NEVIRAPINE suspension

Quốc gia: Hoa Kỳ

Ngôn ngữ: Tiếng Anh

Nguồn: NLM (National Library of Medicine)

Thành phần hoạt chất:

NEVIRAPINE HEMIHYDRATE (UNII: B7XF2TD73C) (NEVIRAPINE - UNII:99DK7FVK1H)

Sẵn có từ:

Aurobindo Pharma Limited

INN (Tên quốc tế):

NEVIRAPINE HEMIHYDRATE

Thành phần:

NEVIRAPINE 50 mg in 5 mL

Tuyến hành chính:

ORAL

Loại thuốc theo toa:

PRESCRIPTION DRUG

Chỉ dẫn điều trị:

Nevirapine oral suspension is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection in adults and pediatric patients 15 days and older [see Clinical Studies (14.1, 14.2)] . Limitations of Use: Based on serious and life-threatening hepatotoxicity observed in controlled and uncontrolled trials, nevirapine oral suspension is not recommended to be initiated, unless the benefit outweighs the risk, in: - adult females with CD4+ cell counts greater than 250 cells/mm3 or - adult males with CD4+ cell counts greater than 400 cells/mm3 [see Warnings and Precautions (5.1)]. Nevirapine oral suspension is contraindicated: - in patients with moderate or severe (Child-Pugh Class B or C, respectively) hepatic impairment [see Warnings and Precautions (5.1)  and Use in Specific Populations (8.7) ]. - for use as part of occupational and non-occupational post-exposure prophylaxis (PEP) regimens [see Warnings and Precautions (5.1)]. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to nevirapine during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Available data from the APR show no difference in the risk of overall major birth defects for nevirapine compared with the background rate for major birth defects of 2.7% in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) [see Data] . The rate of miscarriage is not reported in the APR. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15 to 20%. The background risk of birth defects and miscarriage for the indicated population is unknown. Methodological limitations of the APR include the use of MACDP as the external comparator group. The MACDP population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at <20 weeks gestation. In literature reports, immediate-release nevirapine exposure (Cmin ) can be up to 29% lower during pregnancy. However, as this reduction was not found to be clinically meaningful, dose adjustment is not necessary [see Data] . There is a risk for severe hepatic events in pregnant women exposed to nevirapine [see Clinical Considerations] . In animal reproduction studies, no evidence of adverse developmental outcomes was observed following oral administration of nevirapine during organogenesis in the rat and rabbit, at systemic exposures (AUC) to nevirapine approximately equal (rats) and 50% higher (rabbits) than the exposure in humans at the recommended 400 mg daily dose [see Data] . Clinical Considerations Maternal adverse reactions Severe hepatic events, including fatalities, have been reported in pregnant women receiving chronic nevirapine therapy as part of combination treatment of HIV-1 infection. Regardless of pregnancy status, women with CD4+ cell counts greater than 250 cells/mm3 should not initiate nevirapine unless the benefit outweighs the risk. It is unclear if pregnancy augments the risk observed in non-pregnant women [see Warnings and Precautions (5.1)] . Data Human Data Based on prospective reports to the APR of exposures to nevirapine during pregnancy resulting in live births (including over 1100 exposed in the first trimester and over 1500 exposed in the second/third trimester), the prevalence of birth defects in live births was 3.0% (95% CI: 2.1%, 4.1%) and 3.3% (95% CI: 2.4%, 4.3%) following first and second/third trimester exposure, respectively, to nevirapine-containing regimens, compared with the background birth defect rate of 2.7% in a U.S. reference population of the MACDP. There are several literature reports of chronic administration of immediate-release nevirapine during pregnancy, in which nevirapine pharmacokinetics were compared between pregnancy and postpartum. In these studies, the mean difference in nevirapine Cmin during pregnancy as compared to postpartum ranged from no difference to approximately 29% lower. Animal Data Nevirapine was administered orally to