Mepron Side Effects

Generic Name: atovaquone

Please note - some side effects for Mepron may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Mepron - for the Consumer

Mepron

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Mepron:

Diarrhea; difficulty sleeping; dizziness; headache; increased cough; increased sweating; indigestion; loss of appetite; muscle pain; nausea; runny or stuffy nose; stomach pain; vomiting; weakness.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest or throat; swelling of the mouth, face, lips, or tongue; unusual hoarseness); anxiety; change in the amount of urine produced; dark urine; depression; fever; flu-like symptoms; pale stools; red, swollen, blistered, or peeling skin; severe or persistent stomach pain; shortness of breath; unusual bruising or bleeding; white patches in the mouth; yellowing of the eyes or skin.

Mepron Side Effects - for the Professional

Mepron

Because many patients who participated in clinical trials with Mepron had complications of advanced HIV disease, it was often difficult to distinguish adverse events caused by Mepron from those caused by underlying medical conditions. There were no life-threatening or fatal adverse experiences caused by Mepron.

PCP Prevention Studies

In the dapsone comparative study of Mepron Suspension, adverse experience data were collected only for treatment-limiting events. Among the entire population (n = 1,057), treatment-limiting events occurred at similar frequencies in patients treated with Mepron Suspension or dapsone (Table 6). Among patients who were taking neither dapsone nor atovaquone at enrollment (n = 487), treatment-limiting events occurred in 43% of patients treated with dapsone and 20% of patients treated with Mepron Suspension (P <0.001).In both populations, the type of treatment-limiting events differed between the 2 treatment arms. Hypersensitivity reactions (rash, fever, allergic reaction) and anemia were more common in patients treated with dapsone, while gastrointestinal events (nausea, diarrhea, and vomiting) were more common in patients treated with Mepron Suspension.

Table 7 summarizes the clinical adverse experiences reported by ≥20% of patients in any group in the aerosolized pentamidine comparative study of Mepron Suspension (n = 549), regardless of attribution. The incidence of adverse experiences at the recommended dose was similar to that seen with aerosolized pentamidine. Rash was the only individual adverse experience that occurred significantly more commonly in patients treated with both dosages of Mepron Suspension (39% to 46%) than in patients treated with aerosolized pentamidine (28%). Among patients treated with Mepron Suspension, there was no evidence of a dose-related increase in the incidence of adverse experiences. Treatment-limiting adverse experiences occurred less often in patients treated with aerosolized pentamidine (7%)than in patients treated with 1,500 mg Mepron Suspension once daily (25%, P≤0.001) or 750 mg Mepron Suspension once daily (16%, P = 0.004). The most common adverse experiences requiring discontinuation of dosing in the group receiving 1,500 mg Mepron Suspension once daily were rash (6%), diarrhea (4%), and nausea (3%). The most common adverse experience requiring discontinuation of dosing in the group receiving aerosolized pentamidine was bronchospasm (2%).

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.

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%).

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.

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%).

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%).

ULN = upper limit of normal range.

LLN = lower limit of normal range.

Observed During Clinical Practice

In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of Mepron. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Mepron.

Methemoglobinemia, thrombocytopenia.

Hypersensitivity reactions including angioedema, bronchospasm, and throat tightness.

Vortex keratopathy.

Gastrointestinal Disorders: Pancreatitis.

Skin and Subcutaneous Tissue Disorders: Erythema multiforme.

Renal and Urinary Disorders: Acute renal impairment.

Side Effects by Body System

General

In PCP prevention studies comparing atovaquone to inhaled pentamidine, 16% to 25% of patients discontinued atovaquone and 7% discontinued pentamidine due to adverse events. Rash (6%), diarrhea (4%), and nausea (3%) were the most common reasons for discontinuing atovaquone, while bronchospasm (2%) was the most common reason for discontinuing pentamidine. In studies comparing atovaquone to dapsone, treatment-limiting hypersensitivity reactions were more frequent in the dapsone group (16.1%) and treatment-limiting gastrointestinal side effects were more common in the atovaquone group (up to 4.1%).

