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Friday, September 30, 2016

Quinaglute

Generic Name: quinidine (Oral route, Injection route, Intramuscular route)

KWIN-i-deen

Oral route(Tablet, Extended Release)

Many trials of antiarrhythmic therapy for non-life threatening arrhythmias, has resulted in increased mortality; the risk of active therapy is probably greatest in patients with structural heart disease. In the case of quinidine used to prevent or defer recurrence of atrial flutter/fibrillation, meta-analysis data has shown that the mortality associated with the use of quinidine was more than three times greater than placebo. Another meta-analysis showed that in patients with various non-life-threatening ventricular arrhythmias, the mortality associated with the use of quinidine was consistently greater than that associated with the use of any of a variety of alternative antiarrhythmics .

Oral route(Tablet)

Commonly used brand name(s)

In the U.S.

Cardioquin

Quinaglute

Quinalan

Quinidex Extentabs

Available Dosage Forms:

Tablet

Tablet, Extended Release

Capsule

Solution

Therapeutic Class: Antiarrhythmic, Group IA

Chemical Class: Cinchona Alkaloid

Uses For Quinaglute

Quinidine is used to treat abnormal heart rhythms. It is also used to treat malaria.

Do not confuse this medicine with quinine, which, although related, has different medical uses.

Quinidine is available only with your doctor's prescription.

Before Using Quinaglute

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 this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine 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

Quinidine has not been widely studied in children; however, it is used in children to treat abnormal heart rhythms and to treat malaria. Children may be able to take higher doses than adults and may have fewer side effects (such as vomiting, loss of appetite, and diarrhea) than adults.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing use of quinidine in the elderly with use in other age groups, this medicine is not expected to cause different side effects or problems in older people than it does in younger adults. However, quinidine may remain in the bodies of older adults longer than it does in younger adults, which may increase the risk of side effects and which may require lower doses.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during 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 this medicine, 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 this medicine 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.

Aurothioglucose

Bepridil

Cisapride

Dronedarone

Grepafloxacin

Itraconazole

Levomethadyl

Mesoridazine

Nelfinavir

Pimozide

Posaconazole

Ritonavir

Saquinavir

Sparfloxacin

Terfenadine

Thioridazine

Tipranavir

Voriconazole

Ziprasidone

Using this medicine 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.

Acetazolamide

Ajmaline

Alfuzosin

Amiodarone

Amitriptyline

Amoxapine

Amprenavir

Apomorphine

Aprindine

Arbutamine

Arsenic Trioxide

Asenapine

Astemizole

Atazanavir

Atracurium

Azithromycin

Boceprevir

Chloral Hydrate

Chloroquine

Ciprofloxacin

Citalopram

Clarithromycin

Clomipramine

Colchicine

Crizotinib

Darunavir

Dasatinib

Decamethonium

Delavirdine

Desipramine

Digitoxin

Digoxin

Disopyramide

Dofetilide

Dolasetron

Doxepin

Droperidol

Enflurane

Erythromycin

Etravirine

Flecainide

Fluconazole

Fosamprenavir

Foscarnet

Gatifloxacin

Gemifloxacin

Granisetron

Halofantrine

Haloperidol

Halothane

Hydroquinidine

Ibutilide

Imipramine

Infliximab

Isoflurane

Isradipine

Lanreotide

Lapatinib

Levofloxacin

Lidocaine

Lidoflazine

Lopinavir

Lorcainide

Lumefantrine

Mefloquine

Methadone

Mexiletine

Moxifloxacin

Nalidixic Acid

Nilotinib

Norfloxacin

Nortriptyline

Octreotide

Ofloxacin

Ondansetron

Paliperidone

Pancuronium

Pazopanib

Pentamidine

Perflutren Lipid Microsphere

Pirmenol

Prajmaline

Prilocaine

Probucol

Procainamide

Prochlorperazine

Propafenone

Protriptyline

Quetiapine

Quinidine

Quinine

Ranolazine

Salmeterol

Sodium Phosphate

Sodium Phosphate, Dibasic

Sodium Phosphate, Monobasic

Solifenacin

Sorafenib

Sotalol

Spiramycin

Succinylcholine

Sulfamethoxazole

Sunitinib

Telaprevir

Telavancin

Telithromycin

Tetrabenazine

Toremifene

Trazodone

Trifluoperazine

Trimethoprim

Trimipramine

Tubocurarine

Vandetanib

Vardenafil

Vasopressin

Vecuronium

Vemurafenib

Zolmitriptan

Using this medicine 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.

Abarelix

Amiloride

Aripiprazole

Atenolol

Cimetidine

Clozapine

Dalfopristin

Dextromethorphan

Dicumarol

Fosphenytoin

Galantamine

Ketoconazole

Magaldrate

Magnesium Carbonate

Magnesium Hydroxide

Magnesium Oxide

Magnesium Trisilicate

Metoprolol

Nifedipine

Nisoldipine

Paroxetine

Phenobarbital

Phenytoin

Propranolol

Quinupristin

Rifapentine

Timolol

Tolterodine

Tramadol

Verapamil

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. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

Grapefruit Juice

Proper Use of quinidine

This section provides information on the proper use of a number of products that contain quinidine. It may not be specific to Quinaglute. Please read with care.

Take this medicine exactly as directed. Do not take more of this medicine and do not take it more often than your doctor ordered. Do not miss any doses.

Taking quinidine with food may help lessen stomach upset.

For patients taking the extended-release tablet form of this medicine:

Quinidex Extentabs or Biquin Durules—Swallow the tablets whole; do not break, crush, or chew before swallowing. Note that Biquin Durules may sometimes appear as a whole tablet in the stool; this tablet is just the empty shell that is left after the medicine has been absorbed into the body.

Quinaglute Duratabs or Quin-Release—These tablets may be broken in half; however, they should not be crushed or chewed before swallowing.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For regular (short-acting) oral dosage form (tablets):
- For abnormal heart rhythm:
  - Adults—200 to 650 milligrams (mg) three or four times a day.
  - Children—30 to 40 mg per kilogram (kg) (13.6 to 18.2 mg per pound) of body weight per day. Your doctor may increase the dose if needed.

For long-acting oral dosage form (tablets):
- For abnormal heart rhythm:
  - Adults—300 to 660 mg every eight to twelve hours.
  - Children—30 to 40 mg per kilogram (kg) (13.6 to 18.2 mg per pound) of body weight per day. Your doctor may increase the dose if needed.

For injection dosage form:
- For abnormal heart rhythm:
  - Adults—190 to 380 mg injected into the muscle every two to four hours. Or, up to 0.25 mg per kg (0.11 mg per pound) of body weight per minute in a solution injected into a vein.
  - Children—Dose must be determined by your doctor.
- For malaria:
  - Adults—10 mg per kg (4.54 mg per pound) of body weight in a solution injected slowly into a vein over one to two hours. Then, 0.02 mg per kg (0.009 mg per pound) of body weight per minute is given. Or, 24 mg per kg (10.91 mg per pound) of body weight in a solution injected slowly into a vein over a four-hour period. Then, eight hours after the first dose, 12 mg per kg (5.45 mg per pound) of body weight, injected slowly into a vein over a four-hour period, and repeated every eight hours.
  - Children—Dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Quinaglute

It is very important that your doctor check your progress at regular visits to make sure that the quinidine is working properly and does not cause unwanted effects.

Do not stop taking this medicine without first checking with your doctor, to avoid possible worsening of your condition.

Before having any kind of surgery (including dental surgery) or emergency treatment, tell the medical doctor or dentist in charge that you are taking this medicine.

Dizziness or lightheadedness may occur with this medicine, especially when you get up from a lying or sitting position. Getting up slowly may help.

Fainting may occur with this medicine. Do not drive or do anything else that could be dangerous if fainting occurs.

. Check with your doctor immediately if you faint or experience other side effects with this medicine.

Your doctor may want you to carry a medical identification card or bracelet stating that you are using this medicine.

Quinaglute Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Less common

Abdominal pain and/or yellow eyes or skin

blurred and/or double vision, confusion, delirium, disturbed color perception, headache, noises or ringing in the ear, and/or visual intolerance of light

dizziness or lightheadedness

fainting

fever

Rare

Chest pain, fever, general discomfort, joint pain, joint swelling, muscle pain, and/or skin rash

nosebleeds or bleeding gums

unusual tiredness or weakness and/or pale skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Diarrhea

loss of appetite

muscle weakness

nausea or vomiting

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Quinaglute side effects (in more detail)

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Arrhythmia
Malaria

Quibron-T

theophyllin, anhydrous

Dosage Form: Tablets

Description

Theophylline is structurally classified as a methylxanthine. It occurs as a white, odorless, crystalline powder with a bitter taste. Anhydrous theophylline has the chemical name 1HPurine- 2,6-dione, 3,7-dihydro-1,3-dimethyl-, and is represented by the following structural formula:

The molecular formula of anhydrous theophylline is C7H8N4O2 with a molecular weight of 180.17.

Quibron®-T is available as tablets intended for oral administration, containing 300 mg of anhydrous theophylline per tablet. Quibron®-T is an oral bronchodilator in an immediate-release formulation in the ACCUDOSE® Tablet design. With functional trisects and bisects, Quibron®-T Tablets can be accurately divided into 100-, 150-, and 200-mg segments to provide a variety of dosing increments, as required.

