Glucophage XR

Glucophage XR

metformin

Manufacturer:

Merck

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Metformin hydrochloride.
Description
500 mg: One extended release tablet contains 500mg metformin hydrochloride corresponding to 390mg metformin base.
750 mg: One extended release tablet contains 750 mg metformin hydrochloride corresponding to 585 mg metformin base.
1,000 mg: Each extended release tablet of Glucophage XR 1000mg contains 1000 mg metformin hydrochloride corresponding to 780 mg metformin base.
Excipients/Inactive Ingredients: 500 mg: Magnesium stearate, sodium carboxymethylcellulose, hypromellose.
750 mg and 1,000 mg: Magnesium stearate, Carmellose sodium, Hypromellose.
Action
Pharmacotherapeutic Group: ORAL ANTI-DIABETICS. ATC Code: A10BA02: Gastrointestinal tract and metabolism.
Pharmacology: Pharmacodynamics: Metformin is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial plasma glucose. It does not stimulate insulin secretion and therefore does not produce hypoglycaemia.
Mechanism of action: Metformin may act via 3 mechanisms: reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis; in muscle, by increasing insulin sensitivity, improving peripheral glucose uptake and utilisation; and delay of intestinal glucose absorption.
Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthase.
Metformin increases the transport capacity of all types of membrane glucose transporters (GLUT).
Pharmacodynamic effects: In clinical studies, the major non glycemic effect of metformin is either weight stability or modest weight loss.
In humans, independently of its action on glycaemia, immediate release metformin has favourable effects on lipid metabolism. This has been shown at therapeutic doses in controlled, medium-term or long-term clinical studies: immediate release metformin reduces total cholesterol, LDL cholesterol and triglyceride levels. A similar action has not been demonstrated with the prolonged release formulation, possibly due to the evening administration, and an increase in triglycerides may occur.
Clinical efficacy: Reduction in the risk or delay of type 2 diabetes mellitus: The Diabetes Prevention Program (DPP) was a multicenter randomised controlled clinical trial in adults assessing the efficacy of an intensive lifestyle intervention or metformin to prevent or delay the development of type 2 diabetes mellitus. Inclusion criteria were age ≥25 years, BMI ≥24 kg/m2 (≥22 kg/m2 for Asian-Americans), and impaired glucose tolerance plus a fasting plasma glucose of 95 - 125 mg/dl (or ≤125 mg/dl for American Indians). Patients were either treated with intensive lifestyle intervention, 2x850 mg metformin plus standard lifestyle change, or placebo plus standard lifestyle change. The mean baseline values of the DPP participants (n=3,234 for 2.8 years) were age 50.6±10.7 years, 106.5±8.3 mg/dl fasted plasma glucose, 164.6±17.0 mg/dl plasma glucose two hours after an oral glucose load, and 34.0±6.7 kg/m2 BMI. Intensive lifestyle intervention as well as metformin significantly reduced the risk of developing overt diabetes compared to placebo, 58% (95% CI 48-66%) and 31% (95% CI 17-43%), respectively.
The advantage of the lifestyle intervention over metformin was greater in older persons.
The patients who benefited most from the metformin treatment were aged below 45 years, with a BMI equal or above 35kg/m2, a baseline glucose 2 h value of 9.6-11.0 mmol/l, a baseline HbA1C equal or above 6.0% or with a history of gestational diabetes. To prevent one case of overt diabetes during the three years in the whole population of the DPP, 6.9 patients had to participate in the intensive lifestyle group and 13.9 in the metformin group. The point of reaching a cumulative incidence of diabetes equal to 50% was delayed by about three years in the metformin group compared to placebo.
The Diabetes Prevention Program Outcomes Study (DPPOS) is the long-term follow-up study of the DPP including more than 87% of the original DPP population for long-term follow up.
