Read PLR Articles Directory Pakistan: September 2016

Thursday, September 29, 2016

Viadur

Generic Name: leuprolide (Intradermal route, Intramuscular route, Subcutaneous route)

LOO-proe-lide AS-e-tate

Commonly used brand name(s)

In the U.S.

Eligard

Lupron

Lupron Depot

Lupron Depot-Ped

Viadur

Available Dosage Forms:

Powder for Solution

Powder for Suspension, 3 Month

Solution

Powder for Suspension, 1 Month

Powder for Suspension, 6 Month

Powder for Suspension, 4 Month

Powder for Suspension

Therapeutic Class: Antineoplastic Agent

Pharmacologic Class: Leuprolide

Uses For Viadur

Leuprolide is a man-made version of a hormone that is similar to the one normally released from the hypothalamus gland in the brain. It is used to treat a number of medical problems. These include:

Anemia caused by bleeding of uterine leiomyomas (tumors in the uterus).

Cancer of the prostate, advanced.

Central precocious puberty (CPP), a condition that causes early puberty in boys (before 9 years of age) and in girls (before 8 years of age).

Pain due to endometriosis.

When given regularly to men and boys, leuprolide decreases testosterone levels. Reducing the amount of testosterone in the body is one way of treating cancer of the prostate.

When given regularly to women, leuprolide decreases estrogen levels. Reducing the amount of estrogen in the body is one way of treating endometriosis. By shrinking tumors in the uterus, leuprolide helps stop anemia by decreasing the vaginal bleeding from these tumors. Iron supplements should be used to help treat the anemia.

When given to boys and girls experiencing early puberty, leuprolide slows down the development of the genital areas in both sexes and breast development in girls. This medicine delays puberty in a child only as long as the child continues to receive it.

Suppressing estrogen can cause thinning of the bones or slowing of growth. This is a problem for adult women whose bones are no longer growing like the bones of children. Slowing the growth of bones is a positive effect in girls and boys whose bones grow too fast when puberty begins too early. Boys and girls may benefit by adding inches to their adult height when leuprolide helps their bones grow at the proper and expected rate for children.

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

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although this use is not included in product labeling, leuprolide is used in certain patients with the following medical condition:

Cancer of the breast.

Before Using Viadur

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 performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of leuprolide pediatric injection in children. However, use is not recommended in children younger than 2 years of age. Leuprolide pediatric injection will stop having an effect on a child treated for central precocious puberty soon after the child stops using it, and puberty will advance normally. It is not known if using leuprolide around the time of puberty causes changes in boys' and girls' future abilities to have babies. Their chances of having children later are thought to be normal. It is especially important that you discuss with the child's doctor the benefit of this medicine as well as the risk of using it.

Appropriate studies have not been performed on the relationship of age to the effects of Eligard®, Lupron® injection, Lupron Depot®, Lupron Depot®-3 month, Lupron Depot®-4 month, Lupron Depot®-6 month, or Viadur® in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of Eligard®, Lupron® injection, Lupron Depot®, Lupron Depot®-3 month, Lupron Depot®-4 month, or Lupron Depot®-6 month in the elderly.

No information is available on the relationship of age to the effects of leuprolide pediatric injection and Viadur® in geriatric patients.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	X	Studies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. This drug should not be used in women who are or may become pregnant because the risk clearly outweighs any possible benefit.

Breast Feeding

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

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

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.

Proper Use of leuprolide

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

For leuprolide injections (Eligard®, Lupron® injection, Lupron Depot®, Lupron Depot®-Ped 1-month or 3-month, Lupron Depot®-3 month, Lupron Depot®-4 month, or Lupron Depot®-6 month):

A nurse or other trained health professional may give you this medicine. This medicine is given as a shot under your skin or into a muscle.

You may be taught how to give this medicine at home. Make sure you understand all of the instructions before giving yourself an injection. Do not use more medicine or use it more often than your doctor tells you to.

You will be shown the body areas where this shot can be given. Use a different body area each time you give yourself a shot. Keep track of where you give each shot to make sure you rotate body areas.

Use a new needle and syringe each time you inject your medicine.

Before each injection, look carefully at the medicine to check for any particles or a change in color. You should not use medicine that has changed color or has particles in it.

If you have any questions about any of this, check with your doctor.

Each package of leuprolide injection contains patient directions. Read the instructions carefully and make sure you understand:

How to prepare the injection.

Proper use of disposable syringes.

How to give the injection.

How long the injection is stable.

The long-acting form of this medicine (depot) may be given once every month or once every 3 to 12 months. Your schedule depends on the reason you are using this medicine. To stay on the right schedule with the medicine, make sure you keep all appointments.

If you are to receive the leuprolide implant (Viadur®):

Viadur® is an implant that is surgically placed under the skin of the upper arm. Your doctor will treat the arm with numbing medicine and then cut a small incision to insert the implant with a special tool. The incision will be closed with surgical strips. An adhesive bandage will be placed over the arm and should be left on for 24 hours.

After the implant is put in place, you should keep the arm clean and dry, and should not swim or bathe for 24 hours. You should avoid any heavy lifting or strenuous exercise for 48 hours after the implant is put into the arm.

The surgical strips can be removed after at least 3 days or as soon as the incision is healed.

The implant will be left in place for one year and then removed. If needed, your doctor will then insert a new implant to continue treatment for another year.

Viadur® comes with patient instructions. Read these instructions carefully.

Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

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 cancer of the prostate:
- The dose varies depending on the specific product used.

For central precocious puberty:
- Children 2 years of age and older—Dose is based on body weight and must be determined by your doctor. The starting dose for the once daily product is 50 microgram (mcg) per kilogram (kg) of body weight injected under the skin once a day. The starting dose for the once monthly product is 0.3 milligrams (mg) per kg of body weight or 7.5 mg, 11.25 mg, or 15 mg injected into a muscle every 4 weeks. The 3-month product dose is 11.25 mg or 30 mg injected into a muscle as a single injection every 12 weeks. Your doctor may increase your dose as needed.
- Children younger than 2 years of age—Use is not recommended.

For anemia caused by tumors of the uterus or endometriosis:
- Adults—The dose given depends on the specific product used. Some examples are 3.75 milligrams (mg) injected into a muscle once a month for up to 3 months or 11.25 mg injected into a muscle as a single injection to last for 3 months. .

Missed Dose

This medicine needs to be given on a fixed schedule. If you miss a dose or forget to use your medicine, call your doctor or pharmacist for instructions.

Storage

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

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

The mixed suspension should be discarded if not used right away. Eligard® must be used within 30 minutes after mixing, and Lupron Depot® must be used within 2 hours after mixing.

Throw away used needles in a hard, closed container that the needles cannot poke through. Keep this container away from children and pets.

Precautions While Using Viadur

It is very important that your doctor check the progress of you or your child at regular visits to make sure that this medicine is working properly. Blood and urine tests may be needed to check for unwanted effects.

For female patients: You should not receive this medicine if you are pregnant or may become pregnant. Using this medicine while you are pregnant can harm your unborn baby. If you think you have become pregnant while using the medicine, tell your doctor right away.

For patients receiving leuprolide for central precocious puberty (CPP):

If you are a female patient, you may have occasional bleeding or spotting. If you continue to have heavy bleeding or regular periods after 2 months of using this medicine, call your doctor.

If you develop a rash or irritation at the injection site, check with your doctor right away.

For patients receiving leuprolide for endometriosis or for anemia caused by tumors of the uterus:

For the first few days of treatment, the symptoms of your condition may get worse. This is normal. Do not stop taking this medicine. Talk with your doctor if you have concerns about this.

During the time you are receiving leuprolide, your menstrual period may not be regular or you may not have a menstrual period at all. This is to be expected when being treated with this medicine. If regular menstruation does not begin within 60 to 90 days after you stop receiving this medicine, check with your doctor.

During the time you are receiving leuprolide, you should use birth control methods that do not contain hormones. If you have any questions about this, check with your doctor.

If you suspect you may have become pregnant, stop using this medicine and check with your doctor. There is a chance that continued use of leuprolide during pregnancy could cause birth defects or a miscarriage.

When you first start using this medicine for prostate cancer treatment, some of your symptoms might get worse for a short time. You might also have new symptoms. You might have bone pain, back pain, a tingling or numbness in the body, blood in the urine, or trouble urinating. These symptoms should improve within a few weeks. Tell your doctor if you have any new symptoms or your symptoms get worse.

Patients receiving leuprolide for advanced prostate cancer:

This medicine may affect blood sugar levels. If you notice a change in the results of your blood or urine sugar tests or if you have any questions, check with your doctor.

This medicine may increase your risk of having a heart attack or stroke. Check with your doctor right away if you are having chest pain or discomfort; pain or discomfort in the arms, jaw, back, or neck; confusion; shortness of breath; nausea or vomiting, or sweating.

This medicine can cause changes in heart rhythms, such as a condition called QT prolongation. It may change the way your heart beats and cause fainting or serious side effects in some patients. Contact your doctor right away if you have any symptoms of heart rhythm problems, such as fast, pounding, or irregular heartbeats.

This medicine can cause decreases in bone mineral density, which may lead to osteoporosis or weakened bones. Talk with your doctor about how this risk will affect you.

