|indication=non-infectious diarrhea in adult patients with HIV/AIDS
|indication=non-infectious diarrhea in adult patients with HIV/AIDS
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<!--Contraindications-->
<!--Contraindications-->
|contraindications=* Condition1
|contraindications=* None
<!--Warnings-->
<!--Warnings-->
|warnings=* Description
|warnings=* Risks of Treatment in Patients with Infectious Diarrhea
====Precautions====
If infectious etiologies are not considered, and FULYZAQ 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. Before starting FULYZAQ, rule out infectious etiologies of diarrhea. FULYZAQ is not indicated for the treatment of infectious diarrhea.
* Description
<!--Adverse Reactions-->
<!--Adverse Reactions-->
<!--Clinical Trials Experience-->
<!--Clinical Trials Experience-->
|clinicalTrials=There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
|clinicalTrials= Clinical Trials Experience
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
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.
=====Metabolic and Nutritional=====
A total of 696 HIV-positive patients in three placebo-controlled trials received FULYZAQ for a mean duration of 78 days. Of the total population across the three trials, 229 patients received a dose of 125 mg twice a day for a mean duration of 141 days, 69 patients received a dose of 250 mg twice a day for a mean duration of 139 days, 102 patients received a dose of 250 mg four times a day for a mean duration of 14 days, 54 patients received a dose of 500 mg twice a day for a mean duration of 146 days, and 242 patients received a dose of 500 mg four times a day for a mean duration of 14 days.
Adverse reactions for FULYZAQ that occurred in at least 2% of patients and at a higher incidence than placebo are provided in Table 1.
: [[File:Crofelemer Adv eff.png|none|400px]]
Adverse reactions that occurred in between 1% and 2% of patients taking a 250 mg daily dose of FULYZAQ 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, procedural pain, seasonal allergy, sinusitis and decreased white blood cell count.
=====Musculoskeletal=====
Adverse reactions were similar in patients who received doses greater than 250 mg daily.
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Postmarketing Experience-->
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
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<!--Drug Interactions-->
<!--Drug Interactions-->
|drugInteractions=* Drug
|drugInteractions=Drug Interaction Potential
:* Description
In vitro studies have shown that crofelemer has the potential to inhibit cytochrome P450 isoenzyme 3A and transporters MRP2 and OATP1A2 at concentrations expected in the gut. Due to the minimal absorption of crofelemer, it is unlikely to inhibit cytochrome P450 isoenzymes 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and CYP3A4 systemically [see Clinical Pharmacology (12.3)].
7.2 Nelfinavir, Zidovudine, and Lamivudine
FULYZAQ administration did not have a clinically relevant interaction with nelfinavir, zidovudine, or lamivudine in a drug-drug interaction trial.
<!--Use in Specific Populations-->
<!--Use in Specific Populations-->
|useInPregnancyFDA=* '''Pregnancy Category'''
|FDAPregCat=C
|useInPregnancyFDA=* Reproduction studies performed with crofelemer in rats at oral doses up to 177 times the recommended daily human dose of 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.
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
|useInNursing=* 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 FULYZAQ, 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.
|useInPed=There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
|useInPed=* The safety and effectiveness of FULYZAQ have not been established in pediatric patients less than 18 years of age.
|useInGeri=There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGeri=* Clinical studies with crofelemer did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
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<!--Administration and Monitoring-->
<!--Administration and Monitoring-->
|othersTitle=CD4 Count and HIV Viral Load
|useInOthers=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 crofelemer was similar in patients with baseline CD4 cell count less than 404 cells/μL (lower limit of normal range) (N=388) and patients with baseline CD4 cell counts greater than or equal to 404 cells/μL (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).
|administration=* Oral
|administration=* Oral
* Intravenous
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
* Description
<!--IV Compatibility-->
<!--IV Compatibility-->
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<!--Overdosage-->
<!--Overdosage-->
|overdose====Acute Overdose===
|overdose=* There has been no reported experience with overdosage of crofelemer.
====Signs and Symptoms====
* Description
====Management====
* Description
===Chronic Overdose===
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
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Overview
Crofelemer is a anti-diarrheal that is FDA approved for the treatment of non-infectious diarrhea in adult patients with HIV/AIDS. Common adverse reactions include upper respiratory tract infection, bronchitis, cough, flatulence and increased bilirubin.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indications
FULYZAQ is indicated for symptomatic relief of non-infectious diarrhea in patients with HIV/AIDS on anti-retroviral therapy.
