Proscar 5mg film-coated Tablets

1. Name Of The Medicinal Product

PROSCAR® 5mg film-coated Tablets

(finasteride)

2. Qualitative And Quantitative Composition

Each tablet contains 5 mg of finasteride.

3. Pharmaceutical Form

Blue-coloured, apple-shaped, film

4. Clinical Particulars

4.1 Therapeutic Indications

'Proscar' is indicated for the treatment and control of benign prostatic hyperplasia (BPH) in patients with an enlarged prostate to:

− cause regression of the enlarged prostate, improve urinary flow and improve the symptoms associated with BPH

− reduce the incidence of acute urinary retention and the need for surgery including transurethral resection of the prostate (TURP) and prostatectomy.

4.2 Posology And Method Of Administration

The recommended adult dose is one 5 mg tablet daily, with or without food.

'Proscar' can be administered alone or in combination with the alpha-blocker doxazosin (see section 5.1 'Pharmacodynamic properties').

Although early improvement in symptoms may be seen, treatment for at least six months may be necessary to assess whether a beneficial response has been achieved. Thereafter, treatment should be continued long term.

No dosage adjustment is required in the elderly or in patients with varying degrees of renal insufficiency (creatinine clearances as low as 9 ml/min).

There are no data available in patients with hepatic insufficiency.

'Proscar' is contra-indicated in children.

4.3 Contraindications

'Proscar' is not indicated for use in women or children.

'Proscar' is contraindicated in the following:

• Hypersensitivity to any component of this product

• Pregnancy - Use in women when they are or may potentially be pregnant (see 4.6 Pregnancy and lactation, Exposure to finasteride - risk to male foetus).

4.4 Special Warnings And Precautions For Use

General

To avoid obstructive complications it is important that patients with large residual urine and/or heavily decreased urinary flow are carefully controlled. The possibility of surgery should be an option.

Effects on PSA and prostate cancer detection

No clinical benefit has yet been demonstrated in patients with prostate cancer treated with 'Proscar'. Patients with BPH and elevated serum prostate specific antigen (PSA) were monitored in controlled clinical studies with serial PSAs and prostate biopsies. In these BPH studies, 'Proscar' did not appear to alter the rate of prostate cancer detection, and the overall incidence of prostate cancer was not significantly different in patients treated with 'Proscar' or placebo.

Digital rectal examination, as well as other evaluations for prostate cancer, are recommended prior to initiating therapy with 'Proscar' and periodically thereafter.. Serum PSA is also used for prostate cancer detection. Generally, a baseline PSA>10 ng/ml (Hybritech) prompts further evaluation and consideration of biopsy; for PSA levels between 4 and 10 ng/ml, further evaluation is advisable. There is considerable overlap in PSA levels among men with and without prostate cancer. Therefore, in men with BPH, PSA values within the normal reference range do not rule out prostate cancer regardless of treatment with 'Proscar'. A baseline PSA <4 ng/ml does not exclude prostate cancer.

'Proscar' causes a decrease in serum PSA concentrations by approximately 50% in patients with BPH even in the presence of prostate cancer. This decrease in serum PSA levels in patients with BPH treated with 'Proscar' should be considered when evaluating PSA data and does not rule out concomitant prostate cancer. This decrease is predictable over the entire range of PSA values, although it may vary in individual patients. In patients treated with 'Proscar' for six months or more, PSA values should be doubled for comparison with normal ranges in untreated men. This adjustment preserves the sensitivity and specificity of the PSA assay and maintains its ability to detect prostate cancer.

Any sustained increase in PSA levels of patients treated with finasteride should be carefully evaluated, including consideration of non-compliance to therapy with 'Proscar'.

Drug/laboratory test interactions

Effect on levels of PSA

Serum PSA concentration is correlated with patient age and prostatic volume, and prostatic volume is correlated with patient age. When PSA laboratory determinations are evaluated, consideration should be given to the fact that PSA levels decrease in patients treated with 'Proscar'. In most patients, a rapid decrease in PSA is seen within the first months of therapy, after which time PSA levels stabilise to a new baseline. The post-treatment baseline approximates half of the pre-treatment value. Therefore, in typical patients treated with 'Proscar' for six months or more, PSA values should be doubled for comparison to normal ranges in untreated men. For clinical interpretation, see 4.4 Special warnings and precautions for use, Effects on PSA and prostate cancer detection.

Percent free PSA (free to total PSA ratio) is not significantly decreased by 'Proscar'. The ratio of free to total PSA remains constant even under the influence of 'Proscar'. When percent free PSA is used as an aid in the detection of prostate cancer, no adjustment to its value is necessary.

Breast cancer in men

Breast cancer has been reported in men taking finasteride 5 mg during clinical trials and the post-marketing period. Physicians should instruct their patients to promptly report any changes in their breast tissue such as lumps, pain, gynaecomastia or nipple discharge.

Pediatric use

'Proscar' is not indicated for use in children.

Safety and effectiveness in children have not been established.

Lactose

The tablet contains lactose monohydrate. Patients with any of the following genetic deficiencies should not take this drug: galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.

Hepatic Insufficiency

The effect of hepatic insufficiency on the pharmacokinetics of finasteride has not been studied.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No drug interactions of clinical importance have been identified. Finasteride is metabolized primarily via, but does not appear to affect significantly, the cytochrome P450 3A4 system. Although the risk for finasteride to affect the pharmacokinetics of other drugs is estimated to be small, it is probable that inhibitors and inducers of cytochrome P450 3A4 will affect the plasma concentration of finasteride. However, based on established safety margins, any increase due to concomitant use of such inhibitors is unlikely to be of clinical significance. 'Compounds which have been tested in man have included propranolol, digoxin, glyburide, warfarin, theophylline, and antipyrine and no clinically meaningful interactions were found.

4.6 Pregnancy And Lactation

Pregnancy: 'Proscar' is contra

Because of the ability of Type II 5 α-reductase inhibitors to inhibit conversion of testosterone to dihydrotestosterone, these drugs, including finasteride, may cause abnormalities of the external genitalia of a male foetus when administered to a pregnant woman.

In animal developmental studies, dose-dependent development of hypospadias were observed in the male offspring of pregnant rats given finasteride at doses ranging from 100 μg/kg/day to 100 mg/kg/day, at an incidence of 3.6% to 100%. Additionally, pregnant rats produced male offspring with decreased prostatic and seminal vesicular weights, delayed preputial separation, transient nipple development and decreased anogenital distance, when given finasteride at doses below the recommended human dose. The critical period during which these effects can be induced has been defined in rats as days 16

The changes described above are expected pharmacological effects of Type II 5 α-reductase inhibitors. Many of the changes, such as hypospadias, observed in male rats exposed in utero to finasteride are similar to those reported in male infants with a genetic deficiency of Type II 5 α-reductase. It is for these reasons that 'Proscar' is contra

No effects were seen in female offspring exposed in utero to any dose of finasteride.

Exposure to finasteride

Women should not handle crushed or broken tablets of 'Proscar' when they are or may potentially be pregnant because of the possibility of absorption of finasteride and the subsequent potential risk to a male foetus (see 4.6 Pregnancy and Lactation 'Pregnancy'). 'Proscar' tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets have not been broken or crushed.