This medicine may cause a serious type of allergic reaction called anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash; itching; hoarseness; trouble breathing; trouble swallowing; or any swelling of your hands, face, or mouth while you are using this medicine.

Do not stop using or changing the dose of Lupron® injection without checking first with your doctor.

Before you have any medical tests, tell the medical doctor in charge that you are using this medicine. The results of some tests may be affected by this medicine.

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.

Viadur 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:

For adultsLess common

Fast or irregular heartbeat

Rare

Bone, muscle, or joint pain

fainting

fast or irregular breathing

numbness or tingling of the hands or feet

puffiness or swelling of the eyelids or around the eyes

shortness of breath

skin rash, hives, or itching

sudden, severe decrease in blood pressure and collapse

tightness in the chest or wheezing

troubled breathing

For males only (adults)More common

Arm, back, or jaw pain

bloody or cloudy urine

blurred vision

burning while urinating

chest pain or discomfort

chest tightness or heaviness

difficult or labored breathing

difficult, burning, or painful urination

difficulty with moving

dizziness

frequent urge to urinate

headache

increased urge to urinate during the night

muscle pain or stiffness

nausea

nervousness

pain in the joints

pale skin

pounding in the ears

slow or fast heartbeat

sweating

troubled breathing with exertion

unusual bleeding or bruising

unusual tiredness or weakness

waking to urinate at night

Rare

Pain in the groin or legs (especially in the calves of the legs)

Incidence not known

Altered mental status

cardiovascular collapse

double vision

visual changes

vomiting

For females only (adults)Rare

Anxiety

deepening of voice

increased hair growth

mental depression

mood changes

For childrenRare

Body pain

burning, itching, redness, or swelling at the injection site

skin rash

For females only (children)—expected in first few weeksRare

Vaginal bleeding (continuing)

white vaginal discharge (continuing)

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:

For adultsMore common

Sudden sweating and feelings of warmth (also called hot flashes)

Less common

Bleeding, bruising, burning, itching, pain, redness, or swelling at the injection site

decreased interest in sexual intercourse

swelling of the feet or lower legs

swelling or increased tenderness of the breasts

trouble with sleeping

weight gain

For females only (adults)More common

Light, irregular vaginal bleeding

stopping of menstrual periods

Less common

Burning, dryness, or itching of the vagina

pelvic pain

For males only (adults)More common

Back pain

chills

constipation

cough

diarrhea

fever

general feeling of discomfort or illness

loss of appetite

pain or discomfort at the injection site

redness of the face, neck, arms, and occasionally, upper chest

runny nose

shivering

sleeplessness

sore throat

sudden sweating

trouble sleeping

unable to sleep

unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness

Less common

Bone pain

decreased size of the testicles

inability to have or keep an erection

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: Viadur 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 Viadur resources

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

Viadur Prescribing Information (FDA)

Viadur Implant MedFacts Consumer Leaflet (Wolters Kluwer)

Leuprolide MedFacts Consumer Leaflet (Wolters Kluwer)

Leuprolide Prescribing Information (FDA)

Eligard Consumer Overview

Eligard Prescribing Information (FDA)

Eligard Kit MedFacts Consumer Leaflet (Wolters Kluwer)

Leuprolide Acetate Monograph (AHFS DI)

Lupron Consumer Overview

Lupron Depot Prescribing Information (FDA)

Lupron Depot MedFacts Consumer Leaflet (Wolters Kluwer)

Lupron Depot-PED Prescribing Information (FDA)

Lupron Depot-PED Kit MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Viadur with other medications

Endometriosis
Hirsutism
Precocious Puberty
Prostate Cancer
Uterine Fibroids

Wednesday, September 28, 2016

Encore

In some countries, this medicine may only be approved for veterinary use.

Ingredient matches for Encore

Estradiol

Estradiol is reported as an ingredient of Encore in the following countries:

United States

Oxytetracycline

Oxytetracycline is reported as an ingredient of Encore in the following countries:

United States

International Drug Name Search

Tuesday, September 27, 2016

spironolactone

spir-on-oh-LAK-tone

Oral route(Tablet)

Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats. Spironolactone should be used only in those conditions specified as indications for use. Unnecessary use of this drug should be avoided .

Commonly used brand name(s)

In the U.S.

Aldactone

Available Dosage Forms:

Tablet

Therapeutic Class: Cardiovascular Agent

Pharmacologic Class: Aldosterone Receptor Antagonist

Uses For spironolactone

Spironolactone is used in combination with other medicines to treat high blood pressure (hypertension) and heart failure. It may also be used to treat water retention (edema) in patients with congestive heart failure, liver cirrhosis, or a kidney disorder called nephrotic syndrome.

Spironolactone is also used to diagnose and treat hyperaldosteronism, a condition in which the adrenal gland produces too much hormone called aldosterone.

Spironolactone is a type of a diuretic medicine (water pill) that prevents your body from absorbing too much salt and keeps your potassium levels from getting too low. It can be used to prevent or treat hypokalemia (low potassium levels in the blood).

spironolactone is available only with your doctor’s prescription.

Before Using spironolactone

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 spironolactone, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to spironolactone 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 spironolactone in the pediatric population. Safety and efficacy have not been established.

Geriatric

No information is available on the relationship of age to the effects of spironolactone in geriatric patients.

Pregnancy

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

Breast Feeding

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

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking spironolactone, 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 spironolactone with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

Eplerenone

Triamterene

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

Alacepril

Arginine

Arsenic Trioxide

Benazepril

Captopril

Cilazapril

Delapril

Digoxin

Droperidol

Enalaprilat

Enalapril Maleate

Fosinopril

Imidapril

Levomethadyl

Lisinopril

Lithium

Moexipril

Pentopril

Perindopril

Potassium

Quinapril

Ramipril

Sotalol

Spirapril

Tacrolimus

Temocapril

Trandolapril

Zofenopril

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

Aceclofenac

Acemetacin

Alclofenac

Apazone

Benoxaprofen

Bromfenac

Bufexamac

Carprofen

Clometacin

Clonixin

Dexketoprofen

Diclofenac

Diflunisal

Digitoxin

Dipyrone

Droxicam

Etodolac

Etofenamate

Felbinac

Fenbufen

Fenoprofen

Fentiazac

Floctafenine

Flufenamic Acid

Flurbiprofen

Gossypol

Ibuprofen

Indomethacin

Indoprofen

Isoxicam

Ketoprofen

Ketorolac

Licorice

Lornoxicam

Meclofenamate

Mefenamic Acid

Meloxicam

Nabumetone

Naproxen

Niflumic Acid

Nimesulide

Oxaprozin

Oxyphenbutazone

Phenylbutazone

Pirazolac

Piroxicam

Pirprofen

Propyphenazone

Proquazone

Sulindac

Suprofen

Tenidap

Tenoxicam

Tiaprofenic Acid

Tolmetin

Zomepirac

Interactions with Food/Tobacco/Alcohol

Proper Use of spironolactone

In addition to the use of spironolactone, treatment for your high blood pressure may include weight control and changes in the types of foods you eat, especially foods high in sodium (salt) and potassium. Your doctor will tell you which of these are most important for you. You should check with your doctor before changing your diet.

Many patients who have high blood pressure will not notice any signs of the problem. In fact, many may feel normal. It is very important that you take your medicine exactly as directed and that you keep your appointments with your doctor even if you feel well.

Remember that spironolactone will not cure your high blood pressure, but it does help control it. You must continue to take it as directed if you expect to lower your blood pressure and keep it down. You may have to take high blood pressure medicine for the rest of your life. If high blood pressure is not treated, it can cause serious problems such as heart failure, blood vessel disease, stroke, or kidney disease.

Dosing

The dose of spironolactone 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 spironolactone. If your dose is different, do not change it unless your doctor tells you to do so.

For oral dosage form (tablets):
- For edema:
  - Adults—At first, 100 milligrams (mg) per day, given in either single or divided doses. Your doctor may adjust your dose if needed.
  - Children—Use and dose must be determined by your doctor.
- For heart failure:
  - Adults—At first, 25 milligrams (mg) per day. Your doctor may adjust your dose if needed and tolerated.
  - Children—Use and dose must be determined by your doctor.
- For high blood pressure:
  - Adults—At first, 50 to 100 milligrams (mg) per day, given in either single or divided doses. Your doctor may adjust your dose if needed.
  - Children—Use and dose must be determined by your doctor.
- For low potassium in the blood:
  - Adults—25 to 100 milligrams (mg) per day.
  - Children—Use and dose must be determined by your doctor.
- For too much aldosterone in the body:
  - Adults—400 milligrams (mg) for 4 days, or 400 mg per day for 3 to 4 weeks to diagnose the condition. Then, 100 to 400 mg per day after the diagnosis is confirmed.
  - Children—Use and dose must be determined by your doctor.

Missed Dose

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

Storage

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

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

Precautions While Using spironolactone

It is very important that your doctor check your progress at regular visits to make sure spironolactone is working properly and to decide if you should continue to take it. Blood tests may be needed to check for unwanted effects.

Do not take other medicines unless they have been discussed with your doctor. This especially includes potassium supplements or salt substitutes containing potassium; or certain diuretics such as amiloride (Midamor®, Moduretic®), triamterene (Dyazide®, Dyrenium®, Maxzide®), or other products containing spironolactone (Aldactazide®).

spironolactone may increase the amount of potassium in your blood (hyperkalemia). Stop using spironolactone and check with your doctor right away if you are having abdominal or stomach pain; confusion; difficulty with breathing; irregular heartbeat; nausea or vomiting; nervousness; numbness or tingling in the hands, feet, or lips; shortness of breath; or weakness or heaviness of the legs.

