JUXTAPID- lomitapide mesylate capsule Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

juxtapid- lomitapide mesylate capsule

chiesi usa, inc. - lomitapide mesylate (unii: x4s83cp54e) (lomitapide - unii:82kub0583f) - juxtapid is indicated as an adjunct to a low-fat diet and other lipid-lowering treatments, including ldl apheresis where available, to reduce low-density lipoprotein cholesterol (ldl-c), total cholesterol (tc), apolipoprotein b (apo b), and non-high-density lipoprotein cholesterol (non-hdl-c) in patients with homozygous familial hypercholesterolemia (hofh). limitations of use - the safety and effectiveness of juxtapid have not been established in patients with hypercholesterolemia who do not have hofh, including those with heterozygous familial hypercholesterolemia (hefh). - the effect of juxtapid on cardiovascular morbidity and mortality has not been determined. juxtapid is contraindicated in the following conditions: - pregnancy [see warnings and precautions (5.3) and use in specific populations (8.1)] . - concomitant administration of juxtapid with moderate or strong cyp3a4 inhibitors, as this can increase juxtapid exposure [see warnings and precautions (5.6), drug interactions (7.1), and clinical pharmacology (12.3)]. - patients with moderate or severe hepatic impairment (based on child-pugh category b or c) and patients with active liver disease, including unexplained persistent elevations of serum transaminases [see warnings and precautions (5.1) and use in specific populations (8.7)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to juxtapid during pregnancy. for additional information visit www.juxtapid.com or call the global lomitapide pregnancy exposure registry (per) at 1-877-902-4099. healthcare professionals are encouraged to call the per at 1-877-902-4099 to enroll patients who become pregnant during juxtapid treatment. risk summary based on findings from animal studies, juxtapid use is contraindicated in pregnancy since it may cause fetal harm [see contraindications (4), warnings and precautions (5.3)]. available human data are insufficient to draw conclusions about any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. however, in animal reproduction studies, lomitapide was teratogenic in rats at clinically relevant exposures and in ferrets at exposures estimated to be less than human therapeutic exposure at 60 mg when administered during organogenesis, based on auc comparisons. embryo-fetal lethality was observed in rabbits at 6-times the maximum recommended human dose (mrhd) of 60 mg based on body surface area. if pregnancy is detected, discontinue juxtapid. 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 risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data oral gavage doses of 0.04, 0.4, or 4 mg/kg/day lomitapide given to pregnant rats from gestation day 6 through organogenesis were associated with fetal malformations at ≥2-times human exposure at the mrhd (60 mg) based on plasma auc comparisons. fetal malformations included umbilical hernia, gastroschisis, imperforate anus, alterations in heart shape and size, limb malrotations, skeletal malformations of the tail, and delayed ossification of cranial, vertebral and pelvic bones. oral gavage doses of 1.6, 4, 10, or 25 mg/kg/day lomitapide given to pregnant ferrets from gestation day 12 through organogenesis were associated with both maternal toxicity and fetal malformations at exposures that ranged from less than the human exposure at the mrhd to 5-times the human exposure at the mrhd. fetal malformations included umbilical hernia, medially rotated or short limbs, absent or fused digits on paws, cleft palate, open eye lids, low-set ears, and kinked tail. oral gavage doses of 0.1, 1, or 10 mg/kg/day lomitapide given to pregnant rabbits from gestation day 6 through organogenesis were not associated with adverse effects at systemic exposures up to 3-times the mrhd of 60 mg based on body surface area comparison. treatment at doses of ≥20 mg/kg/day, ≥6-times the mrhd, resulted in embryo-fetal lethality. pregnant female rats given oral gavage doses of 0.1, 0.3, or 1 mg/kg/day lomitapide from gestation day 7 through termination of nursing on lactation day 20 were associated with malformations at systemic exposures equivalent to human exposure at the mrhd of 60 mg based on auc. increased pup mortality occurred at 4-times the mrhd. risk summary there are no data on the presence of lomitapide in human or animal milk, effects on the breastfed infant or on milk production. because of the potential for serious adverse reactions, including hepatotoxicity, advise patients that breastfeeding is not recommended during treatment with juxtapid. pregnancy testing females of reproductive potential should have a negative pregnancy test before starting juxtapid. contraception based on animal studies, juxtapid may cause fetal harm when administered to pregnant women [see use in specific populations (8.1) ]. advise females of reproductive potential to use effective contraception during treatment with juxtapid and for two weeks after the final dose. the use of juxtapid may result in reduced efficacy of oral contraceptives if vomiting or diarrhea occurs. advise patients using oral contraceptives and who experience vomiting or diarrhea to use an effective alternative contraceptive method until 7 days after resolution of symptoms [see drug interactions (7.2)]. safety and effectiveness have not been established in pediatric patients. clinical studies of juxtapid did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dosing for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. patients with end-stage renal disease receiving dialysis should not exceed 40 mg daily since lomitapide exposure in these patients increased approximately 50% compared with healthy volunteers. effects of mild, moderate, and severe renal impairment, including those with end-stage renal disease not yet receiving dialysis, on lomitapide exposure have not been studied. however, it is possible that patients with renal impairment who are not yet receiving dialysis may experience increases in lomitapide exposure exceeding 50% [see clinical pharmacology (12.3)] . patients with mild hepatic impairment (child-pugh a) should not exceed 40 mg daily since the lomitapide exposure in these patients increased approximately 50% compared with healthy volunteers. juxtapid is contraindicated in patients with moderate (child-pugh b) or severe (child-pugh c) hepatic impairment since the lomitapide exposure in patients with moderate hepatic impairment increased 164% compared with healthy volunteers [see contraindications (4) and clinical pharmacology (12.3)] .

