ALOGLIPTIN AND METFORMIN HYDROCHLORIDE tablet, film coated

País: Estats Units

Idioma: anglès

Font: NLM (National Library of Medicine)

ingredients actius:

ALOGLIPTIN BENZOATE (UNII: EEN99869SC) (Alogliptin - UNII:JHC049LO86), Metformin hydrochloride (UNII: 786Z46389E) (Metformin - UNII:9100L32L2N)

Disponible des:

Padagis Israel Pharmaceuticals Ltd

Designació comuna internacional (DCI):

ALOGLIPTIN BENZOATE

Composición:

Alogliptin 12.5 mg

Vía de administración:

ORAL

tipo de receta:

PRESCRIPTION DRUG

indicaciones terapéuticas:

Alogliptin and metformin HCl tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use Alogliptin and metformin HCl tablets should not recommended for use in patients with type 1 diabetes mellitus. Alogliptin and metformin HCl tablets are contraindicated in patients with: - Severe renal impairment (eGFR below 30 mL/min/1.73 m2 ) [see Warnings and Precautions (5.1)]. - Acute or chronic metabolic acidosis, including diabetic ketoacidosis with or without coma. - History of serious hypersensitivity reaction to alogliptin or metformin or any of the excipients, such as anaphylaxis, angioedema and severe cutaneous adverse reactions [see Warnings and Precautions (5.4), Adverse Reactions (6.2)] . Risk Summary Limited available data with alogliptin and metformin HCl tablets or alogliptin in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and 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 mellitus in pregnancy [see Clinical Considerations]. Concomitant administration of alogliptin and metformin in pregnant rats during the period of organogenesis did not cause adverse developmental effects in offspring at maternal exposures up to 28 times and two times the 25 mg and 2000 mg clinical doses, respectively [see Data]. The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes mellitus with a HbA1c >7 and has been reported to be as high as 20-25% in women with HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated Maternal and/or Embryo/Fetal Risk Poorly controlled diabetes mellitus in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes mellitus increases the fetal risk for major malformations, still birth, and macrosomia related morbidity. Data Human Data Published data from postmarketing studies do not report a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin is 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 Alogliptin and Metformin Concomitant administration of alogliptin and metformin in pregnant rats during the period of organogenesis did not cause adverse developmental effects in offspring at a dose of 100 mg/kg alogliptin and 150 mg/kg metformin, or approximately 28 and two times the clinical dose of alogliptin (25 mg) and metformin (2000 mg), respectively based on plasma drug exposure (AUC). Alogliptin Alogliptin administered to pregnant rabbits and rats during the period of organogenesis did not cause adverse developmental effects at doses of up to 200 mg/kg and 500 mg/kg, or 149 times and 180 times the 25 mg clinical dose, respectively, based on plasma drug exposure (AUC). Placental transfer of alogliptin into the fetus was observed following oral dosing to pregnant rats. No adverse developmental outcomes were observed in offspring when alogliptin was administered to pregnant rats during gestation and lactation at doses up to 250 mg/kg (approximately 95 times the 25 mg clinical dose, based on AUC). Metformin HCl Metformin HCl 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 two to six times a clinical dose of 2000 mg based on body surface area (mg/m2 ) for rats and rabbits, respectively. Risk Summary There is no information regarding the presence of alogliptin and metformin or alogliptin in human milk, the effects on the breastfed infant, or the effects on milk production. Alogliptin is present in rat milk. Limited published studies report that metformin is present in human milk [see Data]. However, there is insufficient information to determine 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 alogliptin and metformin HCl tablets and any potential adverse effects on the breastfed infant from alogliptin and metformin HCl tablets 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 (based on AUC) 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. There is the potential for unintended pregnancy with premenopausal women as therapy with metformin may result in ovulation in some premenopausal anovulatory women. The safety and effectiveness of alogliptin and metformin HCl tablets have not been established in pediatric patients. Effectiveness of alogliptin was not demonstrated in a 52 week, randomized, double-blind, placebo-controlled trial (NCT02856113) in 151 pediatric patients aged 10 to 17 years with inadequately controlled type 2 diabetes mellitus. Alogliptin and Metformin HCl Elderly patients are more likely to have decreased renal function. Monitor renal function in the elderly more frequently [see Warnings and Precautions (5.1), Clinical Pharmacology (12.3)] . Of the total number of patients (N = 2095) in clinical safety and efficacy studies, 343 (16.4%) patients were 65 years and older and 37 (1.8%) patients were 75 years and older. No overall differences in safety or effectiveness were observed between these patients and younger patients. Alogliptin Of the total number of patients (N=9052) in clinical safety and efficacy studies treated with alogliptin, 2,257 (24.9%) patients were 65 years and older and 386 (4.3%) patients were 75 years and older. No overall differences in safety or effectiveness were observed between patients 65 years and over and younger patients. Metformin HCl Controlled trials of metformin did not include sufficient numbers of subjects age 65 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, 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 and 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 Contraindications (4), Warnings and Precautions (5.1), Clinical Pharmacology (12.3)]. Metformin is substantially excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of renal impairment. Alogliptin and metformin HCl tablets are 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 (5.1), Clinical Pharmacology (12.3)] . Use of metformin in patients with hepatic impairment has been associated with some cases of lactic acidosis. Alogliptin and metformin HCl tablets are not recommended in patients with hepatic impairment [see Warnings and Precautions (5.1)] .

