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h2-pharma, llc - clonazepam (unii: 5pe9fde8gb) (clonazepam - unii:5pe9fde8gb) - klonopin is useful alone or as an adjunct in the treatment of the lennox-gastaut syndrome (petit mal variant), akinetic, and myoclonic seizures. in patients with absence seizures (petit mal) who have failed to respond to succinimides, klonopin may be useful. some loss of effect may occur during the course of clonazepam treatment (see precautions: loss of effect). klonopin is indicated for the treatment of panic disorder, with or without agoraphobia, as defined in dsm-v. panic disorder is characterized by the occurrence of unexpected panic attacks and associated concern about having additional attacks, worry about the implications or consequences of the attacks, and/or a significant change in behavior related to the attacks. the efficacy of klonopin was established in two 6- to 9-week trials in panic disorder patients whose diagnoses corresponded to the dsm-iiir category of panic disorder (see clinical pharmacology: clinical trials). panic disorder (dsm-v) is characterized by recurrent unexpected panic attacks, i.e., a discrete period of intense fear or discomfort in which four (or more) of the following symptoms develop abruptly and reach a peak within 10 minutes: (1) palpitations, pounding heart or accelerated heart rate; (2) sweating; (3) trembling or shaking; (4) sensations of shortness of breath or smothering; (5) feeling of choking; (6) chest pain or discomfort; (7) nausea or abdominal distress; (8) feeling dizzy, unsteady, lightheaded or faint; (9) derealization (feelings of unreality) or depersonalization (being detached from oneself); (10) fear of losing control; (11) fear of dying; (12) paresthesias (numbness or tingling sensations); (13) chills or hot flushes. the effectiveness of klonopin in long-term use, that is, for more than 9 weeks, has not been systematically studied in controlled clinical trials. the physician who elects to use klonopin for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient (see dosage and administration). klonopin is contraindicated in patients with the following conditions: - history of sensitivity to benzodiazepines - clinical or biochemical evidence of significant liver disease - acute narrow angle glaucoma (it may be used in patients with open angle glaucoma who are receiving appropriate therapy). klonopin contains clonazepam, a schedule iv controlled substance. klonopin is a benzodiazepine and a cns depressant with a potential for abuse and addiction. abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. abuse and misuse of benzodiazepines may lead to addiction. abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death. benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders (see warnings: abuse, misuse, and addiction). the following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo. the following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. death is more often associated with polysubstance use (especially benzodiazepines with other cns depressants such as opioids and alcohol). klonopin may produce physical dependence from continued therapy. physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening. patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who have had longer durations of use (see warnings: dependence and withdrawal reactions). to reduce the risk of withdrawal reactions, use a gradual taper to discontinue klonopin or reduce the dosage (see dosage and administration: discontinuation or dosage reduction of klonopin and warnings: dependence and withdrawal reactions). acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis, hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. more severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures, and suicidality. protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. protracted withdrawal symptoms may last weeks to more than 12 months. as a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used. tolerance to klonopin may develop from continued therapy. tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). tolerance to the therapeutic effect of klonopin may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines. following the short-term treatment of patients with panic disorder in studies 1 and 2 (see clinical pharmacology: clinical trials), patients were gradually withdrawn during a 7-week downward-titration (discontinuance) period. overall, the discontinuance period was associated with good tolerability and a very modest clinical deterioration, without evidence of a significant rebound phenomenon. however, there are not sufficient data from adequate and well-controlled long-term clonazepam studies in patients with panic disorder to accurately estimate the risks of withdrawal symptoms and dependence that may be associated with such use.

