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Key to recommended regimens for prophylaxis against malaria

Codes for regimens Details of regimens for prophylaxis against malaria

- No risk

1 Chemoprophylaxis not recommended, but avoid mosquito bites and consider malaria if fever presents

2 Chloroquine only

3 Chloroquine with proguanil

4 Atovaquone with proguanil hydrochloride or doxycycline or mefloquine

Specific recommendations

Country Comments on risk of malaria and regional or seasonal variation Codes for regimens

Afghanistan Low risk below 2000 m from May–November 1

Very low risk below 2000 m from December–April 1

Algeria Very low risk in remote focus in Illizi department only 1

Andaman and Nicobar Islands

(India)

Low risk 1

Angola High risk 4

Argentina Very low risk in low altitude areas of Salta provinces bordering Bolivia and in Chaco,

Corrientes, and Misiones provinces close to border with Paraguay and Brazil

1

No risk in Iguaçu Falls and areas other than those above -

Armenia No risk 1

Azerbaijan Very low risk 1

Bangladesh High risk in Chittagong Hill Tract districts (but not Chittagong city) 4

Very low risk in Chittagong city and other areas, except Chittagong Hill Tract

districts

1

Belize Low risk in rural areas 1

No risk in Belize district (including Belize city and islands) -

Benin High risk 4

Bhutan Low risk in southern belt districts, along border with India: Chukha, Geyleg-phug,

Samchi, Samdrup Jonkhar, and Shemgang

1

No risk in areas other than those above -

Bolivia Low risk in Amazon basin 1

Low risk in rural areas below 2500 m (other than above) 1

No risk above 2500 m -

Botswana High risk from November–June in northern half, including Okavango Delta area 4

Low risk from July–October in northern half 1

Very low risk in southern half 1

Brazil Low risk in Amazon basin, including city of Manaus 1

Very low risk in areas other than those above 1

No risk in Iguaçu Falls -

Brunei Darussalam Very low risk 1

Burkina Faso High risk 4

Burundi High risk 4

Cambodia Low risk. Mefloquine resistance widespread in western provinces bordering

Thailand

1

Very low risk in Angkor Wat and Lake Tonle Sap, including Siem Reap 1

No risk in Phnom Penh -

Cameroon High risk 4

Cape Verde Individuals travelling to Praia who are at increased risk of malaria (such as longterm travellers and those at risk of severe complications from malaria including

pregnant women, infants and young children, the elderly, and asplenic individuals)

should consider taking antimalarials, seek advice from a travel health advisor. Very

low risk on island of Santiago (Sao Tiago) and Boa Vista

1

Central African Republic High risk 4

Chad High risk 4

BNF 78 Malaria 609

Infection

5

Country Comments on risk of malaria and regional or seasonal variation Codes for regimens

China Low risk in Yunnan and Hainan provinces 1

Very low risk in southern and some central provinces, including Anhui, Ghuizhou,

Hena, Hubei, and Jiangsu below 1500 m

1

Very low risk in areas other than those above and below 1

No risk in Hong Kong -

Colombia Low risk in rural areas below 1600 m 1

Very low risk above 1600 m and in Cartagena 1

Comoros High risk 4

Congo High risk 4

Costa Rica Low risk in Limon province, but not city of Limon (Puerto Limon) 1

Very low risk in areas other than those above 1

Cote d’Ivoire (Ivory Coast) High risk 4

Democratic Republic of the

Congo

High risk 4

Djibouti High risk 4

Dominican Republic Low risk 1

No risk in cities of Santiago and Santo Domingo -

East Timor (Timor-Leste) Risk present 4

Ecuador Low risk in areas below 1500 m including coastal provinces and Amazon basin 1

No risk in Galapagos islands or city of Guayaquil -

Egypt No risk 1

El Salvador Low risk in rural areas of Santa Ana, Ahuachapán, and La Unión provinces in

western part of country; very low risk in other areas

1

Equatorial Guinea High risk 4

Eritrea High risk below 2200 m 4

No risk in Asmara or in areas above 2200 m -

Ethiopia High risk below 2000 m 4

No risk in Addis Ababa or in areas above 2000 m -

French Guiana Risk present (particularly in border areas) except city of Cayenne or Devil’s Island

(Ile du Diable)

4

Low risk in city of Cayenne or Devil’s Island (Ile du Diable) 1

Gabon High risk 4

Gambia High risk 4

Georgia Very low risk in rural south east from June–October 1

Ghana High risk 4

Guatemala Low risk below 1500 m 1

No risk in Guatemala City, Antigua, or Lake Atitlan and above 1500 m -

Guinea High risk 4

Guinea-Bissau High risk 4

Guyana Risk present in all interior regions 4

Very low risk in Georgetown and coastal region 1

Haiti Risk present 3

Honduras Low risk below 1000 m and in Roatán and other Bay Islands 1

No risk in San Pedro Sula or Tegucigalpa and areas above 1000 m -

India Risk present in states of Assam and Orissa, districts of East Godavari, Srikakulam,

Vishakhapatnam, and Vizianagaram in the state of Andhra Pradesh, and districts of

Balaghat, Dindori, Mandla, and Seoni in the state of Madhya Pradesh

4

Low risk in areas other than those above or below (including Goa, Andaman and

Nicobar islands)

1

Exceptional circumstances in low risk areas (dependent on individual risk

assessment)

3

No risk in Lakshadweep islands -

Indonesia High risk in Irian Jaya (Papua) 4

Low risk in Bali, Lombok and islands of Java and Sumatra 1

No risk in city of Jakarta -

Indonesia (Borneo) Low risk 1

610 Protozoal infection BNF 78

Infection

5

Key to recommended regimens for prophylaxis against malaria

Codes for regimens Details of regimens for prophylaxis against malaria

- No risk

1 Chemoprophylaxis not recommended, but avoid mosquito bites and consider malaria if fever presents

2 Chloroquine only

3 Chloroquine with proguanil

4 Atovaquone with proguanil hydrochloride or doxycycline or mefloquine

Specific recommendations

Country Comments on risk of malaria and regional or seasonal variation Codes for regimens

