Adverse reactions are listed as follows by system organ class and frequency. Frequencies are defined as: very common > 1/10, common >1/100 and < 1/10, uncommon >1/1000 and < 1/100, rare >1/10,000 and < 1/1000, very rare < 1/10,000. Very common, common and uncommon frequencies were determined from clinical trial data. Rare and very rare frequencies were generally derived from spontaneous data. The frequency classification "Not known" has been applied to those reactions where a frequency could not be estimated from the available data.
MALARONE contains atovaquone and proguanil hydrochloride, therefore, the adverse events associated with each of these compounds may be expected with MALARONE. At the doses employed for both treatment and prophylaxis of malaria, adverse events are generally mild and of limited duration. There is no evidence of added toxicity following concurrent administration of atovaquone and proguanil.
A summary of adverse events associated with the use of MALARONE, atovaquone or progunail hydrochloride is provided as follows: Blood & Lymphatic system disorders: Common: Anaemia1, neutropenia2. Not Known: Pancytopenia in patients with severe renal impairment4.
Immune system disorders: Not Known: Angioedema, anaphylaxis, vasculitis.
Metabolism and nutritional disorders: Common: Hyponatraemia2, anorexia1. Uncommon: Elevated amylase levels2.
Psychiatric disorders: Rare: Hallucinations1.
Nervous system disorders: Very common: Headache1. Common: Insomnia1, dizziness1.
Gastrointestinal disorders: Very common: Abdominal pain1, nausea2, vomiting1, diarrhoea1. Uncommon: Stomatitis1. Not Known: Gastric intolerance4, oral ulceration4.
Hepatobiliary disorders: Common: Elevated liver enzyme levels2. Not Known: Hepatitis3, Cholestasis4.
Clinical trial data for atovaquone-proguanil indicated that abnormalities in liver function tests were reversible and not associated with untoward clinical events.
Skin and subcutaneous tissue disorders: Common: Rash1. Uncommon: Hair loss1, urticaria1. Not Known: Stevens-Johnson Syndrome3, erthema multiforme3.
General disorders and administration site conditions: Common: Fever1.
Respiratory, thoracic and mediastinal disorders: Common: Cough1.
In clinical trials of MALARONE for prophylaxis of malaria, the most commonly reported adverse events, independent of attributability, were headache, abdominal pain and diarrhoea, and were reported in a similar proportion of subjects receiving MALARONE or placebo.
In clinical trials of MALARONE for treatment of malaria, the most commonly reported adverse events, independent of attributability, were abdominal pain, headache, anorexia, nausea, vomiting, diarrhoea and coughing, and were generally reported in a similar proportion of patients receiving MALARONE or a comparator antimalarial drug.
1. Frequency calculated from atovaquone-proguanil clinical trials
2. Frequency taken from atovaquone label. Patients participating in clinical trials with atovaquone have received higher doses and have often had complications of advance Human Immunodeficiency Virus (HIV) disease. Therefore, the causal relationship between the adverse experiences and atovaquone is difficult to evaluate. These events may have been seen at a lower frequency or not at all in clinical trials with atovaquone-proguanil.
3. Observed from post-marketing spontaneous reports and the frequency is therefore not known.
4. Observed with proguanil and the frequency is therefore not known.