Among the DPPOS participants (n=2776), the cumulative incidence of diabetes at year 15 is 62% in the placebo group, 56% in the metformin group, and 55% in the intensive lifestyle intervention group. Crude rates of diabetes are 7.0, 5.7 and 5.2 cases per 100 person‐years among the placebo, metformin, and intensive lifestyle participants, respectively. Reductions in the diabetes risk were of 18% (hazard ratio (HR) 0.82, 95% CI 0.72-0.93; p=0.001) for the metformin group and 27% (HR 0.73, 95% CI 0.65-0.83; p<0.0001) for the intensive lifestyle intervention group, when compared with the placebo group. For an aggregate microvascular endpoint of nephropathy, retinopathy and neuropathy, the outcome was not significantly different between the treatment groups, but among the participants who had not developed diabetes during DPP/DPPOS, the prevalence of the aggregate microvascular outcome was 28% lower compared with those who had developed diabetes (Risk Ratio 0.72, 95% CI 0.63-0.83; p<0.0001). No prospective comparative data for metformin on macrovascular outcomes in patients with IGT and/or IFG and/or increased HbA1C are available.
Published risk factors for type 2 diabetes include: Asian or black ethnic background, age above 40, dyslipidaemia, hypertension, obesity or being overweight, age, 1st degree family history of diabetes, history of gestational diabetes mellitus, and polycystic ovary syndrome (PCOS).
Consideration must be given to current national guidance on the definition of prediabetes.
Patients at high risk should be identified by a validated risk-assessment tool.
Treatment of type 2 diabetes mellitus: The prospective randomised (UKPDS) study has established the long-term benefit of intensive blood glucose control in overweight type 2 diabetic patients treated with immediate release metformin as first-line therapy after diet failure. Analysis of the results for overweight patients treated with metformin after failure of diet alone showed: a significant reduction of the absolute risk of any diabetes-related complication in the metformin group (29.8 events/ 1000 patient-years) versus diet alone (43.3 events/ 1000 patient-years), p=0.0023, and versus the combined sulphonylurea and insulin monotherapy groups (40.1 events/ 1000 patient-years), p=0.0034.
a significant reduction of the absolute risk of diabetes-related mortality: metformin 7.5 events/1000 patient-years, diet alone 12.7 events/ 1000 patient-years, p=0.017;
a significant reduction of the absolute risk of overall mortality: metformin 13.5 events/ 1000 patient-years versus diet alone 20.6 events/ 1000 patient-years (p=0.011), and versus the combined sulphonylurea and insulin monotherapy groups 18.9 events/ 1000 patient-years (p=0.021);
a significant reduction in the absolute risk of myocardial infarction: metformin 11 events/ 1000 patient-years, diet alone 18 events/ 1000 patient-years (p=0.01).
For metformin used as second-line therapy, in combination with a sulphonylurea, benefit regarding clinical outcome has not been shown.
In type 1 diabetes, the combination of metformin and insulin has been used in selected patients, but the clinical benefit of this combination has not been formally established.
Pharmacokinetics: Absorption: At steady state, similar to the immediate release formulation, Cmax and AUC are not proportionally increased to the administered dose. The AUC after a single oral administration of 2000 mg of metformin extended release tablets is similar to that observed after administration of 1000 mg of metformin immediate release tablets b.i.d.
Intrasubject variability of Cmax and AUC of metformin extended release tablets is comparable to that observed with metformin immediate release tablets.
Metformin absorption from the extended release formulation is not altered by meal composition.
No accumulation is observed after repeated administration of up to 2000 mg of metformin extended release tablets.
500 mg: After an oral dose of the extended release tablet, metformin absorption is significantly delayed compared to the immediate release tablet with a Tmax at 7 hours (Tmax for the immediate release tablet is 2.5 hours).
750 mg: Following a single oral administration of 1500 mg of Glucophage XR 750 mg, a mean peak plasma concentration of 1193 ng/ml is achieved with a median value of 5 hours and a range of 4 to 12 hours. Glucophage XR 750 mg was shown to be bioequivalent to Glucophage XR 500 mg at a 1500 mg dose with respect to Cmax and AUC in healthy fed and fasted subjects.