Check with your doctor right away if you become sick while taking spironolactone, especially with severe or continuing nausea, vomiting, or diarrhea. These conditions may cause you to lose too much water or salt.

Check with your doctor right away if you experience dizziness, fainting, confusion, muscle pain, weakness, and/or a fast heartbeat. Use extra care if you exercise or if the weather is hot. Heavy sweating can cause dehydration (loss of too much water) or electrolyte imbalances (loss of sodium, potassium, or magnesium in the body).

spironolactone may cause swelling of the breasts (gynecomastia) and breast pain in some patients. If you have questions about this, talk to your doctor.

Make sure any doctor or dentist who treats you knows that you are using spironolactone. You may need to stop using spironolactone several days before having medical tests. The results of some tests may be affected by spironolactone.

spironolactone may cause the formation of certain tumors in your body. Check with your doctor right away if you notice an unusual lump anywhere in your body or if you have any unusual signs or symptoms while you are using spironolactone.

spironolactone 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:

Incidence not known

Abdominal or stomach cramping, burning, or tenderness

bloody or black, tarry stools

bloody urine

chills

clay-colored stools

clear or bloody discharge from the nipple

cloudy urine

constipation

cough or hoarseness

dark urine

decrease in urine output or decrease in urine-concentrating ability

decreased appetite

diarrhea

difficulty with swallowing

dimpling of the breast skin

dizziness

fast heartbeat

fever with or without chills

general feeling of tiredness or weakness

headache

heartburn

hives

increased blood pressure

increased thirst

indigestion

inverted nipple

itching

loss of appetite

lower back or side pain

lump in the breast or under the arm

nausea and vomiting

painful or difficult urination

persistent crusting or scaling of the nipple

puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue

redness or swelling of the breast

severe stomach pain

shakiness and unsteady walk

shortness of breath

skin rash

sore on the skin of the breast that does not heal

sore throat

sores, ulcers, or white spots on the lips or in the mouth

swelling of the face, fingers, feet, or lower legs

swollen, painful, or tender lymph glands in the neck, armpit, or groin

tightness in the chest

troubled breathing

unpleasant breath odor

unsteadiness, trembling, or other problems with muscle control or coordination

unusual bleeding or bruising

unusual tiredness or weakness

vomiting of blood or material that looks like coffee grounds

weight gain

wheezing

yellow eyes or skin

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

Symptoms of overdose

Coma

confusion

convulsions

difficulty with breathing

drowsiness

irregular heartbeat

muscle pain or cramps

nervousness

numbness or tingling in the hands, feet, or lips

rash with flat lesions or small raised lesions on the skin

reddened skin

swelling of the ankles or hands

weakness or heaviness of the legs

Incidence not known

Burning feeling in the chest or stomach

sores, welting, or blisters

stomach upset

swelling of the breasts or breast soreness in both females and males

unusual dullness or feeling of sluggishness

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: spironolactone side effects (in more detail)

More spironolactone resources

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

Spironolactone Prescribing Information (FDA)

Spironolactone Professional Patient Advice (Wolters Kluwer)

Spironolactone Monograph (AHFS DI)

Spironolactone MedFacts Consumer Leaflet (Wolters Kluwer)

Aldactone Prescribing Information (FDA)

Aldactone Consumer Overview

Compare spironolactone with other medications

Acne
Alopecia
Edema
Heart Failure
High Blood Pressure
Hirsutism
Hypokalemia
Primary Hyperaldosteronism
Primary Hyperaldosteronism Diagnosis

Fluorouracil 25 mg / ml Injection (Hospira UK Ltd)

1. Name Of The Medicinal Product

Fluorouracil 25mg/ml Injection.

2. Qualitative And Quantitative Composition

Each 1 ml contains 25mg of fluorouracil.

Presentations

250mg / 10ml

500mg / 20ml

2.5g / 100ml

Amount fluorouracil present (as sodium salt) per vial

250mg

500mg

2.5g

For excipients see 6.1

3. Pharmaceutical Form

Solution for injection.

Clear, colourless or slightly yellow solution.

4. Clinical Particulars

4.1 Therapeutic Indications

Fluorouracil may be used alone, or in combination, for the management of common malignancies particularly cancer of the colon and breast.

4.2 Posology And Method Of Administration

Adults:

Selection of an appropriate dose and treatment regime depends upon the condition of the patient, the type of carcinoma being treated and whether fluorouracil is to be administered alone or in combination with other therapy. Initial treatment should be given in hospital and the total daily dose should not exceed 0.8 - 1 gram. It is customary to calculate the dose in accordance with the patient's actual bodyweight unless there is obesity, oedema or some form of abnormal fluid retention such as ascites. Ideal weight is used as the basis for calculation in such cases. The initial dose should be reduced by one-third to one half in patients with any of the following:

1. Cachexia.

2. Major surgery within preceding 30 days.

3. Reduced bone marrow function.

4. Impaired hepatic or renal function.

Initial Treatment:

This may be in the form of an infusion or an injection, the former usually being preferred because of lesser toxicity.

Intravenous infusion:

15mg/kg bodyweight but not more than 1g per infusion, diluted in 300 - 500ml of 5% glucose or 0.9% NaCl injection and given over 4 hours. Alternatively the daily dose may be infused over 30 - 60 minutes or may be given as a continuous infusion over 24 hours. The infusion may be repeated daily until there is evidence of toxicity or a total dose of 12 - 15g has been reached.

Intravenous Injection:

12mg/kg bodyweight may be given daily for 3 days and then, if there is no evidence of toxicity, 6mg/kg on alternate days for 3 further doses.

An alternative regimen is 15mg/kg as a single intravenous injection once a week throughout the course.

Intra-arterial infusion:

5/7.5mg/kg bodyweight daily may be given by 24 hour continuous intra-arterial infusion.

Maintenance therapy:

An initial intensive course may be followed by maintenance therapy providing there are no significant toxic effects.

In all instances, toxic side effects must disappear before maintenance therapy is started.

The initial course of fluorouracil can be repeated after an interval of 4 to 6 weeks from the last dose or, alternatively, treatment can be continued with intravenous injections of 5-15mg/kg bodyweight at weekly intervals.

This sequence constitutes a course of therapy. Some patients have received up to 30g at a maximum rate of 1 g daily.

A more recent alternative method is to give 15mg/kg IV once a week throughout the course of treatment. This obviates the need for an initial period of daily administration.

In combination with irradiation

Irradiation combined with fluorouracil has been found to be useful in the treatment of certain types of metastatic lesions in the lungs and for the relief of pain caused by recurrent, inoperable growth. The standard dose of fluorouracil should be used.

Children:

No recommendations are made regarding the use of fluorouracil in children.

Elderly:

Fluorouracil should be used in the elderly with similar considerations as in younger adults. notwithstanding that incidence of concomitant medical illness is higher in the former group.

4.3 Contraindications

Fluorouracil is contraindicated in seriously debilitated patients or those with bone marrow depression after radiotherapy or treatment with other antineoplastic agents.

Fluorouracil is strictly contraindicated in pregnant or breast feeding women.

Fluorouracil should not be used in the management of non-malignant disease.

4.4 Special Warnings And Precautions For Use

It is recommended that fluorouracil be given only by, or under the strict supervision of , a qualified physician who is conversant with the use of potent antimetabolites.

All patients should be admitted to hospital for initial treatment.

Adequate treatment with fluorouracil is usually followed by leucopenia, the lowest white blood cell (W.B.C.) count commonly being observed between the 7th and 14th day of the first course, but occasionally being delayed for as long as 20 days. The count usually returns to normal by the 30th day. Daily monitoring of platelet and W.B.C. Count is recommended and treatment should be stopped if platelets fall 100,000 per mm³ or the W.B.C. count falls below 3,500 per mm³. If the total count is less than 2000 per mm³, and especially if there is granulocytopenia, it is recommended that the patient be placed in protective isolation in the hospital and treated with appropriate measures to prevent systemic infection.

Treatment should also be stopped at the first sign of oral ulceration or if there is evidence of gastrointestinal side effects such as stomatitis, diarrhoea or bleeding from the gastrointestinal tract or haemorrhage at any site. The ratio between effective and toxic dose is small and therapeutic response is unlikely without some degree of toxicity. Care must be taken therefore, in the selection of patients and adjustment of dosage.

Fluorouracil should be used with caution in patients with reduced renal or liver function or jaundice. Isolated cases of angina, ECG abnormalities and rarely, myocardial infarction have been reported following administration of Fluorouracil. Caution should therefore be exercised in treating patients who experience chest pain during courses of treatment, or patients with a history of heart disease.

There have been reports of increased toxicity in patients who have reduced activity/deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD).

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Various agents have been reported to biochemically modulate the antitumour efficacy or toxicity of Fluorouracil, common drugs include Methotrexate, Metronidazole, Leucovorin as well as Allopurinol and Cimetidine which can affect the availability of the active drug.

Marked elevations of prothrombin time and INR have been reported in a few patients stabilised on warfarin therapy following initiation of fluorouracil regimes.