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h2-pharma llc - hydroxyurea (unii: x6q56qn5qc) (hydroxyurea - unii:x6q56qn5qc) - droxia is indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in patients with sickle cell anemia with recurrent moderate to severe painful crises. droxia is contraindicated in patients who have demonstrated a previous hypersensitivity to hydroxyurea or any other component of its formulation. droxia can cause fetal harm based on findings from animal studies and the drug’s mechanism of action [see clinical pharmacology (12.1)] . there are no data with droxia use in pregnant women to inform a drug-associated risk. in animal reproduction studies, administration of hydroxyurea to pregnant rats and rabbits during organogenesis produced embryotoxic and teratogenic effects at doses 0.8 times and 0.3 times, respectively, the maximum recommended human daily dose on a mg/m2 basis (see data) . advise women of the potential risk to a fetus and to avoid becoming pregnant while being treated with droxia. 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. hydroxyurea has been demonstrated to be a potent teratogen in a wide variety of animal models, including mice, hamsters, cats, miniature swine, dogs, and monkeys at doses within 1-fold of the human dose given on a mg/m2 basis. hydroxyurea is embryotoxic and causes fetal malformations (partially ossified cranial bones, absence of eye sockets, hydrocephaly, bipartite sternebrae, missing lumbar vertebrae) at 180 mg/kg/day (about 0.8 times the maximum recommended human daily dose on a mg/m2 basis) in rats and at 30 mg/kg/day (about 0.3 times the maximum recommended human daily dose on a mg/m2 basis) in rabbits. embryotoxicity was characterized by decreased fetal viability, reduced live litter sizes, and developmental delays. hydroxyurea crosses the placenta. single doses of ≥375 mg/kg (about 1.7 times the maximum recommended human daily dose on a mg/m2 basis) to rats caused growth retardation and impaired learning ability. hydroxyurea is excreted in human milk. because of the potential for serious adverse reactions in a breastfed infant from hydroxyurea, including carcinogenicity, discontinue breastfeeding during treatment with droxia. verify the pregnancy status of females of reproductive potential prior to initiating droxia therapy. droxia can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . advise females of reproductive potential to use effective contraception during and after treatment with droxia for at least 6 months after therapy. advise females to immediately report pregnancy. droxia may damage spermatozoa and testicular tissue, resulting in possible genetic abnormalities. males with female sexual partners of reproductive potential should use effective contraception during and after treatment with droxia for at least 1 year after therapy [see nonclinical toxicology (13.1)] . based on findings in animals and humans, male fertility may be compromised by treatment with droxia. azoospermia or oligospermia, sometimes reversible, has been observed in men. inform male patients about the possibility of sperm conservation before the start of therapy [see adverse reactions (6) and nonclinical toxicology (13.1)] . safety and effectiveness in pediatric patients have not been established. clinical studies of droxia did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. elderly patients may be more sensitive to the effects of hydroxyurea and may require a lower dose regimen. hydroxyurea is excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see dosage and administration (2.2)] . the exposure to hydroxyurea is higher in patients with creatinine clearance of less than 60 ml/min. reduce dosage and closely monitor the hematologic parameters when droxia is to be administered to these patients [see dosage and administration (2.2) and clinical pharmacology (12.3)] . there are no data that support specific guidance for dosage adjustment in patients with hepatic impairment. close monitoring of hematologic parameters is advised in these patients.

