Halobetasol Propionate Ointment

Generic Name: halobetasol propionate

Dosage Form: ointment
Halonate (halobetasol Propionate ointmanet 0.05%)

Halonate Halobetasol Propionate Ointment, 0.05% contains halobetasol propionate, a synthetic corticosteroid

for topical dermatological use. The corticosteroids constitute a class of primarily synthetic

steroids used topically as an anti-inflammatory and anti-pruritic agent.

Chemically halobetasol propionate is 21-chloro-6α, 9-difluoro-11β,17-dihydroxy-16β-methylpregna-1,

4-diene-3-20-dione, 17-propionate, C25H31ClF2O5. It has the following structural formula:

Halobetasol propionate has the molecular weight of 485. It is a white crystalline powder insoluble in water.


Each gram of Halobetasol Propionate Ointment contains 0.5 mg/g of halobetasol propionate in a

base of aluminum stearate, beeswax, pentaerythritol cocoate, petrolatum, propylene glycol, sorbitan

sesquioleate, and stearyl citrate.
Like other topical corticosteroids, halobetasol propionate has anti-inflammatory, antipruritic and

vasoconstrictive actions. The mechanism of the anti-inflammatory activity of the topical corticosteroids,

in general, is unclear. However, corticosteroids are thought to act by the induction of

phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins

control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes

by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is

released from membrane phospholipids by phospholipase A2. The extent of percutaneous absorption of topical corticosteroids is determined by many factors

including the vehicle and the integrity of the epidermal barrier. Occlusive dressings with hydrocortisone

for up to 24 hours have not been demonstrated to increase penetration; however, occlusion

of hydrocortisone for 96 hours markedly enhances penetration. Topical corticosteroids can be absorbed

from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous

absorption.


Human and animal studies indicate that less than 6% of the applied dose of halobetasol propionate

enters the circulation within 96 hours following topical administration of the ointment.

Studies performed with Halobetasol Propionate Ointment indicate that it is in the super-high range

of potency as compared with other topical corticosteroids. Halobetasol Propionate Ointment 0.05% is a superhigh potency corticosteroid indicated for the relief

of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Treatment

beyond two consecutive weeks is not recommended, and the total dosage should not exceed 50 g/week

because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Use

in children under 12 years of age is not recommended.


As with other highly active corticosteroids, therapy should be discontinued when control has been

achieved. If no improvement is seen within 2 weeks, reassessment of the diagnosis may be

necessary.

Halobetasol Propionate Ointment is contraindicated in those patients with a history of hypersensitivity

to any of the components of the preparation.

General:  Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal

(HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of

treatment. Manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria can also be produced

in some patients by systemic absorption of topical corticosteroids while on treatment.


Patients applying a topical steroid to a large surface area or to areas under occlusion should be evaluated

periodically for evidence of HPA axis suppression. This may be done by using the ACTH stimulation,

A.M. plasma cortisol, and urinary free-cortisol tests.  Patients receiving super potent corticosteroids

should not be treated for more than 2 weeks at a time and only small areas should be treated at any one

time due to the increased risk of HPA suppression.


Halobetasol Propionate Ointment produced HPA axis suppression when used in divided doses at 7

grams per day for one week in patients with psoriasis. These effects were reversible upon discontinuation

of treatment.


If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the

frequency of application, or to substitute a less potent corticosteroid. Recovery of HPA axis function

is generally prompt upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms

of glucocorticosteroid insufficiency may occur requiring supplemental systemic corticosteroids.

For information on systemic supplementation, see prescribing information for those products.


Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their

larger skin surface to body mass ratios (see PRECAUTIONS:Pediatric Use).


If irritation develops, Halobetasol Propionate Ointment should be discontinued and appropriate

therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing

failure to heal rather than noting a clinical exacerbation as with most topical products not containing

corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing.

If concomitant skin infections are present or develop, an appropriate antifungal or anti-bacterial

agent should be used. If a favorable response does not occur promptly, use of Halobetasol Propionate

Ointment should be discontinued until the infection has been adequately controlled.


Halobetasol Propionate Ointment should not be used in the treatment of rosacea or perioral dermatitis,

and it should not be used on the face, groin,or in the axillae.


Patients using topical corticosteroids should receive the following information and instructions:


1) The medication is to be used as directed by the physician. It is for external use only. Avoid contact

with the eyes.


2) The medication should not be used for any disorder other than that for which it was prescribed.


3) The treated skin area should not be bandaged, otherwise covered or wrapped, so as to be

occlusive unless directed by the physician.


4) Patients should report to their physician any signs of local adverse reactions.


The following tests may be helpful in evaluating patients for HPA axis suppression: ACTH-stimulation

test; A.M. plasma cortisol test; Urinary freecortisol test.

Long-term animal studies have not been performed to evaluate the carcinogenic potential of halobetasol

propionate.

Positive mutagenicity effects were observed in two genotoxicity assays. Halobetasol propionate

was positive in a Chinese hamster micronucleus test, and in a mouse lymphoma gene mutation

assay in vitro.

Studies in the rat following oral administration at dose levels up to 50 μg/kg/day indicated no impairment

of fertility or general reproductive performance.

In other genotoxicity testing, halobetasol propionate was not found to be genotoxic in the

Ames/Salmonella assay, in the sister chromatid exchange test in somatic cells of the Chinese hamster,

in chromosome aberration studies of germinal and somatic cells of rodents, and in a mammalian spot

test to determine point mutations.

Teratogenic effects: Pregnancy Category C: Corticosteroids have been shown to be teratogenic

in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids

have been shown to be teratogenic after dermal application in laboratory animals.


