Unione Europea - inglese - EMA (European Medicines Agency)

takeda pharmaceuticals international ag ireland branch - maribavir - cytomegalovirus infections - antivirals for systemic use - livtencity is indicated for the treatment of cytomegalovirus (cmv) infection and/or disease that are refractory (with or without resistance) to one or more prior therapies, including ganciclovir, valganciclovir, cidofovir or foscarnet in adult patients who have undergone a haematopoietic stem cell transplant (hsct) or solid organ transplant (sot).consideration should be given to official guidance on the appropriate use of antiviral agents.

Unione Europea - inglese - EMA (European Medicines Agency)

takeda pharma a/s - brentuximab vedotin - lymphoma, non-hodgkin; hodgkin disease - antineoplastic agents - hodgkin lymphomaadcetris is indicated for adult patients with previously untreated cd30+ stage iv hodgkin lymphoma (hl) in combination with doxorubicin, vinblastine and dacarbazine (avd).adcetris is indicated for the treatment of adult patients with cd30+ hl at increased risk of relapse or progression following autologous stem cell transplant (asct).adcetris is indicated for the treatment of adult patients with relapsed or refractory cd30+ hodgkin lymphoma (hl):following asct, orfollowing at least two prior therapies when asct or multi-agent chemotherapy is not a treatment option.systemic anaplastic large cell lymphomaadcetris in combination with cyclophosphamide, doxorubicin and prednisone (chp) is indicated for adult patients with previously untreated systemic anaplastic large cell lymphoma (salcl).adcetris is indicated for the treatment of adult patients with relapsed or refractory salcl.cutaneous t cell lymphomaadcetris is indicated for the treatment of adult patients with cd30+ cutaneous t cell lymphoma (ctcl) after at least 1 prior systemic therapy.

Stati Uniti - inglese - NLM (National Library of Medicine)

