Information for Health Care Providers Prescription Drugs for Malaria
Determine your Patient's Risk
Malaria is transmitted to humans by the bite of an infected female Anopheles mosquito. All travelers to malaria-risk areas, including infants, children, and former residents of these areas, should take an antimalarial drug to prevent malaria. Malaria is always a serious disease and may be a deadly illness. Inform your patients that fever or flu-like illness, either while traveling or after returning home (for up to 1 year or more) may be malaria and that they should seek immediate medical attention.
CDC has several sources of information for health care providers about malaria risk areas, prophylaxis medications, and anti-mosquito measures:
- CDC's Fax Information Service - International Traveler's Health*
This toll-free fax service provides fax documents pertaining to traveler's health. Faxes are available on both general health precautions such as vaccinations, traveler's diarrhea, yellow fever, etc. plus a separate specific fax on malaria risk and prevention for each country in the world.
To request traveler's health faxes, call 1-888-232-3299; listen to the instructions. The document number for the directory of all traveler's health faxes is #000005.
*Identical malaria prevention information is provided at the CDC website and the toll-free Fax Information Service.
- CDC's Traveler's Health website at http://www.cdc.gov/travel/*
The website contains both general traveler's health precautions plus malaria-specific information on malaria-risk areas, prophylaxis, and anti-mosquito measures.
- Malaria Case Management Hotline Health care providers needing assistance with the diagnosis or management of suspected cases of malaria, may call the CDC Malaria Hotline: 770-488-7788 (M-F, 8am-4:30pm, eastern time). Emergency consultation after hours, call: 770-488-7100 and request to speak with a CDC Malaria Branch clinician.
Provide antimalarial drug dosages, schedules, and warnings
Advise patients that antimalarial drugs are most effective if taken exactly on schedule without skipping doses and that their drug should be continued post-travel for the most complete protection. Antimalarial drugs should be purchased before travel; drugs purchased overseas may not be manufactured according to United States standards and may not be effective. They may also be dangerous, contain the wrong drug or an incorrect amount of active drug, or be contaminated.
Halofantrine (marketed as Halfan) is widely used overseas to treat malaria. CDC does not recommend the use of Halfan because of serious cardiac complications, including deaths. Travelers should be advised to avoid Halfan unless they have been diagnosed with life-threatening malaria and no other options are immediately available.
Overdosage of antimalarial drugs can be fatal. Parents should be advised to keep drugs in childproof containers out of the reach of children.
Drugs used in the prophylaxis of malaria
DrugUsageAdult dose Pediatric doseComments
(See Adverse Reactions and Contraindications below)Atovaquone/proguanil(Malarone™)Primary prophylaxis* in areas with chloroquine-resistant or mefloquine-resistant Plasmodium falciparumAdult tablets contain 250 mg atovaquone and 100 mg proguanil hydrochloride.
1 adult tablet orally, daily Pediatric tablets contain 62.5 mg atovaquone and 25 mg proguanil hydrochloride.
11-20 kg: 1 tablet
21-30 kg: 2 tablets
31-40 kg: 3 tablets
> 40 kg: 1 **adult tablet daily
**Adult tablets contain 250mg atovaquone and 100mg proguanil hydrochloride.Contraindicated in persons with severe renal impairment (creatinine clearance < 30mL/min). Atovaquone/proguanil should be taken with food or a milky drink. Not recommended for children < 11 kg, pregnant women, and women breastfeeding infants weighing <11 kg.Chloroquine phosphate (Aralen™ and generic)Primary prophylaxis* only in areas with chloroquine-sensitive P. falciparum300 mg base (500 mg salt) orally, once/week 5 mg/kg base (8.3 mg/kg salt) orally, once/week, up to maximum adult dose of 300mg baseMay exacerbate psoriasisDoxycycline (Many brand names and generic)Primary prophylaxis* in areas with chloroquine-resistant or mefloquine-resistant P. falciparum100 mg orally, daily > 8 years of age: 2 mg/kg up to adult dose of 100mg/dayContraindicated in children < 8 years of age and pregnant womenHydroxychloroquine sulfate (Plaquenil™)An alternative to chloroquine for primary prophylaxis* only in areas with chloroquine-sensitive P. falciparum310 mg base (400 mg salt) orally, once/week 5 mg/kg base (6.5 mg/kg salt) orally, once/week, up to maximum adult dose of 310 mg base.See chloroquine comment.Mefloquine (Lariam™ and generic)Primary prophylaxis* in areas with chloroquine-resistant P. falciparum228 mg base (250 mg salt) orally, once/week **5 -10 kg: 1/8 tablet orally, once/week
**10-20 kg: ¼ tablet once/week
20-30 kg: ½ tablet, once/week
30-45 kg: ¾ tablet once/week
>45 kg: 1 tablet, once/week
**The recommended dose of mefloquine is 5mg/kg body weight once weekly. Approximate tablet fraction is based on this dosage. Exact doses for children weighing less than 10kg should be prepared by a pharmacist (see Chemoprophylaxis for Infants, Children, and Adolescents below).
