McKenna's Pharmacology for Nursing, 2e

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P A R T 2  Chemotherapeutic agents

■■ BOX 12.2  Combination drugs used for malaria prevention and treatment

■■ BOX 12.3  Antibiotics used to treat malaria

Contraindications and cautions Antimalarials are contraindicated in the presence of known allergy to any of these drugs; liver disease or alcoholism, both because of the parasitic invasion of the liver and because of the need for the hepatic metabolism to prevent toxicity ; and breastfeeding because the drugs can enter breast milk and could be toxic to the infant. Another method of feeding the baby should be used if treatment is necessary. These drugs should be avoided during pregnancy because they are associated with birth defects. With mefloquine, which is teratogenic in pre- clinical studies, pregnancy should be avoided during and for 2 months after completion of therapy. Use caution in people with retinal disease or damage because many of these drugs can affect vision and the retina, and the likelihood of problems increases if the retina is already damaged ; with psoriasis or porphyria because of skin damage ; or with damage to mucous membranes, which can occur as a result of the effects of the drug on proteins and protein synthesis. There have been some genetic enzyme differences identified in various groups that predispose them to adverse effects associated with these drugs . See Box 12.4 for cultural considerations and the use of some antimalarials. Oesophageal ulceration has been associated with the use of doxycycline. Therefore, it is important that doxy­ cycline should be administered with adequate amounts of fluid or food and the person should remain sitting or standing for up to 2 hours afterwards to prevent the possible development of oesophageal irritation. Adverse effects A number of adverse effects may be encountered with the use of these antimalarial agents. Central nervous system (CNS) effects include headache and dizziness. Immune reaction effects related to the release of mero- zoites include fever, shaking, chills and malaise. Nausea, vomiting, dyspepsia and anorexia are associated with direct effects of the drug on the GI tract and the effects With the emergence of chloroquine-resistant strains of Plasmodium , the use of quinine and another of the following antibiotics is recommended as a combination therapy for the treatment of uncomplicated or severe malaria caused by strains with unknown resistance: doxycycline: Adult and paediatric (>8 yrs): 100 mg/ day PO for 2 days prior to entering malaria region, continuing during stay and for 2 weeks after leaving. tetracycline: 250 mg PO for 7 days for adults; 25 mg/kg per day PO in divided doses q.i.d. for 7 days for children See Chapter 9 for a full discussion of these drugs.

Two fixed-combination drugs are available for use in the prevention and treatment of malaria. Combining two different preparations in one drug may increase compliance by reducing the number of pills a person has to take, and it conforms to the treatment protocol of taking drugs that affect the protozoa at different stages of their life cycle. P. falciparum malaria. Riamet is contraindicated in the first trimester of pregnancy and women should be advised to use barrier contraceptives while taking it. Breastfeeding should not commence for at least 4 weeks after the last dose as little data exists on effects on the infant. Usual dosage, acute attack: Adult and paediatric (>35 kg or >12 years): 6 doses of 4 tablets PO over 60 hours Paediatric (5–35 kg and >3 months–12 years): 6 doses of 1–3 tablets PO over 60 hours Malarone and Malarone Junior combine atovaquone and proguanil. They are indicated for the prevention of P. falciparum malaria when chloroquine resistance has been reported. They are used for the treatment of uncomplicated P. falciparum malaria when mefloquine has not proved successful, most likely because of resistance. This combination should be used in pregnancy and breastfeeding only if the benefit clearly outweighs the potential risk to the fetus or neonate. Usual dosage, acute attack: Adult: 4 tablets PO as a single daily dose for 3 consecutive days Paediatric (11–20 kg): 1 adult tablet PO daily for 3 consecutive days Paediatric (21–30 kg): 2 adult tablets PO daily as a single daily dose for 3 consecutive days Paediatric (31–40 kg): 3 adult tablets PO daily as a single daily dose for 3 consecutive days Paediatric (>40 kg): 4 adult tablets PO daily as a single daily dose for 3 consecutive days Prevention: Adult: 1 tablet PO daily Riamet is a combination of artemether and lumefantrine. It is indicated for treatment of Paediatric (11–20 kg): 1 junior tablet PO daily Paediatric (21–30 kg): 2 junior tablets PO daily Paediatric (31–40 kg): 3 junior tablets PO daily Paediatric (>40 kg): 1 adult tablet PO daily Prevention should start 1–2 days before exposure and continue throughout plus 7 days after leaving the area.

occurs in the liver; caution should be used in individuals with hepatic dysfunction. Primaquine is readily absorbed and metabolised in the liver. Excretion occurs primarily in the urine. Safety for use during pregnancy has not been established.