Prinzide Information
Prinzide () Use In Pregnancy
When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus.
WARNINGS, Pregnancy, Lisinopril, Fetal/Neonatal Morbidity and Mortality
Prinzide () Description
Prinzide () (Lisinopril-Hydrochlorothiazide) combines 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 ()-1-[ -(1-carboxy-3-phenylpropyl)-L-lysyl]-L-proline dihydrate. Its empirical formula is CHNO•2HO and its structural formula is:
Lisinopril is a white to off-white, crystalline powder, with a molecular weight of 441.52. It is soluble in water, sparingly soluble in methanol, and practically insoluble in ethanol.
Hydrochlorothiazide is 6-chloro-3,4-dihydro-2-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is CHClNOS and its structural formula is:
Hydrochlorothiazide is a white, or practically white, crystalline powder with a molecular weight of 297.73, which is slightly soluble in water, but freely soluble in sodium hydroxide solution.
Prinzide () is available for oral use in two tablet combinations of lisinopril with hydrochlorothiazide: Prinzide () 10-12.5, containing 10 mg lisinopril and 12.5 mg hydrochlorothiazide and Prinzide () 20-12.5, containing 20 mg lisinopril and 12.5 mg hydrochlorothiazide.
Inactive ingredients are calcium phosphate, magnesium stearate, mannitol, and starch. Prinzide () 10-12.5 also contains FD&C Blue #2 aluminum lake. Prinzide () 20-12.5 also contains iron oxide.
Prinzide () Clinical Pharmacology
As a result of its diuretic effects, hydrochlorothiazide increases plasma renin activity, increases aldosterone secretion, and decreases serum potassium. Administration of lisinopril blocks the renin-angiotensin-aldosterone axis and tends to reverse the potassium loss associated with the diuretic.
In clinical studies, the extent of blood pressure reduction seen with the combination of lisinopril and hydrochlorothiazide was approximately additive. The Prinzide () 10-12.5 combination worked equally well in Black and Caucasian patients. The Prinzide () 20-12.5 and Prinzide () 20-25 (a previously - marketed strength) combinations appeared somewhat less effective in Black patients, but relatively few Black patients were studied. In most patients, the antihypertensive effect of Prinzide () was sustained for at least 24 hours.
In a randomized, controlled comparison, the mean antihypertensive effects of Prinzide () 20-12.5 and Prinzide () 20-25 were similar, suggesting that many patients who respond adequately to the latter combination may be controlled with Prinzide () 20-12.5. (See .)
Concomitant administration of lisinopril and hydrochlorothiazide has little or no effect on the bioavailability of either drug. The combination tablet is bioequivalent to concomitant administration of the separate entities.
The mechanism of the antihypertensive effect of thiazides is unknown. Thiazides do not usually affect normal blood pressure.
Hydrochlorothiazide is a diuretic and antihypertensive. It affects the distal renal tubular mechanism of electrolyte reabsorption. Hydrochlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate.
After oral use diuresis begins within two hours, peaks in about four hours and lasts about 6 to 12 hours.
Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. When plasma levels have been followed for at least 24 hours, the plasma half-life has been observed to vary between 5.6 and 14.8 hours. At least 61 percent of the oral dose is eliminated unchanged within 24 hours. Hydrochlorothiazide crosses the placental but not the blood-brain barrier.
Prinzide () Indications And Usage
Prinzide () is indicated for the treatment of hypertension.
These fixed-dose combinations are not indicated for initial therapy (see ).
In using Prinzide () , 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 .)
In considering use of Prinzide () , it should be noted that Black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to non-Blacks. (See .)
Prinzide () Contraindications
Prinzide () is contraindicated in patients who are hypersensitive to any component of 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.
Prinzide () Precautions
Pregnancy Categories C
and D
WARNINGS, Pregnancy, Lisinopril, Fetal/Neonatal Morbidity and Mortality
Clinical studies of Prinzide () did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. In a multiple-dose pharmacokinetic study in elderly versus young hypertensive patients using the lisinopril/hydrochlorothiazide combination, area under the plasma concentration time curve (AUC) increased approximately 120% for lisinopril and approximately 80% for hydrochlorothiazide in older patients.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Evaluation of the hypertensive patient should always include assessment of renal function. (See .)
Prinzide () Adverse Reactions
Prinzide () has been evaluated for safety in 930 patients, including 100 patients treated for 50 weeks or more.
