Fosinopril and hydrochlorothiazide

Fosinopril and Hydrochlorothiazide may be found in some form under the following brand names:

• Monopril HCT

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of fosinopril and hydrochlorothiazide, salt substitutes containing potassium should be avoided. 

Tell your doctor is you are breastfeeding or plan to breastfeed. 

Fosinopril and hydrochlorothiazide has been detected in human breast milk. Because of the possibility for adverse reactions in nursing infants from fosinopril and hydrochlorothiazide, a choice should be made whether to stop nursing or to stop use of this medication. The importance of the drug to the mother should be considered. 

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For fosinopril and hydrochlorothiazide, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to fosinopril and hydrochlorothiazide or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of fosinopril and hydrochlorothiazide combination in the pediatric population. Safety and efficacy have not been established .

Geriatric

Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of fosinopril and hydrochlorothiazide combination in the elderly. However, elderly patients are more likely to have age-related kidney or heart problems, which may require an adjustment of dose in patients receiving fosinopril and hydrochlorothiazide combination .

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking fosinopril and hydrochlorothiazide, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using fosinopril and hydrochlorothiazide with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Aliskiren
• Dofetilide
• Sacubitril

Using fosinopril and hydrochlorothiazide with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aceclofenac
• Acemetacin
• Acetyldigoxin
• Alteplase, Recombinant
• Amiloride
• Amphetamine
• Amtolmetin Guacil
• Arsenic Trioxide
• Aspirin
• Azathioprine
• Azilsartan
• Azilsartan Medoxomil
• Benzphetamine
• Bromfenac
• Bufexamac
• Candesartan Cilexetil
• Canrenoate
• Celecoxib
• Choline Salicylate
• Clonixin
• Cyclophosphamide
• Deslanoside
• Dexibuprofen
• Dexketoprofen
• Dextroamphetamine
• Diclofenac
• Diflunisal
• Digitalis
• Digitoxin
• Digoxin
• Dipyrone
• Droperidol
• Droxicam
• Eplerenone
• Eprosartan
• Etodolac
• Etofenamate
• Etoricoxib
• Everolimus
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Flecainide
• Floctafenine
• Flufenamic Acid
• Flurbiprofen
• Ibuprofen
• Indomethacin
• Irbesartan
• Ketanserin
• Ketoprofen
• Ketorolac
• Levomethadyl
• Lisdexamfetamine
• Lithium
• Lornoxicam
• Losartan
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Mercaptopurine
• Methamphetamine
• Methotrexate
• Metildigoxin
• Morniflumate
• Nabumetone
• Naproxen
• Nepafenac
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Olmesartan Medoxomil
• Ouabain
• Oxaprozin
• Oxyphenbutazone
• Parecoxib
• Phenylbutazone
• Piketoprofen
• Piroxicam
• Potassium
• Proglumetacin
• Propyphenazone
• Proquazone
• Proscillaridin
• Rofecoxib
• Salicylic Acid
• Salsalate
• Sirolimus
• Sodium Salicylate
• Sotalol
• Spironolactone
• Sulindac
• Telmisartan
• Tenoxicam
• Tiaprofenic Acid
• Tolfenamic Acid
• Tolmetin
• Triamterene
• Trimethoprim
• Valdecoxib
• Valsartan