pregnant rats (at 0, 12.5, 25, and 50 mg per kg per day) and rabbits (at 0, 30, 100, and 300 mg per kg per day) through organogenesis (on gestation days 7 through 16, and 6 through 18, respectively). No adverse developmental effects were observed at doses producing systemic exposures (AUC) approximately equivalent to (rats) or approximately 50% higher (rabbits) than human exposure at the recommended daily dose. In rats, decreased fetal body weights were observed at a maternally toxic dose at an exposure approximately 50% higher than the recommended daily dose. Risk Summary The Centers for Disease Control and Prevention recommend that HIV-1 infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection. Published data report that nevirapine is present in human milk [see Data] . There are limited data on the effects of nevirapine on the breastfed infant. There is no information on the effects of nevirapine on milk production. Because of the potential for (1) HIV-1 transmission (in HIV-negative infants), (2) developing viral resistance (in HIV-positive infants), and (3) serious adverse reactions in nursing infants, mothers should not breastfeed if they are receiving nevirapine. Data Based on five publications, immediate-release nevirapine was excreted in breast milk at median concentrations ranging from 4080 to 6795 ng/mL, and the median maternal breast milk to maternal plasma concentration ratio range was 59 to 88%. Reported infant nevirapine median plasma concentrations were low, ranging from 734 to 1140 ng/mL. The estimated nevirapine dose of 704 to 682 mcg/kg/day for infants fed exclusively with breast milk was lower than the daily recommended nevirapine dose for infants. Published literature indicates that rash and hyperbilirubinemia have been seen in infants exposed to nevirapine through breastmilk. Infertility Limited human data are insufficient to determine the risk of infertility in humans. Based on results from animal fertility studies conducted in rats, nevirapine may reduce fertility in females of reproductive potential. It is not known if these effects on fertility are reversible [see Nonclinical Toxicology (13.1)] . The safety, pharmacokinetic profile, and virologic and immunologic responses of nevirapine have been evaluated in HIV-1 infected pediatric subjects aged 3 months to 18 years [see Adverse Reactions (6.1) and Clinical Studies (14.2)] . The safety and pharmacokinetic profile of nevirapine has been evaluated in HIV-1 infected pediatric subjects aged 15 days to less than 3 months [see Adverse Reactions (6.1) and Clinical Studies (14.2)] . The most frequently reported adverse events related to nevirapine in pediatric subjects were similar to those observed in adults, with the exception of granulocytopenia, which was more commonly observed in children receiving both zidovudine and nevirapine [see Adverse Reactions (6.1)  and Clinical Studies (14.2) ]. Clinical trials of nevirapine did not include sufficient numbers of subjects aged 65 and older to determine whether elderly subjects respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. In subjects with renal impairment (mild, moderate or severe), there were no significant changes in the pharmacokinetics of nevirapine. Nevirapine is extensively metabolized by the liver and nevirapine metabolites are extensively eliminated by the kidney. Nevirapine metabolites may accumulate in patients receiving dialysis; however, the clinical significance of this accumulation is not known. No adjustment in nevirapine dosing is required in patients with CrCL greater than or equal to 20 mL per min. The pharmacokinetics of nevirapine have not been evaluated in patients with CrCl less than 20 mL per min. In patients undergoing chronic hemodialysis, an additional 200 mg dose following each dialysis treatment is indicated [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ] . Because increased nevirapine levels and nevirapine accumulation may be observed in patients with serious liver disease, do not administer nevirapine to patients with moderate or severe (Child-Pugh Class B or C, respectively) hepatic impairment [see Contraindications (4), Warnings and Precautions (5.1), and Clinical Pharmacology (12.3)] .

