TACROLIMUS capsule

Land: USA

Sprog: engelsk

Kilde: NLM (National Library of Medicine)

Aktiv bestanddel:

TACROLIMUS (UNII: WM0HAQ4WNM) (TACROLIMUS ANHYDROUS - UNII:Y5L2157C4J)

Tilgængelig fra:

Golden State Medical Supply, Inc.

INN (International Name):

TACROLIMUS

Sammensætning:

TACROLIMUS ANHYDROUS 0.5 mg

Indgivelsesvej:

ORAL

Recept type:

PRESCRIPTION DRUG

Terapeutiske indikationer:

Tacrolimus capsules are indicated for the prophylaxis of organ rejection, in adult patients receiving allogeneic kidney transplant  [see Clinical Studies (14.1)] , liver transplant [see Clinical Studies (14.2)] , and heart transplant [see Clinical Studies (14.3)] , and pediatric patients receiving allogeneic liver transplants [see Clinical Studies (14.2)]  in combination with other immunosuppressants. Additional pediatric use information is approved for Astellas Pharma US, Inc.’s Prograf (tacrolimus) products. However, due to Astellas Pharma US, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information. Tacrolimus capsules are contraindicated in patients with a hypersensitivity to tacrolimus. Tacrolimus injection is contraindicated in patients with a hypersensitivity to HCO-60 (polyoxyl 60 hydrogenated castor oil). Hypersensitivity symptoms reported include dyspnea, rash, pruritus, and acute respiratory distress syndrome [see Adverse Reactions (6)] . There is a pregnancy registry that monitors pregnancy outcomes in women exposed to tacrolimus during pregnancy. The Transplantation Pregnancy Registry International (TPRI) is a voluntary pregnancy exposure registry that monitors outcomes of pregnancy in female transplant recipients and those fathered by male transplant recipients exposed to immunosuppressants including tacrolimus. Healthcare providers are encouraged to advise their patients to register by contacting the Transplantation Pregnancy Registry International at 1-877-955-6877 or https://www.transplantpregnancyregistry.org/. Tacrolimus can cause fetal harm when administered to a pregnant woman. Data from postmarketing surveillance and TPRI suggest that infants exposed to tacrolimus in utero are at a risk of prematurity, birth defects/congenital anomalies, low birth weight, and fetal distress [see Human Data]. Advise pregnant women of the potential risk to the fetus. Administration of oral tacrolimus to pregnant rabbits and rats throughout the period of organogenesis was associated with maternal toxicity/lethality, and an increased incidence of abortion, malformation and embryofetal death at clinically relevant doses (0.5 to 6.9 times the recommended clinical dose range [0.2 to 0.075 mg/kg/day], on a mg/m 2 basis). Administration of oral tacrolimus to pregnant rats after organogenesis and throughout lactation produced maternal toxicity, effects on parturition, reduced pup viability and reduced pup weight at clinically relevant doses (0.8 to 6.9 times the recommended clinical dose range, on a mg/m 2 basis). Administration of oral tacrolimus to rats prior to mating, and throughout gestation and lactation produced maternal toxicity/lethality, marked effects on parturition, embryofetal loss, malformations, and reduced pup viability at clinically relevant doses (0.8 to 6.9 times the recommended clinical dose range, on a mg/m 2 basis). Interventricular septal defects, hydronephrosis, craniofacial malformations and skeletal effects were observed in offspring that died [see Animal Data] . The background risk of major birth defects and miscarriage in the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Risks during pregnancy are increased in organ transplant recipients. The risk of premature delivery following transplantation is increased. Pre-existing hypertension and diabetes confer additional risk to the pregnancy of an organ transplant recipient. Pre-gestational and gestational diabetes are associated with birth defects/congenital anomalies, hypertension, low birth weight and fetal death. Cholestasis of pregnancy (COP) was reported in 7% of liver or liver-kidney (LK) transplant recipients, compared with approximately 1% of pregnancies in the general population. However, COP symptoms resolved postpartum and no long-term effects on the offspring were reported. Tacrolimus may increase hyperglycemia in pregnant women with diabetes (including gestational diabetes). Monitor maternal blood glucose levels regularly [see Warnings and Precautions (5.4)] . Tacrolimus may exacerbate hypertension in pregnant women and increase pre-eclampsia. Monitor and control blood pressure [see Warnings and Precautions (5.7, 5.8)]. Renal dysfunction, transient neonatal hyperkalemia and low birth weight have been reported at the time of delivery in infants of mothers taking tacrolimus. There is an increased risk for premature delivery (< 37 weeks) following transplantation and maternal exposure to tacrolimus. There are no adequate and well controlled studies on the effects of tacrolimus in human pregnancy. Safety data from the TPRI and postmarketing surveillance suggest infants exposed to tacrolimus in utero have an increased risk for miscarriage, pre-term delivery (< 37 weeks), low birth weight (< 2500 g), birth defects/congenital anomalies and fetal distress. TPRI reported 450 and 241 total pregnancies in kidney and liver transplant recipients exposed to tacrolimus, respectively. The TPRI pregnancy outcomes are summarized in Table 16. In the table below, the number of recipients exposed to tacrolimus concomitantly with mycophenolic acid (MPA) products during the preconception and first trimester periods is high (27% and 29% for renal and liver transplant recipients, respectively). Because MPA products may also cause birth defects, the birth defect rate may be confounded and this should be taken into consideration when reviewing the data, particularly for birth defects. Birth defects observed include cardiac malformations, craniofacial malformations, renal/urogenital disorders, skeletal abnormalities, neurological abnormalities and multiple malformations. Kidney Liver Pregnancy Outcomes * 462 253    Miscarriage 24.5% 25%    Live births 331 180       Pre-term delivery (< 37 weeks) 49% 42%       Low birth weight (< 2500 g) 42% 30%       Birth defects 8% † 5% Additional information reported by TPRI in pregnant transplant patients receiving tacrolimus included diabetes during pregnancy in 9% of kidney recipients and 13% of liver recipients, and hypertension during pregnancy in 53% of kidney recipients and 16.2% of liver recipients. Administration of oral tacrolimus to pregnant rabbits throughout organogenesis produced maternal toxicity and abortion at 0.32 mg/kg (0.5 to 1.4 times the recommended clinical dose range [0.2 to 0.075 mg/kg/day], on a mg/m 2 basis). At 1 mg/kg (1.6 to 4.3 times the recommended clinical dose range), embryofetal lethality and fetal malformations (ventricular hypoplasia, interventricular septal defect, bulbous aortic arch, stenosis of ductus arteriosus, omphalocele, gallbladder agenesis, skeletal anomalies) were observed. Administration of 3.2 mg/kg oral tacrolimus (2.6 to 6.9 times the recommended clinical dose range) to pregnant rats throughout organogenesis produced maternal toxicity/lethality, embryofetal lethality and decreased fetal body weight in the offspring of C-sectioned dams; and decreased pup viability and interventricular septal defect in offspring of dams that delivered. In a peri-/postnatal development study, oral administration of tacrolimus to pregnant rats during late gestation (after organogenesis) and throughout lactation produced maternal toxicity, effects on parturition, and reduced pup viability at 3.2 mg/kg (2.6 to 6.9 times the recommended clinical dose range); among these pups that died early, an increased incidence of kidney hydronephrosis was observed. Reduced pup weight was observed at 1.0 mg/kg (0.8 to 2.2 times the recommended clinical dose range). Administration of oral tacrolimus to rats prior to mating, and throughout gestation and lactation, produced maternal toxicity/lethality, embryofetal loss and reduced pup viability at 3.2 mg/kg (2.6 to 6.9 times the recommended clinical dose range). Interventricular septal defects, hydronephrosis, craniofacial malformations and skeletal effects were observed in offspring that died. Effects on parturition (incomplete delivery of nonviable pups) were observed at 1 mg/kg (0.8 to 2.2 times the recommended clinical dose range) [see Nonclinical Toxicology (13.1)] . Controlled lactation studies have not been conducted in humans; however, tacrolimus has been reported to be present in human milk. The effects of tacrolimus on the breastfed infant, or on milk production have not been assessed. Tacrolimus is excreted in rat milk and in peri-/postnatal rat studies; exposure to tacrolimus during the postnatal period was associated with developmental toxicity in the offspring at clinically relevant doses [see Use in Specific Populations (8.1)and Nonclinical Toxicology (13.1)] . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tacrolimus and any potential adverse effects on the breastfed child from tacrolimus or from the underlying maternal condition. Tacrolimus can cause fetal harm when administered to pregnant women. Advise female and male patients of reproductive potential to speak to their healthcare provider on family planning options including appropriate contraception prior to starting treatment with tacrolimus [see Use in Specific Populations (8.1)and Nonclinical Toxicology (13.1)] . Based on findings in animals, male and female fertility may be compromised by treatment with tacrolimus [see Nonclinical Toxicology (13.1)] . Safety and effectiveness have been established in pediatric liver transplant patients. Safety and efficacy in pediatric liver transplant patients less than 16 years of age are based on evidence from active controlled studies that included 56 pediatric patients, 31 of which received tacrolimus. Additionally, 122 pediatric patients were studied in an uncontrolled trial of tacrolimus in living related donor liver transplantation. Pediatric patients generally required higher doses of tacrolimus to maintain blood trough concentrations of tacrolimus similar to adult patients [see Dosage and Administration (2.3), Adverse Reactions (6.1), Clinical Pharmacology (12.3)and Clinical Studies (14.2)] . Additional pediatric use information is approved for Astellas Pharma US, Inc.’s Prograf (tacrolimus) products. However, due to Astellas Pharma US, Inc.’s marketing exclusivity rights, this drug product is not labeled with that information. Clinical trials of tacrolimus did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. The pharmacokinetics of tacrolimus in patients with renal impairment was similar to that in healthy volunteers with normal renal function. However, consideration should be given to dosing tacrolimus at the lower end of the therapeutic dosing range in patients who have received a liver or heart transplant and have pre-existing renal impairment. Further reductions in dose below the targeted range may be required [see Dosage and Administration (2.4)and Clinical Pharmacology (12.3)] . The mean clearance of tacrolimus was substantially lower in patients with severe hepatic impairment (mean Child-Pugh score: > 10) compared to healthy volunteers with normal hepatic function. Close monitoring of tacrolimus trough concentrations is warranted in patients with hepatic impairment [see Clinical Pharmacology (12.3)] . The use of tacrolimus in liver transplant recipients experiencing post-transplant hepatic impairment may be associated with increased risk of developing renal insufficiency related to high whole blood trough concentrations of tacrolimus. These patients should be monitored closely and dosage adjustments should be considered. Some evidence suggests that lower doses should be used in these patients [see Dosage and Administration (2.5)and Clinical Pharmacology (12.3)]. African-American patients may need to be titrated to higher dosages to attain comparable trough concentrations compared to Caucasian patients [see Dosage and Administration (2.2)and Clinical Pharmacology (12.3)] . African-American and Hispanic patients are at increased risk for new onset diabetes after transplant. Monitor blood glucose concentrations and treat appropriately [see Warnings and Precautions (5.4)] .