Small amounts of finasteride have been recovered from the semen in subjects receiving finasteride 5 mg/day. It is not known whether a male foetus may be adversely affected if his mother is exposed to the semen of a patient being treated with finasteride. When the patient's sexual partner is or may potentially be pregnant, the patient is recommended to minimise exposure of his partner to semen.

Lactation: 'Proscar' is not indicated for use in women.

It is not known whether finasteride is excreted in human milk.

4.7 Effects On Ability To Drive And Use Machines

There are no data to suggest that 'Proscar' affects the ability to drive or use machines.

4.8 Undesirable Effects

The most frequent adverse reactions are impotence and decreased libido. These adverse reactions occur early in the course of therapy and resolve with continued treatment in the majority of patients.

The adverse reactions reported during clinical trials and/or post-marketing use are listed in the table below.

Frequency of adverse reactions is determined as follows:

Very common (

System Organ Class	Frequency: adverse reaction
Investigations	Common: decreased volume of ejaculate
Cardiac disorders	Unknown: palpitation
Skin and subcutaneous tissue disorders	Uncommon: rash Unknown: pruritus, urticaria
Immune system disorders	Unknown: hypersensitivity reactions including swelling of the lips and face
Hepatobiliary disorders	Unknown: increased hepatic enzymes
Reproductive system and breast disorders	Common: impotence Uncommon: ejaculation disorder, breast tenderness, breast enlargement Unknown: testicular pain
Psychiatric disorders	Common: decreased libido

In addition, the following has been reported in clinical trials and post-marketing use: male breast cancer (see 4.4 Special warnings and precautions for use).

Medical therapy of prostatic symptoms (MTOPS)

The MTOPS study compared finasteride 5 mg/day (n=768), doxazosin 4 or 8 mg/day (n=756), combination therapy of finasteride 5 mg/day and doxazosin 4 or 8 mg/day (n=786), and placebo (n=737). In this study, the safety and tolerability profile of the combination therapy was generally consistent with the profiles of the individual components. The incidence of ejaculation disorder in patients receiving combination therapy was comparable to the sum of incidences of this adverse experience for the two monotherapies.

Other long-term data

In a 7 year placebo-controlled trial that enrolled 18,882 healthy men, of 9060 had prostate needle biopsy data available for analysis, prostate cancer was detected in 803 (18.4%) men receiving 'Proscar' and 1147 (24.4%) men receiving placebo. In the 'Proscar' group, 280 (6.4%) men had prostate cancer with Gleason scores of 7-10 detected on needle biopsy vs 237 (5.1%) men in the placebo group. Additional analyses suggest that the increase in the prevalence of high-grade prostate cancer observed in the 'Proscar' group may be explained by a detection bias due to the effect of 'Proscar' on prostate volume. Of the total cases of prostate cancer diagnosed in this study, approximately 98% were classified as intracapsular (stage T1 or T2). The relationship between long-term use of 'Proscar' and tumours with Gleason scores of 7-10 is unknown.

Laboratory test findings

When PSA laboratory determinations are evaluated, consideration should be given to the fact that PSA levels are decreased in patients treated with 'Proscar' (see section 4.4 Special warnings and precautions for use). In most patients, a rapid decrease in PSA is seen within the first months of therapy, after which time PSA levels stabilise to a new baseline. The post-treatment baseline approximates half of the pre-treatment value. Therefore, in typical patients treated with 'Proscar' for six months or more, PSA values should be doubled for comparison to normal ranges in untreated men.

For clinical interpretation see 'Special warnings and precautions for use', Effects on prostate-specific antigen (PSA) and prostate cancer detection.

No other difference was observed in patients treated with placebo or 'Proscar' in standard laboratory tests.

4.9 Overdose

No specific treatment of overdosage with 'Proscar' is recommended. Patients have received single doses of 'Proscar' up to 400 mg and multiple doses of 'Proscar' up to 80 mg/day for up to three months without any adverse effects.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Finasteride is a competitive inhibitor of human 5 α-reductase, an intracellular enzyme which metabolises testosterone into the more potent androgen, dihydrotestosterone (DHT). In benign prostatic hyperplasia (BPH), enlargement of the prostate gland is dependent upon the conversion of testosterone to DHT within the prostate. 'Proscar' is highly effective in reducing circulating and intraprostatic DHT. Finasteride has no affinity for the androgen receptor.

In clinical studies of patients with moderate to severe symptoms of BPH, an enlarged prostate on digital rectal examination and low residual urinary volumes, 'Proscar' reduced the incidence of acute retention of urine from 7/100 to 3/100 over four years and the need for surgery (TURP or prostatectomy) from 10/100 to 5/100. These reductions were associated with a 2-point improvement in QUASI-AUA symptom score (range 0-34), a sustained regression in prostate volume of approximately 20% and a sustained increase in urinary flow rate.

Medical therapy of prostatic symptoms

The Medical Therapy of Prostatic Symptoms (MTOPS) Trial was a 4- to 6-year study in 3047 men with symptomatic BPH who were randomised to receive finasteride 5 mg/day, doxazosin 4 or 8 mg/day^*, the combination of finasteride 5 mg/day and doxazosin 4 or 8 mg/day^*, or placebo. The primary endpoint was time to clinical progression of BPH, defined as a

^* Titrated from 1 mg to 4 or 8 mg as tolerated over a 3-week period

5.2 Pharmacokinetic Properties

After an oral dose of ¹⁴C

The oral bioavailability of finasteride is approximately 80%, relative to an intravenous reference dose, and is unaffected by food. Maximum plasma concentrations are reached approximately two hours after dosing and the absorption is complete within 6

In the elderly, the elimination rate of finasteride is somewhat decreased. Half-life is prolonged from a mean half

In patients with chronic renal impairment, whose creatinine clearance ranged from 9¹⁴C

There are no data available in patients with hepatic insufficiency.

Finasteride has been found to cross the blood

5.3 Preclinical Safety Data

Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity, genotoxicity, and carcinogenic potential. Reproduction toxicology studies in male rats have demonstrated reduced prostate and seminal vesicular weights, reduced secretion from accessory genital glands and reduced fertility index (caused by the primary pharmacological effect of finasteride). The clinical relevance of these findings is unclear.

As with other 5-alpha-reductase inhibitors, femininisation of male rat foetuses has been seen with administration of finasteride in the gestation period. Intravenous administration of finasteride to pregnant rhesus monkeys at doses up to 800 ng/day during the entire period of embryonic and foetal development resulted in no abnormalities in male foetuses. This dose is about 60-120 times higher than the estimated amount in semen of a man who have taken 5 mg finasteride, and to which a woman could be exposed via semen. In confirmation of the relevance of the Rhesus model for human foetal development, oral administration of finasteride 2 mg/kg/day (the systemic exposure (AUC) of monkeys was slightly higher (3x) than that of men who have taken 5 mg finasteride, or approximately 1-2 million times the estimated amount of finasteride in semen) to pregnant monkeys resulted in external genital abnormalities in male foetuses. No other abnormalities were observed in male foetuses and no finasteride-related abnormalities were observed in female foetuses at any dose.”