Halobetasol propionate has been shown to be teratogenic in SPF rats and chinchilla-type rabbits

when given systemically during gestation at doses of 0.04 to 0.1 mg/kg in rats and 0.01 mg/kg in

rabbits. These doses are approximately 13, 33 and 3 times, respectively, the human topical dose of

Halobetasol Propionate Ointment. Halobetasol propionate was embryotoxic in rabbits but not in rats.


Cleft palate was observed in both rats and rabbits. Omphalocele was seen in rats, but not in rabbits.


There are no adequate and well-controlled studies of the teratogenic potential of halobetasol propionate

in pregnant women. Halobetasol Propionate Ointment should be used during pregnancy only if

the potential benefit justifies the potential risk to the fetus.

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere

with endogenous corticosteroid production, or cause other untoward effects. It is not known

whether topical administration of corticosteroids could result in sufficient systemic absorption to

produce detectable quantities in human milk. Because many drugs are excreted in human milk,

caution should be exercised when Halobetasol Propionate Ointment is administered to a nursing

woman.

Safety and effectiveness of Halobetasol Propionate Ointment in pediatric patients have not been established

and use in pediatric patients under 12 is not recommended. Because of a higher ratio of skin

surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression

and Cushing’s syndrome when they are treated with topical corticosteroids. They are therefore also at

greater risk of adrenal insufficiency during or after withdrawal of treatment. Adverse effects including

striae have been reported with inappropriate use of topical corticosteroids in infants and children.

HPA axis suppression, Cushing’s syndrome, linear growth retardation, delayed weight gain and

intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations

of adrenal suppression in children include low plasma cortisol levels and an absence of

response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles,

headaches, and bilateral papilledema. Of approximately 850 patients treated with Halobetasol Propionate Ointment in clinical studies,

21% were 61 years and over and 6% were 71 years and over. No overall differences in safety or effectiveness

were observed between these patients and younger patients; and other reported clinical experience

has not identified differences in responses between the elderly and younger patients, but

greater sensitivity of some older individuals cannot be ruled out. In controlled clinical trials, the most frequent adverse events reported for Halobetasol Propionate

Ointment included stinging or burning in 1.6% of the patients. Less frequently reported adverse reactions

were pustulation, erythema, skin atrophy, leukoderma, acne, itching, secondary infection,

telangiectasia, urticaria, dry skin, miliaria, paresthesia, and rash.


The following additional local adverse reactions are reported infrequently with topical corticosteroids,

and they may occur more frequently with high potency corticosteroids, such as Halobetasol

Propionate Ointment. These reactions are listed in an approximate decreasing order of occurrence:

folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic

contact dermatitis, secondary infection, striae and miliaria.

Topically applied Halobetasol Propionate Ointment can be absorbed in sufficient amounts to produce

systemic effects (see PRECAUTIONS).
Apply a thin layer of Halobetasol Propionate Ointment to the affected skin once or twice daily, as

directed by your physician, and rub in gently and completely.


Halobetasol Propionate Ointment is a super-high potency topical corticosteroid; therefore, treatment

should be limited to two weeks, and amounts greater than 50 g/wk should not be used. As with

other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is

seen within 2 weeks, reassessment of diagnosis may be necessary.


Halobetasol Propionate Ointment should not be used with occlusive dressings. Halonate™ is supplied in the following:


(NDC 68712-042-01) one 50 g tube of Halobetasol Propionate Ointment 0.05% packaged with one

4 oz can of ammonium lactate mousse 12%


STORAGE: Store between 15°C and 30°C (59°F and 86°F).


Manufactured by:


G and W Laboratories, Inc.

South Plainfield, NJ  07080



Manufactured for:


JSJ Pharmaceuticals

Charleston, SC  29401

1-800-499-4468

www.jsjpharm.com

HALONATE PAC  halobetasol   ointment

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 68712-042 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength HALOBETASOL PROPIONATE (HALOBETASOL ) HALOBETASOL PROPIONATE 0.5 mg  in 1 g

Inactive Ingredients Ingredient Name Strength ALUMINUM STEARATE   YELLOW WAX   PENTAERYTHRITOL   PETROLATUM   PROPYLENE GLYCOL

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 68712-042-01 50 g In 1 TUBE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA077721	05/01/2010

Labeler - JSJ Pharmaceuticals (615074866)

Establishment
Name	Address	ID/FEI	Operations
G and W Laboratories Inc.		001271188	manufacture

Revised: 07/2010JSJ Pharmaceuticals

More Halobetasol Propionate Ointment resources

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

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Senna-Lax

Pronunciation: SEN-oh-sides
Generic Name: Sennosides
Brand Name: Examples include Senna-Lax and Senokot

Senna-Lax is used for:

Treating constipation.

Senna-Lax is a stimulant laxative. It works by irritating bowel tissues, resulting in bowel movements.

Do NOT use Senna-Lax if:

• you are allergic to any ingredient in Senna-Lax


• you have had recent abdominal surgery or require immediate abdominal surgery


• you have appendicitis; bleeding of the stomach, intestine, or rectum; or an obstruction in your intestines (fecal impaction)

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

Before using Senna-Lax:

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

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


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


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


• if you have congestive heart failure, you are experiencing nausea or vomiting, or you have undiagnosed stomach pain

Some MEDICINES MAY INTERACT with Senna-Lax. However, no specific interactions with Senna-Lax are known at this time.

Ask your health care provider if Senna-Lax may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Senna-Lax:

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

• Take Senna-Lax by mouth with or without food.