QUIBRON®-T TABLETS
	One-third tablet	= 100 mg
	One-half tablet	= 150 mg
	Two-thirds tablet	= 200 mg
	One tablet	= 300 mg

Inactive Ingredients: microcrystalline cellulose, yellow ferric oxide, hydroxypropyl methylcellulose 2910, lactose monohydrate, magnesium stearate, colloidal silicon dioxide, and sodium starch glycolate.

Clinical Pharmacology

Mechanism of Action:

Theophylline has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects).

While the mechanisms of action of theophylline are not known with certainty, studies in animals suggest that bronchodilatation is mediated by the inhibition of two isozymes of phosphodiesterase (PDE III and, to a lesser extent, PDE IV) while non-bronchodilator prophylactic actions are probably mediated through one or more different molecular mechanisms, that do not involve inhibition of PDE III or antagonism of adenosine receptors. Some of the adverse effects associated with theophylline appear to be mediated by inhibition of PDE III (e.g., hypotension, tachycardia, headache, and emesis) and adenosine receptor antagonism (e.g., alterations in cerebral blood flow).

Theophylline increases the force of contraction of diaphragmatic muscles. This action appears to be due to enhancement of calcium uptake through an adenosine-mediated channel.

Serum Concentration-Effect Relationship:

Bronchodilation occurs over the serum theophylline concentration range of 5-20 mcg/mL. Clinically important improvement in symptom control has been found in most studies to require peak serum theophylline concentrations >10 mcg/mL, but patients with mild disease may benefit from lower concentrations. At serum theophylline concentrations >20 mcg/mL, both the frequency and severity of adverse reactions increase. In general, maintaining peak serum theophylline concentrations between 10 and 15 mcg/mL will achieve most of the drug’s potential therapeutic benefit while minimizing the risk of serious adverse events.

Pharmacokinetics:

Overview Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form. Theophylline does not undergo any appreciable pre-systemic elimination, distributes freely into fat-free tissues and is extensively metabolized in the liver.

The pharmacokinetics of theophylline vary widely among similar patients and cannot be predicted by age, sex, body weight or other demographic characteristics. In addition, certain concurrent illnesses and alterations in normal physiology (see Table I) and co-administration of other drugs (see Table II) can significantly alter the pharmacokinetic characteristics of theophylline. Within-subject variability in metabolism has also been reported in some studies, especially in acutely ill patients. It is, therefore, recommended that serum theophylline concentrations be measured frequently in acutely ill patients (e.g., at 24-hr intervals) and periodically in patients receiving long-term therapy, e.g., at 6-12 month intervals. More frequent measurements should be made in the presence of any condition that may significantly alter theophylline clearance (see PRECAUTIONS, Laboratory Tests).

Table I. Mean and range of total body clearance and half-life of theophylline related to age and altered physiological states.
Population characteristics	Total body clearance* mean (range)†† (mL/kg/min)	Half-life mean (range)†† (hr)
Age
Premature neonates postnatal age 3-15 days postnatal age 25-57 days	0.29 (0.09-0.49) 0.64 (0.04-1.2)	30 (17-43) 20 (9.4-30.6)
Term infants postnatal age 1-2 days postnatal age 3-30 weeks	NR† NR†	25.7 (25-26.5) 11 (6-29)
Children 1-4 years 4-12 years 13-15 years 6-17 years	1.7 (0.5-2.9) 1.6 (0.8-2.4) 0.9 (0.48-1.3) 1.4 (0.2-2.6)	3.4 (1.2-5.6) NR† NR† 3.7 (1.5-5.9)
Adults (16-60 years) otherwise healthy non-smoking asthmatics	0.65 (0.27-1.03)	8.7 (6.1-12.8)
Elderly (>60 years) non-smokers with normal cardiac, liver, and renal function	0.41 (0.21-0.61)	9.8 (1.6-18)
Concurrent illness or altered physiological state
Acute pulmonary edema	0.33** (0.07-2.45)	19** (3.1-82)
COPD >60 years, stable non-smoker >1 year	0.54 (0.44-0.64)	11 (9.4-12.6)
COPD with cor pulmonale	0.48 (0.08-0.88)	NR†
Cystic fibrosis (14-28 years)	1.25 (0.31-2.2)	6.0 (1.8-10.2)
Fever associated with acute viral respiratory illness (children 9-15 years)	NR†	7.0 (1.0-13)
Liver disease - cirrhosis acute hepatitis cholestasis	0.31** (0.1-0.7) 0.35 (0.25-0.45) 0.65 (0.25-1.45)	32** (10-56) 19.2 (16.6-21.8) 14.4 (5.7-31,8)
Pregnancy - 1st trimester 2nd trimester 3rd trimester	NR† NR† NR†	8.5 (3.1-13.9) 8.8 (3.8-13.8) 13.0 (8.4-17.6)
Sepsis with multi- organ failure	0.47 (0.19-1.9)	18.8 (6.3-24.1)
Thyroid disease - hypothyroid hyperthyroid	0.38 (0.13-0.57) 0.8 (0.68-0.97)	11.6 (8.2-25) 4.5 (3.7-5.6)
¶ For various North American patient populations from literature reports. Different rates of elimination and consequent dosage requirements have been observed among other peoples.
* Clearance represents the volume of blood completely cleared of theophylline by the liver in one minute. Values listed were generally determined at serum theophylline concentrations <20 mcg/mL; clearance may decrease and half-life may increase at higher serum concentrations due to non-linear pharmacokinetics.
†† Reported range or estimated range (mean ± 2 SD) where actual range not reported.
† NR = not reported or not reported in a comparable format.
** Median

Note: In addition to the factors listed above, theophylline clearance is increased and half-life decreased by low carbohydrate/high protein diets, parenteral nutrition, and daily consumption of charcoal-broiled beef. A high carbohydrate/low protein diet can decrease the clearance and prolong the half-life of theophylline.

Absorption

Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form. After a single dose of 5 mg/kg in adults, a mean peak serum concentration of about 10 mcg/mL (range 5-15 mcg/mL) can be expected 1-2 hr after the dose. Co-administration of theophylline with food or antacids does not cause clinically significant changes in the absorption of theophylline from immediate-release dosage forms.

Distribution

Once theophylline enters the systemic circulation, about 40% is bound to plasma protein, primarily albumin. Unbound theophylline distributes throughout body water, but distributes poorly into body fat. The apparent volume of distribution of theophylline is approximately 0.45 L/kg (range 0.3-0.7 L/kg) based on ideal body weight. Theophylline passes freely across the placenta, into breast milk and into the cerebrospinal fluid (CSF). Saliva theophylline concentrations approximate unbound serum concentrations, but are not reliable for routine or therapeutic monitoring unless special techniques are used. An increase in the volume of distribution of theophylline, primarily due to reduction in plasma protein binding, occurs in premature neonates, patients with hepatic cirrhosis, uncorrected acidemia, the elderly and in women during the third trimester of pregnancy. In such cases, the patient may show signs of toxicity at total (bound + unbound) serum concentrations of theophylline in the therapeutic range (10-20 mcg/mL) due to elevated concentrations of the pharmacologically active unbound drug. Similarly, a patient with decreased theophylline binding may have a sub-therapeutic total drug concentration while the pharmacologically active unbound concentration is in the therapeutic range. If only total serum theophylline concentration is measured, this may lead to an unnecessary and potentially dangerous dose increase. In patients with reduced protein binding, measurement of unbound serum theophylline concentration provides a more reliable means of dosage adjustment than measurement of total serum theophylline concentration. Generally, concentrations of unbound theophylline should be maintained in the range of 6-12 mcg/mL.

Metabolism

Following oral dosing, theophylline does not undergo any measurable firstpass elimination. In adults and children beyond one year of age, approximately 90% of the dose is metabolized in the liver. Biotransformation takes place through demethylation to 1-methylxanthine and 3-methylxanthine and hydroxylation to 1,3-dimethyluric acid. 1- methylxanthine is further hydroxylated, by xanthine oxidase, to 1-methyluric acid. About 6% of a theophylline dose is N-methylated to caffeine. Theophylline demethylation to 3- methylxanthine is catalyzed by cytochrome P-450 1A2, while cytochromes P-450 2E1 and P-450 3A3 catalyze the hydroxylation to 1,3-dimethyluric acid. Demethylation to 1- methylxanthine appears to be catalyzed either by cytochrome P-450 1A2 or a closely related cytochrome. In neonates, the N-demethylation pathway is absent while the function of the hydroxylation pathway is markedly deficient. The activity of these pathways slowly increases to maximal levels by one year of age.

Caffeine and 3-methylxanthine are the only theophylline metabolites with pharmacologic activity. 3-methylxanthine has approximately one tenth the pharmacologic activity of theophylline and serum concentrations in adults with normal renal function are <1 mcg/mL. In patients with end-stage renal disease, 3-methylxanthine may accumulate to concentrations that approximate the unmetabolized theophylline concentration. Caffeine concentrations are usually undetectable in adults regardless of renal function. In neonates, caffeine may accumulate to concentrations that approximate the unmetabolized theophylline concentration and thus, exert a pharmacologic effect.

Both the N-demethylation and hydroxylation pathways of theophylline biotransformation are capacity-limited. Due to the wide intersubject variability of the rate of theophylline metabolism, non-linearity of elimination may begin in some patients at serum theophylline concentrations <10 mcg/mL. Since this non-linearity results in more than proportional changes in serum theophylline concentrations with changes in dose, it is advisable to make increases or decreasesin dose in small increments in order to achieve desired changes in serum theophylline concentrations (see DOSAGE AND ADMINISTRATION, Table VI). Accurate prediction of dose-dependency of theophylline metabolism in patients a prior is not possible, but patients with very high initial clearance rates (i.e., low steady state serum theophylline concentrations at above average doses) have the greatest likelihood of experiencing large changes in serum theophylline concentration in response to dosage changes.