A clinically significant interaction between the antiviral sorivudine and fluorouracil prodrugs, resulting from inhibition of dihydropyrimidine dehydrogenase by sorivudine or chemically related analogues. Caution should be taken when using Fluorouracil in conjunction with medications which may affect dihydropyrimidine dehydrogenase activity.

4.6 Pregnancy And Lactation

Fluorouracil is strictly contraindicated in pregnant or breast feeding women.

4.7 Effects On Ability To Drive And Use Machines

Not applicable

4.8 Undesirable Effects

Diarrhoea, nausea and vomiting are observed quite commonly during therapy and may be treated symptomatically. An anti-emetic may be given for nausea and vomiting.

Alopecia may be seen in a substantial number of cases particularly in females, but is reversible. Other side effects Include dermatitis, pigmentation, changes in the nails , ataxia and fever.

There have been reports of chest pain, tachycardia ,breathlessness and ECG changes after administration of fluorouracil. Special attention is therefore advisable in treating patients with a history of heart disease or those who develop chest pain during treatment.

Systemic fluorouracil treatment has been associated with various types of ocular toxicity. Peripheral neuropathy may occur.

A transient reversible cerebellar syndrome has been reported following fluorouracil treatment. Rarely, a reversible confusional state may occur. Cases of leucoencephalopathy have also been reported.

Additionally several other reports have been noted including:

Incidences of excessive lacrimation, dacryostenosis, visual changes and photophobia.

Palmar-plantar erythrodysesthesia syndrome has been reported as an unusual complication of high dose bolus or protracted continuous therapy for 5-fluorouracil.

4.9 Overdose

The symptoms and signs of overdosage are qualitatively similar to the adverse reactions and should be managed as indicated under "Special Warnings and Precautions and " Undesirable Effects".

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Fluorouracil is an analogue of uracil, a component of ribonucleic acid. The drug is believed to function as an antimetabolite. After intracellular conversion to the active deoxynucleotide, it interferes with the synthesis of DNA by blocking the conversion of deoxyuridylic acid to thymidylic acid by the cellular enzyme thymidylate synthetase. Fluorouracil may also interfere with RNA synthesis.

5.2 Pharmacokinetic Properties

After intravenous administration, fluorouracil is distributed through the body water and disappears from the blood within 3 hours. It is preferentially taken up by actively dividing tissues and tumours after conversion to its nucleotide. Fluorouracil readily enters the C.S.F. and brain tissue.

Following I.V. administration, the plasma elimination half-life averages about 16 minutes and is dose dependent. Following a single I.V. dose of Fluorouracil approximately 15% of the dose is excreted unchanged in the urine within 6 hours; over 90% of this is excreted in the first hour. The remainder is mostly metabolised in the liver by the usual body mechanisms for uracil.

5.3 Preclinical Safety Data

Preclinical information has not been included because the toxicity profile of fluorouracil has been established after many years of clinical use. Please refer to section 4.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sodium hydroxide

Water for Injections.

6.2 Incompatibilities

5-Fluorouracil is incompatible with Carboplatin, Cisplatin, Cytarabine. Diazepam, Doxorubicin, other Anthracyclines and possibly Methotrexate.

Formulated solutions are alkaline and it is recommended that admixture with acidic drugs or preparations should be avoided.

6.3 Shelf Life

Before use: 24 months

In use: Chemical and physical in-use stability has been demonstrated for 5 days at 20-21°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would not normally be longer than 24 hours at 2-8 °C, unless dilution has taken place in controlled and validated aseptic conditions.

6.4 Special Precautions For Storage

Do not store above 25°C. Do not refrigerate or freeze. Keep container in the outer carton.

The pH of fluorouracil injection is 8.9 and the drug has maximal stability over the pH range 8.6 to 9.0.

If a precipitate has formed as a result of exposure to low temperatures, redissolve by heating to 60°C accompanied by vigorous shaking. Allow to cool to body temperature prior to use.

The product should be discarded if it appears brown or dark yellow in solution.

6.5 Nature And Contents Of Container

Type I Conventional Clear Glass Vials with rubber closures.

Type I Clear Onco-Tain^® Vials with rubber closures.

250 mg/10ml: Pack Size 5.

500 mg/20ml: Pack Size 10.

2.5 g/100 ml: Pack Size Singles and 10's.

Not all presentations or pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

Cytotoxic Handling Guidelines

Should be administered only by or under the direct supervision of a qualified physician who is experienced in the use of cancer chemotherapeutic agents.

Fluorouracil Injection should only be prepared for administration by professionals who have been trained in the safe use of the preparation. Preparation should only be carried out in an aseptic cabinet or suite dedicated for the assembly of cytotoxics.

In the event of spillage, operators should put on gloves, face mask, eye protection and disposable apron and mop up the spilled material with a absorbent material kept in the area for that purpose. The area should then be cleaned and all contaminated material transferred to a cytotoxic spillage bag or bin and sealed for incineration.

Contamination

Fluorouracil is an irritant, contact with skin and mucous membranes should be avoided.

In the event of contact with the skin or eyes, the affected area should be washed with copious amounts of water or normal saline. A bland cream may be used to treat the transient stinging of the skin. Medical advice should be sought if the eyes are affected or if the preparation is inhaled or ingested.

Please refer to company for COSHH hazard datasheets.

Preparation Guidelines

a) Chemotherapeutic agents should be prepared for administration only by professionals who have been trained in the safe use of the preparation.

b) Operations such as reconstitution of powder and transfer to syringes should be carried out only under aseptic conditions in a suite or cabinet dedicated for the assembly of cytotoxics.

c) The personnel carrying out these procedures should be adequately protected with clothing, gloves and eye shield.

d) Pregnant personnel are advised not to handle chemotherapeutic agents.

Disposal

Syringes, Onco•Vials^® and adaptors containing remaining solution, absorbent materials, and any other contaminated material should be placed in a thick plastic bag or other impervious container and incinerated at 700°C.

Diluents

Fluorouracil Injection may be diluted with Glucose 5% Injection or Sodium Chloride 0.9% Injection or Water for Injections immediately before parenteral use.

7. Marketing Authorisation Holder

Hospira UK Limited

Queensway,

Royal Leamington Spa,

Warwickshire CV31 3RW

United Kingdom.

8. Marketing Authorisation Number(S)

PL 04515/0024

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of First Authorisation: 20 August 1985

Renewal of Authorisation: 19 July 2004

10. Date Of Revision Of The Text

12 August 2011

Spiriva

Generic Name: tiotropium (Inhalation route)

tye-oh-TROE-pee-um

Commonly used brand name(s)

In the U.S.

Spiriva

Available Dosage Forms:

Capsule

Therapeutic Class: Bronchodilator

Pharmacologic Class: Antimuscarinic

Uses For Spiriva

Tiotropium is used to treat bronchospasm or wheezing caused by chronic obstructive pulmonary disease (COPD). COPD is a lung disease that also includes chronic bronchitis (swelling of the tubes leading to the lungs) and emphysema (damage to the air sacs in the lungs).

Tiotropium belongs to the family of medicines known as bronchodilators. Bronchodilators are breathed in through the mouth to help open up the bronchial tubes (air passages) in the lungs. It is taken by inhalation (an inhaler) and will increase the flow of air to the lungs.

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

Before Using Spiriva

Allergies

Pediatric

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

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of inhaled tiotropium in the elderly.

Pregnancy

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

Breast Feeding

Interactions with Medicines

Interactions with Food/Tobacco/Alcohol

Proper Use of Spiriva

Use this medicine only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. Also, do not stop using this medicine without telling your doctor. To do so may increase the chance of having breathing problems.

Spiriva® capsules should only be used with the HandiHaler® device. Do not swallow the capsule. Spiriva® capsules should only be inhaled through your mouth (oral inhalation). Do not use the HandiHaler® device with any other medicine.

This medicine usually comes with patient instructions. Read them carefully before using the medicine. If you do not understand the instructions or have questions about using the inhaler, talk to your doctor.

Do not allow the powder from the capsules to get in your eyes. If the powder does get in your eyes, it may cause blurred vision and pupil dilation (increased pupil size). If this happens, call your doctor right away.

To use:

Open the HandiHaler® device and the blister containing the capsule.

Put one capsule into the HandiHaler® device.

Press and then release the green piercing button on the side of the HandiHaler® device. Do not press the green button more than once.

Breathe out fully. Do not breathe into the mouthpiece of the HandiHaler® device.

Hold the HandiHaler® base, put the mouthpiece between your lips, and close your lips around the mouthpiece.

Breathe in slowly and deeply through your mouth as you can hear or feel the Spiriva® capsule vibrate. Do not breathe through your nose.

Hold your breath and remove the mouthpiece from your mouth. Then, breathe normally again.

After you are finished, open the mouthpiece and remove the used Spiriva® capsule and throw it away. Do not store any used or unused capsule in the HandiHaler® device.

Rinse the HandiHaler® device with warm water and keep it dry.

Dosing

For oral inhalation dosage form (capsules):
- For bronchospasm caused by COPD:
  - Adults—Two puffs of the powder from one Spiriva® capsule (18 micrograms [mcg]) inhaled through the HandiHaler® device once a day.
  - 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.

Do not use this medicine more than once every 24 hours.

Storage

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.

