breakthrough bleeding. Advise females of reproductive potential to use effective non-hormonal contraception.moexiprilMonitor Closely (1)moexipril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.nabumetoneMonitor Closely (1)drospirenone and nabumetone both increase serum potassium. Modify Therapy/Monitor Closely.nadololMonitor Closely (1)nadolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.naproxenMonitor Closely (1)drospirenone and naproxen both increase serum potassium. Modify Therapy/Monitor Closely.nebivololMonitor Closely (1)nebivolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.noni juiceMonitor Closely (1)drospirenone and noni juice both increase serum potassium. Use Caution/Monitor.norepinephrineMonitor Closely (1)drospirenone increases and norepinephrine decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.octacosanolMinor (1)octacosanol increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.olmesartanMonitor Closely (1)olmesartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.omaveloxoloneSerious - Use Alternative (1)omaveloxolone will decrease the level or effect of drospirenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Omaveloxolone may reduce efficacy of hormonal contraceptives (eg, pill, patch, ring), implants, and progestin-only pills owing to weak CYP3A4 induction.oxaprozinMonitor Closely (1)drospirenone and oxaprozin both increase serum potassium. Modify Therapy/Monitor Closely.parecoxibMonitor Closely (1)drospirenone and parecoxib both increase serum potassium. Modify Therapy/Monitor Closely.penbutololMonitor Closely (1)penbutolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.perindoprilMonitor Closely (1)perindopril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.pindololMonitor Closely (1)pindolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.pirbuterolMonitor Closely (1)drospirenone increases and pirbuterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.piroxicamMonitor Closely (1)drospirenone and piroxicam both increase serum potassium. Modify Therapy/Monitor Closely.pivmecillinamMonitor Closely (1)pivmecillinam increases effects of drospirenone by unspecified interaction mechanism. Use Caution/Monitor. Hyperkalemia.potassium acid phosphateSerious - Use Alternative (1)drospirenone and potassium acid phosphate both increase serum potassium. Avoid or Use Alternate Drug.potassium chlorideSerious - Use Alternative (1)drospirenone and potassium chloride both increase serum potassium. Avoid or Use Alternate Drug.potassium citrateSerious - Use Alternative (1)drospirenone and potassium citrate both increase serum potassium. Avoid or Use Alternate Drug.potassium citrate/citric acidMonitor Closely (1)drospirenone and potassium citrate/citric acid both increase serum potassium. Use Caution/Monitor.potassium iodideMonitor Closely (1)potassium iodide and drospirenone both increase serum potassium. Use Caution/Monitor.potassium phosphates, IVSerious - Use Alternative (1)drospirenone and potassium phosphates, IV both increase serum potassium. Avoid or Use Alternate Drug.propranololMonitor Closely (1)propranolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.quinaprilMonitor Closely (1)quinapril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.ramiprilMonitor Closely (1)ramipril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.reishiMinor (1)reishi increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.ruxolitinibMinor (1)drospirenone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.ruxolitinib topicalMinor (1)drospirenone will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.sacubitril/valsartanMonitor Closely (1)sacubitril/valsartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.salicylates (non-asa)Monitor Closely (1)drospirenone and salicylates (non-asa) both increase serum potassium. Modify Therapy/Monitor Closely.salmeterolMonitor Closely (1)drospirenone increases and salmeterol decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.salsalateMonitor Closely (1)drospirenone and salsalate both increase serum potassium. Modify Therapy/Monitor Closely.shepherd's purseMinor (1)shepherd's purse, drospirenone. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.siltuximabMonitor Closely (1)siltuximab, drospirenone. Other (see comment). Use Caution/Monitor. Comment: CYP450 activity in the liver is down regulated by infection and inflammation stimuli including cytokines (eg, IL-6); inhibition of IL-6 by siltuximab may restore CYP450 enzymatic activity; caution if coadministered with CYP substrates that have a narrow therapeutic index.somapacitanMonitor Closely (1)drospirenone will decrease the level or effect of somapacitan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Oral estrogens may reduce serum insulin-like growth factor I (IGF-1) response to growth hormone (GH) analogs. Higher GH dose may be requiredsomatrogonMonitor Closely (1)drospirenone will decrease the level or effect of somatrogon by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Oral estrogens may reduce serum insulin-like growth factor I (IGF-1) response to growth hormone (GH) analogs. Higher GH dose may be requiredsomatropinMonitor Closely (1)drospirenone will decrease the level or effect of somatropin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Oral estrogens may reduce serum insulin-like growth factor I (IGF-1) response to growth hormone (GH) analogs. Higher GH dose may be requiredsotalolMonitor Closely (1)sotalol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.sparsentanMonitor Closely (1)sparsentan and drospirenone both increase serum potassium. Use Caution/Monitor. Monitor serum potassium frequently.spironolactoneSerious - Use Alternative (2)drospirenone and spironolactone both increase serum potassium. Avoid or Use Alternate Drug. drospirenone, spironolactone. