The risk appears to be related to the intensity and duration of immunosuppression rather than to the use of any specific agent. These effects occurred at systemic exposure levels that are equivalent to or less than the clinical exposure at the recommended dose of 2 g/day for renal transplant recipients. • Abnormalities of the ear (e.g. When comparing rates of transplant rejection, rates of graft loss or adverse event profiles between CellCept patients with and without concomitant telmisartan medication, no clinical consequences of the pharmacokinetic drug-drug interaction were seen.Based on the results of a single dose administration study of recommended doses of oral mycophenolate and IV ganciclovir and the known effects of renal impairment on the pharmacokinetics of CellCept (see section 4.2) and ganciclovir, it is anticipated that co-administration of these agents (which compete for mechanisms of renal tubular secretion) will result in increases in MPAG and ganciclovir concentration. Three patients who received Orkambi had liver-related serious adverse reactions, including 2 reported as transaminase elevations and 1 as hepatic encephalopathy, compared to none in the placebo group.
Therefore, co-administration with strong CYP3A inducers, such as rifampin, rifabutin, phenobarbital, carbamazepine, phenytoin, and St. John's wort (No dose adjustment is recommended when used with moderate or weak CYP3A inducers.Lumacaftor is a strong inducer of CYP3A. The systemic exposure at this dose was approximately 0.5 times the clinical exposure at the recommended clinical dose of 2 g/day for renal transplant patients and approximately 0.3 times the clinical exposure at the recommended clinical dose of 3 g/day for cardiac transplant patients. Examples of fat-containing foods include eggs, avocados, nuts, butter, peanut butter, cheese pizza, whole-milk dairy products (such as whole milk, cheese, and yogurt), etc. Drugs which interfere with MPA's enterohepatic cycle (e.g. It is recommended that the second test should be performed 8 - 10 days after the first test. Orkambi is a combination of lumacaftor and ivacaftor indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who are homozygous for the 2.1 Dosing Information in Adults and Children Age 6 Years and OlderTake two lumacaftor 100 mg/ivacaftor 125 mg tablets every 12 hours with fat-containing food.Liver function decompensation, including liver failure leading to death, has been reported in CF patients with pre-existing cirrhosis with portal hypertension while receiving Orkambi.
Patients should not donate blood during therapy or for at least 6 weeks following discontinuation of mycophenolate. Female patients of childbearing potential should be made aware of the risks and follow the recommendations provided in section 4.6 (e.g. These changes may suggest a 'left shift' in the maturity of neutrophils in haematological investigations, which may be mistakenly interpreted as a sign of infection in immunosuppressed patients such as those that receive CellCept.The most serious gastrointestinal disorders were ulceration and hemorrhage which are known risks associated with mycophenolate mofetil. These events occurred more frequently in the subset of female patients treated with Orkambi who were using hormonal contraceptives (27%) compared to those not using hormonal contraceptives (3%) In Trials 1 and 2, adverse reactions related to increases in blood pressure (The proportion of patients who experienced a systolic blood pressure value >140 mmHg or a diastolic blood pressure >90 mmHg on at least two occasions was 3.6% and 2.2% in patients treated with Orkambi, respectively, compared with 1.6% and 0.5% in patients who received placebo Because post-marketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.Post –marketing cases of liver function decompensation including liver failure leading to death have been reported in CF patients with pre-existing cirrhosis with portal hypertension who were treated with Orkambi Co-administration of lumacaftor/ivacaftor with itraconazole, a strong CYP3A inhibitor, did not impact the exposure of lumacaftor, but increased ivacaftor exposure by 4.3-fold. I'm Kellie, creator of Blackboard Kitchen. Following this period, continue with the recommended daily dose Patients should be instructed to tell their doctor if they stop Orkambi for more than 1 week while they are also taking a strong CYP3A inhibitor because the dose of Orkambi would need to be reduced upon re-initiation. Therefore, it should be avoided in patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome.Caution should be exercised when switching combination therapy from regimens containing immunosuppressants, which interfere with MPA enterohepatic recirculation, e.g. A dose reduction to 2 tablets in the morning and 1 tablet in the evening is recommended for patients with moderate hepatic impairment (Child-Pugh Class B).Studies have not been conducted in patients with severe hepatic impairment (Child-Pugh Class C), but exposure is expected to be higher than in patients with moderate hepatic impairment. Patients on CellCept who develop recurrent infections should have their serum immunoglobulins measured.