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

Leave the capsules in the blister pack until you are ready to use the medicine. Only open one blister at a time when you are ready to remove a capsule and put it in the HandiHaler® device. Once you have opened a blister, use the capsule right away. After using the first capsule, the 2 remaining capsules should be used over the next 2 consecutive days. Capsules that are accidently exposed to air and not intended for immediate use should be discarded.

Precautions While Using Spiriva

It is very important that your doctor check your progress closely while you are using this medicine to see if it is working properly and to help reduce any unwanted effects.

This medicine will not stop bronchospasm that has already started. Your doctor will give you another medicine to use in case of an acute attack.

Tiotropium may cause allergic reactions, including anaphylaxis and angioedema. Stop using the medicine and check with your doctor right away if you develop a skin rash, itching, shortness of breath, or large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs after using this medicine.

This medicine may cause paradoxical bronchospasm, which means your breathing or wheezing will get worse. Paradoxical bronchospasm may be life-threatening. Stop using this medicine and check with your doctor right away if you have coughing, difficulty breathing, shortness of breath, or wheezing after using this medicine.

Check with your doctor right away if you have any changes to your eyes, such as eye pain, eye discomfort, blurred vision, visual halos, or colored images with red eyes while you are using this medicine. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

This medicine may cause dizziness or blurred vision. Avoid driving, using machines, or doing anything else that could be dangerous if you are dizzy or not able to see well.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems, and herbal or vitamin supplements.

Spiriva 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:

More common

Arm, back, or jaw pain

chest pain or discomfort

chest tightness or heaviness

fast or irregular heartbeat

nausea

shortness of breath

sweating

Less common

Cough

difficulty with swallowing

dizziness

hives

itching

painful blisters on the trunk of body

puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue

skin rash

tightness in the chest

unusual tiredness or weakness

wheezing

Rare

Fainting

large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs

palpitations

pounding, or irregular heartbeat or pulse

More common

Acid or sour stomach

belching

bladder pain

bloody or cloudy urine

body aches or pain

chest pain

chills

congestion

cough

difficult, burning, or painful urination

difficulty with breathing

dry mouth

dryness of the throat

ear congestion

fever

frequent urge to urinate

headache

heartburn

hoarseness

indigestion

loss of voice

lower back or side pain

pain or tenderness around the eyes and cheekbones

runny or stuffy nose

sneezing

sore throat

stomach discomfort, upset, or pain

tender, swollen glands in the neck

trouble with swallowing

troubled breathing

unusual tiredness or weakness

voice changes

Less common

Abdominal or stomach pain

bloody nose

blurred vision

burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings

canker sores

difficulty having a bowel movement (stool)

discouragement

feeling sad or empty

flushed, dry skin

fruit-like breath odor

increased hunger

increased thirst

increased urination

irritability

lack of appetite

large amount of cholesterol in the blood

leg pain

loss of interest or pleasure

muscle pain

nausea

painful or difficult urination

skeletal pain

sore mouth or tongue

sores, ulcers, or white spots on the lips or tongue or inside the mouth

sweating

swelling

swelling or inflammation of the mouth

tiredness

trouble concentrating

trouble sleeping

troubled breathing

unexplained weight loss

vomiting

white patches in the mouth and/or on the tongue

Incidence not known

Bloating

change in vision

constipation

diarrhea

itching or red skin

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: Spiriva side effects (in more detail)

More Spiriva resources

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

Spiriva Consumer Overview

Spiriva Prescribing Information (FDA)

Tiotropium MedFacts Consumer Leaflet (Wolters Kluwer)

Spiriva Handihaler Monograph (AHFS DI)

Compare Spiriva with other medications

COPD, Maintenance

Monday, September 26, 2016

Sorine

Dosage Form: tablet
Sorine®

(Sotalol HCl) Tablets

To minimize the risk of induced arrhythmia, patients initiated or reinitiated on sotalol should be placed for a minimum of three days (on their maintenance dose) in a facility that can provide cardiac resuscitation and continuous electrocardiographic monitoring. Creatinine clearance should be calculated prior to dosing. For detailed instructions regarding dose selection and special cautions for people with renal impairment, see DOSAGE AND ADMINISTRATION. Sotalol is also indicated for the maintenance of normal sinus rhythm [delay in time to recurrence of atrial fibrillation/atrial flutter (AFIB/AFL)] in patients with symptomatic AFIB/AFL who are currently in sinus rhythm and is marketed under the brand name BETAPACE AF®. This product is not approved for the AFIB/AFL indication and should not be substituted for BETAPACE AF because only BETAPACE AF is distributed with a patient package insert that is appropriate for patients with AFIB/AFL.

Rx only

Sorine Description

Sorine® (Sotalol HCl) Tablets are an antiarrhythmic drug with Class II (beta-adrenoreceptor blocking) and Class III (cardiac action potential duration prolongation) properties. It is supplied as a white, capsule-shaped tablet for oral administration. Sotalol hydrochloride is a white, crystalline solid with a molecular weight of 308.8. It is hydrophilic, soluble in water, propylene glycol and ethanol, but is only slightly soluble in chloroform. Chemically, sotalol hydrochloride is d,l-N-[4-[1-hydroxy-2-[(1-methylethyl)amino]ethyl]phenyl] methane-sulfonamide monohydrochloride. The molecular formula is C12H20N2O3S•HCl and is represented by the following structural formula:

Sorine® Tablets contain the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, corn starch, stearic acid, magnesium stearate and silicon dioxide.

Sorine - Clinical Pharmacology

Mechanism of Action: Sotalol hydrochloride has both betaadrenoreceptor blocking (Vaughan Williams Class II) and cardiac action potential duration prolongation (Vaughan Williams Class III) antiarrhythmic properties. Sotalol hydrochloride is a racemic mixture of d- and l-sotalol. Both isomers have similar Class III antiarrhythmic effects, while the l-isomer is responsible for virtually all of the beta-blocking activity. The beta-blocking effect of sotalol is non-cardioselective, half maximal at about 80 mg/day and maximal at doses between 320 and 640 mg/day. Sotalol does not have partial agonist or membrane stabilizing activity. Although significant beta-blockade occurs at oral doses as low as 25 mg, significant Class III effects are seen only at daily doses of 160 mg and above.

Information related to an electrophysiologic effect in pediatric patients is approved for Berlex Laboratories' sotalol hydrochloride tablets. However, due to Berlex's marketing exclusivity rights, this drug product is not labeled for pediatric use.

Electrophysiology: Sotalol hydrochloride prolongs the plateau phase of the cardiac action potential in the isolated myocyte, as well as in isolated tissue preparations of ventricular or atrial muscle (Class III activity). In intact animals it slows heart rate, decreases AV nodal conduction and increases the refractory periods of atrial and ventricular muscle and conduction tissue.

In man, the Class II (beta-blockade) electrophysiological effects of sotalol are manifested by increased sinus cycle length (slowed heart rate), decreased AV nodal conduction and increased AV nodal refractoriness. The Class III electrophysiological effects in man include prolongation of the atrial and ventricular monophasic action potentials, and effective refractory period prolongation of atrial muscle, ventricular muscle, and atrio-ventricular accessory pathways (where present) in both the anterograde and retrograde directions. With oral doses of 160 to 640 mg/day, the surface ECG shows dose-related mean increases of 40-100 msec in QT and 10-40 msec in QTc. (See WARNINGS for description of relationship between QTc and Torsade de Pointes type arrhythmias.) No significant alteration in QRS interval is observed.

In a small study (n=25) of patients with implanted defibrillators treated concurrently with sotalol, the average defibrillatory threshold was 6 joules (range 2-15 joules) compared to a mean of 16 joules for a nonrandomized comparative group primarily receiving amiodarone.

Pediatric clinical trial information is approved for Berlex Laboratories' sotalol hydrochloride tablets. However, due to Berlex's marketing exclusivity rights, this drug product is not labeled for pediatric use.

Hemodynamics: In a study of systemic hemodynamic function measured invasively in 12 patients with a mean LV ejection fraction of 37% and ventricular tachycardia (9 sustained and 3 non-sustained), a median dose of 160 mg twice daily of sotalol hydrochloride produced a 28% reduction in heart rate and a 24% decrease in cardiac index at 2 hours post dosing at steady-state. Concurrently, systemic vascular resistance and stroke volume showed nonsignificant increases of 25% and 8%, respectively. Pulmonary capillary wedge pressure increased significantly from 6.4 mmHg to 11.8 mmHg in the 11 patients who completed the study. One patient was discontinued because of worsening congestive heart failure. Mean arterial pressure, mean pulmonary artery pressure and stroke work index did not significantly change. Exercise and isoproterenol induced tachycardia are antagonized by sotalol, and total peripheral resistance increases by a small amount.

In hypertensive patients, sotalol produces significant reductions in both systolic and diastolic blood pressures. Although sotalol hydrochloride is usually well-tolerated hemodynamically, caution should be exercised in patients with marginal cardiac compensation as deterioration in cardiac performance may occur. (See WARNINGS: Congestive Heart Failure.)

