What the FDA changed in these labels

Forms and strengths

Added in this revision

• +Added: Metformin hydrochloride tablets: 500 mg

1 entry reworded without a change of meaning.

Approved uses

Added in this revision

• +Added: to reduce the risk of sustained eGFR decline, end-stage kidney disease and cardiovascular death in adults with type 2 diabetes mellitus and chronic kidney disease.

Removed in this revision

• -Removed: Has not been studied in patients with a history of pancreatitis. Consider another antidiabetic therapy.
• -Removed: Not for treatment of type 1 diabetes mellitus.

1 entry reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Acute Pancreatitis: Has been observed in patients treated with GLP-1 receptor agonists, including OZEMPIC. Discontinue if pancreatitis is suspected.
• +Added: Acute Kidney Injury Due to Volume Depletion: Monitor renal function in patients reporting adverse reactions that could lead to volume depletion.
• +Added: Severe Gastrointestinal Adverse Reactions: Use has been associated with gastrointestinal adverse reactions, sometimes severe. OZEMPIC is not recommended in patients with severe gastroparesis.
• +Added: Acute Gallbladder Disease: If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated.

Removed in this revision

• -Removed: Pancreatitis: Has been reported in clinical trials. Discontinue promptly if pancreatitis is suspected. Do not restart if pancreatitis is confirmed.
• -Removed: Acute Kidney Injury: Monitor renal function in patients with renal impairment reporting severe adverse gastrointestinal reactions.
• -Removed: Acute Gallbladder Disease: If cholelithiasis or cholecystitis are suspected, gallbladder studies are indicated. Risk of Thyroid C-Cell Tumors In mice and rats, semaglutide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure at clinically relevant plasma exposures.

Forms and strengths

Added in this revision

• +Added: Injection: 2 mg/3 mL (0.68 mg/mL) for 4 doses of 0.25 mg and 2 doses of 0.5 mg or 4 doses of 0.5 mg, 4 mg/3 mL (1.34 mg/mL) for 4 doses of 1 mg, and 8 mg/3 mL (2.68 mg/mL) for 4 doses of 2 mg in...
• +Added: Injection: 0.25 mg, 0.5 mg or 1 mg per 0.5 mL in a single-dose prefilled syringe

Removed in this revision

• -Removed: Single-patient-use pen that delivers 0.25 mg or 0.5 mg per injection Injection: 4 mg/3 mL (1.34 mg/mL) available in:
• -Removed: Single-patient-use pen that delivers 1 mg per injection Injection: 8 mg/3 mL (2.68 mg/mL) available in:
• -Removed: Single-patient-use pen that delivers 2 mg per injection

Dosage and administration

Added in this revision

• +Added: To reduce the risk of sustained eGFR decline, end-stage kidney disease and cardiovascular death, increase the dosage to 1 mg once weekly after at least 4 weeks on the 0.5 mg dosage.

Warnings and precautions

Added in this revision

• +Added: Mitochondrial Diseases: Metformin may increase the risk of lactic acidosis in patients with mitochondrial diseases such as mitochondrial encephalopathy with lactic acidosis, and stroke-like episodes (MELAS) syndrome and maternally inherited diabetes and deafness (MIDD).
• +Added: Metformin hydrochloride is not recommended in patients with mitochondrial diseases.
• +Added: If a patient taking metformin hydrochloride develops elevated lactic acid levels (with or without accompanying neurologic signs and symptoms), discontinue metformin hydrochloride.
• +Added: Depending on the clinical context, consider evaluating the patient for MELAS, MIDD, or other mitochondrial disease.

Warnings and precautions

Added in this revision

• +Added: Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists.

1 entry reworded without a change of meaning.

Contraindications

Added in this revision

• +Added: Anaphylaxis and angioedema have occurred with topiramate.

Warnings and precautions

Added in this revision

• +Added: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Reactions Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity has been reported in patients taking topiramate.
• +Added: DRESS may be fatal or life-threatening.
• +Added: DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection.
• +Added: Eosinophilia is often present.
• +Added: Because this disorder is variable in its expression, other organ systems not noted here may be involved.
• +Added: It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident.
• +Added: If such signs or symptoms are present, the patient should be evaluated immediately.
• +Added: QSYMIA should be discontinued if an alternative etiology for the signs or symptoms cannot be established.
• +Added: Anaphylaxis and Angioedema Hypersensitivity reactions, including anaphylaxis and angioedema, have occurred in patients treated with topiramate in the postmarketing setting.
• +Added: If a hypersensitivity reaction occurs, discontinue QSYMIA and initiate appropriate therapy.