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h2-pharma, llc - valganciclovir hydrochloride (unii: 4p3t9qf9nz) (ganciclovir - unii:p9g3ckz4p5) - treatment of cytomegalovirus (cmv) retinitis: valcyte is indicated for the treatment of cmv retinitis in patients with acquired immunodeficiency syndrome (aids) [see clinical studies (14.1)] . prevention of cmv disease: valcyte is indicated for the prevention of cmv disease in kidney, heart, and kidney-pancreas transplant patients at high risk (donor cmv seropositive/recipient cmv seronegative [d+/r-]) [see clinical studies (14.1)] . prevention of cmv disease: valcyte is indicated for the prevention of cmv disease in kidney transplant patients (4 months to 16 years of age) and heart transplant patients (1 month to 16 years of age) at high risk [see clinical studies (14.2)] . valcyte is contraindicated in patients who have had a demonstrated clinically significant hypersensitivity reaction (e.g., anaphylaxis) to valganciclovir, ganciclovir, or any component of the formulation [see adverse reactions (6.1)]. risk summary after oral administration, valganciclovir (prodrug) is converted to ganciclovir (active drug) and, therefore, valcyte is expected to have reproductive toxicity effects similar to ganciclovir. in animal studies, ganciclovir caused maternal and fetal toxicity and embryo-fetal mortality in pregnant mice and rabbits as well as teratogenicity in rabbits at exposures two-times the human exposure. there are no available human data on use of valcyte or ganciclovir in pregnant women to establish the presence or absence of drug-associated risk. the background risk of major birth defects and miscarriage for the indicated populations is unknown. however, the background risk in the u.s. general population of major birth defects is 2–4% and the risk of miscarriage is 15–20% of clinically recognized pregnancies. advise pregnant women of the potential risk to the fetus [see warnings and precautions (5.3), use in specific populations (8.3)]. clinical considerations disease-associated maternal and/or embryo/fetal risk most maternal cmv infections are asymptomatic or they may be associated with a self-limited mononucleosis-like syndrome. however, in immunocompromised patients (i.e., transplant patients or patients with aids) cmv infections may be symptomatic and may result in significant maternal morbidity and mortality. the transmission of cmv to the fetus is a result of maternal viremia and transplacental infection. perinatal infection can also occur from exposure of the neonate to cmv shedding in the genital tract. approximately 10% of children with congenital cmv infection are symptomatic at birth. mortality in these infants is about 10% and approximately 50–90% of symptomatic surviving newborns experience significant morbidity, including mental retardation, sensorineural hearing loss, microcephaly, seizures, and other medical problems. the risk of congenital cmv infection resulting from primary maternal cmv infection may be higher and of greater severity than that resulting from maternal reactivation of cmv infection. data animal data doses resulting in two-times the human exposure of ganciclovir (based on the human auc following a single intravenous infusion of 5 mg per kg of ganciclovir) resulted in maternal and embryo-fetal toxicity in pregnant mice and rabbits as well as teratogenicity in the rabbits. fetal resorptions were present in at least 85% of rabbits and mice. rabbits showed increased embryo-fetal mortality, growth retardation of the fetuses and structural abnormalities of multiple organs of the fetuses including the palate (cleft palate), eyes (anophthalmia/microphthalmia), brain (hydrocephalus), jaw (brachygnathia), kidneys and pancreas (aplastic organs). increased embryo-fetal mortality was also seen in mice. daily intravenous doses of approximately 1.7 times the human exposure (based on auc) administered to female mice prior to mating, during gestation, and during lactation caused hypoplasia of the testes and seminal vesicles in the male offspring, as well as pathologic changes in the nonglandular region of the stomach. data from an ex-vivo human placental model showed that ganciclovir crosses the human placenta. the transfer occurred by passive diffusion and was not saturable over a concentration range of 1 to 10 mg/ml. risk summary no data are available regarding the presence of valganciclovir (prodrug) or ganciclovir (active drug) in human milk, the effects on the breastfed infant, or the effects on milk production. animal data indicate that ganciclovir is excreted in the milk of lactating rats. the centers for disease control and prevention recommend that hiv-infected mothers not breastfeed their infants to avoid risking postnatal transmission of hiv. advise nursing mothers that breastfeeding is not recommended during treatment with valcyte because of the potential for serious adverse events in nursing infants and because of the potential for transmission of hiv [see boxed warning, warnings and precautions (5.1, 5.3, 5.4, 5.5), nonclinical toxicology (13.1)] . pregnancy testing females of reproductive potential should undergo pregnancy testing before initiation of valcyte [see use in specific populations (8.1)] . contraception females because of the mutagenic and teratogenic potential of valcyte, females of reproductive potential should be advised to use effective contraception during treatment and for at least 30 days following treatment with valcyte [see dosage and administration (2.6), warnings and precautions (5.4, 5.5), nonclinical toxicology (13.1)] . males because of its mutagenic potential, males should be advised to use condoms during and for at least 90 days following, treatment with valcyte [see dosage and administration (2.6), warnings and precautions (5.3, 5.5), nonclinical toxicology (13.1)]. infertility valcyte at the recommended doses may cause temporary or permanent female and male infertility [see warnings and precautions (5.3), nonclinical toxicology (13.1)]. data human data in a small, open-label, non-randomized clinical study, adult male renal transplant patients receiving valcyte for cmv prophylaxis for up to 200 days post-transplantation were compared to an untreated control group. patients were followed-up for six months after valcyte discontinuation. among 24 evaluable patients in the valcyte group, the mean sperm density at the end of treatment visit decreased by 11 million/ml from baseline; whereas, among 14 evaluable patients in the control group the mean sperm density increased by 33 million/ml. however, at the follow-up visit among 20 evaluable patients in the valcyte group the mean sperm density was comparable to that observed among 10 evaluable patients in the untreated control group (the mean sperm density at the end of follow-up visit increased by 41 million/ml from baseline in the valcyte group and by 43 million/ml in the untreated group). valcyte for oral solution and