Lotrel amlodipine besylate and benazepril hydrochloride 5 mg; 20 mg Capsule, 100-count
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Dihydropyridine Calcium Channel Blocker class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
The combination of amlodipine and benazepril is used to treat high blood pressure. Amlodipine is in a class of medications called calcium channel blockers. It works by relaxing the blood vessels so the heart does not have to pump as hard. Benazepril is in a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals that tighten the blood vessels, so blood flows more smoothly. High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to...
Read the full MedlinePlus article ↗- Yes, it's very common. Many people need more than one medicine to get their blood pressure under good control. Amlodipine and benazepril work through two completely different pathw...
- Why am I taking two blood pressure medicines in one pill? Is that normal?
- Yes, a dry persistent cough is a well-known side effect of ACE inhibitors like benazepril, the second ingredient in this combination. It's not dangerous, but it can be annoying. Do...
- I've developed a dry, nagging cough since starting this medicine. Is that normal?
Patient education
Supplement & herbal interactions
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
Where does this data come from?
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII 97Z1WI3NDX
A mineral compound of calcium and phosphorus that acts as a filler and binding agent in tablets and capsules. It helps give the medicine its solid shape and may improve how well ingredients blend together.
-
UNII 68401960MK
Crospovidone is a synthetic polymer made from polyvinylpyrrolidone. It acts as a disintegrant, helping tablets break apart quickly in the stomach so the medicine dissolves and absorbs into the body.
-
UNII 1K09F3G675
Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
-
UNII 2G86QN327L
Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
-
UNII ZF94AP8MEY
Hydrogenated castor oil is a processed plant oil made by adding hydrogen to castor oil. It's used as a binder to help hold tablet ingredients together and as a lubricant to prevent sticking during manufacturing.
-
UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
-
UNII J2B2A4N98G
Lactose is a natural sugar derived from milk. In medications, it serves as a filler and binder to add bulk and help hold tablet or capsule ingredients together during manufacturing.
-
UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
-
UNII 6OZP39ZG8H
Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
-
UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
-
UNII 368GB5141J
A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
-
UNII 5856J3G2A2
A starch-based powder made from potatoes and processed with sodium. It acts as a disintegrant, helping the tablet or capsule break apart quickly in the stomach so the medicine can be absorbed.
-
UNII O8232NY3SJ
A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
-
UNII 7SEV7J4R1U
A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
-
UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
15 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $12.208 | $1,220.80 / 100 capsules |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Amlodipine and Benazepril Hydrochloride 5 mg/1; 20 mg 23155-0922-01 | Heritage | 100 capsules | $0.104 | AB | Availability likely | save 99% |
| Amlodipine Besylate and Benazepril Hydrochloride 5 mg/1; 20 mg 55111-0340-01 | Dr.Reddy's | 100 capsules | $0.104 | AB | Availability likely | save 99% |
| Amlodipine and Benazepril Hydrochloride 5 mg/1; 20 mg 57237-0144-01 | Rising | 100 capsules | $0.104 | AB | Availability likely | save 99% |
| Amlodipine and Benazepril Hydrochloride 5 mg/1; 20 mg 65862-0584-01 | Aurobindo | 100 capsules | $0.104 | AB | Availability likely | save 99% |
| Amlodipine Besylate and Benazepril Hydrochloride 5 mg/1; 20 mg 68001-0134-00 | BluePoint | 100 capsules | $0.104 | AB | Availability likely | save 99% |
| Amlodipine Besylate and Benazepril Hydrochloride 5 mg/1; 20 mg 68180-0459-01 | Lupin | 100 capsules | $0.104 | AB | Availability likely | save 99% |
| Lotrel 5 mg/1; 20 mgthis 00078-0406-05 | Novartis | 100 capsules | $12.208 | — | Discontinued | — |
| Amlodipine and Benazepril Hydrochloride 5 mg/1; 20 mg 50090-1042-00 | A-S | 30 capsules | — | AB | FDA listed | — |
| Amlodipine and Benazepril Hydrochloride 5 mg/1; 20 mg 50090-4284-00 | A-S | 30 capsules | — | AB | FDA listed | — |
| Amlodipine Besylate and Benazepril Hydrochloride 5 mg/1; 20 mg 50090-6185-00 | A-S | 30 capsules | — | AB | FDA listed | — |
