USA - engelsk - NLM (National Library of Medicine)

proficient rx lp - levofloxacin (unii: 6gnt3y5lmf) (levofloxacin anhydrous - unii:rix4e89y14) - levofloxacin tablets are indicated for the treatment of adults (≥18 years of age) with mild, moderate, and severe infections caused by susceptible isolates of the designated microorganisms in the conditions listed in this section. levofloxacin  injection is indicated when intravenous administration offers a route of administration advantageous to the patient (e.g., patient cannot tolerate an oral dosage form). levofloxacin tablets are indicated for the treatment of nosocomial pneumonia due to methicillin-susceptible staphylococcus aureus, pseudomonas aeruginosa, serratia marcescens, escherichia coli, klebsiella pneumoniae, haemophilus influenzae, or streptococcus pneumoniae . adjunctive therapy should be used as clinically indicated. where pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an anti-pseudomonal β-lactam is recommended [see clinical studies (14.1)] . levofloxacin tablets are indicated for the treatment of community-acquired pneumonia due to methicillin-sus

USA - engelsk - NLM (National Library of Medicine)

sebela pharmaceuticals inc. - naftifine hydrochloride (unii: 25ur9n9041) (naftifine - unii:4fb1ton47a) - naftin ® gel is an allylamine antifungal indicated for the treatment of interdigital tinea pedis caused by the organisms trichophyton rubrum , trichophyton mentagrophytes , and epidermophyton floccosum . none. risk summary there are no available data on naftin® gel use in pregnant women to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in animal reproduction studies, no adverse effects on embryofetal development were seen at oral doses administered during the period of organogenesis up to 37 times the maximum recommended human dose (mrhd) in pregnant rats or subcutaneous doses administered during the period of organogenesis up to 4 times the mrhd in pregnant rats or 7 times the mrhd in pregnant rabbits ( see data ). all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data systemic embryofetal development studies were conducted in rats and rabbits. for the comparison of animal to human doses, the mrhd is set at 4 g 2% gel per day (1.33 mg/kg/day for a 60 kg individual). oral doses of 30, 100, and 300 mg/kg/day naftifine hydrochloride were administered during the period of organogenesis to pregnant female rats. no treatment-related effects on embryofetal toxicity were noted at doses up to 300 mg/kg/day (37 times the mrhd based on mg/m 2 comparison). subcutaneous doses of 10 and 30 mg/kg/day naftifine hydrochloride were administered during the period of organogenesis to pregnant female rats. no treatment-related effects on embryofetal toxicity were noted at 30 mg/kg/day (4 times the mrhd based on mg/m 2 comparison). subcutaneous doses of 3, 10, and 30 mg/kg/day naftifine hydrochloride were administered during the period of organogenesis to pregnant female rabbits. no treatment-related effects on embryofetal toxicity were noted at 30 mg/kg/day (7 times the mrhd based on mg/m 2 comparison). a peri-and post-natal development study was conducted in rats. oral doses of 30, 100, and 300 mg/kg/day naftifine hydrochloride were administered to female rats from gestational day 14 to lactation day 21. reduced body weight gain of females during gestation and of the offspring during lactation was noted at 300 mg/kg/day (37 times the mrhd based on mg/m 2 comparison). no developmental toxicity was noted at 100 mg/kg/day (12 times the mrhd based on mg/m 2 comparison). risk summary there is no information available on the presence of naftifine hydrochloride in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production after topical application of naftin gel to women who are breastfeeding. it is not known whether naftifine hydrochloride is excreted in human milk. because many drugs are excreted in human milk, caution should be exercised when naftifine hydrochloride is administered to a nursing woman. the lack of clinical data during lactation precludes a clear determination of the risk naftin gel to an infant during lactation. therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for naftin gel and any potential adverse effects on the breastfed infant from naftin gel or from the underlying maternal condition. the safety and effectiveness of naftin® gel have been established in the age group 12 to 18 years of age with interdigital tinea pedis. use of naftin® gel in this age group is supported by evidence from adequate and well controlled trials in adults with additional safety and pk data from an open label trial, conducted in 22 adolescents ≥12 years of age who were exposed to naftin® gel at a dose of approximately 4 g/day  [see clinical pharmacology (12.3)] . safety and effectiveness in pediatric patients <12 years of age have not been established. during clinical trials, 99 subjects (9%) aged 65 years and over were exposed to naftin ® gel. safety and effectiveness were similar to those reported by younger subjects.