6. Pharmaceutical Particulars

6.1 List Of Excipients

Cellulose, Microcrystalline (E460)

Docusate sodium

Lactose monohydrate

Magnesium stearate (E572)

Pregelatinised maize starch

Sodium starch glycollate Type A

Yellow iron oxide (E172)

Hydroxypropylcellulose (E463)

Indigo carmine aluminium lake (E132)

Hypromellose (E464)

Talc

Titanium dioxide (E171)

6.2 Incompatibilities

None reported.

6.3 Shelf Life

Three years.

6.4 Special Precautions For Storage

Do not store above 30°C. Store in the original package.

6.5 Nature And Contents Of Container

Opaque PVC/PE/PVDC blisters lidded with aluminium foil; packs of 28 tablets.

6.6 Special Precautions For Disposal And Other Handling

Women should not handle crushed or broken 'Proscar' Tablets when they are or may potentially be pregnant (see 'Contra-indications, 'Pregnancy and lactation', Exposure to finasteride - risk to male foetus).

7. Marketing Authorisation Holder

Merck Sharp & Dohme Limited

Hertford Road, Hoddesdon, Hertfordshire EN11 9BU, UK.

8. Marketing Authorisation Number(S)

PL 0025/0279.

9. Date Of First Authorisation/Renewal Of The Authorisation

July 1997.

10. Date Of Revision Of The Text

October 2010

LEGAL CATEGORY

POM

© Merck Sharp & Dohme Limited 2010. All rights reserved.

SPC.PSC.10.UK.3326

Nicotrol Inhalation, oral/nebulization

Generic Name: nicotine (Inhalation route)

NIK-oh-teen

Commonly used brand name(s)

In the U.S.

• Nicotrol

In Canada

• Nicorette Inhaler

Available Dosage Forms:

• Aerosol Powder


• Device


• Aerosol Liquid

Therapeutic Class: Smoking Cessation Agent

Pharmacologic Class: Cholinergic

Uses For Nicotrol

Nicotine, in an inhaler is used to help you stop smoking. It is used for up to 6 months as part of a stop-smoking program. This program may include counseling, education, specific behavior change techniques, or support groups.

With the inhaler, nicotine is inhaled through the mouth and is absorbed in the mouth and throat, but not in the lungs. Eight to ten puffs on the inhaler provide about the same amount of nicotine as one puff on an average cigarette. This nicotine takes the place of the nicotine that you would otherwise get from smoking. In this way, the withdrawal effects of not smoking are less severe. Then, as your body adjusts to not smoking, the use of the nicotine inhaler is decreased gradually over several weeks. Finally, use is stopped altogether.

Children, pregnant women, and nonsmokers should not use nicotine inhaler because of harmful effects.

This medicine is available only with your doctor's prescription.

Before Using Nicotrol

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

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

Geriatric

Although appropriate studies on the relationship of age to the effects of nicotine inhaler have not been performed in the geriatric population, no geriatric-specific problems have been documented to date. However, elderly patients are more likely to have age-related kidney, liver, or heart problems, which may require caution and an adjustment in the dose for patients receiving nicotine inhaler. .

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	D	Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk.

Breast Feeding

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.

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 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.

• Clozapine

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

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

• Asthma or other breathing problems or


• Heart attack, history of or


• Heart or blood vessel disease or


• Heart rhythm problems or


• Hypertension (high blood pressure) or


• Overactive thyroid or


• Pheochromocytoma (an adrenal problem) or


• Stomach ulcer or


• Type 1 diabetes mellitus (sugar diabetes)—Use with caution. Nicotine may make these conditions worse.

• Drug abuse or


• Drug dependence—Dependence may be more likely to develop.

• Kidney disease or


• Liver disease—Use with caution. Effects may be increased because of slower removal of the medicine from the body.

Proper Use of nicotine

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

Nicotine inhaler usually comes with patient directions. Read the directions carefully before using this medicine. Ask your doctor if you have any questions.

The nicotine inhaler should be used at or above room temperature (60 °F [16 °C]). Cold temperatures decrease the amount of nicotine you inhale.

You should stop smoking completely before you start using this medicine. If you continue to smoke during treatment, you may have an increased risk of nicotine overdose.

Use this medicine exactly as directed by your doctor. Remember that it is important to participate in a stop-smoking program during treatment. This may make it easier for you to stop smoking.

Wash the mouthpiece of the inhaler with soap and water regularly after each use.

To decrease the risk of becoming dependent on the nicotine inhaler, your doctor may instruct you to stop treatment gradually. This may be done by keeping track of, and steadily reducing, use of the nicotine inhaler or by setting a planned date for stopping use of the inhaler.

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 inhalation dosage form (cartridge):
  
  • To help you stop smoking:
    
    • Adults and older teenagers—At first, 6 to 16 cartridges per day for up to twelve weeks. Your dose is gradually reduced over a period of up to twelve weeks.
    
    
    • Children—Use and 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

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.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Nicotrol

Do not smoke during treatment with the nicotine inhaler because of the risk of nicotine overdose.

Do not use the nicotine inhaler for longer than 6 months if you have stopped smoking because continuing use of nicotine in any form can be harmful and addictive.

Nicotine should not be used in pregnancy. If there is a possibility you might become pregnant, you may want to use some type of birth control. If you think you may have become pregnant, stop taking this medicine immediately and check with your doctor.

Nicotine products must be kept out of the reach of children and pets. Even used nicotine inhaler cartridges contain enough nicotine to cause serious harm in children. If a child chews on or swallows a cartridge, contact your doctor or poison control center at once.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Nicotrol 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

• Fast or irregular heartbeat


• fever with or without chills


• headache


• nausea with or without vomiting


• runny nose


• shortness of breath, tightness in the chest, trouble with breathing, or wheezing


• skin rash, itching, or hives


• tearing of the eyes

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

• Abdominal or stomach pain


• cold sweat


• confusion


• convulsions (seizures)


• disturbed hearing and vision


• drooling


• extreme exhaustion


• pale skin


• slow heartbeat


• tremors

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

• Acid or sour stomach


• belching


• coughing


• heartburn


• indigestion


• mouth and throat irritation


• stomach discomfort, upset, or pain


• stuffy nose

Less common

• Anxiety


• back pain


• change in taste


• diarrhea


• dizziness


• feeling of burning, numbness, tightness, tingling, warmth, or heat


• feelings of drug dependence


• flu-like symptoms


• general pain


• hiccups


• mental depression


• pain in the jaw and neck


• pain in the muscles


• passing of gas


• problems with teeth


• trouble with sleeping


• unusual tiredness or weakness

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: Nicotrol Inhalation,/nebulization side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Nicotrol Inhalation, oral/nebulization resources

• Nicotrol Inhalation, oral/nebulization Side Effects (in more detail)
• Nicotrol Inhalation, oral/nebulization Use in Pregnancy & Breastfeeding
• Nicotrol Inhalation, oral/nebulization Drug Interactions
• Nicotrol Inhalation, oral/nebulization Support Group
• 15 Reviews for Nicotrol Inhalation,/nebulization - Add your own review/rating

Compare Nicotrol Inhalation, oral/nebulization with other medications

• Smoking Cessation

Naltrexone

Class: Opiate Antagonists
VA Class: CN102
Chemical Name: 17-(Cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan-6-one
Molecular Formula: C₂₀H₂₃NO₄C₂₀H₂₃NO₄•HCl
CAS Number: 16590-41-3
Brands: ReVia, Vivitrol

• Hepatic Effects


• 
  

  Possible dose-related hepatotoxicity.^{1 102 226 228 247} Margin between therapeutic and hepatotoxic dosages may be less than fivefold; hepatotoxicity not apparent at usual dosages.^{1 102 247} (See Hepatic Effects under Cautions.)

