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104 PharmacyTimes.org December 2015 S1251N, S1255P, and G1349D. After 24 weeks of treatment of ivacaftor, patients 6 years or older with these selected gat- ing mutations had an average improve- ment in predicted FEV 1 of 7.5%. Quality- of-life scores and changes in body mass index (BMI) favored ivacaftor therapy. In January 2012, outcomes data from these clinical trials prompted the FDA to first approve ivacaftor (Kalydeco) for patients 6 years and older with at least 1 copy of the mutation of G551D. 41,47 Additional evidence was presented, and ivacaftor was approved for patients with other gating mutations as well as the mutation R117H. Most recently, iva- caftor was approved for patients with CF aged 2 to 5 years. Dosing strategies for this therapy can be found in Table 4. 47,52 Appropriate counseling and monitoring is required with ivacaftor as described here. Ivacaftor is a CYP3A substrate and a weak inhibitor of CYP3A, P-glycoprotein, CYP2C8, and CYP2C9. 47 Additionally, coadministra- tion of ivacaftor with CYP3A inducers, such as rifampin, is not recommended. Pharmacists should complete a medica- tion history prior to initiating thera- py in patients, periodically assess for drug interactions, and recommend dose adjustments accordingly. Safety data highlighted that ivacaftor is well tolerated. 43,46,47 Common AEs reported were headache, upper respira- tory tract infection, nasal congestion, rash, and dizziness. 43,47 There was an incidence of liver enzyme increase great- er than 3 times the upper limit of normal in 6% and greater than 5 times the upper limit of normal in 2% of subjects on ivacaftor therapy. Close monitoring of hepatic transaminases is warranted. For individuals initiated on ivacaftor therapy, liver function testing should be performed every 3 months for the first year of therapy and annually thereafter. 47 During monitoring, if the alanine ami- notransferase level or the aspartate ami- notransferase level increases to greater than 5 times the upper limit of normal, ivacaftor should be temporarily discon- tinued until transaminitis has resolved. Researchers studied ivacaftor in indi- viduals who were homozygous for the most common CF-causing mutation, F508del. This therapy was studied in patients 12 years or older with 2 copies of the F508del mutation, but the results did not provide the same clinical effect as seen in ivacaftor in individuals with gating mutations. 48 This study provided additional safety evidence to indicate the treatment was well tolerated. Evidence from this study indicated that mono- therapy with a potentiator was not an effective therapeutic option for patients on ivacaftor monotherapy; rather, it may work in conjunction with a corrector. Lumacaftor Lumacaftor, a corrector, promotes the traf- ficking of mutated CFTR to and insertion into the cell membrane. 13,42 Specifically, lumacaftor corrects the underlying defect in patients with the most common CF-causing mutation, F508del. A phase 2 dose-finding study of 89 homozygous F508del adult subjects on lumacaftor did not provide results as anticipated. 49 There were no statistically significant changes in pulmonary func- tion. A second dose-finding study of lumacaftor dosed at 200 mg daily in con- junction with ivacaftor at 2 dosing strate- gies, 150 mg or 250 mg every 12 hours, was conducted. 50 This study included patients who were heterozygous for the mutation F508del. The study results indi- cated that lumacaftor in combination with CONTINUING EDUCATION TABLE 3: PANCREATIC ENZYME REPLACEMENT THERAPY 30 Brand Source Units per Dosage Lipase Protease Amylase Creon Porcine 3000 6000 12,000 24,000 36,000 9500 19,000 38,000 76,000 114,000 15,000 30,000 60,000 120,000 180,000 Pertzye Porcine 8000 16,000 28,750 57,500 30,250 60,500 Zenpep Porcine 3000 5000 10,000 15,000 20,000 25,000 40,000 10,000 17,000 34,000 51,000 68,000 85,000 136,000 16,000 27,000 55,000 82,000 109,000 136,000 218,000 Pancreaze Porcine 4200 10,500 16,800 21,000 10,000 25,000 40,000 37,000 17,500 43,750 70,000 61,000 Viokace a Porcine 10,400 20,880 39,150 78,300 39,150 78,300 a All are capsules with enteric-coated delayed-release microspheres, except for Viokace.