1,500 mg/day

(n = 175) MEPRON

750 mg/day

(n = 188) Aerosolized

Pentamidine

(n = 186)
Diarrhea 42% 42% 35%
Rash 39% 46% 28%
Headache 28% 31% 22%
Nausea 26% 32% 23%
Cough increased 25% 25% 31%
Fever 25% 31% 18%
Rhinitis 24% 18% 17%
Asthenia 22% 31% 31%
Infection 22% 18% 19%
Abdominal pain 20% 21% 20%
Dyspnea 15% 21% 16%
Vomiting 15% 22% 11%
Patients discontinuing therapy due to an adverse experience 25% 16% 7%
Patients reporting at least 1 adverse experience 98% 96% 89%

Other events occurring in ≥10% of the patients receiving the recommended dose of MEPRON included sweating, flu syndrome, pain, sinusitis, pruritus, insomnia, depression, and myalgia. Bronchospasm occurred more frequently in patients receiving aerosolized pentamidine (11%) than in patients receiving MEPRON 1,500 mg/day (4%) and MEPRON 750 mg/day (2%).

Neither MEPRON nor aerosolized pentamidine was associated with a substantial change from baseline values in any measured laboratory parameter, nor were there any significant differences in any measured laboratory parameter between MEPRON and aerosolized pentamidine. Some patients had laboratory abnormalities considered serious by the investigator or that contributed to discontinuation of therapy.
PCP Treatment Studies
Table 8 summarizes all the clinical adverse experiences reported by ≥5% of the study population during the TMP-SMX comparative study of MEPRON (n = 408), regardless of attribution. The incidence of adverse experiences with MEPRON Suspension at the recommended dose was similar to that seen with the tablet formulation of atovaquone.

Table 8. Treatment-Emergent Adverse Experiences in the TMP-SMX Comparative PCP Treatment Study   Percentage of Patients with Treatment-Emergent Adverse Experience
Treatment-Emergent

Adverse Experience MEPRON

(n = 203) TMP-SMX

(n = 205)
Rash (including maculopapular) 23% 34%
Nausea 21% 44%
Diarrhea 19% 7%
Headache 16% 22%
Vomiting 14% 35%
Fever 14% 25%
Insomnia 10% 9%
Asthenia 8% 8%
Pruritus 5% 9%
Monilia, oral 5% 10%
Abdominal pain 4% 7%
Constipation 3% 17%
Dizziness 3% 8%
Patients discontinuing therapy due to an adverse experience 9% 24%
Patients reporting at least 1 adverse experience 63% 65%

Although an equal percentage of patients receiving MEPRON and TMP-SMX reported at least 1 adverse experience, more patients receiving TMP-SMX required discontinuation of therapy due to an adverse event. Twenty-four percent of patients receiving TMP-SMX were prematurely discontinued from therapy due to an adverse experience versus 9% of patients receiving MEPRON. Four percent of patients receiving MEPRON had therapy discontinued due to development of rash. The majority of cases of rash among patients receiving MEPRON were mild and did not require the discontinuation of dosing. The only other clinical adverse experience that led to premature discontinuation of dosing of MEPRON by more than 1 patient was vomiting (<1%). The most common adverse experience requiring discontinuation of dosing in the TMP-SMX group was rash (8%).