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Drugs (generic and trade name) for the treatment and prevention of malaria

Summary of information, including doses, for the antimalarial drugs routinely used in Canada

ATOVAQUONE-PROGUANIL (ATQ-PG) (Malarone®) (Malarone® Pediatric)
Indication Prevention and treatment of P. falciparum and P. vivax malaria
Adult dosage Adult tablet:
250 mg atovaquone plus 100 mg proguanil hydrochloride

Prevention: 1 tablet daily; start one day before entering malaria-endemic area and continue during exposure and for 7 days after leaving

Treatment:
1,000 mg atovaquone AND 400 mg proguanil (4 tablets) once daily × 3 days
Pediatric dosage Pediatric tablets
62.5 mg atovaquone plus 25 mg proguanil hydrochloride

Prevention: >1 tablet daily; start 1 day before entering malarialarea and continue during exposure and for 7 days after leaving;

  • < 11 kg: see Chapter 5 (based on a pediatric tablet of 62.5 mg atovaquone/25 mg proguanil, the daily doses are ½ pediatric tablet for 5-8 kg, and ¾ pediatric tablet for > 8 to 10 kg)
  • 11-20 kg: 1 pediatric tablet daily
  • > 20-30 kg: 2 pediatric tablets daily (as single dose)
  • > 30-40 kg: 3 pediatric tablets daily (as single dose)
  • > 40 kg: 1 adult tablet daily

Treatment: 20 mg/kg atovaquone AND 8 mg/kg proguanil once daily × 3 days;

  • < 11 kg: (based on a pediatric tablet of 62.5 mg atovaquone/25 mg proguanil, the daily doses are 2 pediatric tablets for 5 to 8 kg, and 3 pediatric tablets for > 8 to 10 kg)
  • 11-20 kg: 1 adult tablet daily
  • >20-30 kg: 2 adult tablets daily
  • >30-40 kg: 3 adult tablets daily
  • > 40 kg: 4 adult tablets daily
Advantage Causal prophylaxis - only have to continue for 7 days after exposure
Disadvantage Daily dosing for prophylaxis
Adverse effects Frequent:
  • Nausea,
  • vomiting,
  • abdominal pain,
  • diarrhea,
  • increased transaminases

Rare:

  • Seizures,
  • rash,
  • mouth ulcers,
  • hepatitis
ARTESUNATE Vial 110 mg powder and vial buffered diluent
Indication Treatment of severe and complicated malaria
Adult dosage Treatment:
2.4 mg/kg intravenous bolus at hours 0, 12, 24 and 48 with possible doses daily for total of 7 days if concurrent doxycycline, ATQ-PG or clindamycin are not tolerated (see Chapter 7)
Pediatric dosage Treatment:
2.4 mg/kg at hours 0, 12, 24 and 48 with possible doses daily for total of 7 days if concurrent doxycycline, ATQ-PG or clindamycin are not tolerated (see Chapter 7)
Advantage Faster response than parenteral quinine; no cardiovascular or hypoglycemic effects
Disadvantage Requires concurrent therapy with second drug
Adverse effects Frequent:
  • Dizziness,
  • nausea,
  • vomiting,
  • anorexia,
  • diarrhea,
  • transient reticulocytopenia,
  • metallic taste during infusion

Occasional:
Urticarial rash

Rare:
Severe allergic reactions (65)
CHLOROQUINE (Novo-Chloroquine) Tablet: 155 mg chloroquine base (250 mg chloroquine diphosphate)
Indication Prevention and treatment in chloroquine- sensitive P. falciparum and P. vivax areas Treatment of, P. ovale, P. malariae and P. knowlesi infections
Adult dosage Prevention: 310 mg base once weekly; start 1 week before entering malaria-endemic area and continue during exposure and for 4 weeks after leaving Treatment: Loading dose of 620 mg base, followed by 310 mg base 6 hours later. This is followed by 310 mg base on each of the next 2 days for a total of 1.55 g base
Pediatric dosage Prevention: 5 mg base/kg once weekly; maximum 310 mg base weekly; start 1 week before entering malaria-endemic area and continue during exposure and for 4 weeks after leaving 15-20 kg: ½ tablet >20-25 kg: ¾ tablet >25-35 kg: 1 tablet >35-50 kg: 1½ tablets > 50 kg: 2 tablets Treatment: Total dose of 25 mg base/kg over 3 days: 10 mg base/kg (not to exceed 620 mg base) on days 1 and 2, 5 mg base/kg on day 3
Advantage Long-term safety data for prophylaxis
Disadvantage Most areas now report chloroquine resistance
Adverse effects Frequent:
  • Pruritis in black-skinned individuals,
  • nausea,
  • headache

Occasional:

  • Skin eruptions,
  • reversible corneal opacity

Rare:

  • Nail and mucous membrane discoloration,
  • partial alopecia,
  • photophobia,
  • nerve deafness,
  • myopathy,
  • retinopathy with daily use,
  • blood dyscrasias,
  • psychosis and
  • seizures
CLINDAMYCIN (Dalacin C®, Apo-Clindamycin, Novo-Clindamycin, Clindamycine, Clindamycin Injection)
Indication Alternative treatment for P. falciparum with a second drug if standard therapy contraindicated
Adult dosage Prevention:
no indication

Treatment oral:
300 mg base every 6 hrs for 7 days

Treatment IV:
10 mg/kg (loading dose) IV followed by 5 mg/kg every 8 hours for 7 days until oral therapy (20 mg/kg/d orally divided TID-QID) is tolerated.