  
  


• 
  

  Contraindicated in patients with acute hepatitis or liver failure;^{1 102 247} carefully weigh potential benefits against possible hepatotoxic risks in patients with active liver disease.^{1 247}

  
  


• 
  

  Instruct patients to discontinue naltrexone and contact a clinician if manifestations of acute hepatitis occur.^{1 247} (See Advice to Patients.)

  
  

REMS:

FDA approved a REMS for naltrexone to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of naltrexone and consists of the following: medication guide and communication plan. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Essentially a pure opiate antagonist.^{1 2 3 7 17 23 102}

Uses for Naltrexone

Opiate Dependence

Used as an adjunct to a medically supervised behavior modification program^{1 35 99 102 147 160 161 162 163 164 165 166 170} in the maintenance of opiate cessation (opiate-free state) in individuals who were formerly physically dependent on opiates and who have successfully undergone detoxification^{1 14 35 102 143 147 158 162 163 164 165} (designated an orphan drug by FDA for this use).²¹⁷

Behavior modification is an integral component in maintaining opiate cessation; behavior modification programs involve supervised programs of counseling, psychologic support and therapy, education, and changes in life-style (social rehabilitation).^{1 2 35 37 102 143 147 159 160 162 170 189 192 193 204}

May diminish or eliminate opiate-seeking behavior by blocking opiate euphoria and by preventing the conditioned abstinence syndrome (i.e., heightened sensitivity to stimuli, abnormal autonomic responses, dysphoria, intense opiate craving) that occurs following opiate withdrawal.^{1 2 27 102 158 190 191}

Efficacy in maintaining long-term cessation appears to be low;^{2 11 14 15 42 123 125 135 161 182 203} poor compliance appears to be the major limiting factor.^{1 2 8 13 42 99 182 204} Because noncompliance with naltrexone is not associated with unpleasant symptoms of withdrawal, compliance depends more on voluntary efforts; successful cessation may be more likely in highly motivated individuals.^{1 2 8 13 15 35 36 99 102 130 147 162 163 167 172}

Has been used for rapid or ultrarapid detoxification in the management of opiate withdrawal† in opiate-dependent individuals, both in inpatient and outpatient settings.²⁴⁶

Rapid opiate detoxification involves the administration of opiate antagonists (e.g., naltrexone and/or naloxone) to shorten the time period of detoxification.²⁴⁶

Ultrarapid detoxification is similar but involves the administration of opiate antagonists while the patient is sedated or under general anesthesia.²⁴⁶ Consider the risk of adverse respiratory and cardiovascular effects associated with this procedure, as well as the costs of general anesthesia and hospitalization.²⁴⁶

Alcohol Dependence

Management of alcohol dependence in conjunction with a behavior modification program^{1 232 233 234 235 236 237 247} involving supervised programs of counseling, psychologic support and therapy, and education and changes in life-style (social rehabilitation).^{1 232 238}

Used IM in individuals who are able to abstain from alcohol in an outpatient setting and are abstinent when treatment is initiated.^{247 249}

Behavior modification is an integral component in maintaining alcohol cessation; naltrexone has not been shown to provide any therapeutic benefit except as part of an appropriate plan of addiction management.^{1 232 234 237 239 245}

When used in conjunction with behavior modification, naltrexone reportedly decreases alcohol craving, reduces alcohol consumption, decreases the number of drinking days, maintains abstinence from alcohol ingestion, and prevents, decreases, or ameliorates the severity of relapse.^{1 232 235 237 238}

Naltrexone is not uniformly effective; the expected effect is a modest improvement in the outcome of conventional therapy.^{1 232 233 244 245}

Naltrexone Dosage and Administration

General

REMS for Parenteral Naltrexone

• 
  

  FDA required and approved a Risk Evaluation and Mitigation Strategy (REMS) for parenteral naltrexone.²⁵⁹

  
  

  The REMS requires that a medication guide be given to the patient each time parenteral naltrexone is dispensed;^{259 260} the goal is to inform patients about serious risks associated with parenteral naltrexone.²⁵⁹ (See Advice to Patients and also see Cautions.)

  
  

Verification of Opiate Abstinence Prior to Initiation of Therapy

• 
  

  Patients who are physically dependent on opiates should complete detoxification prior to initiation of naltrexone therapy.^{1 102}

  
  


• 
  

  Manufacturers recommend that at least 7–10 days elapse between discontinuance of opiates and initiation of naltrexone therapy because of the risk of precipitating opiate withdrawal (see Accidental Precipitation of Withdrawal under Cautions.)^{1 102} This waiting period may vary depending on the dose and duration of action of the opiate;^{1 102 121 162} allow at least 7 days in patients using relatively short-acting opiates (e.g., heroin, hydromorphone, meperidine, morphine) and at least 10–14 days in those using longer-acting opiates (e.g., methadone).²³⁷

  
  


• 
  

  Some clinicians have cautiously precipitated withdrawal using repeated naloxone injections and then rapidly initiated naltrexone therapy with incremental doses of the drug; this procedure can reduce the transition period from opiate dependence to naltrexone maintenance and generally is well accepted by patients.^{14 41 196 207}

  
  


• 
  

  In addition to patient verification of abstinence from opiates, perform urinalysis after the minimum 7- to 10-day waiting period, but prior to administration of naltrexone, to confirm the absence of opiates.^{1 102} If it is uncertain whether the patient is opiate free, perform a naloxone challenge test prior to administering naltrexone.^{1 102 247}

  
  

Naloxone Challenge Test

• 
  

  Perform test prior to induction of naltrexone therapy in patients formerly physically dependent on opiates who have completed detoxification and in those suspected of having been dependent on opiates.^{1 2 14 15 41 102 162 237}

  
  


• 
  

  Test should not be performed in patients who are exhibiting signs and/or symptoms of opiate withdrawal, those whose urine shows evidence of opiates, or those in whom there is a high degree of suspicion that opiates are still being used, since naloxone may precipitate potentially severe opiate withdrawal.^{1 102}

  
  


• 
  

  Do not attempt naltrexone therapy if signs and/or symptoms of opiate withdrawal (e.g., nasal stuffiness, rhinorrhea, lacrimation, yawning, sweating, tremor, abdominal cramps, vomiting, piloerection, myalgia, skin crawling) are evident following administration of the naloxone challenge test;^{1 102} instead, repeat the naloxone challenge test in 24 hours.¹

  
  


• 
  

  Naloxone may be administered IV or sub-Q in the challenge test.¹

  
  


• 
  

  IV challenge test: Draw 0.8 mg of naloxone hydrochloride into a syringe.¹ Administer 0.2 mg initially; while the needle remains in the vein observe the patient for 30 seconds¹⁹⁶ for evidence of opiate withdrawal.¹ Alternatively, some clinicians recommend 15 minutes for the period of observation. If no evidence of withdrawal is observed, inject the remaining 0.6-mg dose and observe the patient for an additional 20 minutes for evidence of withdrawal.¹

  
  