Excretion

In neonates, approximately 50% of the theophylline dose is excreted unchanged in the urine. Beyond the first three months of life, approximately 10% of the theophylline dose is excreted unchanged in the urine. The remainder is excreted in the urine mainly as 1,3-dimethyluric acid (35-40%), 1-methyluric acid (20-25%) and 3- methylxanthine (15-20%). Since little theophylline is excreted unchanged in the urine and since active metabolites of theophylline (i.e., caffeine, 3-methylxanthine) do not accumulate to clinically significant levels even in the face of end-stage renal disease, no dosage adjustment for renal insufficiency is necessary in adults and children >3 months of age. In contrast, the large fraction of the theophylline dose excreted in the urine as unchanged theophylline and caffeine in neonates requires careful attention to dose reduction and frequent monitoring of serum theophylline concentrations in neonates with reduced renal function (See WARNINGS).

Serum Concentrations at Steady State

After multiple doses of theophylline, steady state is reached in 30-65 hours (average 40 hours) in adults. At steady state, on a dosage regimen with 6-hour intervals, the expected mean trough concentration is approximately 60% of the mean peak concentration, assuming a mean theophylline half-life of 8 hours. The difference between peak and trough concentrations is larger in patients with more rapid theophylline clearance. In patients with high theophylline clearance and half-lives of about 4-5 hours, such as children age 1 to 9 years, the trough serum theophylline concentration may be only 30% of peak with a 6-hour dosing interval. In these patients a slow release formulation would allow a longer dosing interval (8-12 hours) with a smaller peak/trough difference.

Special Populations (See Table I for mean clearance and half-life values)

Geriatric The clearance of theophylline is decreased by an average of 30% in healthy elderly adults (>60 yrs) compared to healthy young adults. Careful attention to dose reduction and frequent monitoring of serum theophylline concentrations are required in elderly patients (see WARNINGS).

Pediatrics The clearance of theophylline is very low in neonates (see WARNINGS). Theophylline clearance reaches maximal values by one year of age, remains relatively constant until about 9 years of age and then slowly decreases by approximately 50% to adult values at about age 16. Renal excretion of unchanged theophylline in neonates amounts to about 50% of the dose, compared to about 10% in children older than three months and in adults. Careful attention to dosage selection and monitoring of serum theophylline concentrations are required in pediatric patients (see WARNINGS and DOSAGE AND ADMINISTRATION).

Gender Gender differences in theophylline clearance are relatively small and unlikely to be of clinical significance. Significant reduction in theophylline clearance, however, has been reported in women on the 20th day of the menstrual cycle and during the third trimester of pregnancy.

Race Pharmacokinetic differences in theophylline clearance due to race have not been studied.

Renal Insufficiency Only a small fraction, e.g., about 10%, of the administered theophylline dose is excreted unchanged in the urine of children greater than three months of age and adults. Since little theophylline is excreted unchanged in the urine and since active metabolites of theophylline (i.e., caffeine, 3-methylxanthine) do not accumulate to clinically significant levels even in the face of end-stage renal disease, no dosage adjustment for renal insufficiency is necessary in adults and children >3 months of age. In contrast, approximately 50% of the administered theophylline dose is excreted unchanged in the urine in neonates. Careful attention to dose reduction and frequent monitoring of serum theophylline concentrations are required in neonates with decreased renal function (see WARNINGS).

Hepatic Insufficiency Theophylline clearance is decreased by 50% or more in patients with hepatic insufficiency (e.g., cirrhosis, acute hepatitis, cholestasis). Careful attention to dose reduction and frequent monitoring of serum theophylline concentrations are required in patients with reduced hepatic function (see WARNINGS).

Congestive Heart Failure (CHF) Theophylline clearance is decreased by 50% or more in patients with CHF. The extent of reduction in theophylline clearance in patients with CHF appears to be directly correlated to the severity of the cardiac disease. Since theophylline clearance is independent of liver blood flow, the reduction in clearance appears to be due to impaired hepatocyte function rather than reduced perfusion. Careful attention to dose reduction and frequent monitoring of serum theophylline concentrations are required in patients with CHF (see WARNINGS)

Smokers Tobacco and marijuana smoking appears to increase the clearance of theophylline by induction of metabolic pathways. Theophylline clearance has been shown to increase by approximately 50% in young adult tobacco smokers and by approximately 80% in elderly tobacco smokers compared to non-smoking subjects. Passive smoke exposure has also been shown to increase theophylline clearance by up to 50%. Abstinence from tobacco smoking for one week causes a reduction of approximately 40% in theophylline clearance. Careful attention to dose reduction and frequent monitoring of serum theophylline concentrations are required in patients who stop smoking (see WARNINGS). Use of nicotine gum has been shown to have no effect on theophylline clearance.

Fever Fever, regardless of its underlying cause, can decrease the clearance of theophylline. The magnitude and duration of the fever appear to be directly correlated to the degree of decrease of theophylline clearance. Precise data are lacking, but a temperature of 39°C (102°F) for at least 24 hours is probably required to produce a clinically significant increase in serum theophylline concentrations. Children with rapid rates of theophylline clearance (i.e., those who require a dose that is substantially larger than average [e.g., >22 mg/kg/day] to achieve a therapeutic peak serum theophylline concentration when afebrile) may be at greater risk of toxic effects from decreased clearance during sustained fever. Careful attention to dose reduction and frequent monitoring of serum theophylline concentrations are required in patients with sustained fever (see WARNINGS).

Miscellaneous

Other factors associated with decreased theophylline clearance include the third trimester of pregnancy, sepsis with multiple organ failure, and hypothyroidism. Careful attention to dose reduction and frequent monitoring of serum theophylline concentrations are required in patients with any of these conditions (see WARNINGS). Other factors associated with increased theophylline clearance include hyperthyroidism and cystic fibrosis.

Clinical Studies

In patients with chronic asthma, including patients with severe asthma requiring inhaled corticosteroids or alternate-day oral corticosteroids, many clinical studies have shown that theophylline decreases the frequency and severity of symptoms, including nocturnal exacerbations, and decreases the “as needed” use of inhaled beta-2 agonists. Theophylline has also been shown to reduce the need for short courses of daily oral prednisone to relieve exacerbations of airway obstruction that are unresponsive to bronchodilators in asthmatics.

In patients with chronic obstructive pulmonary disease (COPD), clinical studies have shown that theophylline decreases dyspnea, air trapping, the work of breathing, and improves contractility of diaphragmatic muscles with little or no improvement in pulmonary function measurements.

Indications and Usage

Theophylline is indicated for the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, e.g., emphysema and chronic bronchitis.

Contraindications

QUIBRON®-T ACCUDOSE® Tablets are contraindicated in patients with a history of hypersensitivity to theophylline or other components in the product.

Warnings

Concurrent Illness:

Theophylline should be used with extreme caution in patients with the following clinical conditions due to the increased risk of exacerbation of the concurrent condition:

Active peptic ulcer disease

Seizure disorders

Cardiac arrhythmias (not including bradyarrhythmias)

Conditions That Reduce Theophylline Clearance:

There are several readily identifiable causes of reduced theophylline clearance. If the total daily dose is not appropriately reduced in the presence of these risk factors, severe and potentially fatal theophylline toxicity can occur. Careful consideration must be given to the benefits and risks of theophylline use and the need for more intensive monitoring of serum theophylline concentrations in patients with the following risk factors:

Age

Neonates (term and premature)

Children <1 year

Elderly (>60 years)

Concurrent Diseases

Acute pulmonary edema

Congestive heart failure

Cor-pulmonale

Fever; ≥102° for 24 hours or more; or lesser temperature elevations for longer periods

Hypothyroidism

Liver disease; cirrhosis, acute hepatitis

Reduced renal function in infants <3 months of age

Sepsis with multi-organ failure

Shock

Cessation of Smoking

Drug Interactions Adding a drug that inhibits theophylline metabolism (e.g., cimetidine, erythromycin, tacrine) or stopping a concurrently administered drug that enhances theophylline metabolism (e.g., carbamazepine, rifampin). (see PRECAUTIONS, Drug Interactions, Table II).

When Signs or Symptoms of Theophylline Toxicity Are Present:

Whenever a patient receiving theophylline develops nausea or vomiting, particularly repetitive vomiting, or other signs or symptoms consistent with theophylline toxicity (even if another cause may be suspected), additional doses of theophylline should be withheld and a serum theophylline concentration measured immediately. Patients should be instructed not to continue any dosage that causes adverse effects and to withhold subsequent doses until the symptoms have resolved, at which time the clinician may instruct the patient to resume the drug at a lower dosage (see DOSAGE AND ADMINISTRATION, Dosing Guidelines, Table VI).

Dosage Increases:

Increases in the dose of theophylline should not be made in response to an acute exacerbation of symptoms of chronic lung disease since theophylline provides little added benefit to inhaled beta2-selective agonists and systemically administered corticosteroids in this circumstance and increases the risk of adverse effects. A peak steady-state serum theophylline concentration should be measured before increasing the dose in response to persistent chronic symptoms to ascertain whether an increase in dose is safe. Before increasing the theophylline dose on the basis of a low serum concentration, the clinician should consider whether the blood sample was obtained at an appropriate time in relationship to the dose and whether the patient has adhered to the prescribed regimen (see PRECAUTIONS, Laboratory Tests).