NOTE: Should only use if the traveller is unable to take doxycycline or ATQ--PG
Pediatric dosage Prevention:
no indication

Treatment oral:
5 mg base/kg every 6 hours for 7 days

Treatment IV:
10 mg/kg (loading dose) IV followed by 5 mg/kg every 8 hours for 7 days until oral therapy (20 mg/kg/d orally divided TID-QID) is tolerated.

NOTE: Should only use if the traveller is unable to take doxycycline or ATQ-PG
Advantage Safe in pregnancy and young children
Disadvantage Lower efficacy than ATQ-PG alone or combination of doxycycline plus quinine
Adverse effects Frequent:
  • Diarrhea,
  • rash

Occasional:
Pseudomembranous colitis

Rare:

  • Hepatotoxicity,
  • blood dyscrasias
DOXYCYCLINE (Vibra-Tabs®, Apo-Doxy, Doxycin, Novo-Doxylin, Nu-Doxycycline, ratio-Doxycycline)
Indication Prevention of chloroquine-resistant P. falciparum; treatment of chloroquine-resistant P. falciparum when combined with a second drug
Adult dosage Prevention: 1 tablet (100 mg) once daily; start 1 day before entering malaria-endemic area and continue during exposure and for 4 weeks after leaving Treatment: 1 tablet (100 mg) or 100 mg IV twice daily for 7 days
Pediatric dosage Prevention:
  • < 25 kg or < 8 yr: contraindicated
    • Start 1 day before entering malaria-endemic area and continue during exposure and for 4 weeks after leaving
    • 2 mg base/kg po once daily (max 100 mg daily)
  • 25-35 kg: 50 mg daily
  • > 35-50 kg: 75 mg daily
  • > 50 kg: 100 mg daily

Treatment:

  • < 25 kg or < 8 yr: contraindicated
    2 mg base/kg po or IV twice daily (max. 200 mg daily)
  • 25-35 kg: 50 mg twice daily
  • > 35-50 kg: 75 mg twice daily
  • > 50 kg: 100 mg twice daily for 7 days
Advantage Protection against leptospirosis
Disadvantage Daily dosing required for chemoprophylaxis
Adverse effects Frequent:
  • Gastrointestinal upset,
  • vaginal candidiasis,
  • photosensitivity

Occasional:
Azotemia in renal diseases

Rare:

  • Allergic reactions,
  • blood dyscrasias,
  • esophageal ulceration
HYDROXYCHLOROQUINE (Plaquenil, Apo-Hydroxyquine, Gen-Hydroxychloroquine) Tablet: 155 mg base
Indication Prevention and treatment in chloroquine- sensitive P. falciparum and P. vivax areas Treatment of P. ovale, P. malariae and P. knowlesi infections
Adult dosage Prevention: 310 mg base once weekly; start 1 week before entering malaria-endemic area and continue during exposure and for 4 weeks after leaving Treatment: Loading dose of 620 mg base, followed by 310 mg base 6 hours later. This is followed by 310 mg base on each of the next 2 days for a total of 1.55 g base
Pediatric dosage Prevention: 5 mg base/kg once weekly; maximum 310 mg base weekly; start 1 week before entering malaria-endemic area and continue during exposure and for 4 weeks after leaving Treatment: Total dose of 25 mg base/kg over 3 days: 10 mg base/kg (not to exceed 620 mg base) on days 1 and 2, 5 mg base/kg on day 3
Advantage Long-term safety data for prophylaxis
Disadvantage Most areas now report chloroquine resistance
Adverse effects Frequent:
  • Pruritis in black-skinned individuals,
  • nausea,
  • headache

Occasional:

  • Skin eruptions,
  • reversible corneal opacity

Rare:

  • Nail and mucous membrane discoloration,
  • partial alopecia,
  • photophobia,
  • nerve deafness,
  • myopathy,
  • retinopathy with daily use,
  • blood dyscrasias,
  • psychosis and
  • seizures
MEFLOQUINE (Lariam®, Apo-Mefloquine)
Indication Prevention of P. falciparum
Adult dosage Prevention:
Start at least 1 week (preferably 2–3 weeks) before departure and continue during exposure and for 4 weeks after leaving