USA - engelsk - NLM (National Library of Medicine)

aytu biopharma, inc. - zolpidem tartrate (unii: wy6w63843k) (zolpidem - unii:7k383oqi23) - zolpimist (zolpidem tartrate) is indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation. zolpidem tartrate has been shown to decrease sleep latency for up to 35 days in controlled clinical studies [see clinical studies ( 14)]. the clinical trials performed in support of efficacy were 4-5 weeks in duration with the final formal assessments of sleep latency performed at the end of treatment. zolpimist is contraindicated in patients: zolpimist is contraindicated in patients: - who have experienced complex sleep behaviors after taking zolpimist [see warnings and precautions ( 5.1)] [see warnings and precautions ( 5.1)] - with known hypersensitivity to zolpidem tartrate [ see warnings and precautions ( 5.7)]. pregnancy category c there are no adequate and well-controlled studies of zolpimist in pregnant women. studies in children to asse

USA - engelsk - NLM (National Library of Medicine)

renaissance pharma, inc. - naftifine hydrochloride (unii: 25ur9n9041) (naftifine - unii:4fb1ton47a) - naftifine hydrochloride cream, 2% is indicated for the treatment of: interdigital tinea pedis, tinea cruris, and tinea corporis caused by the organism trichophyton rubrum . none pregnancy category b. there are no adequate and well-controlled studies of naftifine hydrochloride cream, 2% in pregnant women. because animal reproduction studies are not always predictive of human response, naftifine hydrochloride cream, 2% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. the animal multiples of human exposure calculations were based on daily dose body surface area comparison (mg/m2 ) for the reproductive toxicology studies described in this section and in section 13.1. the maximum recommended human dose (mrhd) was set at 8 g 2% cream per day (2.67 mg/kg/day for a 60 kg individual). systemic embryofetal development studies were conducted in rats and rabbits. oral doses of 30, 100 and 300 mg/kg/day naftifine hydrochloride were administered during the period of o

USA - engelsk - NLM (National Library of Medicine)

nucare pharmaceuticals,inc. - naproxen (unii: 57y76r9atq) (naproxen - unii:57y76r9atq) - carefully consider the potential benefits and risks of naproxen delayed-release tablets and other treatment options before deciding to use naproxen delayed-release tablets. use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals ( see warnings: gastrointestinal bleeding, ulceration, and perforation ). naproxen delayed-release tablets are indicated: - for the relief of the signs and symptoms of rheumatoid arthritis - for the relief of the signs and symptoms of osteoarthritis - for the relief of the signs and symptoms of ankylosing spondylitis - for the relief of the signs and symptoms of juvenile arthritis naproxen delayed-release tablets are not recommended for initial treatment of acute pain because the absorption of naproxen is delayed compared to absorption from other naproxen-containing products (see clinical pharmacology, dosage and administration). naproxen de

USA - engelsk - NLM (National Library of Medicine)

proficient rx lp - levofloxacin (unii: 6gnt3y5lmf) (levofloxacin anhydrous - unii:rix4e89y14) - levofloxacin tablets are indicated in adult patients for the treatment of nosocomial pneumonia due to methicillinsusceptible staphylococcus aureus, pseudomonas aeruginosa, serratia marcescens, escherichia coli, klebsiella pneumoniae, haemophilus influenzae, or streptococcus pneumoniae. adjunctive therapy should be used as clinically indicated. where pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an antipseudomonal β-lactam is recommended [see clinical studies (14.1)]. levofloxacin tablets are indicated in adult patients for the treatment of community-acquired pneumonia due to methicillin-susceptible staphylococcus aureus , streptococcus pneumoniae (including multidrug-resistant streptococcus pneumoniae [mdrsp]), haemophilus influenzae, haemophilus parainfluenzae, klebsiella pneumoniae, moraxella catarrhalis, chlamydophila pneumoniae, legionella pneumophila , or mycoplasma pneumoniae [see dosage and administration (2.1) and clinical studies (14.2 )]. mdrsp isolates