Clinical Studies: Sotalol hydrochloride has been studied in life-threatening and less severe arrhythmias. In patients with frequent premature ventricular complexes (VPC), sotalol was significantly superior to placebo in reducing VPCs, paired VPCs and non-sustained ventricular tachycardia (NSVT); the response was dose-related through 640 mg/day with 80-85% of patients having at least a 75% reduction of VPCs. Sotalol was also superior at the doses evaluated, to propranolol (40 to 80 mg TID) and similar to quinidine (200 to 400 mg QID) in reducing VPCs. In patients with life-threatening arrhythmias [sustained ventricular tachycardia/fibrillation (VT/VF)], sotalol was studied acutely [by suppression of programmed electrical stimulation (PES) induced VT and by suppression of Holter monitor evidence of sustained VT] and, in acute responders, chronically.

In a double-blind, randomized comparison of sotalol hydrochloride and procainamide given intravenously (total of 2 mg/kg sotalol hydrochloride vs. 19 mg/kg of procainamide over 90 minutes), sotalol suppressed PES induction in 30% of patients vs. 20% for procainamide (p=0.2).

In a randomized clinical trial [Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) Trial] comparing choice of antiarrhythmic therapy by PES suppression vs. Holter monitor selection (in each case followed by treadmill exercise testing) in patients with a history of sustained VT/VF who were also inducible by PES, the effectiveness acutely and chronically of sotalol was compared with 6 other drugs (procainamide, quinidine, mexiletine, propafenone, imipramine and pirmenol). Overall response, limited to first randomized drug, was 39% for sotalol and 30% for the pooled other drugs. Acute response rate for first drug randomized using suppression of PES induction was 36% for sotalol vs. a mean of 13% for the other drugs. Using the Holter monitoring endpoint (complete suppression of sustained VT, 90% suppression of NSVT, 80% suppression of VPC pairs, and at least 70% suppression of VPCs), sotalol yielded 41% response vs. 45% for the other drugs combined. Among responders placed on long-term therapy identified acutely as effective (by either PES or Holter), sotalol, when compared to the pool of other drugs, had the lowest two-year mortality (13% vs. 22%), the lowest two-year VT recurrence rate (30% vs. 60%), and the lowest withdrawal rate (38% vs. about 75-80%). The most commonly used doses of sotalol hydrochloride in this trial were 320 to 480 mg/day (66% of patients), with 16% receiving 240 mg/day or less and 18% receiving 640 mg or more.

It cannot be determined, however, in the absence of a controlled comparison of sotalol vs. no pharmacologic treatment (e.g., in patients with implanted defibrillators) whether sotalol response causes improved survival or identifies a population with a good prognosis.

In a large, double-blind, placebo controlled secondary prevention (postinfarction) trial (n=1,456), sotalol hydrochloride was given as a non-titrated initial dose of 320 mg once daily. Sotalol did not produce a significant increase in survival (7.3% mortality on sotalol vs. 8.9% on placebo, p=0.3), but overall did not suggest an adverse effect on survival. There was, however, a suggestion of an early (i.e., first 10 days) excess mortality (3% on sotalol vs. 2% on placebo). In a second small trial (n=17 randomized to sotalol) where sotalol was administered at high doses (e.g., 320 mg twice daily) to high-risk post-infarction patients (ejection fraction <40% and either >10 VPC/hr or VT on Holter), there were 4 fatalities and 3 serious hemodynamic/electrical adverse events within two weeks of initiating sotalol.

Pharmacokinetics: In healthy subjects, the oral bioavailability of sotalol hydrochloride is 90-100%. After oral administration, peak plasma concentrations are reached in 2.5 to 4 hours, and steady-state plasma concentrations are attained within 2-3 days (i.e., after 5-6 doses when administered twice daily). Over the dosage range 160-640 mg/day sotalol displays dose proportionality with respect to plasma concentrations. Distribution occurs to a central (plasma) and to a peripheral compartment, with a mean elimination half-life of 12 hours. Dosing every 12 hours results in trough plasma concentrations which are approximately one-half of those at peak.

Sotalol hydrochloride does not bind to plasma proteins and is not metabolized. Sotalol shows very little intersubject variability in plasma levels. The pharmacokinetics of the d and l enantiomers of sotalol are essentially identical. Sotalol hydrochloride crosses the blood brain barrier poorly. Excretion is predominantly via the kidney in the unchanged form, and therefore lower doses are necessary in conditions of renal impairment (see DOSAGE AND ADMINISTRATION). Age per se does not significantly alter the pharmacokinetics of sotalol, but impaired renal function in geriatric patients can increase the terminal elimination half-life, resulting in increased drug accumulation. The absorption of sotalol was reduced by approximately 20% compared to fasting when it was administered with a standard meal. Since sotalol is not subject to first-pass metabolism, patients with hepatic impairment show no alteration in clearance of sotalol.

Pediatric pharmacokinetic information is approved for Berlex Laboratories' sotalol hydrochloride tablets. However, due to Berlex's marketing exclusivity rights, this drug product is not labeled for pediatric use.

Indications and Usage for Sorine

Oral Sorine® (Sotalol HCl) Tablets are indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that in the judgment of the physician are life-threatening. Because of the proarrhythmic effects of sotalol (see WARNINGS), including a 1.5 to 2% rate of Torsade de Pointes or new VT/VF in patients with either NSVT or supraventricular arrhythmias, its use in patients with less severe arrhythmias, even if the patients are symptomatic, is generally not recommended. Treatment of patients with asymptomatic ventricular premature contractions should be avoided.

Initiation of Sorine® (Sotalol HCl) Tablets treatment or increasing doses, as with other antiarrhythmic agents used to treat life-threatening arrhythmias, should be carried out in the hospital. The response to treatment should then be evaluated by a suitable method (e.g., PES or Holter monitoring) prior to continuing the patient on chronic therapy. Various approaches have been used to determine the response to antiarrhythmic therapy, including sotalol.

In the ESVEM Trial, response by Holter monitoring was tentatively defined as 100% suppression of ventricular tachycardia, 90% suppression of nonsustained VT, 80% suppression of paired VPCs, and 75% suppression of total VPCs in patients who had at least 10 VPCs/hour at baseline; this tentative response was confirmed if VT lasting 5 or more beats was not observed during treadmill exercise testing using a standard Bruce protocol. The PES protocol utilized a maximum of three extrastimuli at three pacing cycle lengths and two right ventricular pacing sites. Response by PES was defined as prevention of induction of the following: 1) monomorphic VT lasting over 15 seconds; 2) non-sustained polymorphic VT containing more than 15 beats of monomorphic VT in patients with a history of monomorphic VT; 3) polymorphic VT or VF greater than 15 beats in patients with VF or a history of aborted sudden death without monomorphic VT; and 4) two episodes of polymorphic VT or VF of greater than 15 beats in a patient presenting with monomorphic VT. Sustained VT or NSVT producing hypotension during the final treadmill test was considered a drug failure.

In a multicenter open-label long-term study of sotalol in patients with life-threatening ventricular arrhythmias which had proven refractory to other antiarrhythmic medications, response by Holter monitoring was defined as in ESVEM. Response by PES was defined as non-inducibility of sustained VT by at least double extrastimuli delivered at a pacing cycle length of 400 msec. Overall survival and arrhythmia recurrence rates in this study were similar to those seen in ESVEM, although there was no comparative group to allow a definitive assessment of outcome.

Antiarrhythmic drugs have not been shown to enhance survival in patients with ventricular arrhythmias.

Sotalol is also indicated for the maintenance of normal sinus rhythm [delay in time to recurrence of atrial fibrillation/atrial flutter (AFIB/AFL)] in patients with symptomatic AFIB/AFL who are currently in sinus rhythm and is marketed under the brand name BETAPACE AF. Sorine® is not approved for the AFIB/AFL indication and should not be substituted for BETAPACE AF because only BETAPACE AF is distributed with a patient package insert that is appropriate for patients with AFIB/AFL.

Contraindications

Sorine® (Sotalol HCl) Tablets are contraindicated in patients with bronchial asthma, sinus bradycardia, second and third degree AV block, unless a functioning pacemaker is present, congenital or acquired long QT syndromes, cardiogenic shock, uncontrolled congestive heart failure, and previous evidence of hypersensitivity to sotalol.

Warnings

Mortality: The National Heart, Lung, and Blood Institute's Cardiac Arrhythmia Suppression Trial I (CAST I) was a long-term, multi-center, double-blind study in patients with asymptomatic, non-life-threatening ventricular arrhythmias, 1 to 103 weeks after acute myocardial infarction. Patients in CAST I were randomized to receive placebo or individually optimized doses of encainide, flecainide, or moricizine. The Cardiac Arrhythmia Suppression Trial II (CAST II) was similar, except that the recruited patients had had their index infarction 4 to 90 days before randomization, patients with left ventricular ejection fractions greater than 40% were not admitted, and the randomized regimens were limited to placebo and moricizine.

CAST I was discontinued after an average time-on-treatment of 10 months, and CAST II was discontinued after an average time-on-treatment of 18 months. As compared to placebo treatment, all three active therapies were associated with increases in short-term (14-day) mortality, and encainide and flecainide were associated with significant increases in longer-term mortality as well. The longer-term mortality rate associated with moricizine treatment could not be statistically distinguished from that associated with placebo.