• Take Senna-Lax with a full glass of water (8 oz/240 mL). Drink extra fluids while you are taking Senna-Lax, unless instructed differently by your doctor.


• It is best to take Senna-Lax at bedtime.


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

Ask your health care provider any questions you may have about how to use Senna-Lax.

Important safety information:

• A bowel movement usually occurs in 6 to 12 hours.


• Do not use for longer than 1 week without checking with your doctor.


• Using Senna-Lax for a long time may result in loss of normal bowel function.


• Do not take additional laxatives or stool softeners with Senna-Lax unless directed by your doctor.


• If you notice a sudden change in bowel habits that lasts for 2 weeks or more, stop using Senna-Lax and check with your doctor.


• Senna-Lax may discolor the urine pink to red, or yellow to brown.


• Senna-Lax should be used with extreme caution in CHILDREN younger than 6 years old; safety and effectiveness in these children have not been confirmed.


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

Overuse of laxatives can lead to a DEPENDENCE on laxatives to have a bowel movement. In severe overuse cases, some laxatives have caused damage to the intestines and bowel.

Possible side effects of Senna-Lax:

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

Abdominal discomfort or cramping; diarrhea; nausea.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); kidney inflammation; poor bowel function; rectal bleeding.

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

See also: Senna-Lax side effects (in more detail)

If OVERDOSE is suspected:

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

Proper storage of Senna-Lax:

Store Senna-Lax at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Keep Senna-Lax out of the reach of children and away from pets.

General information:

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


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


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


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

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

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Senna-Lax resources

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

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Mintox Plus Chewable Tablets

Pronunciation: a-LOO-min-uhm/mag-NEE-zee-uhm/si-METH-i-kone
Generic Name: Aluminum/Magnesium/Simethicone
Brand Name: Examples include Gelusil and Mintox Plus

Mintox Plus Chewable Tablets are used for:

Treating acid indigestion, heartburn, gas, and sour stomach. It may also be used for other conditions as determined by your doctor.

Mintox Plus Chewable Tablets are an antacid and antiflatulent. It works by neutralizing acid in the stomach. It also causes the gas produced by some foods to remain dissolved, allowing it to be passed through the system more comfortably.

Do NOT use Mintox Plus Chewable Tablets if:

• you are allergic to any ingredient in Mintox Plus Chewable Tablets


• you are also taking citrate salts (found in some calcium supplements, antacids, and laxatives)

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

Before using Mintox Plus Chewable Tablets:

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

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


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


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


• if you have Alzheimer disease, kidney problems, appendicitis, diarrhea, a stomach blockage, or an ileostomy


• if you have recently had stomach bleeding

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

• Cation exchange resins (eg, sodium polystyrene sulfonate) and citrate salts (found in some calcium supplements, antacids, and laxatives) because they may increase the actions and the risk of Mintox Plus Chewable Tablets's side effects


• Anticoagulants (eg, warfarin), quinidine, or sulfonylureas (eg, glyburide) because their actions and the risk of their side effects may be increased by Mintox Plus Chewable Tablets


• Angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril), beta-blockers (eg, propranolol), bisphosphonates (eg, risedronate), cephalosporins (eg, cephalexin), corticosteroids (eg, hydrocortisone), cyclosporine, delavirdine, digoxin, imidazoles (eg, ketoconazole), mycophenolate, penicillamine, quinolones (eg, ciprofloxacin), tetracyclines (eg, doxycycline), or thyroid hormones (eg, levothyroxine) because their effectiveness may be decreased by Mintox Plus Chewable Tablets, especially when taken at the same time as Mintox Plus Chewable Tablets

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

How to use Mintox Plus Chewable Tablets:

Use Mintox Plus Chewable Tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Mintox Plus Chewable Tablets by mouth with or without food.


• Chew thoroughly before swallowing. Drink a glass of water after swallowing.


• Do not use Mintox Plus Chewable Tablets within 2 hours before or after taking a beta-blocker (eg, propranolol), bisphosphonate (eg, risedronate), cephalosporin (eg, cephalexin), corticosteroid (eg, hydrocortisone), delavirdine, digoxin, imidazole (eg, ketoconazole), penicillamine, or sulfonylurea (eg, glyburide) because their effectiveness may be decreased by Mintox Plus Chewable Tablets.


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

Ask your health care provider any questions you may have about how to use Mintox Plus Chewable Tablets.

Important safety information:

• Do NOT take more than the recommended dose or take the maximum dose for longer than 2 weeks without checking with your doctor.


• If your symptoms do not get better within 2 weeks or if they get worse, or if you experience black, tarry stools or vomit that looks like coffee grounds, check with your doctor.


• Mintox Plus Chewable Tablets has aluminum and magnesium in it. Before you begin taking any new prescription or over-the-counter medicine, read the ingredients to see has aluminum or magnesium in it too. If it does or if you are not sure, check with your doctor or pharmacist.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Mintox Plus Chewable Tablets while you are pregnant. If you are or will be breast-feeding while you use Mintox Plus Chewable Tablets, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Mintox Plus Chewable Tablets:

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

Constipation; diarrhea.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); loss of appetite; muscle weakness; nausea; slow reflexes; vomiting.

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

See also: Mintox Plus side effects (in more detail)

If OVERDOSE is suspected:

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

Proper storage of Mintox Plus Chewable Tablets:

Store Mintox Plus Chewable Tablets between 59 and 86 degrees F (15 and 30 degrees C). Store in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Mintox Plus Chewable Tablets out of the reach of children and away from pets.