takeda pharmaceuticals america, inc. - vedolizumab (unii: 9rv78q2002) (vedolizumab - unii:9rv78q2002) - vedolizumab 300 mg in 5 ml - entyvio is indicated in adults for the treatment of: - moderately to severely active ulcerative colitis (uc). - moderately to severely active crohn's disease (cd). entyvio is contraindicated in patients who have had a known serious or severe hypersensitivity reaction to entyvio or any of its excipients (such as dyspnea, bronchospasm, urticaria, flushing, rash and increased heart rate) [see warnings and precautions (5.1)] . risk summary available data from the organization of teratology information specialists (otis)/mothertobaby entyvio pregnancy registry, published literature and pharmacovigilance in pregnant women have not reliably identified an entyvio-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes (see data) . there are risks to the mother and the fetus associated with inflammatory bowel disease in pregnancy (see clinical considerations) . no fetal harm was observed in animal reproduction studies with intravenous administration of vedolizumab to rabbits and monkeys at dose levels 20 times the recommended human dosage (see data) . the background risk of major birth defects and miscarriage for the indicated populations 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 miscarriage is 15 to 20%, respectively. clinical considerations disease-associated maternal and embryo/fetal risk published data suggest that the risk of adverse pregnancy outcomes in women with inflammatory bowel disease (ibd) is associated with increased disease activity. adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2,500 g) infants, and small for gestational age at birth. fetal/neonatal adverse reactions entyvio administered during pregnancy could affect immune responses in the in utero exposed newborn and infant. the clinical significance of low levels of entyvio in utero-exposed infants is unknown. the safety of administering live or live-attenuated vaccines in exposed infants is unknown. data human data the vedolizumab pregnancy exposure registry conducted by otis/mothertobaby study in the united states and canada collected prospective observational data between 2015 and 2022 to assess the risk of major birth defects in live-born infants of women with ulcerative colitis (uc) or crohn’s disease (cd) treated with vedolizumab during pregnancy. the study compared pregnant patients with uc or cd exposed to vedolizumab with pregnant patients with uc or cd treated with other biological products. the registry included 99 women (58 with uc, 41 with cd) treated with vedolizumab during pregnancy, and 76 women (27 with uc, 49 with cd) exposed to other biological products during pregnancy. the proportion of major birth defects among live-born infants in patients with uc or cd treated with vedolizumab and patients with uc or cd treated with other biological products was 7.4% (7/94) and 5.6% (4/71), respectively. overall, there was no evidence of increased risk for major structural birth defects (adjusted rr 1.07, 95% ci: 0.33, 3.52). the methodological limitations of the registry, including small sample size and the non-randomized design, resulted in a limited ability to estimate the risk of major birth defects and other maternal and infant outcomes. the conclusions from the pregnancy registry were consistent with the published literature and pharmacovigilance. animal data a reproduction study has been performed in pregnant rabbits at single intravenous doses up to 100 mg/kg administered on gestation day 7 (about 20 times the recommended human dosage) and has revealed no evidence of impaired fertility or harm to the fetus due to vedolizumab. a pre- and post-natal development study in monkeys showed no evidence of any adverse effect on pre- and post-natal development at intravenous doses up to 100 mg/kg (about 20 times the recommended human dosage). risk summary data from a clinical lactation study show the presence of vedolizumab in human milk. the mean calculated daily infant dosage was 0.02 mg/kg/day orally (see data) . systemic exposure in a breastfed infant is expected to be low because monoclonal antibodies are largely degraded in the gastrointestinal tract. there are no data on the effects of vedolizumab on the breastfed infant, or the effects on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for entyvio and any potential adverse effects on the breastfed infant from entyvio or from the underlying maternal condition. data a milk-only lactation study was conducted in 9 adult lactating women being treated for active ulcerative colitis or crohn's disease with intravenous entyvio every 8 weeks after reaching steady state and completing the induction phase (entyvio administration at 0, 2, and 6 weeks). mean concentrations of entyvio in human milk ranged from 0.03 to 0.26 mcg/ml. the mean calculated daily infant oral dosage was 0.02 mg/kg/day calculated as a product of the average concentration over the 8-week dosing interval and the standardized milk consumption of 150 ml/kg/day. safety and effectiveness of entyvio in pediatric patients have not been established. clinical trials of entyvio did not include sufficient numbers of subjects aged 65 and over (56 crohn's and ulcerative colitis patients aged 65 and over were treated with entyvio during controlled phase 3 trials) to determine whether they respond differently from younger subjects. however, no overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. entyvio ® (en ti' vee oh) pen (vedolizumab) injection, for subcutaneous use single-dose prefilled pen this instructions for use contains information on how to inject entyvio. your entyvio single-dose prefilled pen - read and follow this instructions for use before you inject entyvio. - your healthcare provider should show you how to use the entyvio pen before you use it for the first time. - entyvio pen is for subcutaneous injection only (inject directly into fatty layer under the skin). - do not shake the prefilled pen. - do not remove the purple cap from the prefilled pen until you are ready to inject. - do not put or press your thumb, fingers, or hand over the yellow needle shield. the yellow needle shield is visible when the purple cap is removed. - do not use the prefilled pen if it is dropped or damaged. storing entyvio - store your prefilled pen in the refrigerator between 36°f to 46°f (2°c to 8°c). - your prefilled pen can be left in its box at room temperature up to 77°f (25°c) for up to 7 days (for example, when traveling). do not use the prefilled pen if it is left out of the refrigerator for more than 7 days. - do not freeze the prefilled pen. - do not leave the prefilled pen in direct sunlight. - throw away the prefilled pen in a fda-cleared sharps disposal container if it has been left out of the refrigerator for more than 7 days, frozen, or left in direct sunlight. see step 14 for instructions on how to throw away (dispose of) the prefilled pen. - always keep entyvio pens, the sharps disposal container, and all medicines out of the reach of children. - do not use the prefilled pen if any of the seals on the box are broken. - do not use the prefilled pen if the expiration date on the box has passed. - do not warm the prefilled pen any other way. - do not let the prefilled pen