| Amlodipine Besylate and Benazepril Hydrochloride 20 mg/1; 5 mg 51655-0201-52 | Northwind | 30 capsules | — | AB | FDA listed | — |
| Amlodipine Besylate and Benazepril Hydrochloride 5 mg/1; 20 mg 68180-0757-01 | Lupin | 100 capsules | — | AB | FDA listed | — |
| Amlodipine Besylate and Benazepril Hydrochloride 5 mg/1; 20 mg 69238-2686-01 | Amneal | 100 capsules | — | — | FDA listed | — |
| Amlodipine Besylate and Benazepril Hydrochloride 5 mg/1; 20 mg 70518-4386-00 | REMEDYREPACK | 90 capsules | — | AB | FDA listed | — |
| Amlodipine and Benazepril Hydrochloride 5 mg/1; 20 mg 71205-0122-30 | Proficient | 30 capsules | — | AB | FDA listed | — |
| Amlodipine and Benazepril Hydrochloride 5 mg/1; 20 mg 71335-0953-01 | Bryant | 30 capsules | — | AB | Discontinued | — |
| Amlodipine Besylate and Benazepril Hydrochloride 5 mg/1; 20 mg 71335-1946-01 | Bryant | 30 capsules | — | AB | FDA listed | — |
| Amlodipine Besylate and Benazepril Hydrochloride 5 mg/1; 20 mg 71335-3095-01 | Bryant | 30 capsules | — | AB | FDA listed | — |
| Amlodipine and Benazepril Hydrochloride 5 mg/1; 20 mg 72162-2360-01 | Bryant | 100 capsules | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.
Where does this data come from?
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00078-0406-05 You're viewing this | 100 CAPSULE in 1 BOTTLE (0078-0406-05) | 1995-03-03 | Discontinued by firm |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | ✓ Available |
| Orange Book / therapeutic-equivalence data | — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope. |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
What does the discontinued status mean for this NDC?
Is the NDC printed on the package the same as the 11-digit billing NDC?
What do the three segments of this NDC mean?
Who lists this product with the FDA?
Do I need a prescription for this product?
Where does this data come from?
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: FETAL TOXICITY When pregnancy is detected, discontinue Lotrel as soon as possible ( 5.1 ). Drugs that act directly on the renin-angiotensin system (RAS) can cause injury and death to the developing fetus ( 5.1 ). WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning.
When pregnancy is detected, discontinue Lotrel as soon as possible ( 5.1 ). Drugs that act directly on the renin-angiotensin system (RAS) can cause injury and death to the developing fetus ( 5.1 ).
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Lotrel is a combination capsule of amlodipine, a dihydropyridine calcium channel blocker (DHP CCB) and benazepril, an angiotensin-converting enzyme (ACE) inhibitor. Lotrel is indicated for the treatment of hypertension in patients not adequately controlled on monotherapy with either agent. ( 1 )
1.1Hypertension Lotrel is indicated for the treatment of hypertension in patients not adequately controlled on monotherapy with either agent.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • Usual starting dose is 2.5/10 mg. ( 2.1 ) • May be used as add-on therapy for patients not adequately controlled with either a dihydropyridine calcium channel blocker or an ACE inhibitor ( 2.2 ) • Patients who experience edema with amlodipine may be switched to Lotrel containing a lower dose of amlodipine. ( 2.1 )
2.1General Considerations The recommended initial dose is amlodipine 2.5 mg/benazepril 10 mg orally once-daily. Begin therapy with Lotrel only after a patient has either (a) failed to achieve the desired antihypertensive effect with amlodipine or benazepril monotherapy, or (b) demonstrated inability to achieve adequate antihypertensive effect with amlodipine therapy without developing edema. The antihypertensive effect of Lotrel is largely attained within 2 weeks.
If blood pressure remains uncontrolled, the dose may be titrated up to amlodipine 10 mg/benazepril 40 mg once-daily. The dosing should be individualized and adjusted according to the patient’s clinical response. In clinical trials of amlodipine/benazepril combination therapy using amlodipine doses of 2.5 to 10 mg and benazepril doses of 10 to 40 mg, the antihypertensive effects increased with increasing dose of amlodipine in all patient groups, and the effects increased with increasing dose of benazepril in nonblack groups.
2.2Replacement Therapy Lotrel may be substituted for the titrated components.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Lotrel (amlodipine/benazepril hydrochloride) capsules are available as follows: 5/10 mg, 5/20 mg, 10/20 mg, and 10/40 mg. Capsules (amlodipine/benazepril hydrochloride mg): 5/10, 5/20, 10/20, 10/40 ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS 1. Do not coadminister aliskiren with angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, including Lotrel in patients with diabetes. 2.