Iran Low risk from March–November in rural south eastern provinces and in north, along

Azerbaijan border in Ardabil, and near Turkmenistan border in North Khorasan

1

Very low risk in areas other than those above 1

Iraq Very low risk from May–November in rural northern area below 1500 m 1

No risk in areas other than those above -

Kenya High risk (except city of Nairobi) 4

Very low risk in the highlands above 2500 m and in city of Nairobi 1

Lao People’s Democratic

Republic (Laos)

Low risk 1

Very low risk in city of Vientiane 1

Liberia High risk 4

Libya No risk 1

Madagascar High risk 4

Malawi High risk 4

Malaysia Low risk in mainland Malaysia 1

Malaysia (Borneo) Low risk in inland areas of Sabah and in inland, forested areas of Sarawak 1

Very low risk in areas other than those above, including coastal areas of Sabah and

Sarawak

1

Mali High risk 4

Mauritania High risk all year in southern provinces, and from July–October in the northern

provinces

4

Low risk from November–June in the northern provinces 1

Mauritius No risk 1

Mayotte Risk present 4

Mexico Very low risk 1

Mozambique High risk 4

Myanmar Low risk 1

Namibia High risk all year in regions of Caprivi Strip, Kavango, and Kunene river, and from

November–June in northern third of country

4

Very low risk in areas other than those above; low risk from July–October in

northern third of country

1

Nepal Low risk below 1500 m, including the Terai district 1

No risk in city of Kathmandu and on typical Himalayan treks -

Nicaragua Low risk (except Managua) 1

Very low risk in Managua 1

Niger High risk 4

Nigeria High risk 4

North Korea Very low risk in some southern areas 1

Pakistan Low risk below 2000 m 1

Very low risk above 2000 m 1

Panama Low risk east of Canal Zone 1

Very low risk west of Canal Zone 1

No risk in Panama City or Canal Zone itself -

Papua New Guinea High risk below 1800 m 4

Very low risk above 1800 m 1

BNF 78 Malaria 611

Infection

5

Country Comments on risk of malaria and regional or seasonal variation Codes for regimens

Paraguay No risk 1

Peru Low risk in Amazon basin along border with Brazil, particularly in Loreto province

and in rural areas below 2000 m including the Amazon basin bordering Bolivia

1

No risk in city of Lima and coastal region south of Chiclayo -

Philippines Low risk in rural areas below 600 m and on islands of Luzon, Mindanao, Mindoro,

and Palawan

1

No risk in cities or on islands of Boracay, Bohol, Catanduanes, Cebu, or Leyte -

Rwanda High risk 4

São Tomé and Principe High risk 4

Saudi Arabia Low risk in south-western provinces along border with Yemen, including below

2000 m in Asir province

1

No risk in cities of Jeddah, Makkah (Mecca), Medina, Riyadh, or Ta’if, or above

2000 m in Asir province

-

Senegal High risk 4

Sierra Leone High risk 4

Solomon Islands High risk 4

Somalia High risk 4

South Africa Risk from September–May in low altitude areas of Mpumalanga and Limpopo,

particularly those bordering Mozambique, Swaziland (Estwatini), and Zimbabwe

(including Kruger National Park)

4

Low risk in north-east KwaZulu-Natal and in designated areas of Mpumalanga and

Limpopo

1

Very low risk in North West Province (adjacent to Molopo river) and Northern Cape

Province (adjacent to Orange river)

1

South Korea Very low risk in northern areas, in Gangwon-do and Gyeonggi-do provinces, and

Incheon city (towards Demilitarized Zone)

1

South Sudan High risk 4

Sri Lanka Low risk north of Vavuniya 1

Very low risk in areas other than those above and below 1

No risk in Colombo or Kandy -

Sudan High risk in central and southern areas; risk also present in rest of country (except

Khartoum)

4

Very low risk in Khartoum 1

Suriname Risk present on the French Guiana border 4

Low risk in areas other than above and below 1

No risk in city of Paramaribo -

Swaziland Risk in northern and eastern regions bordering Mozambique and South Africa,

including all of Lubombo district and Big Bend, Mhlume, Simunye, and Tshaneni

regions

4

Very low risk in the areas other than those above 1

Syria Very low risk in small, remote foci of El Hasakah 1

Tajikistan Very low risk 1

No risk above 2000 m -

Tanzania High risk below 1800 m; risk also in Zanzibar 4

No risk above 1800 m -

Thailand Mefloquine resistance present. Low risk in rural forested borders with Cambodia,

Laos, and Myanmar

1

Very low risk in areas other than those above, including Kanchanaburi (Kwai Bridge) 1

No risk in cities of Bangkok, Chiang Mai, Chiang Rai, Koh Phangan, Koh Samui, and

Pattaya

-

Togo High risk 4

Turkey Very low risk 1

Uganda High risk 4

Uzbekistan Very low risk in extreme south-east 1

Vanuatu Risk present 4

612 Protozoal infection BNF 78

Infection

5

In view of the continuing emergence of resistant strains and

of the different regimens required for different areas expert

advice should be sought on the best treatment course for an

individual traveller. A drug used for chemoprophylaxis

should not be considered for standby treatment for the same

traveller.

Malaria prophylaxis, specific recommendations

Travellers planning journeys across continents can travel

into areas that have different malaria prophylaxis

recommendations. The choice of prophylaxis medication

must reflect overall risk to ensure protection in all areas; it

may be possible to change from one regimen to another.

Those travelling to remote or little-visited areas may require

expert advice. For further information see Recommended

regimens for prophylaxis against malaria, and Public Health

England Guidelines for malaria prevention in travellers from

the United Kingdom.

