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

physicians total care, inc. - pioglitazone hydrochloride (unii: jqt35npk6c) (pioglitazone - unii:x4ov71u42s), metformin hydrochloride (unii: 786z46389e) (metformin - unii:9100l32l2n) - pioglitazone hydrochloride 15 mg - actoplus met is a thiazolidinedione and biguanide combination product indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already treated with a thiazolidinedione and metformin or who have inadequate glycemic control on a thiazolidinedione alone or metformin alone. initiation of actoplus met in patients with established new york heart association (nyha) class iii or iv heart failure is contraindicated (see boxed warning ). in addition, actoplus met is contraindicated in patients with: - renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels ≥ 1.5 mg/dl [males], ≥ 1.4 mg/dl [females], or abnormal creatinine clearance) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia (see warnings, metformin hydrochloride and precautions, general: metformin hydrochloride ). - known hypersensitivity to pioglitazone, metformin or any other component of actop

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

takeda pharmaceuticals america, inc. - pioglitazone hydrochloride (unii: jqt35npk6c) (pioglitazone - unii:x4ov71u42s), metformin hydrochloride (unii: 786z46389e) (metformin - unii:9100l32l2n) - pioglitazone 15 mg - actoplus met xr is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both pioglitazone and metformin is appropriate [see clinical studies (14)] . important limitations of use pioglitazone exerts its antihyperglycemic effect only in the presence of endogenous insulin. actoplus met xr should not be used to treat type 1 diabetes or diabetic ketoacidosis, as it would not be effective in these settings. use caution in patients with liver disease [see warnings and precautions (5.5)]. - initiation in patients with established nyha class iii or iv heart failure [see boxed warning] . - severe renal impairment ( egfr below 30 ml/min/1.73 m2 ) [see warnings and precautions (5.2)]. - use in patients with known hypersensitivity to pioglitazone, metformin or any other component of actoplus met xr. - metabolic acidosis, including diabetic ketoacidosis. diabetic ketoacidosis should be treated with insulin. risk summary