2 entries reworded without a change of meaning.

Adverse reactions

1 entry reworded without a change of meaning.

Stop use and ask a doctor

Added in this revision

• +Added: There have been rare reports of liver injury in people taking orlistat. you develop severe pain in the back or groin, painful urination, blood in your urine, swelling of the legs or feet, or are urinating less often than normal.

1 entry reworded without a change of meaning.

Warnings and precautions

Removed in this revision

• -Removed: Suicidal Behavior and Ideation In SAXENDA adult clinical trials, 9 (0.3%) of 3384 SAXENDA-treated patients and 2 (0.1%) of the 1941 placebo-treated patients reported suicidal ideation; one of these SAXENDA-treated patients attempted suicide.
• -Removed: In a SAXENDA pediatric clinical trial, 1 (0.8%) of the 125 SAXENDA-treated patients died by suicide.
• -Removed: There was insufficient information to establish a causal relationship to SAXENDA.
• -Removed: Patients treated with SAXENDA should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
• -Removed: Discontinue SAXENDA in patients who experience suicidal thoughts or behaviors.
• -Removed: Avoid SAXENDA in patients with a history of suicidal attempts or active suicidal ideation.

Adverse reactions

7 entries reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists.

Removed in this revision

• -Removed: Suicidal Behavior and Ideation Suicidal behavior and ideation have been reported in clinical trials with other weight management products.
• -Removed: Monitor patients treated with ZEPBOUND for the emergence or worsening of depression, suicidal thoughts or behaviors, and/or any unusual changes in mood or behavior.
• -Removed: Discontinue ZEPBOUND in patients who experience suicidal thoughts or behaviors.
• -Removed: Avoid ZEPBOUND in patients with a history of suicidal attempts or active suicidal ideation.

1 entry reworded without a change of meaning.

Adverse reactions

1 entry reworded without a change of meaning.

Approved uses

1 entry reworded without a change of meaning.

Dosage and administration

Added in this revision

• +Added: Important Administration Instructions • RYBELSUS and OZEMPIC tablets are not substitutable on a mg-to-mg basis. • Take one RYBELSUS or OZEMPIC tablet orally once daily on an empty stomach in the morning with water (up to 4 ounces of water).
• +Added: Do not take RYBELSUS or OZEMPIC tablets with other liquids besides water. • Do not take more than one tablet per day. • Swallow tablets whole.
• +Added: Do not split, crush, chew or dissolve in any solution. • After taking RYBELSUS or OZEMPIC tablets, wait at least 30 minutes before eating food, drinking beverages or taking other oral medications. • If a dose is missed, skip the missed dose and take the next dose the following day.
• +Added: Switching Between RYBELSUS and OZEMPIC Tablets • Do not switch between RYBELSUS and OZEMPIC tablets during the initiation phase (Days 1 to 30). • After 30 days of RYBELSUS or OZEMPIC tablet treatment (after the initiation phase), patients may switch between RYBELSUS and OZEMPIC tablet products (see Table 1). • When switching between RYBELSUS and OZEMPIC tablets, initiate the other semaglutide tablet product the day after discontinuing the previous semaglutide tablet product.
• +Added: Switching Between Escalation or Maintenance Dosage of RYBELSUS and OZEMPIC Tablets Switching from OZEMPIC Injection to RYBELSUS or OZEMPIC Tablets Switching from OZEMPIC Injection to RYBELSUS Tablets • Patients taking the 0.5 mg dose of OZEMPIC injection may switch to RYBELSUS tablets. • One week after discontinuing 0.5 mg of subcutaneous OZEMPIC injection, start 7 mg or 14 mg of RYBELSUS orally once daily.
• +Added: Switching from OZEMPIC Injection to OZEMPIC Tablets • Patients taking the 0.5 mg dose of OZEMPIC injection may switch to OZEMPIC tablets. • One week after discontinuing 0.5 mg of subcutaneous OZEMPIC injection, start 4 mg or 9 mg of OZEMPIC tablets orally once daily.