The applicability of these results to other populations (e.g., those without recent myocardial infarction) and to other than Class I antiarrhythmic agents is uncertain. Sotalol hydrochloride is devoid of Class I effects, and in a large (n=1,456) controlled trial in patients with a recent myocardial infarction, who did not necessarily have ventricular arrhythmias, sotalol did not produce increased mortality at doses up to 320 mg/day (see Clinical Studies). On the other hand, in the large postinfarction study using a non-titrated initial dose of 320 mg once daily and in a second small randomized trial in high-risk post-infarction patients treated with high doses (320 mg BID), there have been suggestions of an excess of early sudden deaths.

Proarrhythmia: Like other antiarrhythmic agents, sotalol can provoke new or worsened ventricular arrhythmias in some patients, including sustained ventricular tachycardia or ventricular fibrillation, with potentially fatal consequences. Because of its effect on cardiac repolarization (QTc interval prolongation), Torsade de Pointes, a polymorphic ventricular tachycardia with prolongation of the QT interval and a shifting electrical axis is the most common form of proarrhythmia associated with sotalol, occurring in about 4% of high risk (history of sustained VT/VF) patients. The risk of Torsade de Pointes progressively increases with prolongation of the QT interval, and is worsened also by reduction in heart rate and reduction in serum potassium. (See Electrolyte Disturbances.)

Because of the variable temporal recurrence of arrhythmias, it is not always possible to distinguish between a new or aggravated arrhythmic event and the patient's underlying rhythm disorder. (Note, however, that Torsade de Pointes is usually a drug-induced arrhythmia in people with an initially normal QTc.) Thus, the incidence of drug-related events cannot be precisely determined, so that the occurrence rates provided must be considered approximations. Note also that drug-induced arrhythmias may often not be identified, particularly if they occur long after starting the drug, due to less frequent monitoring. It is clear from the NIH-sponsored CAST (see WARNINGS: Mortality) that some antiarrhythmic drugs can cause increased sudden death mortality, presumably due to new arrhythmias or asystole, that do not appear early in treatment but that represent a sustained increased risk.

Overall in clinical trials with sotalol, 4.3% of 3257 patients experienced a new or worsened ventricular arrhythmia. Of this 4.3%, there was new or worsened sustained ventricular tachycardia in approximately 1% of patients and Torsade de Pointes in 2.4%. Additionally, in approximately 1% of patients, deaths were considered possibly drug-related; such cases, although difficult to evaluate, may have been associated with proarrhythmic events. In patients with a history of sustained ventricular tachycardia, the incidence of Torsade de Pointes was 4% and worsened VT in about 1%; in patients with other, less serious, ventricular arrhythmias and supraventricular arrhythmias, the incidence of Torsade de Pointes was 1% and 1.4%, respectively.

Torsade de Pointes arrhythmias were dose related, as is the prolongation of QT (QTc) interval, as shown in the table below.

Percent Incidence of Torsade de Pointes and Mean QTc Interval by Dose For Patients With Sustained VT/VF
( )Number of patients assessed
*highest on-therapy value
Daily Dose (mg)	Incidence of Torsade de Pointes		Mean QTc* (msec)
80	0	(69)	463	(17)
160	0.5	(832)	467	(181)
320	1.6	(835)	473	(344)
480	4.4	(459)	483	(234)
640	3.7	(324)	490	(185)
>640	5.8	(103)	512	(62)

In addition to dose and presence of sustained VT, other risk factors for Torsade de Pointes were gender (females had a higher incidence), excessive prolongation of the QTc interval (see table below) and history of cardiomegaly or congestive heart failure. Patients with sustained ventricular tachycardia and a history of congestive heart failure appear to have the highest risk for serious proarrhythmia (7%). Of the patients experiencing Torsade de Pointes, approximately two-thirds spontaneously reverted to their baseline rhythm. The others were either converted electrically (D/C cardioversion or overdrive pacing) or treated with other drugs (see OVERDOSAGE). It is not possible to determine whether some sudden deaths represented episodes of Torsade de Pointes, but in some instances sudden death did follow a documented episode of Torsade de Pointes. Although sotalol therapy was discontinued in most patients experiencing Torsade de Pointes, 17% were continued on a lower dose.

Nonetheless, Sorine® (Sotalol HCl) Tablets should be used with particular caution if the QTc is greater than 500 msec on-therapy and serious consideration should be given to reducing the dose or discontinuing therapy when the QTc exceeds 550 msec. Due to the multiple risk factors associated with Torsade de Pointes, however, caution should be exercised regardless of the QTc interval. The table below relates the incidence of Torsade de Pointes to on-therapy QTc and change in QTc from baseline. It should be noted, however, that the highest on-therapy QTc was in many cases the one obtained at the time of the Torsade de Pointes event, so that the table overstates the predictive value of a high QTc.

Relationship Between QTc Interval Prolongation and Torsade de Pointes
( )Number of patients assessed
On-Therapy QTc Interval (msec)	Incidence of Torsade de Pointes		Change in QTc Interval From Baseline (msec)	Incidence of Torsade de Pointes
<500	1.3%	(1787)	<65	1.6%	(1516)
500-525	3.4%	(236)	65-80	3.2%	(158)
525-550	5.6%	(125)	80-100	4.1%	(146)
>550	10.8%	(157)	100-130	5.2%	(115)
			>130	7.1%	(99)

Proarrhythmic events must be anticipated not only on initiating therapy, but with every upward dose adjustment. Proarrhythmic events most often occur within 7 days of initiating therapy or of an increase in dose; 75% of serious proarrhythmias (Torsade de Pointes and worsened VT) occurred within 7 days of initiating sotalol therapy, while 60% of such events occurred within 3 days of initiation or a dosage change. Initiating therapy at 80 mg BID with gradual upward dose titration and appropriate evaluations for efficacy (e.g., PES or Holter) and safety (e.g., QT interval, heart rate and electrolytes) prior to dose escalation, should reduce the risk of proarrhythmia. Avoiding excessive accumulation of sotalol in patients with diminished renal function, by appropriate dose reduction, should also reduce the risk of proarrhythmia (see DOSAGE AND ADMINISTRATION).

Congestive Heart Failure: Sympathetic stimulation is necessary in supporting circulatory function in congestive heart failure, and beta-blockade carries the potential hazard of further depressing myocardial contractility and precipitating more severe failure. In patients who have congestive heart failure controlled by digitalis and/or diuretics, Sorine® should be administered cautiously. Both digitalis and sotalol slow AV conduction. As with all beta-blockers, caution is advised when initiating therapy in patients with any evidence of left ventricular dysfunction. In premarketing studies, new or worsened congestive heart failure (CHF) occurred in 3.3% (n=3257) of patients and led to discontinuation in approximately 1% of patients receiving sotalol. The incidence was higher in patients presenting with sustained ventricular tachycardia/fibrillation (4.6%, n=1363), or a prior history of heart failure (7.3%, n=696). Based on a lifetable analysis, the one-year incidence of new or worsened CHF was 3% in patients without a prior history and 10% in patients with a prior history of CHF. NYHA Classification was also closely associated to the incidence of new or worsened heart failure while receiving sotalol (1.8% in 1395 Class I patients, 4.9% in 1254 Class II patients and 6.1% in 278 Class III or IV patients).

Electrolyte Disturbances: Sorine® should not be used in patients with hypokalemia or hypomagnesemia prior to correction of imbalance, as these conditions can exaggerate the degree of QT prolongation, and increase the potential for Torsade de Pointes. Special attention should be given to electrolyte and acid-base balance in patients experiencing severe or prolonged diarrhea or patients receiving concomitant diuretic drugs.

Conduction Disturbances: Excessive prolongation of the QT interval (>550 msec) can promote serious arrhythmias and should be avoided (see Proarrhythmia above). Sinus bradycardia (heart rate less than 50 bpm) occurred in 13% of patients receiving sotalol in clinical trials, and led to discontinuation in about 3% of patients. Bradycardia itself increases the risk of Torsade de Pointes. Sinus pause, sinus arrest and sinus node dysfunction occur in less than 1% of patients. The incidence of 2nd- or 3rd-degree AV block is approximately 1%.

Recent Acute MI: Sorine® can be used safely and effectively in the long-term treatment of life-threatening ventricular arrhythmias following a myocardial infarction. However, experience in the use of sotalol to treat cardiac arrhythmias in the early phase of recovery from acute MI is limited and at least at high initial doses is not reassuring. (See WARNINGS: Mortality.) In the first 2 weeks post-MI, caution is advised and careful dose titration is especially important, particularly in patients with markedly impaired ventricular function.

The following warnings are related to the beta-blocking activity of Sorine®.

Abrupt Withdrawal: Hypersensitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy. Occasional cases of exacerbation of angina pectoris, arrhythmias and, in some cases, myocardial infarction have been reported after abrupt discontinuation of beta-blocker therapy. Therefore, it is prudent when discontinuing chronically administered Sorine®, particularly in patients with ischemic heart disease, to carefully monitor the patient and consider the temporary use of an alternate betablocker if appropriate. If possible, the dosage of Sorine® should be gradually reduced over a period of one to two weeks. If angina or acute coronary insufficiency develops, appropriate therapy should be instituted promptly. Patients should be warned against interruption or discontinuation of therapy without the physician's advice. Because coronary artery disease is common and may be unrecognized in patients receiving Sorine®, abrupt discontinuation in patients with arrhythmias may unmask latent coronary insufficiency.