Lotrel is contraindicated in patients with a history of angioedema, with or without previous ACE inhibitor treatment, or patients who are hypersensitive to benazepril, to any other ACE inhibitor, to amlodipine, or to any of the excipients of Lotrel. 3. Lotrel is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril).
Do not administer Lotrel within 36 hours of switching to or from a neprilysin inhibitor, e.g., sacubitril/valsartan [see Warnings and Precautions (5.1)] . 4. Do not coadminister aliskiren with ACE inhibitors, including Lotrel, in patients with diabetes.
( 4 ) 5. Lotrel is contraindicated in patients with a history of angioedema or patients who are hypersensitive to benazepril or to amlodipine. ( 4 ) 6.
Lotrel is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer Lotrel within 36 hours of switching to or from a neprilysin inhibitor, e.g., sacubitril/valsartan. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Anaphylactoid reactions, including angioedema ( 5.2 ) • Myocardial infarction or increased angina in patients with obstructive coronary artery disease. ( 5.3 ) • Assess for hypotension and hyperkalemia. ( 5.4 , 5.6 ) • Titrate slowly in patients with impaired hepatic or severely impaired renal function. ( 5.5 , 5.7 )
5.1Fetal Toxicity Lotrel can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations.
Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Lotrel as soon as possible [see Use in Specific Populations (8.1)] .
5.2Angioedema and Anaphylactoid Reactions Head and Neck Angioedema: Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with benazepril. This may occur at any time during treatment. Angioedema associated with edema of the larynx, tongue, or glottis can compromise the airway and be fatal.
If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, discontinue treatment with Lotrel and treat immediately. When involvement of the tongue, glottis, or larynx appears likely to cause airway obstruction, appropriate therapy, e.g., administer subcutaneous epinephrine injection 1:1000 (0.3 to 0.5 mL), promptly [see Adverse Reactions (6)] . Patients with a history of angioedema may be at increased risk for angioedema while receiving Lotrel.
Black patients receiving ACE inhibitors have a higher incidence of angioedema compared to nonblacks. Patients receiving coadministration of ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g., temsirolimus, sirolimus, everolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema [see Drug Interactions (7)] . Intestinal Angioedema: Intestinal angioedema has been reported in patients treated with ACE inhibitors.
These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.
Anaphylactoid Reactions During Desensitization: Two patients undergoing desensitizing treatment with hymenoptera (wasp sting) venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. Anaphylactoid Reactions During Membrane Exposure: Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes and treated concomitantly with an ACE inhibitor. Anaphylactoid reactions have also been reported in patients undergoing low-density lipoprotein apheresis with dextran sulfate absorption.
5.3Increased Angina and/or Myocardial Infarction Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease.
5.4Hypotension Lotrel can cause symptomatic hypotension, sometimes complicated by oliguria, progressive azotemia, acute renal failure, or death. Symptomatic hypotension is most likely to occur in patients who have heart failure, severe aortic or mitral stenosis, obstructive hypertrophic cardiomyopathy or have been volume or salt depleted as a result of diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. Correct volume and salt depletion before starting therapy with benazepril.
If hypotension occurs, place the p…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Discontinuation because of adverse reactions occurred in 4% of Lotrel-treated patients and 3% of placebo-treated patients. The most common reasons for discontinuation of therapy with Lotrel were cough and edema. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates. Lotrel has been evaluated for safety in over 2,991 patients with hypertension; over 500 of these patients were treated for at least 6 months, and over 400 were treated for more than 1 year.
In a pooled analysis of 5 placebo-controlled trials involving Lotrel doses up to 5/20, the reported side effects were generally mild and transient, and there was no relationship between side effects and age, sex, race, or duration of therapy. Discontinuation of therapy due to side effects was required in approximately 4% of patients treated with Lotrel and in 3% of patients treated with placebo. The most common reasons for discontinuation of therapy with Lotrel in these studies were cough and edema (including angioedema).
The peripheral edema associated with amlodipine use is dose-dependent. When benazepril is added to a regimen of amlodipine, the incidence of edema is substantially reduced. The addition of benazepril to a regimen of amlodipine should not be expected to provide additional antihypertensive effect in African-Americans.
