DESCRIPTION
id: 832e7537-152c-4ac5-b4c9-4f9ea63df6aa
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Lisinopril and hydrochlorothiazide tablets, USP combine an angiotensin converting enzyme inhibitor, lisinopril, and a diuretic, hydrochlorothiazide.
Lisinopril, a synthetic peptide derivative, is an oral long-acting angiotensin converting enzyme inhibitor. It is chemically described as (S)-1-[N
2-(1-carboxy-3-phenylpropyl)-L-lysyl]-L-proline dihydrate. Its molecular formula is C21H31N3O5 • 2H2O and its structural formula is:
Lisinopril, USP is a white to off-white, crystalline powder, with a molecular weight of 441.53. It is soluble in water, sparingly soluble in methanol, and practically insoluble in ethanol.
Hydrochlorothiazide is 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its molecular formula is C7H8ClN3O4S2 and its structural formula is:
Hydrochlorothiazide, USP is a white, or practically white, crystalline powder with a molecular weight of 297.72, which is slightly soluble in water, but freely soluble in sodium hydroxide solution.
Lisinopril and hydrochlorothiazide tablets are available for oral use in three tablet combinations of lisinopril with hydrochlorothiazide: lisinopril and hydrochlorothiazide tablets 10 mg/12.5 mg, containing 10 mg lisinopril and 12.5 mg hydrochlorothiazide, lisinopril and hydrochlorothiazide tablets 20 mg/12.5 mg, containing 20 mg lisinopril and 12.5 mg hydrochlorothiazide and lisinopril and hydrochlorothiazide tablets 20 mg/25 mg, containing 20 mg lisinopril and 25 mg hydrochlorothiazide.
Each tablet for oral administration contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, dibasic calcium phosphate (dihydrate), magnesium stearate, mannitol, microcrystalline cellulose, povidone, pregelatinized starch and sodium lauryl sulfate. In addition, the 20 mg/12.5 mg tablets contain D&C Yellow No. 10 Aluminum Lake and the 20 mg/25 mg tablets contain D&C Yellow No. 10 Aluminum Lake and FD&C Blue No. 2 Aluminum Lake.
Lisinopril and Hydrochlorothiazide Tablets USP, 10 mg/12.5 mg, 20 mg/12.5 mg and 20 mg/25 mg Meet USP Dissolution Test 2.
INDICATIONS AND USAGE
id: bf9580aa-5cd9-411e-806d-81d09bead8a7
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
Lisinopril and hydrochlorothiazide tablets are indicated for the treatment of hypertension to lower blood pressure. Lowering blood pressure lowers the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including lisinopril and hydrochlorothiazide.
Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC).
Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.
Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.
Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (eg, on angina, heart failure or diabetic kidney disease). These considerations may guide selection of therapy.
These fixed dose combinations are not indicated for initial therapy (see DOSAGE AND ADMINISTRATION).
In using lisinopril and hydrochlorothiazide tablets, consideration should be given to the fact that an angiotensin-converting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen vascular disease, and that available data are insufficient to show that lisinopril does not have a similar risk (see WARNINGS).
In considering the use of lisinopril and hydrochlorothiazide tablets, it should be noted that ACE inhibitors have been associated with a higher rate of angioedema in black than in nonblack patients (see WARNINGS: Lisinopril).
CONTRAINDICATIONS
id: 9545bd1f-fd8d-42ca-bfb7-2bfa4d0039f4
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Lisinopril and hydrochlorothiazide tablets are contraindicated in patients who are hypersensitive to this product and in patients with a history of angioedema related to previous treatment with an angiotensin-converting enzyme inhibitor and in patients with hereditary or idiopathic angioedema. Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.
Do not coadminister aliskiren with lisinopril and hydrochlorothiazide in patients with diabetes (see PRECAUTIONS: Drug Interactions).
ADVERSE REACTIONS
id: d8461da0-23f4-4278-842a-5d2437866cef
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
Lisinopril and hydrochlorothiazide has been evaluated for safety in 930 patients including 100 patients treated for 50 weeks or more.
In clinical trials with lisinopril and hydrochlorothiazide no adverse experiences peculiar to this combination drug have been observed. Adverse experiences that have occurred have been limited to those that have been previously reported with lisinopril or hydrochlorothiazide.
The most frequent clinical adverse experiences in controlled trials (including open label extensions) with any combination of lisinopril and hydrochlorothiazide were: dizziness (7.5%), headache (5.2%), cough (3.9%), fatigue (3.7%) and orthostatic effects (3.2%) all of which were more common than in placebo-treated patients. Generally, adverse experiences were mild and transient in nature, but see WARNINGS regarding angioedema and excessive hypotension or syncope. Discontinuation of therapy due to adverse effects was required in 4.4% of patients principally because of dizziness, cough, fatigue and muscle cramps.
Adverse experiences occurring in greater than 1% of patients treated with lisinopril plus hydrochlorothiazide in controlled clinical trials are shown below.