Contraindicated in persons allergic to mefloquine and in persons with active depression or a previous history of depression, generalized anxiety disorder, psychosis, schizophrenia, other major psychiatric disorders, or seizures. Not recommended for persons with cardiac conduction abnormalities.PrimaquineAn option for primary prophylaxis* in special circumstances. Call Malaria Hotline (770-488-7788) for additional information.30 mg base (52.6 mg salt) orally, daily 0.6 mg/kg base (1.0 mg/kg salt) up to adult dose, orally, dailyContraindicated in persons with G6PD deficiency. Also contraindicated during pregnancy and lactation unless the infant being breast-fed has a documented normal G6PD level. Use in consultation with malaria experts.PrimaquineUsed for terminal prophylaxis*** to decrease risk of relapses of P. vivax and P. ovale.30 mg base (52.6 mg salt) orally, once/day for 14 days after departure from the malarious area.
Note: The recommended dose of primaquine for terminal prophylaxis has been increased from 15 mg to 30 mg for adults. 0.6 mg/kg base (1.0 mg/kg salt) up to adult dose orally, once/day for 14 days after departure from the malarious area.Note: The recommended dose of primaquine for terminal prophylaxis** has been increasedfrom 0.3 mg/kg to 0.6 mg/kg for children.Indicated for persons who have had prolonged exposure to P. vivax and P. ovale or both. Contraindicated in persons with G6PD deficiency. Also contraindicated during pregnancy and lactation unless the infant being breast-fed has a documented normal G6PD level.
Primary prophylaxis refers to the use of antimalarial drugs to prevent symptoms associated with the blood stage infection; these drugs are taken before, during, and for a period of time after travel in the malaria-risk area.
***Terminal prophylaxis refers to the use of primaquine to lower the risk of relapse from liver stage infection with Plasmodium vivax or P. ovale. Primaquine is taken after departure from the malaria-risk area.
Travel to areas with Chloroquine-resistant P. falciparum
Atovaquone/proguanil (Malarone ™ )
Atovaquone/ proguanil is a fixed combination of two drugs; in the United States, it is marketed as Malarone. Atovaquone/proguanil primary prophylaxis should begin 1-2 days before travel to malarious areas and should be taken daily, at the same time each day, while in the malarious area, and daily for 7 days after leaving such areas.
Doxycycline (brand names and generics)
Doxycycline primary prophylaxis should begin 1-2 days before travel to malarious areas. It should be continued once a day, at the same time each day, during travel in malarious areas, and daily for 4 weeks after the travelers leaves such areas.
Note: There are insufficient data on the antimalarial efficacy of related compounds such as minocycline; optimally, for patients already on minocycline, it should be discontinued prior to travel and doxycycline started. Minocycline can be restarted after the four weeks of post-exposure doxycycline is completed.
Mefloquine (Lariam ™ and generic)
Mefloquine primary prophylaxis should begin 1-2 weeks before travel to malarious areas. It should be continued once a week, on the same day each week, during travel to malarious areas, and for 4 weeks after the traveler leaves such areas.