Important

Settled immigrants (or long-term visitors) to the UK may be

unaware that any immunity they may have acquired while

living in malarious areas is lost rapidly after migration to

the UK, or that any non-malarious areas where they lived

previously may now be malarious.

Malaria, treatment

Advice for healthcare professionals

A number of specialist centres are able to provide advice on

specific problems.

PHE (Public Health England) Malaria Reference Laboratory

(020) 7637 0248 (fax) (prophylaxis only) www.malariareference.co.uk

National Travel Health Network and Centre 0845 602 6712

Monday and Friday: 9–11 a.m. and 1–2 p.m, Tuesday to

Thursday: 9–11 a.m. and 1–3:30 p.m. travelhealthpro.org.uk/

Travel Medicine Team, Health Protection Scotland

(registered users of Travax only) www.travax.nhs.uk (for

registered users of the NHS Travax website only) (0141) 300

1100 (weekdays 2–4 p.m. only)

Birmingham (0121) 424 2358

Liverpool (0151) 705 3100

London 0845 155 5000 (treatment)

Oxford (01865) 225 430

Advice for travellers

Hospital for Tropical Diseases Travel Healthline (020) 7950

7799 www.fitfortravel.nhs.uk

WHO advice on international travel and health www.who.int/

ith

National Travel Health Network and Centre (NaTHNaC)

www.travelhealthpro.org.uk/

Treatment of malaria

Recommendations on the treatment of malaria reflect

guidelines agreed by UK malaria specialists.

If the infective species is not known, or if the infection is

mixed, initial treatment should be as for falciparum malaria

with quinine p. 619, Malarone ® (atovaquone with proguanil

hydrochloride p. 615), or Riamet ® (artemether with

lumefantrine p. 614). Falciparum malaria can progress

rapidly in unprotected individuals and antimalarial

treatment should be considered in those with features of

severe malaria and possible exposure, even if the initial

blood tests for the organism are negative.

Falciparum malaria (treatment)

Falciparum malaria (malignant malaria) is caused by

Plasmodium falciparum. In most parts of the world P.

falciparum is now resistant to chloroquine p. 616 which

should not therefore be given for treatment.

Key to recommended regimens for prophylaxis against malaria

Codes for regimens Details of regimens for prophylaxis against malaria

- No risk

1 Chemoprophylaxis not recommended, but avoid mosquito bites and consider malaria if fever presents

2 Chloroquine only

3 Chloroquine with proguanil

4 Atovaquone with proguanil hydrochloride or doxycycline or mefloquine

Specific recommendations

Country Comments on risk of malaria and regional or seasonal variation Codes for regimens

Venezuela Risk in all areas south of, and including, the Orinoco river and Angel Falls, rural

areas of Apure, Monagas, Sucre, and Zulia states

1

No risk in city of Caracas or on Margarita Island -

Vietnam Low risk in rural areas, and in southern provinces of Tay Ninh, Lam Dong, Dac Lac,

Gia Lai, and Kon Tum

1

No risk in large cities (including Ho Chi Minh City (Saigon) and Hanoi), the Red River

delta, coastal areas north of Nha Trang and Phu Quoc Island

1

Western Sahara No risk 1

Yemen Risk below 2000 m 3

Very low risk on Socrota Island; no risk above 2000 m, including Sana’a city 1

Zambia High risk 4

Zimbabwe High risk all year in Zambezi valley, and from November–June in areas below

1200 m

4

Low risk from July–October in areas below 1200 m; very low risk all year in Harare

and Bulawayo

1

BNF 78 Malaria 613

Infection

5

Quinine, Malarone® (atovaquone with proguanil

hydrochloride), or Riamet® (artemether with lumefantrine)

can be given by mouth if the patient can swallow and retain

tablets and there are no serious manifestations (e.g.

impaired consciousness); quinine should be given by

intravenous infusion if the patient is seriously ill or unable to

take tablets. Mefloquine p. 617 is now rarely used for

treatment because of concerns about resistance.

Oral quinine is given by mouth for 5–7 days, together with

or followed by either doxycycline p. 564 for 7 days or

clindamycin p. 535 for 7 days [unlicensed].

If the parasite is likely to be sensitive, pyrimethamine with

sulfadoxine as a single dose [unlicensed] may be given

(instead of either clindamycin or doxycycline) together with,

or after, a course of quinine.

Alternatively, Malarone ®, or Riamet ® may be given

instead of quinine. It is not necessary to give clindamycin,

doxycycline, or pyrimethamine with sulfadoxine after

Malarone ® or Riamet ® treatment.

If the patient is seriously ill or unable to take tablets, or if

more than 2% of red blood cell are parasitized, quinine

should be given by intravenous infusion [unlicensed] (until

patient can swallow tablets to complete the 7-day course

together with or followed by either doxycycline or

clindamycin).

Specialist advice should be sought in difficult cases (e.g.

very high parasite count, deterioration on optimal doses of

quinine, infection acquired in quinine-resistant areas of

south east Asia) because intravenous artesunate may be

available for ‘named-patient’ use.

Pregnancy

Falciparum malaria is particularly dangerous in pregnancy,

especially in the last trimester. The adult treatment doses or

oral and intravenous quinine (including the loading dose)

can safely be given to pregnant women. Clindamycin should

be given after quinine [unlicensed indication]. Doxycycline

should be avoided in pregnancy (affects teeth and skeletal

development); pyrimethamine with sulfadoxine, Malarone ®,

and Riamet ® are also best avoided until more information is

available. Specialist advice should be sought in difficult cases

(e.g. very high parasite count, deterioration on optimal doses

of quinine, infection acquired in quinine-resistant areas of

south east Asia) because intravenous artesunate may be

available for ‘named patient’ use.

Non-falciparum malaria (treatment)

Non-falciparum malaria is usually caused by Plasmodium

vivax and less commonly by P. ovale and P. malariae. P.

knowlesi is also present in the Asia-Pacific region.