In clinical trials with Prinzide () 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 percent), headache (5.2 percent), cough (3.9 percent), fatigue (3.7 percent) and orthostatic effects (3.2 percent), all of which were more common than in placebo-treated patients. Generally, adverse experiences were mild and transient in nature; but see regarding angioedema and excessive hypotension or syncope. Discontinuation of therapy due to adverse effects was required in 4.4 percent of patients, principally because of dizziness, cough, fatigue and muscle cramps.
Adverse experiences occurring in greater than one percent of patients treated with lisinopril plus hydrochlorothiazide in controlled clinical trials are shown below.
Clinical adverse experiences occurring in 0.3 to 1.0 percent of patients in controlled trials included: Chest pain, abdominal pain, syncope, chest discomfort, fever, trauma, virus infection. Palpitation, orthostatic hypotension. Gastrointestinal cramps, dry mouth, constipation, heartburn. Back pain, shoulder pain, knee pain, back strain, myalgia, foot pain. Decreased libido, vertigo, depression, somnolence. Common cold, nasal congestion, influenza, bronchitis, pharyngeal pain, dyspnea, pulmonary congestion, chronic sinusitis, allergic rhinitis, pharyngeal discomfort. Flushing, pruritus, skin inflammation, diaphoresis. Blurred vision, tinnitus, otalgia. Urinary tract infection.
Prinzide () Overdosage
No specific information is available on the treatment of overdosage with Prinzide () . Treatment is symptomatic and supportive. Therapy with Prinzide () 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.
Following a single oral dose of 20 mg/kg, no lethality occurred in rats and death occurred in one of 20 mice receiving the same dose. The most likely manifestation of overdosage would be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution.
Lisinopril can be removed by hemodialysis. (See .)
Prinzide () Dosage And Administration
Lisinopril is an effective treatment of hypertension in once-daily doses of 10-80 mg, while hydrochlorothiazide is effective in doses of 12.5-50 mg. In clinical trials of lisinopril/hydrochlorothiazide combination therapy using lisinopril doses of 10-80 mg and hydrochlorothiazide doses of 6.25-50 mg, the antihypertensive response rates generally increased with increasing dose of either component.
The side effects (see ) 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 will be associated with both sets of dose-independent side effects, but addition of lisinopril in clinical trials blunted the hypokalemia normally seen with diuretics.
To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.
Prinzide () How Supplied
No. 8439 — Tablets Prinzide () 10-12.5, are blue, hexagon-shaped tablets with code 145 on one side and plain on the other side. Each tablet contains 10 mg of lisinopril and 12.5 mg of hydrochlorothiazide. They are supplied as follows:
No. 8247 — Tablets Prinzide () 20-12.5, are yellow, hexagon-shaped tablets with code MSD/140 on one side and scored on the other side. Each tablet contains 20 mg of lisinopril and 12.5 mg of hydrochlorothiazide. They are supplied as follows:
Prinzide ()
Prinzide () Principal Display Panel - Bottle Label -.
Prinzide () 10-12.5(Lisinopril-Hydrochlorothiazide)
Manuf. for: Merck Sharp & Dohme Corp., a subsidiary ofMERCK & CO., INC.Whitehouse Station, NJ 08889, USA
by:MERCK SHARP & DOHME LTD.Cramlington, Northumberland, UK NE23 3JUMade in UK
Each tablet contains 10 mg lisinopril and 12.5 mg hydrochlorothiazide.
100 Tablets
NDC 0006-0145-58
Store at controlled room temperature, 15-30°C (59-86°F). Protect from excessive light and humidity.
USUAL ADULT DOSAGE: See accompanying circular.
Rx only
7001165600100 | No. 8439
Prinzide () Principal Display Panel - Bottle Label -.
Prinzide () 20-12.5(Lisinopril-Hydrochlorothiazide)
Manuf. for: Merck Sharp & Dohme Corp., a subsidiary ofMERCK & CO., INC.Whitehouse Station, NJ 08889, USA
by:MERCK SHARP & DOHME LTD.Cramlington, Northumberland, UK NE23 3JUMade in UK
Each tablet contains 20 mg lisinopril and 12.5 mg hydrochlorothiazide.
100 Tablets
NDC 0006-0140-58
Store at controlled room temperature, 15-30°C (59-86°F). Protect from excessive light and humidity.
USUAL ADULT DOSAGE: See accompanying circular.
Rx only
7001165700100 | No. 8247