However, all patient groups benefit from the reduction in amlodipine-induced edema. The side effects considered possibly or probably related to study drug that occurred in these trials in more than 1% of patients treated with Lotrel are shown in the table below. Cough was the only adverse event with at least possible relationship to treatment that was more common on Lotrel (3.3%) than on placebo (0.2%).
Percent Incidence in U. S. Placebo-controlled Trials *Edema refers to all edema, such as dependent edema, angioedema, facial edema.
Benazepril/Amlodipine Benazepril Amlodipine Placebo N = 760 N = 554 N = 475 N = 408 Cough 3.3 1.8 0.4
0.2Headache 2.2 3.8 2.9
5.6Dizziness 1.3 1.6 2.3
1.5Edema* 2.1 0.9 5.1
2.2The incidence of edema was greater in patients treated with amlodipine monotherapy (5.1%) than in patients treated with Lotrel (2.1%) or placebo (2.2%). Other side effects considered possibly or probably related to study drug that occurred in U.S. placebo-controlled trials of patients treated with Lotrel or in postmarketing experience were the following: Body as a Whole: Asthenia and fatigue. CNS: Insomnia, nervousness, anxiety, tremor, and decreased libido.
Dermatologic: Flushing, hot flashes, rash, skin nodule, and dermatitis. Digestive: Dry mouth, nausea, abdominal pain, dyspepsia, and esophagitis. Hematologic: Neutropenia Musculoskeletal: cramps, and muscle cramps.
Urogenital: Sexual problems, such as impotence, and polyuria. Monotherapies of benazepril and amlodipine have been evaluated for safety in clinical trials in over 6,000 and 11,000 patients, respectively. The observed adverse reactions to the monotherapies in these trials were similar to those seen in trials of Lotrel.
6.2Postmarketing Experience Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. In postmarketing experience with benazepril, there have been rare reports of Stevens-Johnson syndrome, pancreatitis, hemolytic anemia, pemphi…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS • Potassium supplements/potassium-sparing diuretics: hyperkalemia ( 7.1 ) • Lithium: Increased serum lithium levels; toxicity symptoms ( 7.1 ) • Injectable gold: facial flushing, nausea, vomiting, hypotension ( 7.1 ) • Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Risk of renal dysfunction, loss of antihypertensive effect ( 7.1 ) • Do not exceed doses greater than 20 mg daily of simvastatin ( 7.1 ) • mTOR inhibitors: increased risk of angioedema ( 7.1 ) • Dual inhibition of the RAS: Increased risk of renal impairment, hypotension, and hyperkalemia ( 7.1 ) • Neprilysin inhibitors: increased risk of angioedema ( 7.1 )
7.1Drug/Drug Interactions Amlodipine Simvastatin: Coadministration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily. CYP3A4 Inhibitors: Coadministration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction.
Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A4 inhibitors to determine the need for dose adjustment. CYP3A4 Inducers: No information is available on the quantitative effects of CYP3A4 inducers on amlodipine. Blood pressure should be monitored when amlodipine is coadministered with CYP3A4 inducers (e.g. rifampicin, St.
John’s Wort). Benazepril Potassium Supplements and Potassium-Sparing Diuretics: Benazepril can attenuate potassium loss caused by thiazide diuretics. Potassium-sparing diuretics (spironolactone, amiloride, triamterene, and others) or potassium supplements can increase the risk of hyperkalemia.
If concomitant use of such agents is indicated, the patient’s serum potassium should be monitored frequently. Lithium: Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium. When coadministering Lotrel and lithium, frequent monitoring of serum lithium levels is recommended.
Gold: Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors): In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, including benazepril, may result in deterioration of renal function, including possible acute renal failure.
These effects are usually reversible. Monitor renal function periodically in patients receiving benazepril and NSAID therapy. The antihypertensive effect of ACE inhibitors, including benazepril, may be attenuated by NSAIDs.
Antidiabetic Agents: In rare cases, diabetic patients receiving an ACE inhibitor (including benazepril) concomitantly with insulin or oral antidiabetics may develop hypoglycemia. Such patients should therefore be advised about the possibility of hypoglycemic reactions and should be monitored accordingly. Mammalian Target of Rapamycin (mTOR) Inhibitors: The risk of angioedema may be increased in patients receiving coadministration of ACE inhibitors and mTOR inhibitors (e.g., temsirolimus, sirolimus, everolimus).
Dual Blockade of the Renin-Angiotensin System (RAS): Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors.
