Sanctura

Generic Name: Trospium Chloride
Class: Genitourinary Smooth Muscle Relaxants
VA Class: GU201
Chemical Name: spiro[8-azoniabicyclo[3,2,1]octane-8,1’-pyrrolidinium]-3-[(hydroxydiphenyl-acetyl)- oxy]chloride,(1α, 3β, 5α)
Molecular Formula: C₂₅H₃₀C_lNO₃
CAS Number: 10405-02-4

Introduction

Genitourinary antispasmodic; quaternary ammonium antimuscarinic.^{1 3}

Uses for Sanctura

Overactive Bladder

Management of overactive bladder for the relief of symptoms associated with voiding (e.g., urge urinary incontinence, urgency, frequency).^{1 3 5}

Appears to be as effective as immediate-release preparations of oxybutynin or tolterodine in decreasing urinary frequency;^{2 4 5 6} may be more effective than immediate-release preparations of tolterodine in decreasing urgency incontinence.^{5 6}

May offer no advantage over extended-release anticholinergic preparations for the treatment of overactive bladder.³

Sanctura Dosage and Administration

Administration

Oral Administration

Administer orally twice daily, at least 1 hour before meals or on an empty stomach.¹

Dosage

Available as trospium chloride; dosage expressed in terms of the salt.¹

Adults

Overactive Bladder

Oral

20 mg twice daily.¹

Special Populations

Hepatic Impairment

Use caution in patients with moderate or severe hepatic impairment.¹ (See Special Populations under Pharmacokinetics.)

Renal Impairment

In patients with severe renal impairment (Cl_cr <30 mL/minute), decrease dosage to 20 mg once daily at bedtime.¹

Geriatric Patients

In geriatric patients ≥75 years of age, may decrease dosage to 20 mg once daily based on patient tolerance.¹ (See Geriatric Use under Cautions.)

Cautions for Sanctura

Contraindications

• 
  

  Presence or risk of urinary retention.¹

  
  


• 
  

  Presence or risk of gastric retention.¹

  
  


• 
  

  Presence or risk of risk of uncontrolled angle-closure glaucoma.¹

  
  


• 
  

  Known hypersensitivity to trospium or any ingredient in the formulation.¹

  
  

Warnings/Precautions

General Precautions

Urinary Retention

Risk of urinary retention; use with caution in patients with clinically important bladder outflow obstruction.¹

Decreased GI Motility

Risk of gastric retention; use caution with obstructive GI disorders.¹

May decrease GI motility; use with caution in patents with ulcerative colitis, intestinal atony, or myasthenia gravis.¹

Controlled Angle-closure Glaucoma

Use only if potential benefits outweigh the risks; use with caution and monitor carefully.¹

Specific Populations

Pregnancy

Category C.¹

Lactation

Distributed into milk in rats; not known whether distributed into human milk.¹ Use with caution and only if potential benefit justifies the risk to the infant.¹

Pediatric Use

Safety and efficacy not established.¹

Geriatric Use

In patients ≥75 years of age, possible increased incidence of adverse anticholinergic effects compared with younger adults.¹ (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution in patients with moderate or severe hepatic impairment.¹ (See Special Populations under Pharmacokinetics.)

Renal Impairment

Dosage reduction necessary in patients with severe renal impairment (Cl_cr<30 mL/per minute); not studied in patients with mild or moderate renal impairment¹ (See Renal Impairment under Dosage and Administration and see Special Populations under Pharmacokinetics.) ¹

Common Adverse Effects

Dry mouth,^{1 2 3} constipation.^{1 2}

Interactions for Sanctura

Minimally metabolized by CYP isoenzymes; does not inhibit CYP1A2, 3A4, 2A6, 2C9, 2C19, 2D6, or 2E1 in vitro.^{1 2 7} Pharmacokinetic interactions unlikely with drugs metabolized by CYP isoenzymes or with CYP enzyme inducers or inhibitors.^{1 2 7}

Drugs Eliminated by Active Tubular Secretion

Possible competition for renal secretion, decreased renal elimination, and increased serum concentrations of trospium and/or other drug.¹ Use concomitantly with caution; monitor carefully.¹

Drugs Affected by GI Motility

Potential for altered absorption because of decreased GI motility.¹

Specific Drugs

Drug	Interaction	Comment
Alcohol	Potential for additive sedative effects1
Anticholinergic agents	Potential for additive anticholinergic effects1
Digoxin	Potential for decreased renal elimination and increased serum concentrations of trospium and/or digoxin1 3	Use concomitantly with caution; monitor carefully1
Metformin	Potential decreased renal elimination and increased serum concentrations of trospium and/or metformin1 3	Use concomitantly with caution; monitor carefully1
Morphine	Potential for decreased renal elimination and increased serum concentrations of trospium and/or morphine 1 3	Use concomitantly with caution; monitor carefully1
Pancuronium	Potential for decreased renal elimination and increased serum concentrations of trospium and/or pancuronium1	Use concomitantly with caution; monitor carefully1
Procainamide	Potential for decreased renal elimination and increased serum concentrations of trospium and/or procainamide1 3	Use concomitantly with caution; monitor carefully1
Tenofovir	Potential for decreased renal elimination and increased serum concentrations of trospium and/or tenofovir1	Use concomitantly with caution; monitor carefully1
Vancomycin	Potential for decreased renal elimination and increased serum concentrations of trospium and/or vancomycin1	Use concomitantly with caution; monitor carefully1

Sanctura Pharmacokinetics

Absorption

Bioavailability

Absorption from GI tract is incomplete.^{1 3 5 7}

Mean absolute oral bioavailability is about 9.6%.¹

Food

High-fat meal reduces AUC and peak plasma concentrations by about 70–80%.^{1 3}

Distribution

Extent

In blood, plasma to whole blood ratio is 1.6 to 1.¹

Hydrophilic; theoretically should not cross the blood-brain barrier.^{5 7}

Distributed into milk in rats; not known whether distributed into human milk.¹

Plasma Protein Binding

50–85%.¹

Elimination

Metabolism

Metabolism not fully elucidated;^{1 2 7} major pathway may be ester hydrolysis and subsequent glucuronidation to form inactive metabolites.^{1 7} Minimally metabolized by CYP isoenzymes.^{1 2 7}

Elimination Route

Excreted principally in feces (about 85%) and in urine (5.8%), mainly as unchanged drug.^{1 2 3 5 7}

Active tubular secretion is a major elimination route.¹

Half-life

About 20 hours.^{1 7}

Special Populations

In patients with severe renal impairment (Cl_cr<30 mL/per minute), peak plasma concentrations and AUC increased 2-fold and 4.5-fold, respectively, and an additional elimination phase (half-life of about 33 hours) occurred.^{1 7}

In patients with mild or moderate hepatic impairment, peak plasma concentrations increased (12 or 63%, respectively); AUC was similarly increased.¹

Stability

Storage

Oral

Tablets

20–25°C.¹

ActionsActions

• 
  

  Antagonizes acetylcholine at muscarinic receptors in cholinergically innervated organs.^{1 3 5}

  
  


• 
  

  Parasympatholytic action reduces the tonus of smooth muscle in the urinary bladder.^{1 3}

  
  


• 
  

  Increases maximum cystometric capacity and volume at first detrusor contraction in patients with involuntary detrusor contractions.^{1 5}

  
  


• 
  

  Little or no affinity for nicotinic receptors compared with muscarinic receptors at concentrations achieved following usual therapeutic doses.^{1 7}

  
  

Advice to Patients

• 
  

  Importance of informing patients of potential adverse anticholinergic effects (e.g., dizziness, blurred vision, heat prostration when used in a hot environment).¹

  
  


• 
  

  Importance of taking trospium chloride on an empty stomach or at least 1 hour before meals, and if a dose is skipped, taking the next scheduled dose at least 1 hour before the next meal.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and dietary or herbal supplements as well as any concomitant illnesses.¹

  
  


• 
  

  Importance of using alcohol with caution, since it may enhance drowsiness caused by trospium.¹

  
  


• 
  

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

  
  


• 
  

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

  
  

Preparations

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

Trospium Chloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	20 mg	Sanctura	Odyssey

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.