Dosage
The recommended dose of FULYZAQ is one 125 mg delayed-release tablet taken orally two times a day, with or without food. FULYZAQ tablets should not be crushed or chewed. Tablets should be swallowed whole.
3 DOSAGE FORMS AND STRENGTHS
FULYZAQ is a white, oval, enteric-coated 125 mg delayed-release tablet printed on one side with 125SLXP.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Crofelemer in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Crofelemer in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
The safety and effectiveness of FULYZAQ have not been established in pediatric patients less than 18 years of age.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Crofelemer in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Crofelemer in pediatric patients.
Contraindications
None
Warnings
Risks of Treatment in Patients with Infectious Diarrhea
If infectious etiologies are not considered, and FULYZAQ 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. Before starting FULYZAQ, rule out infectious etiologies of diarrhea. FULYZAQ is not indicated for the treatment of infectious diarrhea.
Adverse Reactions
Clinical Trials Experience
Clinical Trials Experience
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 FULYZAQ for a mean duration of 78 days. Of the total population across the three trials, 229 patients received a dose of 125 mg twice a day for a mean duration of 141 days, 69 patients received a dose of 250 mg twice a day for a mean duration of 139 days, 102 patients received a dose of 250 mg four times a day for a mean duration of 14 days, 54 patients received a dose of 500 mg twice a day for a mean duration of 146 days, and 242 patients received a dose of 500 mg four times a day for a mean duration of 14 days.
Adverse reactions for FULYZAQ that occurred in at least 2% of patients and at a higher incidence than placebo are provided in Table 1.
Adverse reactions that occurred in between 1% and 2% of patients taking a 250 mg daily dose of FULYZAQ 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, procedural pain, seasonal allergy, sinusitis and decreased white blood cell count.
Adverse reactions were similar in patients who received doses greater than 250 mg daily.
Postmarketing Experience
There is limited information regarding Postmarketing Experience of Crofelemer in the drug label.
Body as a Whole
Cardiovascular
Digestive
Endocrine
Hematologic and Lymphatic
Metabolic and Nutritional
Musculoskeletal
Neurologic
Respiratory
Skin and Hypersensitivy Reactions
Special Senses
Urogenital
Miscellaneous
Drug Interactions
Drug Interaction Potential
In vitro studies have shown that crofelemer has the potential to inhibit cytochrome P450 isoenzyme 3A and transporters MRP2 and OATP1A2 at concentrations expected in the gut. Due to the minimal absorption of crofelemer, it is unlikely to inhibit cytochrome P450 isoenzymes 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and CYP3A4 systemically [see Clinical Pharmacology (12.3)].
7.2 Nelfinavir, Zidovudine, and Lamivudine
FULYZAQ administration did not have a clinically relevant interaction with nelfinavir, zidovudine, or lamivudine in a drug-drug interaction trial.
Reproduction studies performed with crofelemer in rats at oral doses up to 177 times the recommended daily human dose of 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.
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Crofelemer in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Crofelemer during labor and delivery.
Nursing Mothers
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 FULYZAQ, 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.
Pediatric Use
The safety and effectiveness of FULYZAQ have not been established in pediatric patients less than 18 years of age.
Geriatic Use
Clinical studies with crofelemer did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients.
Gender
There is no FDA guidance on the use of Crofelemer with respect to specific gender populations.
Race
There is no FDA guidance on the use of Crofelemer with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Crofelemer in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Crofelemer in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Crofelemer in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Crofelemer in patients who are immunocompromised.
CD4 Count and HIV Viral Load
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 crofelemer was similar in patients with baseline CD4 cell count less than 404 cells/μL (lower limit of normal range) (N=388) and patients with baseline CD4 cell counts greater than or equal to 404 cells/μL (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).
Administration and Monitoring
Administration
Oral
Monitoring
There is limited information regarding Monitoring of Crofelemer in the drug label.
IV Compatibility
There is limited information regarding IV Compatibility of Crofelemer in the drug label.
Overdosage
There has been no reported experience with overdosage of crofelemer.
Pharmacology
There is limited information regarding Crofelemer Pharmacology in the drug label.