tablets are indicated for the prevention of cmv disease in pediatric kidney transplant patients 4 months to 16 years of age and in pediatric heart transplant patients 1 month to 16 years of age at risk for developing cmv disease [see indications and usage (1.2), dosage and administration (2.3)]. the use of valcyte for oral solution and tablets for the prevention of cmv disease in pediatric kidney transplant patients 4 months to 16 years of age is based on two single-arm, open-label, non-comparative studies in patients 4 months to 16 years of age. study 1 was a safety and pharmacokinetic study in pediatric solid organ transplant patients (kidney, liver, heart, and kidney/pancreas). valcyte was administered once daily within 10 days of transplantation for a maximum of 100 days post-transplantation. study 2 was a safety and tolerability study where valcyte was administered once daily within 10 days of transplantation for a maximum of 200 days post-transplantation in pediatric kidney transplant patients. the results of these studies were supported by previous demonstration of efficacy in adult patients [see adverse reactions (6.1), clinical pharmacology (12.3), clinical studies (14.2)]. the use of valcyte for oral solution and tablets for the prevention of cmv disease in pediatric heart transplant patients 1 month to 16 years of age is based on two studies (study 1 described above and study 3) and was supported by previous demonstration of efficacy in adult patients [see clinical pharmacology (12.3), clinical studies (14.2)] . study 3 was a pharmacokinetic and safety study of valcyte in pediatric heart transplant patients less than 4 months of age who received a single dose of valcyte oral solution on each of two consecutive days. a physiologically based pharmacokinetic (pbpk) model was developed based on the available pharmacokinetic data from pediatric and adult patients to support dosing in heart transplant patients less than 1 month of age. however, due to uncertainty in model predictions for neonates, valcyte is not indicated for prophylaxis in this age group. the safety and efficacy of valcyte for oral solution and tablets have not been established in children for prevention of cmv disease in pediatric liver transplant patients, in kidney transplant patients less than 4 months of age, in heart transplant patients less than 1 month of age, in pediatric aids patients with cmv retinitis, and in infants with congenital cmv infection. a pharmacokinetic and pharmacodynamic evaluation of valcyte for oral solution was performed in 24 neonates with congenital cmv infection involving the central nervous system. all patients were treated for 6 weeks with a combination of intravenous ganciclovir 6 mg per kg twice daily or valcyte for oral solution at doses ranging from 14 mg per kg to 20 mg per kg twice daily. the pharmacokinetic results showed that in infants greater than 7 days to 3 months of age, a dose of 16 mg per kg twice daily of valcyte for oral solution provided ganciclovir systemic exposures (median auc0-12h =23.6 [range 16.8–35.5] mcg∙ h/ml; n=6) comparable to those obtained in infants up to 3 months of age from a 6 mg per kg dose of intravenous ganciclovir twice daily (auc0-12h =25.3 [range 2.4–89.7] mcg∙ h/ml; n=18) or to the ganciclovir systemic exposures obtained in adults from a 900 mg dose of valcyte tablets twice daily. however, the efficacy and safety of intravenous ganciclovir and of valcyte have not been established for the treatment of congenital cmv infection in infants and no similar disease occurs in adults; therefore, efficacy cannot be extrapolated from intravenous ganciclovir use in adults. studies of valcyte for oral solution or tablets have not been conducted in adults older than 65 years of age. clinical studies of valcyte did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. valcyte is known to be substantially excreted by the kidneys, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because renal clearance decreases with age, valcyte should be administered with consideration of their renal status. renal function should be monitored and dosage adjustments should be made accordingly [see dosage and administration (2.5), warnings and precautions (5.2), use in specific populations (8.6), clinical pharmacology (12.3)]. dose reduction is recommended when administering valcyte to patients with renal impairment [see dosage and administration (2.5), warnings and precautions (5.2), clinical pharmacology (12.3)] . for adult patients on hemodialysis (crcl less than 10 ml/min), valcyte tablets should not be used. adult hemodialysis patients should use ganciclovir in accordance with the dose-reduction algorithm cited in the cytovene® -iv complete product information section on dosage and administration: renal impairment [see dosage and administration (2.5) and clinical pharmacology (12.3)]. the safety and efficacy of valcyte have not been studied in patients with hepatic impairment. be sure that you read, and that you understand and follow these instructions carefully to ensure proper dosing of the oral solution. important: - avoid contact with your skin or eyes. if you come in contact with the contents of the oral solution, wash your skin well with soap and water or rinse your eyes well with plain water. - do not use valcyte for oral solution after the discard date on the bottle. - always use the oral dispenser provided to give or take a dose of valcyte for oral solution. - call your pharmacist if your oral dispenser is lost or damaged, and they will tell you how to continue to give or take a dose of valcyte for oral solution. - ask your healthcare provider or pharmacist to show you how to measure your prescribed dose. to take a dose of valcyte for oral solution, you will need the bottle of medicine and an oral dispenser provided with the medicine (see figure 1) . your pharmacist inserts the bottle adapter in the valcyte for oral solution bottle. - place the tip of the oral dispenser in the mouth. - slowly push down the oral dispenser plunger until the oral dispenser is empty. - remove the plunger from the oral dispenser barrel by pulling the plunger all the way out of the barrel. - rinse the oral dispenser barrel and plunger with water and let them air dry. - when the oral dispenser barrel and plunger are dry, put the plunger back into the oral dispenser barrel for the next use. how should i store valcyte for oral solution? - store solution in the refrigerator at 36°f to 46°f (2°c to 8°c) for no longer than 49 days. - do not freeze. this patient information and instructions for use have been approved by the u.s. food and drug administration. valcyte is a registered trademark of cheplapharm arzneimittel gmbh. distributed by: h2-pharma, llc montgomery, al 36117, usa licensed by: cheplapharm arzneimittel gmbh ziegelhof 24, 17489 greifswald, germany revised: 04/2023 for more information call 1-866-946-3684. © 2023 cheplapharm arzneimittel gmbh. all rights reserved.