Sanctura 20MG Tablets (ALLERGAN DERMATOLOGICS): 30/$85.94 or 90/$242.47

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.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 2005. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Odyssey Pharmaceuticals. Sanctura™ (trospium chloride) tablets prescribing information. East Hanover, NJ; 2004. From Sanctura website (http://www.sanctura.com/Sanctura_Prescribing_Information.pdf).

2. Zinner N, Gittelman M, Harris R et al. Trospium chloride improves overactive bladder symptoms: a multicenter phase II trial. J Urol. 2004; 171:2311-5. [IDIS 519949] [PubMed 15126811]

3. Anon. Trospium Chloride (Sanctura): Another anticholinergic for overactive bladder. Med Lett Drugs Ther. 2004; 46:63-4. [PubMed 15289745]

4. Halaska M, Ralph G, Wiedemann A et al. Controlled, double-blind, multicentre clinical trial to investigate long-term tolerability and efficacy of trospium chloride in patients with detrusor instability. World J Urol. 2003; 20:392-9. [IDIS 519866] [PubMed 12811500]

5. Hashim H, Abrams P. Drug treatment of overactive bladder. Efficacy, cost and quality-of-life considerations. Drugs. 2004; 64:1643-56. [PubMed 15257626]

6. UK Medicines Information Pharmacists Group. Trospium. New Medicines on the market. Evaluated Information for the NHS. 2002 Feb. From UKMi website (http://www.ukmi.nhs.uk/NewMaterial/html/docs/trospium.pdf)

7. Rovner ES. Trospium chloride in the management of overactive bladder. Drugs. 2004; 64:2433-2446. [PubMed 15482001]

More Sanctura resources

• Sanctura Side Effects (in more detail)
• Sanctura Dosage
• Sanctura Use in Pregnancy & Breastfeeding
• Drug Images
• Sanctura Drug Interactions
• Sanctura Support Group
• 11 Reviews for Sanctura - Add your own review/rating

• Sanctura Prescribing Information (FDA)


• Sanctura Advanced Consumer (Micromedex) - Includes Dosage Information


• Sanctura Consumer Overview


• Sanctura MedFacts Consumer Leaflet (Wolters Kluwer)


• Sanctura XR Prescribing Information (FDA)


• Sanctura XR Extended-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Sanctura with other medications

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Methenamine

Pronunciation: meth-EN-a-meen
Generic Name: Methenamine
Brand Name: Examples include Hiprex and Urex

Methenamine is used for:

Preventing urinary tract infections.

Methenamine is a urinary antiseptic. It works by concentrating in the urine as formaldehyde, which kills bacteria in the urine.

Do NOT use Methenamine if:

• you are allergic to any ingredient in Methenamine


• you have kidney problems


• you are taking a sulfonamide (eg, sulfamethizole)

Contact your doctor or health care provider right away if any of these apply to you.

Before using Methenamine:

Some medical conditions may interact with Methenamine. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have diarrhea, a stomach infection, liver or kidney problems, or gout, or you are severely dehydrated

Some MEDICINES MAY INTERACT with Methenamine. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Sulfonamides (eg, sulfamethizole) because they may decrease Methenamine's effectiveness

This may not be a complete list of all interactions that may occur. Ask your health care provider if Methenamine may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Methenamine:

Use Methenamine as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Methenamine by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation.


• Before you begin using an antacid, check with your doctor or pharmacist.


• If you miss a dose of Methenamine, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Methenamine.

Important safety information:

• It is important that your urine be acidic while you are taking Methenamine. Check with your doctor to see if you should eat or avoid certain foods to keep your urine acidic.


• Methenamine may interfere with certain lab tests. Be sure your doctor and lab personnel know you are taking Methenamine.


• Lab tests, including urine pH, may be performed while you use Methenamine. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• PREGNANCY and BREAST-FEEDING: It is not known if Methenamine can cause harm to the fetus. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Methenamine while you are pregnant. Methenamine is found in breast milk. If you are or will be breast-feeding while you use Methenamine, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Methenamine:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Nausea; upset stomach.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blood in the urine.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Methenamine side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.

Proper storage of Methenamine:

Store Methenamine at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Methenamine out of the reach of children and away from pets.

General information:

• If you have any questions about Methenamine, please talk with your doctor, pharmacist, or other health care provider.


• Methenamine is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Methenamine. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Methenamine resources

• Methenamine Side Effects (in more detail)
• Methenamine Dosage
• Methenamine Use in Pregnancy & Breastfeeding
• Drug Images
• Methenamine Drug Interactions
• Methenamine Support Group
• 5 Reviews for Methenamine - Add your own review/rating

• Methenamine Monograph (AHFS DI)


• Methenamine Prescribing Information (FDA)


• methenamine Concise Consumer Information (Cerner Multum)


• methenamine Advanced Consumer (Micromedex) - Includes Dosage Information


• Hiprex Prescribing Information (FDA)

Compare Methenamine with other medications

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NiQuitin Clear 21 mg.

1. Name Of The Medicinal Product

NiQuitin Clear 21 mg

NiQuitin Pre-Quit Clear 21 mg Patch

2. Qualitative And Quantitative Composition

NiQuitin Clear is a transdermal delivery system for topical application available in systems of 22 cm² containing 114 mg nicotine, equivalent to 5.1 mg/cm² of nicotine and delivering 21 mg over 24 hours.

3. Pharmaceutical Form

Transdermal patch.

4. Clinical Particulars

4.1 Therapeutic Indications

NiQuitin Clear relieves and/or prevents craving and nicotine withdrawal symptoms associated with tobacco dependence. It is indicated to aid smokers wishing to quit or reduce prior to quitting, to assist smokers who are unwilling or unable to smoke, and as a safer alternative to smoking for smokers and those around them.

NiQuitin Clear is indicated in pregnant and lactating women making a quit attempt.

If possible, when stopping smoking, NiQuitin Clear should be used in conjunction with a behavioural support programme.

4.2 Posology And Method Of Administration

NiQuitin Clear patches should be applied once a day, at the same time each day and preferably soon after waking, to a non-hairy, clean, dry skin site and worn continuously for 24 hours. The NiQuitin Clear patch should be applied promptly on removal from its protective sachet.

Avoid applying to any skin which is broken, red or irritated. After 24 hours the used patch should be removed and a new patch applied to a fresh skin site. The patch should not be left on for longer than 24 hours. Skin sites should not be reused for at least seven days. Only one patch should be worn at a time.

Patches may be removed before going to bed if desired. However use for 24 hours is recommended to optimise the effect against morning cravings.

Concurrent behavioural support is recommended, as such programmes have been shown to be beneficial for smoking cessation.

Adults (18 years and over)

Abrupt cessation of smoking:

During a quit attempt every effort should be made to stop smoking with NiQuitin Clear.

NiQuitin Clear therapy should usually begin with NiQuitin Clear 21 mg and be reduced according to the following dosing schedule:-

Dose	Duration
Step 1	NiQuitin Clear 21 mg	First 6 weeks
Step 2	NiQuitin Clear 14 mg	Next 2 weeks
Step 3	NiQuitin Clear 7 mg	Last 2 weeks

Light smokers (e.g. those who smoke less than 10 cigarettes per day) are recommended to start at Step 2 (14 mg) for 6 weeks and decrease the dose to NiQuitin Clear 7 mg for the final 2 weeks.

Patients on NiQuitin Clear 21 mg who experience excessive side-effects (please refer to precautions), which do not resolve within a few days, should change to NiQuitin Clear 14mg. This strength should then be continued for the remainder of the 6 week course before stepping down to NiQuitin Clear 7mg for two weeks. If the symptoms persist the patient should be advised to seek the advice of a healthcare professional.

For optimum results, the 10 week treatment course (8 weeks for light smokers or patients who have reduced strength as above), should be completed in full. Treatment with NiQuitin Clear patch may be continued beyond 10 weeks if you need it to stay cigarette free, however those who have quit smoking but have difficulty discontinuing using the patches are recommended to seek additional help and advice from a healthcare professional.

Further courses may be used at a later time, for NiQuitin Clear patch users who continue or resume smoking.

Gradual Cessation:

For smokers who are unwilling or unable to quit abruptly.

The 21 mg patch can be used daily for 2-4 weeks while the user continues to smoke as needed. At the end of the 2-4 weeks the user should quit completely and continue using Step 1 21 mg patch for 6 weeks daily without smoking. Thereafter following the Step 2 and 3 directions for abrupt cessation above. Should the patient feel able to quit completely before their designated quit date they can do so.

