Olmesartan Medoxomil: Package Insert and Label Information (Page 3 of 3)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Olmesartan medoxomil was not carcinogenic when administered by dietary administration to rats for up to 2 years. The highest dose tested (2000 mg/kg/day) was, on a mg/m 2 basis, about 480 times the maximum recommended human dose (MRHD) of 40 mg/day. Two carcinogenicity studies conducted in mice, a 6-month gavage study in the p53 knockout mouse and a 6-month dietary administration study in the Hras2 transgenic mouse, at doses of up to 1000 mg/kg/day (about 120 times the MRHD), revealed no evidence of a carcinogenic effect of olmesartan medoxomil.

Both olmesartan medoxomil and olmesartan tested negative in the in vitro Syrian hamster embryo cell transformation assay and showed no evidence of genetic toxicity in the Ames (bacterial mutagenicity) test. However, both were shown to induce chromosomal aberrations in cultured cells in vitro (Chinese hamster lung) and tested positive for thymidine kinase mutations in the in vitro mouse lymphoma assay. Olmesartan medoxomil tested negative in vivo for mutations in the MutaMouse intestine and kidney and for clastogenicity in mouse bone marrow (micronucleus test) at oral doses of up to 2000 mg/kg (olmesartan not tested).

Fertility of rats was unaffected by administration of olmesartan medoxomil at dose levels as high as 1000 mg/kg/day (240 times the MRHD) in a study in which dosing was begun 2 (female) or 9 (male) weeks prior to mating.

14 CLINICAL STUDIES

14.1 Adult Hypertension

The antihypertensive effects of olmesartan medoxomil have been demonstrated in seven placebo-controlled studies at doses ranging from 2.5 mg to 80 mg for 6 to 12 weeks, each showing statistically significant reductions in peak and trough blood pressure. A total of 2693 patients (2145 olmesartan medoxomil; 548 placebo) with essential hypertension were studied. Olmesartan medoxomil once daily lowered diastolic and systolic blood pressure. The response was dose related, as shown in the following graph. An olmesartan medoxomil dose of 20 mg daily produces a trough sitting blood pressure (BP) reduction over placebo of about 10/6 mmHg and a dose of 40 mg daily produces a trough sitting BP reduction over placebo of about 12/7 mmHg. Olmesartan medoxomil doses greater than 40 mg had little additional effect. The onset of the antihypertensive effect occurred within 1 week and was largely manifest after 2 weeks.

olmesartan medoxomil Dose Response: Placebo-adjusted Reduction in Blood Pressure (mm Hg)

Data above are from seven placebo-controlled studies (2145 olmesartan medoxomil patients, 548 placebo patients). The blood pressure lowering effect was maintained throughout the 24-hour period with olmesartan medoxomil once daily, with trough-to-peak ratios for systolic and diastolic response between 60 and 80%.

The blood pressure lowering effect of olmesartan medoxomil, with and without hydrochlorothiazide, was maintained in patients treated for up to 1 year. There was no evidence of tachyphylaxis during long-term treatment with olmesartan medoxomil or rebound effect following abrupt withdrawal of olmesartan medoxomil after 1 year of treatment.

The antihypertensive effect of olmesartan medoxomil was similar in men and women and in patients older and younger than 65 years. The effect was smaller in black patients (usually a low-renin population), as has been seen with ACE inhibitors, beta-blockers and other angiotensin receptor blockers. Olmesartan medoxomil had an additional blood pressure lowering effect when added to hydrochlorothiazide.

There are no trials of olmesartan medoxomil demonstrating reductions in cardiovascular risk in patients with hypertension, but at least one pharmacologically similar drug has demonstrated such benefits.