Removed in this revision

• -Removed: Overview of RYBELSUS Formulations • There are two RYBELSUS formulations (i.e., formulation R1 and formulation R2) with different recommended dosages.
• -Removed: Refer to recommendations on how to switch from one formulation to another formulation.;
• -Removed: RYBELSUS (formulation R1) includes strengths 3 mg, 7 mg and 14 mg.;
• -Removed: RYBELSUS (formulation R2) includes strengths 1.5 mg, 4 mg and 9 mg. • These formulations are not substitutable on a mg per mg basis. • Use either RYBELSUS formulation R1 or formulation R2; do not use both formulations at the same time. • Do not take more than one tablet per day.
• -Removed: Important Administration Instructions • Take RYBELSUS on an empty stomach in the morning with water (up to 4 ounces of water).
• -Removed: Do not take RYBELSUS with other liquids besides water. • After taking RYBELSUS, wait at least 30 minutes before eating food, drinking beverages or taking other oral medications. • Swallow tablets whole.
• -Removed: Do not split crush or chew. • If a dose is missed, skip the missed dose and take the next dose the following day.
• -Removed: Recommended Starting, Escalation and Maintenance Dosage of RYBELSUS Formulations R1 and R2 RYBELSUS (formulation R1) RYBELSUS (formulation R1) includes the following strengths: 3 mg, 7 mg and 14 mg.
• -Removed: RYBELSUS (formulation R2) RYBELSUS (formulation R2) includes the following strengths: 1.5 mg, 4 mg and 9 mg.
• -Removed: Switching Between RYBELSUS (Formulations R1 or R2) or from OZEMPIC to RYBELSUS Switching Between RYBELSUS Formulations • Do not switch between RYBELSUS formulations during the initiation phase (Days 1-30). • After 30 days of RYBELSUS treatment (after the initiation phase), patients may switch between RYBELSUS formulations (see Table 1). • When switching between the formulations, initiate the other RYBELSUS formulation the day after discontinuing the previous RYBELSUS formulation.
• -Removed: Switching Between Escalation or Maintenance Dosage of RYBELSUS Formulations *Discontinue this formulation and initiate the alternate formulation the day after Switching from OZEMPIC to RYBELSUS (formulation R1) or RYBELSUS (formulation R2) Switching from OZEMPIC to RYBELSUS (formulation R1) • One week after discontinuing 0.5 mg of subcutaneous OZEMPIC, start 7 mg or 14 mg of RYBELSUS (formulation R1) orally once daily. • Switching recommendations for patients taking OZEMPIC 0.25 mg, 1 mg or 2...
• -Removed: Switching from OZEMPIC to RYBELSUS (formulation R2) • One week after discontinuing 0.5 mg of subcutaneous OZEMPIC, start 4 mg or 9 mg of RYBELSUS (formulation R2) orally once daily. • Switching recommendations for patients taking OZEMPIC 0.25 mg, 1 mg or 2 mg subcutaneously once weekly to RYBELSUS (formulation R2) are not available.

2 entries reworded without a change of meaning.

Forms and strengths

2 entries reworded without a change of meaning.

Contraindications

2 entries reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: RYBELSUS and OZEMPIC tablets are not recommended in patients with severe gastroparesis.

Removed in this revision

• -Removed: RYBELSUS is not recommended in patients with severe gastroparesis.

23 entries reworded without a change of meaning.

Adverse reactions

Added in this revision

• +Added: These data reflect exposure of 1,071 patients to semaglutide tablets (3 mg, 7, mg or 14 mg orally once daily) with a mean duration of exposure of 41.8 weeks.

Removed in this revision

• -Removed: These data reflect exposure of 1,071 patients to RYBELSUS with a mean duration of exposure of 41.8 weeks.

22 entries reworded without a change of meaning.

Drug interactions

6 entries reworded without a change of meaning.

Dosage and administration

Added in this revision

• +Added: Important Administration Instructions Inform patients and their caregiver(s) which MOUNJARO presentation (e.g., vial, pre-filled single-dose pen, single-patient-use KwikPen) they will receive and ensure they receive training appropriate for that specific presentation.
• +Added: If the prescribed MOUNJARO presentation changes, ensure patients and caregivers receive appropriate training and instruct them to consult the Instructions for Use for the newly prescribed presentation.
• +Added: After training, a patient may self-inject MOUNJARO if the healthcare provider determines that it can be properly administered, except for the following: MOUNJARO KwikPen is not recommended for self-administration by pediatric patients.
• +Added: MOUNJARO KwikPen is not recommended for self-administration by those who are visually impaired.

Removed in this revision

• -Removed: A patient may self-inject if a healthcare provider determines that it is appropriate.

