Laboratory test abnormalities reported for ≥5% of the study population during the treatment period are summarized in Table 9. Two percent of patients treated with MEPRON and 7% of patients treated with TMP-SMX had therapy prematurely discontinued due to elevations in ALT/AST. In general, patients treated with MEPRON developed fewer abnormalities in measures of hepatocellular function (ALT, AST, alkaline phosphatase) or amylase values than patients treated with TMP-SMX.

Table 9. Treatment-Emergent Laboratory Test Abnormalities in the TMP-SMX Comparative PCP Treatment Study   Percentage of Patients Developing a Laboratory Test Abnormality
Laboratory Test Abnormality MEPRON TMP-SMX
Anemia (Hgb<8.0 g/dL) 6% 7%
Neutropenia (ANC<750 cells/mm3) 3% 9%
Elevated ALT (>5 x ULN) 6% 16%
Elevated AST (>5 x ULN) 4% 14%
Elevated alkaline phosphatase (>2.5 x ULN) 8% 6%
Elevated amylase (>1.5 x ULN) 7% 12%
Hyponatremia (<0.96 x LLN) 7% 26%

ULN = upper limit of normal range.

LLN = lower limit of normal range.

Table 10 summarizes the clinical adverse experiences reported by ≥5% of the primary therapy study population (n = 144) during the comparative trial of MEPRON and intravenous pentamidine, regardless of attribution. A slightly lower percentage of patients who received MEPRON reported occurrence of adverse events than did those who received pentamidine (63% vs 72%). However, only 7% of patients discontinued treatment with MEPRON due to adverse events, while 41% of patients who received pentamidine discontinued treatment for this reason (P <0.001). Of the 5 patients who discontinued therapy with MEPRON, 3 reported rash (4%). Rash was not severe in any patient. No other reason for discontinuation of MEPRON was cited more than once. The most frequently cited reasons for discontinuation of pentamidine therapy were hypoglycemia (11%) and vomiting (9%).

Table 10. Treatment-Emergent Adverse Experiences in the Pentamidine Comparative PCP Treatment Study (Primary Therapy Group)   Percentage of Patients with Treatment-Emergent Adverse Experience
Treatment-Emergent
Adverse Experience MEPRON

(n = 73) Pentamidine

(n = 71)
Fever 40% 25%
Nausea 22% 37%
Rash 22% 13%
Diarrhea 21% 31%
Insomnia 19% 14%
Headache 18% 28%
Vomiting 14% 17%
Cough 14% 1%
Abdominal pain 10% 11%
Pain 10% 10%
Sweat 10% 3%
Monilia, oral 10% 3%
Asthenia 8% 14%
Dizziness 8% 14%
Anxiety 7% 10%
Anorexia 7% 10%
Sinusitis 7% 6%
Dyspepsia 5% 10%
Rhinitis 5% 7%
Taste perversion 3% 13%
Hypoglycemia 1% 15%
Hypotension 1% 10%
Patients discontinuing therapy due to an adverse experience 7% 41%
Patients reporting at least 1 adverse experience 63% 72%

Laboratory test abnormalities reported in ≥5% of patients in the pentamidine comparative study are presented in Table 11. Laboratory abnormality was reported as the reason for discontinuation of treatment in 2 of 73 patients who received MEPRON. One patient (1%) had elevated creatinine and BUN levels and 1 patient (1%) had elevated amylase levels. Laboratory abnormalities were the sole or contributing factor in 14 patients who prematurely discontinued pentamidine therapy. In the 71 patients who received pentamidine, laboratory parameters most frequently reported as reasons for discontinuation were hypoglycemia (11%), elevated creatinine levels (6%), and leukopenia (4%).