LOTREL (amlodipine besylate/benazepril hcl)

There are 5 contraindications. Absolute contraindication.

Contraindication List
Angioedema
Head and neck angioedema
Hereditary angioedema
Intestinal angioedema
Pregnancy

There are 12 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Bone marrow depression
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Dehydration
Disease of liver
Hymenoptera venom desensitization therapy
Hyperkalemia
Hyponatremia
Hypotension
Neutropenic disorder
Renal artery stenosis
Severe aortic valve stenosis

There are 1 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Hemodialysis with high-flux membrane

There are 37 severe adverse reactions.

More Frequent	Less Frequent
None.	Hyperkalemia Hypotension

Rare/Very Rare

Abnormal hepatic function tests Acute myocardial infarction Acute pancreatitis Acute renal failure Agranulocytosis Anaphylaxis Angioedema Atrial fibrillation Black tarry stools Bradycardia Cardiac arrhythmia Depersonalization Depression Drug-induced hepatitis Erythema multiforme Extrapyramidal disease Head and neck angioedema Hemolytic anemia Hypersensitivity pneumonitis Hypertonia Hypotension Intestinal angioedema Jaundice Laryngeal edema Leukopenia Neutropenic disorder Obstructive hyperbilirubinemia Pancreatitis Pemphigus Progressive angina pectoris Pulmonary edema Purpura Stevens-johnson syndrome Thrombocytopenic disorder Ventricular tachycardia

There are 79 less severe adverse reactions.

More Frequent	Less Frequent
Acute abdominal pain Cough Drowsy Edema Headache disorder Nausea Peripheral edema	Dizziness Drowsy Fatigue Flushing Nausea Orthostatic hypotension Palpitations Skin rash

Rare/Very Rare

Abnormal sexual function Alopecia Angina Anorexia Arthralgia Arthritis Asthma Back pain Bronchitis Chest pain Chills Conjunctivitis Constipation Cramps Diarrhea Dream disorder Drug-induced hot flash Dysgeusia Dysphagia Dyspnea Epistaxis Erectile dysfunction Flatulence Flushing Gastritis General weakness Gingival hyperplasia Gynecomastia Hyperglycemia Hyperhidrosis Hypoesthesia Increased urinary frequency Infection Insomnia Libido changes Maculopapular rash Malaise Myalgia Nervousness Nocturia Ocular pain Osteoarthritis Paresthesia Peripheral ischemia Peripheral neuropathy Polydipsia Pruritus of skin Sinusitis Skin photosensitivity Skin rash Symptoms of anxiety Syncope Tachycardia Tinnitus Tremor Urinary tract infection Vasculitis Vertigo Vision impairment Visual changes Vomiting Weight gain Weight loss Xerostomia

Benazepril can cause fetal harm when administered to pregnant females. Use of medications that impact the RAS, such as benazepril, during the second and third trimesters of pregnancy decreases fetal renal function and increases fetal/neonatal morbidity and mortality. Oligohydramnios caused by medications that act on the RAS can result in fetal lung hypoplasia, skeletal deformations (including skull hypoplasia), anuria, hypotension, renal failure, and death.

Discontinue benazepril as soon as possible when pregnancy is detected. In the rare case that there is no appropriate alternative to therapy with drugs affecting the RAS, apprise the mother of the potential hazard to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment.

Based on the week of pregnancy, fetal testing may be appropriate. However, patients and clinicians should be aware that oligohydramnios may not manifest until after the fetus has sustained irreversible injury. Closely observe neonates with a history of in utero exposure to benazepril for hypotension, oliguria, and hyperkalemia.

If oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required. Monitor pregnant females with hypertension carefully and manage accordingly.

The manufacturers state that there are limited data on use of amlodipine in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. There is some data indicating that amlodipine crosses the placenta in measurable quantities in the third trimester of pregnancy. Hypertension in pregnancy is a major cause of maternal, fetal or neonatal morbidity and mortality.

Maternal risks include pre-eclampsia, gestational diabetes, premature delivery, placental abruption, delivery complications (e.g., need for cesarean section, postpartum hemorrhage), stroke, pulmonary edema, thromboembolic events, multiple organ failure (liver, kidney) and disseminated intravascular coagulation. Fetal risks include intrauterine growth restriction, prematurity, and intrauterine death. Neonates may require prolonged high-level care and experience morbidity.

Pregnant women with hypertension should be carefully monitored and managed accordingly. Teratogenicity or other embryo-fetal toxicity was not observed when pregnant rats and rabbits were treated orally with a different salt form of amlodipine (amlodipine maleate) at doses up to 10 mg/kg per day (approximately 10 and 20 times the maximum recommended human dose (MRHD) based on body surface area, respectively) during their respective periods of major organogenesis. However, when amlodipine maleate at doses up to 10 mg amlodipine/kg per day was administered to rats for 14 days prior to mating and throughout gestation, litter size decreased approximately 50%, and a 5-fold increase in the number of intrauterine deaths was observed at this dose equivalent to 10 times the MDRD. Amlodipine maleate has also been shown to prolong both the gestation period and the duration of labor in rats at this dose.

Benazepril and benazeprilat (active metabolite of benazepril) are distributed into human milk in minimal amounts. Because of the unknown effects of benazepril or benazeprilat in nursing infants, a decision should be made whether to discontinue nursing or benazepril, taking into account the potential risk in breast-feeding infants and the importance of the drug to the woman. The manufacturer states limited available data from a published clinical lactation study reported 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 have been observed; there is no available information on the effects of amlodipine on milk production.

No substantial differences in safety and efficacy have been observed in geriatric patients relative to younger adults, but increased sensitivity cannot be ruled out. Because geriatric patients are more likely to have decreased renal function, dosage should be selected cautiously; it may be useful to monitor renal function in such patients. In geriatric patients, amlodipine clearance is decreased and AUC is increased by about 40-60%.

Therefore, amlodipine dosage should be selected carefully, usually initiating therapy with dosages at the lower end of the recommended range (i.e., 2.5 mg daily). The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly also should be considered. Clinical studies of amlodipine did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients; however, other clinical experience has not revealed age-related differences in response or tolerance.