sit in direct sunlight. - do not take the prefilled pen out of its tray until you are ready to inject. - alcohol pad - cotton ball or gauze - sharps disposal container (see step 14 "throw away (dispose of) the prefilled pen") - do not shake the prefilled pen. - do not remove the purple cap from the prefilled pen until step 9 . - do not use the prefilled pen if the expiration date on the prefilled pen has passed. - do not use the prefilled pen if the medicine is cloudy or has particles floating in it. - do not use the prefilled pen if any part of it is damaged. - do not inject into the same spot you used for your last injection. - do not inject into moles, scars, bruises, or skin that is tender, hard, red, or damaged. - do not touch or blow on the cleaned injection site before you inject. - the needle is inside the yellow needle shield (under purple cap). - do not put or press your thumb, fingers, or hand over the yellow needle shield. - do not put the purple cap back on. this could accidentally start the injection. - hold the prefilled pen so you can see the viewing window. - place the yellow end of the prefilled pen flat on your skin at 90 degrees to the injection site (see figure j ). - the needle is inside the yellow needle shield. - do not push down on the prefilled pen until you are ready to inject. - you may hear a first click when the injection starts. - you may hear a second click. this is not the end of the injection. - continue holding the prefilled pen with constant pressure and watch the window turn purple. - you will see a small amount of gray in the viewing window. this is normal. - if the viewing window did not fill with purple, you may not have received your full dose. call your pharmacy or healthcare provider. - when you remove the prefilled pen, if the window has not turned purple, or it looks like the medicine is still coming out of the prefilled pen, this means you have not received a full dose. call your pharmacy or healthcare provider right away. - you may see a small amount of blood at the injection site. if you do, press on your skin with a cotton ball or gauze. - throw away the remaining supplies in your household trash or sharps disposal container. - if you do not have a fda-cleared sharps disposal container, you may use a household container that is: - made of heavy-duty plastic, - can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, - upright and stable during use, - leak-resistant, and - properly labeled to warn of hazardous waste inside the container. - when your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. there may be local or state laws about how you should throw away needles and syringes. - for more information about safe sharps disposal, and for specific information about sharps disposal in the state you live in, go to the fda's website at: http://www.fda.gov/safesharpsdisposal. this instructions for use has been approved by the u.s. food and drug administration. approved: 9/2023 entyvio® (en ti' vee oh) (vedolizumab) injection, for subcutaneous use single-dose prefilled syringe this instructions for use contains information on how to inject entyvio. your entyvio single-dose prefilled syringe - read and follow this instructions for use before you inject entyvio. - your healthcare provider should show you how to use the entyvio prefilled syringe before you use it for the first time. - entyvio prefilled syringe is for subcutaneous injection only (inject directly into fatty layer under the skin). - do not shake the prefilled syringe. - do not remove the needle cap from the prefilled syringe until you are ready to inject. - do not use the prefilled syringe if it is dropped or damaged. - each prefilled syringe has a needle guard. it will automatically cover the needle after the injection is completed to reduce the risk of accidental needle sticks. storing entyvio - store your prefilled syringe in the refrigerator between 36°f to 46°f (2°c to 8°c). - your prefilled syringe can be left in its box at room temperature up to 77°f (25°c) for up to 7 days (for example, when traveling). do not use the prefilled syringe if it is left out of the refrigerator for more than 7 days. - do not freeze the prefilled syringe. - do not leave the prefilled syringe in direct sunlight. - throw away the prefilled syringe in a fda-cleared sharps disposal container if it has been left out of the refrigerator for more than 7 days, frozen, or left in direct sunlight. see step 14 for instructions on how to throw away (dispose of) the prefilled syringe. - always keep entyvio prefilled syringes, the sharps disposal container, and all medicines out of the reach of children. - do not use the prefilled syringe if any of the seals on the box are broken. - do not use the prefilled syringe if the expiration date on the box has passed. - do not warm the prefilled syringe any other way. - do not let the prefilled syringe sit in direct sunlight. - do not take the prefilled syringe out of its tray until you are ready to inject. - alcohol pad - cotton ball or gauze - sharps disposal container (see step 14 "throw away (dispose of) the prefilled syringe") - do not lift from the purple plunger. - do not shake the prefilled syringe. - do not remove the needle cap from the prefilled syringe until step 9 . - do not use the prefilled syringe if the expiration date on the prefilled syringe has passed. - do not use the prefilled syringe if the medicine is cloudy or has particles floating in it. - do not use the prefilled syringe if any part of it is damaged. - do not try to remove air bubbles from the prefilled syringe. - do not inject into the same spot you used for your last injection. - do not inject into moles, scars, bruises, or skin that is tender, hard, red, or damaged. - do not touch or blow on the cleaned injection site before you inject. - do not touch or pull back the purple plunger. - do not touch or re-cap the needle. - do not use a prefilled syringe with a bent or broken needle. - hold the pinch until the injection is completed. - avoid touching the plunger until the needle is inserted. - keep pressure on the plunger and take the needle out of the skin. - if you are not able to start or cannot complete the injection by pushing the plunger all the way down, you may not have received your full dose. call your pharmacy or healthcare provider. - you may see a small amount of blood at the injection site. if you do, press on your skin with a cotton ball or gauze. - throw away the remaining supplies in your household trash or sharps disposal container. - if you do not have a fda-cleared sharps disposal container, you may use a household container that is: - made of heavy-duty plastic, - can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, - upright and stable during use, - leak-resistant, and - properly labeled to warn of hazardous waste inside the container. - when your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. there may be local or state laws about how you should throw away needles and syringes. - for more information about safe sharps disposal, and for specific information about sharps disposal in the state you live in, go to the fda's website at: http://www.fda.gov/safesharpsdisposal. this instructions for use has been approved by the u.s. food and drug administration. approved: 9/2023

