PrandiMet (Repaglinide and metformin) is an orally available anti-diabetic medicine that is used as an adjunct to diet and exercise for the treatment of adult patients with diabetes mellitus type 2.
PrandiMet (Repaglinide and metformin) Indications:
-
Diabetes mellitus Type 2:
- Used for management of type 2 diabetes mellitus, in adults currently receiving or not adequately controlled on metformin and/or a glinide, along with diet an excercise.
PrandiMet (Repaglinide and metformin) Dose in Adults
PrandiMet (Repaglinide and metformin) Dose in the treatment of type 2 Diabetes mellitus: Oral:
Note: Daily divided doses 2 to 3 times a day, taken along with food.
- Maximum single dose: Repaglinide 4 mg/metformin 1,000 mg
- Maximum daily dose: Repaglinide 10 mg/metformin 2,500 mg/day
-
Patients currently taking repaglinide and metformin:
- To achieve desired glycemic control, starting dosages of repaglinide and metformin should be in accordance with but not greater than the patient's existing doses.
-
Patients inadequately controlled with metformin monotherapy:
- Initial dosage: twice daily with food, 1 mg of repaglinide and 500 mg of metformin.
- Reduce the likelihood of repaglinide-induced hypoglycemia by titrating gradually.
-
Patients inadequately controlled with glinide monotherapy:
- Metformin 500 mg twice daily, together with repaglinide at no more than the patient's present dose, was the recommended initial dosage.
- To lessen metformin-induced gastrointestinal adverse effects, titrate gradually.
-
Dosage adjustment for concomitant therapy:
- Concomitant use with clopidogrel:
- Initial dose: Repaglinide 0.5 mg before every meal (maximum dose: 4 mg/day).
- Concomitant use with cyclosporine:
- Do not exceed 6mg/day of repaglinide
- Concomitant use with clopidogrel:
Use in Children:
Not indicated.
Pregnancy Risk Factor C
- Metformin crosses over to the placenta.
- Talk to individual agents.
Breastfeeding: Repaglinide or metformin
- Breast milk contains metformin; repaglinide does not exist.
- Due to the potential risk of hypoglycemia, breastfeeding is not advised.
PrandiMet (Repaglinide and metformin) Dose in Kidney Disease:
-
eGFR >45mL/minute/1.73m2
- There is no need to adjust the dosage
-
eGFR 30 - 45 mL/minute/1.73m2
- Pre-existing impairment
- Not recommended to initiate therapy
- Therapy: eGFR should be between 30 and 45mL/minute/1.73m2.
- Continued therapy is a good option.
- Metformin therapy should be continued. Reduce Metformin dosage by 50% (maximum Metformin 1,000 mg/day) while monitoring renal function every 3 months.
- Pre-existing impairment
-
eGFR 30mL/minute/1.73m2
- Contraindicated
PrandiMet (Repaglinide and metformin) Dose in Liver disease:
- Metformin should be avoided as liver disease can lead to lactic acidosis.
- Metformin continued use in diabetics with liver dysfunction (cirrhosis) has been successful.
- However, it may have a survival benefit for certain patients.
- Patients at high risk of lactic acidosis (eg renal impairment, alcohol abuse) should be treated with caution. Avoid hepatic impairment.
Side Effects of PrandiMet (Repaglinide and metformin):
-
Central nervous system:
- Headache
-
Endocrine & metabolic:
- Hypoglycemia
-
Gastrointestinal:
- Diarrhea
- Nausea
-
Respiratory:
- Upper respiratory tract infection
Contraindications to PrandiMet (Repaglinide and metformin):
- Hypersensitivity to metformin, repaglinide or any other component of the formulation
- Grave renal impairment (GFR 30mL/min/1.73m2)
- Chronic or acute metabolic acidosis (including diabetic ketoacidosis)
- Gemfibrozil may be administered simultaneously.
