Oseni Prescribing Information
- Thiazolidinediones, including pioglitazone, which is a component of OSENI®, cause or exacerbate congestive heart failure in some patients[see.]
5.1 Congestive Heart FailureAlogliptinIn the EXAMINE trial which enrolled patients with type 2 diabetes mellitus and recent acute coronary syndrome, 106 (3.9%) of patients treated with alogliptin and 89 (3.3%) of patients treated with placebo were hospitalized for congestive heart failure.
PioglitazonePioglitazone, like other thiazolidinediones, can cause dose-related fluid retention when used alone or in combination with other antidiabetic medications and is most common when pioglitazone is used in combination with insulin. Fluid retention may lead to or exacerbate congestive heart failure
[see Boxed Warning, Contraindications (4)and Adverse Reactions (6.1)].Consider the risks and benefits of OSENI prior to initiating treatment in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment. Observe these patients for signs and symptoms of congestive heart failure. Advise patients about the symptoms of congestive heart failure and to immediately report such symptoms. If congestive heart failure develops while taking OSENI, consider discontinuation of OSENI or dosage reduction of pioglitazone in OSENI
(6.1)]. - After initiation of OSENI and after dose increases, monitor patients carefully for signs and symptoms of heart failure (e.g., excessive, rapid weight gain, dyspnea and/or edema). If congestive heart failure develops while taking OSENI, consider discontinuation of OSENI or dosage reduction of pioglitazone in OSENI[see.]
5.1 Congestive Heart FailureAlogliptinIn the EXAMINE trial which enrolled patients with type 2 diabetes mellitus and recent acute coronary syndrome, 106 (3.9%) of patients treated with alogliptin and 89 (3.3%) of patients treated with placebo were hospitalized for congestive heart failure.
PioglitazonePioglitazone, like other thiazolidinediones, can cause dose-related fluid retention when used alone or in combination with other antidiabetic medications and is most common when pioglitazone is used in combination with insulin. Fluid retention may lead to or exacerbate congestive heart failure
[see Boxed Warning, Contraindications (4)and Adverse Reactions (6.1)].Consider the risks and benefits of OSENI prior to initiating treatment in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment. Observe these patients for signs and symptoms of congestive heart failure. Advise patients about the symptoms of congestive heart failure and to immediately report such symptoms. If congestive heart failure develops while taking OSENI, consider discontinuation of OSENI or dosage reduction of pioglitazone in OSENI
(6.1)]. - OSENI is not recommended in patients with symptomatic heart failure[see.]
5.1 Congestive Heart FailureAlogliptinIn the EXAMINE trial which enrolled patients with type 2 diabetes mellitus and recent acute coronary syndrome, 106 (3.9%) of patients treated with alogliptin and 89 (3.3%) of patients treated with placebo were hospitalized for congestive heart failure.
PioglitazonePioglitazone, like other thiazolidinediones, can cause dose-related fluid retention when used alone or in combination with other antidiabetic medications and is most common when pioglitazone is used in combination with insulin. Fluid retention may lead to or exacerbate congestive heart failure
[see Boxed Warning, Contraindications (4)and Adverse Reactions (6.1)].Consider the risks and benefits of OSENI prior to initiating treatment in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment. Observe these patients for signs and symptoms of congestive heart failure. Advise patients about the symptoms of congestive heart failure and to immediately report such symptoms. If congestive heart failure develops while taking OSENI, consider discontinuation of OSENI or dosage reduction of pioglitazone in OSENI
(6.1)]. - Initiation of OSENI in patients with established New York Heart Association (NYHA) Class III or IV heart failure is contraindicated[see.and
4 CONTRAINDICATIONSOSENI is contraindicated in patients with:
- Established NYHA Class III or IV heart failure at the time of OSENI initiation[see Boxed Warning].
- A history of serious hypersensitivity reaction to alogliptin, pioglitazone, or any of the excipients in OSENI. Reactions such as anaphylaxis, angioedema and severe cutaneous adverse reactions have been reported[see Warnings and Precautions (5.3), Adverse reactions (6.2)].
- In patients with established NYHA Class III or IV heart failure at the time of OSENI initiation.