In PCP treatment studies, 9% of patients discontinued atovaquone due to side effects, compared to 24% of patients receiving sulfamethoxazole-trimethoprim. The most common reason for discontinuation in both treatment groups was rash (atovaquone, 4%; sulfamethoxazole-trimethoprim, 8%). In studies comparing intravenous pentamidine and atovaquone, 63% of patients in the atovaquone group and 72% of patients in the pentamidine group reported side effects. Treatment was discontinued in 7% of the atovaquone patients and 41% of the pentamidine patients due to adverse events; the most common reasons were rash (4%) in the atovaquone group and hypoglycemia (11%) and vomiting (9%) in the pentamidine group.

Gastrointestinal

Gastrointestinal side effects are among the most common and have included nausea (up to 40%), diarrhea (up to 42%), vomiting (up to 22%), abdominal pain (up to 21%), oral monilia (up to 10%), taste perversion (3%), and constipation (3%). The incidence of side effects was higher in patients in PCP treatment studies than in prevention studies. Seven percent of patients experience anorexia and 5% of patients experience dyspepsia, although these are difficult to attribute to the drug due to the serious underlying diseases in the patients who receive atovaquone. Hyperamylasemia has been reported in 8% of patients. Pancreatitis has also been reported during postmarketing experience.

Dermatologic

Dermatologic side effects have included rash (up to 46%), pruritus (greater than or equal to 10%), exfoliative dermatitis, photosensitivity, and toxic epidermal necrolysis. Erythema multiforme, Stevens-Johnson syndrome, and skin desquamation have been reported during postmarketing experience in patients receiving multiple drug treatment including atovaquone.

Hepatic

Hepatic side effects have included elevated ALT (greater than 5 times ULN, 6%), elevated AST (greater than 5 times ULN, 4%), elevated alkaline phosphatase (greater than 2.5 times ULN, up to 8%), and increased amylase (greater than 1.5 times ULN, up to 8%) in patients being treated for PCP. Therapy was discontinued in 2% of patients receiving atovaquone due to ALT/AST elevations, compared to 7% of patients being treated with sulfamethoxazole-trimethoprim. Hepatomegaly has also been reported. Rarely, hepatitis and at least one case of fatal liver failure have been reported during postmarketing experience.

Hematologic

Hematologic side effects have included anemia (up to 6%) and neutropenia (up to 5%), but may be due to underlying disease. Methemoglobinemia and thrombocytopenia have also been reported.

Metabolic

Metabolic side effects have included hyponatremia (up to 10%), hyperglycemia (9%), and hypoglycemia (1%).

Other

Other side effects have included fever (up to 40%), asthenia (up to 31%), flu syndrome (greater than or equal to 10%), pain (greater than or equal to 10%), infection (up to 22%), sweating (greater than or equal to 10%), and malaise, but some may be due to underlying disease. Fatigue, night sweats, and burning sensation of the tongue have also been reported.

Respiratory

Respiratory side effects have included dyspnea (up to 21%), increased cough (up to 25%), rhinitis (up to 24%), sinusitis (greater than or equal to 10%), bronchospasm (up to 4%), and pneumonia.

Nervous system

Nervous system side effects have included insomnia (up to 19%), dizziness (up to 8%), headache (up to 31%), anxiety (7%), and depression (greater than or equal to 10%).

Musculoskeletal

Musculoskeletal side effects have included myalgia (greater than or equal to 10%).

Hypersensitivity

Hypersensitivity reactions have included rash, erythema multiforme, exfoliative dermatitis, and allergic reactions (unspecified, up to 1.1%).

Renal

Renal side effects have included elevated creatinine (1%) and elevated BUN (1%). Acute renal impairment has been reported during postmarketing experience.

Cardiovascular

Cardiovascular side effects have included hypotension (1%).

Ocular

Ocular side effects have included vortex keratopathy during postmarketing experience.

Immunologic

Immunologic side effects have included hypersensitivity reactions including angioedema, bronchospasm, throat tightness, and urticaria during postmarketing experience.

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