• 
  

  Sub-Q challenge test: Draw 0.8 mg of naloxone hydrochloride into a syringe.¹ Inject the entire 0.8-mg dose and observe the patient for 20 minutes for evidence of opiate withdrawal.¹

  
  


• 
  

  If evidence of opiate withdrawal is present, delay naltrexone therapy and repeat the naloxone challenge test in 24 hours with the 0.8-mg dose; repeat the test every 24 hours until results are negative.^{1 196}

  
  


• 
  

  If it is uncertain whether the patient is opiate free or is undergoing opiate withdrawal following an initial test, repeat the naloxone challenge test with a 1.6-mg IV dose.¹

  
  

Administration

Administer orally or by IM injection.^{1 102 247}

Do not administer parenteral preparation by IV or sub-Q injection; do not administer into fatty tissue.^{247 257}

Oral Administration

Administer orally;^{1 102} minimize adverse GI effects by taking with food¹²³ or antacids¹³¹ or after meals.^{9 102 131 143}

Patients should take naltrexone as directed and not attempt self-administration of opiates during therapy with the drug.^{1 102} (See Risks Associated with Self-administration of Opiates During Naltrexone Therapy under Cautions.)

IM Administration

IM preparation may be used in individuals who are able to abstain from alcohol in an outpatient setting and are abstinent when treatment is initiated.^{247 249}

Administer by deep IM injection into the upper outer quadrant of the gluteal muscle every 4 weeks (or once a month); alternate buttocks for subsequent injections.²⁴⁷

Administer only with needle and other components of dose pack supplied by manufacturer.²⁴⁷

Use aspiration to avoid inadvertent injection into a blood vessel.^{247 257}

Do not administer by IV or sub-Q injection; do not inadvertently administer into fatty tissue.^{247 257} Inadvertent sub-Q injection may increase likelihood of severe injection site reactions.²⁴⁷ (See Local Reactions under Cautions.)

Evaluate the patient's body habitus prior to each injection to ensure that the 1.5-inch needle supplied by the manufacturer is adequate for gluteal IM injection in that patient.²⁴⁷ Consider alternative treatment for any patient whose body habitus (i.e., gluteal fat thickness) precludes IM injection with the provided needle.^{247 261}

Reconstitution

Consult manufacturer’s labeling for instructions for using components of dose pack for reconstitution.²⁴⁷

Allow dose pack to reach room temperature before reconstituting.²⁴⁷

Reconstitute vial labeled as containing 380 mg of naltrexone extended-release microspheres with 3.4 mL of diluent; shake vigorously for 1 minute.²⁴⁷ Use only the diluent supplied by the manufacturer.²⁴⁷ Administer immediately.²⁴⁷

Dosage

Available for oral administration as naltrexone hydrochloride; dosage expressed in terms of the salt.¹

Available for IM administration as naltrexone.²⁴⁷

Adults

Opiate Dependence

Induction of Therapy for Opiate Cessation

Oral

Initiate induction regimen following completion of opiate detoxification and verification that the patient is free of opiates.¹⁰² (See General under Dosage and Administration.)

Initially, 25 mg; if no evidence of withdrawal is present, begin 50 mg daily.¹

Alternatively, some clinicians have administered 12.5 mg initially, followed by incremental increases of 12.5 mg daily until the usual dosage of 50 mg daily has been achieved.^{62 99 123 196}

Maintenance Therapy for Opiate Cessation

Oral

50 mg daily following induction of therapy.^{1 2 11 24 25 28 99 102}

Alternatively, flexible dosing schedules have been suggested in an attempt to improve compliance.^{1 2 35 62 99 102 122 138 157 158 161 164 196} Administration of larger doses at longer intervals (e.g., 48–72 hours) may reduce opiate antagonist activity somewhat, but may improve compliance.^{1 102 121} Single doses >50 mg may increase risk of hepatic injury; weigh possible risks against probable benefits of flexible dosing.¹

• Flexible Naltrexone Hydrochloride Dosing Schedules for Maintenance Therapy for Opiate Cessation


• 
  

  50 mg daily Monday through Friday and 100 mg on Saturday^{1 102}

  
  


• 
  

  100 mg every other day^{1 102}

  
  


• 
  

  150 mg every third day^{1 102}

  
  


• 
  

  100 mg on Monday and Wednesday and 150 mg on Friday^{1 8 35 99 102 121 122 123 157 158 164}

  
  


• 
  

  150 mg on Monday and 200 mg on Thursday¹⁹⁶

  
  

Ingestion of the naltrexone dose generally should be observed in a clinic setting or by a responsible family member to ensure compliance, in which case, regimens requiring less frequent visits may be more acceptable to the patient.^{8 99 102 182 194 196}

Monitor patient compliance by random testing of urine for naltrexone and 6-β-naltrexol or for the presence of opiates.^{62 102 161}

Optimum duration of maintenance therapy not established;¹²¹ base on individual requirements and response.¹⁰²

In patients who discontinue naltrexone prematurely and then desire to resume therapy following a relapse to opiate abuse, perform urinalysis for the presence of opiates and, if necessary, a naloxone challenge test prior to resuming therapy.^{161 196} If there is evidence of opiate dependence, conduct detoxification prior to reinitiation of naltrexone therapy.^{102 161}

Opiate Detoxification†

Oral

Various dosage regimens have been used for rapid or ultrarapid detoxification† of opiate dependence.^{2 38 162 168 169 246}

The following regimen of naltrexone, given in conjunction with clonidine to attenuate withdrawal manifestations, has been studied.³⁸

Day of Detoxification Therapy	Clonidine Hydrochloride	Naltrexone Hydrochloride
Day 1	0.005 mg/kg initially; then titrated according to the severity of withdrawal and the adverse effects induced by clonidine2 38
Day 2	Administered every 4 hours to attenuate the withdrawal induced by naltrexone38	Administered every 4 hours; 1 mg initially; then increased in 1-mg increments during the daytime on day 2 38
Day 3	Administered every 4 hours to attenuate the withdrawal induced by naltrexone; highest mean dosage was 2.3 mg daily on day 338	Administered every 4 hours; dosage increased in 2-mg increments during the daytime on day 338
Day 4	Administered only as needed to reduce signs and symptoms of withdrawal38	10 mg 3 times daily38
Day 5	Administered only as needed to reduce signs and symptoms of withdrawal38	50 mg once daily2 38

Alcohol Dependence

Oral

50 mg once daily,^{1 234 237} following verification that the patient is free of opiates.¹ (See General under Dosage and Administration.)

Optimum duration of therapy not established;²³⁷ safety and efficacy established only in short-term (up to 12 weeks) studies.^{1 231 232 233 234 236 237}

IM

380 mg every 4 weeks or once a month following verification that the patient is free of opiates. ²⁴⁷ (See General under Dosage and Administration.)