General information:

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


• Mintox Plus Chewable Tablets are to be used only by the patient for whom it is prescribed. Do not share it with other people.


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


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

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

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Mintox Plus resources

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

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Tobi 300 mg / 5 ml Nebuliser Solution (Novartis Pharmaceuticals UK Ltd)

1. Name Of The Medicinal Product

TOBI^®

300 mg/5 mL Nebuliser Solution

2. Qualitative And Quantitative Composition

One ampoule of 5mL contains tobramycin 300mg as a single dose.

For excipients, see 6.1.

3. Pharmaceutical Form

Nebuliser solution.

Clear, slightly yellow solution.

4. Clinical Particulars

4.1 Therapeutic Indications

Long-term management of chronic pulmonary infection due to Pseudomonas aeruginosa in cystic fibrosis (CF) patients aged 6 years and older.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology And Method Of Administration

TOBI® is supplied for use via inhalation and is not for parenteral use.

Posology

The recommended dose for adults and children is one ampoule twice daily for 28 days. The dose interval should be as close as possible to 12 hours and not less than 6 hours. After 28 days of therapy, patients should stop TOBI therapy for the next 28 days. A cycle of 28 days of active therapy and 28 days of rest from treatment should be maintained.

Dosage is not adjusted for weight. All patients should receive one ampoule of TOBI (300 mg of tobramycin) twice daily.

Controlled clinical studies, conducted for a period of 6 months using the following TOBI dosage regimen, have shown that improvement in lung function was maintained above baseline during the 28 day rest periods.

TOBI Dosing Regimen in Controlled Clinical Studies

Cycle 1	Cycle 2	Cycle 3
28 Days	28 Days	28 Days	28 Days	28 Days	28 Days
TOBI 300 mg twice daily plus standard care	standard care	TOBI 300 mg twice daily plus standard care	standard care	TOBI 300 mg twice daily plus standard care	standard care

Safety and efficacy have been assessed in controlled and open label studies for up to 96 weeks (12 cycles), but have not been studied in patients under the age of 6 years, patients with forced expiratory volume in 1 second (FEV₁) <25% or>75% predicted, or patients colonised with Burkholderia cepacia.

Therapy should be initiated by a physician experienced in the management of cystic fibrosis. Treatment with TOBI should be continued on a cyclical basis for as long as the physician considers the patient is gaining clinical benefit from the inclusion of TOBI in their treatment regimen. If clinical deterioration of pulmonary status is evident, additional anti-pseudomonal therapy should be considered. Clinical studies have shown that a microbiological report indicating in vitro drug resistance does not necessarily preclude a clinical benefit for the patient.

Method of administration

The contents of one ampoule should be emptied into the nebuliser and administered by inhalation over approximately a 15-minute period using a hand-held PARI LC PLUS reusable nebuliser with a suitable compressor. Suitable compressors are those which, when attached to a PARI LC Plus nebuliser, deliver a flow rate of 4-6 L/min and/or a back pressure of 110-217 kPa. The manufacturers' instructions for the care and use of the nebuliser and compressor should be followed.

TOBI is inhaled whilst the patient is sitting or standing upright and breathing normally through the mouthpiece of the nebuliser. Nose clips may help the patient breathe through the mouth. The patient should continue their standard regimen of chest physiotherapy. The use of appropriate bronchodilators should continue as thought clinically necessary. Where patients are receiving several different respiratory therapies it is recommended that they are taken in the following order: bronchodilator, chest physiotherapy, other inhaled medicinal products, and finally TOBI.

Maximum tolerated daily dose

The maximum tolerated daily dose of TOBI has not been established.

4.3 Contraindications

Administration of TOBI is contraindicated in any patient with known hypersensitivity to any aminoglycoside or any of the excipients (section 6.1).

4.4 Special Warnings And Precautions For Use

General Warnings

For information on pregnancy and lactation see 4.6.

TOBI should be used with caution in patients with known or suspected renal, auditory, vestibular or neuromuscular dysfunction, or with severe, active haemoptysis.

The Serum concentration of tobramycin should only be monitored through venipuncture and not finger prick blood sampling, which is a non validated dosing method. It has been observed that contamination of the skin of the fingers from the preparation and nebulisation of TOBI may lead to falsely increased serum levels of the drug. This contamination cannot be completely avoided by hand washing before testing.

Bronchospasm

Bronchospasm can occur with inhalation of medicinal products and has been reported with nebulised tobramycin. The first dose of TOBI should be given under supervision, using a pre-nebulisation bronchodilator if this is part of the current regimen for the patient. FEV₁ should be measured before and after nebulisation. If there is evidence of therapy-induced bronchospasm in a patient not receiving a bronchodilator the test should be repeated, on a separate occasion, using a bronchodilator. Evidence of bronchospasm in the presence of bronchodilator therapy may indicate an allergic response. If an allergic response is suspected TOBI should be discontinued. Bronchospasm should be treated as medically appropriate.

Neuromuscular disorders

TOBI should be used with great caution in patients with neuromuscular disorders such as parkinsonism or other conditions characterised by myasthenia, including myasthenia gravis, as aminoglycosides may aggravate muscle weakness due to a potential curare-like effect on neuromuscular function.

Nephrotoxicity

Although nephrotoxicity has been associated with parenteral aminoglycoside therapy, there was no evidence of nephrotoxicity during clinical trials with TOBI.

The product should be used with caution in patients with known or suspected renal dysfunction and serum concentrations of tobramycin should be monitored. Patients with severe renal impairment, i.e., serum creatinine>2 mg/dL (176.8 μmol/L), were not included in the clinical studies.