Primaquine (primary prophylaxis)
If other antimalarial drugs cannot be used and in consultation with malaria experts (CDC Malaria Hotline 770-488-7788), primaquine may be used to prevent malaria while the traveler is in the malaria-risk area (primary prophylaxis).
Note: Travelers must be tested for G6PD deficiency (glucose-6-phosphate-dehydrogenase) and have a documented G6PD level in the normal range before primaquine use.
Primaquine primary prophylaxis should begin 1-2 days before travel to the malaria-risk area. It should be continued once a day, at the same time each day, while in the malaria-risk area, and daily for 7 days after leaving the malaria-risk area.
Travel to Areas with mefloquine-resistant P. falciparum
Mefloquine-resistant P. falciparum is present in eastern Burma (states of Shah, Kayin, and Kayah), the western provinces of Cambodia that border Thailand, and the provinces of Thailand that border Burma and Cambodia.
Either atovaquone/proguanil or doxycycline can be used by travelers to these areas.
Travel to areas with chloroquine-sensitive P. falciparum
Chloroquine (Aralen™, Plaquenil™, and generic)
In areas where chloroquine-resistant P. falciparum has not been reported, either chloroquine phosphate (Aralen and generic) or hydroxychloroquine sulfate (Plaquenil) may be used. Less evidence exists on hydroxychloroquine sulfate's effectiveness as an antimalarial drug.
Chloroquine primary prophylaxis should begin 1-2 weeks before travel to malarious areas. It should be continued once a week, on the same day of the week, during travel to malarious areas and for 4 weeks after a traveler leaves such areas.
Travelers unable to take chloroquine should take atovaquone/proguanil, doxycycline, mefloquine, or primaquine; these drugs are also effective against chloroquine-sensitive P. falciparum.
Adverse Reactions and Contraindications
The drugs used for antimalarial prophylaxis are generally well tolerated. However, side effects can occur. Minor side effects usually do not require stopping the drug. Travelers with serious side effects should be advised to see their health care provider.
The most common adverse effects reported in persons using atovaquone/proguanil for prophylaxis are abdominal pain, nausea, vomiting, and headache. Atovaquone/proguanil should not be used in infants <11kg, pregnant women, women breast-feeding infants <11kg, or patients with severe renal impairment (creatinine clearance <30mL/min).
Chloroquine phosphate and Hydroxychloroquine sulfate
Side effects that can occur include gastrointestinal disturbance, headache, dizziness, blurred vision, insomnia, and pruritus, but generally these effects do not require that the drug be discontinued. High doses of chloroquine, such as those used to treat rheumatoid arthritis, have been associated with retinopathy; this serious side effect appears to be extremely unlikely when chloroquine is used for routine weekly malaria prophylaxis. Chloroquine and related compounds may exacerbate psoriasis.
Doxycycline can cause sun sensitivity, usually manifested as an exaggerated sunburn reaction. Travelers on doxycycline should be advised to protect themselves by avoiding prolonged sun exposure and by using sunscreen that absorbs long-wave UVA radiation.
Doxycycline use may be associated with an increased frequency of Candida vaginitis. Travelers should be advised to take an over-the-counter yeast medication or a prescription drug or cream.
Gastrointestinal side effects (nausea or vomiting) may be minimized by taking the drug with a meal and a full glass of water. Travelers should be advised not to take doxycycline before going to bed to avoid esophagitis.
Doxycycline should not be taken by persons allergic to tetracyclines, pregnant women, and by children <8 years of age.
Mefloquine has been associated with rare serious adverse reactions (including psychoses or seizures) at prophylactic doses; these reactions are more frequent with the higher doses used for treatment. Other side effects that occur with prophylactic doses include gastrointestinal disturbance, headache, insomnia, abnormal dreams, visual disturbances, depression, anxiety disorder, and dizziness.
Mefloquine is contraindicated for use by travelers with a known hypersensitivity to mefloquine and in persons with active depression or a history of depression, or in persons with generalized anxiety disorder, psychosis, schizophrenia, or other psychiatric disturbances. Mefloquine is contraindicated in persons with a history of seizures (not including the type of seizure caused by high fever in childhood). Mefloquine is not recommended for persons with cardiac conduction abnormalities.