Chloroquine is the drug of choice for the treatment of nonfalciparum malaria (but chloroquine-resistant P. vivax has

been reported in the Indonesian archipelago, the Malay

Peninsula, including Myanmar, and eastward to Southern

Vietnam).

For the treatment of chloroquine-resistant non-falciparum

malaria, Malarone ® [unlicensed indication], quinine, or

Riamet ® [unlicensed indication] can be used; as with

chloroquine, primaquine p. 618 should be given for radical

cure.

Chloroquine alone is adequate for P. malariae and P.

knowlesi infections but in the case of P. vivax and P. ovale, a

radical cure (to destroy parasites in the liver and thus prevent

relapses) is required. This is achieved with primaquine

[unlicensed] given after chloroquine, with the dose

dependent on the infecting organism. For a radical cure,

primaquine [unlicensed] is then given for 14 days, with the

dose also dependent on the infecting organism.

Parenteral

Parenteral If the patient is unable to take oral therapy,

quinine can be given by intravenous infusion [unlicensed],

changed to oral chloroquine as soon as the patient’s

condition permits.

Pregnancy

The adult treatment doses of chloroquine can be given for

non-falciparum malaria. In the case of P. vivax or P. ovale,

however, the radical cure with primaquine should be

postponed until the pregnancy is over; instead chloroquine

should be continued, given weekly during the pregnancy.

ANTIPROTOZOALS › ANTIMALARIALS

Artemether with lumefantrine 28-May-2018

l INDICATIONS AND DOSE

Treatment of acute uncomplicated falciparum malaria |

Treatment of chloroquine-resistant non-falciparum

malaria

▶ BY MOUTH

▶ Adult (body-weight 35 kg and above): Initially 4 tablets,

followed by 4 tablets for 5 doses each given at 8, 24, 36,

48 and 60 hours (total 24 tablets over 60 hours)

l UNLICENSED USE Use in treatment of non-falciparum

malaria is an unlicensed indication.

l CONTRA-INDICATIONS Family history of congenital QT

interval prolongation .family history of sudden death . history of arrhythmias . history of clinically relevant

bradycardia . history of congestive heart failure

accompanied by reduced left ventricular ejection fraction

l CAUTIONS Avoid in Acute porphyrias p. 1058 . electrolyte

disturbances

l INTERACTIONS → Appendix 1: antimalarials

l SIDE-EFFECTS

▶ Common or very common Abdominal pain . appetite

decreased . arthralgia . asthenia . cough . diarrhoea . dizziness . gait abnormal . headache . movement disorders . myalgia . nausea . palpitations . QT interval prolongation . sensation abnormal . skin reactions . sleep disorders . vomiting

▶ Uncommon Drowsiness

▶ Frequency not known Angioedema

l PREGNANCY Toxicity in animal studies with artemether.

Manufacturer advises use only if potential benefit

outweighs risk.

l BREAST FEEDING Manufacturer advises avoid

breastfeeding for at least 1 week after last dose. Present in

milk in animal studies.

l HEPATIC IMPAIRMENT Manufacturer advises caution in

severe impairment (no information available)—monitor

ECG and plasma potassium concentration.

l RENAL IMPAIRMENT Manufacturer advises caution in

severe impairment.

Monitoring In severe renal impairment monitor ECG and

plasma potassium concentration.

l MONITORING REQUIREMENTS Monitor patients unable to

take food (greater risk of recrudescence).

l DIRECTIONS FOR ADMINISTRATION Tablets may be crushed

just before administration.

l PATIENT AND CARER ADVICE

Driving and skilled tasks Dizziness may affect performance

of skilled tasks (e.g. driving).

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Tablet

CAUTIONARY AND ADVISORY LABELS 21

▶ Riamet (Novartis Pharmaceuticals UK Ltd)

Artemether 20 mg, Lumefantrine 120 mg Riamet tablets |

24 tablet P £22.50

614 Protozoal infection BNF 78

Infection

5

Artenimol with piperaquine

phosphate 18-Jun-2018

(Piperaquine tetraphosphate with

dihydroartemisinin)

l INDICATIONS AND DOSE

Treatment of uncomplicated falciparum malaria

▶ BY MOUTH

▶ Child 6 months–17 years (body-weight 7–12 kg): 0.5 tablet

once daily for 3 days, max. 2 courses in 12 months;

second course given at least 2 months after first course

▶ Child 6 months–17 years (body-weight 13–23 kg): 1 tablet

once daily for 3 days, max. 2 courses in 12 months;

second course given at least 2 months after first course

▶ Child 6 months–17 years (body-weight 24–35 kg): 2 tablets

once daily for 3 days, max. 2 courses in 12 months;

second course given at least 2 months after first course

▶ Child 6 months–17 years (body-weight 36–74 kg): 3 tablets

once daily for 3 days, max. 2 courses in 12 months;

second course given at least 2 months after first course

▶ Child 6 months–17 years (body-weight 75–99 kg): 4 tablets

once daily for 3 days, max. 2 courses in 12 months;

second course given at least 2 months after first course

▶ Adult (body-weight 36–74 kg): 3 tablets once daily for

3 days, max. 2 courses in 12 months; second course

given at least 2 months after first course

▶ Adult (body-weight 75–99 kg): 4 tablets once daily for

3 days, max. 2 courses in 12 months; second course

given at least 2 months after first course

l CONTRA-INDICATIONS Acute myocardial infarction . bradycardia . congenital long QT syndrome . electrolyte

disturbances .family history of sudden death . heart failure

with reduced left ventricular ejection fraction . history of

symptomatic arrhythmias . left ventricular hypertrophy . risk factors for QT interval prolongation . severe

hypertension

l INTERACTIONS → Appendix 1: antimalarials

l SIDE-EFFECTS

▶ Common or very common Anaemia . arrhythmias (in adults) . asthenia . conjunctivitis (in children). eosinophilia .fever . headache (uncommon in children). leucocytosis (in

children). leucopenia (in children). neutropenia (in

children). QT interval prolongation .thrombocytopenia

(in children)