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hyperkalemia.succinylcholineMonitor Closely (1)drospirenone and succinylcholine both increase serum potassium. Modify Therapy/Monitor Closely.sulfadiazineMinor (1)drospirenone increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.sulfamethoxazoleMinor (2)drospirenone, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia. drospirenone increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.sulfasalazineMonitor Closely (1)drospirenone and sulfasalazine both increase serum potassium. Modify Therapy/Monitor Closely.sulfisoxazoleMinor (1)drospirenone increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.sulindacMonitor Closely (1)drospirenone and sulindac both increase serum potassium. Modify Therapy/Monitor Closely.tazemetostatMonitor Closely (1)drospirenone will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.telmisartanMonitor Closely (1)telmisartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.temocillinMonitor Closely (1)temocillin increases effects of drospirenone by unspecified interaction mechanism. Use Caution/Monitor. Hyperkalemia.terbutalineMonitor Closely (1)drospirenone increases and terbutaline decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.ticarcillinMonitor Closely (1)ticarcillin increases effects of drospirenone by unspecified interaction mechanism. Use Caution/Monitor. Hyperkalemia.timololMonitor Closely (1)timolol and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.tinidazoleMonitor Closely (1)drospirenone will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tizanidineMinor (1)tizanidine increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.tolfenamic acidMonitor Closely (1)drospirenone and tolfenamic acid both increase serum potassium. Modify Therapy/Monitor Closely.tolmetinMonitor Closely (1)drospirenone and tolmetin both increase serum potassium. Modify Therapy/Monitor Closely.tolvaptanMonitor Closely (1)drospirenone and tolvaptan both increase serum potassium. Modify Therapy/Monitor Closely.torsemideMonitor Closely (1)drospirenone increases and torsemide decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.trandolaprilMonitor Closely (1)trandolapril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.treprostinilMinor (1)treprostinil increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.triamtereneSerious - Use Alternative (2)drospirenone and triamterene both increase serum potassium. Avoid or Use Alternate Drug. drospirenone, triamterene. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Hyperkalemia.trimethoprimMinor (1)drospirenone, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.valoctocogene roxaparvovecMonitor Closely (1)drospirenone and valoctocogene roxaparvovec both increase Other (see comment). Use Caution/Monitor. Medications that may cause hepatotoxicity when combined with valoctogene roxaparvovec may potentiate the risk of elevated liver enzymes. Closely monitor these medications and consider alternative medications in case of potential drug interactions.valsartanMonitor Closely (1)valsartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.voclosporinMonitor Closely (1)voclosporin and drospirenone both increase serum potassium. Use Caution/Monitor.warfarinMonitor Closely (1)drospirenone increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.xipamideMonitor Closely (1)xipamide increases effects of drospirenone by pharmacodynamic synergism. Use Caution/Monitor. >10% Unscheduled bleeding, cycle 1 (64.4%) Unscheduled bleeding, cycle 13 (40.3%) 1-10% Acne (3.8%) Metrorrhagia (2.8%) Headache (2.7%) Breast pain (2.2%) Weight increased (1.9%) Dysmenorrhea (1.9%) Nausea (1.8%) Vaginal hemorrhage (1.7%) Libido decreased (1.3%) Breast tenderness (1.2%) Menstruation irregular (1.2%) Contraindications Renal impairment Adrenal insufficiency Presence or history of cervical cancer or progestin-sensitive cancers Liver tumors, benign or malignant, or hepatic impairment Undiagnosed abnormal uterine bleeding Cautions Use leads to decreased estradiol serum levels; unknown if clinically relevant loss of bone mineral density may occur Some studies suggest COC containing progestin and estradiol associated with increased risk of cervical cancer or intraepithelial neoplasia; however, controversy continues about the extent to which such findings may be due to differences in sexual behavior and other