The approval was based on data from a 24-week open-label, two-part phase 3 study (ClinicalTrials.gov Identifier: NCT04537793) that evaluated the efficacy and safety of Trikafta in 75 children 2 to . No evidence of tumorigenicity from tezacaftor was observed in male and female rats at oral doses up to 50 and 75 mg/kg/day (approximately 1 and 2 times the MRHD based on summed AUCs of tezacaftor and its metabolites in males and females, respectively). Therefore, the dose of Trikafta should be reduced when used concomitantly with moderate or strong CYP3A inhibitors [see Dosage and Administration (2.3), Drug Interactions (7.2) and Clinical Pharmacology (12.3)]. The morning dose packets contain a fixed-dose combination of elexacaftor, tezacaftor, and ivacaftor oral granules. Ivacaftor has the following structural formula: Elexacaftor and tezacaftor bind to different sites on the CFTR protein and have an additive effect in facilitating the cellular processing and trafficking of select mutant forms of CFTR (including F508del-CFTR) to increase the amount of CFTR protein delivered to the cell surface compared to either molecule alone. Take one morning dose packet in the morning. Trikafta is supplied as: The elexacaftor 80 mg, tezacaftor 40 mg and ivacaftor 60 mg oral granules are supplied as white to off-white, sweetened, unflavored granules approximately 2 mm in diameter enclosed in unit-dose packets each containing 80 mg of elexacaftor, 40 mg of tezacaftor and 60 mg of ivacaftor. The elexacaftor 50 mg, tezacaftor 25 mg, and ivacaftor 37.5 mg tablets are supplied as light orange, capsule-shaped tablets; each containing 50 mg of elexacaftor, 25 mg of tezacaftor and 37.5 mg of ivacaftor. Trikafta is indicated for the treatment of cystic fibrosis (CF) in patients who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Co-administration of ivacaftor or tezacaftor/ivacaftor with digoxin, a sensitive P-gp substrate, increased digoxin AUC by 1.3-fold, consistent with weak inhibition of P-gp by ivacaftor. seizure medicines such as phenobarbital, carbamazepine (TEGRETOL, antifungal medicines including ketoconazole, itraconazole (such as SPORANOX, antibiotics including telithromycin, clarithromycin (such as BIAXIN. Patients should be advised to contact their health care provider if they have questions. Four such wallets are placed in a printed outer carton. Lower brain levels of P-glycoprotein activity in younger rats resulted in higher brain levels of tezacaftor and M1-TEZ. Avoid use of Trikafta in patients with pre-existing advanced liver disease (e.g., cirrhosis, portal hypertension, ascites, hepatic encephalopathy) unless the benefits are expected to outweigh the risks. Trikafta is supplied as: The elexacaftor 100 mg, tezacaftor 50 mg and ivacaftor 75 mg oral granules are supplied as white to off-white, sweetened, unflavored granules approximately 2 mm in diameter enclosed in unit-dose packets each containing 100 mg of elexacaftor, 50 mg of tezacaftor and 75 mg of ivacaftor. Inform patients that abnormality of the eye lens (cataract) has been noted in some children and adolescents receiving ivacaftor-containing regimens. The FDA approved package insert lists several mutations that are responsive to Kalydeco,Symdeko and Trikafta. Decreased fetal body weights were observed at a maternally toxic dose that produced exposures 5 times the MRHD (based on summed AUCs of ivacaftor and its metabolites). 7.3 Ciprofloxacin With the exception of sex differences in rash, the safety profile of Trikafta was generally similar across all subgroups of patients, including analysis by age, sex, baseline percent predicted FEV1 (ppFEV1) and geographic regions. The safety profile of Trikafta is based on data from 510 CF patients aged 12 years and older in two double-blind, controlled trials of 24 weeks and 4 weeks treatment duration (Trials 1 and 2). In a clinical study, following multiple doses of elexacaftor, tezacaftor and ivacaftor for 10 days, subjects with moderately impaired hepatic function (Child-Pugh Class B, score 7-9) had 25% higher AUC and 12% higher Cmax for elexacaftor, 73% higher AUC and 70% higher Cmax for M23-ELX, 36% higher AUC and 24% higher Cmax for combined elexacaftor and M23-ELX, 20% higher AUC but similar Cmax for tezacaftor and 1.5-fold higher AUC and 10% higher Cmax for ivacaftor compared with healthy subjects matched for demographics [see Dosage and Administration (2.2), Warnings and Precautions (5.1), Adverse