1%) had elevated amylase levels. In this trial, elevated levels of amylase occurred in subjects (8% versus 4%) receiving MEPRON tablets or pentamidine, respectively.
6.2 Postmarketing Experience
The following adverse reactions have been identified during post-approval use of MEPRON suspension. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic System Disorders
Methemoglobinemia, thrombocytopenia.
Immune System Disorders
Hypersensitivity reactions including angioedema, bronchospasm, throat tightness, and urticaria.
Eye Disorders
Vortex keratopathy.
Gastrointestinal Disorders
Pancreatitis.
Hepatobiliary Disorders
Hepatitis, fatal liver failure.
Skin and Subcutaneous Tissue Disorders
Erythema multiforme, Stevens-Johnson syndrome, and skin desquamation.
Renal and Urinary Disorders
Acute renal impairment.
7 DRUG INTERACTIONS
7.1 Rifampin/Rifabutin
Concomitant administration of rifampin or rifabutin and MEPRON suspension is known to reduce atovaquone concentrations [see Clinical Pharmacology (12.3)]. Concomitant administration of MEPRON suspension and rifampin or rifabutin is not recommended.
7.2 Tetracycline
Concomitant administration of tetracycline and MEPRON suspension has been associated with a reduction in plasma concentrations of atovaquone [see Clinical Pharmacology (12.3)]. Caution should be used when prescribing tetracycline concomitantly with MEPRON suspension. Monitor patients for potential loss of efficacy of MEPRON if coadministration is necessary.
7.3 Metoclopramide
Metoclopramide may reduce the bioavailability of atovaquone and should be used only if other antiemetics are not available [see Clinical Pharmacology (12.3)].
7.4 Indinavir
Concomitant administration of atovaquone and indinavir did not result in any change in the steady-state AUC and Cmax of indinavir but resulted in a decrease in the Ctrough of indinavir [see Clinical Pharmacology (12.3)]. Caution should be exercised when prescribing MEPRON suspension with indinavir due to the decrease in trough concentrations of indinavir. Monitor patients for potential loss of efficacy of indinavir if coadministration with MEPRON suspension is necessary.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. MEPRON should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Atovaquone was not teratogenic and did not cause reproductive toxicity in rats at plasma concentrations up to 2 to 3 times the estimated human exposure (dose of 1,000 mg/kg/day in rats). Atovaquone caused maternal toxicity in rabbits at plasma concentrations that were approximately one-half the estimated human exposure. Mean fetal body lengths and weights were decreased and there were higher numbers of early resorption and post‑implantation loss per dam (dose of 1,200 mg/kg/day in rabbits). It is not clear whether these effects were caused by atovaquone directly or were secondary to maternal toxicity. Concentrations of atovaquone in rabbit fetuses averaged 30% of the concurrent maternal plasma concentrations. In a separate study in rats given a single 14C‑radiolabelled dose (1,000 mg/kg), concentrations of radioc |
