Archive for the ‘mefloquine’ Tag

What are the salt & base equivalents for antimalarials?   Leave a comment

by convention, quinine dosage is given in salt units while its derivatives are usually given in base units, except for mefloquine which is complicated. The highlighted units below are the ones in common use. Remember to state clearly whether you are referring to the base or salt when writing the prescription! This discussion applies to oral formulations only.

Quinine sulphate: 300mg salt = 250mg base

Chloroquine phosphate: 150mg base = 250mg salt

Hydroxychloroquine: 155mg base = 200mg salt

Mefloquine hydrochloride: 250mg salt = 228mg base (in the United States)
(however, in some countries mefloquine is available as 250mg base which = 274mg salt; in these countries I presume that “250mg mefloquine” refers to the base formulation, and patients receive a 9.6% higher dosage than their counterparts elsewhere. But, most internationally-recognised publications refer to the 250mg salt formulation available in the US.)

Amodiaquine hydrochloride: 200mg base = 260mg salt

Primaquine phosphate: 15mg base = 26.3mg salt
 

Ref:

  1. White NJ. The Treatment of Malaria. N Engl J Med 1996 Sep 12;335(11):800-806.
  2. Freedman DO. Malaria Prevention in Short-Term Travelers. N Engl J Med 2008 Aug 7;359(6);603-12. Table 3, Drug Regimes for Prophylaxis Against Malaria; p.608.
  3. Lariam package insert (Roche – US), rev Sep 2008 (PDF file)
  4. Drugs.com (Archived) [Internet]. c2000-2009 [revised 2001 Jan 24; cited 2009 May 8]. Available from:
    http://www.drugs.com/mmx/mefloquine-hydrochloride.html#citec00139613

Malaria Endemic and Resistance Patterns of the World   1 comment

links below lead to the CDC public-access website, updated July 2011

Malaria endemicity:

for more detailed information by country, see Yellow Fever & Malaria Information by Country, CDC website.

 

Malaria resistance:
Most notably resistance of P. falciparum to chloroquine and mefloquine. Updated 10 Oct 2011.

  • Resistance to chloroquine: all areas except the Carribean, Central America west of the Panama Canal, and some countries in the Middle East.
  • Resistance to Fansidar: Amazon river basin of S. America, much of Southeast Asia and other parts of Asia, large parts of Africa.
  • Resistance to mefloquine: borders of Thailand with Myanmar and Cambodia, western provinces of Cambodia, eastern states of Myanmar, Myanmar-China border, along the Laos-Myanmar border and adjacent Thai-Cambodia border, and southern Vietnam. see Distribution of mefloquine-resistant malaria in Indochina

 
Ref:
CDC Travelers’ Health — Yellow Book 2012. Chap 3: Infectious Diseases Related to Travel: Malaria [Internet]. Atlanta (GA): Centers for Disease Control and Prevention; 2011 Jul 1. [updated 2011 Jul 1; cited 2011 Oct 10]. Available at:
http://wwwnc.cdc.gov/travel/yellowbook/2012/chapter-3-infectious-diseases-related-to-travel/malaria.htm

Chemopropylaxis & dosage for travel to malaria-endemic countries   Leave a comment

CQ-sensitive areas
chloroquine (or hydroxychloroquine) as first line, if contraindicated then one of the others
(map: see here)
Pregnancy: avoid travel to malaria-endemic areas; if travel is unavoidable, use CQ as first line, otherwise mefloquine (but data limited for use of MQ in first trimester).

CQ-resistant areas
mefloquine as first line, if contraindicated then Malarone or doxycycline
(map: see here)
Pregnancy: MQ only. Both the WHO and the CDC recommend that pregnant women try not to travel to malaria-endemic areas. If travel is unavoidable, the trip should preferably be delayed to after the first trimester, as data is limited on use of MQ in the first trimester.

MQ-resistant areas
doxycycline or Malarone
(map: see here)
Pregnancy: consult infectious disease/malaria specialist

Terminal prophylaxis or presumptive anti-relapse therapy
primaquine. Indicated only for persons who have had prolonged or obvious intense exposure to infective mosquitoes in areas where there is a substantial risk of P. vivax or P. ovale transmission (for eg. missionaries and Peace Corps volunteers).
Pregnancy: PQ is contraindicated as it causes haemolytic anaemia in utero. When terminal prophylaxis is indicated, continue CQ/MQ prophylaxis until delivery, after which PQ may be started.

Legend:
CQ = chloroquine; HCQ = hydroxychloroquine
MQ = mefloquine
PQ = primaquine

 

Notes on other regimes:

  1. Halofantrine is not recommended by CDC for malaria prophylaxis.

  2. Primaquine may be used by itself as a primary prophylaxis regime in special circumstances when patients cannot tolerate any of the other drugs, but only after consulting with an infectious disease/malaria expert. Dosage is orally 30mg base daily (0.5mg base/kg/day for children up to adult dose) starting 1-2 days before entering, and continuing for 7 days after leaving the malarious area.