Closely monitor blood pressure, renal function and electrolytes in patient…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary Lotrel can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the RAS during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the RAS from other antihypertensive agents.
When pregnancy is detected, discontinue Lotrel as soon as possible. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death.
Pregnant women with hypertension should be carefully monitored and managed accordingly. Fetal/Neonatal Adverse Reactions Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death. Perform serial ultrasound examinations to assess the intra-amniotic environment.
Fetal testing may be appropriate, based on the week of gestation. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. If oligohydramnios is observed, consider alternative drug treatment.
Closely observe neonates with histories of in utero exposure to Lotrel for hypotension, oliguria, and hyperkalemia. In neonates with a history of in utero exposure to Lotrel, if oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function.
Data Animal Data Benazepril and Amlodipine: When rats received benazepril:amlodipine at doses ranging from 5:2.5 to 50:25 mg/kg/day, dystocia was observed at an increasing dose-related incidence at all doses tested. On a body surface area basis, the 2.5 mg/kg/day dose of amlodipine is twice the amlodipine dose delivered when the maximum recommended dose of Lotrel is given to a 60 kg patient. Similarly, the 5 mg/kg/day dose of benazepril is approximately equivalent with the benazepril dose delivered when the maximum recommended dose of Lotrel is given to a 60 kg patient.
No teratogenic effects were seen when benazepril and amlodipine were administered in combination to pregnant rats or rabbits. Rats received doses of up to 50:25 mg (benazepril:amlodipine)/kg/day (12 times the MRHD on a body surface area basis, assuming a 60 kg patient). Rabbits received doses of up to 1.5:0.75 mg/kg/day (equivalent to the maximum recommended dose of Lotrel given to a 60 kg patient).
8.2Lactation Risk Summary Minimal amounts of unchanged benazepril and of benazeprilat are excreted into the breast milk of lactating women treated with benazepril, so that a newborn child ingesting nothing but breast milk would receive less than 0.1% of the maternal doses of benazepril and benazeprilat. Limited available data from a published clinical lactation study reports that amlodipine is present in human milk at an estimated median relative infant dose of 4.2%. No adverse effects of amlodipine on the breastfed infant…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Lotrel can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the RAS during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the RAS from other antihypertensive agents.
When pregnancy is detected, discontinue Lotrel as soon as possible. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death.
Pregnant women with hypertension should be carefully monitored and managed accordingly. Fetal/Neonatal Adverse Reactions Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death. Perform serial ultrasound examinations to assess the intra-amniotic environment.
Fetal testing may be appropriate, based on the week of gestation. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. If oligohydramnios is observed, consider alternative drug treatment.
Closely observe neonates with histories of in utero exposure to Lotrel for hypotension, oliguria, and hyperkalemia. In neonates with a history of in utero exposure to Lotrel, if oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function.
Data Animal Data Benazepril and Amlodipine: When rats received benazepril:amlodipine at doses ranging from 5:2.5 to 50:25 mg/kg/day, dystocia was observed at an increasing dose-related incidence at all doses tested. On a body surface area basis, the 2.5 mg/kg/day dose of amlodipine is twice the amlodipine dose delivered when the maximum recommended dose of Lotrel is given to a 60 kg patient. Similarly, the 5 mg/kg/day dose of benazepril is approximately equivalent with the benazepril dose delivered when the maximum recommended dose of Lotrel is given to a 60 kg patient.
No teratogenic effects were seen when benazepril and amlodipine were administered in combination to pregnant rats or rabbits. Rats received doses of up to 50:25 mg (benazepril:amlodipine)/kg/day (12 times the MRHD on a body surface area basis, assuming a 60 kg patient). Rabbits received doses of up to 1.5:0.75 mg/kg/day (equivalent to the maximum recommended dose of Lotrel given to a 60 kg patient).
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use In geriatric patients, exposure to amlodipine is increased, thus consider lower initial doses of Lotrel [see Clinical Pharmacology (12.3)] . Of the total number of patients who received Lotrel in U.S. clinical studies of Lotrel, over 19% were 65 years or older while about 2% were 75 years or older. Overall differences in effectiveness or safety were not observed between these patients and younger patients.
Clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
🆘 Overdosage ▾
10 OVERDOSAGE Only a few cases of human overdose with amlodipine have been reported. One patient was asymptomatic after a 250 mg ingestion; another, who combined 70 mg of amlodipine with an unknown large quantity of a benzodiazepine, developed refractory shock and died. Human overdoses with any combination of amlodipine and benazepril have not been reported.