As the rate of theophylline clearance may be dose-dependent (i.e., steady-state serum concentrations may increase disproportionately to the increase in dose), an increase in dose based upon a sub-therapeutic serum concentration measurement should be conservative. In general, limiting dose increases to about 25% of the previous total daily dose will reduce the risk of unintended excessive increases in serum theophylline concentration (see DOSAGE AND ADMINISTRATION, Table VI).

Precautions

General:

Careful consideration of the various interacting drugs and physiologic conditions that can alter theophylline clearance and require dosage adjustment should occur prior to initiation of theophylline therapy, prior to increases in theophylline dose, and during follow-up (see WARNINGS). The dose of theophylline selected for initiation of therapy should be low and, if tolerated, increased slowly over a period of a week or longer with the final dose guided by monitoring serum theophylline concentrations and the patient’s clinical response (see DOSAGE AND ADMINISTRATION, Table V).

Monitoring Serum Theophylline Concentrations:

Serum theophylline concentration measurements are readily available and should be used to determine whether the dosage is appropriate. Specifically, the serum theophylline concentration should be measured as follows:

When initiating therapy to guide final dosage adjustment after titration

Before making a dose increase to determine whether the serum concentration is subtherapeutic in a patient who continues to be symptomatic.

Whenever signs or symptoms of theophylline toxicity are present.

Whenever there is a new illness, worsening of a chronic illness or a change in the patient’s treatment regimen that may alter theophylline clearance (e.g., fever >102°F sustained for ³24 hours, hepatitis, or drugs listed in Table II are added or discontinued).

To guide a dose increase, the blood sample should be obtained at the time of the expected peak serum theophylline concentration; 1-2 hours after a dose at steady-state. For most patients, steady-state will be reached after 3 days of dosing when no doses have been missed, no extra doses have been added, and none of the doses have been taken at unequal intervals. A trough concentration (i.e., at the end of the dosing interval) provides no additional useful information and may lead to an inappropriate dose increase since the peak serum theophylline concentration can be two or more times greater than the trough concentration with an immediate-release formulation. If the serum sample is drawn more than two hours after the dose, the results must be interpretedwith caution since the concentration may not be reflective of the peak concentration. In contrast, when signs or symptoms of theophylline toxicity are present, the serum sample should be obtained as soon as possible, analyzed immediately, and the result reported to the clinician without delay. In patients in whom decreased serum protein binding is suspected (e.g., cirrhosis, women during the third trimester of pregnancy), the concentration of unbound theophylline should be measured and the dosage adjusted to achieve an unbound concentration of 6- 12 mcg/mL.

Saliva concentrations of theophylline cannot be used reliably to adjust dosage without special techniques.

Effects on Laboratory Tests:

As a result of its pharmacological effects, theophylline at serum concentrations within the 10-20 mcg/mL range modestly increases plasma glucose (from a mean of 88 mg% to 98 mg%), uric acid (from a mean of 4 mg/dL to 6 mg/dL), free fatty acids (from a mean of 451µeq/l to 800 µeq/l, total cholesterol (from a mean of 140 vs 160 mg/dL), HDL (from a mean of 36 to 50 mg/dL), HDL/LDL ratio (from a mean of 0.5 to 0.7), and urinary free cortisol excretion (from a mean of 44 to 63 mcg/24 hr). Theophylline at serum concentrations within the 10-20 mcg/mL range may also transiently decrease serum concentrations of triiodothyronine (144 before, 131 after one week and 142 ng/dL after 4 weeks of theophylline). The clinical importance of these changes should be weighed against the potential therapeutic benefit of theophylline in individual patients.

Information for Patients:

The patient (or parent/care giver) should be instructed to seek medical advice whenever nausea, vomiting, persistent headache, insomnia or rapid heart beat occurs during treatment with theophylline, even if another cause is suspected. The patient should be instructed to contact their clinician if they develop a new illness, especially if accompanied by a persistent fever, if they experience worsening of a chronic illness, if they start or stop smoking cigarettes or marijuana, or if another clinician adds a new medication or discontinues a previously prescribed medication. Patients should be instructed to inform all clinicians involved in their care that they are taking theophylline, especially when a medication is being added or deleted from their treatment. Patients should be instructed to not alter the dose, timing of the dose, or frequency of administration without first consulting their clinician. If a dose is missed, the patient should be instructed to take the next dose at the usually scheduled time and to not attempt to make up for the missed dose.

Drug Interactions:

Theophylline interacts with a wide variety of drugs. The interaction may be pharmacodynamic, i.e., alterations in the therapeutic response to theophylline or another drug or occurrence of adverse effects without a change in serum theophylline concentration. More frequently, however, the interaction is pharmacokinetic, i.e., the rate of theophylline clearance is altered by another drug resulting in increased or decreased serum theophylline concentrations. Theophylline only rarely alters the pharmacokinetics of other drugs.

The drugs listed in Table II have the potential to produce clinically significant pharmacodynamic or pharmacokinetic interactions with theophylline. The information in the “Effect” column of Table II assumes that the interacting drug is being added to a steadystate theophylline regimen. If theophylline is being initiated in a patient who is already taking a drug that inhibits theophylline clearance (e.g., cimetidine, erythromycin), the dose of theophylline required to achieve a therapeutic serum theophylline concentration will be smaller. Conversely, if theophylline is being initiated in a patient who is already taking a drug that enhances theophylline clearance (e.g., rifampin), the dose of theophylline required to achieve a therapeutic serum theophylline concentration will be larger. Discontinuation of a concomitant drug that increases theophylline clearance will result in accumulation of theophylline to potentially toxic levels, unless the theophylline dose is appropriately reduced. Discontinuation of a concomitant drug that inhibits theophylline clearance will result in decreased serum theophylline concentrations, unless the theophylline dose is appropriately increased.

The drugs listed in Table III have either been documented not to interact with theophylline or do not produce a clinically significant interaction (i.e., <15% change in theophylline clearance).

The listing of drugs in Tables II and III are current as of October 8, 1996. New interactions are continuously being reported for theophylline, especially with new chemical entities. The clinician should not assume that a drug does not interact with theophylline if it is not listed in Table II. Before addition of a newly available drug in a patient receiving theophylline, the package insert of the new drug and/or the medical literature should be consulted to determine if an interaction between the new drug and theophylline has been reported.

Table II. Clinically significant drug interactions with theophylline*.
Drug	Type of Interaction	Effect**
Adenosine	Theophylline blocks adenosine receptors.	Higher doses of adenosine may be required to achieve desired effect.
Alcohol	A single large dose of alcohol (3 mL/kg of whiskey) decreases theophylline clearance for up to 24 hours.	30% increase
Allopurinol	Decreases theophylline clearance at allopurinol doses ≥600 mg/day.	25% increase
Aminoglutethimide	Increases theophylline clearance by induction of microsomal enzyme activity.	25% decrease
Carbamazepine	Similar to aminoglutethimide.	30% decrease
Cimetidine	Decreases theophylline clearance by inhibiting cytochrome P450 1A2.	70% increase
Ciprofloxacin	Similar to cimetidine.	40% increase
Clarithromycin	Similar to erythromycin.	25% increase
Diazepam	Benzodiazepines increase CNS concentrations of adenosine, a potent CNS depressant, while theophylline blocks adenosine receptors.	Larger diazepam doses may be required to produce desired level of sedation. Discontinuation of theophylline without reduction of diazepam dose may result in respiratory depression.
Disulfiram	Decreases theophylline clearance by inhibiting hydroxylation and demethylation.	50% increase
Enoxacin	Similar to cimetidine.	300% increase
Ephedrine	Synergistic CNS effects	Increased frequency of nausea, nervousness, and insomnia.
Erythromycin	Erythromycin metabolite decreases theophylline clearance by inhibiting cytochrome P450 3A3.	35% increase. Erythromycin steady-stateserum concentrations decrease by a similar amount.
Estrogen	Estrogen containing oral contraceptives decrease theophylline clearance in a dose-dependent fashion. The effect of progesterone on theophylline clearance is unknown.	30% increase
Flurazepam	Similar to diazepam.	Similar to diazepam.
Fluvoxamine	Similar to cimetidine.	Similar to cimetidine.
Halothane	Halothane sensitizes the myocardium to catecholamines, theophylline increases release of endogenous catecholamines.	Increased risk of ventricular arrhythmias.
Interferon, human recombinant alpha-A	Decreases theophylline clearance.	100% increase
Isoproterenol (IV)	Increases theophylline clearance.	20% decrease
Ketamine	Pharmacologic	May lower theophylline seizure threshold.
Lithium	Theophylline increases renal lithium clearance.	Lithium dose required to achieve a therapeutic serum concentration increased an average of 60%.
Lorazepam	Similar to diazepam.	Similar to diazepam.
Methotrexate (MTX)	Decreases theophylline clearance.	20% increase after low dose MTX, higher dose MTX may have a greater effect.
Mexiletine	Similar to disulfiram.	80% increase
Midazolam	Similar to diazepam.	Similar to diazepam.
Moricizine	Increases theophylline clearance.	25% decrease
Pancuronium	Theophylline may antagonize non-depolarizing neuromuscular blocking effects; possibly due to phosphodiesterase inhibition.	Larger dose of pancuronium may be required to achieve neuromuscular blockade.
Pentoxifylline	Decreases theophylline clearance.	30% increase
Phenobarbital (PB)	Similar to aminoglutethimide.	25% decrease after two weeks of concurrent PB.
Phenytoin	Phenytoin increases theophylline clearance by increasing microsomal enzyme activity. Theophylline decreases phenytoin absorption.	Serum theophylline and phenytoin concentrations decrease about 40%.
Propafenone	Decreases theophylline clearance and pharmacologic interaction.	40% increase. Beta-2 blocking effect may decrease efficacy of theophylline.
Propranolol	Similar to cimetidine and pharmacologic interaction.	100% increase. Beta-2 blocking effect may decrease efficacy of theophylline.
Rifampin	Increases theophylline clearance by increasing cytochrome P4501A2 and 3A3 activity.	20-40% decrease
Sulfinpyrazone	Increases theophylline clearance by increasing demethylation and hydroxylation. Decreases renal clearance of theophylline.	20% decrease
Tacrine	Similar to cimetidine, also increases renal clearance of theophylline.	90% increase
Thiabendazole	Decreases theophylline clearance.	190% increase
Ticlopidine	Decreases theophylline clearance.	60% increase
Troleandomycin	Similar to erythromycin.	33-100% increase depending on troleandomycin dose.
Verapamil	Similar to disulfiram.	20% increase
* Refer to PRECAUTIONS, Drug Interactions for further information regarding table.
** Average effect on steady state theophylline concentration or other clinical effect for pharmacologic interactions. Individual patients may experience larger changes in serum theophylline concentration than the value listed.

