FDA Drug Approvals: Primary Care — Year in Review 2018

Mary L Windle, PharmD


January 15, 2019

Other New Drugs

Annovera (segesterone/ethinyl estradiol)

Segesterone/ethinyl estradiol is a reusable vaginal ring contraceptive that can be used for an entire year. The ring is inserted vaginally and should remain in place for 21 days, and then removed for 7 days, during which a withdrawal bleed occurs. The placement and removal cycle is repeated every 4 weeks for 13 cycles. Segesterone/ethinyl estradiol vaginal ring has not been adequately studied in women with a body mass index greater than 29 kg/m2.

Two 1-year multicenter trials (n >2000) were conducted in healthy and sexually active women with regular menstrual cycles. The pooled pregnancy rate, evaluated by the Pearl Index, was 2.98 pregnancies per 100 woman-years of use. (Annovera prescribing information)

Orilissa (elagolix)

Elagolix is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist. It inhibits endogenous GnRH signaling by binding competitively to GnRH receptors in the pituitary gland. Administration of elagolix results in dose-dependent suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to decreased blood concentrations of the ovarian sex hormones estradiol and progesterone. It is indicated for moderate-to-severe pain associated with endometriosis.

Approval of elagolix was based on two replicate phase 3 clinical trials (n=872). Improvement of dysmenorrhea was reported in 43.4-46.4% of women in the lower-dose elagolix groups and 72.4-75.8% in the higher-dose elagolix groups, compared with 19.6-22.7% in the placebo groups (P <.001 for all comparisons). Nonmenstrual pelvic pain improvement was reported by 49.8-50.4% of women in the lower-dose elagolix groups and 54.5-57.8% in the higher-dose groups, compared with 36.5% in the placebo groups (P=.003 and P <.001, respectively). (N Engl J Med. 2017 Jul 6;377(1):28-40)

Both elagolix doses are associated with hypoestrogenic adverse effects, including hot flushes, elevated serum lipids, and greater decreases from baseline in bone mineral density compared with women who received placebo. Because of this, treatment duration recommendations are specified for each dosage regimen.

Lokelma (sodium zirconium cyclosilicate)

Sodium zirconium cyclosilicate is a potassium binder indicated for adults with hyperkalemia. Nonabsorbed zirconium silicate preferentially captures potassium in exchange for hydrogen and sodium, resulting in increased fecal potassium excretion by binding and reducing the free potassium concentration in the GI lumen. Because of its delayed onset of action, it is not indicated for emergency treatment of life-threatening hyperkalemia.

Sodium zirconium cyclosilicate preferentially captures potassium in exchange for hydrogen and sodium, which reduces the free potassium concentration in the lumen of the GI tract and thereby lowers the serum potassium level. Like patiromer, sodium zirconium cyclosilicate should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action.

Approval was based on the HARMONIZE clinical trial in patients with serum potassium levels of 5.1 mEq/L or higher. In the open-label phase, serum potassium levels declined from 5.6 mEq/L at baseline to 4.5 mEq/L at 48 hours. Median time to normalization was 2.2 hours, with 84% of patients achieving normokalemia by 24 hours and 98% by 48 hours. In the randomized phase, serum potassium was significantly lower during days 8-29 with all three zirconium cyclosilicate doses versus placebo (4.8 mEq/L, 4.5 mEq/L, and 4.4 mEq/L for 5 g, 10 g, and 15 g, respectively; 5.1 mEq/L for placebo; P <.001 for all comparisons).

The HARMONIZE trial also included patients with heart failure who were maintained on renin-angiotensin-aldosterone system inhibitors (RAASi), which are known to cause elevated serum potassium levels. Compared with placebo, all three zirconium cyclosilicate doses lowered potassium and effectively maintained normokalemia for 28 days in patients with heart failure without the need to adjust RAASi regimens. (JAMA. 2014 Dec 3;312(21):2223-33)

Sodium zirconium cyclosilicate transiently increases gastric pH, which can change the absorption of coadministered drugs that exhibit pH-dependent solubility, potentially leading to altered efficacy or safety of these drugs when coadministered. In general, administer pH-dependent medications either 2 hours before or after sodium zirconium cyclosilicate. (Eur J Heart Fail. 2015 Oct;17(10):1050-6)

Motegrity (prucalopride)

Prucalopride, a selective serotonin type 4 (5-HT4) receptor agonist, elicits prokinetic actions that simulate colonic peristalsis, which increases bowel motility. It is indicated for adults with chronic idiopathic constipation (stirCIC).

Approval for CIC was based on an integrated analysis of six main clinical trials lasting a minimum of 12 weeks (n=2484). Results showed significantly more patients treated with prucalopride achieved an average of three or more spontaneous, complete bowel movements per week over 12 weeks than those given placebo (27.8% vs 13.2%; P<.001). A rapid response was seen with prucalopride as early as week 1, with improvements maintained throughout 12 weeks of treatment. (Motegrity (prucalopride) prescribing information)


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