Resumen del producto:

Alogliptin and metformin HCl tablets are available in the following strengths and packages: 12.5 mg/500 mg tablet: pale yellow, oblong, film-coated tablets with "12.5/500" debossed on one side and "322M" debossed on the other side, available in: 12.5 mg/1000 mg tablet: pale yellow, oblong, film-coated tablets with "12.5/1000" debossed on one side and "322M" debossed on the other side, available in: Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Keep container tightly closed.

Estat d'Autorització:

New Drug Application Authorized Generic

Informació per a l'usuari

FILM COATED
Padagis Israel Pharmaceuticals Ltd
----------
This Medication Guide has been approved by the U.S. Food
and Drug Administration.
ALK334 R9
July 2023
MEDICATION GUIDE
alogliptin and metformin hydrochloride
tablets
Read this Medication Guide carefully before you start taking
alogliptin with metformin hydrochloride
tablets and each time you get a refill. There may be new information.
This information does not take the
place of talking with your doctor about your medical condition or
treatment. If you have any questions
about alogliptin with metformin hydrochloride tablets, ask your doctor
or pharmacist.
What is the most important information I should know about alogliptin
with metformin hydrochloride
tablets?
Alogliptin with metformin hydrochloride tablets can cause serious side
effects, including:
1.
Lactic Acidosis. Metformin, one of the medicines in alogliptin with
metformin hydrochloride
tablets, can cause a rare but serious condition called lactic acidosis
(a buildup of an acid in the
blood) that can cause death. Lactic acidosis is a medical emergency
and must be treated in the
hospital.
Call your doctor right away if you have any of the following symptoms,
which could be signs of lactic
acidosis:
•
you feel cold in your hands or feet
•
you feel dizzy or lightheaded
•
you have a slow or irregular heartbeat
•
you feel very weak or tired
•
you have unusual (not normal) muscle pain
•
you have trouble breathing
•
you feel sleepy or drowsy
•
you have stomach pains, nausea or vomiting
Most people who have had lactic acidosis with metformin have other
things that, combined with
metformin, led to the lactic acidosis. Tell your doctor if you have
any of the following, because you have
a higher chance for getting lactic acidosis with alogliptin with
metformin hydrochloride tablets if you:
•
have severe kidney problems or your kidneys are affected by certain
x-ray tests that use injectable
dye
•
have liver problems
•
drink alcohol very often, or drink a lot of alcohol in short-term
"binge"

Fitxa tècnica

ALOGLIPTIN AND METFORMIN HYDROCHLORIDE- ALOGLIPTIN AND METFORMIN
HYDROCHLORIDE TABLET, FILM COATED
PADAGIS ISRAEL PHARMACEUTICALS LTD
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ALOGLIPTIN AND
METFORMIN HCL TABLETS SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR
ALOGLIPTIN AND METFORMIN HCL TABLETS.
ALOGLIPTIN AND METFORMIN HYDROCHLORIDE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2013
WARNING: LACTIC ACIDOSIS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
POSTMARKETING CASES OF METFORMIN-ASSOCIATED LACTIC ACIDOSIS HAVE
RESULTED IN DEATH,
HYPOTHERMIA, HYPOTENSION, AND RESISTANT BRADYARRHYTHMIAS. SYMPTOMS
INCLUDED
MALAISE, MYALGIAS, RESPIRATORY DISTRESS, SOMNOLENCE, AND ABDOMINAL
PAIN.
LABORATORY ABNORMALITIES INCLUDED ELEVATED BLOOD LACTATE LEVELS, ANION
GAP ACIDOSIS,
INCREASED LACTATE/PYRUVATE RATIO; AND METFORMIN PLASMA LEVELS
GENERALLY GREATER
THAN 5 MCG/ML. (5.1)
RISK FACTORS INCLUDE RENAL IMPAIRMENT, CONCOMITANT USE OF CERTAIN
DRUGS, AGE ≥65
YEARS OLD, RADIOLOGICAL STUDIES WITH CONTRAST, SURGERY AND OTHER
PROCEDURES, HYPOXIC
STATES, EXCESSIVE ALCOHOL INTAKE, AND HEPATIC IMPAIRMENT. STEPS TO
REDUCE THE RISK
OF AND MANAGE METFORMIN-ASSOCIATED LACTIC ACIDOSIS IN THESE HIGH RISK
GROUPS ARE
PROVIDED IN THE FULL PRESCRIBING INFORMATION. (5.1)
IF LACTIC ACIDOSIS IS SUSPECTED, DISCONTINUE ALOGLIPTIN AND METFORMIN
HCL TABLETS AND
INSTITUTE GENERAL SUPPORTIVE MEASURES IN A HOSPITAL SETTING. PROMPT
HEMODIALYSIS IS
RECOMMENDED. (5.1)
INDICATIONS AND USAGE
Alogliptin and metformin HCl tablets are a combination of alogliptin,
a dipeptidyl-peptidase-4 (DPP-4)
inhibitor and metformin hydrochloride (HCl), a biguanide, indicated as
an adjunct to diet and exercise to
improve glycemic control in adults with type 2 diabetes mellitus. (1)
Limitations of Use: Should not be used in patients with type 1
diabetes mellitus. (1)
DOSAGE AND ADMINISTRATION
Individualize the starting dosage based on the patient's current
regimen. (2.1)
G