Warnings and precautions
-
Cardiovascular effects
- It is not advised to use NPH insulin in combination. In seven investigations, six myocardial ischemia incidents in individuals receiving repaglinide plus insulin were documented.
- To determine the safety of this combination, further evaluation is necessary.
-
Hypoglycemia
- Repaglinide may cause severe hypoglycemia. This risk can be increased by changing your meal times, exercise levels, taking coadministered medications or using it in conjunction with other anti-hypoglycemic agents.
- Patients with diabetes, long-term hypoglycemia, and diabetic neuropathy may experience symptoms that are less severe.
- Patients at high risk for hypoglycemia and those with reduced symptoms of hypoglycemia should be monitored more often.
-
Lactic acidosis: [US Boxed Warning]
- Metformin-associated lactosis has been linked to death, hypothermia and hypotension in post-marketing cases.
- The symptoms include malaise, myalgias and respiratory distress as well as nonspecific symptoms such as abdominal pain, somnolence, stomach pain, or nausea.
- Anion gap acidosis and increased blood lactate levels (>5 mg/L) are additional symptoms. Plasma levels of metformin are often higher than 5 mg/mL.
- Patients with renal impairment, concomitant intake of certain drugs (eg carbonic anhydrase inhibiters such as topiramate), >=65, having a radiologic scan with contrast, surgery, and other procedures, hypoxic conditions (eg acute heart failure), excessive alcohol consumption, and hepatic impairment are all risk factors for lactic acidosis.
- If you suspect lactic acidosis, discontinue use immediately. It is best to get hemodialysis as soon as possible.
- Patients with diabetes who are receiving metformin should suspect lactic acidosis if they have signs of acidosis, but not ketoacidosis.
- Patients with hypoxemia, sepsis or dehydration should stop taking metformin.
- Lactic acidosis and accumulation risk rises with renal function impairment.
-
Concentrations of Vitamin B12:
- Vitamin B-12 deficiency is a common side effect of long-term metformin usage.
- Long-term treatment with vitamin B-12 should be monitored regularly, especially for patients suffering from anemia or neuropathy.
-
Bariatric surgery
- Absorption altered:
- After surgery, take immediate-release tablets.
- The anatomical and transit changes may alter the absorption.
- Extended-release tablets can have a decreased effect after gastric bypass. This is due to the direct bypassing of the stomach and proximal bowel with gastric bypass, or a faster gastric emptying and transit with sleeve gastricectomy.
- As long as normal renal function remains intact, it is not necessary to reduce metformin doses after gastric bypass.
- Hypoglycemia
- Following a gastric bypass, gastric band, or sleeve gastroplasty, hypoglycemia may worsen.
- These methods may restore insulin secretion and sensitivity in part or in full (gastric bypass is the most effective, followed closely by the sleeve then finally the band).
- First-phase insulin secretion and hepatic insulin sensitivity have both been demonstrated to considerably increase in the days following gastric bypass or sleeve gastrectomy.
- The effects of these operations could remain longer on peripheral insulin sensitivity. This could occur three to twelve months after surgery.
- It is recommended to select antidiabetic drugs that are not hypoglycemic.
- Absorption altered:
-
Heart Failure:
-
- Metformin can be used for patients with stable or irreversible heart failure.
- Avoid use in patients who are unstable or have heart failure.
- Hypoperfusion may increase the risk of developing lactic acidosis.
- According to the American Heart Association, metformin may be a substance that makes myocardial dysfunction worse (magnitude major). (AHA, 2016 [Page]).
- Patients with heart disease may live longer and see fewer hospital readmissions if they take metformin.
-
-
Hepatic impairment
- Due to the possibility of lactic acidosis, the manufacturer suggests that patients with impaired liver function should be avoided.
- Metformin may have a survival benefit for certain patients who have diabetes with liver dysfunction.
-
Renal impairment
- Patients with decreased renal function may experience hypoglycemia more frequently.
- Large amounts of metformin are eliminated via the kidney.