  3. Chloroquine + proguanil (CQ+PG) was still offered as an alternate regime by UK guidelines in 2007 for UK residents who travel to chloroquine-resistant areas (except sub-Saharan Africa), the rationale being that chloroquine resistance is considered incomplete in many areas and protection could be extended by the addition of proguanil. Although theoretically safer (especially for pregnant women), this regime is complicated; and, in light of waning efficacy in many parts of the world, and better availability and experience with using Malarone and mefloquine, I do not advise traveler to Asia take the CQ+PG combination, unless recommended by an infectious-disease expert.

  4. Maloprim (pyrimethamine 12.5mg + dapsone 100mg) has largely been superseded by Malarone, mainly due to its requirement for daily dosing, low therapeutic ratio, and risk of agranulocytosis. It is not recommended anymore for malaria prophylaxis in several parts of the world, including UK and USA; however it remains useful as an alternate regime if travelers are unable to tolerate any of the other regimes.

 

Recommended Dosages

  1. Chloroquine: orally 300mg base once weekly (5mg base/kg/week in children, up to adult dose) starting 2 weeks before entering, and continuing for 4 weeks after leaving malarious area

    • SE: GI disturbance, headache, dizziness, pruritus in African descent, rarely blood dyscrasias; retinopathy in overdose

    • CI: epilepsy, psychosis, psoriasis, QTc prolongation, myasthenia gravis; caution in severe renal failure

    • DI: increases toxicity of mefloquine, cyclosporin, digoxin; increased risk of ventricular arrhythmias with amiodarone, moxifloxacin

    • Pregnancy: chloroquine has not been found to have any harmful effects on the fetus when used in the recommended doses for malaria prophylaxis

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  3. Hydroxychloroquine (Plaquenil): orally 310mg base once weekly (5mg base/kg/week in children, up to adult dose) same regime as chloroquine

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  5. Malarone(250mg atovaquone + 100mg proguanil): orally one adult tab daily, start 1-2 days before entering, and continuing for 7 days after leaving malarious area. (paeds dosing, see here)

    • SE: gastric intolerance, diarrhoea, headache; occasionally stomatitis and mouth ulcers with proguanil

    • CI: children <5kg; CCT<30ml/min and dialysis; avoid in pregnancy but no evidence of foetal harm in inadvertent conception

    • DI: possible interaction with indinavir, zidovudine

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  7. Mefloquine (Lariam): orally 228mg base weekly (4.6mg base/kg/week in children, up to adult dose) beginning 2 weeks before entering, and continuing for 4 weeks after leaving malarious area.

    • SE: GI, headache, seizures, psychosis, insomnia, abnormal dreams, mood changes, visual disturbances, sensory/motor neuropathies, tremor, ataxia, AV block, prolonged QTc; not recommended for pilots and other occupations that require fine psychomotor skills or coordination

    • CI: known psychiatric disorders, depression, seizures, cardiac conduction abn; no evidence to suggest CI in underwater diving but may complicate decompression sickness and narcosis by lowering seizure threshold, hence to be avoided if possible

    • preferably start 3 weeks before travel to assess for tolerability

    • safe for use in renal failure and dialysis

    • Pregnancy: considered safe after first trimester; data is limited on use during first trimester

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  9. Doxycycline: orally 100mg daily (2mg/kg/day in children up to adult dose) starting 1-2 days before entering, and continuing for 4 weeks after leaving malarious area

    • SE: photosensitivity, gastritis, esophagitis, candidiasis, vaginal thrush

      take with full glass of water, and remain upright 30min

    • CI: pregnancy, children <8y

    • DI: increases anticoagulant effect of warfarin; increases toxicity of cyclosporin; avoid taking oral typhoid vaccine Ty21a within 24h

    • safe for use in renal failure
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  11. Primaquine as terminal prophylaxis: orally 30mg base daily (children: 0.6mg base/kg/d) for 14 days, to start after leaving malarious area; usually coinciding with the final 2 weeks of primary prophylaxis, but may be taken immediately after regime is completed

    • SE: GI upset on empty stomach, methaemoglobinaemia

    • CI: G6PD deficiency, pregnancy; also in breastfeeding unless baby has documented normal G6PD levels

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Ref:

  1. Freedman DO. Malaria Prevention in Short-Term Travelers. N Engl J Med 2008 Aug 7;359(6):603-12.

  2. CDC Travelers’ Health — Yellow Book 2008. Chap 4: Prevention of Specific Infectious Diseases: Malaria [Internet]. Atlanta (GA): Centers for Disease Control and Prevention; 2007 June 20. [updated 2009 Apr 17; cited 2009 Apr 20]. Available at:
    http://wwwn.cdc.gov/travel/yellowBookCh4-Malaria.aspx

  3. Chiodini P, Hill D, Lalloo D, Lea G, Walker E, Whitty C and Bannister B. Guidelines for malaria prevention in travellers from the United Kingdom. London, Health Protection Agency, January 2007.