Reactions (6) and Use in Specific Populations (8.7)]. In an EFD study in pregnant rats dosed during the period of organogenesis from gestation Days 6-17, elexacaftor was not teratogenic and did not affect fetal survival at exposures up to 9 times the MRHD (based on summed AUC for elexacaftor and its metabolite at maternal doses up to 40 mg/kg/day). These CBD candies offer a simple and flexible . Examples include eggs, butter, peanut butter, whole-milk dairy products (such as whole milk, cheese and yogurt), etc. No evidence of tumorigenicity was observed in male and female Tg.rasH2 transgenic mice at tezacaftor doses up to 500 mg/kg/day. Tear or cut the packet open along the cut line. The printing ink contains ammonium hydroxide, iron oxide black, propylene glycol, and shellac. For patients with a history of hepatobiliary disease or liver function test elevations, more frequent monitoring should be considered [see Dosage and Administration (2.2), Adverse Reactions (6), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)]. The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: 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 clinical practice. In an EFD study in pregnant rats dosed during the period of organogenesis from gestation Days 6-17 and in pregnant rabbits dosed during the period of organogenesis from gestation Days 7-20, tezacaftor was not teratogenic and did not affect fetal development or survival at exposures up to 3 and 0.2 times, respectively the MRHD (based on summed AUCs of tezacaftor and M1-TEZ). Medically reviewed by Drugs.com. The light blue tablet is marked with 'V 75' and contains the medicine ivacaftor. Both tablets are for oral administration. Patients received tezacaftor 100 mg qd/ivacaftor 150 mg q12h during a 4-week, open-label run-in period and were then randomized and dosed to receive Trikafta or tezacaftor 100 mg qd/ivacaftor 150 mg q12h during a 4-week, double-blind treatment period. The proportion of patients who had systolic blood pressure >140 mmHg and 10 mmHg increase from baseline on at least two occasions was 4% in Trikafta-treated patients and 1% in placebo-treated patients. If used , TRIKAFTA should be used with caution at a reduced dose (see Table 2) Lift here to open Mix entire contents of each packet of oral granules with one teaspoon (5 mL) of age-appropriate soft food or liquid that is at or below room temperature. The ivacaftor 59.5 mg oral granules are supplied as white to off-white, sweetened, unflavored granules approximately 2 mm in diameter enclosed in unit-dose packets each containing 59.5 mg of ivacaftor. Therefore, co-administration with strong CYP3A inducers is not recommended [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)]. The active ingredients of Trikafta are described below. Take 2 light orange tablets in the morning. Each unit-dose packet contains 100 mg of elexacaftor, 50 mg of tezacaftor, 75 mg of ivacaftor or 80 mg of elexacaftor, 40 mg of tezacaftor, 60 mg of ivacaftor and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose, hypromellose acetate succinate, lactose monohydrate, magnesium stearate, mannitol, sodium lauryl sulfate, and sucralose. Store Trikafta at room temperature between 68F to 77F (20C to 25C). Elexacaftor has the following structural formula: Tezacaftor is a white to off-white solid that is practically insoluble in water (<5 microgram/mL). Following multiple doses of tezacaftor and ivacaftor for 10 days, subjects with moderately impaired hepatic function had an approximately 36% higher AUC and a 10% higher in Cmax for tezacaftor and a 1.5-fold higher AUC but similar Cmax for ivacaftor compared with healthy subjects matched for demographics. Each tablet is debossed with "T50" on one side and plain on the other. trikafta (elexacaftor, tezacaftor, ivacaftor) oral granules 100 mg/50 mg/75 mg Co-packaged with (ivacaftor) oral granules 75 mg. 100 mg 50 mg 75 mg and 75 mg. 56 packets Carton contains: 4 individual wallets with 14 packets per wallet. Elexacaftor and ivacaftor are not substrates for OATP1B1 or OATP1B3; tezacaftor is a substrate for OATP1B1, but not OATP1B3. The mean ppFEV1 at baseline, following the 4-week, open-label run-in period with tezacaftor/ivacaftor was 60.9% (range: 35.0%, 89.0%). Trikafta is supplied as: The elexacaftor 100 mg, tezacaftor 50 mg, and ivacaftor 75 mg tablets are supplied as orange, capsule-shaped tablets; each containing 100 mg of elexacaftor, 50 mg of tezacaftor and 75 mg of