Reduction in smoking:

For smokers who wish to cut down with no immediate plans to quit.

A patch can be used while the user continues to smoke as needed. The user should reduce the number of cigarettes smoked as far as possible and to refrain from smoking as long as possible. Users should be encouraged to stop smoking completely as soon as possible.

If users are still feeling the need to use the patches on a regular basis 6 months after the start of treatment and have still been unable to undertake a permanent quit attempt, then it is recommended to seek additional help and advice from a healthcare professional.

Temporary Abstinence

Apply a patch to control troublesome withdrawal symptoms including craving during the period when smoking is being avoided. Users should be encouraged to stop smoking completely as soon as possible.

If users are still feeling the need to use the patches on a regular basis 6 months after the start of treatment and have still been unable to undertake a permanent quit attempt, then it is recommended to seek additional help and advice from a healthcare professional.

Adolescents and children

Adolescents (12 to 17 years) should follow the schedule of treatment for abrupt cessation of smoking as given above. Where adolescents are not ready or not able to stop smoking abruptly, advice from a healthcare professional should be sought.

Safety and effectiveness in children who smoke has not been evaluated. NiQuitin Clear is not recommended for use in children under 12 years of age.

4.3 Contraindications

NiQuitin Clear is contraindicated in patients with hypersensitivity to the system, the active substance, or any of the excipients.

NiQuitin Clear patches should not be used by non-smokers, occasional smokers or children under 12.

4.4 Special Warnings And Precautions For Use

The risks associated with the use of NRT are substantially outweighed in virtually all circumstances by the well established dangers of continued smoking.

Patients hospitalised for MI, severe dysrhythmia or CVA who are considered to be haemodynamically unstable should be encouraged to stop smoking with non-pharmacological interventions. If this fails, NiQuitin Clear patches may be considered, but as data on safety in this patient group are limited, initiation should only be under medical supervision. Once patients are discharged from hospital they can use NRT as normal.

Diabetes Mellitus: Patients with diabetes mellitus should be advised to monitor their blood sugar levels more closely than usual when NRT is initiated as catecholamines released by nicotine can affect carbohydrate metabolism.

Allergic reactions: Susceptibility to angioedema and urticaria.

Atopic or eczematous dermatitis (due to localised patch sensitivity): In the case of severe or persistent local reactions at the site of application (e.g. severe erythema, pruritus or oedema) or a generalised skin reaction (e.g. urticaria, hives or generalised skin rashes), users should be instructed to discontinue use of NiQuitin Clear and contact their physicians.

Contact sensitisation: Patients with contact sensitisation should be cautioned that a serious reaction could occur from exposure to other nicotine-containing products or smoking.

A risk benefit assessment should be made by an appropriate healthcare professional for patients with the following conditions:

• Renal and hepatic impairment: Use with caution in patients with moderate to severe hepatic impairment and/or severe renal impairment as the clearance of nicotine or its metabolites may be decreased with the potential for increased adverse effects.

• Phaeochromocytoma and uncontrolled hyperthyroidism: Use with caution in patients with uncontrolled hyperthyroidism or phaeochromocytoma as nicotine causes release of catecholamines.

Danger in small children: Doses of nicotine tolerated by adult and adolescent smokers can produce severe toxicity in small children that may be fatal. Products containing nicotine should not be left where they may be misused, handled or ingested by children. The patches should be folded in half with the adhesive side innermost and disposed of with care.

Stopping smoking: Polycyclic aromatic hydrocarbons in tobacco smoke induce the metabolism of drugs catalysed by CYP 1A2 (and possibly by CYP 1A1). When a smoker stops this may result in a slower metabolism and a consequent rise in blood levels of such drugs.

Transferred dependence: Transferred dependence is rare and is both less harmful and easier to break than smoking dependence.

Safety on handling: NiQuitin Clear is potentially a dermal irritant and can cause contact sensitisation. Care should be taken during handling and in particular contact with the eyes and nose avoided. After handling, wash hands with water alone as soap may increase nicotine absorption.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No clinically relevant interactions between nicotine replacement therapy and other drugs have definitely been established, however nicotine may possibly enhance the haemodynamic effects of adenosine.

4.6 Pregnancy And Lactation

Pregnancy

Stopping smoking is the single most effective intervention for improving the health of both the pregnant smoker and her baby, and the earlier abstinence is achieved the better. However, if the mother cannot (or is considered unlikely to) quit without pharmacological support, NRT may be used as the risk to the foetus is lower than that expected with smoking tobacco. Stopping completely is by far the best option but NRT may be used in pregnancy as a safer alternative to smoking. Because of the potential for nicotine-free periods, intermittent dose forms are preferable, but patches may be necessary if there is significant nausea and/or vomiting. If patches are used they should, if possible, be removed at night when the foetus would not normally be exposed to nicotine.

Lactation

The relatively small amounts of nicotine found in breast milk during NRT use are less hazardous to the infant than second-hand smoke. Intermittent dose forms would minimize the amount of nicotine in breast milk and permit feeding when levels were at their lowest.

4.7 Effects On Ability To Drive And Use Machines

Not applicable.

4.8 Undesirable Effects

NRT may cause adverse reactions similar to those associated with nicotine administered by other means, including smoking. These may be attributable to the pharmacological effects of nicotine, some of which are dose dependent. At recommended doses NiQuitin Clear patches have not been found to cause any serious adverse effects. Excessive use of NiQuitin Clear patches by those who have not been in the habit of inhaling tobacco smoke could possibly lead to nausea, faintness or headaches.

Subjects quitting smoking by any means could expect to suffer from asthenia, headache, dizziness, sleep disturbance, coughing or influenza-like illness. Certain symptoms which have been reported such as depression, irritability, nervousness, restlessness, mood lability, anxiety, drowsiness, impaired concentration and insomnia may be related to withdrawal symptoms associated with smoking cessation.

The following undesirable effects have been reported in clinical trials or spontaneously post-marketing.

Immune System Disorders

Uncommon >1/1000; <1/100: hypersensitivity NOS* Very rare <1/10000: anaphylactic reactions

Psychiatric

Very common >1/10: sleep disorders including abnormal dreams and insomnia

Common >1/100; <1/10: nervousness

Nervous system disorders

Very Common >1/10: headache, dizziness

Common >1/100; <1/10: tremor

Cardiac Disorders

Common >1/100; <1/10: palpitations

Uncommon >1/1000; <1/100: tachycardia NOS

Respiratory, Thoracic and Mediastinal Disorders

Common >1/100; <1/10: dyspnoea, pharyngitis, cough

Gastrointestinal Disorders

Very Common >1/10: nausea, vomiting

Common >1/100; <1/10: dyspepsia, abdominal pain upper, diarrhoea NOS, dry mouth, constipation

Skin and Subcutaneous Tissue Disorders

Common >1/100; <1/10: sweating increased

Very rare >1/100000; <1/10000: dermatitis allergic*, dermatitis contact*, photosensitivity

Musculoskeletal and Connective Tissue Disorders

Common >1/100; <1/10: arthralgia, myalgia

General Disorders and Administration Site Conditions

Very common >1/10: application site reactions NOS*

Common >1/100; <1/10: chest pain, pain in limb, pain NOS, asthenia, fatigue

Uncommon >1/1000; <1/100: malaise, influenza-like illness

*see below

Application site reactions, including transient rash, itching, burning, tingling, numbness, swelling, pain and urticaria are the most frequent undesirable effects of NiQuitin patch. The majority of these topical reactions are minor and resolve quickly following removal of the patch. Pain or sensation of heaviness in the limb or area around which the patch is applied (e.g. chest) may be reported.

Hypersensitivity reactions, including contact dermatitis and allergic dermatitis have also been reported. In the case of severe or persistent local reactions at the application site (e.g. severe erythema, pruritus or oedema) or a generalised skin reaction (e.g. urticaria, hives or generalised skin rashes) users should be instructed to discontinue use of NiQuitin and contact their physician.

If there is a clinically significant increase in cardiovascular or other effects attributable to nicotine, the NiQuitin dose should be reduced or discontinued.