14.2 Pediatric Hypertension

The antihypertensive effects of olmesartan medoxomil in the pediatric population were evaluated in a randomized, double-blind study involving 302 hypertensive patients aged 6 to 16 years. The study population consisted of an all-black cohort of 112 patients and a mixed racial cohort of 190 patients, including 38 black patients. The etiology of the hypertension was predominantly essential hypertension (87% of the black cohort and 67% of the mixed cohort). Patients who weighed 20 to <35 kg were randomized to 2.5 or 20 mg of olmesartan medoxomil once daily and patients who weighed ≥35 kg were randomized to 5 or 40 mg of olmesartan medoxomil once daily. At the end of 3 weeks, patients were re-randomized to continuing olmesartan medoxomil or to taking placebo for up to 2 weeks. During the initial dose-response phase, olmesartan medoxomil significantly reduced both systolic and diastolic blood pressure in a weight-adjusted, dose-dependent manner. Overall, the two dose levels of olmesartan medoxomil (low and high) significantly reduced systolic blood pressure by 6.6 and 11.9 mmHg from the baseline, respectively. These reductions in systolic blood pressure included both drug and placebo effect. During the randomized withdrawal to placebo phase, mean systolic blood pressure at trough was 3.2 mmHg lower and mean diastolic blood pressure at trough was 2.8 mmHg lower in patients continuing olmesartan medoxomil than in patients withdrawn to placebo. These differences were statistically different. As observed in adult populations, the blood pressure reductions were smaller in black patients.

In the same study, 59 patients aged 1 to 5 years who weighed ≥5 kg received 0.3 mg/kg of olmesartan medoxomil once daily for three weeks in an open-label phase and then were randomized to receiving olmesartan medoxomil or placebo in a double-blind phase. At the end of the second week of withdrawal, the mean systolic/diastolic blood pressure at trough was 3/3 mmHg lower in the group randomized to olmesartan medoxomil; this difference in blood pressure was not statistically significant (95% C.I. -2 to 7/-1 to 7).

16 HOW SUPPLIED/STORAGE AND HANDLING

Olmesartan Medoxomil Tablets, USP supplied as yellow, round, film coated tablets, non-scored tablets containing 5 mg of olmesartan medoxomil, as white, round, film coated, non-scored tablets containing 20 mg of olmesartan medoxomil, and as white, oval-shaped, film coated, non-scored tablets containing 40 mg of olmesartan medoxomil. Tablets are debossed with SG on one side and 339, 340 or 341 on the other side of the 5, 20, and 40 mg tablets, respectively.

Tablets are supplied as follows:

5 mg

20 mg

40 mg

Bottle of 30 NDC 50228-339-30 NDC 50228-340-30 NDC 50228-341-30
Bottle of 90 NDC 50228-339-90 NDC 50228-340-90 NDC 50228-341-90
Bottle of 1000 NDC 50228-339-10 NDC 50228-340-10 NDC 50228-341-10

Storage
Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature].

17 PATIENT COUNSELING INFORMATION

Pregnancy: Advise female patients of childbearing age about the consequences of exposure to olmesartan medoxomil during pregnancy. Discuss treatment options with women planning to become pregnant. Tell patients to report pregnancies to their physicians as soon as possible [see Warnings and Precautions ( 5.1) and Use in Specific Populations ( 8.1)].

Lactation: Advise nursing women not to breastfeed during treatment with olmesartan medoxomil [see Use in Specific Populations ( 8.2)].

Hyperkalemia: Advise patients not to use potassium supplements or salt substitutes that contain potassium without consulting their healthcare provider [see Drug Interactions ( 7.1)].

Manufactured by:
ScieGen Pharmaceuticals, Inc.
Hauppauge, NY 11788 USA

R X only

Rev: 1/2021

Package/Label Principal Display Panel

NDC 50228-339-30

Olmesartan Medoxomil Tablets, USP

5 mg

30 Tablets Rx Only

ScieGen Pharmaceuticals, Inc.

20 mg
(click image for full-size original)

NDC 50228-339-90

Olmesartan Medoxomil Tablets, USP

5 mg

90 Tablets Rx Only

ScieGen Pharmaceuticals, Inc.

5 mg
(click image for full-size original)

NDC 50228-339-10

Olmesartan Medoxomil Tablets, USP

5 mg

1,000 Tablets Rx Only

ScieGen Pharmaceuticals, Inc.

5 mg
(click image for full-size original)

NDC 50228-340-30

Olmesartan Medoxomil Tablets, USP

20 mg

30 Tablets Rx Only

ScieGen Pharmaceuticals, Inc.

5 mg
(click image for full-size original)

NDC 50228-340-90

Olmesartan Medoxomil Tablets, USP

20 mg

90 Tablets Rx Only

ScieGen Pharmaceuticals, Inc.

