Prophylaxis of Plasmodium falciparum malaria in adults and children weighing between 11 kg and 40 kg

Treatment of malaria, simple (uncomplicated) access to Plasmodium falciparum, in children weighing ≥ 5 kg and
Consideration should be given to official and local recommendations concerning the local prevalence of resistance to antimalarial drugs, the official recommendations will normally include recommendations circulated by the World Health Organization (WHO) and recommendations Of the local health authorities

Dosage

The dosage for prophylaxis and treatment of simple P. falciparum malaria in children is determined on the basis of body weight.

Prophylaxis

Dosage, in adults and children weighing between 11-40 kg

Dosage, daily

Body weight interval (kg)

Atovaquone

(Mg)

Proguanil

(Mg)

Number of tablets

44136

62,5

25

1 tablet, ATOVAQUONE / PROGUANIL TEVA 62.5 mg / 25 mg CHILDREN, tablet, film
21-30

125

50

2 tablets, ATOVAQUONE / PROGUANIL TEVA 62.5 mg / 25 mg CHILDREN, tablet, film
31-40

187,5

75

3 tablets, ATOVAQUONE / PROGUANIL TEVA 62.5 mg / 25 mg CHILD, tablet, film
> 40

250

100

Adults and children over 40 kg should take 1 tablet per day of ATOVAQUONE / PROGUANIL TEVA 250 mg / 100 mg film-coated tablet. Code>
The safety and efficacy of ATOVAQUONE / PROGUANIL TEVA 62.5 mg / 25 mg CHILDREN, tablet, film-coated in the prophylaxis of malaria in children, weighing less than 11 kg have not been studied

The prophylaxis will be

· Started 24 or 48 hours before the day of arrival in the endemic area

· Continued for the duration of the stay

· Continued 7 days after leaving the endemic area

The safety and efficacy of atovaquone / proguanil have been demonstrated in studies of up to 12 weeks duration in semi-immunized subjects residing in endemic areas (see section on pharmacodynamic properties ).

TREATMENT

Dosage in children weighing between 5 and 11 kg

Dosage, daily

Body Weight Range (kg)

Atovaquone

(Mg)

Proguanil

(Mg)

Scheme
42587

125

50

2 tablets, ATOVAQUONE / PROGUANIL TEVA 62.5 mg / 25 mg CHILDREN, tablet, film-coated daily for 3 consecutive days
42652

187,5

75

Tablet, ATOVAQUONE / PROGUANIL TEVA 62.5 mg / 25 mg CHILD, tablet, film-coated daily for 3 consecutive days
The safety and efficacy of atovaquone / proguanil in the prophylaxis of malaria in children weighing less than 5 kg have not been established.

ATOVAQUONE / PROGUANIL TEVA 250 mg / 100 mg tablet is more suitable than the form ATOVAQUONE / PROGUANIL TEVA 62.5 mg / 25 mg CHILD, tablet, film-coated for the treatment of P. falciparum malaria The child weighing at least 11 kg. It is advisable to consult the tablet PCR, dosed at 250 mg / 100 mg for the recommended dosage in this weight category. These 250 mg / 100 mg tablets were dosed four times higher than the tablets of ATOVAQUONE / PROGUANIL TEVA 62.5 mg / 25 mg CHILDREN film-coated tablet
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Dosage in case of insufficiency, hepatic

There are no studies in children with hepatic impairment. However, an adult pharmacokinetic study indicates that no dose adjustment is required in patients with mild to moderate hepatic impairment. Although no studies have been performed in patients with severe hepatic impairment, no special precautions or dosage adjustments are contemplated (see Properties, Pharmacokinetics).

Dosage in patients with renal insufficiency

There are no studies in children with renal impairment. However, adult pharmacokinetic studies indicate that no dose adjustment is required in patients with mild to moderate renal impairment. Due to lack of information, ATOVAQUONE / PROGUANIL, TEVA 62.5 mg / 25 mg CHILD, film-coated tablet is contraindicated in the prophylaxis of malaria in adults and children with Kidney failure, severe (creatinine clearance

The data obtained in the pediatric population are derived from two studies whose primary objective was to evaluate the safety of the pediatric formulation of atovaquone / proguanil in (non-immune) patients traveling in endemic areas . In these trials, a total of 93 travelers weighing less than 40 kg received atovaquone / proguanil and 93 received an antimalarial prophylactic regimen (81, chloroquine / proguanil and 12 mefloquine). The majority of subjects traveled to Africa, and the average length of stay was between 2 and 3 weeks. No malaria cases were observed in the subjects who participated in these studies