Current clinical practice suggests baseline renal function should be assessed. Urea and creatinine levels should be reassessed after every 6 complete cycles of TOBI therapy (180 days of nebulised aminoglycoside therapy). If there is evidence of nephrotoxicity, all tobramycin therapy should be discontinued until trough serum concentrations fall below 2 μg/mL. TOBI therapy may then be resumed at the physician's discretion. Patients receiving concomitant parenteral aminoglycoside therapy should be monitored as clinically appropriate taking into account the risk of cumulative toxicity.

Ototoxicity

Ototoxicity, manifested as both auditory and vestibular toxicity, has been reported with parenteral aminoglycosides. Vestibular toxicity may be manifested by vertigo, ataxia or dizziness. Auditory toxicity, as measured by complaints of hearing loss or by audiometric evaluations, did not occur with TOBI therapy during controlled clinical studies. In open label studies and post-marketing experience, some patients with a history of prolonged previous or concomitant use of intravenous aminoglycosides have experienced hearing loss. Physicians should consider the potential for aminoglycosides to cause vestibular and cochlear toxicity and carry out appropriate assessments of auditory function during TOBI therapy. In patients with a predisposing risk due to previous prolonged, systemic aminoglycoside therapy it may be necessary to consider audiological assessment before initiating TOBI therapy. The onset of tinnitus warrants caution as it is a sentinel symptom of ototoxicity. If a patient reports tinnitus or hearing loss during aminoglycoside therapy the physician should consider referring them for audiological assessment. Patients receiving concomitant parenteral aminoglycoside therapy should be monitored as clinically appropriate taking into account the risk of cumulative toxicity.

Haemoptysis

Inhalation of nebulised solutions may induce a cough reflex. The use of TOBI in patients with active, severe haemoptysis should be undertaken only if the benefits of treatment are considered to outweigh the risks of inducing further haemorrhage.

Microbial Resistance

In clinical studies, some patients on TOBI therapy showed an increase in aminoglycoside Minimum Inhibitory Concentrations for P. aeruginosa isolates tested. There is a theoretical risk that patients being treated with nebulised tobramycin may develop P. aeruginosa isolates resistant to intravenous tobramycin (see 5.1).

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

In clinical studies, patients taking TOBI concomitantly with dornase alfa, β-agonists, inhaled corticosteroids, and other oral or parenteral anti-pseudomonal antibiotics, demonstrated adverse experience profiles which were similar to those of the control group.

Concurrent and/or sequential use of TOBI with other medicinal products with nephrotoxic or ototoxic potential should be avoided. Some diuretics can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue. TOBI should not be administered concomitantly with furosemide, urea or mannitol.

Other medicinal products that have been reported to increase the potential toxicity of parenterally administered aminoglycosides include:

Amphotericin B, cefalotin, ciclosporin, tacrolimus, polymyxins (risk of increased nephrotoxicity);

Platinum compounds (risk of increased nephrotoxicity and ototoxicity);

Anticholinesterases, botulinum toxin (neuromuscular effects).

4.6 Pregnancy And Lactation

TOBI should not be used during pregnancy or lactation unless the benefits to the mother outweigh the risks to the foetus or baby.

Pregnancy

There are no adequate data from the use of tobramycin administered by inhalation in pregnant women. Animal studies do not indicate a teratogenic effect of tobramycin (see 5.3 Preclinical data). However, aminoglycosides can cause foetal harm (e.g., congenital deafness) when high systemic concentrations are achieved in a pregnant woman. If TOBI is used during pregnancy, or if the patient becomes pregnant while taking TOBI, she should be informed of the potential hazard to the foetus.

Lactation

Systemic tobramycin is excreted in breast milk. It is not known if administration of TOBI will result in serum concentrations high enough for tobramycin to be detected in breast milk. Because of the potential for ototoxicity and nephrotoxicity with tobramycin in infants, a decision should be made whether to terminate nursing or discontinue TOBI therapy

4.7 Effects On Ability To Drive And Use Machines

On the basis of reported adverse drug reactions, TOBI is presumed to be unlikely to produce an effect on the ability to drive and use machinery.

4.8 Undesirable Effects

In controlled clinical trials, dysphonia and tinnitus were the only undesirable effects reported in significantly more patients treated with TOBI; (13% TOBI vs 7% control) and (3% TOBI vs 0% control) respectively. These episodes of tinnitus were transient and resolved without discontinuation of TOBI therapy, and were not associated with permanent loss of hearing on audiogram testing. The risk of tinnitus did not increase with repeated cycles of exposure to TOBI.

Additional undesirable effects, some of which are common sequelae of the underlying disease, but where a causal relationship to TOBI could not be excluded were: sputum discoloured, respiratory tract infection, myalgia, nasal polyps and otitis media.