- In patients with a history of serious hypersensitivity reaction to alogliptin, pioglitazone, or any of the excipients in OSENI.
]5.1 Congestive Heart FailureAlogliptinIn the EXAMINE trial which enrolled patients with type 2 diabetes mellitus and recent acute coronary syndrome, 106 (3.9%) of patients treated with alogliptin and 89 (3.3%) of patients treated with placebo were hospitalized for congestive heart failure.
PioglitazonePioglitazone, like other thiazolidinediones, can cause dose-related fluid retention when used alone or in combination with other antidiabetic medications and is most common when pioglitazone is used in combination with insulin. Fluid retention may lead to or exacerbate congestive heart failure
[see Boxed Warning, Contraindications (4)and Adverse Reactions (6.1)].Consider the risks and benefits of OSENI prior to initiating treatment in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment. Observe these patients for signs and symptoms of congestive heart failure. Advise patients about the symptoms of congestive heart failure and to immediately report such symptoms. If congestive heart failure develops while taking OSENI, consider discontinuation of OSENI or dosage reduction of pioglitazone in OSENI
(6.1)]. - Established NYHA Class III or IV heart failure at the time of OSENI initiation
Dosage and Administration (2.1 Important Dosage and Administration Information
2.2 Recommended Dosage and Administration Recommended Starting Dosage Based on Current Regimen Individualize the starting dosage of OSENI based on the patient's current regimen and the available strengths of OSENI (see Table 1).
Dosage Titration for Additional Glycemic Control Titrate the OSENI dosage gradually, as needed, after assessing therapeutic response and tolerability, up to a maximum dosage of 25 mg of alogliptin and 45 mg of pioglitazone once daily. 2.3 Recommended Dosage for Patients with Renal Impairment
2.4 Recommendations for Congestive Heart Failure Starting Dosage in Patients with NYHA Class I or II Congestive Heart Failure For patients with preexisting NYHA Class I or II congestive heart failure, the recommended starting dosage of OSENI is 25 mg of alogliptin and 15 mg of pioglitazone [see Boxed Warningand Warnings and Precautions (5.1)]. Monitoring for Fluid Retention and Dosage Modifications for Congestive Heart Failure After initiation of OSENI or with dosage increase, monitor patients carefully for adverse reactions related to fluid retention as has been seen with pioglitazone (e.g., weight gain, edema and signs and symptoms of congestive heart failure). If congestive heart failure develops while taking OSENI, consider discontinuation of OSENI or dosage reduction of pioglitazone in OSENI [see Boxed Warningand Warnings and Precautions (5.1)] .2.5 Coadministration with Strong CYP2C8 Inhibitors The maximum recommended dosage of OSENI is 25 mg of alogliptin and 15 mg of pioglitazone once daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors [see Drug Interactions (7.1)and Clinical Pharmacology (12.3)] . | 06/2024 |
OSENI is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
- Obtain liver tests prior to initiation.
- OSENI may be taken with or without food. ()2.1 Important Dosage and Administration Information
- Obtain liver tests (serum alanine and aspartate aminotransferases, alkaline phosphatase, and total bilirubin) prior to initiating OSENI[see Warnings and Precautions (5.4)].
- Take OSENI orally once daily. Do not split tablets.
- OSENI may be taken with or without food[see Clinical Pharmacology (12.3)].
- If a dose is missed, do not double the next dose.
- Individualize the starting dose of OSENI based on the patient’s current regimen and concurrent medical condition but do not exceed a daily dose of alogliptin 25 mg and pioglitazone 45 mg. ()2.2 Recommended Dosage and AdministrationRecommended Starting Dosage Based on Current RegimenIndividualize the starting dosage of OSENI based on the patient's current regimen and the available strengths of OSENI (see Table 1).