Processing

An open-label randomized parallel-group study was undertaken in Gabon in 200 children weighing between 5 kg and 11 kg with confirmed and uncomplicated P. falciparum malaria. Treatment with pediatric tablets of the combination, atovaquone / proguanil or amodiaquine suspension. In the intention-to-treat population, the cure rate was 87% in the group at 28 days, atovaquone / proguanil (87/100 subjects). In the per-protocol population, the cure rate at 28 days was 95% in the atovaquone / proguanil group (87/92 subjects). The parasitological cure rates for the atovaquone / proguanil group were 88% and 95% for the ITT and PP populations, respectively.
If symptoms are present, patients should be cautioned that they should not drive or use machinery or engage in activities that could be hazardous to them or to others. Other

Hypersensitivity to the active ingredients or to any of the excipients indicated in the heading
The combination of atovaquone / proguanil is contraindicated in the prophylaxis of malaria at. Falciparum in patients with severe renal impairment (creatinine clearance

In patients with malaria and diarrhea or vomiting, it is preferable to consider other antimalarial treatment. If atovaquone / proguanil treatment is nevertheless used in these patients, the parasitaemia and the clinical condition of the patient should be closely monitored.
The combination of atovaquone / proguanil has not been evaluated in the treatment of pernicious cerebral access (cerebral malaria) or in severe or complicated forms of malaria such as increased parasitaemia, pulmonary edema Or renal insufficiency

Severe allergic reactions (including anaphylactic reactions) have sometimes been reported in patients using the combination of atovaquone / proguanil. In the event of an allergic reaction (see section 4.3), administration of atovaquone / proguanil should be discontinued, and appropriate treatment should be instituted.

The atovaquone / proguanil association was shown to be inactive on the hypnozotic forms of Plasmodium vivax and the treatment of Plasmodium vivax malaria with atovaquone / proguanil in monotherapy resulted in frequent relapses. A complementary, effective treatment against hypnozoites should be administered to travelers highly exposed to Plasmodium vivax or Plasmodium ovale and those developing malaria caused by one of these two species of parasites

The re-emergence of an epidemic of malaria by recrudescence of Plasmodium falciparum parasitaemia after initial treatment, led by the atovaquone / proguanil combination, as well as a failure of prophylaxis, must evoke resistance from Parasite and requires the use of another schizonticidal antimalarial to treat access.

Parasitemia should be closely monitored in patients during concomitant administration of tetracycline (see section Interactions with other medicinal products and other forms of interaction).

Concomitant administration of atovaquone / proguanil with efavirenz or boosted protease inhibitors should be avoided as much as possible (see section Interactions with other medicinal products and other forms of interaction). Concomitant administration of the combination of atovaquone / proguanil with rifampicin or rifabutin is not recommended (see section Interaction with other medicinal products and other forms of interaction). >

Concomitant administration of atovaquone / proguanil and metoclopramide is not recommended. (See also Interactions with other medicinal products and other forms of interaction).



Atovaquone may increase levels of etoposide and its metabolite (see Interactions with other medicinal products and other forms of interactions).

In patients with severe renal insufficiency (creatinine clearance

Not applicable.

There is insufficient experience to predict the consequences of atovaquone / proguanil overdosage or to propose specific management. However, in the case reports of atovaquone overdose, the observed effects corresponded to the known undesirable effects of the drug. In case of overdose, the patient should be monitored and symptomatic treatment appropriate.

Pregnancy

The safety of atovaquone / proguanil in pregnant women has not been established and the potential risk is unknown.
Maternal toxicity was observed in pregnant rabbits in a teratogenicity study (see section Preclinical safety data).
The use of the combination of atovaquone / proguanil should be considered in the pregnant woman only after evaluating the benefit of the treatment for the mother in relation to the potential risk to the fetus.

Proguanil, one of the components of the atovaquone / proguanil combination, works by inhibiting the parasite's dihydrofolate reductase.
There is no clinical evidence that folate supplementation decreases, the efficacy of the drug. For women of childbearing age receiving supplementation, folate for the prevention of neural tube defects, at birth, these supplements should be continued during treatment with atovaquone / proguanil.

Breastfeeding

In a study in rats, concentrations of atovaquone in breast milk accounted for 30% of maternal plasma concentrations. It is not known whether atovaquone passes into breast milk, in women

Proguanil is excreted in breast milk in small quantities

The combination of atovaquone / proguanil should not be used during breastfeeding.
Fertility

No data on the effects of association on fertility are available, but according to animal studies the two molecules, atovaquone and proguanil, showed no effect on fertility.

In clinical trials with atovaquone / proguanil in the treatment of malaria, the most frequently reported adverse reactions were pain, abdominal pain, headache, anorexia, nausea, vomiting, diarrhea and cough. >

In the clinical trials conducted with atovaquone / proguanil in the prophylactic treatment of malaria, the most commonly reported adverse events were headache, abdominal pain and diarrhea.

Reported adverse events of suspected (or at least possible) causality in clinical trials as well as spontaneous post-marketing notifications are summarized in the table below.
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The following convention was used to classify frequencies: very common (≥1 / 10), frequent (≥1 / 100 to;