Table III. Drugs that have been documented not to interact with theophylline or drugs that produce no clinically significant interaction with theophylline.*
albuterol, systemic and inhaled	lomefloxacin
amoxicillin	mebendazole
ampicillin, with or without sulbactam	medroxyprogesterone
atenolol	methylprednisolone
azithromycin	metronidazole
caffeine, dietary ingestion	metoprolol
cefaclor	nadolol
co-trimoxazole (trimethoprim and sulfamethoxazole)	nifedipine
diltiazem	nizatidine
dirithromycin	norfloxacin
enflurane	ofloxacin
famotidine	omeprazole
felodipine	prednisone, prednisolone
finasteride	ranitidine
hydrocortisone	rifabutin
isoflurane	roxithromycin
isoniazid	sorbitol (purgative doses do not inhibit theophylline absorption)
isradipine	sucralfate
influenza vaccine	terbutaline, systemic
ketoconazole	terfenadine
	tetracycline
	tocainide
* Refer to PRECAUTIONS, Drug Interactions for information regarding table.

The Effect of Other Drugs on Theophylline Serum Concentration Measurements:

Most serum theophylline assays in clinical use are immunoassays which are specific for theophylline. Other xanthines such as caffeine, dyphylline, and pentoxifylline are not detected by these assays. Some drugs (e.g.,cefazolin, cephalothin), however, may interfere with certain HPLC techniques. Caffeine and xanthine metabolites in neonates or patients with renal dysfunction may cause the reading from some dry reagent office methods to be higher than the actual serum theophylline concentration.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term carcinogenicity studies have been carried out in mice (oral doses 30-150 mg/kg)and rats (oral doses 5-75 mg/kg). Results are pending.

Theophylline has been studied in Ames salmonella, in vivo and in vitro cytogenetics, micronucleus and Chinese hamster ovary test systems and has not been shown to be genotoxic.

In a 14 week continuous breeding study, theophylline, administered to mating pairs of B6C3F1 mice at oral doses of 120, 270 and 500 mg/kg (approximately 1.0- 3.0 times the human dose on a mg/m2 basis) impaired fertility, as evidenced by decreases in the number of live pups per litter, decreases in the mean number of litters per fertile pair, and increases in the gestation period at the high dose as well as decreases in the proportion of pups born alive at the mid and high dose. In 13 week toxicity studies, theophylline was administered to F344 rats and B6C3F1 mice at oral doses of 40-300 mg/kg (approximately 2.0 times the human dose on a mg/m2 basis). At the high dose, systemic toxicity was observed in both species including decreases in testicular weight.

Pregnancy

CATEGORY C:

There are no adequate and well-controlled studies in pregnant women. Additionally, there are no teratogenicity studies in non-rodents (e.g., rabbits). Theophylline was not shown to be teratogenic in CD-1 mice at oral doses up to 400 mg/kg, approximately 2.0 times the human dose on a mg/m2 basis or in CD-1 rats at oral doses up to 260 mg/kg, approximately 3.0 times the recommended human dose on a mg/m2 basis. At a dose of 220 mg/kg, embryotoxicity was observed in rats in the absence of maternal toxicity.

Nursing Mothers:

Theophylline is excreted into breast milk and may cause irritability or other signs of mild toxicity in nursing human infants. The concentration of theophylline in breast milk is about equivalent to the maternal serum concentration. An infant ingesting a liter of breast milk containing 10-20 mcg/mL of theophylline a day is likely to receive 10-20 mg of theophylline per day. Serious adverse effects in the infant are unlikely unless the mother has toxic serum theophylline concentrations.

Pediatric Use

Theophylline is safe and effective for the approved indications in pediatric patients. The maintenance dose of theophylline must be selected with caution in pediatric patients since the rate of theophylline clearance is highly variable across the age range of neonates to adolescents (see CLINICAL PHARMACOLOGY, Table I, WARNINGS, and DOSAGE AND ADMINISTRATION, Table V). Due to the immaturity of theophylline metabolic pathways in infants under the age of one year, particular attention to dosage selection and frequent monitoring of serum theophylline concentrations are required when theophylline is prescribed to pediatric patients in this age group.

Geriatric Use:

Elderly patients are at significantly greater risk of experiencing serious toxicity from theophylline than younger patients due to pharmacokinetic and pharmacodynamic changes associated with aging. Theophylline clearance is reduced in patients greater than 60 years of age, resulting in increased serum theophylline concentrations in response to a given theophylline dose. Protein binding may be decreased in the elderly resulting in a larger proportion of the total serum theophylline concentration in the pharmacologically active unbound form. Elderly patients also appear to be more sensitive to the toxic effects of theophylline after chronic overdosage than younger patients. For these reasons, the maximum daily dose of theophylline in patients greater than 60 years of age ordinarily should not exceed 400 mg/day unless the patient continues to be symptomatic and the peak steady state serum theophylline concentration is <10 mcg/mL (see DOSAGE AND ADMINISTRATION). Theophylline doses greater than 400 mg/day should be prescribed with caution in elderly patients.

Adverse Reactions

Adverse reactions associated with theophylline are generally mild when peak serum theophylline concentrations are <20 mcg/mL and mainly consist of transient caffeine-like adverse effects such as nausea, vomiting, headache, and insomnia. When peak serum theophylline concentrations exceed 20 mcg/mL, however, theophylline produces a wide range of adverse reactions including persistent vomiting, cardiac arrhythmias, and intractable seizures which can be lethal (see OVERDOSAGE). The transient caffeine-like adverse reactions occur in about 50% of patients when theophylline therapy is initiated at doses higher than recommended initial doses (e.g.,>300 mg/day in adults and >12 mg/kg/day in children beyond >1 year of age). During the initiation of theophylline therapy, caffeine-like adverse effects may transiently alter patient behavior, especially in school age children, but this response rarely persists. Initiation of theophylline therapy at a low dose with subsequent slow titration to a predetermined age-related maximum dose will significantly reduce the frequency of these transient adverse effects (seeDOSAGE AND ADMINISTRATION, Table V). In a small percentage of patients (<3% of children and <10% of adults) the caffeine-like adverse effects persist during maintenance therapy, even at peak serum theophylline concentrations within the therapeutic range (i.e., 10-20 mcg/mL). Dosage reduction may alleviate the caffeine-like adverse effects in

Quinapril Hydrochloride

Class: Angiotensin-Converting Enzyme Inhibitors
VA Class: CV800
Chemical Name: [3S-[2[R*(R)],3R*]]-2-[2-[[1-Ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1,2 ,3,4-tetrahydro-3-isoquinolinecarboxylic acid monohydrochloride
Molecular Formula: C₂₅H₃₀N₂O₅•HCl
CAS Number: 82586-55-8
Brands: Accupril, Accuretic

May cause fetal and neonatal morbidity and mortality if used during pregnancy.¹ ⁴⁷ ⁶⁵ ⁶⁶ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

If pregnancy is detected, discontinue quinapril as soon as possible.¹ ⁴⁷ ⁶⁶

Introduction

Nonsulfhydryl ACE inhibitor.¹ ² ³ ⁴⁷

Uses for Quinapril Hydrochloride

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).¹ ² ⁴ ¹¹ ²⁸ ⁴⁷

One of several preferred initial therapies in hypertensive patients with heart failure, postmyocardial infarction, high coronary disease risk, diabetes mellitus, chronic renal failure, and/or cerebrovascular disease.⁵⁰

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.⁵⁰

CHF

Management of symptomatic CHF, usually in conjunction with cardiac glycosides, diuretics, and β-adrenergic blocking agents.¹

Diabetic Nephropathy

A first-line agent in the treatment of diabetic nephropathy† in hypertensive patients with type 2 diabetes mellitus.⁴² ⁵⁴ ⁵⁵ ⁵⁶ ⁵⁷ ⁵⁸ ⁵⁹ ⁶⁰ ⁶¹

Quinapril Hydrochloride Dosage and Administration

General

Hypertension

Quinapril/hydrochlorothiazide fixed combinations should not be used for initial treatment of hypertension.⁴⁷

Administration

Oral Administration

Administer orally once or twice daily.¹ ⁴⁷

Manufacturer makes no specific recommendation regarding administration of quinapril with meals;¹ ⁴⁷ administer quinapril/hydrochlorothiazide fixed combinations without regard to meals.⁴⁷ (See Food under Pharmacokinetics.)