Tóm tắt sản phẩm:

Nevirapine Oral Suspension, USP is a white to off-white homogenous suspension containing 50 mg nevirapine (as nevirapine hemihydrate) in each 5 mL. Nevirapine suspension is supplied in HDPE bottles with child-resistant closures.                          100 mL Bottle                           NDC 65862-057-11                          240 mL Bottle                           NDC 65862-057-24 Storage Nevirapine Oral Suspension, USP should be stored at 20 ° to 25 ° C (68 ° to 77 ° F); excursions permitted to 15 ° to 30 ° C (59 ° to 86 ° F) [see USP Controlled Room Temperature]. Store in a safe place out of the reach of children.

Tình trạng ủy quyền:

Abbreviated New Drug Application

Tờ rơi thông tin

Aurobindo Pharma Limited
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MEDICATION GUIDE
Nevirapine Oral Suspension, USP
(ne vir' a peen)
What is the most important information I should know about nevirapine
oral suspension?
Nevirapine oral suspension can cause severe liver and skin problems
that may lead to death. These problems
can happen at any time during treatment, but your risk is higher
during the first 18 weeks of treatment.
Nevirapine oral suspension can cause serious side effects, including:
• Severe liver problems. Some people taking nevirapine oral
suspension may develop severe liver problems
that can lead to liver failure and the need for a liver transplant, or
death. If you have liver problems, you may
get a rash.
• Women have a higher risk of developing liver problems during
treatment with nevirapine oral
suspension than men.
• People who have abnormal liver test results before starting
nevirapine oral suspension and people with
hepatitis B or C also have a greater risk of getting liver problems.
People who have higher CD4+ cell counts when they begin nevirapine
oral suspension have a higher risk
of liver problems, especially:
• Women with CD4+ counts higher than 250 cells/mm3. This group has
the highest risk.
• Men with CD4+ counts higher than 400 cells/mm3.
Stop taking nevirapine oral suspension and call your doctor right away
if you have any of the following
symptoms of liver problems with or without a skin rash:
• dark (tea colored) urine
• yellowing of your skin or whites of your eyes
• light-colored bowel movements (stools)
• fever
• feeling sick to your stomach (nausea)
• feel unwell or like you have the flu
• pain or tenderness on your right side below your ribs
• tiredness
• loss of appetite
• Severe skin reactions and rash. Some skin reactions and rashes may
be severe, life-threatening, and in some
people, may lead to death. Most severe skin reactions and rashes
happen in the first 6 weeks of treatment
with nevirapine oral suspension.
• Women have a higher risk of developing a rash during tre

Đặc tính sản phẩm

NEVIRAPINE - NEVIRAPINE SUSPENSION
AUROBINDO PHARMA LIMITED
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
NEVIRAPINE ORAL
SUSPENSION SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION
FOR NEVIRAPINE ORAL
SUSPENSION.
NEVIRAPINE ORAL SUSPENSION
INITIAL U.S. APPROVAL: 1996
WARNING: LIFE-THREATENING (INCLUDING FATAL) HEPATOTOXICITY AND SKIN
REACTIONS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
FATAL AND NON-FATAL HEPATOTOXICITY HAVE BEEN REPORTED IN PATIENTS
TAKING
NEVIRAPINE. DISCONTINUE IMMEDIATELY IF CLINICAL HEPATITIS OR
TRANSAMINASE ELEVATIONS
COMBINED WITH RASH OR OTHER SYSTEMIC SYMPTOMS OCCUR. DO NOT RESTART
NEVIRAPINE
AFTER RECOVERY. (5.1)
FATAL AND NON-FATAL SKIN REACTIONS, INCLUDING STEVENS-JOHNSON
SYNDROME, TOXIC
EPIDERMAL NECROLYSIS, AND HYPERSENSITIVITY REACTIONS, HAVE BEEN
REPORTED.
DISCONTINUE IMMEDIATELY IF SEVERE SKIN REACTIONS, HYPERSENSITIVITY
REACTIONS, OR ANY
RASH WITH SYSTEMIC SYMPTOMS OCCUR. CHECK TRANSAMINASE LEVELS
IMMEDIATELY FOR ALL
PATIENTS WHO DEVELOP A RASH IN THE FIRST 18 WEEKS OF TREATMENT. DO NOT
RESTART
NEVIRAPINE AFTER RECOVERY. (5.2)
MONITORING DURING THE FIRST 18 WEEKS OF THERAPY IS ESSENTIAL. EXTRA
VIGILANCE IS
WARRANTED DURING THE FIRST 6 WEEKS OF THERAPY, WHICH IS THE PERIOD OF
GREATEST RISK
OF THESE EVENTS. (5.1, 5.2)
INDICATIONS AND USAGE
Nevirapine is an NNRTI indicated in combination with other
antiretroviral agents for the treatment of
human immunodeficiency virus (HIV-1) infection in adults and pediatric
patients 15 days and older. (1)
Limitations of Use:
Based on serious and life-threatening hepatotoxicity observed in
controlled and uncontrolled trials,
nevirapine is not recommended to be initiated, unless the benefit
outweighs the risk, in:
adult females with CD4 cell counts greater than 250 cells/mm
adult males with CD4 cell counts greater than 400 cells/mm (1, 5.1)
DOSAGE AND ADMINISTRATION
The 14-day lead-in period must be strictly followed; it has been
demonstrated to reduc