USA - engelsk - NLM (National Library of Medicine)

pd-rx pharmaceuticals, inc. - metoprolol tartrate (unii: w5s57y3a5l) (metoprolol - unii:geb06nhm23) - metoprolol tartrate tablets are indicated for the treatment of hypertension in adult patients, to lower blood pressure. lowering blood pressure lowers the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including metoprolol. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than 1 drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program’s joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. the largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmhg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). these considerations may guide selection of therapy. metoprolol tartrate tablets may be administered with other antihypertensive agents. metoprolol tartrate tablets are indicated in the long-term treatment of angina pectoris, to reduce angina attacks and to improve exercise tolerance. metoprolol tartrate tablets are indicated in the treatment of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality when used alone or in conjunction with intravenous metoprolol. metoprolol tartrate tablets are contraindicated in severe bradycardia, second- or third-degree heart block, cardiogenic shock, systolic blood pressure <100, decompensated heart failure, sick sinus syndrome (unless a permanent pacemaker is in place), and in patients who are hypersensitive to any component of this product. available data from published observational studies have not demonstrated an association of adverse developmental outcomes with maternal use of metoprolol during pregnancy (see data) . untreated hypertension and myocardial infarction during pregnancy can lead to adverse outcomes for the mother and the fetus (see clinical considerations) . in animal reproduction studies, metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages of 500 mg/kg/day, approximately 11 times the daily dose of 450 mg in a 60-kg patient on a mg/m 2 basis. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. pregnant women with hypertension should be carefully monitored and managed accordingly. metoprolol crosses the placenta. neonates born to mothers who are receiving metoprolol during pregnancy, may be at risk for hypotension, hypoglycemia, bradycardia, and respiratory depression. observe neonates and manage accordingly. data from published observational studies did not demonstrate an association of major congenital malformations and use of metoprolol in pregnancy. the published literature has reported inconsistent findings of intrauterine growth retardation, preterm birth and perinatal mortality with maternal use of metoprolol during pregnancy; however, these studies have methodological limitations hindering interpretation. methodological limitations include retrospective design, concomitant use of other medications, and other unadjusted confounders that may account for the study findings including the underlying disease in the mother. these observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages of 500 mg/kg/day, i.e., 11 times, on a mg/m 2 basis, the daily dose of 450 mg in a 60-kg patient. no fetal abnormalities were observed when pregnant rats received metoprolol orally up to a dose of 200 mg/kg/day, i.e., 4 times, the daily dose of 400mg in a 60-kg patient. limited available data from published literature report that metoprolol is present in human milk. the estimated daily infant dose of metoprolol received from breastmilk ranges from 0.05 mg to less than 1 mg. the estimated relative infant dosage was 0.5% to 2% of the mother's weight-adjusted dosage (see data) . no adverse reactions of metoprolol on the breastfed infant have been identified. there is no information regarding the effects of metoprolol on milk production. for a lactating woman who is a slow metabolizer of metoprolol, monitor the breastfed infant for bradycardia and other symptoms of beta-blockade such as dry mouth, skin or eyes, diarrhea or constipation. in a report of 6 mothers taking metoprolol, none reported adverse effects in her breastfed infant. limited published cases estimate the infant daily dose of metoprolol received from breast milk range from 0.05 mg to less than 1 mg. in 2 women who were taking unspecified amount of metoprolol, milk samples were taken after one dose of metoprolol. the estimated amount of metoprolol and alpha-hydroxymetoprolol in breast milk is reported to be less than 2% of the mother's weight-adjusted dosage. in a small study, breast milk was collected every 2 to 3 hours over one dosage interval, in three mothers (at least 3 months postpartum) who took metoprolol of unspecified amount. the average amount of metoprolol present in breast milk was 71.5 mcg/day (range 17.0 to 158.7). the average relative infant dosage was 0.5% of the mother's weight-adjusted dosage. based on the published literature, beta-blockers (including metoprolol) may cause erectile dysfunction and inhibit sperm motility. in animal fertility studies, metoprolol has been associated with reversible adverse effects on spermatogenesis starting at oral dose level of 3.5 mg/kg in rats, which would correspond to a dose of 34 mg/day in humans in mg/m 2 equivalent, although other studies have shown no effect of metoprolol on reproductive performance in male rats. no evidence of impaired fertility due to metoprolol was observed in rats [see nonclinical toxicology (13.1)] . safety and effectiveness of metoprolol tartrate tablets have not been established in pediatric patients. clinical studies of metoprolol tartrate tablets in hypertension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience in hypertensive patients has not identified differences in responses between elderly and younger patients. in worldwide clinical trials of metoprolol tartrate tablets in myocardial infarction, where approximately 478 patients were over 65 years of age (0 over 75 years of age), no age-related differences in safety and effectiveness were found. other reported clinical experience in myocardial infarction has not identified differences in response between the elderly and younger patients. in general, use a low initial starting dose in elderly patients given their greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. no studies have been performed with metoprolol tartrate tablets in patients with hepatic impairment. because metoprolol tartrate tablets are metabolized by the liver, metoprolol blood levels are likely to increase substantially with poor hepatic function. therefore, initiate therapy at doses lower than those recommended for a given indication; and increase doses gradually in patients with impaired hepatic function. the systemic availability and half-life of metoprolol in patients with renal failure do not differ to a clinically significant degree from those in normal subjects. no reduction in dosage is needed in patients with chronic renal failure [see clinical pharmacology (12.3)].