- Evaluate the renal function before beginning treatment. Additionally, you can use eGFR to frequently check on your development.
- With growing renal impairment, the danger of metformin buildup or lactic acidosis will rise.
- Assess risk vs. benefit if eGFR is between 30 and 45 mL
- Metformin therapy should be continued. Reduce Metformin dosage by 50% (maximum Metformin 1,000 mg/day) while monitoring renal function every 3 months.
- Contraindicated for eGFR lower than 30ml
- Metformin disposition may be affected by concomitant medication that can affect renal function (i.e., tubular secretion).
- Metformin should be administered to patients suffering from dehydration or prerenal azotemia.
-
Stress-related disorders:
- Give insulin and cease therapy if the patient is under stress (fever, trauma, infection, or surgery).
Repaglinide and metformin: Drug Interaction
|
Abemaciclib |
May raise the level of metFORMIN in the serum. |
|
Abiraterone Acetate |
May elevate CYP2C8 substrates' serum levels (High risk with Inhibitors). |
|
Alpha-Lipoic Acid |
May enhance the hypoglycemic effect of Antidiabetic Agents. |
|
Androgens |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. |
|
Antidiabetic Agents |
May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. |
|
Bictegravir |
May increase the serum concentration of MetFORMIN. |
|
Bosentan |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Carbonic Anhydrase Inhibitors |
May enhance the adverse/toxic effect of MetFORMIN. Specifically, the risk of developing lactic acidosis may be increased. Exceptions: Brinzolamide; Dorzolamide. |
|
Cephalexin |
May increase the serum concentration of MetFORMIN. |
|
CYP3A4 Inducers (Moderate) |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
CYP3A4 Inhibitors (Strong) |
May increase the serum concentration of Repaglinide. Management: The addition of a CYP2C8 inhibitor to this drug combination may substantially increase the magnitude of increase in repaglinide exposure. |
|
Dalfampridine |
MetFORMIN may increase the serum concentration of Dalfampridine. Dalfampridine may increase the serum concentration of MetFORMIN. |
|
Deferasirox |
May increase the serum concentration of Repaglinide. |
|
Direct Acting Antiviral Agents (HCV) |
May enhance the hypoglycemic effect of Antidiabetic Agents. |
|
Dofetilide |
MetFORMIN may increase the serum concentration of Dofetilide. |
|
Eltrombopag |
May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. |
|
Erdafitinib |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
Erdafitinib |
OCT2 Substrates' serum concentration can rise. |
|
Erythromycin (Systemic) |
Repaglinide serum levels might rise. Management: The extent of the rise in repaglinide exposure may be significantly increased by adding a CYP2C8 inhibitor to this medication combination. |
|
Glycopyrrolate (Systemic) |
May raise the level of metFORMIN in the serum. |
|
Guanethidine |
May strengthen an anti-diabetic agent's hypoglycemic impact. |
|
Herbs (Hypoglycemic Properties) |
Possibly makes hypoglycemia-associated agents more effective. |
|
HMG-CoA Reductase Inhibitors (Statins) |
Repaglinide serum levels might rise. |
|
Hyperglycemia-Associated Agents |
May reduce an anti-diabetic agent's therapeutic efficacy. |
|
Hypoglycemia-Associated Agents |
May intensify other hypoglycemia-associated agents' hypoglycemic effects. |
|
Hypoglycemia-Associated Agents |
The hypoglycemic effect of hypoglycemia-associated agents may be strengthened by antidiabetic agents. |
|
Isavuconazonium Sulfate |
May raise the level of metFORMIN in the serum. |
|
Ivosidenib |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
LamoTRIgine |
May raise the level of metFORMIN in the serum. Management: Coadministration of these medications is not advised, according to the Canadian pharmaceutical monograph for lamotrigine. |
|
Leflunomide |
Repaglinide serum levels might rise. Particularly, leflunomide's active metabolite may raise repaglinide levels. |
|
Letermovir |
Repaglinide serum levels might rise. Management: If letermovir is taken with repaglinide, watch out for any increased effects or toxicities (such as hypoglycemia). Repaglinide should not be taken while letermovir and cyclosporine are being administered together. |
|
Maitake |
