Guidelines for Administration of Injectable Artesunate for Severe Malaria

GUIDELINES FOR ADMINISTRATION OF INJECTABLE ARTESUNATE W FOR SEVERE MALARIA RECOMMENDEDHO TREATMENT 2 PRODUCT DESCRIPTION 1 5 CALCULATE THE DOSE 6 ADMINISTER Ar tesunate Calculate and withdraw the required dose 60 Dose: For children < 20 kg: 3.0 mg/kg mg nate IV: slow bolus 3-4 ml per IM: Inject slowly. Spread ml 5 For children > 20 kg and adults: 2.4 mg/kg in ml according to route of administration: e minute. the doses of more than 1 ml 2 ml over different sites Sodium Can be given by intravenous route (IV) or intramuscular route (IM). Bicarbonat Saline solution For intravenous route (IV) For intramuscular route (IM) for babies and 5 ml for IV is the preferred route of administration. adults. Concentration: 10 mg/ml Concentration: 20 mg/ml Please refer to the patient information leaflet for more information. Artesunate Bicarbonate Saline 3.0 mg x body weight (kg) 3.0 mg x body weight (kg) powder 60mg ampoule solution * * Water for injection is not an appropriate dilutant Ar Ar Ar tesunate tesunat tesunate IV artesunate solution IM artesunate solution 30 at 60 at 120 at

mg e mg e mg e concentration 10 mg/ml concentration 20 mg/ml l

t m Round up to the next whole number Round up to the next whole number

a 1

Ar di

So tesunate B 60 mg nat Example: Example: ml e 5 WEIGHArtesunate THEe PATIENT 60mg ml 1 1 Dose needed (ml) for 8 kg child: Dose needed (ml) for 8 kg child: Sodium Bicarbonat Saline solution 3.0 x 8 = 2.4 ml 3.0 x 8 = 1.2 ml

10 20 ml 5 2.4 ml rounded up to 3 ml 1.2 ml rounded up to 2 ml DETERMINEArtesunat THEate NUMBER OF VIALS NEEDED DOSING SCHEDULE Artesunate Artesunate Ar 7 mg mg e

60 60 ml

tesunate 1 l 1m A rtesu mg nat nate 30 o

b bonate 60m

r um g ate

dium

Saline solution 2 60 ca Weight Dose Weight Dose

So Bi

So Bica Weight less than mg25 kg 26-50 kg 51-75 kg 76-100 kg 1. Give 3 parenteral doses over 24 hours as Ar kg mg ml kg mg ml indicated in the opposite table 120 tesunate Less than 20 kg 6 - 7 20 2 6 - 7 20 1 60 mg vial 1 mg ate 2 3 4

Ar Ar Ar 8 - 10 30 3 8 - 10 30 2 2. Give parenteral doses for a minimum of 24 hours tesunate tesunat tesunate at at at Ar Ar Ar 30mg e 60mg e 120 e tesunate tesunat tesunate mg 30 at 60 at 120 at once started irrespective of the patients ability to 11 - 13 mg 40e mg e4 mg e 11 - 13 40 2

tolerate oral treatment earlier. l

t m

a 1

r u

Artesunateate 14 - 16 50 5 14 - 16 B 50 3 l

t m

a 1

r u

S 60mg Bi 17 - 20 60 6 17 - 20 60 3 • Day 1 Dose 1: on admission (0 Hours) Artesunate RECONSTITUTE 60mg Dose 2: 12 hours later Artesunate 3 mg Activate the drug: artesunate powder + bicarbonate ampoule60 Artesunat e(immediately before use)

Artesunate 60mg Concentration: 10 mg/ml Concentration: 20 mg/ml ml

60mg 1

l 1m

bonate

r • Day 2 Dose 3: 24 hours after first dose

ml 5

Sodium Bica 2.4 mg x bodyArtesunat weightate (kg) 2.4 mg x body weight (kg) Inject full contents of CArtesunate Shake until dissolved. DArtesunatThee reconstituted solution Ar A e mg mg

B ml

60 60

tesunate 1 l 1m A rtesu mg nat naArte Ar 30 Ar o

b bonate 60m te tesunat tesunate

r um g sunate ate

dium

Saline solution bicarbonate ampoule (1 ml) Solution will be cloudy. will clear in about 2 mins. 30 at 60 at 12060 at ca

So Bi

So Bica mgIV eartesunatemg e solutionmg mge IM artesunate solution -- When the patient can take oral medication, prescribe Arte Artesunat Artesunate into artesunate vial. Discard if not clear. sunateml Ar