If a dose is missed, reschedule administration with a health-care professional as soon as possible.²⁴⁷

Therapy may be initiated with parenteral preparation; not necessary to initiate therapy with oral naltrexone and then switch to parenteral preparation.²⁴⁷

Special Populations

Hepatic Impairment

Alcohol Dependence

IM

Dosage adjustment not needed in patients with mild to moderate (Child-Pugh class A or B) hepatic impairment.²⁴⁷

Renal Impairment

Alcohol Dependence

IM

Dosage adjustment not needed in patients with mild renal impairment (Cl_cr of 50–80 mL/minute).²⁴⁷

Cautions for Naltrexone

Contraindications

• 
  

  Patients receiving opiate agonists (except for emergency situations).^{1 102 247}

  
  


• 
  

  Nondetoxified patients physically dependent on opiates, including those receiving maintenance treatment with opiates (e.g., methadone).^{1 102 247}

  
  


• 
  

  Patients experiencing acute opiate withdrawal.^{1 102 247}

  
  


• 
  

  Patients who experience opiate withdrawal following administration of the naloxone challenge test or in patients in whom urinalysis for the presence of opiates is positive.^{1 102 247}

  
  


• 
  

  Patients with acute hepatitis or hepatic failure.^{1 247}

  
  


• 
  

  Patients with known hypersensitivity to the drug or any ingredient in the formulation.^{1 247} Not known whether cross-sensitivity exists between naltrexone and naloxone or phenanthrene-derivative opiate agonists (e.g., codeine, morphine, oxymorphone).¹

  
  

Warnings/Precautions

Warnings

Hepatic Effects

Possible dose-related hepatocellular injury, manifested as increases in serum hepatic enzyme concentrations.^{1 102 226 228 247} (See Boxed Warning.)

Manufacturers state that naltrexone-induced hepatocellular injury appears to be a direct toxic rather than an idiosyncratic effect.¹ Some clinicians suggest that liver function abnormalities may be caused by noroxymorphone, a minor metabolite of naltrexone that has opiate agonist activity.^{196 206}

Manufacturer of oral naltrexone recommends monitoring liver function at intervals deemed appropriate for the naltrexone dosage employed and the clinical status of the patient.¹

Local Reactions

IM injection associated with injection site reactions (e.g., tenderness, induration, pain, pruritus, ecchymosis, nodules, swelling) in most patients.²⁴⁷ Cellulitis,²⁴⁷ hematoma,²⁴⁷ abscess,²⁴⁷ sterile abscess,²⁴⁷ and necrosis²⁴⁷ also reported.²⁴⁷ Injection site reactions occur predominantly in females.²⁴⁷

Some reactions may be very severe, result in substantial scarring, or require surgery, including debridement of necrotic tissue.²⁴⁷ Inadvertent sub-Q injection may increase likelihood of a severe injection reaction.²⁴⁷

Patients should monitor the injection site and contact clinician if injection site reactions worsen or persist.^{257 258} (See Advice to Patients.) Promptly evaluate patients with signs of abscess, cellulitis, necrosis, or extensive swelling to determine if referral to a surgeon is warranted.²⁴⁷

Verification of Opiate Abstinence Prior to Initiation of Therapy

Naltrexone may precipitate mild to severe withdrawal in patients physically dependent on opiates.^{1 2 7 11 15 31 35 38 42 82 247}

To minimize the risk of precipitating signs and symptoms of withdrawal, instruct opiate-dependent individuals who are candidates for naltrexone therapy to remain free of opiates for a minimum of 7–10 days prior to initiating therapy with the drug.^{1 102 247}

Absence of opiates in urine is frequently insufficient evidence that a patient is free of opiates.^{1 102 247} If it is uncertain whether the patient is opiate free, perform a naloxone challenge test prior to administering naltrexone.^{1 102 247} (See Naloxone Challenge Test under Dosage and Administration.)

Risks Associated with Self-administration of Opiates During Naltrexone Therapy

Self-administration of large doses of opiates in an attempt to overcome the antagonist activity of naltrexone may produce signs and symptoms of acute opiate overdosage (e.g., respiratory arrest, circulatory collapse, death).^{1 247}

Signs and symptoms of opiate overdosage also may occur following administration of smaller doses of opiate agonists relatively long after the last naltrexone dose or in an amount that results in a longer duration of agonist activity than the antagonist activity of naltrexone and its metabolites.^{1 247}

Advise patients of the serious consequences of self-administration of opiates during naltrexone therapy.^{1 102 247} (See Advice to Patients.)

Eosinophilic Pneumonia

Eosinophilic pneumonia reported rarely in patients receiving parenteral naltrexone.²⁴⁷ Consider eosinophilic pneumonia in patients with pneumonia who have not responded to anti-infective therapy.²⁴⁷

General Precautions

Therapeutic Use of Opiates in Naltrexone-treated Patients

In an emergency situation when adequate analgesia can be achieved only by administration of an opiate agonist in naltrexone-treated patients, cautious administration of an opiate may afford adequate analgesia, but higher than usual dosages may be required.^{1 102} Whenever possible, use nonopiate analgesics, regional analgesia, conscious sedation with a benzodiazepine, or general anesthesia.^{1 102 247}

If an opiate is required as a component of anesthesia or analgesia, the patient should be continuously monitored in an anesthesia care setting by individuals who are trained in the use of anesthetic agents and in the management of respiratory depressant effects of potent opiates and who are not involved in the conduct of the surgical or diagnostic procedure.²⁴⁷

Respiratory depression produced by the opiate may be deeper and more prolonged.^{1 102} Patients may experience apparent nonopiate receptor-induced effects such as facial swelling, pruritus, generalized erythema, or bronchoconstriction that are probably caused by opiate-induced histamine release and/or other mechanisms.¹

Use of a short-acting opiate with minimal respiratory depression is preferable; adjust dosage of the opiate agonist carefully according to individual requirements and response.^{1 102} Closely monitor the patient in a setting equipped and staffed by health-care personnel appropriately trained in CPR.^{1 247}

Discontinue oral naltrexone ≥48 hours prior to elective surgical procedures requiring opiate analgesia.¹²¹

Avoid use of other opiate-agonist-containing preparations (e.g., those used for the management of cough or diarrhea) when alternative nonopiate therapy is available, since adequate therapeutic benefit may be difficult to achieve with an opiate.^{1 102}

Accidental Precipitation of Withdrawal

Accidental ingestion of naltrexone has precipitated severe withdrawal in some patients physically dependent on opiates; signs and symptoms of withdrawal usually appeared within 5 minutes of naltrexone ingestion and continued for up to 48 hours.^{1 31 102 124}

Suicide

Increased risk of suicide in substance abusers with or without depression;^{1 247} risk is not abated by naltrexone therapy.¹

Individuals with Bleeding Disorders

Use IM preparation with caution in individuals with thrombocytopenia or a coagulation disorder (e.g., hemophilia).²⁴⁷

Specific Populations

Pregnancy

Category C.^{1 102 247}

Not known whether naltrexone affects the duration of labor and delivery.^{1 102 247}

Lactation

Naltrexone and the active metabolite (6-β-naltrexol) are distributed into human milk.^{247 254} Discontinue nursing or the drug.²⁴⁷

Pediatric Use

Safety and efficacy not established in children <18 years of age.^{1 102 121 247 248}

Hepatic Impairment

Contraindicated in patients with acute hepatitis or hepatic failure.^{1 102 247} (See Boxed Warning and see Hepatic Effects under Cautions.)

