Zemimet SR Special Precautions

General: Zemimet SR 50/1000 mg should not be used in patients with type 1 diabetes and must not be used for the treatment of diabetic ketoacidosis.
Hypersensitive reaction: As Zemimet SR 50/1000 mg 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 gemigliptin. Therefore, patients should be informed of the characteristic symptoms of acute pancreatitis: persistent, severe abdominal pain. If pancreatitis is suspected, Zemimet SR 50/1000 mg 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: Patients receiving Zemimet SR 50/1000 mg in combination with a sulfonylurea or with insulin may be at risk for hypoglycemia. Therefore, a reduction in the dose of the sulfonylurea or insulin maybe necessary.
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), Zemimet SR 50/1000 mg 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 (see Contraindications and Interactions).
Patients and/or care-givers should be informed of the risk of lactic acidosis. Lactic acidosis is characterised by acidotic dyspnea, abdominal pain, muscle cramps, asthenia and hypothermia followed by coma. In case of suspected symptoms, the patient should stop taking Zemimet SR 50/1000 mg 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 (see Overdosage).
Renal function: Metformin and gemigliptin are excreted by the kidney. 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.
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) (see Interactions).
eGFR should be assessed before treatment initiation and regularly thereafter (see Dosage & Administration). It is not recommended to initiate treatment with Zemimet SR 50/1000 mg in patients with an eGFR ≥ 30 mL/min/1.73 m² and < 45 mL/min/1.73 m². If eGFR falls to levels persistently below 45 mL/min/1.73m² during treatment, assess the benefit and risk of continuing therapy (see Dosage & Administration and Contraindications).
Cardiac Impairment: There is limited clinical experience in patients with New York Heart Association (NYHA) Class I, II cardiac status in the case of gemigliptin. Therefore, Zemimet SR 50/1000 mg should be used with caution in this population. Zemimet SR 50/1000 mg should be avoided in patients with NYHA Class III, IV cardiac status (see Dosage & Administration).
Surgery: As Zemimet SR 50/1000 mg contains metformin, the treatment should be discontinued 48 hours before elective surgery with general, spinal or epidural anaesthesia. Zemimet SR 50/1000 mg 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 50/1000 mg 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 (see Interactions).
Regular monitoring of thyroid-stimulating hormone (TSH) levels is recommended in patients with hypothyroidism (see Adverse Reactions).
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 (see Adverse Reactions).
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.
Co-administration with strong moderate CYP3A4 inducers such as rifampicin (rifampin), phenytoin, carbamazepine and including moderate CYP3A4 inducers dexamethasone, rifabutin, and phenobarbital is not recommended (see Interactions).
The caution is required when co-administration with inhibitors of OCT2 to patients with renal impairment (see Interactions).
The tablet shells may be present in the feces. Patients should be advised that this is normal.
Zemimet SR 50/1000 mg should not be used with alcohol containing products.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed with Zemimet SR 50/1000 mg. However, patients should be alerted to the risk of hypoglycemia when Zemimet SR 50/1000 mg is used in combination with other anti-diabetic medicinal products known to cause hypoglycemia (e.g. sulfonylureas).
Use in Pregnancy & Lactation: Pregnant women or breastfeeding women should avoid taking Zemimet SR 50/1000 mg (see Use in Pregnancy & Lactation).