▶ Uncommon Abdominal pain (very common in children). appetite decreased (very common in children). arthralgia . cardiac conduction disorder. cough (very common in

children). diarrhoea (very common in children). dizziness

(in adults). epistaxis (in children). hepatic disorders . hypochromia (in children). increased risk of infection

(very common in children). lymphadenopathy (in

children). myalgia (in adults). nausea .rhinorrhoea (in

children). seizure . skin reactions (very common in

children). splenomegaly (in children). stomatitis (in

children).thrombocytosis (in children). vomiting (very

common in children)

l PREGNANCY Teratogenic in animal studies—manufacturer

advises use only if other antimalarials cannot be used.

l BREAST FEEDING Manufacturer advises avoid—present in

milk in animal studies.

l HEPATIC IMPAIRMENT Manufacturer advises caution in

jaundice or in moderate to severe failure (no information

available)—monitor ECG and plasma potassium

concentration.

Monitoring Manufacturer advises monitor ECG and

plasma-potassium concentration in moderate to severe

hepatic impairment.

l RENAL IMPAIRMENT No information available in moderate

to severe impairment.

Monitoring Manufacturer advises monitor ECG and

plasma-potassium concentration in moderate to severe

renal impairment.

l MONITORING REQUIREMENTS

▶ Consider obtaining ECG in all patients before third dose

and 4–6 hours after third dose. If QTC interval more than

500 milliseconds, discontinue treatment and monitor ECG

for a further 24–48 hours.

▶ Obtain ECG as soon as possible after starting treatment

then continue monitoring in those taking medicines that

increase plasma-piperaquine concentration, in children

who are vomiting, in females, or in the elderly.

l DIRECTIONS FOR ADMINISTRATION Tablets to be taken at

least 3 hours before and at least 3 hours after food. Tablets

may be crushed and mixed with water immediately before

administration.

l PATIENT AND CARER ADVICE Patients or carers should be

given advice on how to administer tablets containing

piperaquine phosphate with artenimol.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Tablet

▶ Eurartesim (Logixx Pharma Solutions Ltd) A

Artenimol 40 mg, Piperaquine phosphate 320 mg Eurartesim

320mg/40mg tablets | 12 tablet P £40.00

Atovaquone with proguanil

hydrochloride 28-May-2019

l INDICATIONS AND DOSE

MALARONE ® 250MG/100MG

Prophylaxis of falciparum malaria, particularly where

resistance to other antimalarial drugs suspected

▶ BY MOUTH

▶ Adult (body-weight 40 kg and above): 1 tablet once daily,

to be started 1–2 days before entering endemic area

and continued for 1 week after leaving

Treatment of acute uncomplicated falciparum malaria |

Treatment of non-falciparum malaria

▶ BY MOUTH

▶ Adult: 4 tablets once daily for 3 days

DOSE EQUIVALENCE AND CONVERSION

▶ Each tablet of Malarone ® contains 250 mg of

atovaquone and 100 mg of proguanil hydrochloride.

l UNLICENSED USE Not licensed for treatment of nonfalciparum malaria.

l CAUTIONS Diarrhoea or vomiting (reduced absorption of

atovaquone). efficacy not evaluated in cerebral or

complicated malaria (including hyperparasitaemia,

pulmonary oedema or renal failure)

l INTERACTIONS → Appendix 1: antimalarials

l SIDE-EFFECTS

▶ Common or very common Abdominal pain . appetite

decreased . cough . depression . diarrhoea . dizziness . fever . headache . nausea . skin reactions . sleep disorders . vomiting

▶ Uncommon Alopecia . anxiety . blood disorder. hyponatraemia . oral disorders . palpitations

▶ Frequency not known Hallucination . hepatic disorders . photosensitivity reaction . seizure . Stevens-Johnson

syndrome .tachycardia . vasculitis

l PREGNANCY Manufacturer advises use only if potential

benefit outweighs risk. See also Pregnancy in Malaria,

prophylaxis p. 607.

l BREAST FEEDING Use only if no suitable alternative

available.

BNF 78 Malaria 615

Infection

5

l RENAL IMPAIRMENT Avoid for malaria prophylaxis (and if

possible for malaria treatment) if eGFR less than

30 mL/minute/1.73m2

.

l PATIENT AND CARER ADVICE Warn travellers about

importance of avoiding mosquito bites, importance of

taking prophylaxis regularly, and importance of

immediate visit to doctor if ill within 1 year and especially

within 3 months of return.

l NATIONAL FUNDING/ACCESS DECISIONS

NHS restrictions Drugs for malaria prophylaxis are not

prescribable in NHS primary care; health authorities may

investigate circumstances under which antimalarials are

prescribed.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Tablet

CAUTIONARY AND ADVISORY LABELS 21

▶ Malarone (GlaxoSmithKline UK Ltd)

Proguanil hydrochloride 100 mg, Atovaquone 250 mg Malarone

250mg/100mg tablets | 12 tablet P £25.21 DT = £25.21

Chloroquine

l INDICATIONS AND DOSE

Active rheumatoid arthritis (administered on expert

advice)| Systemic and discoid lupus erythematosus

(administered on expert advice)