Primaquine can cause an hemolysis in G6PD-deficient persons, which can be fatal. Before primaquine is used, G6PD deficiency MUST be ruled out by appropriate laboratory testing.
Changing Medications During Chemoprophylaxis as a Result of Side Effects
Antimalarial drugs have different modes of action that affect the parasite at different stages of the life cycle. If medications need to be changed because of side effects, there are some special considerations. Travelers who start mefloquine or doxycycline but must switch to atovaquone/proguanil during or after travel must continue their atovaquone/proguanil for 4 weeks after switching or 1 week after returning, whichever is longer .
Assistance with the management of travelers who need to discontinue their antimalarial drug and switch to another is available at the CDC Malaria Hotline (770-488-7788).
Chemoprophylaxis for Infants, Children and Adolescents
Children of any age can contract malaria; all children traveling to a malaria-risk area should take an antimalarial drug. In the United States, antimalarial drugs are available only in tablet form and most taste quite bitter. Pediatric dosages should be carefully calculated based on the child's current weight; children's dosages should never exceed adult dosage.
Full-service (compounding) pharmacists can pulverize tablets, weigh out the precise dose, and place the dose in a gelatin capsule. Advise parents to open the gelatin capsule and mix the drug with something sweet such as applesauce, chocolate syrup, or jelly and to give the drug on a full stomach to minimize stomach upset and vomiting. Parents should allow sufficient time before travel to allow preparation of these dosages.
Additional information on preventing malaria in infants and children is available by requesting document #380012 or visiting the website: Preventing Malaria in Infants and Children.
Overdosage of antimalarial drugs can be fatal. Medication should be stored in childproof containers out of the reach of infants and children.
Chemoprophylaxis during Pregnancy and Lactation
Malaria infection in pregnant women can be more severe than in nonpregnant women. In addition, malaria can increase the risk for adverse pregnancy outcomes, including prematurity, abortion, and stillbirth. Because malaria is such a serious illness in pregnancy and because no chemoprophylactic regimen is completely effective, women who are pregnant or likely to become pregnant should be advised to avoid travel to a malaria-risk area.
If travel cannot be avoided, then use of an effective antimalarial drug is essential.
Travel during Pregnancy to areas with chloroquine-sensitive P. falciparum
Chloroquine phosphate or hydroxychloroquine sulfate are recommended for pregnant women traveling to areas with chloroquine-sensitive P. falciparum. Chloroquine has not been found to have any harmful effects on the fetus when used in the recommended doses for weekly prophylaxis.
Travel during Pregnancy to areas with chloroquine-resistant P. falciparum
Mefloquine is the only medication recommended for prophylaxis during pregnancy. Studies indicate that use during second and third trimesters is not associated with adverse fetal or pregnancy outcomes. More limited data suggest it is also safe during the first trimester.
Atovaquone/proguanil is not recommended during pregnancy due to a lack of sufficient safety data. Doxycycline is contraindicated during pregnancy because of the known risks of tetracycline on fetal development, including discoloration and dysplasia of the teeth and inhibition of bone growth. Primaquine should not be used during pregnancy because the drug may pass to a G6PD-deficient fetus and cause hemolytic anemia in utero .
Advice on the management of pregnant travelers is available; call the CDC Malaria Hotline at 770-488-7788.
Very small amounts of chloroquine and mefloquine are excreted in breast milk; the amount of drug is not sufficient to harm the infant nor is the quantity sufficient to protect the child from malaria. Breastfeeding infants should receive the recommended dosages of antimalarials found in the table above.
Very limited data are available on the use of doxycycline in lactating women; most experts consider the theoretical possibility of adverse events to be remote.
Primaquine should only be given to lactating women if both the woman and her infant have been tested for G6PD deficiency and have documented normal G6PD levels.
Because safety data is not yet available, atovaquone/proguanil is not currently recommended for women breastfeeding infants <11kg.
Additional information on preventing malaria in the pregnant woman is available by requesting document# 380008 or by viewing the website: Preventing Malaria in the Pregnant Woman.
