A Multi-Center, Open-Label, Pharmacokinetic Drug Interaction Study of Erenumab and a Combined Oral Contraceptive in Healthy Females

Abstract

Background Erenumab is a human anti-calcitonin gene-related peptide monoclonal antibody developed for migraine prevention. Migraine predominately affects women of childbearing age; thus, it is important to determine potential drug–drug interactions between a common oral contraceptive and drugs used to treat migraine. Objectives We sought to evaluate potential drug–drug interactions between erenumab and a common oral contraceptive. Methods Healthy women received three cycles of a norgestimate/ethinyl estradiol-containing oral contraceptive with a single 140-mg subcutaneous dose of erenumab during cycle three. Norgestimate metabolites (norgestrel and norelgestromin) and ethinyl estradiol pharmacokinetics were evaluated in the absence and presence of erenumab. Primary endpoint was peak plasma concentration ( C max ) and area under concentration-time curve from time 0 to 24 h (AUC tau ). Luteinizing hormone, follicle-stimulating hormone, and progesterone concentrations were evaluated as pharmacodynamic markers. Results Erenumab did not influence the pharmacokinetics of norelgestromin, norgestrel, or ethinyl estradiol. Least-squares mean estimates (90% confidence interval) for C max ratios were 1.05 (0.90–1.23), 1.06 (0.97–1.16), and 1.04 (0.88–1.22) for norelgestromin, norgestrel, and ethinyl estradiol, respectively. Respective AUC tau ratios were 1.02 (0.94–1.12), 1.03 (0.96–1.10), and 1.02 (0.91–1.14). Luteinizing hormone, follicle-stimulating hormone, and progesterone concentrations were similar after exposure to oral contraceptive alone and with erenumab. Conclusion Erenumab did not alter the pharmacokinetics of the active components of an estrogen/progestin combination oral contraceptive. Thus, no change in contraceptive efficacy is expected with erenumab. Trial Registration ClinicalTrials.gov NCT02792517.

Different Doses of Erenumab for Preventive Treatment of Episodic Migraine: A Systematic Review and Network Meta-Analysis

“…From the pharmacokinetics perspective, as mAbs are eliminated via catabolic pathways, they may not compete directly with other small molecule drugs that are mainly eliminated via hepatic, renal, or biliary processes [32]. A study conducted in 2017 found that subcutaneous erenumab did not in uence the effect of estrogen/progestin combination oral contraceptives among healthy females [33]. A placebocontrolled trial investigating co-administration of erenumab 140 mg and sumatriptan 12 mg have found no additional effect on averages of mean arterial pressure or on the pharmacokinetics of sumatriptan [34].…”

Effects of Lemborexant on the Pharmacokinetics of Oral Contraceptives: Results From a Phase 1 Drug‐Drug Interaction Study in Healthy Females

“…Both these hormones are well-known active ingredients of several approved OCs. 7 During period 2, subjects were administered lemborexant 10 mg for 10 days starting on day 5 in the evening following the last OC PK sample. During period 3, lemborexant 10 mg was administered in the evening on days 15-18.…”

Monoclonal Antibodies Targeting CGRP: From Clinical Studies to Real-World Evidence—What Do We Know So Far?

“…From Phase I studies [ 5 , 7 , 8 , 9 ], assessing the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of erenumab, it was shown that erenumab is a safe and well tolerable drug with linear PK for doses above from 70 mg, typical IgG2 mAb behavior, and a highly potent CGRP receptor inhibitor profile. At 70 mg, the estimated elimination half-life of erenumab is 21 days, supporting monthly subcutaneous dosing and thus improving patient compliance [ 5 , 8 , 10 ].…”