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and , in turn , their fertility . Residents are still expected to work 28-hour shifts without sleeping while pregnant .
Ariela Marshall , MD , of Mayo Clinic in Minnesota , helped create an infertility task force with the American Medical Women ’ s Association ( AMWA ), which held its first national physician fertility summit in June 2021 . The summit included sessions on egg freezing , insurance coverage for fertility treatment , and infertility and mental health . The association is also advocating for more accommodations for physicians who wish to start families , such as giving women the option to front-load their residency work if they know they want to try to become pregnant later in their training .
“ We ’ re educating med students and premed students about fertility issues so that they are aware of them ,” said Roberta Gebhard , DO , governance chair and former president of AMWA . “ People say you can ’ t be a mom and a physician , and we ’ re telling you that you can , but you need to keep your options open .”
Source : The New York Times , September 13 , 2021 .
IMBRUVICA ® ( ibrutinib ) IMBRUVICA ® ( ibrutinib )
Additional Important Adverse Reactions : Cardiovascular Events : Data on cardiovascular events are based on randomized controlled trials with IMBRUVICA ( n = 2,115 ; median treatment duration of 19.1 months for 1,157 patients treated with IMBRUVICA and 5.3 months for 958 patients in the control arm ). The incidence of ventricular tachyarrhythmias ( ventricular extrasystoles , ventricular arrhythmias , ventricular fibrillation , ventricular flutter , and ventricular tachycardia ) of any grade was 1.0 % versus 0.4 % and of Grade 3 or greater was 0.3 % versus 0 % in patients treated with IMBRUVICA compared to patients in the control arm . The incidence of atrial fibrillation and atrial flutter of any grade was 8.4 % versus 1.6 % and for Grade 3 or greater was 4.0 % versus 0.5 % in patients treated with IMBRUVICA compared to patients in the control arm . In addition , the incidence of cardiac failure of any grade was 1.7 % versus 0.5 % and for Grade 3 or greater was 1.2 % versus 0.3 % in patients treated with IMBRUVICA compared to patients in the control arm .
The incidence of ischemic cerebrovascular events ( cerebrovascular accidents , ischemic stroke , cerebral ischemia , and transient ischemic attack ) of any grade was 1 % versus 0.4 % and Grade 3 or greater was 0.5 % versus 0.2 % in patients treated with IMBRUVICA compared to patients in the control arm , respectively .
Diarrhea : In randomized controlled trials ( n = 2,115 ; median treatment duration of 19.1 months for 1,157 patients treated with IMBRUVICA and 5.3 months for 958 patients in the control arm ), diarrhea of any grade occurred at a rate of 43 % of patients treated with IMBRUVICA compared to 19 % of patients in the control arm . Grade 3 diarrhea occurred in 3 % versus 1 % of IMBRUVICAtreated patients compared to the control arm , respectively . Less than 1 % ( 0.3 %) of subjects discontinued IMBRUVICA due to diarrhea compared with 0 % in the control arm .
Based on data from 1,605 of these patients , the median time to first onset was 21 days ( range , 0 to 708 ) versus 46 days ( range , 0 to 492 ) for any grade diarrhea and 117 days ( range , 3 to 414 ) versus 194 days ( range , 11 to 325 ) for Grade 3 diarrhea in IMBRUVICA-treated patients compared to the control arm , respectively . Of the patients who reported diarrhea , 85 % versus 89 % had complete resolution , and 15 % versus 11 % had not reported resolution at time of analysis in IMBRUVICA-treated patients compared to the control arm , respectively . The median time from onset to resolution in IMBRUVICAtreated subjects was 7 days ( range , 1 to 655 ) versus 4 days ( range , 1 to 367 ) for any grade diarrhea and 7 days ( range , 1 to 78 ) versus 19 days ( range , 1 to 56 ) for Grade 3 diarrhea in IMBRUVICA-treated subjects compared to the control arm , respectively .
Visual Disturbance : In randomized controlled trials ( n = 2,115 ; median treatment duration of 19.1 months for 1,157 patients treated with IMBRUVICA and 5.3 months for 958 patients in the control arm ), blurred vision and decreased visual acuity of any grade occurred in 11 % of patients treated with IMBRUVICA ( 9 % Grade 1 , 2 % Grade 2 , no Grade 3 or higher ) compared to 6 % in the control arm ( 5 % Grade 1 and < 1 % Grade 2 and 3 ).
Based on data from 1,605 of these patients , the median time to first onset was 91 days ( range , 0 to 617 ) versus 100 days ( range , 2 to 477 ) in IMBRUVICAtreated patients compared to the control arm , respectively . Of the patients who reported visual disturbances , 60 % versus 71 % had complete resolution and 40 % versus 29 % had not reported resolution at the time of analysis in IMBRUVICA-treated patients compared to the control arm , respectively . The median time from onset to resolution was 37 days ( range , 1 to 457 ) versus 26 days ( range , 1 to 721 ) in IMBRUVICA-treated subjects compared to the control arm , respectively .
Long-Term Safety The safety data from long-term treatment with IMBRUVICA over 5 years of 1,284 patients ( treatment-naïve CLL / SLL n = 162 , relapsed / refractory CLL / SLL n = 646 , relapsed / refractory MCL n = 370 , and WM n = 106 ) were analyzed . The median treatment duration was 51 months ( range , 0.2 to 98 months ) for CLL / SLL , 11 months ( range , 0 to 87 months ) for MCL , and 47 months ( range , 0.3 to 61 months ) for WM . The cumulative rate of hypertension increased over time . The prevalence for Grade 3 or greater hypertension was 4 % ( year 0-1 ), 7 % ( year 1-2 ), 9 % ( year 2-3 ), 9 % ( year 3-4 ), and 9 % ( year 4-5 ); the overall incidence for the 5-year period was 11 %.