Table 1: Recommended Starting Dosage Based on the Patient’s Current Regimen Current Regimen Starting Dosage of OSENI (alogliptin/pioglitazone)For dosage recommendations for patients with renal impairment and/or congestive heart failure, [see Dosage and Administration (2.3, 2.4)].Not treated with either alogliptin or pioglitazone 25 mg/15 mg or 25 mg/30 mg Alogliptin 25 mg/15 mg or 25 mg/30 mg Pioglitazone 25 mg/15 mg, 25 mg/30 mg, or 25 mg/45 mg Alogliptin and pioglitazone Select a dosage that is as close as possible to the current dosage of alogliptin and pioglitazone Dosage Titration for Additional Glycemic ControlTitrate the OSENI dosage gradually, as needed, after assessing therapeutic response and tolerability, up to a maximum dosage of 25 mg of alogliptin and 45 mg of pioglitazone once daily.
- The recommended starting dosage in patients with NYHA Class I or II congestive heart failure is 25 mg of alogliptin and 15 mg of pioglitazone ()2.4 Recommendations for Congestive Heart FailureStarting Dosage in Patients with NYHA Class I or II Congestive Heart FailureFor patients with preexisting NYHA Class I or II congestive heart failure, the recommended starting dosage of OSENI is 25 mg of alogliptin and 15 mg of pioglitazone[see Boxed Warningand Warnings and Precautions (5.1)].Monitoring for Fluid Retention and Dosage Modifications for Congestive Heart FailureAfter initiation of OSENI or with dosage increase, monitor patients carefully for adverse reactions related to fluid retention as has been seen with pioglitazone (e.g., weight gain, edema and signs and symptoms of congestive heart failure).If congestive heart failure develops while taking OSENI, consider discontinuation of OSENI or dosage reduction of pioglitazone in OSENI[see Boxed Warningand Warnings and Precautions (5.1)].
- Prior to initiation, assess renal function with creatinine clearance (CrCl) ()2.3 Recommended Dosage for Patients with Renal Impairment
- Assess renal function prior to initiation of OSENI and periodically thereafter[see Use in Specific Populations (8.6)].
- The recommended dosage of OSENI in patients with mild renal impairment (creatinine clearance [CrCl] ≥60 mL/min) is the same as the recommended dosage in patients with normal renal function[see Dosage and Administration (2.1)].
- The recommended dosage of OSENI for patients with moderate renal impairment (CrCl ≥30 to <60 mL/min) is 12.5 mg of alogliptin and 30 mg of pioglitazone once daily.
- OSENI is not recommended for patients with severe renal impairment (CrCl ≥15 to <30 mL/min) or ESRD (CrCl <15 mL/min or requiring hemodialysis) because these patients require a lower dosage of alogliptin than what is available in the fixed dose combination product, OSENI[see Use in Specific Populations (8.6)and Clinical Pharmacology (12.3)].
- Mild renal impairment (creatinine clearance [CrCl] ≥60 mL/min): same as the recommended dosage in patients with normal renal function.
- Moderate renal impairment (CrCl ≥30 to <60 mL/min): 12.5 mg of alogliptin and 30 mg of pioglitazone once daily.
- Severe renal impairment (CrCl ≥15 to <30 mL/min) or ESRD (CrCl <15 mL/min or requiring hemodialysis): not recommended.
| Pharmaceutical form | Strength (alogliptin/ pioglitazone) | Color | Shape | Markings (on one side) |
|---|---|---|---|---|
| film-coated tablets | 12.5 mg/30 mg | Pale peach | Round biconvex | “A/P” and “12.5/30” |
| film-coated tablets | 25 mg/15 mg | Yellow | Round biconvex | “A/P” and “25/15” |
| film-coated tablets | 25 mg/30 mg | Peach | Round biconvex | “A/P” and “25/30” |
| film-coated tablets | 25 mg/45 mg | Red | Round biconvex | “A/P” and “25/45” |
- Females and Males of Reproductive Potential: Advise premenopausal females of the potential for an unintended pregnancy. ()
8.3 Females and Males of Reproductive PotentialDiscuss the potential for unintended pregnancy with premenopausal women as therapy with pioglitazone, like other thiazolidinediones, may result in ovulation in some anovulatory women.
- Pediatrics: safety and effectiveness have not been established. ()
8.4 Pediatric UseSafety and effectiveness of OSENI in pediatric patients have not been established.
OSENI 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, 5.5, 5.6, 5.7)].