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

takeda pharmaceuticals america, inc. - pioglitazone hydrochloride (unii: jqt35npk6c) (pioglitazone - unii:x4ov71u42s), metformin hydrochloride (unii: 786z46389e) (metformin - unii:9100l32l2n) - pioglitazone 15 mg - actoplus met is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both pioglitazone and metformin is appropriate [see clinical studies (14)] . important limitations of use pioglitazone exerts its antihyperglycemic effect only in the presence of endogenous insulin. actoplus met should not be used to treat type 1 diabetes or diabetic ketoacidosis, as it would not be effective in these settings. use caution in patients with liver disease [see warnings and precautions (5.5)] . risk summary limited data with actoplus met or pioglitazone in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk (see data). there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see clinical considerations]. in animal reproduction studies, no adverse developmental effects were observed when pioglitazone was administered to pregnant rats and rabbits during organogenesis at exposures up to 5 and 35 times the 45 mg clinical dose, respectively, based on body surface area. no adverse developmental effects were observed when metformin was administered to pregnant sprague dawley rats and rabbits during the period of organogenesis at doses up to 2 to 6 times, respectively, a 2000 mg clinical dose, based on body surface area (see data). the estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with a hba1c >7 and has been reported to be as high as 20 to 25% in women with a hba1c >10. the estimated background risk of miscarriage for the indicated population is unknown. in the us 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. clinical considerations disease-associated maternal and/or embryo/fetal risk poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, still birth and delivery complications. poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity. data human data published data from postmarketing studies have not reported a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin was used during pregnancy. however, these studies cannot definitely establish the absence of any metformin-associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. animal data pioglitazone and metformin hydrochloride animal reproduction studies were not conducted with the combined products in actoplus met. the following data are based on studies conducted with the individual components of actoplus met. pioglitazone pioglitazone administered to pregnant rats during organogenesis did not cause adverse developmental effects at a dose of 20 mg/kg (~5 times the 45 mg clinical dose), but delayed parturition and reduced embryo-fetal viability at 40 and 80 mg/kg, or ≥9 times the 45 mg clinical dose, by body surface area. in pregnant rabbits administered pioglitazone during organogenesis, no adverse developmental effects were observed at 80 mg/kg (~35 times the 45 mg clinical dose), but reduced embryo-fetal viability at 160 mg/kg, or ~69 times the 45 mg clinical dose, by body surface area. when pregnant rats received pioglitazone during late gestation and lactation, delayed postnatal development, attributed to decreased body weight, occurred in offspring at maternal doses of 10 mg/kg and above or ≥2 times the 45 mg clinical dose, by body surface area. metformin hydrochloride metformin hydrochloride did not cause adverse developmental effects when administered to pregnant sprague dawley rats and rabbits up to 600 mg/kg/day during the period of organogenesis. this represents an exposure of about 2 to 6 times a 2000 mg clinical dose based on body surface area (mg/m2 ) for rats and rabbits, respectively. risk summary there is no information regarding the presence of actoplus met or pioglitazone in human milk, the effects on the breastfed infant, or the effects on milk production. pioglitazone is present in rat milk; however, due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk. limited published studies report that metformin is present in human milk (see data) . however, there is insufficient information on the effects of metformin on the breastfed infant and no available information on the effects of metformin on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for actoplus met and any potential adverse effects on the breastfed infant from actoplus met or from the underlying maternal condition. data published clinical lactation studies report that metformin is present in human milk which resulted in infant doses approximately 0.11% to 1% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 0.13 and 1. however, the studies were not designed to definitely establish the risk of use of metformin during lactation because of small sample size and limited adverse event data collected in infants. discuss the potential for unintended pregnancy with premenopausal women as therapy with actoplus met, may result in ovulation in some anovulatory women. safety and effectiveness of actoplus met in pediatric patients have not been established. actoplus met is not recommended for use in pediatric patients based on adverse effects observed in adults, including fluid retention and congestive heart failure, fractures, and urinary bladder tumors [see warnings and precautions (5.1, 5.3, 5.6, 5.7)]. pioglitazone a total of 92 patients (15.2%) treated with pioglitazone in the three pooled 16 to 26 week double-blind, placebo-controlled, monotherapy trials were ≥65 years old and two patients (0.3%) were ≥75 years old. in the two pooled 16 to 24 week add-on to sulfonylurea trials, 201 patients (18.7%) treated with pioglitazone were ≥65 years old and 19 (1.8%) were ≥75 years old. in the two pooled 16 to 24 week add-on to metformin trials, 155 patients (15.5%) treated with pioglitazone were ≥65 years old and 19 (1.9%) were ≥75 years old. in the two pooled 16 to 24 week add-on to insulin trials, 272 patients (25.4%) treated with pioglitazone were ≥65 years old and 22 (2.1%) were ≥75 years old. in proactive trial, 1068 patients (41.0%) treated with pioglitazone were ≥65 years old and 42 (1.6%) were ≥75 years old. in pharmacokinetic studies with pioglitazone, no significant differences were observed in pharmacokinetic parameters between elderly and younger patients [see clinical pharmacology (12.3)] . although clinical experiences have not identified differences in effectiveness and safety between the elderly (≥65 years) and younger patients, these conclusions are limited by small sample sizes for patients ≥75 years old. metformin hydrochloride controlled clinical studies of metformin did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients, although other reported clinical experience has not identified differences in responses between the elderly and young patients. 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 and the higher risk of lactic acidosis. assess renal function more frequently in elderly patients [see warnings and precautions (5.2), dosage and administration (2.2)]. metformin is substantially excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of renal impairment. actoplus met is contraindicated in severe renal impairment, patients with an egfr below 30 ml/min/1.73 m2 [see dosage and administration (2.2), contraindications (4), warnings and precautions (5.2), clinical pharmacology (12.3)]. use of metformin in patients with hepatic impairment has been associated with some cases of lactic acidosis. actoplus met is not recommended in patients with hepatic impairment [see warnings and precautions (5.2)] .