KALETRA- lopinavir and ritonavir tablet, film coated Statele Unite ale Americii - engleză - NLM (National Library of Medicine)

kaletra- lopinavir and ritonavir tablet, film coated

nucare pharmaceuticals,inc. - lopinavir (unii: 2494g1jf75) (lopinavir - unii:2494g1jf75), ritonavir (unii: o3j8g9o825) (ritonavir - unii:o3j8g9o825) - kaletra is indicated in combination with other antiretroviral agents for the treatment of hiv-1 infection in adults and pediatric patients 14 days and older. limitations of use: - genotypic or phenotypic testing and/or treatment history should guide the use of kaletra. the number of baseline lopinavir resistance-associated substitutions affects the virologic response to kaletra [see microbiology ( 12.4)] . - kaletra is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., toxic epidermal necrolysis, stevens-johnson syndrome, erythema multiforme, urticaria, angioedema) to any of its ingredients, including ritonavir. - kaletra is contraindicated with drugs that are highly dependent on cyp3a for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening reactions [see drug interactions ( 7.1) and clinical pharmacology ( 12.3)] . alpha 1- adrenoreceptor antagonist: alfuzosin antianginal: ranolazine antiarrhythmic: dronedarone anti-gout: colchicine antipsychotics: lurasidone, pimozide ergot derivatives: dihydroergotamine, ergotamine, methylergonovine gi motility agent: cisapride hepatitis c direct acting antiviral: elbasvir/grazoprevir hmg-coa reductase inhibitors: lovastatin, simvastatin microsomal triglyceride transfer protein (mttp) inhibitor: lomitapidemicrosomal triglyceride transfer protein (mttp) inhibitor: lomitapide pde5 inhibitor: sildenafil (revatio ® ) when used for the treatment of pulmonary arterial hypertension sedative/hypnotics: triazolam, orally administered midazolam - alpha 1- adrenoreceptor antagonist: alfuzosin - antianginal: ranolazine - antiarrhythmic: dronedarone - anti-gout: colchicine - antipsychotics: lurasidone, pimozide - ergot derivatives: dihydroergotamine, ergotamine, methylergonovine - gi motility agent: cisapride - hepatitis c direct acting antiviral: elbasvir/grazoprevir - hmg-coa reductase inhibitors: lovastatin, simvastatin - microsomal triglyceride transfer protein (mttp) inhibitor: lomitapidemicrosomal triglyceride transfer protein (mttp) inhibitor: lomitapide - pde5 inhibitor: sildenafil (revatio ® ) when used for the treatment of pulmonary arterial hypertension - sedative/hypnotics: triazolam, orally administered midazolam - kaletra is contraindicated with drugs that are potent cyp3a inducers where significantly reduced lopinavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance and cross-resistance [see drug interactions ( 7.2) and clinical pharmacology ( 12.3)] . anticancer agents: apalutamide antimycobacterial: rifampin herbal products: st. john's wort (hypericum perforatum) - anticancer agents: apalutamide - antimycobacterial: rifampin - herbal products: st. john's wort (hypericum perforatum) pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to kaletra during pregnancy. physicians are encouraged to register patients by calling the antiretroviral pregnancy registry at 1-800-258-4263. risk summary available data from the antiretroviral pregnancy registry show no difference in the risk of overall major birth defects compared to the background rate for major birth defects of 2.7% in the u.s. reference population of the metropolitan atlanta congenital defects program (macdp) (see data) . the estimated background rate of miscarriage in clinically recognized pregnancies in the u.s. general population is 15-20%. the background risk for major birth defects and miscarriage for the indicated population is unknown. methodological limitations of the apr include the use of macdp as the external comparator group. the macdp population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at <20 weeks gestation (see data) . no treatment-related malformations were observed when lopinavir in combination with ritonavir was administered to pregnant rats or rabbits; however embryonic and fetal developmental toxicities occurred in rats administered maternally toxic doses. clinical considerations dose adjustments during pregnancy and the postpartum period administer 400/100 mg of kaletra twice daily in pregnant patients with no documented lopinavir-associated resistance substitutions [see dosage and administration ( 2.5) and clinical pharmacology ( 12.3)] . there are insufficient data to recommend kaletra dosing for pregnant patients with any documented lopinavir-associated resistance substitutions. no dose adjustment of kaletra is required for patients during the postpartum period. once daily kaletra dosing is not recommended in pregnancy. avoid use of kaletra oral solution during pregnancy due to the ethanol content. kaletra oral solution contains the excipients ethanol, approximately 42% (v/v and propylene glycol, approximately 15%. data human data kaletra was evaluated in 12 hiv-infected pregnant women in an open-label pharmacokinetic trial [see clinical pharmacology ( 12.3)] . no new trends in the safety profile were identified in pregnant women dosed with kaletra compared to the safety described in non-pregnant adults, based on the review of these limited data. antiretroviral pregnancy registry data: based on prospective reports from the antiretroviral pregnancy registry (apr) of over 3,000 exposures to lopinavir containing regimens (including over 1,000 exposed in the first trimester), there was no difference between lopinavir and overall birth defects compared with the background birth defect rate of 2.7% in the u.s. reference population of the metropolitan atlanta congenital defects program. the prevalence of birth defects in live births was 2.1% (95% ci: 1.4%-3.0%) following first-trimester exposure to lopinavir-containing regimens and 3.0% (95% ci: 2.4%-3.8%) following second and third trimester exposure to lopinavir-containing regimens. based on prospective reports from the apr of over 5,000 exposures to ritonavir containing regimens (including over 2,000 exposures in the first trimester) there was no difference between ritonavir and overall birth defects compared with the u.s. background rate (macdp). the prevalence of birth defects in live births was 2.2% (95% ci: 1.7%-2.8%) following first-trimester exposure to ritonavir-containing