▶ BY MOUTH USING TABLETS

▶ Adult: 155 mg daily; maximum 2.5 mg/kg per day

Prophylaxis of malaria

▶ INITIALLY BY MOUTH USING SYRUP

▶ Child 4–5 weeks (body-weight up to 4.5 kg): 25 mg once

weekly, started 1 week before entering endemic area

and continued for 4 weeks after leaving

▶ Child 6 weeks–5 months (body-weight 4.5–7 kg): 50 mg

once weekly, started 1 week before entering endemic

area and continued for 4 weeks after leaving

▶ Child 6–11 months (body-weight 8–10 kg): 75 mg once

weekly, started 1 week before entering endemic area

and continued for 4 weeks after leaving

▶ Child 1–2 years (body-weight 11–14 kg): 100 mg once

weekly, started 1 week before entering endemic area

and continued for 4 weeks after leaving

▶ Child 3–4 years (body-weight 15–16.4 kg): 125 mg once

weekly, started 1 week before entering endemic area

and continued for 4 weeks after leaving

▶ Child 5–7 years (body-weight 16.5–24 kg): 150 mg once

weekly, alternatively (by mouth using tablets) 155 mg

once weekly, started 1 week before entering endemic

area and continued for 4 weeks after leaving

▶ Child 8–13 years (body-weight 25–44 kg): 225 mg once

weekly, alternatively (by mouth using tablets) 232.5 mg

once weekly, started 1 week before entering endemic

area and continued for 4 weeks after leaving

▶ INITIALLY BY MOUTH USING TABLETS

▶ Child 14–17 years (body-weight 45 kg and above): 310 mg

once weekly, alternatively (by mouth using syrup)

300 mg once weekly, started 1 week before entering

endemic area and continued for 4 weeks after leaving

▶ Adult (body-weight 45 kg and above): 310 mg once

weekly, alternatively (by mouth using syrup) 300 mg

once weekly, started 1 week before entering endemic

area and continued for 4 weeks after leaving

Treatment of non-falciparum malaria

▶ BY MOUTH

▶ Child: Initially 10 mg/kg (max. per dose 620 mg), then

5 mg/kg after 6–8 hours (max. per dose 310 mg), then

5 mg/kg daily (max. per dose 310 mg) for 2 days

▶ Adult: Initially 620 mg, then 310 mg after 6–8 hours,

then 310 mg daily for 2 days, approximate total

cumulative dose of 25 mg/kg of base

P. vivax or P. ovale infection during pregnancy while

radical cure is postponed

▶ BY MOUTH

▶ Adult: 310 mg once weekly

DOSE EQUIVALENCE AND CONVERSION

▶ Doses expressed as chloroquine base.

▶ Each tablet contains 155 mg of chloroquine base

(equivalent to 250 mg of chloroquine phosphate).

Syrup contains 50 mg/5 mL of chloroquine base

(equivalent to 80 mg/5 mL of chloroquine phosphate).

DOSES AT EXTREMES OF BODY-WEIGHT

▶ With oral use in adults In active rheumatoid arthritis and

systemic and discoid lupus erythematosus, to avoid

excessive dosage in obese patients, the daily maximum

dose should be calculated on the basis of ideal body

weight.

l UNLICENSED USE Chloroquine doses for the treatment and

prophylaxis of malaria in BNF publications may differ from

those in product literature.

IMPORTANT SAFETY INFORMATION

▶ In adults

Ocular toxicity is unlikely if the dose of chloroquine

phosphate does not exceed 4 mg/kg daily (equivalent to

chloroquine base approx. 2.5 mg/kg daily).

l CAUTIONS Acute porphyrias p. 1058 . diabetes (may lower

blood glucose). elderly .G6PD deficiency . long-term

therapy (regular ophthalmic examination recommended

by manufacturers). may aggravate myasthenia gravis . may

exacerbate psoriasis . neurological disorders, especially

epilepsy (may lower seizure threshold)—avoid for

prophylaxis of malaria if history of epilepsy . severe gastrointestinal disorders

CAUTIONS, FURTHER INFORMATION

▶ Screening for retinopathy

▶ In adults A review group convened by the Royal College of

Ophthalmologists has updated guidelines on screening for

chloroquine and hydroxychloroquine retinopathy

(Hydroxychloroquine and Chloroquine Retinopathy:

Recommendations on Screening 2018). Chloroquine appears

to be more retinotoxic than hydroxychloroquine.

Screening recommendations for chloroquine:

. All patients planning to be on long-term treatment

should receive a baseline examination (including fundus

photography and spectral domain optical coherence

tomography) within 6-12 months of treatment

initiation;

. Annual screening is recommended in all patients who

have taken chloroquine for greater than 1 year.

l INTERACTIONS → Appendix 1: antimalarials

l SIDE-EFFECTS

▶ Rare or very rare Cardiomyopathy . hallucination . hepatitis

▶ Frequency not known Abdominal pain . agranulocytosis . alopecia . anxiety . atrioventricular block . bone marrow

disorders . confusion . corneal deposits . depression . diarrhoea . eye disorders . gastrointestinal disorder. headache . hearing impairment. hypoglycaemia . hypotension . insomnia . interstitial lung disease . movement disorders . myopathy . nausea . neuromyopathy . neutropenia . personality change . photosensitivity

reaction . psychotic disorder. QT interval prolongation . seizure . severe cutaneous adverse reactions (SCARs). skin

reactions .thrombocytopenia .tinnitus .tongue protrusion . vision disorders . vomiting

616 Protozoal infection BNF 78

Infection

5

SIDE-EFFECTS, FURTHER INFORMATION Side-effects which

occur at doses used in the prophylaxis or treatment of

malaria are generally not serious.

Overdose Chloroquine is very toxic in overdosage;

overdosage is extremely hazardous and difficult to treat.

Urgent advice from the National Poisons Information

Service is essential. Life-threatening features include

arrhythmias (which can have a very rapid onset) and

convulsions (which can be intractable).

l PREGNANCY Benefit of use in prophylaxis and treatment

in malaria outweighs risk. For rheumatoid disease, it is not

necessary to withdraw an antimalarial drug during

pregnancy if the disease is well controlled.

l BREAST FEEDING Present in breast milk and breastfeeding should be avoided when used to treat rheumatic

disease. Amount in milk probably too small to be harmful

when used for malaria.

l HEPATIC IMPAIRMENT Manufacturer advises caution,

particularly in cirrhosis.

l RENAL IMPAIRMENT Manufacturers advise caution.