Educate Your Patients on the Signs and Symptoms of Malaria
Advise your patients that they can still contract malaria despite prophylaxis and anti-mosquito measures. Inform travelers that fever or flu-like illness, either while traveling or after returning home (for up to 1 year or more), may be malaria and that they should seek immediate medical attention.
Malaria can be effectively treated early in the course of the disease; however, delay of appropriate treatment can have serious or even fatal consequences. Travelers who choose not to take an antimalarial drug or who are on a less than effective regimen (chloroquine in a chloroquine-resistant risk area) or who may be in very remote areas can be given a self-treatment course of atovaquone/proguanil.
Travelers on atovaquone/proguanil as their antimalarial drug regimen should not use atovaquone/proguanil as their self-treatment drug and should use an alternative self-treatment regimen; call the Malaria Hotline (770-488-7788) for advice on the management of travelers who cannot use atovaquone/proguanil for self-treatment.
Presumptive self-treatment regimen
Drug Adult DosePediatric dose CommentsAtovaquone/proguanil (Malarone). Self-treatment drug to be used if professional medical care is not available within 24 hours. Medical care should be sought immediately after treatment. 4 tablets (each dose contains 1,000 mg atovaquone and 400mg proguanil) orally as a single daily dose for 3 consecutive days. Daily dose to be taken for 3 consecutive days using adult-strength tablets:
11-20 kg: 1 tablet
21-30 kg: 2 tablets
31-40kg: 3 tablets
> 41kg: 4 tablets
Contraindicated in persons with severe renal impairment (creatinine clearance <30mL/min). Not recommended for self-treatment in persons on atovaquone/proguanil prophylaxis. Not currently recommended for children <11kg, pregnant women, and women breastfeeding infants <11kg.
Travelers should be advised to take their presumptive self-treatment promptly if they have a fever, chills, or other influenza-like illness and if professional medical is not available within 24 hours. Travelers should be advised to seek medical care immediately after self-treatment.
Prevention of Mosquito Bites
Malaria is transmitted by the bite of an infected Anopheles mosquito; these mosquitoes usually bite between dusk and dawn. Advise your patients to remain indoors, if possible, in a screened or air-conditioned area during the peak biting period. If out-of-doors, travelers should be advised to wear long-sleeved shirts, long pants, and hats and to apply insect repellent to exposed skin. Insect repellents that contain DEET (diethylmethyltoluamide) are the most effective repellents against a wide range of vectors.
Advise your patients to follow these precautions:
Travelers should also take a flying-insect spray on their trip to help clear rooms of mosquitoes. The product should contain a pyrethroid insecticide; these insecticides quickly kill flying insects, including mosquitoes.
- Read and follow the directions and precautions on the product label.
- Use only when outdoors and wash skin with soap and water after coming indoors.
- Do not breathe in, swallow, or get into the eyes. (DEET is toxic if swallowed). If using a spray product, apply DEET to your face by spraying your hands and rubbing the product carefully over the face, avoiding eyes and mouth.
- Do not put repellent on wounds or broken skin.
- Higher concentrations of DEET may have a longer repellent effect; however, concentrations over 50% provide no added protection.
- Timed-release DEET products may have a longer repellent effect than liquid products.
- DEET may be used on adults, children, and infants older than 2 months of age. Protect infants by using a carrier draped with mosquito netting with an elastic edge for a tight fit.
- Children under 10 years old should not apply insect repellent themselves. Do not apply to young children's hands or around eyes and mouth.
- Pregnant women should use insect repellents containing DEET, as recommended for other adults, but use sparingly. Wash off with soap and water after coming indoors.
Travelers not staying in well-screened or air-conditioned rooms should take additional precautions, including sleeping under mosquito netting (bed nets). Bed nets sprayed with the insecticide permethrin are more effective; permethrin both repels and kills mosquitoes. In the United States, permethrin is available as a spray or liquid (e.g. Permanone) to treat clothes and bed nets. Overseas, bed nets may be purchased that have already been treated with permethrin.
Permethrin or another insecticide, deltamethrin , may be purchased overseas to treat bed nets and clothes.
Date: July 8, 2005 Content Source: National Center for Infectious Diseases, Division of Global Migration and Quarantine