regimens and 2.9% (95% ci: 2.4%-3.6%) following second and third trimester exposure to ritonavir-containing regimens. for both lopinavir and ritonavir, sufficient numbers of first trimester exposures have been monitored to detect at least a 1.5 fold increase in risk of overall birth defects and a 2 fold increase in risk of birth defects in the cardiovascular and genitourinary systems. animal data embryonic and fetal developmental toxicities (early resorption, decreased fetal viability, decreased fetal body weight, increased incidence of skeletal variations and skeletal ossification delays) occurred in rats administered lopinavir in combination with ritonavir (on gestation days 6-17) at a maternally toxic dosage. based on auc measurements, the drug exposures in rats at the toxic doses were approximately 0.7 times (for lopinavir) and 1.8 times (for ritonavir) the exposures in humans at the recommended therapeutic dose (400/100 mg twice daily). in a pre- and post-natal study in rats, a developmental toxicity (a decrease in survival in pups between birth and postnatal day 21) occurred. no embryonic and fetal developmental toxicities were observed in rabbits administered lopinavir in combination with ritonavir (on gestation days 6-18) at a maternally toxic dosage. based on auc measurements, the drug exposures in rabbits at the toxic doses were approximately 0.6 times (for lopinavir) and similar to (for ritonavir) the exposures in humans at the recommended therapeutic dose (400/100 mg twice daily). risk summary the centers for disease control and prevention recommend that hiv-1 infected mothers not breastfeed their infants to avoid risking postnatal transmission of hiv-1. because of the potential for: 1) hiv transmission (in hiv-negative infants), 2) developing viral resistance (in hiv- positive infants), and 3) adverse reactions in the breastfed infant, instruct mothers not to breastfeed if they are receiving kaletra. contraception use of kaletra may reduce the efficacy of combined hormonal contraceptives. advise patients using combined hormonal contraceptives to use an effective alternative contraceptive method or an additional barrier method of contraception [see drug interactions ( 7.3)] . the safety, efficacy, and pharmacokinetic profiles of kaletra in pediatric patients below the age of 14 days have not been established. kaletra should not be administered once daily in pediatric patients. an open-label, multi-center, dose-finding trial was performed to evaluate the pharmacokinetic profile, tolerability, safety and efficacy of kaletra oral solution containing lopinavir 80 mg/ml and ritonavir 20 mg/ml at a dose of 300/75 mg/m 2 twice daily plus two nrtis in hiv-infected infants ≥14 days and < 6 months of age. results revealed that infants younger than 6 months of age generally had lower lopinavir auc 12 than older children (6 months to 12 years of age), however, despite the lower lopinavir drug exposure observed, antiviral activity was demonstrated as reflected in the proportion of subjects who achieved hiv-1 rna <400 copies/ml at week 24 [see adverse reactions ( 6.2), clinical pharmacology ( 12.3), clinical studies ( 14.4)] . safety and efficacy in pediatric patients > 6 months of age was demonstrated in a clinical trial in 100 patients. the clinical trial was an open-label, multicenter trial evaluating the pharmacokinetic profile, tolerability, safety, and efficacy of kaletra oral solution containing lopinavir 80 mg/ml and ritonavir 20 mg/ml in 100 antiretroviral naïve and experienced pediatric patients ages 6 months to 12 years. dose selection for patients 6 months to 12 years of age was based on the following results. the 230/57.5 mg/m 2 oral solution twice daily regimen without nevirapine and the 300/75 mg/m 2 oral solution twice daily regimen with nevirapine provided lopinavir plasma concentrations similar to those obtained in adult patients receiving the 400/100 mg twice daily regimen (without nevirapine) [see adverse reactions ( 6.2), clinical pharmacology ( 12.3), clinical studies ( 14.4)] . a prospective multicenter, open-label trial evaluated the pharmacokinetic profile, tolerability, safety and efficacy of high-dose kaletra with or without concurrent nnrti therapy (group 1: 400/100 mg/m 2 twice daily + ≥ 2 nrtis; group 2: 480/120 mg/m 2 twice daily + ≥ 1 nrti + 1 nnrti) in 26 children and adolescents ≥ 2 years to < 18 years of age who had failed prior therapy. patients also had saquinavir mesylate added to their regimen. this strategy was intended to assess whether higher than approved doses of kaletra could overcome protease inhibitor cross-resistance. high doses of kaletra exhibited a safety profile similar to those observed in previous trials; changes in hiv-1 rna were less than anticipated; three patients had hiv-1 rna <400 copies/ml at week 48. cd4+ cell count increases were noted in the eight patients who remained on treatment for 48 weeks [see adverse reactions ( 6.2), clinical pharmacology ( 12.3)] . a prospective multicenter, randomized, open-label study evaluated the efficacy and safety of twice-daily versus once-daily dosing of kaletra tablets dosed by weight as part of combination antiretroviral therapy (cart) in virologically suppressed hiv-1 infected children (n=173). children were eligible when they were aged < 18 years, ≥ 15 kg in weight, receiving cart that included kaletra, hiv-1 ribonucleic acid (rna) < 50 copies/ml for at least 24 weeks and able to swallow tablets. at week 24, efficacy (defined as the proportion of subjects with plasma hiv-1 rna less than 50 copies per ml) was significantly higher in subjects receiving twice daily dosing compared to subjects receiving once daily dosing. the safety profile was similar between the two treatment arms although there was a greater incidence of diarrhea in the once daily treated subjects. clinical studies of kaletra did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. in general, appropriate caution should be exercised in the administration and monitoring of kaletra in elderly patients reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. kaletra is principally metabolized by the liver; therefore, caution should be exercised when administering this drug to patients with hepatic impairment, because lopinavir concentrations may be increased [see warnings and precautions ( 5.4) and clinical pharmacology ( 12.3)] .