In the POSTMARKETING phase, undesirable effects have been reported at the following frequencies:
Infections and infestations
Rare:	Laryngitis
Very Rare:	Oral candidiasis, fungal infection
Blood and lymphatic system disorders
Very Rare:	Lymphadenopathy
Immune system disorders
Very Rare:	Hypersensitivity
Metabolism and nutrition disorders
Rare:	Anorexia
Nervous system disorders
Rare:	Headache, dizziness, aphonia
Very Rare:	Somnolence
Ear and labyrinth disorders
Rare:	Tinnitus, hearing loss
Very Rare:	Ear disorder, ear pain
Respiratory, thoracic and mediastinal disorders
Uncommon:	Dysphonia, dyspnoea, cough, pharyngitis
Rare:	Bronchospasm, chest discomfort, lung disorder, productive cough, haemoptysis, epistaxis, rhinitis, asthma
Very Rare:	Hyperventilation, hypoxia, sinusitis
Gastrointestinal disorders
Rare:	Dysgeusia, nausea, mouth ulceration, vomiting
Very Rare:	Diarrhoea, abdominal pain
Skin and subcutaneous tissue disorders
Rare:	Rash
Very Rare:	Urticaria, pruritus
Musculoskeletal, connective tissue and bone disorders
Very Rare:	Back pain
General disorders and administration site conditions
Rare:	Asthenia, pyrexia, chest pain, pain
Very Rare:	Malaise
Investigations
Rare:	Pulmonary function test decreased

In open label studies and post-marketing experience, some patients with a history of prolonged previous or concomitant use of intravenous aminoglycosides have experienced hearing loss (see 4.4). Parenteral aminoglycosides have been associated with hypersensitivity, ototoxicity and nephrotoxicity (see 4.3, 4.4).

4.9 Overdose

Administration by inhalation results in low systemic bioavailability of tobramycin. Symptoms of aerosol overdose may include severe hoarseness.

In the event of accidental ingestion of TOBI , toxicity is unlikely as tobramycin is poorly absorbed from an intact gastrointestinal tract.

In the event of inadvertent administration of TOBI by the intravenous route, signs and symptoms of parenteral tobramycin overdose may occur that include dizziness, tinnitus, vertigo, loss of hearing acuity, respiratory distress and/or neuromuscular blockade and renal impairment.

Acute toxicity should be treated with immediate withdrawal of TOBI, and baseline tests of renal function should be undertaken. Tobramycin serum concentrations may be helpful in monitoring overdose. In the case of any overdosage, the possibility of drug interactions with alterations in the elimination of TOBI or other medicinal products should be considered.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group (ATC code)

Aminoglycoside Antibacterials J01GB01

General properties

Tobramycin is an aminoglycoside antibiotic produced by Streptomyces tenebrarius. It acts primarily by disrupting protein synthesis leading to altered cell membrane permeability, progressive disruption of the cell envelope and eventual cell death. It is bactericidal at concentrations equal to or slightly greater than inhibitory concentrations.

Breakpoints

Established susceptibility breakpoints for parenteral administration of tobramycin are inappropriate in the aerosolised administration of the medicinal product. Cystic fibrosis (CF) sputum exhibits an inhibitory action on the local biological activity of nebulised aminoglycosides. This necessitates sputum concentrations of aerosolised tobramycin to be some ten and twenty–five fold above the Minimum Inhibitory Concentration (MIC) for, respectively, P. aeruginosa growth suppression and bactericidal activity. In controlled clinical trials, 97% of patients receiving TOBI achieved sputum concentrations 10 fold the highest P. aeruginosa MIC cultured from the patient, and 95% of patients receiving TOBI achieved 25 fold the highest MIC. Clinical benefit is still achieved in a majority of patients who culture strains with MIC values above the parenteral breakpoint.

Susceptibility

In the absence of conventional susceptibility breakpoints for the nebulised route of administration, caution must be exercised in defining organisms as susceptible or insusceptible to nebulised tobramycin.

In clinical studies with TOBI, most patients with P. aeruginosa isolates with tobramycin MICs <128 µg/mL at baseline showed improved lung function following treatment with TOBI. Patients with a P. aeruginosa isolate with a MIC

Based upon in vitro data and/or clinical trial experience, the organisms associated with pulmonary infections in CF may be expected to respond to TOBI therapy as follows:

Susceptible	Pseudomonas aeruginosa Haemophilus influenzae Staphylococcus aureus
Insusceptible	Burkholderia cepacia Stenotrophomonas maltophilia Alcaligenes xylosoxidans

Treatment with the TOBI regimen in clinical studies showed a small but clear increase in tobramycin, amikacin and gentamicin Minimum Inhibitory Concentrations for P. aeruginosa isolates tested. Each additional 6 months of treatment resulted in incremental increases similar in magnitude to that observed in the 6 months of controlled studies. The most prevalent aminoglycoside resistance mechanism seen in P. aeruginosa isolated from chronically infected CF patients is impermeability, defined by a general lack of susceptibility to all aminoglycosides. P. aeruginosa isolated from CF patients has also been shown to exhibit adaptive aminoglycoside resistance that is characterised by a reversion to susceptibility when the antibiotic is removed.

Other Information

There is no evidence that patients treated with up to 18 months of TOBI were at a greater risk for acquiring B. cepacia, S. maltophilia or A. xylosoxidans, than would be expected in patients not treated with TOBI. Aspergillus species were more frequently recovered from the sputum of patients who received TOBI; however, clinical sequelae such as Allergic Bronchopulmonary Aspergillosis (ABPA) were reported rarely and with similar frequency as in the control group.

5.2 Pharmacokinetic Properties

Absorption and distribution

Sputum concentrations: Ten minutes after inhalation of the first 300 mg dose of TOBI, the average sputum concentration of tobramycin was 1,237 μg/g (range: 35 to 7,414 μg/g). Tobramycin does not accumulate in sputum; after 20 weeks of therapy with the TOBI regimen, the average sputum concentration of tobramycin 10 minutes after inhalation was 1,154 μg/g (range: 39 to 8,085 μg/g). High variability of sputum tobramycin concentrations was observed. Two hours after inhalation, sputum concentrations declined to approximately 14% of tobramycin levels measured at 10 minutes after inhalation.