4.9 Overdose

Symptoms: The minimum lethal dose of nicotine in a non-tolerant man has been estimated to be 40 to 60mg. Symptoms of acute nicotine poisoning include nausea, salivation, abdominal pain, diarrhoea, sweating, headache, dizziness, disturbed hearing and marked weakness. In extreme cases, these symptoms may be followed by hypotension, rapid or weak or irregular pulse, breathing difficulties, prostration, circulatory collapse and terminal convulsions.

Management of an overdose: All nicotine intake should stop immediately and the patient should be treated symptomatically. Artificial respiration with oxygen should be instituted if necessary. Activated charcoal reduces the gastro-intestinal absorption of nicotine.

Overdose from topical exposure: The NiQuitin Clear system should be removed immediately if the patient shows signs of overdosage and the patient should seek immediate medical care. The skin surface may be flushed with water and dried. No soap should be used since it may increase nicotine absorption. Nicotine will continue to be delivered into the bloodstream for several hours after removal of the system because of a depot of nicotine in the skin.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic classification: N07BA01

(Anti-smoking agents: N07BA, Nicotine 01)

Nicotine, the chief alkaloid in tobacco products and a naturally occurring autonomic drug, is an agonist at nicotine receptors in the peripheral and central nervous system and has pronounced CNS and cardiovascular effects. Withdrawal from nicotine in addicted individuals is characterised by craving, nervousness, restlessness, irritability, mood lability, anxiety, drowsiness, sleep disturbances, impaired concentration, increased appetite, minor somatic complaints (headache, myalgia, constipation, fatigue) and weight gain. Withdrawal symptoms, such as cigarette craving, may be controlled in some individuals by steady-state plasma levels lower than those for smoking.

In clinically controlled trials, nicotine withdrawal symptoms were alleviated as well as craving. The severity of craving was reduced by at least 35% at all times of day during the first two weeks of abstinence, compared to placebo (p<0.05).

5.2 Pharmacokinetic Properties

Absorption

Following transdermal application, the skin rapidly absorbs nicotine released initially from the patch adhesive. The plasma concentrations of nicotine reach a plateau within 2-4 hours after initial application of NiQuitin Clear with relatively constant plasma concentrations persisting for 24 hours or until the patch is removed. Approximately 68% of the nicotine released from the patch enters systemic circulation and the remainder of the released nicotine is lost via vaporisation from the edge of the patch.

With continuous daily application of NiQuitin Clear (worn for 24 hours), dose-dependent steady state plasma nicotine concentrations are achieved following the second NiQuitin Clear application and are maintained throughout the day. These steady state maximum concentrations are approximately 30% higher than those following a single application of NiQuitin Clear.

Plasma concentrations of nicotine are proportional to dose for the three dosage forms of NiQuitin Clear. The mean plasma steady state concentrations of nicotine are approximately 17 ng/ml for the 21 mg/day patch, 12 ng/ml for the 14 mg /day patch and 6 ng/ml for the 7 mg/day patch. For comparison, half-hourly smoking of cigarettes produces average plasma concentrations of approximately 44 ng/ml.

The pronounced early peak in nicotine blood levels seen with inhalation of cigarette smoke is not observed with NiQuitin Clear.

Distribution

Following removal of NiQuitin Clear, plasma nicotine concentrations decline with an apparent mean half-life of 3 hours, compared with 2 hours for IV administration due to continued absorption of nicotine from the skin depot. If NiQuitin Clear is removed most non-smoking patients will have non-detectable nicotine concentrations in 10 to 12 hours.

A dose of radio-labelled nicotine given intravenously showed a distribution of radioactivity corresponding to the blood supply with no organ selectively taking up nicotine. The volume of distribution of nicotine is approximately 2.5 l/kg.

Metabolism

The major elimination organ is the liver and average plasma clearance is about 1.2 l/min; the kidney and the lung also metabolise nicotine. More than 20 metabolites of nicotine have been identified, all of which are believed to be pharmacologically inactive. The principal metabolites are cotinine and trans-3-hydroxycotinine. Steady state plasma cotinine concentrations exceed nicotine by 10-fold. The half-life of nicotine ranges from 1 to 2 hours and cotinine's between 15 and 20 hours.

Excretion

Both nicotine and its metabolites are excreted through the kidneys and about 10% of nicotine is excreted unchanged in the urine. As much as 30% may be excreted in the urine with maximum flow rates and extreme urine acidification (pH

There were no differences in nicotine kinetics between men and women using nicotine patches. Obese men using nicotine patch had significantly lower AUC and Cmax values compared with normal weight men. Linear regression of AUC vs total body weight showed the expected inverse relationship (AUC decreases as weight increases). Nicotine kinetics were similar for all sites of application on the upper body and upper outer arm.

5.3 Preclinical Safety Data

The general toxicity of nicotine is well known and taken into account in the recommended posology. Nicotine was not mutagenic in appropriate assays. The results of carcinogenicity assays did not provide any clear evidence of a tumorigenic effect of nicotine. In studies in pregnant animals, nicotine showed maternal toxicity, and consequential mild fetal toxicity. Additional effects included pre- and postnatal growth retardation and delays and changes in postnatal CNS development.

Effects were only noted following exposure to nicotine at levels in excess of those which will result from recommended use of NiQuitin Clear. Effects on fertility have not been established.

Comparison of the systemic exposure necessary to elicit these adverse responses from preclinical test systems with that associated with the recommended use of NiQuitin Clear indicate that the potential risk is low and outweighed by the demonstrable benefit of nicotine therapy in smoking cessation. However, NiQuitin Clear should only be used by pregnant women on medical advice if other forms of treatment have failed.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Drug Reservoir:	Ethylene Vinyl Acetate Copolymer
Occlusive Backing:	Polyethylene Terephthalate/ Ethylene vinyl acetate
Rate Controlling Membrane:	Polyethylene Film
Contact Adhesive:	Polyisobutylene B100 and B12 SFN
Protective Layer:	Siliconised Polyester Film
Printing Ink:	White ink

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

36 months.

6.4 Special Precautions For Storage

None stated.

6.5 Nature And Contents Of Container

7 or 14 patches in a carton. Each patch is rectangular and is comprised of clear backing and a protective liner which is removed prior to use. Each patch is contained in a laminate sachet.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Beecham Group PLC

980 Great West Road

Brentford

Middlesex

TW8 9GS

United Kingdom

T/A GlaxoSmithKline Consumer Healthcare

Brentford

TW8 9GS

8. Marketing Authorisation Number(S)

PL 00079/ 0356

9. Date Of First Authorisation/Renewal Of The Authorisation

23^rd June 2000

10. Date Of Revision Of The Text

21^st December 2010

Glucagon

Pronunciation: GLOO-ka-gon
Generic Name: Glucagon
Brand Name: GlucaGen

Glucagon is used for:

Treating severe low blood sugar in patients with diabetes who are unable to take sugar by mouth. Glucagon also may be used for other conditions as determined by your doctor.

Glucagon is a hormone. It works by stimulating the liver to release glucose into the blood.

Do NOT use Glucagon if:

• you are allergic to any ingredient in Glucagon, including lactose


• you have certain tumors on your adrenal gland (pheochromocytoma) or pancreas (insulinoma)

Contact your doctor or health care provider right away if any of these apply to you.

Before using Glucagon:

Some medical conditions may interact with Glucagon. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have adrenal gland problems, heart problems, chronic low blood sugar, a certain tumor on your pancreas (glucagonoma), or diabetes


• if you are malnourished or have been unable to eat, or if you have been fasting for a long period of time

Some MEDICINES MAY INTERACT with Glucagon. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Anticoagulants (eg, warfarin) because the risk of their side effects, including increased risk of bleeding, may be increased by Glucagon


• Beta-blockers (eg, propranolol) or indomethacin because they may decrease Glucagon's effectiveness


• Anticholinergics (eg, tolterodine) because the risk of stomach or bowel side effects may be increased

This may not be a complete list of all interactions that may occur. Ask your health care provider if Glucagon may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Glucagon:

Use Glucagon as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Glucagon. Talk to your pharmacist if you have questions about this information.


