate or enantate) in 1ml ampoule For schizophrenia and other psychoses tablet, 2 mg, 5 mg; injection, 5 mg in 1-ml ampoule For schizophrenia and other psychoses tablet, 25 mg (hydrochloride) Tricyclic antidepressant. Also used for neuropathic pain Cochrane Library: range of reviews in schizophrenia CE6 one SR shows global improvement in short and medium term but AEs make it unacceptable to many 24.2 Drugs used in mood disorders 24.2.1 Drugs used in depressive disorders *amitriptyline Cochrane Library: range of reviews in depression CE6 SRs show effective but frequent AEs 24.2.2 Drugs used in bipolar disorders carbamazepine (10, 11) scored tablet, 100 mg, 200 mg EDL10 New section on drugs used in bipolar disorders. Used in bipolar (manic depressive) disorder in patients unresponsive to lithium. lithium carbonate (2, 4) capsule or tablet, 300 mg EDL10 New section on drugs used in bipolar disorders. Prophylaxis and Section 3 Page 9 of 14 Serum levels need to be monitored WHO Model List of Essential Drugs (EDL) with rational and evidence where available 11th edition (Nov. 1999) By Therapeutic Group treatment of mania and bipolar disorder valproic acid (7, 11) enteric coated tablet, 200 mg, 500 mg (sodium salt) For manic episodes associated with bipolar disorder 24.3 Drugs used in generalized anxiety and sleep disorders *diazepam (1b) scored tablet, 2 mg, 5 mg Anxiolytic and hypnotic Cochrane Library: No reviews but RCTs exist EDL8 For panic attacks and obsessivecompulsive disorders CE6. SR evidence for effectiveness in obsessive-compulsive disorders. 24.4 Drugs used for obsessive compulsive disorders and panic attacks clomipramine capsules, 10 mg, 25 mg (hydrochloride) 25. DRUGS ACTING ON THE RESPIRATORY TRACT 25.1 Antiasthmatic drugs *aminophylline (2) injection, 25 mg/ml in 10 ml ampoule For acute severe asthma. Plasma concentration should be monitored *beclometasone inhalation (aerosol), 50 micrograms per dose (dipropionate); 250 micrograms (dipropionate) per dose EDL2 For non systemic corticosteroid prophylaxis for asthma *epinephrine (adrenaline) injection, 1 mg (as hydrochloride or hydrogen tartrate) in 1-ml ampoule For acute anaphylaxis *ipratropium bromide inhalation, 20 micrograms/metered dose EDL10 CE6 conflicting evidence of effect in children due to small studies *salbutamol tablet, 2 mg, 4 mg; inhalation (aerosol), 100 micrograms (as sulfate) per dose; syrup, 2 mg/5 ml; injection, 50 micrograms (as sulfate)/ml in 5-ml ampoule; respirator solution for use in nebulizers, 5 mg (as For treatment and prophylaxis of mild to moderate asthma CE6 evidence of benefit in children in early treatment but no increase in benefit after 1 year Section 3 Page 10 of 14 CE6 Inhaled steroids more effective than theophylline, cromoglicate or long acting beta agonists WHO Model List of Essential Drugs (EDL) with rational and evidence where available 11th edition (Nov. 1999) By Therapeutic Group sulfate)/ml *theophylline (10, 11) tablet, 100 mg, 200 mg, 300 mg EDL9 (300mg added EDL11 for compliance) Bronchodilator for acute airways obstruction and acute severe asthma (B) inhalation (aerosol), 20 mg (sodium salt) per dose EDL2 Prophylaxis of asthma (1a) oral solution, 3.5 mg (bromide)/5 ml EDL10 Replaces codeine more widely available-less likely to lead to drug abuse CE6 evidence of increase of symptom free days but insufficient evidence on benefits vs. harm Complementary drug *cromoglicic acid 25.2 Antitussives *dextromethorphan 26. SOLUTIONS CORRECTING WATER, ELECTROLYTE AND ACID-BASE DISTURBANCES 26.1 Oral oral rehydration salts (for glucose -electrolyte solution) see section 17.7.1 Replaces fluid and salts lost in acute diarrhoea potassium chloride powder for solution To prevent and treat potassium depletion e.g. with diuretic use glucose injectable solution, 5% isotonic, 10% isotonic; 50% hypertonic Fluid replacement, glucose replacement or as calorie source (50%) glucose with sodium chloride injectable solution, 4% glucose, 0.18% sodium chloride (equivalent to Na+ 30 EDL2 Fluid replacement ED11 Committee asked for a revised formula of rehydration fluid that contains micronutrients to be considered 26.2 Parenteral Section 3 Page 11 of 14 Cochrane Library: One review