|
(n=141) |
|
Diarrhea
|
53%
|
12%
|
Nausea/Vomiting
|
26%
|
8%
|
Flatulence
|
12%
|
6%
|
Asthenia
|
9%
|
6%
|
Indigestion
|
7%
|
4%
|
Abdominal Discomfort
|
6%
|
5%
|
Headache
|
6%
|
5%
|
|
|
|
Carbonic anhydrase inhibitors frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with metformin hydrochloride tablets may increase the risk for lactic acidosis.
|
|
Consider more frequent monitoring of these patients.
|
|
Topiramate, zonisamide, acetazolamide or dichlorphenamide.
|
|
|
|
Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors) could increase systemic exposure to metformin and may increase the risk for lactic acidosis
|
|
Consider the benefits and risks of concomitant use with metformin hydrochloride tablets.
|
|
Ranolazine, vandetanib, dolutegravir, and cimetidine.
|
|
|
|
Alcohol is known to potentiate the effect of metformin on lactate metabolism.
|
|
Warn patients against excessive alcohol intake while receiving metformin hydrochloride tablets.
|
|
|
|
Coadministration of metformin hydrochloride tablets with an insulin secretagogue (e.g., sulfonylurea) or insulin may increase the risk of hypoglycemia.
|
|
Patients receiving an insulin secretagogue or insulin may require lower doses of the insulin secretagogue or insulin.
|
|
|
|
Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control.
|
|
When such drugs are administered to a patient receiving metformin hydrochloride tablets, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving metformin hydrochloride tablets, observe the patient closely for hypoglycemia.
|
|
Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid.
|
|
|
|
|
500 mg single dose (24) 850 mg single dose (74) d 850 mg three times daily for 19 doses e(9) |
1.03 (±0.33) 1.60 (±0.38) 2.01 (±0.42) |
2.75 (±0.81) 2.64 (±0.82) 1.79 (±0.94) |
600 (±132) 552 (±139) 642 (±173) |
850 mg single dose (23) 850 mg three times daily for 19 dosese (9) |
1.48 (±0.5) 1.90 (±0.62) |
3.32 (±1.08) 2.01 (±1.22) |
491 (±138) 550 (±160) |
850 mg single dose (12) |
2.45 (±0.70) |
2.71 (±1.05) |
412 (±98) |
|
1.86 (±0.52) 4.12 (±1.83) 3.93 (±0.92) |
3.20 (±0.45) 3.75 (±0.50) 4.01 (±1.10) |
384 (±122) 108 (±57) 130 (±90) |
|
|
|
|
||
|
|
||||
No dosing adjustments required for the following: |
|||||
Glyburide
|
5 mg
|
850 mg
|
metformin
|
0.91
‡
|
0.93
‡
|
Furosemide
|
40 mg
|
850 mg
|
metformin
|
1.09
‡
|
1.22
‡
|
Nifedipine
|
10 mg
|
850 mg
|
metformin
|
1.16
|
1.21
|
Propranolol
|
40 mg
|
850 mg
|
metformin
|
0.90
|
0.94
|
Ibuprofen
|
400 mg
|
850 mg
|
metformin
|
1.05
‡
|
1.07
‡
|
|
|||||
Cimetidine
|
400 mg
|
850 mg
|
metformin
|
1.40
|
1.61
|
|
|||||
Topiramate
|
100 mg
§
|
500 mg
§
|
metformin
|
1.25
§
|
1.17
|
|
|
|
|
||
|
|
||||
|
|||||
Glyburide
|
5 mg
|
850 mg
|
glyburide
|
0.78
‡
|
0.63
‡
|
Furosemide
|
40 mg
|
850 mg
|
furosemide
|
0.87
‡
|
0.69
‡
|
Nifedipine
|
10 mg
|
850 mg
|
nifedipine
|
1.10
§
|
1.08
|
Propranolol
|
40 mg
|
850 mg
|
propranolol
|
1.01
§
|
1.02
|
Ibuprofen
|
400 mg
|
850 mg
|
ibuprofen
|
0.97
¶
|
1.01
¶
|
Cimetidine
|
400 mg
|
850 mg
|
cimetidine
|
0.95
§
|
1.01
|
Tablets (n=141) |
|
|
|
|
|
|
|
Baseline
|
241.5
|
237.7
|
NS*
|
Change at FINAL VISIT
|
–53.0
|
6.3
|
0.001
|
|
|
|
|
Baseline
|
8.4
|
8.2
|
NS*
|
Change at FINAL VISIT
|
–1.4
|
0.4
|
0.001
|
|
|
|
|
|
||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Baseline
|
250.5
|
247.5
|
253.9
|
NS*
|
NS*
|
NS*
|
Change at FINAL VISIT
|
–63.5
|
13.7
|
–0.9
|
0.001
|
0.001
|
0.025
|
|
|
|
|
|
|
|
Baseline
|
8.8
|
8.5
|
8.9
|
NS*
|
NS*
|
0.007
|
Change at FINAL VISIT
|
–1.7
|
0.2
|
–0.4
|
0.001
|
0.001
|
0.001
|
Tablets |
|
|
|
|
|
|
|
Baseline
|
162.4
|
192.3
|
|
Change at FINAL VISIT
|
–42.9
|
21.4
|
<0.001
|
|
Metformin Hydrochloride Tablets 500 mg Twice Daily | Metformin Hydrochloride Extended – release Tablets | |
1000 mgOnce Daily | 1500 mg Once Daily | ||
Baseline Change at FINAL VISIT (95% CI) |
|
|
|
7.06
|
6.99
|
7.02
|
|
0.14a
|
0.27
|
0.13
|
|
(–0.04, 0.31)
|
(0.11, 0.43)
|
(–0.02, 0.28)
|
|
Baseline Change at FINAL VISIT (95% CI) |
|
|
|
127.2 |
131.0
|
131.4
|
|
14.0
|
11.5
|
7.6
|
|
(7.0, 21.0)
|
(4.4, 18.6)
|
(1.0, 14.2)
|