Dosage

Available as quinapril hydrochloride; dosage expressed in terms of quinapril.¹ ⁴⁷

Pediatric Patients

Hypertension†

Oral

Some experts recommend an initial dosage of 5–10 mg once daily.⁶² Increase dosage as necessary to a maximum dosage of 80 mg once daily.⁶²

Adults

Hypertension

Oral

Initially, 10 or 20 mg once daily as monotherapy.¹ ² ³ ¹¹ ²⁸ ⁵⁰ Adjust dosage at ≥2-week intervals to achieve BP control.¹

In patients currently receiving diuretic therapy, discontinue diuretic, if possible, 2–3 days before initiating quinapril.¹ May cautiously resume diuretic therapy if BP not controlled adequately with quinapril alone.¹ If diuretic cannot be discontinued, increase sodium intake and initiate quinapril at 5 mg daily under close medical supervision for several hours and until BP has stabilized.¹

Usual dosage: 20–80 mg daily, given in 1 dose or 2 divided doses.¹ ²⁸ ⁵⁰

If effectiveness diminishes toward end of dosing interval in patients treated once daily, consider increasing dosage or administering drug in 2 divided doses.¹ ²⁸

Quinapril/Hydrochlorothiazide Combination Therapy

Oral

If BP is not adequately controlled by monotherapy with quinapril or hydrochlorothiazide, can switch to the fixed-combination preparation containing quinapril 10 mg and hydrochlorothiazide 12.5 mg or, alternatively, quinapril 20 mg and hydrochlorothiazide 12.5 mg.⁴⁷ Adjust dosage of either or both drugs according to patient’s response.⁴⁷

If BP is controlled by monotherapy with hydrochlorothiazide 25 mg daily but potassium loss is problematic, can switch to fixed-combination preparation containing quinapril 10 mg and hydrochlorothiazide 12.5 mg or, alternatively, quinapril 20 mg and hydrochlorothiazide 12.5 mg.⁴⁷

If BP is controlled with quinapril 20 mg and hydrochlorothiazide 25 mg (administered separately) and if no clinically important electrolyte disturbance is observed, can switch to the fixed-combination preparation containing these corresponding doses for convenience.⁴⁷

CHF

Oral

Initially, 5 mg twice daily.¹ Monitor closely for ≥2 hours until BP has stabilized.¹ To minimize risk of hypotension, reduce diuretic dosage, if possible.¹

Adjust dosage at weekly intervals to reach usual dosage.¹

Usual dosage: 20–40 mg daily, given in 2 equally divided doses.¹

Prescribing Limits

Pediatric Patients

Hypertension†

Oral

Maximum 80 mg daily.⁶²

Special Populations

Renal Impairment

Hypertension

Oral

Initially, 10 mg once daily in adults with Cl_cr >60 mL/minute; 5 mg once daily in those with Cl_cr 30–60 mL/minute; or 2.5 mg once daily in those with Cl_cr 10–30 mL/minute.¹ Titrate at 2-week intervals until BP is controlled.¹ (See Renal Impairment under Cautions.)

Quinapril/hydrochlorothiazide fixed combinations are not recommended in patients with severe renal impairment (Cl_cr ≤30 mL/minute or S_cr >3 mg/dL).⁴⁷

CHF

Oral

Initially (first day), 5 mg in patients with moderate renal impairment (Cl_cr >30 mL/minute) or 2.5 mg in patients with severe renal impairment (Cl_cr 10–30 mL/minute) under close medical supervision.¹ If well tolerated, administer as twice-daily regimen on subsequent days.¹ Titrate at weekly intervals based on clinical and hemodynamic response.¹

Geriatric Patients

Hypertension

Oral

Initially, 10 mg once daily as monotherapy.¹ Adjust dosage at ≥2-week intervals to achieve BP control.¹

Cautions for Quinapril Hydrochloride

Contraindications

Known hypersensitivity (e.g., history of angioedema) to quinapril or another ACE inhibitor.¹ ⁴⁷

Warnings/Precautions

Warnings

Hepatic Effects

Clinical syndrome that usually is manifested initially by cholestatic jaundice and may progress to fulminant hepatic necrosis (occasionally fatal) reported rarely with ACE inhibitors.¹ ⁴⁷

If jaundice or marked elevation of liver enzymes occurs, discontinue drug and monitor patient.¹ ⁴⁷

Hypotension

Possible symptomatic hypotension, sometimes associated with oliguria and/or progressive azotemia and, rarely, acute renal failure and/or death.¹ ⁴⁷ Patients at particular risk include those with intensive diuretic therapy or recent increase in diuretic dose, dialysis, or severe volume and/or salt depletion.¹ ⁴⁷

Risk of marked hypotension in patients with CHF.¹ ⁴⁷ Potential for MI or stroke in patients with ischemic cardiovascular or cerebrovascular disease.¹ ⁴⁷

Hypotension may occur in patients undergoing surgery or during anesthesia with agents that produce hypotension; recommended treatment is fluid volume expansion.¹ ⁴⁷

To minimize potential for hypotension, consider recent antihypertensive therapy, extent of BP elevation, sodium intake, fluid status, and other clinical conditions.¹ ⁴⁷ May minimize potential for hypotension by withholding diuretic therapy (except in patients with CHF), reducing diuretic dosage, and/or increasing sodium intake (except in patients with CHF) prior to initiation of quinapril.¹ ⁴⁷ (See Dosage under Dosage and Administration.)

In patients at risk of excessive hypotension, initiate therapy under close medical supervision; monitor closely for first 2 weeks following initiation of quinapril or any increase in quinapril or diuretic dosage.¹ ⁴⁷

If excessive hypotension occurs, immediately place patient in supine position and, if necessary, administer IV infusion of 0.9% sodium chloride solution.¹ ⁴⁷ Quinapril therapy usually can be continued following restoration of volume and BP.¹ ⁴⁷ If symptomatic hypotension develops, dosage reduction or discontinuance of quinapril or diuretic may be necessary.¹ ⁴⁷

Hematologic Effects

Neutropenia and agranulocytosis reported with captopril; risk appears to depend principally on presence of renal impairment and/or presence of collagen vascular disease.¹ ⁴⁷ Data insufficient to rule out similar incidence of agranulocytosis with quinapril.¹ ⁴⁷

Consider monitoring leukocytes in patients with collagen vascular disease and/or renal disease.¹ ⁴⁷

Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when used during pregnancy.¹ ⁴⁷ ⁶⁵ ⁶⁶ (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.⁶⁶

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.⁶⁵ ⁶⁶

Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.⁶⁶ Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.¹ ⁴⁷

Sensitivity Reactions

Anaphylactoid reactions and/or head and neck angioedema possible; if associated with laryngeal edema, may be fatal.¹ ⁴⁷ ^b Immediate medical intervention (e.g., epinephrine) for involvement of tongue, glottis, or larynx.¹ ⁴⁷

Intestinal angioedema reported; sometimes occurs in patients with no prior history of facial angioedema.¹ ^b Manifestations include abdominal pain (with or without nausea or vomiting).¹ ^b Consider intestinal angioedema in the differential diagnosis of patients receiving ACE inhibitors presenting with abdominal pain.¹ ^b

Anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing LDL apheresis with dextran sulfate absorption or following initiation of hemodialysis that utilized high-flux membrane.¹ ⁴⁷

Life-threatening anaphylactoid reactions reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom.¹ ⁴⁷

Contraindicated in patients with a history of angioedema associated with ACE inhibitors.¹ ⁴⁷

General Precautions

Renal Effects

Transient increases in BUN and S_cr possible, especially in patients with preexisting renal impairment or those receiving concomitant diuretic therapy.¹ ⁴⁷ Possible increases in BUN and S_cr in patients with unilateral or bilateral renal artery stenosis; generally reversible following discontinuance of ACE inhibitor and/or diuretic.¹ ⁴⁷

Possible oliguria, progressive azotemia, and, rarely, acute renal failure and/or death in patients with severe CHF.¹ ⁴⁷

Closely monitor renal function for the first few weeks of therapy in hypertensive patients with unilateral or bilateral renal-artery stenosis.¹ ⁴⁷ Some patients may require dosage reduction or discontinuance of ACE inhibitor or diuretic.¹ ⁴⁷

Hyperkalemia

Possible hyperkalemia, especially in patients with renal impairment or diabetes mellitus and those receiving drugs that can increase serum potassium concentration (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes).¹ ⁴⁷ (See Specific Drugs under Interactions.)

Monitor serum potassium concentration carefully in these patients.¹ ⁴⁷

Cough

Persistent and nonproductive cough; resolves after drug discontinuance.¹ ⁴⁷

Use of Fixed Combinations

When used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.⁴⁷

Specific Populations

Pregnancy

Category C (1st trimester); Category D (2nd and 3rd trimesters).¹ ⁴⁷ (See Fetal/Neonatal Morbidity and Mortality under Cautions and see Boxed Warning.)