on crystalloids and colloids WHO Model List of Essential Drugs (EDL) with rational and evidence where available 11th edition (Nov. 1999) By Therapeutic Group mmol/l, Cl- 30 mmol/l) potassium chloride (2) solution, 11.2% in 20-ml ampoule, (equivalent to K+ 1.5 mmol/ml, Cl- 1.5 mmol/ml) To prevent and treat potassium depletion sodium chloride injectable solution, 0.9% isotonic (equivalent to Na+ 154 mmol/l, Cl- 154 mmol/l); injectable solution, 0.18% (Na+ 30 mmol/l, Cl- 30 mmol/l) + glucose, 4% Fluid replacement sodium hydrogen carbonate injectable solution, 1.4% isotonic (equivalent to Na+ 167 mmol/l, HCO3- 167 mmol/l); solution, 8.4% in 10-ml ampoule (equivalent to NA+ 1000 mol/l, HCO3-1000 mol/l) Used to control metabolic acidosis and emergency treatment of hyperkalaemia *sodium lactate, compound solution injectable solution Used to control metabolic acidosis 2-ml, 5-ml, 10-ml ampoules Sterile diluent Must be diluted before administration Is this now called Sodium Lactate Solution ? 26.3 Miscellaneous water for injection ED11 Committee asked for a revised formula of rehydration fluid that contains micronutrients to be considered 27. VITAMINS AND MINERALS ascorbic acid tablet, 50 mg EDL2 Originally in hexavitamin EDL1 Vitamin C *ergocalciferol iodine (8) Cochrane Library: one review and RCTs capsule or tablet, 1.25 mg (50,000 IU); oral solution, 250 micrograms/ml (10,000 IU/ml) EDL2 Originally in hexavitamin EDL1 Cochrane Library: one review and RCTs iodized oil, 0.5 ml (240 mg of iodine/ml), 1 ml (480 mg iodine/1 ml) in ampoule (oral or injectable); solution, 0.57 ml (308 mg iodine) EDL6 For prophylaxis of goitre where iodine deficiency is endemic Cochrane Library: No review but RCTs exist Section 3 Page 12 of 14 WHO Model List of Essential Drugs (EDL) with rational and evidence where available 11th edition (Nov. 1999) By Therapeutic Group in dispenser bottle; capsule, 200 mg. *nicotinamide tablet, 50 mg EDL2 Originally in hexavitamin EDL1 Vitamin B group Cochrane Library: one review on nutritional supplements and RCTs pyridoxine tablet, 25 mg (hydrochloride) Vitamin B6 Cochrane Library: one review on nutritional supplements and RCTs *retinol sugar-coated tablet, 10,000 IU (as palmitate) (5.5 mg); capsule, 200,000 IU (as palmitate) (110 mg); oral oily solution 100,000 IU (as palmitate)/ml in multidose dispenser; watermiscible injection 100,000 IU (as palmitate) (55 mg) in 2-ml ampoule EDL2 Originally in hexavitamin EDL1 Cochrane Library: 3 reviews on vitamin A tablet, 5 mg EDL2 Originally in hexavitamin EDL1 riboflavin Vitamin A High doses should be used with caution Vitamin B2 Cochrane Library: one review on nutritional supplements and RCTs *sodium fluoride in any appropriate formulation EDL2 Where water supplies are not fluoridated-prophylaxis of dental caries Cochrane Library: No review but RCTs exist. 2 DARE reports thiamine tablet, 50 mg (hydrochloride) EDL2 Originally in hexavitamin EDL1 Cochrane Library: one review on nutritional supplements and RCTs Vitamin B1 Complementary drug calcium gluconate (C), (2, 8) injection, 100 mg/ml in 10-ml ampoule For hypocalcaemia and hypocalcaemic tetany Phil Wiffen Notes: +It can be assumed that drugs were on the original EDL (EDL1) unless there is a later reference to a subsequent EDL list ++ level of evidence used. Section 3 Page 13 of 14 WHO Model List of Essential Drugs (EDL) with rational and evidence where available 11th edition (Nov. 1999) By Therapeutic Group CE6 refers to Clinical Evidence Issue 6 December 2001. SR - systematic review, RCT -randomised controlled trial, Cochrane Library: 2002 Issue 1 DARE database of abstracts of reviews from NHS centre in York England published on their website (http://nhscrd.york.ac.uk/ ) and the Cochrane Library: ADR- Adverse drug effect AE- adverse effects. Comment. The review of evidence is minimal to give an indication of what is available. Some sections such as section 8 where drugs are used for a number of indications need a thorough work up beyond the scope of this first trawl. Other areas need to be linked to WHO guidelines which are also being reviewed in the light of available evidence. Phil Wiffen email phil.wiffen @pru.ox.ac.uk Feb2002 Section 3 Page 14 of 14