European Union - English - EMA (European Medicines Agency)

acino pharma gmbh  - clopidogrel - peripheral vascular diseases - antithrombotic agents - clopidogrel is indicated in adults for the prevention of atherothrombotic events in:patients suffering from myocardial infarction (from a few days until less than 35 days), ischaemic stroke (from 7 days until less than 6 months) or established peripheral arterial disease.patients suffering from acute coronary syndrome:- non st segment elevation acute coronary syndrome (unstable angina or non q wave myocardial infarction), including patients undergoing a stent placement following percutaneous coronary intervention, in combination with acetylsalicylic acid (asa).- st segment elevation acute myocardial infarction, in combination with asa in medically treated patients eligible for thrombolytic therapy.for further information please refer to section 5.1.

European Union - English - EMA (European Medicines Agency)

acino pharma gmbh - clopidogrel - peripheral vascular diseases; stroke; myocardial infarction - antithrombotic agents - clopidogrel is indicated in adults for the prevention of atherothrombotic events in:patients suffering from myocardial infarction (from a few days until less than 35 days), ischaemic stroke (from 7 days until less than 6 months) or established peripheral arterial disease.for further information please refer to section 5.1.

European Union - English - EMA (European Medicines Agency)

acino pharma gmbh - clopidogrel - peripheral vascular diseases; stroke; myocardial infarction - antithrombotic agents - clopidogrel is indicated in adults for the prevention of atherothrombotic events in:patients suffering from myocardial infarction (from a few days until less than 35 days), ischaemic stroke (from 7 days until less than 6 months) or established peripheral arterial disease.for further information please refer to section 5.1.

European Union - English - EMA (European Medicines Agency)

taw pharma (ireland) limited - clopidogrel hydrochloride - peripheral vascular diseases; stroke; myocardial infarction; acute coronary syndrome - antithrombotic agents - , , , , secondary prevention of atherothrombotic events, , clopidogrel is indicated in: , - adult patients suffering from myocardial infarction (from a few days until less than 35 days), ischaemic stroke (from 7 days until less than 6 months) or established peripheral arterial disease., - adult patients suffering from acute coronary syndrome:,    - non-st segment elevation acute coronary syndrome (unstable angina or non-q-wave myocardial infarction), including patients undergoing a stent placement following percutaneous coronary intervention, in combination with acetylsalicylic acid (asa).,     - st segment elevation acute myocardial infarction, in combination with asa in medically treated patients eligible for thrombolytic therapy., , in patients with moderate to high-risk transient ischaemic attack (tia) or minor ischaemic stroke (is), clopidogrel in combination with asa is indicated in:, - adult patients with moderate to high-risk tia (abcd2  score ≥4) or minor is (nihss  ≤3) within 24 hours of either the tia or is event. , , prevention of atherothrombotic and thromboembolic events in atrial fibrillation, in adult patients with atrial fibrillation who have at least one risk factor for vascular events, are not suitable for treatment with vitamin k antagonists (vka) and who have a low bleeding risk, clopidogrel is indicated in combination with asa for the prevention of atherothrombotic and thromboembolic events, including stroke., , for further information please refer to section 5.1. , , ,

