Drug interactions between rifamycin antibiotics and hormonal contraception: a systematic review.

BACKGROUND: Rifamycin antibiotics are commonly used for treatment of tuberculosis, but may reduce the effectiveness of hormonal contraception (HC). OBJECTIVES: To determine whether interactions between rifamycins and HC result in decreased effectiveness or increased toxicity of either therapy. SEARCH STRATEGY: We searched MEDLINE, Embase, Cochrane and clinicaltrials.gov through May 2017. SELECTION CRITERIA: We included trials, cohort, and case-control studies addressing pregnancy rates, pharmacodynamics or pharmacokinetic (PK) outcomes when HC and rifamycins were administered together versus apart. Of 7291 original records identified, 11 met inclusion criteria after independent review by two authors. DATA COLLECTION AND ANALYSIS: Two authors independently abstracted study details and assessed study quality using the United States Preventive Services Task Force grading system. Findings are reported descriptively. MAIN RESULTS: Studies only addressed combined oral contraceptives (COCs) and none reported pregnancy rates. Quality ranged from good to poor. Rifampin increased the frequency of ovulation in two of four studies, and reduced estrogen and/or progestin exposure in five studies. Rifabutin led to smaller PK changes than rifampin in two studies. In one study each, rifaximin and rifalazil did not alter hormone PK. CONCLUSIONS: No studies evaluated pregnancy risk or non-oral HCs. PK and ovulation outcomes support a clinically concerning drug interaction between COCs and rifampin, and to a lesser extent rifabutin. Data are limited for other rifamycins. TWEETABLE ABSTRACT: Rifampin and rifabutin reduce systemic exposure of oral contraceptives, but no studies have evaluated pregnancy risk.

Intracameral administration of neurotensin induces miosis in the rabbit.

The present investigation was designed to evaluate the effect of selected peptides on pupillary diameter and intraocular pressure (IOP) in rabbits. Intracameral (IC) administration of neurotensin (NT) in doses of 5-100 micrograms produced a significant, long lasting and dose-dependent decrease in pupillary diameter without affecting IOP. NT-induced miosis appears to be relatively specific because a variety of peptides including Gn-RH, somatostatin, met-enkephalin, bombesin, leu-enkephalin or NT1-6, (a biologically inactive N-terminal fragment of NT), produced no effect on pupillary diameter; only substance P produced miosis similar to NT when tested in a dose equimolar to 30 micrograms of NT. In addition, peripheral (intravenous) administration of NT (100 micrograms/kg) was equally ineffective. Inhibition of prostaglandin synthesis with indomethacin, did not prevent subsequent NT-induced miosis. Finally, IC administration of an effective dose of NT (30 micrograms) did not alter the protein concentration in the aqueous humor. These results indicate that NT-induced miosis is not mediated by endogenous prostaglandins and that this effect of NT does not appear to involve disruption of the blood-aqueous barrier, suggesting that NT may play a role in regulation of pupillary diameter.