• Carefully follow the instructions for use, and be sure family members, friends, and coworkers know how and when to give you Glucagon. Contact your health care provider if you have questions about use. Symptoms of low blood sugar include: sweating; dizziness; irregular heartbeat; tremor; hunger; restlessness; tingling in the hands, feet, lips, or tongue; lightheadedness; inability to concentrate; headache; drowsiness; sleep disturbances; anxiety; blurred vision; slurred speech; depressed mood; irritability; abnormal behavior; unsteady movement; personality changes; seizures; loss of consciousness; confusion.


• Seek medical attention immediately after use. You may need further medical evaluation. Tell the doctor or health care provider that you have received an injection of glucagon.


• Do not use Glucagon if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.


• After mixing, use immediately. Throw away any unused portion. Do not use Glucagon after the date stamped on the bottle.


• Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.


• If you miss a dose of Glucagon, contact your doctor right away.

Ask your health care provider any questions you may have about how to use Glucagon.

Important safety information:

• Always carry a quick source of sugar such as candy or glucose tablets to take at the first warning sign of a low blood sugar reaction.


• Glucagon should only be given if the patient is unconscious, is having a seizure, or is confused and not able to eat sugar by mouth.


• Once the patient is awake and able to swallow after giving Glucagon, give a fast-acting source of sugar (eg, regular soft drink, fruit juice) and a long-acting source of sugar (eg, crackers and cheese, meat sandwich).


• Make sure your relatives or close friends know that medical attention is always required if you become unconscious. Patients who are unconscious because of high blood sugar will not respond to Glucagon and should not be given candy or glucose tablets.


• Check blood or urine sugar levels closely, as directed by your doctor.


• Lab tests, including blood glucose levels, may be performed while you use Glucagon. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Glucagon while you are pregnant. It is not known if Glucagon is found in breast milk. If you are or will be breast-feeding while you use Glucagon, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Glucagon:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Nausea; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing or swallowing; tightness in the chest; swelling of the mouth, face, lips, throat, or tongue); fainting; fast or slow heartbeat; severe headache or dizziness.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Glucagon side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include diarrhea; fast heartbeat; nausea; severe headache or dizziness; vomiting.

Proper storage of Glucagon:

Before mixing, store Glucagon for up to 24 months between 68 and 77 degrees F (20 and 25 degrees C). Do not freeze. Store in the original packaging away from heat, moisture, and light. Do not store in the bathroom. After mixing, use immediately. Do not use Glucagon after the expiration date printed on the package. Keep Glucagon out of the reach of children and away from pets.

General information:

• If you have any questions about Glucagon, please talk with your doctor, pharmacist, or other health care provider.


• Glucagon is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Glucagon. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Glucagon resources

• Glucagon Side Effects (in more detail)
• Glucagon Use in Pregnancy & Breastfeeding
• Glucagon Drug Interactions
• Glucagon Support Group
• 0 Reviews for Glucagon - Add your own review/rating

Compare Glucagon with other medications

• Diagnosis and Investigation
• Hypoglycemia

Axid

Generic Name: nizatidine (ni ZA ti deen)

Brand Names: Axid, Axid AR, Axid Pulvules

What is nizatidine?

Nizatidine is in a group of drugs called histamine-2 blockers. Nizatidine works by decreasing the amount of acid the stomach produces.

Nizatidine is used to treat ulcers in the stomach and intestines. Nizatidine also treats heartburn and erosive esophagitis caused by gastroesophageal reflux disease (GERD), a condition in which acid backs up from the stomach into the esophagus.

Nizatidine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about nizatidine?

You should not use this medication if you are allergic to nizatidine or similar medications such as ranitidine (Zantac), cimetidine (Tagamet), or famotidine (Pepcid).

Before taking nizatidine, tell your doctor if you have kidney or liver disease, or stomach cancer or other problems.

Avoid taking cimetidine (Tagamet), ranitidine (Zantac), or famotidine (Pepcid) while you are taking nizatidine, unless your doctor has told you to.

Nizatidine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Nizatidine may be only part of a complete program of treatment that also includes changes in diet or lifestyle habits. Follow your doctor's instructions very closely.

Heartburn is often confused with the first symptoms of a heart attack. Seek emergency medical attention if you have chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, and a general ill feeling.

What should I discuss with my healthcare provider before taking nizatidine?

Heartburn is often confused with the first symptoms of a heart attack. Seek emergency medical attention if you have chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, and a general ill feeling.

You should not use this medication if you are allergic to nizatidine or similar medications such as ranitidine (Zantac), cimetidine (Tagamet), or famotidine (Pepcid).

To make sure you can safely take nizatidine, tell your doctor if you have any of these other conditions:

• kidney disease;


• liver disease; or


• 
  

  stomach cancer or other problems.

  
  

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Nizatidine can pass into breast milk and may harm a nursing baby. You should not breast-feed while taking this medication. Do not give this medication to a child younger than 12 years old without the advice of a doctor.

How should I take nizatidine?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Measure liquid medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Although most ulcers heal within 4 weeks of nizatidine treatment, it may take up to 8 to 12 weeks of using this medicine before your ulcer heals. For best results, keep using the medication as directed. Talk with your doctor if your symptoms do not improve after 6 weeks of treatment.

This medication can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using nizatidine.

Nizatidine may be only part of a complete program of treatment that also includes changes in diet or lifestyle habits. Follow your doctor's instructions very closely.

Store at room temperature away from moisture, heat, and light. Throw away any unused nizatidine liquid that is older than 30 days.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include blurred vision, watery eyes, drooling, nausea, vomiting, or diarrhea.

What should I avoid' while taking nizatidine?

Nizatidine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Avoid drinking alcohol. It can increase the risk of damage to your stomach.

Avoid taking cimetidine (Tagamet), ranitidine (Zantac), or famotidine (Pepcid) while you are taking nizatidine, unless your doctor has told you to.

Nizatidine side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using nizatidine and call your doctor at once if you have a serious side effect such as:

• 
  

  pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;

  
  


• 
  

  unusual bleeding, purple or red pinpoint spots under your skin;

  
  


• 
  

  skin rash, bruising, severe tingling, numbness, pain, muscle weakness;

  
  


• 
  

  fever, confusion; or

  
  


• 
  

  jaundice (yellowing of the skin or eyes).

  
  

Less serious side effects may include:

• 
  

  headache, dizziness;

  
  


• 
  

  mild rash;

  
  


• 
  

  diarrhea; or

  
  


• 
  

  runny or stuffy nose, sore throat, cough.

  
  

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect nizatidine?

Tell your doctor about all other medications you use, especially aspirin.

There may be other drugs that can interact with nizatidine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Axid resources

• Axid Side Effects (in more detail)
• Axid Use in Pregnancy & Breastfeeding
• Axid Drug Interactions
• Axid Support Group
• 0 Reviews for Axid - Add your own review/rating

• Axid Prescribing Information (FDA)


• Axid Consumer Overview


• Axid Monograph (AHFS DI)


• Axid MedFacts Consumer Leaflet (Wolters Kluwer)


• Nizatidine Prescribing Information (FDA)


• Nizatidine Professional Patient Advice (Wolters Kluwer)


• Axid AR Prescribing Information (FDA)

Compare Axid with other medications

• Duodenal Ulcer
• Duodenal Ulcer Prophylaxis
• Erosive Esophagitis
• GERD
• Indigestion
• Stomach Ulcer

Where can I get more information?

• Your pharmacist can provide more information about nizatidine.