USA - engelsk - NLM (National Library of Medicine)

pd-rx pharmaceuticals, inc. - meloxicam (unii: vg2qf83cgl) (meloxicam - unii:vg2qf83cgl) - meloxicam tablets are indicated for relief of the signs and symptoms of osteoarthritis [ see clinical studies ( 14.1) ]. meloxicam tablets are indicated for relief of the signs and symptoms of rheumatoid arthritis [ see clinical studies ( 14.1) ]. meloxicam tablets are indicated for relief of the signs and symptoms of pauciarticular or polyarticular course juvenile rheumatoid arthritis in patients who weigh ≥60 kg [ see dosage and administration ( 2.4) and clinical studies ( 14.2) ]. meloxicam tablets are contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to meloxicam or any components of the drug product [ see warnings and precautions ( 5.7, 5.9) ] - history of asthma, urticaria, or other allergic-type reac

USA - engelsk - NLM (National Library of Medicine)

sun pharmaceutical industries, inc. - bosentan (unii: q326023r30) (bosentan anhydrous - unii:xul93r30k2) - bosentan is indicated for the treatment of pulmonary arterial hypertension (pah) (who group 1): - in adults to improve exercise ability and to decrease clinical worsening. studies establishing effectiveness included predominantly patients with who functional class ii-iv symptoms and etiologies of idiopathic or heritable pah (60%), pah associated with connective tissue diseases (21%), and pah associated with congenital heart disease with left-to-right shunts (18%) [see clinical studies (14.1)] . use of bosentan is contraindicated in females who are or may become pregnant. to prevent pregnancy, females of reproductive potential must use two reliable forms of contraception during treatment and for one month after stopping bosentan [see boxed warning, warnings and precautions (5.2), drug interactions (7.2), use in specific populations (8.1)] . coadministration of cyclosporine a and bosentan resulted in markedly increased plasma concentrations of bosentan. therefore, concomitant use of bosentan and cyclosporine a is contraindicated [see cytochrome p450 drug interactions (7.1)]. an increased risk of liver enzyme elevations was observed in patients receiving glyburide concomitantly with bosentan. therefore coadministration of glyburide and bosentan is contraindicated [see cytochrome p450 drug interactions (7.1)] . bosentan is contraindicated in patients who are hypersensitive to bosentan or any component of the product. observed reactions include drug reaction with eosinophilia and systemic symptoms (dress), anaphylaxis, rash, and angioedema [see adverse reactions (6.2), description (11)] . risk summary based on data from animal reproduction studies, bosentan may cause fetal harm, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy [see contraindications (4.1)]. there are limited data on bosentan use in pregnant women. in animal reproduction studies, oral administration of bosentan to pregnant rats at 2-times the maximum recommended human dose (mrhd) on a mg/m2 basis caused teratogenic effects in rats, including malformations of the head, mouth, face, and large blood vessels [see animal data] . advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. data animal data bosentan was teratogenic in rats given oral doses two times the mrhd (on a mg/m2 basis). in an embryo-fetal toxicity study in rats, bosentan showed dose-dependent teratogenic effects, including malformations of the head, mouth, face and large blood vessels. bosentan increased stillbirths and pup mortality at oral doses 2 and 10 times the mrhd (on a mg/m2 basis). although birth defects were not observed in rabbits given oral doses of up to the equivalent of 10.5 g/day in a 70 kg person, plasma concentrations of bosentan in rabbits were lower than those reached in the rat. the similarity of malformations induced by bosentan and those observed in endothelin-1 knockout mice and in animals treated with other endothelin receptor antagonists indicates that embryo-fetal toxicity is a class effect of these drugs. risk summary data from a case report describe the presence of bosentan in human milk. there is insufficient information about the effects of bosentan on the breastfed infant and no information on the effects of bosentan on milk production. because of the potential for serious adverse reactions, such as fluid retention and hepatotoxicity, in breastfed infants from bosentan, advise women not to breastfeed during treatment with bosentan. pregnancy testing verify the pregnancy status of females of reproductive potential prior to initiating bosentan, monthly during treatment and one