Dose adjustments Only partially excreted by the kidneys

and reduction of the dose is not required for prophylaxis of

malaria except in severe impairment.

For rheumatoid arthritis and lupus erythematosus,

reduce dose.

l MONITORING REQUIREMENTS

▶ In adults Manufacturers recommend regular

ophthalmological examination but the evidence of

practical value is unsatisfactory.

▶ In children Ophthalmic examination with long-term

therapy.

l PATIENT AND CARER ADVICE Warn travellers going to

malarious areas about importance of avoiding mosquito

bites, importance of taking prophylaxis regularly, and

importance of immediate visit to doctor if ill within 1 year

and especially within 3 months of return.

l NATIONAL FUNDING/ACCESS DECISIONS

NHS restrictions Drugs for malaria prophylaxis are not

prescribable in NHS primary care; health authorities may

investigate circumstances under which antimalarials are

prescribed.

l EXCEPTIONS TO LEGAL CATEGORY Can be sold to the public

provided it is licensed and labelled for the prophylaxis of

malaria.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug. Forms available

from special-order manufacturers include: oral solution

Oral solution

CAUTIONARY AND ADVISORY LABELS 5

▶ Malarivon (Wallace Manufacturing Chemists Ltd)

Chloroquine phosphate 16 mg per 1 ml Malarivon 80mg/5ml syrup

| 75 ml P £30.00 DT = £30.00

Tablet

CAUTIONARY AND ADVISORY LABELS 5

▶ Avloclor (Alliance Pharmaceuticals Ltd)

Chloroquine phosphate 250 mg Avloclor 250mg tablets | 20 tablet P £8.59 DT = £8.59

Chloroquine with proguanil

The properties listed below are those particular to the

combination only. For the properties of the components

please consider, chloroquine p. 616, proguanil hydrochloride

p. 618.

l INDICATIONS AND DOSE

Prophylaxis of malaria

▶ BY MOUTH

▶ Adult: (consult product literature)

l INTERACTIONS → Appendix 1: antimalarials

l EXCEPTIONS TO LEGAL CATEGORY Can be sold to the public

provided it is licensed and labelled for the prophylaxis of

malaria.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Tablet

▶ Paludrine/Avloclor (Alliance Pharmaceuticals Ltd)

Paludrine/Avloclor tablets anti-malarial travel pack | 112 tablet p

£13.50

Mefloquine 05-Aug-2018

l INDICATIONS AND DOSE

Treatment of malaria

▶ BY MOUTH

▶ Adult: (consult product literature)

Prophylaxis of malaria

▶ BY MOUTH

▶ Child (body-weight 5–15 kg): 62.5 mg once weekly, dose

to be started 2–3 weeks before entering endemic area

and continued for 4 weeks after leaving

▶ Child (body-weight 16–24 kg): 125 mg once weekly, dose

to be started 2–3 weeks before entering endemic area

and continued for 4 weeks after leaving

▶ Child (body-weight 25–44 kg): 187.5 mg once weekly,

dose to be started 2–3 weeks before entering endemic

area and continued for 4 weeks after leaving

▶ Child (body-weight 45 kg and above): 250 mg once

weekly, dose to be started 2–3 weeks before entering

endemic area and continued for 4 weeks after leaving

▶ Adult (body-weight 45 kg and above): 250 mg once

weekly, dose to be started 2–3 weeks before entering

endemic area and continued for 4 weeks after leaving

l UNLICENSED USE Mefloquine doses in BNF Publications

may differ from those in product literature.

▶ In children Not licensed for use in children under 5 kg

body-weight and under 3 months.

l CONTRA-INDICATIONS Avoid for prophylaxis if history of

psychiatric disorders (including depression) or convulsions

. avoid for standby treatment if history of convulsions . history of blackwater fever

l CAUTIONS Cardiac conduction disorders . epilepsy (avoid

for prophylaxis). not recommended in infants under

3 months (5 kg)(in children).traumatic brain injury

CAUTIONS, FURTHER INFORMATION

▶ Neuropsychiatric reactions Mefloquine is associated with

potentially serious neuropsychiatric reactions. Abnormal

dreams, insomnia, anxiety, and depression occur

commonly. Psychosis, suicidal ideation, and suicide have

also been reported. Psychiatric symptoms such as

insomnia, nightmares, acute anxiety, depression,

restlessness, or confusion should be regarded as

potentially prodromal for a more serious event. Adverse

reactions may occur and persist up to several months after

discontinuation because mefloquine has a long half-life.

For a prescribing checklist, and further information on

side-effects, particularly neuropsychiatric side-effects,

which may be associated with the use of mefloquine for

malaria prophylaxis, see the Guide for Healthcare

Professionals provided by the manufacturer.

l INTERACTIONS → Appendix 1: antimalarials

l SIDE-EFFECTS

▶ Common or very common Anxiety . depression . diarrhoea . dizziness . gastrointestinal discomfort. headache . nausea . skin reactions . sleep disorders . vision disorders . vomiting

▶ Frequency not known Acute kidney injury . agranulocytosis . alopecia . aplastic anaemia . appetite decreased . arrhythmias . arthralgia . asthenia . behaviour abnormal .