Use with caution in patients with hepatic impairment.¹ When administered orally, possible increased systemic exposure to the drug.¹

Renal Impairment

Use with caution in patients with moderate to severe renal impairment.^{1 247}

Common Adverse Effects

Treatment of opiate dependence: insomnia,¹ anxiety,¹ nervousness,¹ abdominal pain and cramps,¹ nausea,¹ vomiting,¹ fatigue,¹ joint and muscle pain,¹ headache.¹

Treatment of alcohol dependence: nausea,^{1 247} headache,^{1 247} dizziness,^{1 247} nervousness,¹ fatigue,¹ insomnia,^{1 247} vomiting,^{1 247} anxiety,^{1 247} somnolence,^{1 247} injection site reaction.^{247 257}

Interactions for Naltrexone

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Clonidine	Concomitant administration may reduce the duration of opiate withdrawal by decreasing opiate-induced postsynaptic supersensitivity38 168 230
Disulfiram	Both drugs are potentially hepatotoxic1	Manufacturers recommend concomitant use only if the potential benefits justify the possible risks1
Opiate agonists	Patients receiving naltrexone may not benefit therapeutically from opiate-containing preparations, including those used for the management of cough and cold, diarrhea, and pain1 102 247 Naltrexone can precipitate potentially severe opiate withdrawal1 102 247	Avoid use of opiate-containing preparations during naltrexone therapy when alternative nonopiate therapy is available1 Avoid use of naltrexone in patients receiving opiates or in nondetoxified patients physically dependent on opiates1 102 247
Phenothiazines (thioridazine)	Possible increased lethargy and somnolence1 220 221 222 237
Tests, urinary opiates	Possible interference with some enzymatic assays for opiates1 247 No interference reported with thin-layer (TLC), gas-liquid (GLC), or high-performance liquid (HPLC) chromatography assays for methadone or morphine1
Tests, urinary quinine	No interference reported with TLC, GLC, or HPLC methods1

Naltrexone Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely (about 96%) absorbed following oral administration,^{1 2 3 22 67 71 72 100 102 105} but undergoes extensive first-pass metabolism in the liver;^{1 2 3 33 62 71 102} only 5–40% reaches systemic circulation unchanged.^{1 2 67 71 72 74 102}

Peak plasma concentrations of naltrexone and the active metabolite (6-β-naltrexol) usually occur within 1 hour following oral administration.^{1 71 72}

Following IM administration of the extended-release injection, naltrexone is released slowly and gradually from the microspheres by diffusion and erosion as the polylactide co-glycolide polymer degrades.^{247 249 251 252} Peak plasma concentrations of naltrexone and the active metabolite (6-β-naltrexol) occur in about 2–3 days; ^{247 251 252} steady-state plasma concentrations of naltrexone and 6-β-naltrexol are attained by the end of the dosing interval after the first injection.^{247 251}

Following administration of a single IM dose of naltrexone 380 mg, total naltrexone exposure is three- to fourfold higher and 6-β-naltrexol exposure is 3.4-fold lower than exposure following oral administration of naltrexone 50 mg daily for 28 days.^{247 251}

Onset

Onset of opiate antagonism occurred 15–30 minutes following oral administration in a limited number of patients who had been receiving morphine chronically.²⁵

Decreases opiate craving within 3–5 weeks after start of oral naltrexone in individuals formerly dependent on opiates;^{42 66 158 160} reduction in opiate craving has occurred during the first week of therapy in some individuals, with further decreases occurring in subsequent weeks.^{102 182}

Duration

Duration of opiate antagonist activity appears to be dose dependent^{1 7 12 102} and is longer than that of equipotent doses of naloxone.^{5 7 22 25 33 72}

Special Populations

Changes in oral bioavailability appear to be related to severity of liver disease.¹ AUC increased 5- or 10-fold in patients with compensated or decompensated cirrhosis, respectively.¹

Following IM administration, plasma concentrations of naltrexone and 6-β-naltrexol in individuals with mild to moderate hepatic impairment (Child-Pugh class A and B) are similar to those in healthy individuals with normal hepatic function.^{247 252}

Distribution

Extent

Widely distributed throughout the body;^{69 75} considerable interindividual variation in distribution parameters during the first 24 hours following a single oral dose.^{62 71 72}

Not known whether naltrexone and/or its metabolites cross the placenta.²¹⁷ Naltrexone and 6-β-naltrexol are distributed into human milk.^{247 254}

Plasma Protein Binding

Approximately 21–28%.^{1 2 76 77 102 247}

Elimination

Metabolism

Metabolized in the liver principally by reduction of the 6-keto group of naltrexone to an active metabolite, 6-β-naltrexol (6-β-hydroxynaltrexone); ^{1 2 33 62 67 72 84 100 101 102}

Chlorex-A 12 Suspension

Pronunciation: KLOR-fen-IR-a-meen /FEN-il-EF-rin/pir-IL-a-meen
Generic Name: Chlorpheniramine/Phenylephrine/Pyrilamine
Brand Name: Examples include Nalex-A 12 and Phena-S 12

Chlorex-A 12 Suspension is used for:

Relieving symptoms of sinus congestion, pressure, runny nose, and sneezing due to colds, upper respiratory tract infections, and allergies. It may also be used for other conditions as determined by your doctor.

Chlorex-A 12 Suspension is an antihistamine and decongestant combination. The antihistamine works by blocking the action of histamine, which helps reduce symptoms such as watery eyes and sneezing. The decongestant promotes sinus and nasal drainage, which relieves congestion and pressure.

Do NOT use Chlorex-A 12 Suspension if:

• you are allergic to any ingredient in Chlorex-A 12 Suspension


• you have severe high blood pressure, severe heart blood vessel disease, rapid heartbeat, or severe heart problems


• you are unable to urinate or are having an asthma attack


• you take droxidopa, sodium oxybate (GHB) or if you have taken furazolidone or a monoamine oxidase inhibitor (MAOI) (eg, phenelzine) within the last 14 days

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

Before using Chlorex-A 12 Suspension:

Some medical conditions may interact with Chlorex-A 12 Suspension. 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 a history of adrenal gland problems (eg, adrenal gland tumor); heart problems (eg, cor pulmonale; fast, slow, or irregular heartbeat; heart disease); high blood pressure; diabetes; blood vessel problems; stroke; glaucoma or increased pressure in the eye; seizures; or thyroid problems


• if you have a history of asthma or other breathing problems, chronic cough, lung problems (eg, chronic bronchitis, emphysema), chronic obstructive pulmonary disease (COPD), or sleep apnea


• if you have a blockage of your bladder, stomach, or bowels; ulcers; trouble sleeping; trouble urinating; an enlarged prostate or other prostate problems

Some MEDICINES MAY INTERACT with Chlorex-A 12 Suspension. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Digoxin or droxidopa because the risk of irregular heartbeat or heart attack may be increased


• Beta-blockers (eg, propranolol), catechol-O-methyltransferase (COMT) inhibitors (eg, tolcapone), furazolidone, indomethacin, linezolid, MAOIs (eg, phenelzine), sodium oxybate (GHB), or tricyclic antidepressants (eg, amitriptyline) because they may increase the risk of Chlorex-A 12 Suspension's side effects


• Bromocriptine or hydantoins (eg, phenytoin) because the risk of their side effects may be increased by Chlorex-A 12 Suspension


• Guanadrel, guanethidine, mecamylamine, methyldopa, or reserpine because their effectiveness may be decreased by Chlorex-A 12 Suspension

This may not be a complete list of all interactions that may occur. Ask your health care provider if Chlorex-A 12 Suspension 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 Chlorex-A 12 Suspension:

Use Chlorex-A 12 Suspension as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Chlorex-A 12 Suspension may be taken with or without food.