month after stopping treatment with bosentan. the patient should contact her physician immediately for pregnancy testing if onset of menses is delayed or pregnancy is suspected. if the pregnancy test is positive, the physician and patient must discuss the risks to her, the pregnancy, and the fetus. contraception drug interaction studies show that bosentan reduces serum levels of the estrogen and progestin in oral contraceptives. based on these findings, hormonal contraceptives (including oral, injectable, transdermal, and implantable contraceptives) may be less effective for preventing pregnancy in patients using bosentan and should not be used as a patient’s only contraceptive method [see drug interactions (7.2)] . females of reproductive potential using bosentan must use two acceptable methods of contraception during treatment and for 1 month after treatment with bosentan. patients may choose one highly effective form of contraception (intrauterine devices (iud) or tubal sterilization) or a combination of methods (hormone method with a barrier method or two barrier methods). if a partner’s vasectomy is the chosen method of contraception, a hormone or barrier method must be used along with this method. counsel patients on pregnancy planning and prevention, including emergency contraception, or designate counseling by another healthcare provider trained in contraceptive counseling [see boxed warning]. infertility males decreased sperm counts have been observed in patients receiving bosentan. based on these findings and findings in animals, bosentan may impair fertility in males of reproductive potential. it is not known whether effects on fertility would be reversible [see warnings and precautions (5.6), adverse reactions (6.1), nonclinical toxicology (13.1)]. juvenile animal toxicity data in a juvenile rat toxicity study, rats were treated from day 4 postpartum to adulthood (day 69 postpartum). decreased body weights, absolute weights of testes and epididymides, and reduced number of sperm in epididymides were observed after weaning. no effect on testis histology or sperm morphology and function was seen. the noael was 4 times (at day 4 postpartum) and 2 times (day 69 postpartum) the human therapeutic exposure, respectively. no effects on general development, sensory, cognitive function and reproductive performance were detected at the highest dose tested in juvenile rats, 7 times the therapeutic exposure in children with pah. clinical studies of bosentan did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. because there is in vitro and in vivo evidence that the main route of excretion of bosentan is biliary, liver impairment could be expected to increase exposure (cmax and auc) of bosentan. the pharmacokinetics of bosentan have not been evaluated in patients with severe liver impairment (child-pugh class c). in patients with moderate hepatic impairment (child-pugh class b), the systemic exposures to bosentan and its active metabolite increased significantly. bosentan should generally be avoided in patients with moderate or severe liver impairment. pharmacokinetics of bosentan were not altered in patients with mild impairment of hepatic function (child-pugh class a) [see dosage and administration (2.6), warnings and precautions (5.1), pharmacokinetics (12.3)] . the effect of renal impairment on the pharmacokinetics of bosentan is small and does not require dosing adjustment [see pharmacokinetics (12.3)] .

USA - engelsk - NLM (National Library of Medicine)

alvogen inc. - bosentan (unii: q326023r30) (bosentan anhydrous - unii:xul93r30k2) - bosentan tablets are indicated for the treatment of pulmonary arterial hypertension (pah) (who group 1): - in adults to improve exercise ability and to decrease clinical worsening. studies establishing effectiveness included predominantly patients with who functional class ii-iv symptoms and etiologies of idiopathic or heritable pah (60%), pah associated with connective tissue diseases (21%), and pah associated with congenital heart disease with left-to-right shunts (18%) [see clinical studies (14.1)]. use of bosentan tablets is contraindicated in females who are or may become pregnant. to prevent pregnancy, females of reproductive potential must use two reliable forms of contraception during treatment and for one month after stopping bosentan tablets. [see boxed warning, warnings and precautions (5.2), drug interactions (7.2), use in specific populations (8.1)]. co-administration of cyclosporine a and bosentan resulted in markedly increased plasma concentrations of bosentan. therefore, concomitant use of bo