|
Percent of Patients in Controlled Studies
|
|
Lisinopril-Hydrochlorthiazide
(n = 930)
Incidence
(discontinuation)
|
Placebo
(n = 207)
Incidence
|
|
Dizziness
|
7.5 (0.8)
|
1.9
|
|
Headache
|
5.2 (0.3)
|
1.9
|
|
Cough
|
3.9 (0.6)
|
1
|
|
Fatigue
|
3.7 (0.4)
|
1
|
|
Orthostatic Effects
|
3.2 (0.1)
|
1
|
|
Diarrhea
|
2.5 (0.2)
|
2.4
|
|
Nausea
|
2.2 (0.1)
|
2.4
|
|
Upper Respiratory Infection
|
2.2 (0)
|
0
|
|
Muscle Cramps
|
2 (0.4)
|
0.5
|
|
Asthenia
|
1.8 (0.2)
|
1
|
|
Paresthesia
|
1.5 (0.1)
|
0
|
|
Hypotension
|
1.4 (0.3)
|
0.5
|
|
Vomiting
|
1.4 (0.1)
|
0.5
|
|
Dyspepsia
|
1.3 (0)
|
0
|
|
Rash
|
1.2 (0.1)
|
0.5
|
|
Impotence
|
1.2 (0.3)
|
0
|
Clinical adverse experiences occurring in 0.3% to 1% of patients in controlled trials and rarer, serious, possibly drug-related events reported in marketing experience are listed below:
Body as a Whole:
Chest pain, abdominal pain, syncope, chest discomfort, fever, trauma, virus infection.
Cardiovascular:
Palpitation, orthostatic hypotension.
Digestive:
Gastrointestinal cramps, dry mouth, constipation, heartburn.
Musculoskeletal:
Back pain, shoulder pain, knee pain, back strain, myalgia, foot pain.
Nervous/Psychiatric:
Decreased libido, vertigo, depression, somnolence.
Respiratory:
Common cold, nasal congestion, influenza, bronchitis, pharyngeal pain, dyspnea, pulmonary congestion, chronic sinusitis, allergic rhinitis, pharyngeal discomfort.
Skin:
Flushing, pruritus, skin inflammation, diaphoresis, cutaneous pseudolymphoma.
Special Senses:
Blurred vision, tinnitus, otalgia.
Urogenital:
Urinary tract infection.
Angioedema:
Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported (see WARNINGS).
In rare cases, intestinal angioedema has been reported in post marketing experience.
Hypotension:
In clinical trials, adverse effects relating to hypotension occurred as follows: hypotension (1.4%), orthostatic hypotension (0.5%), other orthostatic effects (3.2%). In addition syncope occurred in 0.8% of patients (see WARNINGS).
Cough:
See PRECAUTIONS: General: Lisinopril: Cough
OVERDOSAGE
id: 0e4bf038-2cb3-44ee-8f53-53a078c741ff
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5
No specific information is available on the treatment of overdosage with lisinopril and hydrochlorothiazide. Treatment is symptomatic and supportive. Therapy with lisinopril and hydrochlorothiazide should be discontinued and the patient observed closely. Suggested measures include induction of emesis and/or gastric lavage, and correction of dehydration, electrolyte imbalance and hypotension by established procedures.
DOSAGE AND ADMINISTRATION
id: cf1b36d3-0527-4be0-9bf0-361da12a3533
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
Lisinopril monotherapy is an effective treatment of hypertension in once daily doses of 10 mg to 80 mg, while hydrochlorothiazide monotherapy is effective in doses of 12.5 mg to 50 mg per day. In clinical trials of lisinopril/hydrochlorothiazide combination therapy using lisinopril doses of 10 mg to 80 mg and hydrochlorothiazide doses of 6.25 mg to 50 mg, the antihypertensive response rates generally increased with increasing dose of either component.
The side effects (see WARNINGS) of lisinopril are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of lisinopril and hydrochlorothiazide may be associated with either or both dose-independent or dose-dependent side effects, but addition of lisinopril in clinical trials blunted the hypokalemia normally seen with diuretics.
To minimize dose-dependent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.
HOW SUPPLIED
id: 8440d743-e692-4837-987a-35791b084da4
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Lisinopril and Hydrochlorothiazide Tablets, USP are available containing lisinopril, USP 10 mg and hydrochlorothiazide, USP 12.5 mg, lisinopril, USP 20 mg and hydrochlorothiazide, USP 12.5 mg or lisinopril, USP 20 mg and hydrochlorothiazide, USP 25 mg.
The 10 mg/12.5 mg tablets are white round, unscored tablets debossed with LH1 on one side of the tablet and M on the other side. They are available as follows:
NDC 60429-201-90 bottles of 90 tablets
NDC 60429-201-01 bottles of 100 tablets
NDC 60429-201-10 bottles of 1000 tablets
The 20 mg/12.5 mg tablets are yellow round, unscored tablets debossed with LH2 on one side of the tablet and M on the other side. They are available as follows:
NDC 60429-202-90 bottles of 90 tablets
NDC 60429-202-01 bottles of 100 tablets
NDC 60429-202-10 bottles of 1000 tablets
The 20 mg/25 mg tablets are green round, unscored tablets debossed with LH3 on one side of the tablet and M on the other side. They are available as follows:
NDC 60429-203-90 bottles of 90 tablets
NDC 60429-203-01 bottles of 100 tablets
NDC 60429-203-10 bottles of 1000 tablets
Repackaging Information
id: 5d0b3242-1a78-4cd6-bd76-6247c009530a
displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5
Please reference the
How Supplied
section listed above for a description of individual tablets. This drug product has been received by Aphena Pharma – TN in a manufacturer or distributor packaged configuration and repackaged in full compliance with all applicable cGMP regulations. The package configurations available from Aphena are listed below:
| Count |
10/12.5mg
|
| 30 |
43353-976-30 |
| 90 |
43353-976-60 |
| Count |
20/12.5mg
|
| 90 |
43353-968-60 |
| 180 |
43353-968-80 |
| Count |
20/25mg
|
| 90 |
43353-977-60 |
Store between 20°-25°C (68°-77°F). See USP Controlled Room Temperature. Dispense in a tight light-resistant container as defined by USP. Keep this and all drugs out of the reach of children.
Repackaged by:
Cookeville, TN 38506
20160620DH