Australia - inglese - Department of Health (Therapeutic Goods Administration)

takeda pharmaceuticals australia pty ltd - pantoprazole, quantity: 22.57 mg (equivalent: pantoprazole, qty 20 mg) - tablet, enteric coated - excipient ingredients: iron oxide yellow; povidone; polysorbate 80; crospovidone; purified water; hypromellose; titanium dioxide; sodium carbonate; sodium lauryl sulfate; triethyl citrate; propylene glycol; mannitol; methacrylic acid copolymer; calcium stearate; butan-1-ol; isopropyl alcohol; iron oxide red; strong ammonia solution; iron oxide black; ethanol; shellac; sulfuric acid - somac heartburn relief is indicated for symptomatic relief of heartburn, acid regurgitation and other symptoms associated with gastro-oesophageal reflux disease (gord).

Australia - inglese - Department of Health (Therapeutic Goods Administration)

takeda pharmaceuticals australia pty ltd - vedolizumab, quantity: 331.2 mg - injection, powder for - excipient ingredients: polysorbate 80; arginine hydrochloride; histidine; sucrose; histidine hydrochloride monohydrate - ulcerative colitis,treatment of adult patients with moderate to severe ulcerative colitis who have had an inadequate response with, lost response to, or are intolerant to either conventional therapy or a tumour necrosis factor-alpha (tnf-alpha) antagonist.,crohn?s disease,treatment of adult patients with moderate to severe crohn?s disease who have had an inadequate response with, lost response to, or are intolerant to either conventional therapy or a tumour necrosis factor-alpha (tnf-alpha) antagonist.,pouchitis,entyvio is indicated for the treatment of adult patients with moderate to severe chronic pouchitis, who have undergone proctocolectomy and ileal pouch anal anastomosis for ulcerative colitis, and have had an inadequate response with or lost response to antibiotic therapy.

Australia - inglese - Department of Health (Therapeutic Goods Administration)

takeda pharmaceuticals australia pty ltd - brentuximab vedotin, quantity: 50 mg - injection, powder for - excipient ingredients: citric acid monohydrate; trehalose dihydrate; sodium citrate dihydrate; polysorbate 80 - hodgkin lymphoma,treatment of patients with previously untreated cd30+ stage iii or stage iv hodgkin lymphoma (hl) in combination with doxorubicin, vinblastine, and dacarbazine (avd).,treatment of adult patients with cd30+ hl at higher risk of relapse or progression following asct.,treatment of adult patients with relapsed or refractory cd30+ hl:,1. following autologous stem cell transplant (asct) or,2. following at least two prior therapies when asct or multi-agent chemotherapy is not a treatment option.,peripheral t-cell lymphoma,treatment of adult patients with previously untreated cd30+ peripheral t-cell lymphoma (ptcl) in combination with cyclophosphamide, doxorubicin, and prednisone (chp).,treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (salcl).,cutaneous t cell lymphoma,treatment of adult patients with cd30+ cutaneous t-cell lymphoma (ctcl) after at least 1 prior systemic therapy.

Australia - inglese - Department of Health (Therapeutic Goods Administration)

takeda pharmaceuticals australia pty ltd - alogliptin benzoate, quantity: 17 mg - tablet, film coated - excipient ingredients: croscarmellose sodium; macrogol 8000; hypromellose; hyprolose; mannitol; titanium dioxide; iron oxide yellow; microcrystalline cellulose; magnesium stearate; shellac; ethanol absolute; iron oxide black; 1-butanol - nesina is indicated to improve glycaemic control in adult patients (>= 18 years old) with type 2 diabetes mellitus when diet and exercise do not provide adequate glycaemic control, as add on to metformin, a sulphonylurea, a thiazolidinedione, insulin (with or without metformin), or in combination with metformin and a thiazolidinedione when dual therapy does not provide adequate glycaemic control.

Australia - inglese - Department of Health (Therapeutic Goods Administration)

takeda pharmaceuticals australia pty ltd - alogliptin benzoate, quantity: 8.5 mg - tablet, film coated - excipient ingredients: titanium dioxide; croscarmellose sodium; magnesium stearate; mannitol; macrogol 8000; hyprolose; hypromellose; iron oxide red; microcrystalline cellulose; shellac; ethanol absolute; iron oxide black; 1-butanol - nesina is indicated to improve glycaemic control in adult patients (>= 18 years old) with type 2 diabetes mellitus when diet and exercise do not provide adequate glycaemic control, as add on to metformin, a sulphonylurea, a thiazolidinedione, insulin (with or without metformin), or in combination with metformin and a thiazolidinedione when dual therapy does not provide adequate glycaemic control.

Australia - inglese - Department of Health (Therapeutic Goods Administration)

takeda pharmaceuticals australia pty ltd - alogliptin benzoate, quantity: 34 mg - tablet, film coated - excipient ingredients: iron oxide red; titanium dioxide; mannitol; magnesium stearate; croscarmellose sodium; hypromellose; microcrystalline cellulose; macrogol 8000; hyprolose; shellac; ethanol absolute; iron oxide black; 1-butanol - nesina is indicated to improve glycaemic control in adult patients (>= 18 years old) with type 2 diabetes mellitus when diet and exercise do not provide adequate glycaemic control, as add on to metformin, a sulphonylurea, a thiazolidinedione, insulin (with or without metformin), or in combination with metformin and a thiazolidinedione when dual therapy does not provide adequate glycaemic control.

Stati Uniti - inglese - 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)] .