Postmarketing Experience : The following adverse reactions have been identified during postapproval use of IMBRUVICA . Because these reactions are reported voluntarily from a population of uncertain size , it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure .
• Hepatobiliary disorders : hepatic failure including acute and / or fatal events , hepatic cirrhosis
• Respiratory disorders : interstitial lung disease
• Metabolic and nutrition disorders : tumor lysis syndrome
• Immune system disorders : anaphylactic shock , angioedema , urticaria
• Skin and subcutaneous tissue disorders : Stevens-Johnson Syndrome ( SJS ), onychoclasis , panniculitis , neutrophilic dermatoses
• Infections : hepatitis B reactivation
• Nervous system disorders : peripheral neuropathy
DRUG INTERACTIONS Effect of CYP3A Inhibitors on Ibrutinib : The coadministration of IMBRUVICA with a strong or moderate CYP3A inhibitor may increase ibrutinib plasma concentrations [ see Clinical Pharmacology ( 12.3 ) in Full Prescribing Information ]. Increased ibrutinib concentrations may increase the risk of drug-related toxicity . Dose modifications of IMBRUVICA are recommended when used concomitantly with posaconazole , voriconazole and moderate CYP3A inhibitors [ see Dosage and Administration ( 2.3 ) in Full Prescribing Information ]. Avoid concomitant use of other strong CYP3A inhibitors . Interrupt IMBRUVICA if these inhibitors will be used short-term ( such as anti-infectives for seven days or less ) [ see Dosage and Administration ( 2.3 ) in Full Prescribing Information ]. Avoid grapefruit and Seville oranges during IMBRUVICA treatment , as these contain strong or moderate inhibitors of CYP3A . Effect of CYP3A Inducers on Ibrutinib : The coadministration of IMBRUVICA with strong CYP3A inducers may decrease ibrutinib concentrations . Avoid coadministration with strong CYP3A inducers [ see Clinical Pharmacology ( 12.3 ) in Full Prescribing Information ].
USE IN SPECIFIC POPULATIONS Pregnancy : Risk Summary : IMBRUVICA can cause fetal harm based on findings from animal studies . There are no available data on IMBRUVICA use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage . In animal reproduction studies , administration of ibrutinib to pregnant rats and rabbits during the period of organogenesis at exposures up to 2-20 times the clinical doses of 420-560 mg daily produced embryofetal toxicity including structural abnormalities ( see Data ). Advise pregnant women of the potential risk to a fetus . 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 2-4 % and 15-20 %, respectively . Data : Animal Data : Ibrutinib was administered orally to pregnant rats during the period of organogenesis at doses of 10 , 40 and 80 mg / kg / day . Ibrutinib at a dose of 80 mg / kg / day was associated with visceral malformations ( heart and major vessels ) and increased resorptions and post-implantation loss . The dose of 80 mg / kg / day in rats is approximately 14 times the exposure ( AUC ) in patients with MCL or marginal zone lymphoma ( MZL ) and 20 times the exposure in patients with CLL / SLL or Waldenström ’ s Macroglobulinemia ( WM ) administered the dose of 560 mg daily and 420 mg daily , respectively . Ibrutinib at doses of 40 mg / kg / day or greater was associated with decreased fetal weights . The dose of 40 mg / kg / day in rats is approximately 6 times the exposure ( AUC ) in patients with MCL administered the dose of 560 mg daily . Ibrutinib was also administered orally to pregnant rabbits during the period of organogenesis at doses of 5 , 15 , and 45 mg / kg / day . Ibrutinib at a dose of 15 mg / kg / day or greater was associated with skeletal variations ( fused sternebrae ) and ibrutinib at a dose of 45 mg / kg / day was associated with increased resorptions and post-implantation loss . The dose of 15 mg / kg / day in rabbits is approximately 2.0 times the exposure ( AUC ) in patients with MCL and 2.8 times the exposure in patients with CLL / SLL or WM administered the dose of 560 and 420 mg daily , respectively . Lactation : Risk Summary : There is no information regarding the presence of ibrutinib or its metabolites in human milk , the effects on the breastfed child , or the effects on milk production . Because of the potential for serious adverse reactions in the breastfed child , advise women not to breastfeed during treatment with IMBRUVICA and for 1 week after the last dose . Females and Males of Reproductive Potential : Pregnancy Testing : Verify pregnancy status in females of reproductive potential prior to initiating IMBRUVICA . Contraception : Females : IMBRUVICA can cause fetal harm when administered to pregnant women [ see Use in Specific Populations ]. Advise females of reproductive potential to use effective contraception during treatment with IMBRUVICA and for 1 month after the last dose . Males : Advise males with female partners of reproductive potential to use effective contraception during treatment with IMBRUVICA and for 1 month following the last dose . Pediatric Use : The safety and effectiveness of IMBRUVICA in pediatric patients has not been established . Geriatric Use : Of the 1,124 patients in clinical studies of IMBRUVICA , 64 % were ≥ 65 years of age , while 23 % were ≥75 years of age . No overall differences in effectiveness were observed between younger and older patients . Anemia ( all grades ), pneumonia ( Grade 3 or higher ), thrombocytopenia , hypertension , and atrial fibrillation occurred more frequently among older patients treated with IMBRUVICA . Hepatic Impairment : Avoid use of IMBRUVICA in patients with severe hepatic impairment ( Child-Pugh class C ). The safety of IMBRUVICA has not been evaluated in patients with mild to severe hepatic impairment by Child- Pugh criteria .