2 entries reworded without a change of meaning.

Forms and strengths

Added in this revision

• +Added: The multi-dose vials and single-patient-use KwikPen each contain 4 doses:

1 entry reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Never Share a MOUNJARO KwikPen Between Patients Never share MOUNJARO KwikPen between patients, even if the pen needle is changed.
• +Added: Sharing poses a risk for transmission of blood-borne pathogens.

Dosage and administration

Added in this revision

• +Added: Important Administration Instructions Inform patients and their caregiver(s) which ZEPBOUND presentation (e.g., vial, prefilled single-dose pen, single-patient-use KwikPen) they will receive and ensure they receive training appropriate for that specific presentation.
• +Added: If the prescribed ZEPBOUND presentation changes, ensure patients and caregivers receive appropriate training and instruct them to consult the Instructions for Use for the newly prescribed presentation.
• +Added: Prior to initiation, train patients and their caregiver(s) on proper injection technique for the prescribed ZEPBOUND presentation.
• +Added: After training, a patient may self-inject ZEPBOUND if the healthcare provider determines that it can be properly administered, except for the following: ZEPBOUND KwikPen is not recommended for self-administration by those who are visually impaired.

Removed in this revision

• -Removed: Important Administration Instructions Prior to initiation of ZEPBOUND, train patients and caregivers on proper injection technique.
• -Removed: Refer to the accompanying Instructions for Use for complete administration instructions with illustrations.

Forms and strengths

Added in this revision

• +Added: The multi-dose vials and single-patient-use KwikPen each contain 4 doses:

1 entry reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Never Share a ZEPBOUND KwikPen Between Patients Never share ZEPBOUND KwikPen between patients, even if the pen needle is changed.
• +Added: Sharing poses a risk for transmission of blood-borne pathogens.

Dosage and administration

Added in this revision

• +Added: Instruct patients using MOUNJARO vials to use a syringe appropriate for dose administration (e.g., a 1 mL syringe capable of measuring a 0.5 mL or 0.6 mL dose) and always use a new syringe and needle for each injection.

Removed in this revision

• -Removed: Instruct patients using the single-dose vial to use a syringe appropriate for dose administration (e.g., a 1 mL syringe capable of measuring a 0.5 mL dose).

Forms and strengths

Added in this revision

• +Added: Injection: Clear, colorless to slightly yellow solution in pre-filled single-dose pens, single-dose vials, or multi-dose vials, each available in the following strengths:

Removed in this revision

• -Removed: Injection: Clear, colorless to slightly yellow solution in pre-filled single-dose pens or single-dose vials, each available in the following strengths: 2.5 mg/0.5 mL 5 mg/0.5 mL 7.5 mg/0.5 mL 10 mg/0.5 mL 12.5 mg/0.5 mL 15 mg/0.5 mL

Dosage and administration

Added in this revision

• +Added: Instruct patients using ZEPBOUND vials to use a syringe appropriate for dose administration (e.g., a 1 mL syringe capable of measuring a 0.5 mL or 0.6 mL dose) and always use a new syringe and needle for each injection.

Removed in this revision

• -Removed: Instruct patients using the single-dose vial to use a syringe appropriate for dose administration (e.g., a 1 mL syringe capable of measuring a 0.5 mL dose).

Forms and strengths

Added in this revision

• +Added: Injection: Clear, colorless to slightly yellow solution in pre-filled single-dose pens, single-dose vials, or multi-dose vials, each available in the following strengths:

Removed in this revision

• -Removed: Injection: Clear, colorless to slightly yellow solution in pre-filled single-dose pens or single-dose vials, each available in the following strengths: 2.5 mg/0.5 mL 5 mg/0.5 mL 7.5 mg/0.5 mL 10 mg/0.5 mL 12.5 mg/0.5 mL 15 mg/0.5 mL

Approved uses

1 entry reworded without a change of meaning.

Dosage and administration

Added in this revision

• +Added: A patient may self-inject if a healthcare provider determines that it is appropriate.

2 entries reworded without a change of meaning.

Warnings and precautions

Added in this revision

• +Added: Severe gastrointestinal adverse reactions have also been reported postmarketing with GLP-1 receptor agonists.

3 entries reworded without a change of meaning.

Drug interactions

Added in this revision

• +Added: Mitotane Avoid concomitant use of ALDACTONE and mitotane.
• +Added: Spironolactone reduces mitotane plasma levels.