KALETRA ORAL SOLUTION Israel - engleză - Ministry of Health

kaletra oral solution

abbvie biopharmaceuticals ltd, israel - lopinavir; ritonavir - solution (oral) - ritonavir 20 mg/ml; lopinavir 80 mg/ml - ritonavir - kaletra is indicated in combination with other antiretroviral agents for the treatment of hiv-1 infection.

KALETRA ORAL SOLUTION Israel - engleză - Ministry of Health

kaletra oral solution

abbvie biopharmaceuticals ltd, israel - lopinavir; ritonavir - solution (oral) - ritonavir 20 mg/ml; lopinavir 80 mg/ml - ritonavir - kaletra is indicated in combination with other antiretroviral agents for the treatment of hiv-1 infection.

GP CLARITHROMYCIN XR FILM-COATED TABLET 500MG Singapore - engleză - HSA (Health Sciences Authority)

gp clarithromycin xr film-coated tablet 500mg

goldplus universal pte ltd - clarithromycin citrate eqv clarithromycin - tablet, film coated, extended release - clarithromycin citrate eqv clarithromycin 500mg

Simvastatin 80 mg Film-coated Tablets Irlanda - engleză - HPRA (Health Products Regulatory Authority)

simvastatin 80 mg film-coated tablets

mcdermott laboratories ltd., t/a gerard laboratories - simvastatin - film-coated tablet - 80 milligram(s) - hmg coa reductase inhibitors; simvastatin