ivacaftor. Trikafta is a prescription medicine used for the treatment of cystic fibrosis (CF) in people aged 2 years and older who have at least one copy of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or another mutation that is responsive to treatment with Trikafta. Potential for other drugs to affect elexacaftor/tezacaftor/ivacaftor. If used in patients with moderate hepatic impairment, Trikafta should be used with caution at a reduced dose (see Table 2). Drug interaction studies were performed with elexacaftor, tezacaftor and/or ivacaftor and other drugs likely to be co-administered or drugs commonly used as probes for pharmacokinetic interaction studies [see Drug Interactions (7)]. Use with caution in patients with severe (eGFR <30 mL/min/1.73 m2) renal impairment or end-stage renal disease [see Clinical Pharmacology (12.3)]. and ivacaftor and 7 tablets of ivacaftor), (elexacaftor, tezacaftor and ivacaftor) Carton contains: 4 individual Ivacaftor may inhibit CYP2C9; therefore, monitoring of the international normalized ratio (INR) during co-administration of Trikafta with warfarin is recommended. FOR INITIAL REQUESTS ONLY: For patients age 12 years and older: Is patient's FEV1 40-90% inclusive, obtained while the patient is NOT receiving Trikafta is not expected to have an impact on the efficacy of oral contraceptives. Patients had a ppFEV1 at screening between 40-90%. The dosage of Trikafta should be reduced when co-administered with strong CYP3A inhibitors [see Dosage and Administration (2.3), Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)]. Ivacaftor impaired fertility and reproductive performance indices in male and female rats at 200 mg/kg/day (approximately 7 and 5 times, respectively, the MRHD based on summed AUCs of ivacaftor and its metabolites). Trikafta tablets are supplied in a co-packaged blister pack sealed into a printed wallet, containing elexacaftor, tezacaftor and ivacaftor fixed-dose combination tablets and ivacaftor tablets. Treatment is not recommended for patients with moderate hepatic impairment (Child-Pugh Class B, score 7-9). In Trial 4 (patients aged 2 to less than 6 years who had at least one F508del mutation or a mutation known to be responsive to Trikafta, the mean absolute change in sweat chloride from baseline through Week 24 was -57.9 mmol/L (95% CI: -61.3, -54.6). Each tablet is printed with the characters "V 150" in black ink on one side and plain on the other. Ciprofloxacin had no clinically relevant effect on the exposure of tezacaftor or ivacaftor and is not expected to affect the exposure of elexacaftor. Trikafta is for oral use. No adverse developmental effects were observed after oral administration of elexacaftor, tezacaftor or ivacaftor to pregnant rats from the period of organogenesis through lactation at doses that produced maternal exposures approximately 1 time, approximately 1 time and 3 times the exposures at the MRHD, respectively [based on summed AUCs of parent and metabolite(s)] (see Data). The active ingredients of TRIKAFTA are described below. Elexacaftor is a white solid that is practically insoluble in water (<1 mg/mL). Instructions for Administration of Oral Granules. Elexacaftor did not cause reproductive system toxicity in male rats at 55 mg/kg/day and female rats at 25 mg/kg/day, equivalent to approximately 6 times and 4 times the MRHD, respectively (based on summed AUCs of elexacaftor and its metabolite). Pediatric Patients 12 to Less Than 18 Years of Age. Although there are no animal reproduction studies with the concomitant administration of elexacaftor, tezacaftor and ivacaftor, separate reproductive and developmental studies were conducted with each active component of Trikafta in pregnant rats and rabbits. Trikafta oral granules (age 2 to less than 6 years weighing less than 14 kg): The white and blue packets each contain the medicines elexacaftor, tezacaftor, and ivacaftor. Placental transfer of elexacaftor was observed in pregnant rats. Take Trikafta exactly as your doctor tells you to take it. The elexacaftor, tezacaftor and ivacaftor tablets are orange, capsuleshaped, and debossed with "T100" on one side and plain on the other. The safety profile of patients in these trials was similar to that observed in Trial 1 [see Adverse Reactions (6)]. are breastfeeding or planning to breastfeed. In Trial 1 [ see Adverse Reactions ( 6 ) ] the exposure of tezacaftor or and... 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