Using fosinopril and hydrochlorothiazide with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aceclofenac
• Acemetacin
• Aminolevulinic Acid
• Amtolmetin Guacil
• Azosemide
• Bepridil
• Bromfenac
• Bufexamac
• Bumetanide
• Bupivacaine
• Bupivacaine Liposome
• Capsaicin
• Carbamazepine
• Celecoxib
• Cholestyramine
• Choline Salicylate
• Clonixin
• Dexibuprofen
• Dexketoprofen
• Diclofenac
• Diflunisal
• Dipyrone
• Droxicam
• Ethacrynic Acid
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Floctafenine
• Flufenamic Acid
• Flurbiprofen
• Furosemide
• Ginkgo
• Gold Sodium Thiomalate
• Gossypol
• Ibuprofen
• Indomethacin
• Ketoprofen
• Ketorolac
• Licorice
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Morniflumate
• Nabumetone
• Naproxen
• Nepafenac
• Nesiritide
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Oxaprozin
• Oxyphenbutazone
• Parecoxib
• Phenylbutazone
• Piketoprofen
• Piretanide
• Piroxicam
• Proglumetacin
• Propionic Acid
• Propyphenazone
• Proquazone
• Rofecoxib
• Salicylic Acid
• Salsalate
• Sodium Salicylate
• Sulindac
• Tenoxicam
• Tiaprofenic Acid
• Tolfenamic Acid
• Tolmetin
• Topiramate
• Torsemide
• Valdecoxib

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of fosinopril and hydrochlorothiazide. Make sure you tell your doctor if you have any other medical problems, especially:

• Angioedema, history of—May increase the risk of this condition occurring again .

• Anuria (not able to pass urine)—fosinopril and hydrochlorothiazide should not be used in patients with this condition .

• Asthma, bronchial—fosinopril and hydrochlorothiazide may cause sensitivity reactions .

• Congestive heart failure (severe) or
• Dehydration or
• Diarrhea or
• Hyponatremia (low sodium in the blood) or
• Kidney disease—These conditions may cause the blood pressure to fall too low with fosinopril and hydrochlorothiazide .

• Diabetes or
• Gout or
• Hypercholesterolemia (high cholesterol in the blood) or
• Hyperuricemia (high uric acid in the blood) or
• Liver disease or
• Systemic lupus erythematosus (SLE)—These conditions may be made worse .

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about fosinopril and hydrochlorothiazide, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about fosinopril and hydrochlorothiazide. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using fosinopril and hydrochlorothiazide.

Review Date: October 4, 2017

Fosinopril sodium is a white to off-white crystalline powder, soluble (>100 mg/mL) in water, in ethanol and in methanol, and slightly soluble in hexane. Fosinopril sodium is designated chemically as L-proline, 4-cyclohexyl-1-[[[2-methyl-1-(1-oxopropoxy)- propoxy](4-phenylbutyl)phosphinyl]acetyl]-, sodium salt, trans-; its structural formula is:

Its empirical formula is C30H45NNaO7P, and its molecular weight is 585.65.

Fosinoprilat, the active metabolite of fosinopril, is a non-sulfhydryl angiotensin-converting enzyme inhibitor. Fosinopril is converted to fosinoprilat by hepatic cleavage of the ester group.

Hydrochlorothiazide, USP is a white, or practically white, practically odorless, crystalline powder. It is slightly soluble in water; freely soluble in sodium hydroxide solution, in n-butylamine, and in dimethylformamide; sparingly soluble in methanol; and insoluble in ether, in chloroform, and in dilute mineral acids. Hydrochlorothiazide is designated chemically as 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide; its structural formula is:

Its empirical formula is C7H8ClN3O4S2 and its molecular weight is 297.73. Hydrochlorothiazide is a thiazide diuretic.

Fosinopril sodium and hydrochlorothiazide tablets are a combination of fosinopril sodium and hydrochlorothiazide, USP. It is available for oral use in two tablet strengths: fosinopril sodium and hydrochlorothiazide tablets 10/12.5, containing 10 mg of fosinopril sodium and 12.5 mg of hydrochlorothiazide, USP; and fosinopril sodium-hydrochlorothiazide tablets 20/12.5, containing 20 mg of fosinopril sodium and 12.5 mg of hydrochlorothiazide, USP. The inactive ingredients of the tablets include carnauba wax, crospovidone, lactose anhydrous, lactose monohydrate, starch, red iron oxide and zinc stearate.

Anaphylactoid and Possibly Related Reactions

Presumably because angiotensin-converting enzyme inhibitors affect the metabolism of eicosanoids and polypeptides, including endogenous bradykinin, patients receiving ACE inhibitors (including fosinopril sodium and hydrochlorothiazide) may be subject to a variety of adverse reactions, some of them serious.

