Source: FDA, National Drug Code (US) Revision Year: 2020
None.
Before starting MYTESI, rule out infectious etiologies of diarrhea. If infectious etiologies are not considered, and MYTESI is initiated based on a presumptive diagnosis of non-infectious diarrhea, then there is a risk that patients with infectious etiologies will not receive the appropriate treatments, and their disease may worsen. MYTESI is not indicated for the treatment of infectious diarrhea.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
A total of 696 HIV-positive patients in three placebo-controlled trials received MYTESI for a mean duration of 78 days. Of the total population across the three trials, 229 patients received a dosage of 125 mg twice a day for a mean duration of 141 days, and 171 patients received one of four higher than recommended dosages for a mean duration of 139 days (N=69) 14 days (N=102), 146 days (N=54), and 14 days (N=242), respectively.
Adverse reactions in patients treated with MYTESI 125 mg twice daily that occurred in at least 2% of patients and at a higher incidence than placebo are provided in Table 1.
Table 1. Common Adverse Reactions* in HIV-Positive Patients in Three Placebo-Controlled Trials:
| Adverse Reaction | MYTESI 125 mg Twice Daily N = 229 n (%) | Placebo N = 274 n (%) |
|---|---|---|
| Upper respiratory tract infection | 13 (6) | 4 (2) |
| Bronchitis | 9 (4) | 0 |
| Cough | 8 (4) | 3 (1) |
| Flatulence | 7 (3) | 3 (1) |
| Increased bilirubin | 7 (3) | 3 (1) |
| Nausea | 6 (3) | 4 (2) |
| Back pain | 6 (3) | 4 (2) |
| Arthralgia | 6 (3) | 0 |
| Urinary tract infection | 5 (2) | 2 (1) |
| Nasopharyngitis | 5 (2) | 2 (1) |
| Musculoskeletal pain | 5 (2) | 1 (<1) |
| Hemorrhoids | 5 (2) | 0 |
| Giardiasis | 5 (2) | 0 |
| Anxiety | 5 (2) | 1 (<1) |
| Increased alanine aminotransferase | 5 (2) | 3 (1) |
| Abdominal distension | 5 (2) | 1 (<) |
* occurring in at least 2% of patients and at a higher incidence than placebo
Less common adverse reactions that occurred in between 1% and 2% of patients taking 125 mg twice daily of MYTESI were abdominal pain, acne, increased aspartate aminotransferase, increased conjugated bilirubin, increased unconjugated blood bilirubin, constipation, depression, dermatitis, dizziness, dry mouth, dyspepsia, gastroenteritis, herpes zoster, nephrolithiasis, pain in extremity, pollakiuria, sinusitis and decreased white blood cell count.
MYTESI administration did not have a clinically relevant interaction with nelfinavir, zidovudine, or lamivudine in a drug-drug interaction trial [see Clinical Pharmacology (12.3)].
Pregnancy Category C.
Reproduction studies performed with crofelemer in rats at oral doses up to 177 times the recommended daily human dose of 250 mg (approximately 4.2 mg/kg) revealed no evidence of impaired fertility or harm to the fetus. In pregnant rabbits, crofelemer at an oral dose of about 96 times the recommended daily human dose of 4.2 mg/kg caused abortions and resorptions of fetuses. However, it is not clear whether these effects are related to the maternal toxicity observed. A pre- and postnatal development study performed with crofelemer in rats at oral doses of up to 177 times the recommended daily human dose of 4.2 mg/kg revealed no evidence of adverse pre- and postnatal effects in offspring. There are, however, no adequate, well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
It is not known whether crofelemer is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from MYTESI, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
The safety and effectiveness of MYTESI have not been established in pediatric patients.
Clinical studies with MYTESI did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients.
No dose modifications are recommended with respect to CD4 cell count and HIV viral load, based on the findings in subgroups of patients defined by CD4 cell count and HIV viral load.
The safety profile of MYTESI was similar in patients with baseline CD4 cell count less than 404 cells/microL (lower limit of normal range) (N=388) and patients with baseline CD4 cell counts greater than or equal to 404 cells/microL (N=289).
The safety profile of crofelemer was similar in patients with baseline HIV viral loads less than 400 copies/mL (N=412) and patients with baseline HIV viral loads greater than or equal to 400 copies/mL (N=278).
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