Lactation

Distributed into milk.¹ ⁴⁷ Caution if used in nursing women.⁴⁷ ³ ⁴

Pediatric Use

Safety and efficacy remain to be fully established in children;¹ ⁴⁷ however, some experts have recommended dosages for hypertension based on current limited clinical experience.⁶²

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹ ⁴⁷ However, cautious dosing recommended due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.¹ ⁴⁷

Renal Impairment

Deterioration of renal function may occur. (See Renal Effects under Cautions.)¹ ⁴⁷

Initial dosage adjustment recommended in patients with renal impairment.¹ (See Renal Impairment under Dosage and Administration.) Safety and efficacy not established in patients with Cl_cr <10 mL/minute.¹ ⁴⁷

Quinapril/hydrochlorothiazide fixed combinations are not recommended in patients with severe renal impairment (Cl_cr ≤30 mL/minute or S_cr >3 mg/dL).⁴⁷

Hepatic Impairment

Use with caution in patients with hepatic impairment or progressive liver disease.⁴⁷

Blacks

BP reduction may be smaller in black patients compared with nonblack patients;¹ ²⁴ ²⁵ ⁴⁷ ⁴⁸ ⁴⁹ however, no apparent population difference during combined therapy with ACE inhibitor and thiazide diuretic.¹¹ ²⁴ ²⁶ ²⁷ ²⁸ ⁴⁷ Use in combination with a diuretic.¹¹ ⁴²

Higher incidence of angioedema reported with ACE inhibitors in blacks compared with other races.¹ ⁴⁷ ⁴⁹ ⁵⁰

Common Adverse Effects

Patients with hypertension: Headache, dizziness, fatigue, cough, nausea, vomiting, abdominal pain.¹ ⁴⁷ With fixed combination preparation, myalgia, virus infection, rhinitis, back pain, diarrhea, upper respiratory tract infection, insomnia, somnolence, bronchitis, dyspepsia, asthenia, pharyngitis, vasodilation, vertigo, chest pain.⁴⁷

Patients with CHF: Dizziness, cough, fatigue, nausea, vomiting, chest pain, hypotension, dyspnea, diarrhea, headache, myalgia, rash, back pain, increased serum creatinine concentration, increased BUN.¹

Interactions for Quinapril Hydrochloride

Drugs That Interact with Magnesium

Possible decreased absorption of drugs that interact with magnesium, possibly due to high magnesium content in quinapril-containing preparations.¹ ⁴⁷

Specific Drugs

Drug	Interaction	Comments
Atorvastatin	Pharmacokinetic interaction unlikely¹
Cimetidine	Pharmacokinetic interaction unlikely¹ ⁴⁷
Digoxin	Pharmacokinetic interaction unlikely¹ ⁴⁷
Diuretics	Increased hypotensive effect¹ ⁴⁷	If possible, discontinue diuretic before initiating quinapril¹ ⁴⁷ (See Dosage under Dosage and Administration)
Diuretics, potassium-sparing (amiloride, spironolactone, triamterene)	Enhanced hyperkalemic effect¹ ⁴⁷	Use with caution; monitor serum potassium concentrations frequently¹ ⁴⁷
Lithium	Increased serum lithium concentrations; possible toxicity¹ ⁴⁷	Monitor serum lithium concentrations frequently¹ ⁴⁷
Potassium supplements or potassium-containing salt substitutes	Enhanced hyperkalemic effect¹ ⁴⁷	Use with caution; monitor serum potassium concentrations frequently¹ ⁴⁷
Propranolol	Pharmacokinetic interaction unlikely¹ ⁴⁷
Tetracycline	Decreased tetracycline absorption¹ ⁴⁷
Warfarin	Pharmacologic interaction unlikely¹ ⁴⁷

Quinapril Hydrochloride Pharmacokinetics

Absorption

Bioavailability

About 60% of oral dose is absorbed.¹ ⁴⁷

Peak plasma concentrations of quinapril and quinaprilat are achieved within 1 and 2 hours, respectively.¹ ⁴⁷

Onset

Following a single oral dose, antihypertensive effects are observed within 1 hour, with peak BP reduction at 2–4 hours.¹ ⁴⁷

During chronic therapy, maximum antihypertensive effect is achieved after 1–2 weeks.¹ ⁴⁷

Duration

Inhibition of >80% of ACE activity persists for about 24 hours.¹ ⁴⁷ Inhibition of 75% of the pressor response to angiotensin I persists for about 4 hours.¹ ⁴⁷

Food

High-fat meals result in moderate (25–30%) reductions in rate and extent of absorption of quinapril.¹ ⁴⁷ When quinapril/hydrochlorothiazide combination is administered with high-fat meals, rate of quinapril absorption is reduced by 14%, but extent of absorption is unaffected.⁴⁷

Special Populations

Decreased quinaprilat concentrations in patients with alcoholic cirrhosis.¹ ⁴⁷

Distribution

Extent

Quinapril and quinaprilat do not cross the blood-brain barrier.¹ ⁴⁷

Crosses the placenta in rats.¹ ⁴⁷ Distributed into human milk.¹ ⁴⁷

Plasma Protein Binding

97% for both quinapril and quinaprilat.¹ ⁴⁷

Elimination

Metabolism

Metabolized principally to an active metabolite, quinaprilat (approximately 38% of oral dose).¹ ⁴⁷

Elimination Route

Eliminated principally in urine (as metabolites).¹ ⁴⁷

Not removed by hemodialysis or peritoneal dialysis.¹ ⁴⁷

Half-life

Quinaprilat: Elimination: 2 hours; prolonged terminal phase of 25 hours.¹ ⁴⁷

Special Populations

In patients with renal impairment, elimination half-life increases with decreasing Cl_cr.¹ ⁴⁷

Decreased elimination of quinaprilat in patients ≥65 years of age.¹ ⁴⁷

Stability

Storage

Oral

Tablets

Conventional tablets: 15–30°C.¹ Protect from light.¹

Fixed combination tablets: 20–25°C.⁴⁷

ActionsActions

Prodrug; not pharmacologically active until hydrolyzed in the liver to quinaprilat.¹ ² ³ ⁴⁷

Suppresses the renin-angiotensin-aldosterone system.¹ ⁴⁷

Advice to Patients

Risk of angioedema, anaphylactoid reactions, or other sensitivity reactions.¹ ⁴⁷ Importance of reporting sensitivity reactions (e.g., edema of face, eyes, lips, tongue, or extremities; hoarseness; swallowing or breathing with difficulty) immediately to clinician and of discontinuing the drug.¹ ⁴⁷

Importance of reporting signs of infection (e.g., sore throat, fever).¹ ⁴⁷

Risk of hypotension.¹ ⁴⁷ Importance of informing clinicians promptly if lightheadedness or fainting occurs.¹ ⁴⁷

Importance of adequate fluid intake; risk of volume depletion with excessive perspiration, dehydration, vomiting, or diarrhea.¹ ⁴⁷

Risks of use during pregnancy.¹ ⁴⁷ ⁶⁵ ⁶⁶ (See Boxed Warning.)

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (including salt substitutes containing potassium).¹ ⁴⁷

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹ ⁴⁷

Importance of advising patients of other important precautionary information.¹ ⁴⁷ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Quinapril Hydrochloride
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	5 mg (of quinapril)*	Accupril (scored)	Pfizer
			Quinapril Hydrochloride Tablets	Ranbaxy
		10 mg (of quinapril)*	Accupril	Pfizer
			Quinapril Hydrochloride Tablets	Ranbaxy
		20 mg (of quinapril)*	Accupril	Pfizer
			Quinapril Hydrochloride Tablets	Ranbaxy
		40 mg (of quinapril)*	Accupril	Pfizer
			Quinapril Hydrochloride Tablets	Ranbaxy

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Quinapril Hydrochloride Combinations
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	10 mg (of quinapril) with Hydrochlorothiazide 12.5 mg*	Accuretic (with povidone; scored)	Pfizer
			Quinapril Hydrochloride and Hydrochlorothiazide Tablets	Mylan
			Quinaretic	Amide
		20 mg (of quinapril) with Hydrochlorothiazide 12.5 mg*	Accuretic (with povidone)	Pfizer
			Quinapril Hydrochloride and Hydrochlorothiazide Tablets	Mylan
			Quinaretic	Amide
		20 mg (of quinapril) with Hydrochlorithiazide 25 mg*	Accuretic (with povidone)	Pfizer
			Quinapril Hydrochloride and Hydrochlorothiazide Tablets	Mylan
			Quinaretic	Amide

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Accupril 10MG Tablets (PFIZER U.S.): 30/$66.99 or 90/$175.98

Accupril 20MG Tablets (PFIZER U.S.): 30/$66.99 or 90/$176.97

Accupril 40MG Tablets (PFIZER U.S.): 30/$66.99 or 90/$176.97

Accupril 5MG Tablets (PFIZER U.S.): 30/$65.97 or 90/$167.84

Accuretic 10-12.5MG Tablets (PFIZER U.S.): 30/$59.99 or 90/$179.98

Accuretic 20-12.5MG Tablets (PFIZER U.S.): 30/$64.2 or 90/$166.24

Accuretic 20-25MG Tablets (PFIZER U.S.): 30/$60.99 or 90/$182.97

Quinapril HCl 10MG Tablets (GREENSTONE): 30/$19.99 or 90/$50.97

Quinapril HCl 20MG Tablets (LUPIN PHARMACEUTICALS): 30/$26.97 or 90/$59.97

Quinapril HCl 40MG Tablets (LUPIN PHARMACEUTICALS): 30/$21.99 or 90/$50.97

Quinapril HCl 5MG Tablets (GREENSTONE): 30/$21.99 or 90/$50.97

Quinapril-Hydrochlorothiazide 10-12.5MG Tablets (MYLAN): 30/$35.99 or 90/$89.97

Quinapril-Hydrochlorothiazide 20-25MG Tablets (MYLAN): 90/$86.99 or 100/$95.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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2. Wadworth AN, Brogden RN. Quinapril: a review of its pharmacological properties, and therapeutic efficacy in cardiovascular disorders. Drugs. 1991; 41:378-99. [PubMed 1711445]

3. Anon. Quinapril for hypertension. Med Lett Drugs Ther. 1992; 34:27-8. [PubMed 1542279]

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5. Squibb. Capoten (captopril) tablets prescribing information. In: Physician’s desk reference. 47th ed. Montvale, NJ: Medical Economics Company Inc; 1993:2356-62.