Angioedema of the face, extremities, lips, tongue, glottis and larynx has been reported in patients treated with angiotensin-converting enzyme inhibitors. Angioedema associated with laryngeal edema can be fatal. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, treatment with fosinopril sodium and hydrochlorothiazide should be discontinued and appropriate therapy instituted immediately. When involvement of the tongue, glottis, or larynx appears likely to cause airway obstruction, appropriate therapy, e.g., subcutaneous epinephrine injection 1:1000 (0.3 mL to 0.5 mL) should be promptly administered (see PRECAUTIONSand ADVERSE REACTIONS).

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.

Two patients undergoing desensitizing treatment with hymenoptera venom while receiving ACE inhibitors sustained life-threatening anaphylactoid reactions. In the same patients, these reactions were avoided when ACE inhibitors were temporarily withheld, but they reappeared upon inadvertent rechallenge.

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.

Hypotension

Fosinopril sodium and hydrochlorothiazide can cause symptomatic hypotension. Like other ACE inhibitors, fosinopril has been only rarely associated with hypotension in uncomplicated hypertensive patients. Symptomatic hypotension is most likely to occur in patients who have been volume- and/or salt-depleted as a result of prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. Volume and/or salt depletion should be corrected before initiating therapy with fosinopril sodium and hydrochlorothiazide.

Fosinopril sodium and hydrochlorothiazide should be used cautiously in patients receiving concomitant therapy with other antihypertensives. The thiazide component of fosinopril sodium and hydrochlorothiazide may potentiate the action of other antihypertensive drugs, especially ganglionic or peripheral adrenergic-blocking drugs. The antihypertensive effects of the thiazide component may also be enhanced in the post-sympathectomy patient.

In patients with congestive heart failure, with or without associated renal insufficiency, ACE inhibitor therapy may cause excessive hypotension, which may be associated with oliguria, azotemia, and (rarely) with acute renal failure and death. In such patients, fosinopril sodium and hydrochlorothiazide therapy should be started under close medical supervision; they should be followed closely for the first 2 weeks of treatment and whenever the dose of fosinopril or diuretic is increased.

If hypotension occurs, the patient should be placed in a supine position and, if necessary, treated with intravenous infusion of physiological saline. Fosinopril sodium and hydrochlorothiazide treatment usually can be continued following restoration of blood pressure and volume.

Impaired Renal Function

Fosinopril sodium and hydrochlorothiazide should be used with caution in patients with severe renal disease. Thiazides may precipitate azotemia in such patients, and the effects of repeated dosing may be cumulative.

When the renin-angiotensin-aldosterone system is inhibited by ACE inhibitors, changes in renal function may be anticipated in susceptible individuals. In patients with severe congestive heart failure, whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin-converting enzyme inhibitors (including fosinopril) may be associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death.

In some studies of hypertensive patients with unilateral or bilateral renal artery stenosis, treatment with ACE inhibitors has been associated with increases in blood urea nitrogen and serum creatinine; these increases were reversible upon discontinuation of ACE inhibitor therapy, concomitant diuretic therapy, or both. When such patients are treated with fosinopril sodium and hydrochlorothiazide, renal function should be monitored during the first few weeks of therapy.

Some ACE-inhibitor-treated hypertensive patients with no apparent pre-existing renal vascular disease have developed increases in blood urea nitrogen and serum creatinine, usually minor and transient, especially when the ACE inhibitor has been given concomitantly with a diuretic. Dosage reduction of fosinopril sodium and hydrochlorothiazide may be required. Evaluation of the hypertensive patient should always include assessment of renal function (see DOSAGE AND ADMINISTRATION).