Can make blood glucose lowering medications more effective at lowering blood sugar. |
|
Monoamine Oxidase Inhibitors |
Can make blood glucose lowering medications more effective at lowering blood sugar. |
|
Ombitasvir, Paritaprevir, and Ritonavir |
May intensify the hazardous or harmful effects of metFORMIN. In particular, there may be a higher chance of developing lactic acidosis. |
|
Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir |
May intensify the hazardous or harmful effects of metFORMIN. In particular, there may be a higher chance of developing lactic acidosis. |
|
Ondansetron |
May raise the level of metFORMIN in the serum. |
|
Pegvisomant |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. |
|
Prothionamide |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. |
|
Quinolones |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. |
|
Ritodrine |
May diminish the therapeutic effect of Antidiabetic Agents. |
|
Salicylates |
May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. |
|
Sarilumab |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
Selective Serotonin Reuptake Inhibitors |
Can make blood glucose lowering medications more effective at lowering blood sugar. |
|
Siltuximab |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
Tecovirimat |
Repaglinide serum levels might rise. |
|
Teriflunomide |
May increase the serum concentration of Repaglinide. |
|
Thiazide and Thiazide-Like Diuretics |
May reduce an anti-diabetic agent's therapeutic efficacy. |
|
Tocilizumab |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
Topiramate |
May intensify the hazardous or harmful effects of metFORMIN. |
|
Trimethoprim |
Repaglinide's metabolism might be slowed down. |
|
Trimethoprim |
May raise the level of metFORMIN in the serum. |
|
Trospium |
Trospium serum levels may drop when taking metFORMIN. |
|
Vandetanib |
May raise the level of metFORMIN in the serum. |
|
Verapamil |
May lessen MetFORMIN's therapeutic impact. |
|
Cimetidine |
May raise the level of metFORMIN in the serum. Due to the possibility of higher metformin concentrations and toxicity, management for patients using metformin should look into alternatives to cimetidine (including lactic acidosis). |
|
Clopidogrel |
Repaglinide serum levels might rise. Management: If at all feasible, avoid using clopidogrel and repaglinide together; if necessary, keep the daily maximum dose of repaglinide to 4 mg. According to some non-US labelling, this is prohibited. |
|
CycloSPORINE (Systemic) |
Repaglinide serum levels might rise. Management: When using cyclosporine at the same time as repaglinide, the daily dose should be kept to a maximum of 6 mg, and repaglinide symptoms should be continuously watched for. |
|
CYP3A4 Inducers (Strong) |
May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. |
|
Dabrafenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). |
|
Dabrafenib |
May decrease the serum concentration of CYP2C8 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C8 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). |
|
Dolutegravir |
May raise the level of metFORMIN in the serum. Management: Take into account the advantages and disadvantages of this pairing. When taken together, dolutegravir and metformin should not exceed a combined daily dose of 1,000 mg. When using metformin concurrently, keep an eye out for any increased side effects or toxicities (including lactic acidosis). |
|
Enzalutamide |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. |
|
Iodinated Contrast Agents |
May intensify the hazardous or harmful effects of metFORMIN. Lactic acidosis associated with metformin can be brought on by renal impairment that may be brought on by iodinated contrast agents. Management: The guidance on management differs. For more information, consult the medication interaction monograph in its entirety. Exceptions: Ethiodized oil, diatrizoate sodium, and diatrizoate meglumine. |
|
Lorlatinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. |
|
MiFEPRIStone |
May increase the serum concentration of CYP2C8 Substrates (High risk with Inhibitors). Management: Use CYP2C8 substrates at the lowest recommended dose, and monitor closely for adverse effects (including myopathy), during and in the 2 weeks following mifepristone treatment. |
|