• Shake well before using.


• Use a measuring device marked for medicine dosing. Ask your pharmacist for help if you are unsure of how to measure your dose.


• If you miss a dose of Chlorex-A 12 Suspension and you are taking it regularly, 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 Chlorex-A 12 Suspension.

Important safety information:

• Chlorex-A 12 Suspension may cause dizziness, drowsiness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Chlorex-A 12 Suspension with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Do not drink alcohol or use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using Chlorex-A 12 Suspension; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.


• Do not take diet or appetite control medicines while you are taking Chlorex-A 12 Suspension without checking with your doctor.


• Some of these products contain phenylalanine. If you must have a diet that is low in phenylalanine, ask your pharmacist if it is in your product.


• Before you start any new medicine, check the label to see if it has a decongestant or antihistamine in it too. If it does or if you are not sure, check with your doctor or pharmacist.


• Do NOT take more than the recommended dose or use for longer than prescribed without checking with your doctor.


• If your symptoms do not get better within 5 to 7 days or if they get worse, check with your doctor.


• Chlorex-A 12 Suspension may cause you to become sunburned more easily. Avoid the sun, sunlamps, or tanning booths until you know how you react to Chlorex-A 12 Suspension. Use a sunscreen or wear protective clothing if you must be outside for more than a short time.


• Chlorex-A 12 Suspension may interfere with skin allergy tests. If you are scheduled for a skin test, talk to your doctor. You may need to stop taking Chlorex-A 12 Suspension for a few days before the tests.


• Tell your doctor or dentist that you take Chlorex-A 12 Suspension before you receive any medical or dental care, emergency care, or surgery.


• Use Chlorex-A 12 Suspension with caution in the ELDERLY; they may be more sensitive to its effects, especially confusion, dizziness, drowsiness, dry mouth, excitability, low blood pressure, and trouble urinating.


• Caution is advised when using Chlorex-A 12 Suspension in CHILDREN; they may be more sensitive to its effects, especially excitability.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Chlorex-A 12 Suspension while you are pregnant. Chlorex-A 12 Suspension may be found in breast milk. Do not breast-feed while taking Chlorex-A 12 Suspension.

Possible side effects of Chlorex-A 12 Suspension:

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:

Constipation; diarrhea; dizziness; drowsiness; dry mouth, nose, or throat; excitability; headache; loss of appetite; nausea; nervousness or anxiety; trouble sleeping; upset stomach; vomiting; weakness.

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); blurred vision or other vision changes; confusion; difficulty urinating or inability to urinate; fast or irregular heartbeat; fever, chills, or persistent sore throat; hallucinations; mood or mental changes; persistent trouble sleeping; restlessness; seizures; severe dizziness, drowsiness, lightheadedness, or headache; tremor.

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: Chlorex-A2 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 blurred vision; confusion; hallucinations; ringing in the ears; seizures; severe dizziness, lightheadedness, or headache; severe drowsiness; unusually fast, slow, or irregular breathing; unusually fast, slow, or irregular heartbeat; vomiting.

Proper storage of Chlorex-A 12 Suspension:

Store Chlorex-A 12 Suspension 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 Chlorex-A 12 Suspension out of the reach of children and away from pets.

General information:

• If you have any questions about Chlorex-A 12 Suspension, please talk with your doctor, pharmacist, or other health care provider.


• Chlorex-A 12 Suspension 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 Chlorex-A 12 Suspension. 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.

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• Chlorex-A 12 Drug Interactions
• Chlorex-A 12 Support Group
• 0 Reviews for Chlorex-A2 - Add your own review/rating

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Avar LS Cleanser

Pronunciation: SUL-fa-SEET-a-mide SOE-dee-um/SUL-fur
Generic Name: Sulfacetamide Sodium/Sulfur
Brand Name: Avar LS Cleanser

Avar LS Cleanser is used for:

Treating acne, rosacea, and oily, flaky skin (seborrhea). It may also be used for other conditions as determined by your doctor.

Avar LS Cleanser is a sulfonamide antibiotic and keratolytic combination. The sulfonamide works by killing bacteria and the keratolytic works by shedding the top layer of skin.

Do NOT use Avar LS Cleanser if:

• you are allergic to any ingredient in Avar LS Cleanser


• you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to any other sulfonamide medicine, such as acetazolamide, celecoxib, certain diuretics (eg, hydrochlorothiazide), glyburide, probenecid, sulfamethoxazole, valdecoxib, or zonisamide


• you have kidney disease

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

Before using Avar LS Cleanser:

Some medical conditions may interact with Avar LS Cleanser. 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 eczema or a history of lupus

Some MEDICINES MAY INTERACT with Avar LS Cleanser. Because little, if any, of Avar LS Cleanser is absorbed into the blood, the risk of it interacting with another medicine is low.

Ask your health care provider if Avar LS Cleanser 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 Avar LS Cleanser:

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

• Avar LS Cleanser is for use on the skin only. Avar LS Cleanser may stain clothing and the skin if too much is used.


• Wash your hands before and immediately after using Avar LS Cleanser.


• Wet the skin and apply a generous amount of medicine to the affected area. Massage gently into the skin for 10 to 20 seconds, working into a full lather. Rinse well and pat dry.


• If the affected area becomes excessively dry, check with your doctor. You may need to rinse the medicine off the skin sooner or use it less often.


• Avar LS Cleanser works best if it is used at the same time(s) each day.


• Continue to use Avar LS Cleanser even if your condition improves. Do not miss any doses.


• If you miss a dose of Avar LS Cleanser, use 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 use 2 doses at once.

Ask your health care provider any questions you may have about how to use Avar LS Cleanser.

Important safety information:

• Avar LS Cleanser is for external use only. Do not get it in your eyes, nose, or mouth. If you get it in any of these areas, rinse right away with cool tap water.


• Talk with your doctor before you use any other medicines or cleansers on your skin.


• Do not apply Avar LS Cleanser to open wounds or to damaged or burned skin without first checking with your doctor.


• If you use topical products too often, your condition may become worse.


• Avar LS Cleanser should be used with extreme caution in CHILDREN younger than 12 years old; safety and effectiveness in these children have not been confirmed.


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

Possible side effects of Avar LS Cleanser:

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:

Mild dryness, redness, scaling, stinging, or burning of the skin.

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); butterfly-shaped rash on the face; cracked or extremely dry skin; fever, chills, or sore throat; joint pain; red, swollen, blistered, or peeling skin; seizures; severe skin redness or scaling; skin inflammation or irritation; unusual tiredness or weakness; yellowing of the skin or eyes.

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: Avar LS 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. Avar LS Cleanser may be harmful if swallowed. Symptoms of ingestion may include change in the amount of urine; nausea; vomiting.

Proper storage of Avar LS Cleanser:

Store Avar LS Cleanser at room temperature, between 59 and 77 degrees F (15 and 25 degrees C). Keep the container tightly closed. Store away from heat and light. Do not freeze. Keep Avar LS Cleanser out of the reach of children and away from pets.

General information:

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


• Avar LS Cleanser 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 Avar LS Cleanser. 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 Avar LS resources

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

• Avar LS Cleanser Concise Consumer Information (Cerner Multum)


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