European Union - English - EMA (European Medicines Agency)

teva pharma b.v.  - clopidogrel (as hydrobromide) - peripheral vascular diseases; acute coronary syndrome; myocardial infarction; stroke - antithrombotic agents - prevention of atherothrombotic eventsclopidogrel is indicated in:adult patients suffering from myocardial infarction (from a few days until less than 35 days), ischaemic stroke (from 7 days until less than 6 months) or established peripheral arterial disease;adult patients suffering from acute coronary syndrome: non-st segment elevation acute coronary syndrome (unstable angina or non-q-wave myocardial infarction), including patients undergoing a stent placement following percutaneous coronary intervention, in combination with acetylsalicylic acid (asa);st segment elevation acute myocardial infarction, in combination with asa in medically treated patients eligible for thrombolytic therapy.prevention of atherothrombotic and thromboembolic events in atrial fibrillationin adult patients with atrial fibrillation who have at least one risk factor for vascular events, are not suitable for treatment with vitamin-k antagonists (vka) and who have a low bleeding risk, clopidogrel is indicated in combination with asa for the prevention of atherothrombotic and thromboembolic events, including stroke.

United States - English - NLM (National Library of Medicine)

h2-pharma, llc - fenofibrate (unii: u202363uos) (fenofibrate - unii:u202363uos) - fenofibrate 50 mg - fenofibrate capsules are indicated as adjunctive therapy to diet to reduce elevated low-density lipoprotein cholesterol (ldl-c), total cholesterol (total-c), triglycerides (tg) and apolopoprotein b (apo b), and to increase high-density lipoprotein cholesterol (hdl-c) in adult patients with primary hypercholesterolemia or mixed dyslipidemia. fenofibrate capsules are also indicated as adjunctive therapy to diet for treatment of adult patients with severe hypertriglyceridemia. improving glycemic control in diabetic patients showing fasting chylomicronemia will usually obviate the need for pharmacologic intervention. markedly elevated levels of serum triglycerides (e.g. > 2,000 mg/dl) may increase the risk of developing pancreatitis. the effect of fenofibrate therapy on reducing this risk has not been adequately studied. fenofibrate at a dose equivalent to 150 mg was not shown to reduce coronary heart disease morbidity and mortality in 2 large, randomized controlled trials of patients with type 2 diabetes mellitu

United States - English - NLM (National Library of Medicine)