European Union - English - EMA (European Medicines Agency)

zoetis belgium sa - selamectin, sarolaner - antiparasitic products, insecticides and repellents, macrocyclic lactones, , combinations - cats - for cats with, or at risk from, mixed parasitic infestations by ticks and fleas, lice, mites, gastrointestinal nematodes or heartworm.the veterinary medicinal product is exclusively indicated when use against ticks and one or more of the other target parasites is indicated at the same time.

European Union - English - EMA (European Medicines Agency)

zoetis belgium sa - canine distemper virus, strain cdv bio 11/a, canine adenovirus type 2, strain cav-2 bio 13, canine parvovirus type 2b, strain cpv-2b bio 12/b and canine parainfluenza type 2 virus, strain cpiv-2 bio 15 (all live attenuated) - immunologicals for canidae, live viral vaccines - dogs - active immunisation of dogs from six weeks of age.to prevent mortality and clinical signs caused by canine distemper virus,to prevent mortality and clinical signs caused by canine adenovirus type 1,to prevent clinical signs and reduce viral excretion caused by canine adenovirus type 2,to prevent clinical signs, leukopenia and viral excretion caused by canine parvovirus,to prevent clinical signs and reduce viral excretion caused by canine parainfluenza virus.

European Union - English - EMA (European Medicines Agency)

zoetis belgium sa - canine parainfluenza type-2 virus, strain cpiv-2 bio 15 (live attenuated) - immunologicals for canidae, live viral vaccines - dogs - active immunisation of dogs from six weeks of age to prevent clinical signs (nasal and ocular discharge) and reduce viral excretion caused by canine parainfluenza virus.

European Union - English - EMA (European Medicines Agency)

zoetis belgium sa. - canine parainfluenza type 2 virus, strain cpiv-2 bio 15 (live attenuated), leptospira interrogans serogroup australis serovar bratislava, strain mslb 1088, l. interrogans serogroup icterohaemorrhagiae serovar icterohaemorrhagiae, strain mslb 1089, l. interrogans serogroup canicola serovar canicola, strain mslb 1090 and l. kirschneri serogroup grippotyphosa serovar grippotyphosa, strain mslb 1091 (all inactivated) - immunologicals for canidae, live viral and inactivated bacterial vaccines - dogs - active immunisation of dogs from six weeks of age. - to prevent clinical signs and reduce viral excretion caused by canine parainfluenza virus, - to prevent clinical signs, infection and urinary excretion caused by leptospira serovars bratislava, canicola, grippotyphosa and icterohaemorrhagiae. onset of immunity: immunity has been demonstrated from 3 weeks after completion of the primary course for cpiv and from 4 weeks after completion of the primary course for leptospira components. duration of immunity: at least one year following the primary vaccination course for all components of versican plus pi/l4.

European Union - English - EMA (European Medicines Agency)

zoetis belgium sa - selamectin, sarolaner - antiparasitic products, insecticides and repellents - cats - for cats with, or at risk from, mixed parasitic infestations by ticks and fleas, lice, mites, gastrointestinal nematodes or heartworm. the veterinary medicinal product is exclusively indicated when use against ticks and one or more of the other target parasites is indicated at the same time.

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

plus cosmetica s.a. - alcohol (unii: 3k9958v90m) (alcohol - unii:3k9958v90m) - uses * sanitizer antibacterial helps eliminate bacteria on hands and arms. this product is not a substitute of hands and soap hand washing. avoid contact with broken or damaged skin stop use and ask a doctor if * irritation develops while using this product uses * sanitizer antibacterial helps eliminate bacteria on hands and arms. this product is not a substitute of hands and soap hand washing. avoid contact with broken or damaged skin

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

plus cosmetica s.a. - alcohol (unii: 3k9958v90m) (alcohol - unii:3k9958v90m) - uses * sanitizer antibacterial helps eliminate bacteria on hands and arms. this product is not a substitute of hands and soap hand washing. avoid contact with broken or damaged skin stop use and ask a doctor if * irritation develops while using this product uses * sanitizer antibacterial helps eliminate bacteria on hands and arms. this product is not a substitute of hands and soap hand washing. avoid contact with broken or damaged skin