See also: Axid side effects (in more detail)

Captopril

Class: Angiotensin-Converting Enzyme Inhibitors
VA Class: CV800
CAS Number: 62571-86-2
Brands: Capoten, Capozide

• 
  

  May cause fetal and neonatal morbidity and mortality if used during pregnancy.^{401 402} (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  
  


• 
  

  If pregnancy is detected, discontinue captopril as soon as possible.^{115 402}

  
  

Introduction

Sulfhydryl ACE inhibitor.^{1 3 4 5}

Uses for Captopril

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).^{100 115 215 259 316 317}

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.³⁸²

Can be used as monotherapy for initial management of uncomplicated hypertension;¹¹⁵ however, thiazide diuretics are preferred by JNC 7.³⁸²

Nephropathy

Stabilization or improvement of effective renal blood flow and glomerular filtration rate and reduction of proteinuria in hypertensive^{115 141 142 143 174 187 188 189 281 323} or normotensive^{115 162} patients with moderately impaired renal function,^{141 143 174 323} moderate to severe renal disease,^{141 323} or diabetic nephropathy.^{141 142 143 187 188 189 268 334}

CHF

Management of symptomatic CHF, usually in conjunction with cardiac glycosides, diuretics, and β-adrenergic blocking agents.^{115 210 246 247 248 249 250 252 253 254 256 257 292 304 319 320 321 333 377}

Left Ventricular Dysfunction after AMI

Treatment of clinically stable patients with left ventricular dysfunction (ejection fraction ≤40%) to improve survival following MI and to reduce the incidence of overt heart failure and subsequent hospitalizations for CHF.^{115 319 321 374}

Captopril Dosage and Administration

Administration

Oral Administration

Administer orally 1 hour before meals to maximize absorption.¹¹⁵

Dosage

Pediatric Patients

Hypertension

Oral

Dosage has been reduced in proportion to body weight; titrate carefully.¹¹⁵ Some experts recommend an initial dosage of 0.9–1.5 mg/kg daily (given as 0.3–0.5 mg/kg 3 times daily).³⁹⁸ Increase dosage as necessary to a maximum of 6 mg/kg daily.³⁹⁸

Adults

Hypertension

Oral

Initially, 25 mg 2 or 3 times daily.^{115 316 382} If BP is not adequately controlled after 1–2 weeks, increase dosage to 50 mg 2 or 3 times daily.¹¹⁵

Lower initial dosages (e.g., 6.25 mg twice daily to 12.5 mg 3 times daily) may be effective in some patients, particularly those already receiving a diuretic.^a (See Hypotension under Cautions.)

Usual dosage: Manufacturers recommend 25–150 mg 2 or 3 times daily (usually not necessary to exceed 450 mg daily).^{115 316} JNC 7 recommends 25–100 mg daily given in 2 divided doses; JNC 7 recommends adding another drug, if needed, rather than continuing to increase dosage.³⁸²

If combination therapy is initiated with captopril/hydrochlorothiazide fixed-combination preparation, captopril 25 mg and hydrochlorothiazide 15 mg daily initially;^{102 259} adjust dosage (generally at 6-week intervals) by administering each drug separately or by advancing the fixed-combination preparation.^{102 259}

Hypertensive Crises

Oral

25 mg 2 or 3 times daily, initiated promptly under close supervision with frequent monitoring of BP.¹¹⁵ May continue previous diuretic therapy, but discontinue other hypotensive agents.¹¹⁵ May increase dosage at intervals of ≤24 hours under continuous supervision until optimum BP response is attained or 450 mg daily is given.¹¹⁵ Adjunctive therapy with other hypotensive agents may be necessary.^a

Acute therapy (e.g., 12.5–25 mg, repeated once or twice if necessary at intervals of 30–60 minutes or longer) has been effective^{231 232 236 259} in adults with hypertensive urgencies†^{231 232 259} and emergencies†.^{233 234 235 236 237 238 259 310}

Nephropathy

Diabetic Nephropathy

Oral

25 mg 3 times daily.^{115 262}

CHF

Oral

Manufacturers recommend initial dosage of 25 mg 3 times daily;¹¹⁵ in patients with normal or low BP who may be volume- and/or salt-depleted, initial dosage of 6.25 or 12.5 mg 3 times daily.¹¹⁵ Increase dosage gradually to 50 mg 3 times daily; delay further dosage increases for ≥2 weeks to assess response.¹¹⁵

Some clinicians recommend initial dosage of 6.25 or 12.5 mg 3 times daily, with gradual titration over several weeks to 50 mg 3 times daily, regardless of BP, salt/volume status, or concomitant diuretic therapy.^{321 333 377} Generally titrate dosage to prespecified target (i.e., ≥150 mg daily) or highest tolerated dosage rather than according to response.^{333 377}

Left Ventricular Dysfunction after AMI

Oral

Manufacturers recommend initiation of therapy ≥3 days post-MI with single dose of 6.25 mg, followed by 12.5 mg 3 times daily.¹¹⁵ Increase dosage over next several days to 25 mg 3 times daily and then over next several weeks (as tolerated) to 50 mg 3 times daily.¹¹⁵

Some clinicians recommend initiation of therapy <24 hours post-MI with initial dose of 6.25 mg, followed by 12.5 mg 2 hours later, 25 mg 10–12 hours later, and then 50 mg twice daily as tolerated.³¹⁹ Recommended maintenance dosage: 50 mg 3 times daily.¹¹⁵

Prescribing Limits

Pediatric Patients

Hypertension

Oral

Maximum 6 mg/kg daily.³⁹⁸

Adults

Hypertension

Oral

Maximum 450 mg daily.¹¹⁵

Dosage of captopril/hydrochlorothiazide fixed-combination generally should not exceed captopril 150 mg and hydrochlorothiazide 50 mg daily.¹⁰²

CHF

Oral

Maximum dosage recommended by manufacturer and some experts is 450 mg daily.^{115 333} Other experts suggest maximum dosage of 50 mg 3 times daily.³⁷⁷

Special Populations

Renal Impairment

Manufacturers recommend initial dosage of <75 mg daily; increase dosage in small increments at 1- to 2-week intervals.¹¹⁵ After desired therapeutic effect has been attained, slowly reduce dosage to minimum effective level.¹¹⁵

Patients with Cl_cr 10–50 mL/minute: 75% of usual captopril dosage or administration of usual dose every 12–18 hours suggested by some clinicians.²¹¹

Cl_cr <10 mL/minute: 50% of usual dosage or administration of usual dose every 24 hours suggested by some clinicians.²¹¹

Patients undergoing hemodialysis may require supplemental dose after dialysis.²¹¹

Fixed-combination captopril/hydrochlorothiazide tablets usually are not recommended for patients with severe renal impairment.¹⁰²

Geriatric Patients

Hypertension

Usual adult dosages generally have been used; dosages of 6.25–12.5 mg 1–4 times daily used occasionally.¹⁷⁵

Volume-and/or Salt-Depleted Patients

Correct volume and/or salt depletion prior to initiation of therapy or initiate therapy under close medical supervision using lower initial dosage.^{115 116 148 153} (See Dosage: CHF, under Dosage and Administration.)

Cautions for Captopril

Contraindications

• 
  

  Known hypersensitivity (e.g. history of angioedema) to captopril or another ACE inhibitor.^{115 147 325 326 333}

  
  

Warnings/Precautions

Warnings

Hematologic Effects

Possible neutropenia or agranulocytosis; risk of neutropenia appears to depend principally on degree of renal impairment and presence of collagen vascular disease (e.g., systemic lupus erythematosus, scleroderma).¹¹⁵

Use with caution and only after careful risk/benefit assessment in patients with collagen vascular disease or those taking drugs known to affect leukocytes or immune response.¹¹⁵

If used in patients with renal impairment, determine complete and differential leukocyte counts prior to initiation of therapy, at about 2-week intervals for the first 3 months of therapy, and periodically thereafter.¹¹⁵ Discontinue therapy if confirmed neutrophil count is <1000/mm³.¹¹⁵

Proteinuria

Proteinuria possible, particularly in patients with prior renal disease and/or those receiving relatively high dosages (>150 mg daily).¹¹⁵ Usually occurs by the 8th month of treatment^{1 3 46} and subsides or clears within 6 months whether or not therapy is continued;¹¹⁵ however, may persist in some patients.^a

Hypotension

Possible excessive hypotension, particularly in volume- and/or salt-depleted patients (e.g., those treated with diuretics or undergoing dialysis, patients with severe CHF).^{1 5 17 23 25 31 66 85 115 116 148 154 156}

Hypotension may occur in patients undergoing surgery or during anesthesia with agents that produce hypotension; recommended treatment is fluid volume expansion.¹¹⁵

Transient hypotension is not a contraindication to additional doses; may reinstate therapy cautiously after BP is stabilized (e.g., with volume expansion).¹¹⁵

To minimize potential for hypotension, consider recent antihypertensive therapy, extent of BP elevation, sodium intake, fluid status, and other clinical conditions.^a (See Special Populations under Dosage and Administration.) Discontinue other antihypertensive therapy, if possible, 1 week before initiating captopril, except in patients with severe hypertension.^{115 a} Withholding diuretic therapy and/or increasing sodium intake approximately 3–7 days prior to initiation of captopril may minimize potential for severe hypotension.^{115 116 148 153}

