proguanil


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Related to proguanil: mefloquine

atovaquone/proguanil

(a-toe-va-kwone/pro-gwa-nil),

Malarone

(trade name)

Classification

Therapeutic: antimalarials
Pregnancy Category: C

Indications

Prevention of malaria caused by Plasmodium falciparum, including chloroquine-resistant strains.Treatment of acute, uncomplicated P. falciparum malaria; effective for many drug-resistant strains.

Action

Atovaquone is a selective inhibitor of parasite mitochondrial transport.
Proguanil's metabolite, cycloguanil, is a dihydrofolate reductase inhibitor.
Both interfere with pyrimidine synthesis required for nucleic acids and replication are active against both erthrythrocytic and exoerythrocytic stages of Plasmodiumspp.

Therapeutic effects

Prevention/treatment of malarial illness and its sequelae.

Pharmacokinetics

Absorption: Atovaquone—variably absorbed following oral administration, food enhances absorption; Proguanil—well absorbed following oral administration.
Distribution: Proguanil— enters breast milk in small quantities.
Protein Binding: Atovaquone—>99%.
Metabolism and Excretion: Atovaquone—undergoes enterohepatic recycling, >94% eliminated unchanged in feces; Proguanil— metabolized mostly by the CYP2C19 enzyme system and is converted to cycloguanil, the pharmacologically active metabolite.
Half-life: Atovaquone—adults: 2–3 days, children: 1–2 days Cycloguanil—Adults: 8.3 hr, elderly: 14.9 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
atovaquone POunknown1–8 hr; 24–96 hr†24 hr
proguanil POunknownunknown24 hr
† Two peaks are due to enterohepatic recycling.

Contraindications/Precautions

Contraindicated in: Hypersensitivity to atovaquone or proguanil; Severe renal impairment (CCr <30 mL/min.
Use Cautiously in: Nausea or vomiting; may require repeat dosing and/or prophylactic use of anti-emetics; Severe malaria; oral agents are insufficient; Geriatric: Dose carefully, considering age-realated decrease in body mass, hepatic/renal/cardiac function, concurrent disease states and drug therapy; Obstetric: Pregnancy; malaria is a more serious illness, consider risk/benefit of travel to endemic areas, use only if potential benefit outweighs risk to the fetus.; Lactation: Use cautiously; proguanil enters breast milk; Pediatric: Safe and effective use in children <5 kg has not been established.

Adverse Reactions/Side Effects

Prophylaxis of Malaria

Central nervous system

  • dizziness
  • dreams
  • headache
  • insomnia

Ear, Eye, Nose, Throat

  • visual difficulties

Gastrointestinal

  • abdominal pain
  • oral ulcers

Treatment of Malaria

Central nervous system

  • headache (most frequent)
  • dizziness
  • weakness

Gastrointestinal

  • abdominal pain (most frequent)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • anorexia
  • ↑ liver enzymes

Dermatologic

  • pruritus (↑ in children)
  • photosensitivity

Hematologic

  • neutropenias

Miscellaneous

  • allergic reactions including anaphylaxis

Interactions

Drug-Drug interaction

Rifampin, rifabutin, metoclopramide and tetracylcine ↓ atovaquone levels.Atovaquone ↓ trough levels of indinavir ; use cautiously.

Route/Dosage

Prevention of Malaria
Oral (Adults and Children > 40 kg) One adult strength tablet (atovaquone 250 mg/proguanil 100 mg) once daily 1–2 days prior to entering endemic area and continued for seven days following return.
Oral (Children 31–40 kg) Three pediatric tablets (atovaquone 187.5 mg/proguanil 75 mg) once daily 1–2 days prior to entering endemic area and continued for seven days following return.
Oral (Children 21–30 kg) Two pediatric tablets (atovaquone 125 mg/proguanil 50 mg) once daily 1–2 days prior to entering endemic area and continued for seven days following return.
Oral (Children 11–20 kg) One pediatric tablet (atovaquone 62.5 mg/proguanil 25 mg) once daily 1–2 days prior to entering endemic area and continued for seven days following return.
Treatment of Malaria
Oral (Adults and Children 40) Four adult tablets (total daily dose atovaquone 1 g/proguanil 400 mg) as a single daily dose for 3 consecutive days.
Oral (Children 31–40 kg) Three adult tablets (total daily dose atovaquone 750 mg/proguanil 300 mg) once daily for 3 days.
Oral (Children 21–30 kg) Two adult tablets (total daily dose atovaquone 500 mg/proguanil 300 mg) once daily for 3 days.
Oral (Children 11–20 kg) One adult strength tablet (total daily dose atovaquone 250 mg/proguanil 150 mg) once daily for three days.
Oral (Children 9–10 kg) Three pediatric tablets (total daily dose atovaquone 187.5 mg/proguanil 75 mg once daily for three days.
Oral (Children 5–8 kg) Two pediatric tablets (total daily dose atovaquone 125 mg/proguanil 50 mg) once daily for three days.