6. Reviewers’ comments in Enalaprilat/Enalapril 24:32.04 (personal observations).

7. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The 1984 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Ann Intern Med. 1984; 144:1045-57.

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13. Packer M, Lee WH, Medina N. Functional renal insufficiency during long-term therapy with captopril and enalapril in severe chronic heart failure. Ann Intern Med. 1987; 106:346-54. [IDIS 226752] [PubMed 3028221]

14. Packer M, Lee WH, Yushak M. Comparison of captopril and enalapril in patients with severe chronic heart failure. N Engl J Med. 1986; 315:847-53. IDIS 221364.

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18. Riegger GA. The effects of ACE inhibitors on exercise capacity in the treatment of congestive heart failure. J Cardiovasc Pharmacol. 1990; 15(Suppl 2):S41-6.

19. Frank GJ. Does the duration of action of angiotensin converting enzyme inhibitors affect their safety and adverse effects? J Hypertension. 1989; 7(Suppl 5):S17-22.

20. Baker DW, Konstam MA, Bottorff M. Management of heart failure JAMA. 1994; 272:1361-6.

21. Young JB. Angiotensin-converting enzyme inhibitors in heart failure: new strategies justified by recent clinical trials. Int J Cardiol. 1994; 43:151-63. [PubMed 8181869]

22. Sharpe N. ACE inhibitors versus diuretics: when to choose which drug: Cardiovasc Drugs Ther. 1993; 7:877-9. Abstract.

23. Magestro P (Parke-Davis, Morris Plains, NJ); personal communication.

24. Saundes E. Tailoring treatment to minority patients. Am J. 1990; 88(Suppl 3B):21-3S.

25. Chrysant SG, Danise K, Kern DC et al. Racial differences in pressure, volume and renin interrelationships in essential hypertension, Hypertension. 1979; 1:136-41.

26. Holland OB, Kuhnert L, Campbell WB et al. Synergistic effect of captopril with hydrochlorothiazide for the treatment of low-renin hypertensive black patients. Hypertension. 1983; 5:235-9. [PubMed 6337951]

27. Ferguson RK, Vlasses PH, Rotmesch HH. Clinical applications of angiotensin-enzyme inhibitors. Am J Med. 1984; 77:690-8.

28. Parke-Davis. Accupril (quinapril hydrochloride) tablets prescribing information. In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997(Suppl A):A241.

29. Rey E, LeLorier J, Burgess E et al. Report of the Canadian Hypertension Society consensus conference: 3. pharmacologic treatment of hypertensive disorders in pregnancy. CMAJ. 1997; 157:1245-54. [IDIS 396283] [PubMed 9361646]

30. American College of Obstetricians and Gynecologists. ACOG technical bulletin No. 219: hypertension in pregnancy. 1996 Jan.

31. Hanssens M, Keirse MJ, Van Assche FA. Fetal and neonatal effects of treatment with angiotensin-converting enzyme inhibitors in pregnancy. Obstet Gynecol. 1991; 78:128-35. [IDIS 284531] [PubMed 2047053]

32. Brent Rl, Beckman D. Angiotensin-converting enzyme inhibitors, an embryopathic class of drugs with unique properties: information for clinical teratology counselors. Teratology. 1991; 43:543-6. [PubMed 1882342]

33. Piper JM, Ray WA, Rosa FW. Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors. Obstet Gynecol. 1992; 80:429-32. [IDIS 300973] [PubMed 1495700]

34. Sibai BM. Treatment of hypertension in pregnant women. N Engl J Med. 1996; 335:257-65. [IDIS 369138] [PubMed 8657243]

35. Barr M, Cohen MM. ACE inhibitor fetopathy and hypocalvaria: the kidney-skull connection. Teratology. 1991; 44:485-95. [PubMed 1771591]

36. US Food and Drug Administration. Dangers of ACE inhibitors during pregnancy. FDA Med Bull. 1992; 22:2.

37. Pitt B, Zannad F, Remme WJ et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999; 341:709-17. [IDIS 431313] [PubMed 10471456]

38. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure: approaches to the prevention of heart failure. Am J Cardiol. 1999; 83:9A-38A.

39. Weber KT. Aldosterone and spironolactone in heart failure. N Engl J Med. 1999; 341:753-4. [IDIS 431314] [PubMed 10471464]

40. Anon. Spironolactone for heart failure. Med Lett Drugs Ther. 1999; 41:81-2. [PubMed 10505071]

41. Packer M, Poole-Wilson PA, Armstrong PW et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. Circulation. 1999; 100:2312-8. [IDIS 440440] [PubMed 10587334]

42. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Bethesda, MD: National Institutes of Health; 1997 Nov. (NIH publication No. 98-4080.)

43. Izzo JL, Levy D, Black HR. Importance of systolic blood pressure in older Americans. Hypertension. 2000; 35:1021-4. [PubMed 10818056]

44. Frohlich ED. Recognition of systolic hypertension for hypertension. Hypertension. 2000; 35:1019-20. [PubMed 10818055]

45. Bakris GL, Williams M, Dworkin L et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000; 36:646-61. [IDIS 452007] [PubMed 10977801]

46. Associated Press (American Diabetes Association). Diabetics urged: drop blood pressure. Chicago, IL; 2000 Aug 29. Press Release from web site.

47. Parke Davis. Accuretic (quinapril hydrochloride/hydrochlorothiazide) tablets prescribing information. New York, NY; 2001 Sep.

48. Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. JAMA. 2002; 288:3039-60. [IDIS 490723] [PubMed 12479770]

49. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288:2981-97. [IDIS 490721] [PubMed 12479763]

50. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) Express. Bethesda, MD: May 14 2003. From NIH website. (Also published in JAMA. 2003; 289.

51. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2003; 26(Suppl 1):S80-2.

52. Guidelines Committee. 2003 European Society of Hypertension–European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertension. 2003; 21:1011-53.

53. Novartis. Diovan (valsartan) tablets prescribing information. East Hanover, NJ; 2002 Aug.

54. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2002; 25:134-47. [IDIS 479088] [PubMed 11772914]

55. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2002; 25(Suppl 1):S33-43.

56. American Diabetes Association. Clinical Practice Recommendations 2002. Position Statement. Diabetic nephropathy. Diabetes Care. 2002; 25(Suppl 1):S85-9.

57. Lewis EJ, Hunsicker LG, Bain RP et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1993; 329:1456-62. [IDIS 321612] [PubMed 8413456]

58. Remuzzi G. Slowing the progression of diabetic nephropathy. N Engl J Med. 1993; 329:1496-7. [PubMed 8413463]

59. Kaplan NM. Choice of initial therapy for hypertension. JAMA. 1996; 275:1577-80. [IDIS 365188] [PubMed 8622249]

60. Viberti G, Mogensen CE, Groop LC et al. Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. JAMA. 1994; 271:275-9. [IDIS 324307] [PubMed 8295285]

61. Fournier A. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1994; 330:937. [PubMed 8114873]

62. National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and a

Friday, September 30, 2016

Quinaglute

Commonly used brand name(s)

Uses For Quinaglute

Before Using Quinaglute

Allergies

Pediatric

Geriatric

Pregnancy

Breast Feeding

Interactions with Medicines

Interactions with Food/Tobacco/Alcohol

Other Medical Problems

Proper Use of quinidine

Dosing

Missed Dose

Storage

Precautions While Using Quinaglute

Quinaglute Side Effects

More Quinaglute resources

Compare Quinaglute with other medications

Quibron-T

Description

Clinical Pharmacology

Mechanism of Action:

Serum Concentration-Effect Relationship:

Pharmacokinetics:

Clinical Studies

Indications and Usage

Contraindications

Warnings

Concurrent Illness:

Conditions That Reduce Theophylline Clearance:

When Signs or Symptoms of Theophylline Toxicity Are Present:

Dosage Increases:

Precautions

General:

Monitoring Serum Theophylline Concentrations:

Effects on Laboratory Tests:

Information for Patients:

Drug Interactions:

The Effect of Other Drugs on Theophylline Serum Concentration Measurements:

Carcinogenesis, Mutagenesis, Impairment of Fertility

Pregnancy

Nursing Mothers:

Pediatric Use

Geriatric Use:

Adverse Reactions

Quinapril Hydrochloride

Introduction

Uses for Quinapril Hydrochloride

Hypertension

CHF

Diabetic Nephropathy

Quinapril Hydrochloride Dosage and Administration

General

Hypertension

Administration

Oral Administration

Dosage

Pediatric Patients

Hypertension†

Oral

Adults

Hypertension

Oral

Quinapril/Hydrochlorothiazide Combination Therapy

CHF

Oral

Prescribing Limits

Pediatric Patients

Hypertension†

Oral

Special Populations

Renal Impairment

Hypertension

Oral

CHF

Oral

Geriatric Patients