Initiate therapy in patients with CHF under close medical supervision; monitor closely for first 2 weeks following initiation of captopril or any increase in captopril or diuretic dosage.¹¹⁵

Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when used during pregnancy.^{102 115 239 240 241 402} (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.⁴⁰²

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.^{401 402}

Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.⁴⁰² Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.²³⁹

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.^{102 115 370}

If jaundice or marked elevation of liver enzymes occurs, discontinue drug and monitor patient.¹¹⁵

Sensitivity Reactions

Anaphylactoid reactions and/or angioedema possible; if associated with laryngeal edema, may be fatal.^{115 333} Immediate medical intervention (e.g., epinephrine) for involvement of tongue, glottis, or larynx.¹¹⁵ Intestinal angioedema possible; consider in differential diagnosis of patients who develop abdominal pain.¹¹⁵

Anaphylactoid reactions reported in patients receiving ACE inhibitors while undergoing LDL apheresis with dextran sulfate absorption^{115 275 276 277} or following initiation of hemodialysis that utilized high-flux membrane.^{102 115 242 243 244}

Life-threatening anaphylactoid reactions reported in at least 2 patients receiving ACE inhibitors while undergoing desensitization treatment with hymenoptera venom.^{102 155 278}

Not recommended in patients with a history of angioedema associated with or unrelated to ACE inhibitors.^a

General Precautions

Renal Effects

Transient increases in BUN and S_cr possible, especially in patients with preexisting renal impairment, sodium depletion, or hypovolemia; patients with renovascular hypertension, particularly those with bilateral renal-artery stenosis or those with renal-artery stenosis in a solitary kidney;^{5 86 115 117 122 123 124 207 208 209 333 372} or patients with chronic or severe hypertension in whom the glomerular filtration rate may decrease transiently.^{1 115}

Possible increases in BUN and S_cr in patients with CHF;^{115 206 333} rapidity of onset and magnitude may depend in part on degree of sodium depletion.^{148 156 206 372}

Closely monitor renal function following initiation of therapy in such patients.^{86 87 115 117 122 123 124 333 372} Some patients may require dosage reduction or discontinuance of ACE inhibitor or diuretic and/or adequate sodium repletion.^{115 156 206 207 209}

Hyperkalemia

Possible hyperkalemia,^{5 7 38 69 70 85 115 122 125 126 162 163 164 177} especially in patients with impaired renal function, CHF, or diabetes mellitus and those receiving drugs that can increase serum potassium concentration (e.g., potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes).^{38 85 115 125 126 148 162 163 164 333 372} (See Interactions.)

Monitor serum potassium concentration carefully in these patients.^{126 162 163}

Cough

Persistent and nonproductive cough; resolves after drug discontinuance.^{102 115 333}

Valvular Stenosis

Possible risk of decreased coronary perfusion in patients with aortic stenosis when treated with captopril.^{a 115}

Use of Fixed Combinations

When used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.¹⁰²

Specific Populations

Pregnancy

Category C (1st trimester); Category D (2nd and 3rd trimesters).¹¹⁵ (See Fetal/Neonatal Morbidity and Mortality under Cautions and see Boxed Warning.)

Lactation

Distributed into milk.¹¹⁵ Discontinue nursing or the drug.¹¹⁵

Pediatric Use

Safety and efficacy not established; however, captopril has been used in children.¹¹⁵ Manufacturer states that captopril should be used only when other measures for controlling BP have not been effective.¹¹⁵

Possible excessive, prolonged, and unpredictable decreases in BP and associated complications (e.g., oliguria, seizures) in infants.¹¹⁵

Renal Impairment

Systemic exposure to captopril may be increased.¹¹⁵ (See Special Populations under Pharmacokinetics.) Initial dosage adjustment recommended in patients with severe renal impairment.¹¹⁵ (See Renal Impairment under Dosage and Administration.)

Deterioration of renal function may occur.^{115 211} Possible increased risk of neutropenia/agranulocytosis,¹¹⁵ proteinuria,¹¹⁵ and hyperkalemia.¹¹⁵ (See Warnings and General Precautions under Cautions.)

Use of captopril/hydrochlorothiazide fixed combination usually is not recommended in patients with severe renal impairment.¹⁰²

Blacks

BP reduction may be smaller in black patients compared with nonblack patients;^{115 139 177 178 179 180 181 351} however, no apparent population difference during combined therapy with ACE inhibitor and thiazide diuretic.^{179 193 194 217 218 219 316} Use in combination with a diuretic.^{179 193 194 217 218 219 316}

Higher incidence of angioedema reported with ACE inhibitors in blacks compared with other races.^{102 115 325 326 327 351 379 380}

Common Adverse Effects

Rash, pruritus, cough, dysgeusia, proteinuria, tachycardia, chest pain, palpitations.¹¹⁵

Interactions for Captopril

Specific Drugs and Laboratory Tests

Drug	Interaction	Comments
Adrenergic neuron blocking agents (guanethidine)	Possible increased hypotensive effect115	Use with caution115
Antacids	Decreased rate and extent of captopril absorption197 201	Clinical importance is uncertain197 201
Antidiabetic agents, oral	Possible hypoglycemia in diabetic patients101	Consider risk of hypoglycemia if used concomitantly101
Allopurinol	Pharmacokinetic interaction unlikely115
β-adrenergic blocking agents	Increased (but less than additive) hypotensive effect115
Cimetidine	Neuropathy reporteda	Further documentation of interaction necessarya
Digoxin	Possible increased serum digoxin concentrations in patients with CHF198 199 200	Monitor serum digoxin concentration;198 200 reduction of digoxin dosage not required upon initiation of captopril198
Diuretics	Possible additive hypotensive effectsa Pharmacokinetic interaction with furosemide unlikely115	Adjust dosage carefullya (see Dosage under Dosage and Administration)
Diuretics, potassium-sparing (amiloride, spironolactone, triamterene)	Possible hyperkalemia, especially in patients with renal impairment162 329 331 335	Use cautiously and only if hypokalemia is documented; monitor serum potassium carefully;85 115 125 126 148 162 163 164 discontinue or reduce dosage of potassium-sparing diuretic as necessary85 126 148 162 163
Insulin	Possible hypoglycemia in diabetic patients101	Consider risk of hypoglycemia101
Lithium	Possible increased serum lithium concentrations, particularly in patients receiving concomitant diuretic therapy115	Use with caution; monitor serum lithium concentrations frequently115
NSAIAs	Possible decreased antihypertensive response to captopril;283 284 285 286 287 288 289 290 333 364 potential for acute reduction of renal function;285 291 possible attenuation of hemodynamic actions of ACE inhibitors in patients with CHF333 364	Monitor BP carefully and be alert for evidence of impaired renal function;285 if interaction is suspected, discontinue NSAIA or modify captopril dosage or use another hypotensive agent285 286
Potassium supplements or potassium-containing salt substitutes	Possible hyperkalemia, especially in patients with renal impairment162	Use cautiously and only if hypokalemia is documented; monitor serum potassium carefully;85 115 125 126 148 162 163 164 discontinue or reduce dosage of potassium supplement as necessary85 126 148 162 163
Probenecid	Possible increased blood concentrations of captopril and its metabolites203 204 205 213
Test for urine acetone	Possible false-positive results with sodium nitroprusside reagent54 115
Vasodilating agents (e.g., hydralazine, nitrates, prazosin)	Possible increased hypotensive effect115	If possible, discontinue vasodilating agent before starting captopril; if vasodilating agent is resumed during captopril therapy, administer with caution and possibly at a lower dosage115

Captopril Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration in fasting individuals,^{19 20 84 115} with peak blood concentration attained in 1 hour.¹⁹ Approximately 60–75% of an oral dose is absorbed.^{19 20 84 115}

Onset

Hypotensive effect may be apparent within 15 minutes^{5 6 16 23} and usually is maximal in 1–2 hours after a single oral dose.^{1 3 10 15 16 17 21 24 29} Several weeks of therapy may be required before full effect on BP is achieved.^{1 3 5 16 21 28}

Duration

Duration of action generally is 2–6 hours but appears to increase with increasing doses.^a

Food

Food may decrease absorption of captopril by up to 25–40%;^{1 3 115 191 195 196 197 202} effect may not be clinically important.^{191 192 195}

