Estraderm (estradiol) / Novartis - LARVOL DELTA

Development of breakthrough bleeding model of combined-oral contraceptives utilizing model-based meta-analysis. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Data from 25 studies containing BTB information of 4 progestins (desogestrel, drospirenone, gestodene, and levonorgestrel) in combination with ethinyl estradiol (EE) at various dose levels was used for this analysis...BTB typically returns to baseline within 3 months at the highest (30 μg) dose, whereas it can take significantly longer to reestablish a regular bleeding pattern at lower EE doses (15 and 20 μg), irrespective of the progestin used. The dose-response relationships established for BTB across different progestin/EE combinations can now be used to support the selection of optimal COC dosing/treatment regimens and serve as the scientific basis for evaluating the impact of clinically relevant factors, including drug-drug interactions and demographics, on BTB."

Journal • Retrospective data

Drug-drug interactions of icenticaftor (QBW251) with a 5-probe cytochrome P450 cocktail and oral contraceptives. (PubMed, Clin Transl Sci) - "with monophasic OC containing 30-μg EE and 150-μg LVG once daily reduced the plasma exposure of both components by approximately 50% and led to increased levels of follicle-stimulating hormone and luteinizing hormone. These results provide valuable guidance for the use of icenticaftor in patients taking concomitant medications that are substrates of CYP enzymes or patients using OCs."

Clinical • Journal • CYP2C19 • CYP3A4

Linking solid-state phenomena via energy differences in `archetype crystal structures'. (PubMed, IUCrJ) - "Archetype crystal structures are distinguished from crystal structure prediction trial structures in that an experimental reference structure is required for them. Categorization into archetype structures also has practical relevance, leading to a new practice of disorder modelling in experimental least-squares refinement alluded to in the above-mentioned publication."

Journal

Midostaurin drug interaction profile: a comprehensive assessment of CYP3A, CYP2B6, and CYP2C8 drug substrates, and oral contraceptives in healthy participants. (PubMed, Cancer Chemother Pharmacol) - "Midostaurin neither inhibits nor induces CYP3A4 and CYP2C8, and weakly induces CYP2B6. Midostaurin at steady state has no clinically relevant PK interaction on hormonal contraceptives. All treatments were well tolerated."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CYP3A4 • FLT3

"So, @Novartis how come I won't get my estradiol patches before -May-? I kind of need my medicine." (@Henchgirls)

Pharmacokinetic Interaction Between the MEK1/MEK2 Inhibitor Trametinib and Oral Contraceptives Containing Norethindrone and Ethinyl Estradiol in Female Patients With Solid Tumors. (PubMed, Clin Pharmacol Drug Dev) - "Coadministration of trametinib and COCs was generally well tolerated in this study, with observed safety signals consistent with the known safety profile of trametinib and no new reported safety events. Overall, the findings indicate that hormonal COCs can be coadministered in female patients who receive trametinib monotherapy without compromising the contraceptive efficacy."

Journal • PK/PD data • Endocrine Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Oral Cancer • Solid Tumor • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • MAP2K2

Phase 1/1b study of novel oral selective estrogen receptor degrader (SERD) LSZ102 for estrogen receptor-positive (ER+) advanced breast cancer (ABC) with progression on endocrine therapy (ET) (SABCS 2018) - "...Median age was 60 years, 75% (n=43) of pts had an ECOG PS of 0, 56% (n=32) had received prior fulvestrant, and 58% (n=33) had received prior CDK4/6 inhibitors; median number of prior lines of therapy (all settings) was 6... In heavily pretreated pts, LSZ102 was well tolerated, demonstrated antitumor activity, and achieved effective exposure levels based on PK and pharmacodynamics. Food intake did not appear to significantly alter the PK profile of LSZ102. Dose escalation for LSZ102 in combination with ribociclib or alpelisib is ongoing and will be reported in a future analysis."

P1 data • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

A Drug-Drug Interaction Study to Assess the Effect of Trametinib on the Pharmacokinetics of an Oral Contraceptive in Female Patients With Solid Tumors (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Novartis Pharmaceuticals; Trial completion date: Jan 2019 ➔ May 2019; Trial primary completion date: Jan 2019 ➔ Jan 2019

Trial completion date • Trial primary completion date • Biosimilar • Long-acting Reversible Contraceptives • Solid Tumor

Identification of atherosclerosis-related prioritizing metabolites based on a multi-omics composite network. (PubMed, Exp Ther Med) - "...Particularly, metabolites Tretinoin and Estraderm not only have high relation scores, but also contain more degrees. Moreover, we obtained 24 co-expression genes that may be regarded as the targets of atherosclerosis therapy. Therefore, identification of metabolite prioritizations by the composite network integrated the information of genes, phenotypes and metabolites may be available to diagnose atherosclerosis, and can provide the potential therapeutic strategies for atherosclerosis."

Journal

Prioritization of candidate metabolites for postmenopausal osteoporosis using multi-omics composite network. (PubMed, Exp Ther Med) - "Tretinoin was the member of the top 5 metabolites, and estraderm was a metabolite with the seventh interaction score. A series of metabolites, tretinoin and estraderm might be closely associated with the onset and progression of PO."

Journal

Osilodrostat Has No Clinically Relevant Effect on the Pharmacokinetic (PK) Profile of a Monophasic Oral Contraceptive in Healthy Females Receiving Cortisol Replacement Therapy (ENDO 2019) - "...Hydrocortisone was tapered/discontinued during TP3 (D20-28)... Concomitant treatment of osilodrostat (highest dose used in Phase 3 trials) with a single OC dose did not result in clinically relevant changes in OC PK parameters, suggesting that OC can be given with osilodrostat and provide adequate contraception.*Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference."

Clinical • PK/PD data

Osilodrostat Has No Clinically Relevant Effect on the Pharmacokinetic (PK) Profile of a Monophasic Oral Contraceptive in Healthy Females Receiving Cortisol Replacement Therapy (ENDO 2019) - "...At the end of TP3 (2 days after last hydrocortisone dose), 79% of subjects had ACTH-stimulated serum cortisol below the protocol-defined threshold, although all had normal unstimulated levels at study end; these Results may be related to high osilodrostat doses, hydrocortisone supplementation, timing of first stimulation test after last hydrocortisone dose or another factor... Concomitant treatment of osilodrostat (highest dose used in Phase 3 trials) with a single OC dose did not result in clinically relevant changes in OC PK parameters, suggesting that OC can be given with osilodrostat and provide adequate contraception."

Clinical • PK/PD data

Estradiol matrix patches for pubertal induction: stability of cut pieces at different temperatures. (PubMed, Endocr Connect) - "Unused Estraderm MX, Systen, and Oesclim patch pieces may be stored for at least one month at ≤+35ºC. Where estradiol patches for children are not available, cut pieces of these or similar patches can be used for pubertal induction. The Estradot patch was too small to properly cut into low doses and not stable in elevated temperatures."

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