h2-pharma, llc - capecitabine (unii: 6804dj8z9u) (capecitabine - unii:6804dj8z9u) - xeloda is indicated for the: - adjuvant treatment of patients with stage iii colon cancer as a single agent or as a component of a combination chemotherapy regimen. - perioperative treatment of adults with locally advanced rectal cancer as a component of chemoradiotherapy. - treatment of patients with unresectable or metastatic colorectal cancer as a single agent or as a component of a combination chemotherapy regimen. xeloda is indicated for the: - treatment of patients with advanced or metastatic breast cancer as a single agent if an anthracycline- or taxane-containing chemotherapy is not indicated. - treatment of patients with advanced or metastatic breast cancer in combination with docetaxel after disease progression on prior anthracycline-containing chemotherapy. xeloda is indicated for the: - treatment of adults with unresectable or metastatic gastric, esophageal, or gastroesophageal junction cancer as a component of a combination chemotherapy regimen. - treatment of adults with her2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma who have not received prior treatment for metastatic disease as a component of a combination regimen. xeloda is indicated for the adjuvant treatment of adults with pancreatic adenocarcinoma as a component of a combination chemotherapy regimen. xeloda is contraindicated in patients with history of severe hypersensitivity reaction to fluorouracil or capecitabine [see adverse reactions (6.1)] . risk summary based on findings in animal reproduction studies and its mechanism of action [see clinical pharmacology (12.1)] , xeloda can cause fetal harm when administered to a pregnant woman. available human data with xeloda use in pregnant women is not sufficient to inform the drug-associated risk. in animal reproduction studies, administration of capecitabine to pregnant animals during the period of organogenesis caused embryolethality and teratogenicity in mice and embryolethality in monkeys at 0.2 and 0.6 times the exposure (auc) in patients receiving the recommended dose of 1,250 mg/m2 twice daily, respectively (see 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 oral administration of capecitabine to pregnant mice during the period of organogenesis at a dose of 198 mg/kg/day caused malformations and embryo lethality. in separate pharmacokinetic studies, this dose in mice produced 5'-dfur auc values that were approximately 0.2 times the auc values in patients administered the recommended daily dose. malformations in mice included cleft palate, anophthalmia, microphthalmia, oligodactyly, polydactyly, syndactyly, kinky tail and dilation of cerebral ventricles. oral administration of capecitabine to pregnant monkeys during the period of organogenesis at a dose of 90 mg/kg/day, caused fetal lethality. this dose produced 5'-dfur auc values that were approximately 0.6 times the auc values in patients administered the recommended daily dose. risk summary there is no information regarding the presence of capecitabine or its metabolites in human milk, or on its effects on milk production or the breastfed child. capecitabine metabolites were present in the milk of lactating mice (see data) . because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with xeloda and for 1 week after the last dose. data lactating mice given a single oral dose of capecitabine excreted significant amounts of capecitabine metabolites into the milk. xeloda can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . pregnancy testing verify pregnancy status in females of reproductive potential prior to initiating xeloda. contraception females advise females of reproductive potential to use effective contraception during treatment with xeloda and for 6 months after the last dose. males based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with xeloda and for 3 months after the last dose [see nonclinical toxicology (13.1)]. infertility based on animal studies, xeloda may impair fertility in females and males of reproductive potential [see nonclinical toxicology (13.1)] . the safety and effectiveness of xeloda in pediatric patients have not been established. safety and effectiveness were assessed, but not established in two single arm studies in 56 pediatric patients aged 3 months to <17 years with newly diagnosed gliomas. in both trials, pediatric patients received an investigational pediatric formulation of capecitabine concomitantly with and following completion of radiation therapy (total dose of 5580 cgy in 180 cgy fractions). the relative bioavailability of the investigational formulation to xeloda was similar. the adverse reaction profile was consistent with that of adults, with the exception of laboratory abnormalities which occurred more commonly in pediatric patients. the most frequently reported laboratory abnormalities (per-patient incidence ≥ 40%) were increased alt (75%), lymphocytopenia (73%), hypokalemia (68%), thrombocytopenia (57%), hypoalbuminemia (55%), neutropenia (50%), low hematocrit (50%), hypocalcemia (48%), hypophosphatemia (45%) and hyponatremia (45%). of 7938 patients with colorectal cancer who were treated with xeloda, 33% were older than 65 years. of the 4536 patients with metastatic breast cancer who were treated with xeloda, 18% were older than 65 years. of 1951 patients with gastric, esophageal, or gastrointestinal junction cancer who were treated with xeloda, 26% were older than 65 years. of 364 patients with pancreatic cancer who received adjuvant treatment with xeloda, 47% were 65 years or older. no overall differences in efficacy were observed comparing older versus younger patients with colorectal cancer, gastric, esophageal or gastrointestinal junction cancer, or pancreatic cancer using the approved recommended dosages and treatment regimens. older patients experience increased gastrointestinal toxicity due to xeloda compared to younger patients. deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly leucovorin and fluorouracil [see drug interactions (7.1)]. the exposure of capecitabine and its inactive metabolites (5-dfur and fbal) increases in patients with clcr <50 ml/min as determined by cockcroft-gault [see clinical pharmacology (12.3)] . reduce the dosage for patients with clcr of 30 to 50 ml/min [see dosage and administration (2.6)] . there is limited experience with xeloda in patients with clcr <30 ml/min, and a dosage has not been established in those patients. if no treatment alternative exists, xeloda could be administered to such patients on an individual basis applying a reduced starting dose, close monitoring of a patient's clinical and biochemical data and dose modifications guided by observed adverse reactions. the exposure of capecitabine increases in patients with mild to moderate hepatic impairment. the effect of severe hepatic impairment on the safety and pharmacokinetics of xeloda is unknown [see clinical pharmacology (12.3)]. monitor patients with hepatic impairment more frequently for adverse reactions.