PRINZIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PRINZIDE (PRINZIDE).

How it works

PRINZIDE is a combination of lisinopril (an ACE inhibitor) and hydrochlorothiazide (a thiazide diuretic). Lisinopril inhibits angiotensin-converting enzyme, reducing angiotensin II formation, leading to vasodilation and decreased aldosterone secretion. Hydrochlorothiazide inhibits sodium and chloride reabsorption in the distal convoluted tubule, promoting diuresis and reducing plasma volume.

What the body does with it

Metabolism	Lisinopril: minimally metabolized; excreted unchanged in urine. Hydrochlorothiazide: not extensively metabolized; eliminated mainly by renal tubular secretion.
Excretion	Lisinopril is excreted unchanged in urine (100% renal elimination); hydrochlorothiazide is excreted 95% renally as unchanged drug and 5% via bile.
Half-life	Lisinopril: terminal half-life 12 hours (effective half-life 30 hours due to prolonged ACE binding). Hydrochlorothiazide: terminal half-life 6-15 hours (biphasic, initial phase 2-4 h, terminal phase 6-15 h) with prolonged terminal phase in renal impairment.
Protein binding	Lisinopril: 25% bound to plasma proteins. Hydrochlorothiazide: 40-68% bound, primarily to albumin.
Volume of Distribution	Lisinopril: Vd ~2 L/kg (extensive tissue distribution). Hydrochlorothiazide: Vd ~0.8 L/kg (distributes into extracellular fluid; crosses placenta).
Bioavailability	Lisinopril: oral bioavailability 25% (not affected by food). Hydrochlorothiazide: oral bioavailability 65-75% (increases with food due to enhanced absorption).
Onset of Action	Oral: antihypertensive effect occurs within 1 hour for lisinopril, peak at 4-6 hours; diuretic effect for hydrochlorothiazide begins at 2 hours, peak at 4-6 hours.
Duration of Action	Lisinopril: 24 hours (once-daily dosing). Hydrochlorothiazide: 6-12 hours (antihypertensive effect may persist up to 24 hours with chronic use).

Classification & Brands

Dosing & administration

Oral, 1-2 tablets daily; each tablet contains 25 mg hydrochlorothiazide and 5 mg lisinopril. Adjust based on blood pressure response; maximum daily dose: 2 tablets.

Dosage form	TABLET
Renal impairment	CrCl 30-80 mL/min: initial dose 1 tablet daily; CrCl 10-29 mL/min: initial dose 0.5 tablet daily; CrCl <10 mL/min: not recommended.
Liver impairment	Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce initial dose by 50%; Child-Pugh Class C: contraindicated.
Pediatric use	Not recommended for children under 18 years due to lack of safety and efficacy data.
Geriatric use	Start with lower initial dose (0.5 tablet daily) due to age-related decline in renal function and increased sensitivity; monitor electrolytes and renal function closely.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PRINZIDE (PRINZIDE).

Breastfeeding	Hydrochlorothiazide is excreted in breast milk in low amounts (M/P ratio unknown, but estimated 0.1-0.5); lisinopril is excreted in trace amounts. In general, ACE inhibitors are considered compatible with breastfeeding, but caution with hydrochlorothiazide as it may suppress lactation. Monitor infant for hypotension and electrolyte disturbances.
Teratogenic Risk	First trimester: Increased risk of congenital malformations, particularly cardiovascular and central nervous system defects (based on ACE inhibitor class). Second and third trimesters: Fetal renal dysfunction, oligohydramnios, skull ossification defects, hypotension, and anuria; risk of neonatal renal failure and death. Avoid use in pregnancy; discontinue as soon as pregnancy is detected.