Serum concentrations: The median serum concentration of tobramycin 1 hour after inhalation of a single 300 mg dose of TOBI by CF patients was 0.95 μg/mL (range: below limit of quantitation [BLQ] – 3.62μg/mL). After 20 weeks of therapy on the TOBI regimen, the median serum tobramycin concentration 1 hour after dosing was 1.05 μg/mL (range: BLQ- 3.41μg/mL).

Elimination

The elimination of tobramycin administered by the inhalation route has not been studied.

Following intravenous administration, systemically absorbed tobramycin is eliminated principally by glomerular filtration. The elimination half-life of tobramycin from serum is approximately 2 hours. Less than 10% of tobramycin is bound to plasma proteins.

Unabsorbed tobramycin following TOBI administration is probably eliminated primarily in expectorated sputum.

5.3 Preclinical Safety Data

Preclinical data reveal that the main hazard for humans, based on studies of safety pharmacology, repeated dose toxicity, genotoxicity, or toxicity to reproduction, consists of renal toxicity and ototoxicity. In repeated dose toxicity studies, target organs of toxicity are the kidneys and vestibular/cochlear functions. In general, toxicity is seen at higher systemic tobramycin levels than are achievable by inhalation at the recommended clinical dose.

No reproduction toxicology studies have been conducted with tobramycin administered by inhalation, but subcutaneous administration at doses of 100 mg/kg/day in rats and the maximum tolerated dose of 20 mg/kg/day in rabbits, during organogenesis, was not teratogenic. Teratogenicity could not be assessed at higher parenteral doses in rabbits as they induced maternal toxicity and abortion. Based on available data from animals a risk of toxicity (e.g. ototoxicity) at prenatal exposure levels cannot be excluded.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sodium chloride

Water for injections

Sulphuric acid and sodium hydroxide for pH adjustment

6.2 Incompatibilities

In the absence of compatibilities studies, this medicinal product must not be mixed with any other medicinal product in the nebuliser.

6.3 Shelf Life

3 years.

For single use. The contents of the whole ampoule should be used immediately after opening (see section 6.6). Discard any remaining contents.

6.4 Special Precautions For Storage

Store at 2-8°C. Store in the original package in order to protect from light.

After removal from the refrigerator, or if refrigeration is unavailable, TOBI pouches (intact or opened) may be stored at up to 25°C for up to 28 days.

TOBI solution is normally slightly yellow, but some variability in colour may be observed, which does not indicate loss of activity if the product has been stored as recommended.

6.5 Nature And Contents Of Container

TOBI is supplied in 5 mL single-use low density polyethylene ampoules. One outer carton contains a total of 56, 112 or 168 ampoules comprising 4, 8 or 12 sealed foil pouches, respectively. Each foil pouch contains 14 ampoules packed in a plastic tray.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

TOBI is a sterile, non-pyrogenic, aqueous preparation for single use only. As it is preservative-free, the contents of the whole ampoule should be used immediately after opening and any unused solution discarded. Opened ampoules should never be stored for re-use.

7. Marketing Authorisation Holder

Novartis Pharmaceuticals UK Limited

Frimley Business Park

Frimley

Camberley

Surrey

GU167SR

8. Marketing Authorisation Number(S)

PL 00101/0935

9. Date Of First Authorisation/Renewal Of The Authorisation

18 September 2006 / 09 December 2009

10. Date Of Revision Of The Text

23 September 2010

LEGAL CATEGORY

POM

alprazolam

al-PRA-zoe-lam

Commonly used brand name(s)

In the U.S.

• Gabazolamine-0.5


• Niravam


• Xanax


• Xanax XR

In Canada

• Alti-Alprazolam

Available Dosage Forms:

• Tablet


• Tablet, Disintegrating


• Solution


• Tablet, Extended Release

Therapeutic Class: Antianxiety

Pharmacologic Class: Benzodiazepine, Short or Intermediate Acting

Uses For alprazolam

Alprazolam is used to relieve symptoms of anxiety, including anxiety caused by depression. It is also used to treat panic disorder in some patients.

Alprazolam is a benzodiazepine. Benzodiazepines belong to the group of medicines called central nervous system (CNS) depressants, which are medicines that slow down the nervous system.

alprazolam is available only with your doctor's prescription.

Before Using alprazolam

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 alprazolam, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to alprazolam 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 alprazolam 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 alprazolam in the elderly. However, severe drowsiness, dizziness, confusion, clumsiness, or unsteadiness are more likely to occur in the elderly, who are usually more sensitive than younger adults to the effects of alprazolam. Elderly patients may require a lower dose to help reduce unwanted effects.

Pregnancy

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

Breast Feeding

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

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 alprazolam, 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 alprazolam 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.

• Delavirdine


• Indinavir


• Itraconazole


• Ketoconazole

Using alprazolam 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.

• Alfentanil


• Amobarbital


• Anileridine


• Aprobarbital


• Boceprevir


• Butabarbital


• Butalbital


• Carisoprodol


• Chloral Hydrate


• Chlorzoxazone


• Codeine


• Dantrolene


• Digoxin


• Ethchlorvynol


• Fentanyl


• Fluconazole


• Fospropofol


• Hydrocodone


• Hydromorphone


• Levorphanol


• Meperidine


• Mephenesin


• Mephobarbital


• Meprobamate


• Metaxalone


• Methocarbamol


• Methohexital


• Morphine


• Morphine Sulfate Liposome


• Oxycodone


• Oxymorphone


• Pentobarbital


• Phenobarbital


• Primidone


• Propoxyphene


• Remifentanil


• Secobarbital


• Sodium Oxybate


• Sufentanil


• Tapentadol


• Thiopental


• Voriconazole


• Zolpidem

Using alprazolam 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.