Non-Allergic Bronchospasm (e.g., chronic bronchitis and emphysema): PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD IN GENERAL NOT RECEIVE BETA-BLOCKERS. It is prudent, if Sorine® (Sotalol HCl) Tablets are to be administered, to use the smallest effective dose, so that inhibition of bronchodilation produced by endogenous or exogenous catecholamine stimulation of beta2 receptors may be minimized.

Anaphylaxis: While taking beta-blockers, patients with a history of anaphylactic reaction to a variety of allergens may have a more severe reaction on repeated challenge, either accidental, diagnostic or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat the allergic reaction.

Major Surgery: Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.

Diabetes: In patients with diabetes (especially labile diabetes) or with a history of episodes of spontaneous hypoglycemia, Sorine® should be given with caution since beta-blockade may mask some important premonitory signs of acute hypoglycemia; e.g., tachycardia.

Sick Sinus Syndrome: Sorine® should be used only with extreme caution in patients with sick sinus syndrome associated with symptomatic arrhythmias, because it may cause sinus bradycardia, sinus pauses or sinus arrest.

Thyrotoxicosis: Beta-blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-blockade which might be followed by an exacerbation of symptoms of hyperthyroidism, including thyroid storm.

Precautions

Renal Impairment: Sotalol hydrochloride is mainly eliminated via the kidneys through glomerular filtration and to a small degree by tubular secretion. There is a direct relationship between renal function, as measured by serum creatinine or creatinine clearance, and the elimination rate of sotalol. Guidance for dosing in conditions of renal impairment can be found under “DOSAGE AND ADMINISTRATION”.

Drug Interactions

Drugs undergoing CYP450 metabolism: Sotalol is primarily eliminated by renal excretion; therefore, drugs that are metabolized by CYP450 are not expected to alter the pharmacokinetics of sotalol. Sotalol is not expected to inhibit or induce any CYP450 enzymes, therefore, it is not expected to alter the PK of drugs that are metabolized by these enzymes.

Antiarrhythmics: Class Ia antiarrhythmic drugs, such as disopyramide, quinidine and procainamide and other Class III drugs (e.g., amiodarone) are not recommended as concomitant therapy with Sorine®, because of their potential to prolong refractoriness (see WARNINGS). There is only limited experience with the concomitant use of Class Ib or Ic antiarrhythmics. Additive Class II effects would also be anticipated with the use of other beta-blocking agents concomitantly with Sorine®.

Digoxin: Single and multiple doses of Sorine® do not substantially affect serum digoxin levels. Proarrhythmic events were more common in sotalol-treated patients also receiving digoxin; it is not clear whether this represents an interaction or is related to the presence of CHF, a known risk factor for proarrhythmia, in the patients receiving digoxin. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia.

Calcium blocking drugs: Sorine® should be administered with caution in conjunction with calcium-blocking drugs because of possible additive effects on atrioventricular conduction or ventricular function. Additionally, concomitant use of these drugs may have additive effects on blood pressure, possibly leading to hypotension.

Catecholamine-depleting agents: Concomitant use of catecholamine-depleting drugs, such as reserpine and guanethidine, with a beta-blocker may produce an excessive reduction of resting sympathetic nervous tone. Patients treated with Sorine® plus a catecholamine depletor should therefore be closely monitored for evidence of hypotension and/or marked bradycardia which may produce syncope.

Insulin and oral antidiabetics: Hyperglycemia may occur, and the dosage of insulin or antidiabetic drugs may require adjustment. Symptoms of hypoglycemia may be masked.

Beta-2-receptor stimulants: Beta-agonists such as salbutamol, terbutaline and isoprenaline may have to be administered in increased dosages when used concomitantly with Sorine®.

Clonidine: Beta-blocking drugs may potentiate the rebound hypertension sometimes observed after discontinuation of clonidine; therefore, caution is advised when discontinuing clonidine in patients receiving Sorine®.

Other: No pharmacokinetic interactions were observed with hydrochlorthiazide or warfarin.

Antacids: Administration of sotalol within 2 hours of antacids containing aluminum oxide and magnesium hydroxide should be avoided because it may result in a reduction in Cmax and AUC of 26% and 20%, respectively, and consequently in a 25% reduction in the bradycardic effect at rest. Administration of the antacid 2 hours after sotalol has no effect on the pharmacokinetics or pharmacodynamics of sotalol.

Drugs prolonging the QT interval: Sorine® should be administered with caution in conjunction with other drugs known to prolong the QT interval such as Class I and Class III antiarrhythmic agents, phenothiazines, tricyclic antidepressants, astemizole, bepridil, certain oral macrolides, and certain quinolone antibiotics (see WARNINGS).

Drug/Laboratory Test Interactions

The presence of sotalol in the urine may result in falsely elevated levels of urinary metanephrine when measured by fluorimetric or photometric methods. In screening patients suspected of having a pheochromocytoma and being treated with sotalol, a specific method, such as a high performance liquid chromatographic assay with solid phase extraction (e.g., J. Chromatogr. 385:241, 1987) should be employed in determining levels of catecholamines.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of carcinogenic potential was observed in rats during a 24-month study at 137-275 mg/kg/day (approximately 30 times the maximum recommended human oral dose [MRHD] as mg/kg or 5 times the MRHD as mg/m2) or in mice, during a 24-month study at 4141-7122 mg/kg/day (approximately 450-750 times the MRHD as mg/kg or 36-63 times the MRHD as mg/m2).

Sotalol has not been evaluated in any specific assay of mutagenicity or clastogenicity.

No significant reduction in fertility occurred in rats at oral doses of 1000 mg/kg/day (approximately 100 times the MRHD as mg/kg or 9 times the MRHD as mg/m2) prior to mating, except for a small reduction in the number of offspring per litter.

Pregnancy Category B: Reproduction studies in rats and rabbits during organogenesis at 100 and 22 times the MRHD as mg/kg (9 and 7 times the MRHD as mg/m2), respectively, did not reveal any teratogenic potential associated with sotalol HCl. In rabbits, a high dose of sotalol HCl (160 mg/kg/day) at 16 times the MRHD as mg/kg (6 times the MRHD as mg/m2) produced a slight increase in fetal death likely due to maternal toxicity. Eight times the maximum dose (80 mg/kg/day or 3 times the MRHD as mg/m2) did not result in an increased incidence of fetal deaths. In rats, 1000 mg/kg/day sotalol HCl, 100 times the MRHD (18 times the MRHD as mg/m2), increased the number of early resorptions, while at 14 times the maximum dose (2.5 times the MRHD as mg/m2), no increase in early resorptions was noted. However, animal reproduction studies are not always predictive of human response.

Although there are no adequate and well-controlled studies in pregnant women, sotalol HCl has been shown to cross the placenta, and is found in amniotic fluid. There has been a report of subnormal birth weight with sotalol. Therefore, Sorine® (Sotalol HCl) Tablets should be used during pregnancy only if the potential benefit outweighs the potential risk.

Nursing Mothers: Sotalol is excreted in the milk of laboratory animals and has been reported to be present in human milk. Because of the potential for adverse reactions in nursing infants from sotalol, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use: The safety and effectiveness of sotalol in children have not been established. However, information relating to the clinical pharmacology in children is approved for Berlex Laboratories' sotalol hydrochloride tablets. Due to Berlex's marketing exclusivity rights, this drug product is not labeled for pediatric use.

Adverse Reactions

During premarketing trials, 3186 patients with cardiac arrhythmias (1363 with sustained ventricular tachycardia) received oral sotalol, of whom 2451 received the drug for at least two weeks. The most important adverse effects are Torsade de Pointes and other serious new ventricular arrhythmias (see WARNINGS), occurring at rates of almost 4% and 1%, respectively, in the VT/VF population. Overall, discontinuation because of unacceptable side-effects was necessary in 17% of all patients in clinical trials, and in 13% of patients treated for at least two weeks. The most common adverse reactions leading to discontinuation of sotalol are as follows: fatigue 4%, bradycardia (less than 50 bpm) 3%, dyspnea 3%, proarrhythmia 3%, asthenia 2%, and dizziness 2%.

Occasional reports of elevated serum liver enzymes have occurred with sotalol therapy but no cause and effect relationship has been established. One case of peripheral neuropathy which resolved on discontinuation of sotalol and recurred when the patient was rechallenged with the drug was reported in an early dose tolerance study. Elevated blood glucose levels and increased insulin requirements can occur in diabetic patients.

The following table lists as a function of dosage the most common (incidence of 2% or greater) adverse events, regardless of relationship to therapy and the percent of patients discontinued due to the event, as collected from clinical trials involving 1292 patients with sustained VT/VF.

Incidence (%) of Adverse Events and Discontinuations DAILY DOSE
*Because patients are counted at each dose level tested, the Any Dose column cannot be determined by adding across the doses.
Body System	160mg (n=832)	240mg (n=263)	320mg (n=835)	480mg (n=459)	640mg (n=324)	Any Dose* (n=1292)	% PatientsDiscontinued(n=1292)
Body as a whole
infection	1	2	2	2	3	4	<1
fever	1	2	3	2	2	4	<1
localized pain	1	1	2	2	2	3	<1
Cardiovascular
dyspnea

Thursday, September 29, 2016

Viadur

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Wednesday, September 28, 2016

Encore

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Tuesday, September 27, 2016

spironolactone

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Fluorouracil 25 mg / ml Injection (Hospira UK Ltd)

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Spiriva

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