SAFYRAL

Last Updated: January 28, 2011

 

Manufacturer: Bayer Healthcare Pharmaceuticals Inc. Pharmacological Class: Combination oral contra­ceptive (OC) (progestin + estrogen) + folate. Active Ingredient(s): Drospirenone 3mg, ethinyl estradiol 30micrograms, levomefolate calcium 0.451mg (21 tablets); levomefolate calcium 0.451mg (7 tablets).

Indication(s):

Oral contraception. To raise folate ­levels in women who choose to use an OC for contraception.

Pharmacology:

Combined OCs ­reduce the risk of pregnancy primarily by ­inhibiting ovulation. This product combines drospirenone, an analogue of spiro­nolactone that has both antimineralocorticoid and anti­androgenic activities, with an estrogen plus ­folate supplementation. Levomefolate calcium 0.451mg (equivalent to folic acid 0.4mg) is included for reducing the risk of neural tube defects in a pregnancy conceived while taking the product or shortly after discontinuing the product.

Clinical Trials:

The approval of Safyral (Yasmin + levo­mefolate calcium) was based on two clinical trials. One study, a multicenter, randomized, double-blind, active control, parallel group trial, investigated plasma folate and red blood cell folate levels over 24 weeks in a population that consumed folate-fortified foods in the US. Over the study period, the group given Yaz (drospirenone 3mg/ethinyl estradiol 20mcg) + levo­me­folate 0.451mg had higher plasma folate levels and higher RBC folate levels than the group given Yaz alone.

In a study conducted in Germany in a population that did not consume folate-fortified foods, the effect on the plasma and RBC folate and circulating folate metab­olites was examined for Yasmin (dros­pirenone 3mg/ethinyl estradiol 30mcg) + folic acid 0.4mg com­pared to Yasmin + levomefolate calcium 0.451mg. After achiev­ing steady state by week 24 (treatment phase), both plasma and RBC folate levels fell during the 20 week Yasmin-only (elimination) phase of the 44 week study.

In large clinical trials with Yasmin, pregnancy rates were <1 per 100 women-years of use.

Legal Classification:

Rx

Adults:

1 tablet daily for 28 days; repeat. Take at the same time daily. Use Day 1 or Sunday start for 1^st ­cycle; use backup method for first 7 days.

Children:

Premenarchal: not applicable.

Contraindication(s):

Renal impairment. Adrenal insufficiency. High risk of arterial or venous thrombotic disease (eg, smokers or migraineurs over age 35, history of DVT or thromboembolism, cerebrovascular or coronary artery disease, thrombogenic valvular disease, atrial fibrillation, subacute bacterial endo­car­di­tis, hypercoag­u­lopathies, uncontrolled hypertension, diabetes with vascular disease, headaches with focal neurologic symptoms). Breast or other estrogen or progestin-sensitive neoplasms. Hepatic disease or tumors. Undiagnosed abnormal uterine bleeding. Pregnancy (Category X).

Warnings/Precautions:

Discontinue if thrombotic event, unexplained visual changes, or jaundice occurs, and at least 4 weeks before through 2 weeks after surgery associated with increased risk of throm­bo­embo­lism. Hyper­kalemia or risk thereof. Diabetes. Prediabetes. Uncon­trolled dyslipidemias. Pregnancy-related chole­sta­sis. Depression. Evaluate significant changes in headaches, irregular uterine bleeding, amenorrhea. Monitor blood pressure. Nursing mothers: not recommended.

Interaction(s):

May potentiate drugs that can cause hyper­kalemia in chronic use (eg, ACE ­inhibitors, ARBs, NSAIDs, K⁺ sparing diuretics, K⁺ supplementation, heparin, aldosterone blockers) (check serum K⁺ during 1^st cycle). May be antagonized by CYP3A4 or other enzyme inducers (eg, barbiturates, bosentan, carba­maz­e­pine, felbamate, griseofulvin, oxcarbazepine, phenyt­oin, rifampin, St. John’s wort, topiramate) (use backup contraception). May be affected by pro­tease inhibitors, acet­aminophen, ascorbic acid, itraconazole, ketoconazole. May antagonize lam­o­tri­gine. May affect laboratory tests (eg, coagulation factors, lipids, glucose tol­er­ance, binding proteins). May need dose adjustment of thyroid hor­mones. May mask vitamin B12 deficiency (folate).

Adverse Reaction(s):

Hypertension, nausea, vomiting, break­through bleeding, amenorrhea, transient delay of ovulation after discontinuation, edema, chloasma, masto­dynia, headache, intolerance to contact lenses. Increased risk of gallbladder disease, thromboembolic disorders.

How Supplied:

Packs—3 (3x28 day cycles)

Last Updated:

7/14/2011