Loading dose – see text on page 76 (section on mefloquine) 250 mg once weekly

Treatment:
Not routinely recommended (see Chapter 7)
Pediatric dosage Prevention:
Start at least 1 week (preferably 2–3 weeks) before departure and continue during exposure and for 4 weeks after leaving

Loading dose – see text on page 76 (section on mefloquine) 5 mg/kg once weekly

  • < 5 kg: no data (see Chapter 4 and Chapter 5)
  • 5–10 kg: 1/8 tablet
  • > 10–20 kg: ¼ tablet
  • > 20–30 kg: ½ tablet
  • > 30–45 kg: ¾ tablet
  • > 45 kg: 1 tablet

Treatment:
Not routinely recommended (see Chapter 7)
Advantage Weekly dosing
Long-term safety data
Disadvantage There have been occasional publicized cases of severe intolerance to mefloquine, which may result in increased concern. If mefloquine is the best choice but concern is expressed, consider either a loading dose or start 3 weeks before departure to test for tolerability
Adverse effects Frequent:
  • Dizziness,
  • headache,
  • sleep disorders,
  • nightmares,
  • nausea,
  • vomiting,
  • diarrhea

Occasional:

  • Sensory and motor neuropathies,
  • seizures,
  • abnormal coordination,
  • confusion,
  • hallucinations,
  • forgetfulness,
  • emotional problems,
  • including anxiety,
  • aggression,
  • agitation,
  • depression,
  • mood changes,
  • panic attacks,
  • psychotic or paranoid reactions,
  • restlessness

Rare:
Suicidal ideation and suicide (relation to drug administration not established)
PRIMAQUINE (Primaquine phosphate)
Indication Prevention of chloroquine-resistant P. falciparum; terminal prophylaxis for P. vivax andP. ovale (PART); radical cure for P. vivax and P. ovale bloodstream infections
Adult dosage Prevention:
Primary prophylaxis 30 mg base daily.
Start 1 day before entering malarial area and continue during exposure and for 7 days after leaving

Terminal prophylaxis (PART) or radical cure:
30 mg base/day for 14 days
Pediatric dosage Prevention:
Primary prophylaxis 0.5 mg base/kg daily.
Start 1 day before entering malarial area and continue during exposure and for 7 days after leaving

Terminal prophylaxis or radical cure:
0.5 mg base/kg daily for 14 days
Advantage Causal prophylaxis - only have to continue for 7 days after exposure
Disadvantage Daily dosing
Require G6PD testing (see Chapter 4)
Adverse effects Occasional:
  • GI upset,
  • hemolysis in G6PD deficiency,
  • methemoglobinemia
QUINIDINE GLUCONATE-SULPHATE
a

Where possible, refer the person to a compounding pharmacy, and dose at 5 mg/kg once weekly; tablet cannot be accurately subdivided into ¼ or 1/8 portions
Adult dosage Prevention:
no indication

Treatment:
see Chapter 7, Box 7.1
Pediatric dosage Prevention:
no indication

Treatment:
Disadvantage Parenteral therapy requires cardiac monitoring
Adverse effects Frequent:
  • Vomiting,
  • cramps,
  • cinchonism
    • tinnitus,
    • nausea,
    • headache,
    • blurred vision

Occasional:

  • Widening of QRS complex,
  • cardiac disturbance,
  • fever,
  • delirium,
  • rashes

Rare:
Acute hemolytic anemia
QUININE DIHYDROCHLORIDE
Adult dosage Prevention:
no indication

Treatment:
see Chapter 7, Box 7.1
Pediatric dosage Prevention:
no indication

Treatment:
see Chapter 7, Box 7.1
Adverse effects Frequent:
  • Cinchonism
    • tinnitus,
    • nausea,
    • headache,
    • blurred vision
  • hypoglycemia

Occasional:

  • Cardiac conduction disturbances,
  • hypersensitivity

Rare:
Hemolysis
QUININE SULPHATE (Novo-Quinine®, Apo-Quinine, Quinine-Odan)
Adult dosage Prevention:
no indication

Treatment oral:
500 mg base 3 times daily for 3-7 days (7 days for SE Asia)

IV: see Chapter 7, Box 7.1
Pediatric dosage Prevention:
no indication

Treatment oral:
7.5 mg base/kg (max 500 mg base) 3 times daily for 3-7 days (7 days for SE Asia)

IV: see Chapter 7, Box 7.1
Adverse effects Similar to above

Abbreviations:

  • ATQ-PG, atovaquone-proguanil;
  • IV, intravenous;
  • ART, artemisinin-based combination therapy;
  • G6PD, glucose-6-phosphate dehydrogenase;
  • GI, gastrointestinal;
  • P., Plasmodium;
  • po, by mouth;
  • q, every;
  • QID, 4 times/day;
  • SE, southeast;
  • TID, 3 times/day.

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