ATOVACUONA/HIDROCLORURO DE PROGUANIL VIATRIS

Posology Prophylaxis Prophylaxis should • commence 24 or 48 hours prior to entering a malaria-endemic area, • continue during the period of the stay, • continue for 7 days after leaving the area. In residents (semi-immune subjects) of endemic areas, the safety and effectiveness of atovaquone/proguanil has been established in studies of up to 12 weeks.

In non-immune subjects, the average duration of exposure in clinical studies was 27 days. Dosage in Adults One tablet daily. Atovaquone/Proguanil hydrochloride is not recommended for malaria prophylaxis in persons under 40 kg bodyweight.

Other pharmaceutical strengths may be more appropriate for malaria prophylaxis in persons weighing under 40 kg. Treatment Adults Four tablets as a single dose for three consecutive days. Children Dosage/day Body weight range (kg) No.

2). Hepatic Impairment A pharmacokinetic study indicates that no dosage adjustments are needed in patients with mild to moderate hepatic impairment. 2). Renal Impairment Pharmacokinetic studies indicate that no dosage adjustments are needed in patients with mild to moderate renal impairment.

In patients with severe renal impairment (creatine clearance <30 mL/min) alternatives to atovaquone/proguanil hydrochloride for treatment of acute P. 2). For prophylaxis of P. falciparum malaria in patients with several renal impairments see Section

In clinical trials of atovaquone/proguanil in the treatment of malaria, the most commonly reported adverse reactions were abdominal pain, headache, anorexia, nausea, vomiting, diarrhoea and coughing. In clinical trials of atovaquone/proguanil for prophylaxis of malaria, the most commonly reported adverse reactions were headache, abdominal pain and diarrhoea.

The following table provides a summary of adverse reactions that have been reported to have a suspected (at least possible) causal relationship to treatment with atovaquone/proguanil in clinical trials and spontaneous post-marketing reports.

The following convention is used for the classification of frequency: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); not known (cannot be estimated from the available data).

There are limited long-term safety data in children. In particular, the long-term effects of atovaquone/proguanil on growth, puberty and general development have not been studied. 4) Vasculitis3 Metabolism and nutrition disorders Hyponatraemia1 Anorexia Elevated amylase levels1 Psychiatric disorders Abnormal dreams Depression Anxiety Hallucinations Panic attack Crying Nightmares Psychotic disorder Nervous system disorders Headache Insomnia Dizziness Seizure Cardiac disorders Palpitations Tachycardia Respiratory, thoracic and mediastinal disorders Cough Gastrointestinal disorders Nausea1 Vomiting Diarrhoea Abdominal pain Stomatitis Gastric intolerance3 Oral ulceration3 Hepatobiliary disorders Elevated liver enzymes1 Hepatitis Cholestasis3 Skin and subcutaneous tissue disorders Pruritus Rash Hair loss Urticaria Stevens- Johnson Syndrome Erythema multiforme Blister Skin exfoliation Photosensitivity reactions General disorders and administration site conditions Fever 1.

Frequency taken from atovaquone label. Patients participating in clinical trials with atovaquone have received higher doses and have often had complications of advanced Human Immunodeficiency Virus (HIV) disease. These events may have been seen at a lower frequency or not at all in clinical trials with atovaquone/proguanil.

2. Observed from post-marketing spontaneous reports and the frequency is therefore unknown. 3. Observed with proguanil. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard.

The safety and effectiveness of atovaquone/proguanil hydrochloride tablets for prophylaxis of malaria in patients who weigh less than 40 kg, or in the treatment of malaria in paediatric patients who weigh less than 11 kg has not been established.

Persons taking atovaquone/proguanil hydrochloride for prophylaxis or treatment of malaria should take a repeat dose if they vomit within 1 hour of dosing. In the event of diarrhoea, normal dosing should be continued. Absorption of atovaquone may be reduced in patients with diarrhoea or vomiting, but diarrhoea or vomiting was not associated with reduced efficacy in clinical trials of atovaquone/proguanil for malaria prophylaxis.

However, as with other antimalarial agents, subjects with diarrhoea or vomiting should be advised to continue with malaria prevention measures by complying with personal protection measures (repellents, impregnated bednets). In patients with acute malaria who present with diarrhoea or vomiting, alternative therapy should be considered.

If atovaquone/proguanil hydrochloride is used to treat malaria in these patients, parasitaemia and the patient’s clinical condition should be closely monitored. Atovaquone/proguanil has not been evaluated for the treatment of cerebral malaria or other severe manifestations of complicated malaria including hyperparasitaemia, pulmonary oedema or renal failure.

Occasionally, severe allergic reactions (including anaphylaxis) have been reported in patients taking atovaquone/proguanil. 8) atovaquone/proguanil hydrochloride should be discontinued promptly and appropriate treatment initiated. Atovaquone/proguanil has been shown to have no efficacy against hypnozoites of Plasmodium vivax as parasite relapse occurred commonly when P.

vivax malaria was treated with atovaquone/proguanil alone. Travellers with intense exposure to P. vivax or P. ovale, and those who develop malaria caused by either of these parasites, will require additional treatment with a drug that is active against hypnozoites.

In the event of recrudescent infections due to P. falciparum after treatment with atovaquone/proguanil hydrochloride, or failure of chemoprophylaxis with atovaquone/proguanil, patients should be treated with a different blood schizonticide as such events can reflect a resistance of the parasite.

5). 5). Concurrent use of metoclopramide is not recommended. 5). 5). 5). In patients with severe renal impairment (creatinine clearance <30 mL/min) alternatives to atovaquone/proguanil for treatment of acute P. 2). This medicinal product contains lactose.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

3. Method of administration The daily dose should be taken with food or a milky drink (to ensure maximum absorption of atovaquone) at the same time each day. If patients are unable to tolerate food, atovaquone/proguanil hydrochloride should be administered, but systemic exposure of atovaquone will be reduced.

In the event of vomiting within 1 hour of dosing a repeat dose should be taken. 1. Atovaquone/Proguanil hydrochloride is contraindicated for prophylaxis of P. falciparum malaria in patients with severe renal impairment (creatinine clearance <30 mL/min).