In scattered reports of human overdoses with benazepril and other ACE inhibitors, there are no reports of death. Treatment: Patients should be admitted to hospital and, generally, should be managed in an intensive care setting, with continuous monitoring of cardiac function, blood gases, and blood biochemistry. Emergency supportive measures such as artificial ventilation or cardiac pacing should be instituted if appropriate.
In the event of a potentially life-threatening oral overdose, use induction of vomiting or gastric lavage and/or activated charcoal to remove the drug from the gastrointestinal tract (only if presented within 1 hour after ingestion of Lotrel). Other clinical manifestations of overdose should be managed symptomatically based on modern methods of intensive care. To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison-Control Center.
Telephone numbers of certified poison-control centers are listed in the Physicians’ Desk Reference (PDR). In managing overdose, consider the possibilities of multiple-drug overdoses, drug-drug interactions, and unusual drug kinetics in your patient. The most likely effect of overdose with Lotrel is vasodilation, with consequent hypotension and tachycardia.
Simple repletion of central fluid volume (Trendelenburg positioning, infusion of crystalloids) may be sufficient therapy, but pressor agents (norepinephrine or high-dose dopamine) may be required. With abrupt return of peripheral vascular tone, overdoses of other dihydropyridine calcium channel blockers have sometimes progressed to pulmonary edema, and patients must be monitored for this complication. Analyses of bodily fluids for concentrations of amlodipine, benazepril, or their metabolites are not widely available.
Such analyses are, in any event, not known to be of value in therapy or prognosis. No data are available to suggest physiologic maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of amlodipine, benazepril, or their metabolites. Benazeprilat is only slightly dialyzable; attempted clearance of amlodipine by hemodialysis or hemo-perfusion has not been reported, but amlodipine’s high protein binding makes it unlikely that these interventions will be of value.
Angiotensin II could presumably serve as a specific antagonist-antidote to benazepril, but angiotensin II is essentially unavailable outside of scattered research laboratories.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Benazepril Benazepril and benazeprilat inhibit ACE in human subjects and in animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex.
Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion. The latter decrease may result in a small increase of serum potassium. Hypertensive patients treated with benazepril and amlodipine for up to 56 weeks had elevations of serum potassium up to 0.2 mEq/L [see Warnings and Precautions (5.6)] .
Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity. In animal studies, benazepril had no inhibitory effect on the vasopressor response to angiotensin II and did not interfere with the hemodynamic effects of the autonomic neurotransmitters acetylcholine, epinephrine, and norepinephrine. ACE is identical to kininase, an enzyme that degrades bradykinin.
Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of Lotrel remains to be elucidated. While the mechanism through which benazepril lowers blood pressure is believed to be primarily suppression of the renin-angiotensin aldosterone system, benazepril has an antihypertensive effect even in patients with low-renin hypertension. Amlodipine Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle.
Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells.
Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa = 8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect.
Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.
12.2Pharmacodynamics Benazepril Single and multiple doses of 10 mg or more of benazepril cause inhibition of plasma ACE activity by at least 80% to 90% for at least 24 hours after dosing. For up to 4 hours after a 10 mg dose, pressor responses to exogenous angiotensin I were inhibited by 60% to 90%. Administration of benazepril to patients with mild-to-moderate hypertension results in a reduction of both supine and standing blood pressure to about the same extent, with no compensatory tachycardia.
Symptomatic postural hypotension is infrequent, although it can occur in patients who are salt and/or volume depleted [see Warnings and Precautions (5.4)] . The antihypertensive effects of benazepril were not appreciably different in patients receiving high- or low-sodium diets. In normal human volunteers, single doses of benazepril caused an increase in renal blood flow but had no effect on glomerular filtration rate.
Amlodipine Following administration of therapeutic doses to patients with hypertension, amlodipine produces vasodilation resulting in a reduction of supine and standing blood pressures. These decreases in blood pressure are not accompanied by…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Benazepril Benazepril and benazeprilat inhibit ACE in human subjects and in animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex.
Inhibition of ACE results in decreased plasma angiotensin II, which leads to decreased vasopressor activity and to decreased aldosterone secretion. The latter decrease may result in a small increase of serum potassium. Hypertensive patients treated with benazepril and amlodipine for up to 56 weeks had elevations of serum potassium up to 0.2 mEq/L [see Warnings and Precautions (5.6)] .
Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity. In animal studies, benazepril had no inhibitory effect on the vasopressor response to angiotensin II and did not interfere with the hemodynamic effects of the autonomic neurotransmitters acetylcholine, epinephrine, and norepinephrine. ACE is identical to kininase, an enzyme that degrades bradykinin.
Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of Lotrel remains to be elucidated. While the mechanism through which benazepril lowers blood pressure is believed to be primarily suppression of the renin-angiotensin aldosterone system, benazepril has an antihypertensive effect even in patients with low-renin hypertension. Amlodipine Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle.
Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells.
Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa = 8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect.
Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Lotrel is available as capsules containing amlodipine besylate (6.9 mg or 13.9 mg, equivalent to 5 mg or 10 mg of amlodipine respectively), with 10 mg, 20 mg, or 40 mg of benazepril hydrochloride providing for the following available combinations: 5/10 mg, 5/20 mg, 10/20 mg, and 10/40 mg. All strengths are packaged in bottles of 100 capsules. Capsules are imprinted with “Lotrel” and appropriate code.
Dose Capsule Color/Code NDC Code Bottle of 100 5/10 mg light brown with 2 white bands/2260 NDC 0078-0405-05 5/20 mg pink with 2 white bands/2265 NDC 0078-0406-05 10/20 mg purple (amethyst) with 2 white bands/0364 NDC 0078-0364-05 10/40 mg dark blue with 2 white bands/0379 NDC 0078-0379-05 Storage: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). [See USP controlled room temperature]. Protect from moisture. Dispense in tight container (USP).
📋 Description ▾
11 DESCRIPTION Lotrel is a combination of amlodipine besylate and benazepril hydrochloride. Benazepril hydrochloride is a white to off-white crystalline powder, soluble (greater than 100 mg/mL) in water, in ethanol, and in methanol. Benazepril hydrochloride’s chemical name is 3-[[1-(ethoxycarbonyl)-3-phenyl-(1S)-propyl]amino]-2,3,4,5-tetrahydro-2-oxo-1 H -1-(3S)-benzazepine-1-acetic acid monohydrochloride; its structural formula is: Its empirical formula is C 24 H 28 N 2 O 5 •HCl, and its molecular weight is 460.96.
Benazeprilat, the active metabolite of benazepril, is a nonsulfhydryl ACE inhibitor. Benazepril is converted to benazeprilat by hepatic cleavage of the ester group. Amlodipine besylate is a white to pale yellow crystalline powder, slightly soluble in water and sparingly soluble in ethanol.
Its chemical name is (R,S)3-ethyl-5-methyl-2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate benzenesulfonate; its structural formula is: Its empirical formula is C 20 H 25 ClN 2 O 5 •C 6 H 6 O 3 S, and its molecular weight is 567.1. Amlodipine besylate is the besylate salt of amlodipine, a dihydropyridine calcium channel blocker. Lotrel is available as capsules containing amlodipine besylate (6.9 mg or 13.9 mg, equivalent to 5 mg or 10 mg of amlodipine respectively), with 10 mg, 20 mg, or 40 mg of benazepril hydrochloride providing for the following available combinations: 5/10 mg, 5/20 mg, 10/20 mg, and 10/40 mg.
The inactive ingredients of the capsules are calcium phosphate, cellulose compounds, colloidal silicon dioxide, crospovidone, gelatin, hydrogenated castor oil (not present in 10/40 mg strength), iron oxides, lactose monohydrate, magnesium stearate, polysorbate 80, silicon dioxide, sodium lauryl sulfate, sodium starch (potato) glycolate, starch (corn), talc, and titanium dioxide. Benazepril hydrochloride structural formula Amlodipine besylate structural formula
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Pregnancy: Advise female patients of childbearing age about the consequences of exposure to Lotrel during pregnancy. Discuss treatment options with women planning to become pregnant.
Ask patients to report pregnancies to their physicians as soon as possible [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)] . Symptomatic Hypotension: Advise patients that lightheadedness can occur, especially during the first days of therapy, and that it should be reported to their healthcare provider. Tell patients that if syncope occurs to discontinue Lotrel until the physician has been consulted.
Caution all patients that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of lightheadedness and possible syncope [see Warnings and Precautions (5.4)] . Hyperkalemia: Advise patients not to use salt substitutes without consulting their healthcare provider [see Drug Interactions (7)] . T2021-38