20 mg
(click image for full-size original)

NDC 50228-340-10

Olmesartan Medoxomil Tablets, USP

20 mg

1,000 Tablets Rx Only

ScieGen Pharmaceuticals, Inc.

20 mg
(click image for full-size original)

NDC 50228-341-30

Olmesartan Medoxomil Tablets, USP

40 mg

30 Tablets Rx Only

ScieGen Pharmaceuticals, Inc.

40 mg
(click image for full-size original)

NDC 50228-341-90

Olmesartan Medoxomil Tablets, USP

40 mg

90 Tablets Rx Only

ScieGen Pharmaceuticals, Inc.

40 mg
(click image for full-size original)

NDC 50228-341-10

Olmesartan Medoxomil Tablets, USP

40 mg

1,000 Tablets Rx Only

ScieGen Pharmaceuticals, Inc.

40 mg
(click image for full-size original)
OLMESARTAN MEDOXOMIL olmesartan medoxomil tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:50228-339
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
OLMESARTAN MEDOXOMIL (OLMESARTAN) OLMESARTAN MEDOXOMIL 5 mg
Inactive Ingredients
Ingredient Name Strength
CROSCARMELLOSE SODIUM
HYPROMELLOSE, UNSPECIFIED
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
POLYETHYLENE GLYCOL 6000
STARCH, CORN
MICROCRYSTALLINE CELLULOSE
TALC
TITANIUM DIOXIDE
FERRIC OXIDE YELLOW
Product Characteristics
Color yellow Score no score
Shape ROUND Size 5mm
Flavor Imprint Code SG;339
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:50228-339-30 30 TABLET, FILM COATED in 1 BOTTLE None
2 NDC:50228-339-90 90 TABLET, FILM COATED in 1 BOTTLE None
3 NDC:50228-339-10 1000 TABLET, FILM COATED in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA208130 06/29/2018
OLMESARTAN MEDOXOMIL olmesartan medoxomil tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:50228-340
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
OLMESARTAN MEDOXOMIL (OLMESARTAN) OLMESARTAN MEDOXOMIL 20 mg
Inactive Ingredients
Ingredient Name Strength
CROSCARMELLOSE SODIUM
HYPROMELLOSE, UNSPECIFIED
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
POLYETHYLENE GLYCOL 6000
STARCH, CORN
MICROCRYSTALLINE CELLULOSE
TALC
TITANIUM DIOXIDE
Product Characteristics
Color white Score no score
Shape ROUND Size 8mm
Flavor Imprint Code SG;340
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:50228-340-30 30 TABLET, FILM COATED in 1 BOTTLE None
2 NDC:50228-340-90 90 TABLET, FILM COATED in 1 BOTTLE None
3 NDC:50228-340-10 1000 TABLET, FILM COATED in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA208130 06/29/2018
OLMESARTAN MEDOXOMIL olmesartan medoxomil tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:50228-341
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
OLMESARTAN MEDOXOMIL (OLMESARTAN) OLMESARTAN MEDOXOMIL 40 mg
Inactive Ingredients
Ingredient Name Strength
CROSCARMELLOSE SODIUM
HYPROMELLOSE, UNSPECIFIED
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
POLYETHYLENE GLYCOL 6000
STARCH, CORN
MICROCRYSTALLINE CELLULOSE
TALC
TITANIUM DIOXIDE
Product Characteristics
Color white Score no score
Shape OVAL Size 15mm
Flavor Imprint Code SG;341
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:50228-341-30 30 TABLET, FILM COATED in 1 BOTTLE None
2 NDC:50228-341-90 90 TABLET, FILM COATED in 1 BOTTLE None
3 NDC:50228-341-10 1000 TABLET, FILM COATED in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA208130 06/29/2018
Labeler — ScieGen Pharmaceuticals, Inc. (079391286)
Registrant — ScieGen Pharmaceuticals, Inc. (079391286)
Establishment
Name Address ID/FEI Operations
ScieGen Pharmaceuticals, Inc. 079391286 analysis (50228-339), analysis (50228-340), analysis (50228-341), manufacture (50228-339), manufacture (50228-340), manufacture (50228-341)

Revised: 01/2021 ScieGen Pharmaceuticals, Inc.

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