1,000 mg: Following a single oral administration in the fed state of one tablet of Glucophage XR 1000 mg, a mean peak plasma concentration of 1214 ng/ml is achieved with a median time of 5 hours (range of 4 to 10 hours). Glucophage XR 1000 mg was shown to be bioequivalent to Glucophage XR 500 mg at a 1000 mg dose with respect to Cmax and AUC in healthy fed and fasted subjects.
When the 1000 mg extended release tablet is administered in fed conditions the AUC is increased by 77% (Cmax is increased by 26% and Tmax is slightly prolonged by about 1 hour).
500 mg and 750 mg: When the extended release tablet is administered in fasting conditions the AUC is decreased by 30% (both Cmax and Tmax are unaffected).
Distribution: Plasma protein binding is negligible. Metformin partitions into erythrocytes. The blood peak is lower than the plasma peak and appears at approximately the same time. The red blood cells most likely represent a secondary compartment of distribution. The mean volume of distribution (Vd) ranged between 63-276 l.
Metabolism: Metformin is excreted unchanged in the urine. No metabolites have been identified in humans.
Elimination: Renal clearance of metformin is > 400 ml/min, indicating that metformin is eliminated by glomerular filtration and tubular secretion. Following an oral dose, the apparent terminal elimination half-life is approximately 6.5 hours. When renal function is impaired, renal clearance is decreased in proportion to that of creatinine and thus the elimination half-life is prolonged, leading to increased levels of metformin in plasma.
Characteristics in specific groups of patients: Renal impairment: The available data in subjects with moderate renal insufficiency are scarce and no reliable estimation of the systemic exposure to metformin in this subgroup as compared to subjects with normal renal function could be made. Therefore, the dose adaptation should be made upon clinical efficacy/tolerability considerations (see Dosage & Administration).
Toxicology: Preclinical safety data: Preclinical data reveal no special hazard for humans based on conventional studies on safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity reproduction.
Indications/Uses
Reduction in the risk or delay of the onset of type 2 diabetes mellitus in adult, overweight patients with IGT* and/or IFG*, and/or increased HbA1C* who are: at high risk for developing overt type 2 diabetes (see Pharmacology: Pharmacodynamics under Actions) and still progressing towards type 2 diabetes mellitus despite implementation of intensive lifestyle change for 3 to 6 months.
Treatment with Glucophage XR must be based on a risk score incorporating appropriate measures of glycaemic control and including evidence of high cardiovascular risk (see Pharmacology: Pharmacodynamics under Actions).
Lifestyle modifications should be continued when metformin is initiated, unless the patient is unable to do so because of medical reasons.
*IGT: Impaired Glucose Tolerance; IFG: Impaired Fasting Glucose.
Treatment of type 2 diabetes mellitus in adults, when dietary management and exercise alone does not result in adequate glycaemic control. Glucophage XR may be used as monotherapy or in combination with other oral antidiabetic agents, or with insulin.
500 and 750 mg: A reduction of diabetic complications has been shown in overweight type 2 diabetic patients treated with immediate release metformin as first-line therapy after diet failure (see Pharmacology: Pharmacodynamics under Actions).
Dosage/Direction for Use
Adults with normal renal function (GFR ≥90 mL/min): Reduction in the risk or delay of the onset of type 2 diabetes: Metformin should only be considered where intensive lifestyle modifications for 3 to 6 months have not resulted in adequate glycaemic control.
The therapy should be initiated with one tablet Glucophage XR 500 mg once daily with the evening meal.
After 10 to 15 days dose adjustment on the basis of blood glucose measurements is recommended (OGTT and/or FPG and/or HbA1C values to be within the normal range). A slow increase of dose may improve gastro-intestinal tolerability.
500 mg: The maximum recommended dose is 4 tablets (2000 mg) once daily with the evening meal.
750 mg: The maximum recommended dose of Glucophage XR 750 mg is 2 tablets (1500 mg) once daily with the evening meal.