Warnings & precautions

■ FDA Black Box Warning

Fetal toxicity: Drugs acting directly on the renin-angiotensin system can cause morbidity and death in the developing fetus. Discontinue as soon as possible when pregnancy is detected.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to lisinopril, hydrochlorothiazide, or sulfonamides","History of ACE inhibitor-induced angioedema","Pregnancy (second and third trimesters)","Anuria","Concomitant use with aliskiren in patients with diabetes mellitus"]

Clinical Precautions

Precautions

["Angioedema (risk increased in black patients, prior history)","Hypotension (especially in volume-depleted patients)","Renal impairment (monitor renal function)","Electrolyte disturbances (hyperkalemia, hyponatremia, hypomagnesemia)","Acute angle-closure glaucoma (sulfonamide-related)"]

Clinical Tips & Counseling

Drug interactions

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PRINZIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PRINZIDE (PRINZIDE).

How it works

What the body does with it

Metabolism	Lisinopril: minimally metabolized; excreted unchanged in urine. Hydrochlorothiazide: not extensively metabolized; eliminated mainly by renal tubular secretion.
Excretion	Lisinopril is excreted unchanged in urine (100% renal elimination); hydrochlorothiazide is excreted 95% renally as unchanged drug and 5% via bile.
Half-life	Lisinopril: terminal half-life 12 hours (effective half-life 30 hours due to prolonged ACE binding). Hydrochlorothiazide: terminal half-life 6-15 hours (biphasic, initial phase 2-4 h, terminal phase 6-15 h) with prolonged terminal phase in renal impairment.
Protein binding	Lisinopril: 25% bound to plasma proteins. Hydrochlorothiazide: 40-68% bound, primarily to albumin.
Volume of Distribution	Lisinopril: Vd ~2 L/kg (extensive tissue distribution). Hydrochlorothiazide: Vd ~0.8 L/kg (distributes into extracellular fluid; crosses placenta).
Bioavailability	Lisinopril: oral bioavailability 25% (not affected by food). Hydrochlorothiazide: oral bioavailability 65-75% (increases with food due to enhanced absorption).
Onset of Action	Oral: antihypertensive effect occurs within 1 hour for lisinopril, peak at 4-6 hours; diuretic effect for hydrochlorothiazide begins at 2 hours, peak at 4-6 hours.
Duration of Action	Lisinopril: 24 hours (once-daily dosing). Hydrochlorothiazide: 6-12 hours (antihypertensive effect may persist up to 24 hours with chronic use).

Classification & Brands

Dosing & administration

Oral, 1-2 tablets daily; each tablet contains 25 mg hydrochlorothiazide and 5 mg lisinopril. Adjust based on blood pressure response; maximum daily dose: 2 tablets.

Dosage form	TABLET
Renal impairment	CrCl 30-80 mL/min: initial dose 1 tablet daily; CrCl 10-29 mL/min: initial dose 0.5 tablet daily; CrCl <10 mL/min: not recommended.
Liver impairment	Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce initial dose by 50%; Child-Pugh Class C: contraindicated.
Pediatric use	Not recommended for children under 18 years due to lack of safety and efficacy data.
Geriatric use	Start with lower initial dose (0.5 tablet daily) due to age-related decline in renal function and increased sensitivity; monitor electrolytes and renal function closely.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for PRINZIDE (PRINZIDE).

Breastfeeding	Hydrochlorothiazide is excreted in breast milk in low amounts (M/P ratio unknown, but estimated 0.1-0.5); lisinopril is excreted in trace amounts. In general, ACE inhibitors are considered compatible with breastfeeding, but caution with hydrochlorothiazide as it may suppress lactation. Monitor infant for hypotension and electrolyte disturbances.
Teratogenic Risk	First trimester: Increased risk of congenital malformations, particularly cardiovascular and central nervous system defects (based on ACE inhibitor class). Second and third trimesters: Fetal renal dysfunction, oligohydramnios, skull ossification defects, hypotension, and anuria; risk of neonatal renal failure and death. Avoid use in pregnancy; discontinue as soon as pregnancy is detected.

Warnings & precautions

■ FDA Black Box Warning

Fetal toxicity: Drugs acting directly on the renin-angiotensin system can cause morbidity and death in the developing fetus. Discontinue as soon as possible when pregnancy is detected.