Zemimet SR Special Precautions

General: Zemimet SR is not a substitute for insulin in insulin-requiring patients and should not be used in patients with type 1 diabetes.
Hypersensitive reaction: As Zemimet SR contains gemigliptin and metformin, it should not be used in patients who have had any serious hypersensitivity reaction to a dipeptidyl peptidase 4 (DPP4) inhibitor or a biguanide.
Acute pancreatitis: Pancreatitis has been reported in patients taking DPP-4 inhibitors including gemigliptin. Therefore, patients should be informed of the characteristic symptoms of acute pancreatitis: persistent, severe abdominal pain. If pancreatitis is suspected, gemigliptin should be discontinued and should not be restarted. Caution should be exercised in patients with a history of pancreatitis.
Use with medicinal products known to cause hypoglycemia: Sulfonylurea or insulin is known to cause hypoglycemia. Therefore, a lower dose of sulfonylurea may be required to reduce the risk of hypoglycemia when used in combination with Zemimet SR.
Severe and disabling arthralgia: There have been post-marketing reports of severe and disabling arthralgia in patients taking other DPP-4 inhibitors. The time to onset of symptoms following initiation of drug therapy varied from one day to years. Patients experienced relief of symptoms upon discontinuation of the medication. A subset of patients experienced a recurrence of symptoms when restarting the same drug or a different DPP-4 inhibitor. Consider DPP-4 inhibitors as a possible cause for severe joint pain and discontinue drug if appropriate.
Lactic acidosis: Lactic acidosis, a rare but serious metabolic complication, most often occurs at acute worsening of renal function or cardiorespiratory illness or sepsis. Metformin accumulation occurs at acute worsening of renal function and increases the risk of lactic acidosis.
In case of dehydration (severe vomiting, diarrhea, fever or reduced fluid intake), metformin should be temporarily discontinued and contact with a health care professional is recommended.
Medicinal products that can acutely impair renal function (such as antihypertensives, diuretics and NSAIDs) should be initiated with caution in metformin-treated patients. Other risk factors for lactic acidosis are excessive alcohol intake, hepatic insufficiency, inadequately controlled diabetes, ketosis, prolonged fasting and any conditions associated with hypoxia, as well as concomitant use of medicinal products that may cause lactic acidosis.
Patients and/or caregivers should be informed of the risk of lactic acidosis. Lactic acidosis is characterized by acidotic dyspnea, abdominal pain, muscle cramps, asthenia, and hypothermia followed by coma. In case of suspected symptoms, the patient should stop taking metformin and seek immediate medical attention. Diagnostic laboratory findings are decreased blood pH (<7.35), increased plasma lactate levels (>5 mmol/L) and an increased anion gap and lactate/pyruvate ratio.
Diagnosis: Lactic acidosis is characterised by acidotic dyspnoea, abdominal pain and hypothermia followed by coma. Diagnostic laboratory findings are decreased blood pH, plasma lactate levels above 5 mmol/L, and an increased anion gap and lactate/pyruvate ratio. If metabolic acidosis is suspected, treatment with the medicinal product should be discontinued and the patient hospitalised immediately.
Renal function: Metformin and gemigliptin are excreted by the kidneys. Metformin-related lactic acidosis increases with the degree of impairment of renal function; serum creatinine concentrations should be determined regularly: at least once a year in patients with normal renal function; at least two to four times a year in patients with serum creatinine levels at or above the upper limit of normal and in elderly patients.
GFR should be assessed before treatment initiation and regularly thereafter. Zemimet SR is contraindicated in patients with GFR <30 mL/min and should be temporarily discontinued in the presence of conditions that alter renal function.
Decreased renal function in elderly patients is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example, when initiating anti-hypertensive or diuretic therapy or when starting treatment with a nonsteroidal anti-inflammatory drug (NSAID).
Bullous pemphigoid: There have been post-marketing reports of bullous pemphigoid requiring hospitalization in patients taking other DPP-4 inhibitors. In reported cases, patients typically recovered with topical or systemic immunosuppressive treatment and discontinuation of the DPP-4 inhibitor. Patients should be instructed to report development of blisters or erosions to their doctors while receiving Zemimet SR. If bullous pemphigoid is suspected, Zemimet SR should be discontinued and a dermatologist should be consulted for diagnosis and proper treatment.
Surgery: As Zemimet SR contains metformin, the treatment should be discontinued 48 hours before elective surgery with general, spinal, or epidural anaesthesia. Zemimet SR should not usually be resumed earlier than 48 hours afterwards and only after renal function has been re-evaluated and found to be normal.
Administration of iodinated contrast agent: The intravascular administration of iodinated contrast agents in radiological studies can lead to renal failure which has been associated with lactic acidosis in patients receiving metformin. Therefore, Zemimet SR must be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal.
Regular monitoring of thyroid-stimulating hormone (TSH) levels is recommended in patients with hypothyroidism.
Long-term treatment with metformin has been associated with a decrease in vitamin B12 serum levels which may cause peripheral neuropathy. Monitoring of the vitamin B12 level is recommended.
Other precautions: All patients should continue their diet with a regular distribution of carbohydrate intake during the day. Overweight patients should continue their energy-restricted diet.
The usual laboratory tests for diabetes monitoring should be performed regularly.
The tablet shells may be present in the feces. Patients should be advised that this is normal.
Effects on ability to drive and use machines: When driving or using machines, caution should be exercised as dizziness has been reported. In addition, patients should be alerted to the risk of hypoglycemia when Zemimet SR is used in combination with other anti-diabetic medicinal products known to cause hypoglycemia (e.g. sulfonylureas, insulin).