1,000 mg: The maximum recommended dose of Glucophage XR is 2 tablets (2000 mg) once daily with the evening meal.
It is recommended to regularly monitor (every 3-6 months) the glycaemic status (OGTT and/or FPG and/or HbA1c value) as well as the risk factors to evaluate whether treatment needs to be continued, modified or discontinued.
A decision to re-evaluate therapy is also required if the patient subsequently implements improvements to diet and/or exercise, or if changes to the medical condition will allow increased lifestyle interventions to be possible.
Monotherapy or combination with other oral antidiabetic agents: 500 and 750 mg: The usual starting dose is one tablet once daily with the evening meal.
After 10 to 15 days the dose should be adjusted on the basis of blood glucose measurements. A slow increase of dose may improve gastro-intestinal tolerability.
500 mg: The maximum recommended dose is 4 tablets daily.
Dosage increases should be made in increments of 500mg every 10-15 days, up to a maximum of 2000mg once daily with the evening meal.
750 mg: The maximum recommended dose is 2 tablets once daily with the evening meal.
In patients already treated with metformin tablets, the starting dose of Glucophage XR should be equivalent to the daily dose of metformin immediate release tablets.
If transfer from another oral antidiabetic agent is intended: discontinue the other agent and initiate Glucophage XR at the dose indicated previously.
1,000 mg: Glucophage XR 1000 mg should be taken once daily with the evening meal at a maximum recommended dose of 2 tablets per day.
Glucophage XR 1000 mg is intended as a maintenance therapy for patients treated with either 1000 mg or 2000 mg of metformin hydrochloride. On switch, the daily dose of Glucophage XR should be equivalent to the daily dose of metformin hydrochloride.
In patients treated with metformin hydrochloride at a dose above 2000 mg daily, switching to Glucophage XR is not recommended.
For patients new to metformin hydrochloride, the usual starting dose of Glucophage XR is 500 mg or 750 mg once daily given with the evening meal. After 10 to 15 days the dose should be adjusted on the basis of blood glucose measurements. A slow increment in dose may improve gastrointestinal tolerability.
If glycaemic control is not achieved on 2000 mg metformin hydrochloride extended release once daily, patients may be switched to standard metformin hydrochloride immediate-release to a maximum dose of 3000 mg daily.
In the event of transfer from another oral antidiabetic agent, titration should begin with Glucophage XR 500 mg before switching to Glucophage XR 1000 mg as indicated previously.
Combination with insulin: Metformin and insulin may be used in combination therapy to achieve better blood glucose control.
500 mg: The usual starting dose of Glucophage XR is one tablet once daily with the evening meal, while insulin dosage is adjusted on the basis of blood glucose measurements.
750 mg: The usual starting dose of Glucophage XR is one tablet once daily up to a maximum of 1500 mg with the evening meal, while insulin dosage is adjusted on the basis of blood glucose measurements.
1,000 mg: The usual starting dose of Glucophage XR is one tablet 500 mg or 750 mg once daily with the evening meal, while insulin dosage is adjusted on the basis of blood glucose measurements. After titration, switch to Glucophage XR 1000 mg should be considered.
Elderly: Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function. Regular assessment of renal function is necessary (see Precautions).
Benefit in the reduction of risk or delay of the onset of type 2 diabetes mellitus has not been established in patients 75 years and older (see Pharmacology: Pharmacodynamics under Actions) and metformin initiation is therefore not recommended in these patients (see Precautions).
Renal impairment: A GFR should be assessed before initiation of treatment with metformin containing products and at least annually thereafter. In patients at an increased risk of further progression of renal impairment and in the elderly, renal function should be assessed more frequently, e.g. every 3-6 months. (See table.)

Click on icon to see table/diagram/image

Paediatric Population: In the absence of available data, Glucophage XR should not be used in children.