Availability

Adult ablets : atovaquone 250 mg/proguanil 100 mg
Pediatric tablets : atovaquone 62.5 mg/proguanil 25 mg

Nursing implications

Nursing assessment

  • Malaria: Assess patient for improvement in signs and symptoms of condition daily throughout therapy.
  • Lab Test Considerations: Monitor CBC periodically throughout therapy. May cause neutropenia.
    • May cause ↑ AST and ALT. Monitor liver function tests periodically during therapy.

Potential Nursing Diagnoses

Risk for infection (Indications)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • For malaria prophylaxis, therapy should be started 1–2 days prior to potential exposures and continued for 7 days after leaving the area.
  • For treatment of malaria, take once daily for 3 days.
  • Oral: Administer with food or a milky drink to minimize GI distress. Tablets may be crushed and mixed with condensed milk just prior to administration for children with difficulty swallowing tablets.

Patient/Family Teaching

  • Instruct patient to take medication exactly as directed and continue full course of therapy, even if feeling better. If vomiting occurs within 1 hr of dose, may take a repeat dose. Take missed doses as soon as remembered, unless almost time for next dose. Do not double doses.
  • Review methods of minimizing exposure to mosquitoes with patients receiving atovaquone/proguanil prophylactically (use insect repellent, wear long-sleeved shirt and long trousers, use screen or netting).
  • Advise patient to wear protective clothing and sunscreen to avoid photosensitivity reactions.
  • Advise female patients to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Risk of death and serious complications is higher with Falciparum malaria. Advise pregnant women anticipating travel to malarious area to discuss risks with health care professional.

Evaluation/Desired Outcomes

  • Prevention of or improvement in signs and symptoms of malaria.

proguanil

(prō-gwä′nəl)
n.
A drug, C11H16ClN5, used in its hydrochloride form as an antimalarial, usually in combination with atovaquone.

proguanil

[progwahn′il]
an antimalarial agent administered orally as the hydrochloride salt. Its use in the United States is limited because of the development of drug-resistant malarial parasites.

proguanil

An antimalarial drug mainly used for prevention (as a prophylactic). A brand name is Paludrine. The drug is on the WHO official list. Formulated in conjunction with ATOVAQUONE, it is produced under the brand name Malarone.
References in periodicals archive ?
Atovaquone Proguanil is indicated for the prophylaxis and treatment of acute, uncomplicated p.
As regards the antimalarial chemoprophylaxis, chloroquine + proguanil were administered.
Antimalarial First reported Difference drug Introduced resistance (Years) Quinine 1632 1910 278 Chloroquine 1945 1957 12 Proguanil 1948 1949 1 Sulphadoxine- Pyremethamine 1967 1967 0 Mefloquine 1977 1981 5 Atovaquone 1996 1996 0 Table II.
Comparison of adverse events associated with use of mefloquine and combination of chloroquine and proguanil as antimalarial prophylaxis: Postal and telephone survey of travellers.
A mechanism for the synergistic antimalarial action of atovaquone and proguanil.
Malarone, a newly marketed combination of proguanil and atovaquone, offers the advantage of few side effects and a convenient weekly dosing schedule.
Malarone is a combination of atovaquone and proguanil.
For example, the antimalarial drug proguanil is administered as the prodrug and requires activation by CYP2C19.
Each tablet contains 250 mg of atovaquone and 100 mg of proguanil, but a lower-dose tablet is available for children under 88 pounds.
Treatment relies on drugs such as chloroquine, mepacrine and proguanil.
In the patient with QTc lengthening (460 ms; reference value <440 ms), artesunate treatment (total dose 480 mg) was changed to artemether/lumefantrine (4 tablets, each with 20 mg artemether and 120 mg lumefantrine) and then to atovaquone/ proguanil (4 tablets/d for 3 d, each with 250 mg atovaquone and 100 mg proguanil) because of persistent QTc lengthening (560 ms) accompanied by low potassium levels (<3 mmol/L; reference range 3.
Nasdaq: MYL) today announced that it has launched Atovaquone and Proguanil Hydrochloride Tablets, 62.