MEPRON

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE MEPRON oral suspension is a quinone antimicrobial drug indicated for: • Prevention of Pneumocystis jirovecii pneumonia (PCP) in adults and adolescents aged 13 years and older who cannot tolerate trimethoprim-sulfamethoxazole (TMP-SMX). ( 1.1 ) • Treatment of mild-to-moderate PCP in adults and adolescents aged 13 years and older who cannot tolerate TMP-SMX. ( 1.2 ) Limitations of Use ( 1.3 ) : • Treatment of severe PCP (alveolar arterial oxygen diffusion gradient [(A-a)DO 2 ] >45 mm Hg) with MEPRON has not been studied. • The efficacy of MEPRON in subjects who are failing therapy with TMP-SMX has also not been studied. 1.1 Prevention of Pneumocystis jirovecii Pneumonia MEPRON oral suspension is indicated for the prevention of Pneumocystis jirovecii pneumonia (PCP) in adults and adolescents (aged 13 years and older) who cannot tolerate trimethoprim-sulfamethoxazole (TMP-SMX). 1.2 Treatment of Mild-to-Moderate Pneumocystis jirovecii Pneumonia MEPRON oral suspension is indicated for the acute oral treatment of mild-to-moderate PCP in adults and adolescents (aged 13 years and older) who cannot tolerate TMP-SMX. 1.3 Limitations of Use Clinical experience with MEPRON for the treatment of PCP has been limited to subjects with mild-to-moderate PCP (alveolar-arterial oxygen diffusion gradient [(A-a)DO 2 ] ≤45 mm Hg). Treatment of more severe episodes of PCP with MEPRON has not been studied. The efficacy of MEPRON in subjects who are failing therapy with TMP-SMX has also not been studied. Dosage and administration 2 DOSAGE AND ADMINISTRATION • Prevention of PCP: 1,500 mg (10 mL) once daily with food ( 2.1 ) • Treatment of PCP: 750 mg (5 mL) twice daily with food for 21 days ( 2.2 ) • Supplied in foil pouches and bottles: o Foil Pouch: For a 5-mL dose, take entire contents by mouth either by dispensing into a spoon or cup or directly into the mouth. For a 10-mL dose, take entire contents of 2 pouches. ( 2.3 ) o Bottle: Shake bottle gently before use. ( 2.3 ) 2.1 Dosage for the Prevention of P. jirovecii Pneumonia The recommended oral dosage is 1,500 mg (10 mL) once daily administered with food. 2.2 Dosage for the Treatment of Mild-to-Moderate P. jirovecii Pneumonia The recommended oral dosage is 750 mg (5 mL) twice daily (total daily dose = 1,500 mg) administered with food for 21 days. 2.3 Important Administration Instructions Administer MEPRON oral suspension with food to avoid low plasma atovaquone concentrations that may limit response to therapy [see Warnings and Precautions ( 5.1 ), Clinical Pharmacology ( 12.3 )]. MEPRON Foil Pouch • Open each 5-mL pouch by folding along the dotted line and tearing open at horizontal slit as directed by arrow on pouch. • For a 5-mL dose, take entire contents either by placing directly into the mouth or by dispensing into a dosing spoon (5 mL) or cup prior to administration by mouth. • For a 10-mL dose, take the entire contents of 2 pouches. MEPRON Bottle Shake bottle gently before administering the recommended dosage. Warnings and cautions 5 WARNINGS AND PRECAUTIONS • Failure to administer MEPRON oral suspension with food may result in lower plasma atovaquone concentrations and may limit response to therapy. Patients with gastrointestinal disorders may have limited absorption resulting in suboptimal atovaquone concentrations. ( 5.1 ) • Hepatotoxicity: Elevated liver chemistry tests and cases of hepatitis and fatal liver failure have been reported. ( 5.2 ) • Severe Cutaneous Adverse Reactions (SCARs): Cases of SCARs such as Stevens-Johnson Syndrome (SJS) have been reported. SCARs can be life-threatening or fatal. If symptoms or signs of SCARs develop, discontinue MEPRON immediately and institute appropriate therapy. ( 5.3 ) 5.1 Risk of Limited Oral Absorption Absorption of orally administered MEPRON oral suspension is limited but can be significantly increased when the drug is taken with food. Failure to administer MEPRON oral suspension with food may result in lower plasma atovaquone concentrations and may limit response to therapy. Consider therapy with other agents in patients who have difficulty taking MEPRON oral suspension with food or in patients who have gastrointestinal disorders that may limit absorption of oral medications [see Clinical Pharmacology ( 12.3 )]. 5.2 Hepatotoxicity Cases of cholestatic hepatitis, elevated liver enzymes, and fatal liver failure have been reported in patients treated with atovaquone [see Adverse Reactions ( 6.2 )]. If treating patients with severe hepatic impairment, closely monitor patients following administration of MEPRON. 5.3 Severe Cutaneous Adverse Reactions Cases of severe cutaneous adverse reactions (SCARs), including Stevens‑Johnson Syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), and erythema multiforme (EM) have been reported in patients treated with MEPRON [see Adverse Reactions ( 6.2 )]. SCARs can be life‑threatening or fatal. If symptoms or signs of