BNF 78 Malaria 617

Infection

5

cardiac conduction disorders . cataract. chest pain . chills . concentration impaired . confusion . cranial nerve

paralysis . delusional disorder. depersonalisation . drowsiness . dyspnoea . encephalopathy . eye disorder. fever. flushing . gait abnormal . hallucination . hearing

impairment. hepatic disorders . hyperacusia . hyperhidrosis . hypertension. hypotension . leucocytosis . leucopenia . malaise . memory loss . mood altered . movement disorders . muscle complaints . muscle

weakness . nephritis . nerve disorders . oedema . palpitations . pancreatitis . paraesthesia . pneumonia . pneumonitis . psychosis . seizure . self-endangering

behaviour. speech disorder. Stevens-Johnson syndrome . suicidal tendencies . syncope .thrombocytopenia .tinnitus .tremor. vertigo

l ALLERGY AND CROSS-SENSITIVITY Contra-indicated in

patients with hypersensitivity to quinine.

l CONCEPTION AND CONTRACEPTION Manufacturer advises

adequate contraception during prophylaxis and for

3 months after stopping (teratogenicity in animal studies).

l PREGNANCY Manufacturer advises avoid (particularly in

the first trimester) unless the potential benefit outweighs

the risk; however, studies of mefloquine in pregnancy

(including use in the first trimester) indicate that it can be

considered for travel to chloroquine-resistant areas.

l BREAST FEEDING Present in milk but risk to infant

minimal.

l HEPATIC IMPAIRMENT Manufacturer advises avoid in

severe impairment—elimination may be prolonged.

l RENAL IMPAIRMENT Manufacturer advises caution.

l DIRECTIONS FOR ADMINISTRATION Tablet may be crushed

and mixed with food such as jam or honey just before

administration.

l PATIENT AND CARER ADVICE Manufacturer advises that

patients receiving mefloquine for malaria prophylaxis

should be informed to discontinue its use if

neuropsychiatric symptoms occur and seek immediate

medical advice so that mefloquine can be replaced with an

alternative antimalarial. Travellers should also be warned

about importance of avoiding mosquito bites,

importance of taking prophylaxis regularly, and

importance of immediate visit to doctor if ill within 1 year

and especially within 3 months of return.

A patient alert card should be provided.

Driving and skilled tasks Dizziness or a disturbed sense of

balance may affect performance of skilled tasks (e.g.

driving); effects may occur and persist up to several

months after stopping mefloquine.

l NATIONAL FUNDING/ACCESS DECISIONS

NHS restrictions Drugs for malaria prophylaxis are not

prescribable in NHS primary care; health authorities may

investigate circumstances under which antimalarials are

prescribed.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug.

Tablet

CAUTIONARY AND ADVISORY LABELS 10, 21, 27

▶ Lariam (Cheplapharm Arzneimittel GmbH)

Mefloquine (as Mefloquine hydrochloride) 250 mg Lariam 250mg

tablets | 8 tablet P £14.53 DT = £14.53

Primaquine

l INDICATIONS AND DOSE

Adjunct in the treatment of non-falciparum malaria

caused by P.vivax infection

▶ BY MOUTH

▶ Adult: 30 mg daily for 14 days

Adjunct in the treatment of non-falciparum malaria

caused by P.ovale infection

▶ BY MOUTH

▶ Adult: 15 mg daily for 14 days

Adjunct in the treatment of non-falciparum malaria

caused by P.vivax infection in patients with mild G6PD

deficiency (administered on expert advice)| Adjunct in

the treatment of non-falciparum malaria caused by

P.ovale infection in patients with mild G6PD deficiency

(administered on expert advice)

▶ BY MOUTH

▶ Adult: 45 mg once weekly for 8 weeks

Treatment of mild to moderate pneumocystis infection (in

combination with clindamycin)

▶ BY MOUTH

▶ Adult: 30 mg daily, this combination is associated with

considerable toxicity

l UNLICENSED USE Not licensed.

l CAUTIONS G6PD deficiency . systemic diseases associated

with granulocytopenia (e.g. juvenile idiopathic arthritis,

rheumatoid arthritis, lupus erythematosus)

l INTERACTIONS → Appendix 1: antimalarials

l SIDE-EFFECTS

▶ Common or very common Abdominal pain . appetite

decreased . nausea . vomiting

▶ Uncommon Haemolytic anaemia (more common in G6PD

deficiency) . leucopenia . methaemoglobinaemia

l PREGNANCY Risk of neonatal haemolysis and

methaemoglobinaemia in third trimester.

l BREAST FEEDING No information available; theoretical

risk of haemolysis in G6PD-deficient infants.

l PRE-TREATMENT SCREENING Before starting primaquine,

blood should be tested for glucose-6-phosphate

dehydrogenase (G6PD) activity since the drug can cause

haemolysis in G6PD-deficient patients. Specialist advice

should be obtained in G6PD deficiency.

l MEDICINAL FORMS There can be variation in the licensing of

different medicines containing the same drug. Forms available

from special-order manufacturers include: oral suspension

Tablet

▶ Primaquine (Non-proprietary)

Primaquine (as Primaquine phosphate) 7.5 mg Primaquine 7.5mg

tablets | 100 tablet £199.70

Primaquine (as Primaquine phosphate) 15 mg Primaquine 15mg

tablets | 100 tablet P s

Proguanil hydrochloride

l INDICATIONS AND DOSE

Prophylaxis of malaria

▶ BY MOUTH

▶ Child 4–11 weeks (body-weight up to 6 kg): 25 mg once

daily, dose to be started 1 week before entering

endemic area and continued for 4 weeks after leaving

▶ Child 3–11 months (body-weight 6–9 kg): 50 mg once daily,

dose to be started 1 week before entering endemic area

and continued for 4 weeks after leaving

▶ Child 1–3 years (body-weight 10–15 kg): 75 mg once daily,

dose to be started 1 week before entering endemic area

and continued for 4 weeks after leaving

▶ Child 4–7 years (body-weight 16–24 kg): 100 mg once

daily, dose to be started 1 week before entering

endemic area and continued for 4 weeks after leaving

▶ Child 8–12 years (body-weight 25–44 kg): 150 mg once

daily, dose to be started 1 week before entering

endemic area and continued for 4 weeks after leaving

618 Protozoal infection BNF 78

Infection

5

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