Mitotane |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. |
|
Patiromer |
May decrease the serum concentration of MetFORMIN. Management: Administer metformin at least 3 hours before or 3 hours after patiromer. |
|
Ranolazine |
May increase the serum concentration of MetFORMIN. Management: Limit the metformin dose to a maximum of 1,700 mg per day when used together with ranolazine 1,000 mg twice daily. Monitor patients for metformin toxicities, including lactic acidosis and carefully weigh the risks and benefits of this combination. |
|
RifAMPin |
May lower the level of Repaglinide in the serum. Management: Take into account alternatives to this fusion. This interaction may be significantly impacted by the timing of the dose; in clinical investigations, the least significant interaction was observed when repaglinide was administered one hour after rifampin (compared to 0, 12, or 24 h). |
|
St John's Wort |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Specific contraindications may apply to some combinations. the relevant manufacturer's label. |
|
Tafenoquine |
MATE1 Substrates' serum concentration might rise. Management: If using MATE substrates with tafenoquine cannot be avoided, check carefully for signs of toxicity and take into account using a lower dose of the MATE substrate in accordance with the labelling of that substrate. |
|
Tafenoquine |
OCT2 Substrates' serum concentration can rise. Management: If using OCT2 substrates with tafenoquine cannot be avoided, watch closely for any signs of toxicity and take into account using a lower dose of the OCT2 substrate in accordance with the labelling of that substrate. |
|
Tolvaptan |
May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. |
|
Alcohol (Ethyl) |
May enhance the adverse/toxic effect of MetFORMIN. Specifically, alcohol may potentiate the risk of lactic acidosis. |
|
Atazanavir |
Repaglinide serum levels might rise. Treatment: Ritonavir should not be taken at the same time as atazanavir or any other CYP2C8 substrates with a narrow therapeutic index. No major interactions are anticipated when repaglinide is administered with atazanavir that has been enhanced by ritonavir. |
|
Gemfibrozil |
Repaglinide serum levels might rise. Itraconazole may improve the impact of gemfibrozil on repaglinide when added. |
Monitoring parameters:
Regular evaluation of
- Fasting blood glucose
- Postprandial blood glucose
- Hemoglobin A should be taken at least once every 6 months for patients with stable glycemic control. It should also be taken at once every 3 months for patients not meeting their treatment goals or who are undergoing therapy change.
- Monitoring of hemoglobin/hematocrit and red blood cell indexes (eg, hemoglobin/hematocrit) is recommended for both initial and ongoing monitoring.
- Before starting treatment, it is important to check your renal function (eGFR). This should be done at least once a year if you have eGFR between 45 and 60 mL/minute/1.73m2; or every 3 months if you have eGFR between 30 and 45 mL/minute/1.73m2.
- Long-term treatment with vitamin B-12 requires that you monitor your serum levels regularly
- Folate levels (if you suspect megaloblastic anemia).
How to administer PrandiMet (Repaglinide and metformin)?
- Oral: To reduce the chance of hypoglycemia/GI distress, administer up to 30 minutes before meals.
- In the case of a skipped meal, do not administer the dose.
Mechanism of action of PrandiMet (Repaglinide and metformin):
- It's a combination of metformin and Repaglinide.
- Metformin and Repaglinide work together to increase glycemic control through two different mechanisms.
- The membrane depolarizes as a result of blocking potassium channels that are ATP-dependent. Calcium enters calcium channels more effectively as a result of this. Additionally, pancreatic beta cells are stimulated to secrete insulin by the intracellular calcium.
- Metformin reduces intestinal absorption and hepatic glucose production. Additionally, it improves insulin sensitivity and peripheral glucose absorption and utilisation. Reach out to specific agents (Metformin or Repaglinide).
International Brand Names of Repaglinide and metformin:
- PrandiMet
- Fulaihe
- Magicnorm
- Panmeglin
- Repanorm M
- Replitza
Repaglinide and metformin Brand Names in Pakistan:
No Brands Available in Pakistan.