Overdosage
Hypoglycaemia has not been seen with metformin doses of up to 85 g, although lactic acidosis has occurred in such circumstances. High overdose or concomitant risks of metformin may lead to lactic acidosis. Lactic acidosis is a medical emergency and must be treated in hospital. The most effective method to remove lactate and metformin is haemodialysis.
Contraindications
Hypersensitivity to metformin or to any of the excipients listed in Description.
Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis).
Diabetic pre-coma.
Severely reduced kidney function (GFR <30 mL/min).
Acute conditions with the potential to alter renal function such as: dehydration, severe infection, shock.
Disease which may cause tissue hypoxia (especially acute disease, or worsening of chronic disease) such as: decompensated heart failure, respiratory failure, recent myocardial infarction, shock.
Hepatic insufficiency, acute alcohol intoxication, alcoholism.
Special Precautions
Lactic acidosis: Lactic acidosis, a very 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 diarrhoea or vomiting, 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 (see Contraindications and Interactions).
Patients and/or care-givers should be informed of the risk of lactic acidosis. Lactic acidosis is characterised by acidotic dyspnoea, 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.
Cardiac function: Patients with heart failure are more at risk of hypoxia and renal insufficiency. In patients with stable chronic heart failure, metformin may be used with a regular monitoring of cardiac and renal function.
For patients with acute and unstable heart failure, metformin is contraindicated (see Contraindications).
Administration of iodinated contrast agents: Intravascular administration of iodinated contrast agents may lead to contrast induced nephropathy, resulting in metformin accumulation and an increased risk of lactic acidosis. Metformin should be discontinued prior to or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable, see Dosage & Administration and Interactions.
Surgery: Metformin must be discontinued at the time of surgery with general, spinal or epidural anaesthesia. Therapy may be restarted no earlier than 48 hours following surgery or resumption of oral nutrition and provided that renal function has been re-evaluated and found to be stable.
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.
Metformin alone never causes hypoglycaemia, although caution is advised when it is used in combination with insulin or other oral antidiabetics (e.g. sulphonylureas or meglitinides).
The tablet shells may be present in the faeces. Patients should be advised that this is normal.
Effects on ability to drive and use machines: Metformin monotherapy does not cause hypoglycaemia and therefore has no effect on the ability to drive or to use machines.
However, patients should be alerted to the risk of hypoglycaemia when metformin is used in combination with other antidiabetic agents (e.g. sulphonylureas, insulin, or meglinitides).
Renal function: GFR should be assessed before treatment initiation and regularly thereafter, see Dosage & Administration. Metformin is contraindicated in patients with GFR<30 mL/min and should be temporarily discontinued in the presence of conditions that alter renal function, see Contraindications.
Use in Elderly: Due to the limited therapeutic efficacy data in the reduction of risk or delay of type 2 diabetes in patients 75 years and older, metformin initiation is not recommended in these patients.
Use In Pregnancy & Lactation
Pregnancy: Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with increased risk of congenital abnormalities and perinatal mortality. A limited amount of data from the use of metformin in pregnant women does not indicate an increased risk of congenital abnormalities. Animal studies do not indicate harmful effects with respect to pregnancy, embryonic or fetal development, parturition or postnatal development (see Pharmacology: Toxicology: Preclinical safety data under Actions). When the patient plans to become pregnant and during pregnancy, it is recommended that impaired glycaemic control or diabetes is not treated with metformin but insulin be used to maintain blood glucose levels as close to normal as possible to reduce the risk of malformations of the foetus.
Breast-feeding: Metformin is excreted into human breast milk. No adverse effects were observed in breastfed newborns/infants. However, as only limited data are available, breastfeeding is not recommended during metformin treatment. A decision on whether to discontinue breast-feeding should be made, taking into account the benefit of breast-feeding and the potential risk to adverse effect on the child.
Fertility: Fertility of male or female rats was unaffected by metformin when administered at doses as high as 600 mg/kg/day, which is approximately three times the maximum recommended human daily dose based on body surface area comparisons.
Adverse Reactions
In post marketing data and in controlled clinical studies, adverse event reporting in patients treated with Glucophage XR was similar in nature and severity to that reported in patients treated with Glucophage immediate release.