Produkt oversigt:

Tacrolimus Capsules, USP are available containing the equivalent of 0.5 mg, 1 mg or 5 mg of anhydrous tacrolimus, USP. The 0.5 mg capsules are hard-shell gelatin capsules with a light orange opaque cap and a gray opaque body filled with white to off-white powder. The capsules are axially printed with MYLAN over 2045 in black ink on both the cap and the body. They are available as follows: NDC 60429-377-01 bottles of 100 capsules The 1 mg capsules are hard-shell gelatin capsules with a light blue opaque cap and a gray opaque body filled with white to off-white powder. The capsules are axially printed with MYLAN over 2046 in black ink on both the cap and the body. They are available as follows: NDC 60429-378-01 bottles of 100 capsules The 5 mg capsules are hard-shell gelatin capsules with a rubine red opaque cap and a gray opaque body filled with white to off-white powder. The capsules are axially printed with MYLAN over 2047 in black ink on both the cap and the body. They are available as follows: NDC 60429-379-01 bottles of 100 capsules Store and Dispense: Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Tacrolimus can cause fetal harm. Tacrolimus capsules should not be opened or crushed. Avoid inhalation or direct contact with skin or mucous membranes of the powder contained in tacrolimus capsules. If such contact occurs, wash the skin thoroughly with soap and water; if ocular contact occurs, rinse eyes with water. In case a spill occurs, wipe the surface with a wet paper towel. Follow applicable special handling and disposal procedures 1 .

Autorisation status:

Abbreviated New Drug Application

Produktets egenskaber

TACROLIMUS- TACROLIMUS CAPSULE
GOLDEN STATE MEDICAL SUPPLY, INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
TACROLIMUS CAPSULES. THESE HIGHLIGHTS DO NOT INCLUDE ALL THE
INFORMATION NEEDED TO USE
TACROLIMUS CAPSULES SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR
TACROLIMUS CAPSULES.
TACROLIMUS CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 1994
WARNING: MALIGNANCIES AND SERIOUS INFECTIONS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
INCREASED RISK FOR DEVELOPING SERIOUS INFECTIONS AND MALIGNANCIES WITH
TACROLIMUS
CAPSULES OR OTHER IMMUNOSUPPRESSANTS THAT MAY LEAD TO HOSPITALIZATION
OR DEATH. (
5.1, 5.2)
RECENT MAJOR CHANGES
Warnings and Precautions, Cannabidiol Drug Interactions ( 5.17)
08/2023
INDICATIONS AND USAGE
Tacrolimus capsules are a calcineurin-inhibitor immunosuppressant
indicated for the prophylaxis of organ
rejection in adult patients receiving allogeneic liver, kidney, or
heart transplants, and pediatric patients
receiving allogenic liver transplants in combination with other
immunosuppressants. ( 1.1)
DOSAGE AND ADMINISTRATION
Administer capsules consistently with or without food. ( 2.1)
Therapeutic drug monitoring is recommended. ( 2.1, 2.6)
Avoid eating grapefruit or drinking grapefruit juice. ( 2.1)
See dosage adjustments for African-American patients ( 2.2), hepatic
and renal impaired. ( 2.4, 2.5)
For complete dosing information, see Full Prescribing Information.
ADULT
Patient
Population
Initial Oral Dosage
Whole Blood Trough Concentration Range
Kidney Transplant
With
azathioprine
0.2 mg/kg/day capsules,
divided in two doses, every
12 hours
Month 1-3: 7-20 ng/mL
Month 4-12: 5-15 ng/mL
With MMF/IL-2
receptor
antagonist
0.1 mg/kg/day capsules,
divided in two doses, every
12 hours
Month 1-12: 4-11 ng/mL
Liver Transplant
With
corticosteroids
only
0.1-0.15 mg/kg/day
capsules, divided in two
doses, every
12 hours
Month 1-12: 5-20 ng/mL
Heart Transplant
With
azathioprine
or MMF
0.075 mg/kg/day capsules,
divided in two doses, every
12 hours
Month 1-3: 10-20 ng/mL
Mont