30 at5 e 60 ate 120 ate concentration 10 mg/ml tesunate concentration 20 mg/ml l

t m

a 1 mg n mg o

r mg u

Sodi Artesunatate 120 Bi a full 3-day course of recommended first line oral Artesunate Artesunate Round up to the next whole number mg ate Round up to the next whole number Ar Ar l Ar mg mg e

60 tesunate 60 tesunate ml

tesunate 1 l 1m A

rt nat 5 m esu mg

n o l

m a Artemisinin Combination Therapy (ACT).

a 1 te 30

bonate

r u 60

ate at c m

Sod Bi

r um 60 60 g e ate Artesunate Ar Ar Ar

dium

Saline solution mg mg 60 Example:te tesunat tesunate Example:ca 60mg sunate

So Bi

So Bica mg 30 at at 120 at mg e 60mg e mg e e The first dose of ACT should be taken l between at 1m Dose needed (ml) for 26 kg child: Dose needed (ml) for 26 kg child: m Ar

Artesunate l ate e

t m

a 1 Artesunate n

r u

S B 8 and 12 hours after the last injection of artesunate. 60mg arbon tesunate c Saline solution Sodiu 60mg

Bi 120 2.4 x 26 2.4 x 26 ml 5 mg ate ate = 6.24 ml = 3.12 ml Artesunate Artesunate -- Until the patient is able to take oral medication,

Artesunate Artesunate 60mg ml

Ar 5 10 20 e mg mg

60 60 ml

tesunate 1 l 1m A Artesunate rtesu mg nat nate 30 o

b bonate Artesunate 60m 60mg

r um g ate ml

dium

Saline solution

Artesunate bicarbonate 60mg 60 1

l 1m

So Bi continue parenteral treatment (one dose a day)

So Artesunate Bica 6.24 ml roundedmg up to 7 ml 3.12 ml rounded up to 4 ml

bonate

60mg r ml

Sodium Bica 5 powder ampoule Ar atAre Ar Ar Saline solution tesunateArtesunattesunate tesunate for a maximum of 7 days. Artesunate Artesunate 30 at 60 at 120 at tesunate mg e mg e Ar mg e 120

e mg mg ml

60 60 tesunate ml

1 l 1m Art Weight Dose Weight Dose esun mg nat ate 30 o mg

b ate bonate 60 ate m

r um g ate Artesunate

dium

Saline solution 60 Artesunate ca Artesunate Ar

So Bi

So Bica

e l

t m

a mg 1 mg mg

60 60 ml

Artesunateon

m ate

b A

tesunate 1

l 1m c rt -- A course of injectable artesunate should always be

Sod Bi A kg kg esunat rt mg ml mg ml nat Artesunateate Artesunate esu mg 60 nate 30 o

b bonate m 60m

g r

r um 60mg e g ate

dium

Saline solution 60 ca

So Bi

So 60mg Ar 60mg Bica Artesunate Artesunate mg l tesunate ate at 5 m followed by a 3-day course of ACT. 60mg 20 - 25 6060mg e 6 20 - 25 60 3 Artesunate 120 Ar 60mg tesunate ate Artesunateate e l 120 mg at DILUTE 1m 60mg 26m - 29 70 7 mg ate 26 - 29 70 4 arbon c Saline solution Sodiu • Evaluate the patient’s progress regularly. Reconstituted artesunate + saline solution (or dextrose 5%) Bi Artesunate Artesunate 30 - 33 80 608mg 30 - 33 80 4 4 Ar Ar ml

60mg tesunate 1

ml l

1m tesunate

ml 5 5 Artesunate bonate ate r Artesunatate Volume for dilution a Artesunate 60mg ml te IV Artesunate IM 34 - 37 90 9 34 - 37 90 5

Artesunate Artesunate 60mg 1

l 1m

Sodium Bica Ar mg mg mg e 60

60 60 ml

tesunate 1 l

1m Artesunate ate bonate Artesunate A ate

r rtesu mg nat nate 30 o

b bonate 60m

r um g

Saline solution

Sodium ate Bica

dium

Saline solution 60 ca

So Bi

So Bica 60mg mg 60mg 38 - 41 100 10 38 - 41 100 5 IMPORTANT ml Bicarbonate solution volume 1 ml 1 ml ml 1 5 Ar IMPORTANT Arte tesunate Artesunateate Artesunate sunat 60 m 42 - 45 110 11 42mg - 45g 110 6 Artesunate 120 60 e mg Artesunate 60mg Saline solutionmg volume 5 ml 2 ml 60 ate Artesunate 60mg ml • Prepare a fresh solution for each administration.