During treatment initiation, the most common adverse reactions are nausea, vomiting, diarrhoea, abdominal pain and loss of appetite, which resolve spontaneously in most cases.
The following adverse reactions may occur with Glucophage XR.
Frequencies are defined as follows: very common: >1/10; common >1/100, <1/10; uncommon >1/1,000, <1/100; rare >1/10,000, <1/1,000; very rare <1/10,000.
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Metabolism and nutrition disorders: Very rare: Lactic acidosis (see Precautions).
Decrease of vitamin B12 absorption with decrease of serum levels during long-term use of metformin. Consideration of such an aetiology is recommended if a patient presents with megaloblastic anaemia.
Nervous system disorders: Common: Taste disturbance.
Gastrointestinal disorders: Very common: Gastrointestinal disorders such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite. These undesirable effects occur most frequently during initiation of therapy and resolve spontaneously in most cases. A slow increase of the dose may also improve gastrointestinal tolerability.
Hepatobiliary disorders: Very rare: Isolated reports of liver function tests abnormalities or hepatitis resolving upon metformin discontinuation.
Skin and subcutaneous tissue disorders: Very rare: Skin reactions such as erythema, pruritus, urticaria.
Drug Interactions
Concomitant use not recommended: Alcohol: Alcohol intoxication is associated with an increased risk of lactic acidosis, particularly in case of fasting, malnutrition or hepatic impairment.
Iodinated contrast agents: Metformin must be discontinued prior to or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable, see Dosage & Administration and Precautions.
Combinations requiring precautions for use: Some medicinal products can adversely affect renal function which may increase the risk of lactic acidosis, e.g. NSAIDs, including selective cyclo-oxygenase (COX) II inhibitors, ACE inhibitors, angiotensin II receptor antagonists and diuretics, especially loop diuretics. When starting or using such products in combination with metformin, close monitoring of renal function is necessary.
Medicinal products with intrinsic hyperglycaemic activity (e.g. glucocorticoids (systemic and local routes) and sympathomimetics): More frequent blood glucose monitoring may be required, especially at the beginning of treatment. If necessary, adjust the metformin dosage during therapy with the other drug and upon its discontinuation.
Organic cation transporters (OCT): Metformin is a substrate of both transporters OCT1 and OCT2. Co-administration of metformin with: Inhibitors of OCT1 (such as verapamil) may reduce efficacy.
Inducers of OCT1 (such as rifampicin) may increase gastrointestinal absorption and efficacy of metformin.
Inhibitors of OCT2 (such as cimetidine, dolutegravir, ranolazine, trimethoprime, vandetanib, isavuconazole) may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration.
Inhibitors of both OCT1 and OCT2 (such as crizotinib, olaparib) may alter efficacy and renal elimination of metformin.
Caution is therefore advised, especially in patients with renal impairment, when these drugs are co-administered with metformin, as metformin plasma concentration may increase. If needed, dose adjustment of metformin may be considered as OCT inhibitors/inducers may alter the efficacy of metformin.
Caution For Usage
Instructions for use (and handling): 500 mg: Not applicable.
Special precautions for disposal: 1,000 mg: No special requirements.
Incompatibilities: None.
Storage
Store at room temperature. Protect from moisture, freezing and excessive heat. Store below 30°C.
Shelf-Life: 500 mg: 36 months.
750 mg and 1,000 mg: 3 years.
MIMS Class
ATC Classification
A10BA02 - metformin ; Belongs to the class of biguanides. Used in the treatment of diabetes.
Presentation/Packing
ER tab 500 mg (white to off-white, biconvex, debossed on one side with '500') x 60's. 750 mg (white to off-white, capsule-shaped, biconvex, debossed on one side with '750' and on the other side 'Merck') x 60's. 1,000 mg (white to off-white, capsule shaped, biconvex, debossed on one side with '1000' and on the other side with 'Merck') x 60's.
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