Neutropenia/Agranulocytosis

Another angiotensin-converting enzyme inhibitor, captopril, has been shown to cause agranulocytosis and bone marrow depression, rarely in uncomplicated patients (incidence probably less than once per 10,000 exposures), but more frequently (incidence possibly as great as once per 1,000 exposures) in patients with renal impairment, especially those who also have a collagen-vascular disease such as systemic lupus erythematosus or scleroderma. Available data from clinical trials of fosinopril are insufficient to show that fosinopril does not cause agranulocytosis at similar rates. Monitoring of white blood cell counts should be considered in patients with collagen-vascular disease, especially if the disease is associated with impaired renal function.

Neutropenia/agranulocytosis has also been associated with thiazide diuretics.

Fetal Toxicity

Pregnancy Category D

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 Fosinopril and Hydrochlorothiazide as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.

In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Fosinopril and Hydrochlorothiazide, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Fosinopril and Hydrochlorothiazide for hypotension, oliguria, and hyperkalemia (see PRECAUTIONS, Pediatric Use).

Intrauterine exposure to thiazide diuretics is associated with fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that occurred in adults.

No teratogenic effects of fosinopril were seen in studies of pregnant rats and rabbits. On a mg/kg basis, the doses used were up to 180 times (in rats) and one time (in rabbits) the maximum recommended human dose. No teratogenic effects of Fosinopril and Hydrochlorothiazide were seen in studies of pregnant rats and rabbits. On a mg/kg (Fosinopril and Hydrochlorothiazide) basis, the doses used were up to 188/94 times (in rats) and 0.6/0.3 times (in rabbits) the maximum recommended human dose.

Impaired Hepatic Function

Rarely, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. A patient receiving fosinopril sodium and hydrochlorothiazide who develops jaundice or marked elevation of hepatic enzymes should discontinue fosinopril sodium and hydrochlorothiazide tablets and receive appropriate medical follow-up.

Fosinopril sodium and hydrochlorothiazide should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. Also, since the metabolism of fosinopril to fosinoprilat is normally dependent upon hepatic esterases, patients with impaired liver function could develop elevated plasma levels of fosinopril. In a study of patients with alcoholic or biliary cirrhosis the rate (but not the extent) of hydrolysis to fosinoprilat was reduced. In these patients the clearance of fosinoprilat was reduced, and the area under the fosinoprilat-time curve was approximately doubled.

Systemic Lupus Erythematosus

Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.

Fosinopril Sodium and Hydrochlorothiazide Tablets, for oral administration, are available as

10 mg/12.5 mg

Light pink, round, debossed with “E” over “341” on one side and plain on the other side and supplied as:

NDC 0185-0341-01 bottles of 100

NDC 0185-0341-10 bottles of 1000

20 mg/12.5 mg

Dark pink, round, debossed with “E” over “342” on one side and scored on the other side and supplied as:

NDC 0185-0342-01 bottles of 100

NDC 0185-0342-10 bottles of 1000

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from moisture by keeping bottle tightly closed.

To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Distributed by

Sandoz Inc.

Princeton, NJ 08540

OS8219

Rev. April 2016

MF0341REV04/16

NDC 0185-0341-01

Fosinopril Sodium and Hydrochlorothiazide Tablets

10 mg/12.5 mg

Rx only

100 Tablets

Sandoz

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). Protect from moisture by keeping bottle tightly closed.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber signs of infection, signs of high blood sugar (confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit), signs of kidney problems (urinary retention, blood in urine, change in amount of urine passed, weight gain), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of fluid and electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, nausea, or vomiting), cough that will not go away, angina, edema, depression, dysuria, burning or numbness feeling, severe abdominal pain, vision changes, or eye pain (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Fosinopril 10 to 40 mg-Hydrochlorothiazide 12.5 to 37.5 mg orally per day

Comments: The effect of fosinopril 10 mg-hydrochlorothiazide 12.5 mg was similar to the effect seen with monotherapy using either fosinopril 40 mg or hydrochlorothiazide 37.5 mg.

Use: Treatment of hypertension when the desired effect has not been achieved with monotherapy or as substitution for the titrated individual components.