factors Discontinue if jaundice or acute or chronic disturbances of liver function develop; do not resume until LFTs return to normal and causation identified; drospirenone contraindicated with hepatic impairment or benign or malignant liver tumors Consider possibility of ectopic pregnancy in women who become pregnant or report lower abdominal pain Progestins may decrease insulin sensitivity; patients with diabetes may be at greater risk of hyperglycemia and may require additional medication adjustments or monitoring Bleeding irregularities (eg, breakthrough or intracyclic bleeding or spotting) may occur, especially during the first 3 months; may resolve over time or by changing to different contraceptive; if persists, evaluate for causes (eg, pregnancy, malignancy) Carefully observe females for history of depression and discontinue drospirenone if depression recurs to a serious degree Thromboembolic risk Thromboembolism risk with combined oral contraceptives containing drospirenone and ethinyl estradiol higher than those containing some other progestins plus ethinyl estradiol Epidemiological studies have not indicated an association between progestin-only preparations and an increased risk of myocardial infarction, cerebral thromboembolism, or venous thromboembolism Discontinue if arterial or venous thromboembolic events occur; consider discontinuing with prolonged immobilization due to surgery or illness Hyperkalemia Drospirenone has antimineralocorticoid activity, including the potential for hyperkalemia in high-risk females, comparable to spironolactone 25 mg Contraindicated in females with conditions that predispose to hyperkalemia (eg, renal impairment, hepatic impairment, adrenal insufficiency, long-term coadministration with strong CYP3A4 inhibitor) Drug interaction overview Effects of other drug on hormonal contraception Drugs or herbal products that induce certain enzymes, including CYP3A4, may decrease systemic concentrations of hormonal contraceptives and potentially diminish the effectiveness or increase breakthrough bleeding Instruct women to use a nonhormonal backup contraceptive for 28 days after discontinuing the enzyme inducer Strong CYP3A4 inhibitors may result in a moderate increase of drospirenone systemic exposure Effects of drospirenone on other drugs Potential for increased serum potassium concentration if drospirenone coadministered with other drugs that increase potassium levels Pregnancy Based on epidemiologic studies and meta-analyses, there is little or no increased risk of birth defects in the children of females who inadvertently use oral progestins during early pregnancy Discontinue if pregnancy occurs, as there is no reason to use hormonal contraceptives during pregnancy Human data Epidemiologic studies and meta-analyses have not found increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following maternal use of oral progestins before conception or during early pregnancy Lactation Negligible amounts of drospirenone are excreted in the breast milk At therapeutic doses, no effects on breastfed newborns/infants are anticipated Human data After daily administration of 4 mg, the average drospirenone concentration in breast milk over 24-hour period is 5.6 ng/mL Based on this concentration, the estimated average infant daily dosages for an exclusively breastfed infant is 840 ng/kg/day (relative infant dose is 1.5%) Pregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Spironolactone analogue with antimineralocorticoid and antiandrogenic activity; suppresses luteinizing hormone and ovulation by binding to the progesterone receptor; also alters cervical mucus, causing unfavorable sperm penetration; changes to the endometrial lining may decrease implantation Absorption Peak plasma time: 2-6 hr Peak plasma concentration: 27 ng/mL (single ingestion); 41 ng/mL (steady state [~10 days]) Distribution Vd: 4 L/kg Protein bound: 95-97% (albumin) Metabolism Extensively metabolized Nonactive metabolites: Acid form of drospirenone (formed by opening of lactone ring) and 4,5-dihydrodrospirenone (formed by reduction and subsequent sulfation) Drospirenone is also subject to oxidative metabolism catalyzed by CYP3A4 Elimination Half-life: ~30 hr Excretion: Nearly complete after ~10 days; amounts excreted in feces slightly higher compared with urine Oral Administration Swallow table whole once daily Take every day at about the same time of the day so that the interval between 2 tablets is always 24 hr Missed dose(s) 1 active tablet missed: Take missed tablet as soon as possible; continue taking 1 tablet/day until pack finished ≥2 active tablets missed: Take the last missed tablet as soon as possible; continue 1 tablet/day until the pack is finished (1 or more missed tablet[s] will remain in the blister pack); instruct patient to use additional nonhormonal contraception (eg, condoms or spermicide) as backup if patient has sex within 7 days after missing tablets ≥1 insert tablets missed: Skip the missed pill days and continue taking 1 tablet/day until pack finished Vomiting or diarrhea If vomiting or diarrhea occurs within