Artesunate 60mg 1

l 1m

Artesunate Saline solution 46 - 50 120 12 46 - 50 120 6 60mg bonate

r l ml Artesunate Artesunate

60mg 1

l 1m Sodium Bica • Discard any unused solution after use. Water for injection is not 5 m ate l at bonate Ar Ar 60 60 r Total volume 6 tesunatml e 3 ml tesunate mg mg e More than 20 kg More

Sodium Bica 51 - 54 130 13 51 - 54 130 7 5 m 60 ate an appropriate60 atdilutant e l Ar Ar e at tesunate mg mg 1m tesunate Artesunateate m 55ate - 58 140ate 14 55 - 58 140 7 arbon e c Saline solution 60mg Artesunate 60 mg solution concentration 10 mg/ml 20 mg/ml l Sodiu Bi at 1m Ar Ar l m tesunate tesunate ml 59 - 62 150 15 59 - 62 150 8 5 m

ml 1

ml 5 60 ate 60 at 5 arbon mg mg e c Saline solution This document is intended to demonstrate to health workers how to prepare and Ar Ar Artesunate Artesunate Sodiu l Artesunate Bi e l Artesunate tesunate tesunate 60mg 60mg 63 - 66 160 16 63 - 66 160 8 ml at 60mg 1m

60mg Withdraw1 all the air C Inject required volume D Artesunate solution l 1m 5 m administer injectable artesunate, a treatment for severe malaria. It is not intended to ate A at m

B Saline solution

bonate r 60 60 e mg mg Saline solution arbon

Sodium Bica from the vial. of saline into the is now ready for use. c Saline solution 67Sodiu - 70 170 17 67 - 70 170 9 provide personal medical advice. The responsibility for the interpretation and use of this Bi

ml Ar Ar Ar

te tesunat tesunate e l sunate 5 30 at at 120 at at mg e 60mg e mg e 1m reconstituted solution. material lies with the reader. In no event shall MMV be liable for damages arising from m A rtesunat

ml Artesunateate Artesunate

60 m Artesunate 5 71 - 75 180 18 60mg g e 71 - 75 180 9 arbon

60mg c Saline solution l

t its use. mg m

a 1

Sodiu 60 n

r u

S Bi Artesunate Bi 60mg

5 m ml ate at 5 60 60 e mg mg Artesunate document can only be made upon MMV’s written authorization. 60mg 80 - 83 200 20 80 - 83 200 10

Artesunate e l A rtesunat at Artesunateate Ar Artesunate 60 1m Ar m 60mg tesunate 60mg g e m tesunate Art Artesunateate Artesunate esunat 60 60mg ate mg arbon 84 - 87 210 21 84 - 87 210 11 60mg a e Saline solution c Saline solution te Sodiu Bi 60mg

ml 88 - 91 220 22 88 - 91 220 11 5

ml ml

ml 1

5 ate Artesunateate Artesunate Artesunate Artesunate Artesunate Artesunate 60mg Ar Artesunate 60mg mg mg e

60 60 ml

tesunate 1 l 1m A mg Artesunate rtesu mg Ar nat 60 n 92 - 95 230 23 92 - 95 o 230 12 Artesunate saline ate 30

Ar b bonate 60m

r um g tesunate mg 60mg ate tesunate

dium 60 di

Saline solution 60 ca

So Bi

So Bica mg Saline solution ate a reconstituted solution Saline solution te 96 - Ar100 240 24 96 - 100 240 12 Ar tesunate Art 120 esunat Ar ml Artesunateate Artesunate 60 tesunate m 60mg g e ml tesunate 1 1. World Health Organization (WHO) List of Prequalified Medicinal Products (http://apps.who.int/prequal/query/ProductRegistry.aspx?list=ma):5 artesunate injectable, reference N° MA051, mg ate 60mg ate a Remark: the upper limit for each weight band is 0.9 kg e.g. 14 - 16 kg covers Ar prequalifiedAr on 05-Nov-2010. Artesunate te tesunate tesunate 60mg 2. World Health Organization, Management of Severe Malaria - A practical handbook - Third edition - April 2013 - (http://www.who.int/malaria/publications/atoz/9789241548526/en/index.html) 14 - 16.9 kg.

ate Saline solution © MMV 20141029 ate Ar ml Artesunateate ml Ar 1 5 tesunate tesunate ml ate a 60mg ml 1 te 5 Artesunate Artesunate 60mg 60mg ml

ml 1 5 Saline solution Artesunate Artesunate 60mg

Saline solution ml

60mg 1 l Artesunate 1m

bonate 60mg r

Sodium Bica

Saline solution

Artesunate Artesunate l ate at 5 m 60mg 60mg e

e l at 1m

arbon c Saline solution Sodiu

Artesunate 60mg

Saline solution

Art Artesunateate Artesunate esunat 60 m 60mg g e 60mg

Artesunate Artesunate ate ate

ml 1 5

Artesunate 60mg

Saline solution