Distribution

Extent

Appears to be rapidly distributed into most body tissues, except CNS.^{1 5}

Crosses the placenta and is distributed into milk.¹¹⁵

Plasma Protein Binding

25–30%^{1 3 22} (mainly albumin).³

Elimination

Metabolism

About half the absorbed dose is rapidly metabolized.^{3 5 19} Captopril and its metabolites may undergo reversible interconversions.³

Elimination Route

Excreted in urine (95%) as unchanged drug (40–50%) and metabolites.^{3 19 20 22 115}

Half-life

<2 hours.¹¹⁵

Special Populations

Elimination half-life is about 20–40 hours in patients with Cl_cr <20 mL/minute ³ and up to 6.5 days in anuric patients.^{5 22}

Stability

Storage

Oral

Tablets

Tight containers at ≤30°C.¹¹⁵

Tablets (Captopril and Hydrochlorothiazide)

Tight containers at ≤30°C.¹⁰²

ActionsActions

• 
  

  Suppresses the renin-angiotensin-aldosterone system.¹

  
  

Advice to Patients

• 
  

  Risk of angioedema, anaphylactoid reactions, or other sensitivity reactions.¹¹⁵ 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.¹¹⁵

  
  


• 
  

  Importance of reporting signs of infection (e.g., sore throat, fever).¹¹⁵

  
  


• 
  

  Risk of hypotension.¹¹⁵ Importance of informing clinicians promptly if lightheadedness or fainting occurs.¹¹⁵

  
  


• 
  

  Importance of adequate fluid intake; risk of volume depletion with excessive perspiration, dehydration, vomiting, or diarrhea.¹¹⁵

  
  


• 
  

  Importance of not discontinuing or interrupting therapy unless instructed by a clinician.¹¹⁵

  
  


• 
  

  Risks of use during pregnancy.^{115 401 402} (See Boxed Warning.)

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (including salt substitutes containing potassium) as well as any concomitant illnesses.¹¹⁵

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹¹⁵

  
  


• 
  

  Importance of taking 1 hour before meals.¹¹⁵

  
  


• 
  

  Importance of advising patients of other important precautionary information.¹¹⁵ (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

Captopril

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	12.5 mg*	Capoten (scored)	Par
		25 mg*	Capoten (scored)	Par
		50 mg*	Capoten (scored)	Par
		100 mg*	Capoten (scored)	Par

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

Captopril and Hydrochlorothiazide

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	25 mg Captopril and Hydrochlorothiazide 15 mg*	Capozide (scored)	Par
			Captopril and Hydrochlorothiazide Tablets	Endo, Mylan, Sandoz, Teva
		25 mg Captopril and Hydrochlorothiazide 25 mg*	Capozide (scored)	Par
			Captopril and Hydrochlorothiazide Tablets	Endo, Mylan, Sandoz, Teva
		50 mg Captopril and Hydrochlorothiazide 15 mg*	Capozide (scored)	Par
			Captopril and Hydrochlorothiazide Tablets	Endo, Mylan, Sandoz, Teva
		50 mg Captopril and Hydrochlorothiazide 25 mg*	Capozide (scored)	Par
			Captopril and Hydrochlorothiazide Tablets	Endo, Mylan, Sandoz, Teva

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.

Capozide 50-25MG Tablets (PAR): 30/$95.99 or 90/$269.98

Captopril 100MG Tablets (WEST-WARD): 90/$19.99 or 180/$29.97

Captopril 12.5MG Tablets (WEST-WARD): 100/$12.99 or 200/$18.98

Captopril 25MG Tablets (TEVA PHARMACEUTICALS USA): 90/$13.99 or 180/$26.99

Captopril 50MG Tablets (WEST-WARD): 100/$16.99 or 200/$22.97

Captopril-Hydrochlorothiazide 25-15MG Tablets (MYLAN): 90/$47.99 or 270/$114.97

Captopril-Hydrochlorothiazide 25-25MG Tablets (MYLAN): 90/$44.99 or 270/$125.99

Captopril-Hydrochlorothiazide 50-15MG Tablets (TEVA PHARMACEUTICALS USA): 60/$53.99 or 180/$154.98

Captopril-Hydrochlorothiazide 50-25MG Tablets (MYLAN): 60/$53.99 or 180/$154.99

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.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions April 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

1. ER Squibb & Sons, Inc. Capoten prescribing information. Princeton, NJ; 1981 Mar.

3. ER Squibb & Sons, Inc. Capoten (captopril) monograph. Princeton, NJ; 1981 Apr.

4. Atkinson AB, Robertson JIS. Captopril in the treatment of clinical hypertension and cardiac failure. Lancet. 1979; 2:836-9. [IDIS 102581] [PubMed 90928]

5. Heel RC, Brogden RN, Speight TM et al. Captopril: a preliminary review of its pharmacological properties and therapeutic efficacy. Drugs. 1980; 20:409-52. [IDIS 134943] [PubMed 7009133]

6. Ferguson RK, Turini GA, Brunner HR et al. A specific orally active inhibitor of angiotensin-converting enzyme in man. Lancet. 1977; 1:775-8. [IDIS 78256] [PubMed 66571]

7. Gavras H, Brunner HR, Turini GA et al. Antihypertensive effect of the oral angiotensin converting-enzyme inhibitor SQ 14225 in man. N Engl J Med. 1978; 298:991-5. [IDIS 80115] [PubMed 205788]

8. Larochelle P, Genest J, Kuchel O et al. Effect of captopril (SQ 14225) on blood pressure, plasma renin activity and angiotensin I converting enzyme activity. Can Med Assoc J. 1979; 121:309-16. [IDIS 100999] [PubMed 223756]

9. Swartz S, Williams GH, Hollenberg NK et al. Increase in prostaglandins during converting enzyme inhibition. Clin Sci. 1980; 59(Suppl):133-5S.

10. Brunner HR, Gavras H, Waeber B et al. Oral angiotensin-converting enzyme inhibitor in long-term treatment of hypertensive patients. Ann Intern Med. 1979; 90:19-23. [IDIS 96700] [PubMed 217289]

11. Johnston CI, Millar JA, McGrath BP et al. Long-term effects of captopril (SQ 14225) on blood-pressure and hormone levels in essential hypertension. Lancet. 1979; 2:493-6. [IDIS 103099] [PubMed 90216]

12. McCaa CS, Langford HG, Cushman WC et al. Response of arterial blood pressure, plasma renin activity and aldosterone concentration to long-term administration of captopril to patients with severe, treatment-resistant malignant hypertension. Clin Sci. 1979; 57(Suppl):371-3S.

13. Fagard R, Amery A, Reybrouck T et al. Acute and chronic systemic and pulmonary hemodynamic effects of angiotensin converting enzyme inhibition with captopril in hypertensive patients. Am J Cardiol. 1980; 46:295-300. [IDIS 122485] [PubMed 6250392]

14. Maruyama A, Ogihara T, Naka T et al. Long-term effects of captopril in hypertension. Clin Pharmacol Ther. 1980; 28:316-23. [IDIS 123828] [PubMed 6996895]

15. Mimran A, Brunner HR, Turini GA et al. Effect of captopril on renal vascular tone in patients with essential hypertension. Clin Sci. 1979; 57(Suppl):421-3S. [IDIS 109948] [PubMed 519950]

16. Case DB, Atlas SA, Laragh JH et al. Clinical experience with blockade of the renin-angiotensin-aldosterone system by an oral converting-enzyme inhibitor (SQ 14,225, captopril) in hypertensive patients. Prog Cardiovasc Dis. 1978; 21:195-206. [PubMed 214819]

17. Morganti A, Pickering TG, Lopez-Ovejero JA et al. Endocrine and cardiovascular influences of converting enzyme inhibition with SQ 14225 in hypertensive patients in the supine position and during head-up tilt before and after sodium depletion. J Clin Endocrinol Metab. 1980; 50:748-54. [IDIS 124889] [PubMed 6245101]

19. Kripalani KJ, McKinstry DN, Singhvi SM et al. Disposition of captopril in normal subjects. Clin Pharmacol Ther. 1980; 27:636-41. [IDIS 113124] [PubMed 6989546]

20. McKinstry DN, Kripalani KJ, Migdalof BH et al. The effe