• Amprenavir


• Aprepitant


• Carbamazepine


• Cimetidine


• Clarithromycin


• Desipramine


• Desogestrel


• Dienogest


• Drospirenone


• Erythromycin


• Estradiol Cypionate


• Estradiol Valerate


• Ethinyl Estradiol


• Ethynodiol Diacetate


• Etonogestrel


• Fluoxetine


• Fosaprepitant


• Imipramine


• Kava


• Levonorgestrel


• Medroxyprogesterone Acetate


• Mestranol


• Nefazodone


• Norelgestromin


• Norethindrone


• Norgestimate


• Norgestrel


• Rifapentine


• Ritonavir


• Roxithromycin


• Sertraline


• St John's Wort


• Telaprevir


• Theophylline


• Troleandomycin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

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

• Depression or


• Epilepsy or history of seizures or


• Lung disease—Use with caution. May make these conditions worse.

• Glaucoma, acute narrow angle—Should not be used in patients with this condition.

• Kidney disease or


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

Proper Use of alprazolam

Take alprazolam only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

Swallow the extended-release tablet whole with a full glass of water. Do not break, crush, or chew it.

If you are using the orally disintegrating tablet, make sure your hands are dry before you handle the tablet. Do not remove the tablets from the bottle until you are ready to take it. Place the tablet immediately on the top of your tongue. It should melt quickly and be swallowed with saliva.

If you are using the oral solution, measure the oral liquid with a marked measuring spoon, oral syringe, or medicine cup.

Dosing

The dose of alprazolam 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 alprazolam. 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 anxiety:
  
  • For oral dosage forms (solution, tablets, or orally disintegrating tablets):
    
    • Adults—At first, 0.25 to 0.5 milligram (mg) three times a day. Your doctor may increase your dose if needed. However, the dose is usually not more than 4 mg a day.
    
    
    • Older adults—At first, 0.25 milligram (mg) two or three times a day. Your doctor may increase your dose if needed.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  


• For panic disorder:
  
  • For oral dosage form (extended-release tablets):
    
    • Adults—At first, 0.5 to 1 milligram (mg) taken in the morning once a day. Your doctor may increase your dose if needed. However, the dose is usually not more than 10 mg a day.
    
    
    • Older adults—At first, 0.5 milligram (mg) taken in the morning once a day. Your doctor may increase your dose if needed.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For oral dosage forms (solution, tablets, or orally disintegrating tablets):
    
    • Adults—At first, 0.5 milligram (mg) three times a day. Your doctor may increase your dose if needed. However, the dose is usually not more than 10 mg a day.
    
    
    • Older adults—At first, 0.25 milligram (mg) two or three times a day. Your doctor may increase your dose if needed.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of alprazolam, 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.

It is very important to protect the orally disintegrating tablets from moisture. Remove and throw away any cotton packaging from the medicine bottle when you first use the medicine.

Precautions While Using alprazolam

It is very important that your doctor check your progress at regular visits to make sure alprazolam is working properly. Blood tests may be needed to check for any unwanted effects.

Using alprazolam while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

Do not take itraconazole (Sporanox®) or ketoconazole (Nizoral®) while you are using alprazolam. Using any of them together with alprazolam may increase the chance of serious side effects.

If you develop any unusual and strange thoughts or behavior while you are taking alprazolam, be sure to discuss it with your doctor. Some changes that have occurred in people taking alprazolam are like those seen in people who drink alcohol and then act in a manner that is not normal. Other changes may be more unusual and extreme, such as confusion, worsening of depression, hallucinations (seeing, hearing, or feeling things that are not there), suicidal thoughts, and unusual excitement, nervousness, or irritability.

Alprazolam may cause some people, especially older persons, to become drowsy, dizzy or less alert than they are normally. Make sure you know how you react to alprazolam before you drive, use machines, or do anything else that could be dangerous if you are dizzy, or are not alert or able to see well.

Do not stop taking alprazolam without checking with your doctor first. Your doctor may want you to gradually reduce the amount you are using before stopping it completely. This may help prevent a worsening of your condition and reduce the possibility of withdrawal symptoms, such as convulsions (seizures), stomach or muscle cramps, sweating, tremors, vomiting, or unusual behavior.

alprazolam will add to the effects of alcohol and other central nervous system (CNS) depressants. CNS depressants are medicines that slow down the nervous system, which may cause drowsiness or make you less alert. Some examples of CNS depressants are antihistamines or medicine for hay fever, allergies, or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; barbiturates (used for seizures); muscle relaxants; or anesthetics (numbing medicines), including some dental anesthetics. This effect may last for a few days after you stop taking alprazolam. Check with your doctor before taking any of the above while you are using alprazolam.

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.

alprazolam 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

• Being forgetful


• changes in patterns and rhythms of speech


• clumsiness or unsteadiness


• difficulty with coordination


• discouragement


• drowsiness


• feeling sad or empty


• irritability


• lack of appetite


• lightheadedness


• loss of interest or pleasure


• relaxed and calm


• shakiness and unsteady walk


• sleepiness or unusual drowsiness


• slurred speech


• tiredness


• trouble concentrating


• trouble in speaking


• trouble performing routine tasks


• trouble sleeping


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


• unusual tiredness or weakness

Less common

• Abdominal or stomach pain


• blurred vision


• body aches or pain


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


• changes in behavior


• chills


• clay-colored stools


• confusion about identity, place, and time


• cough


• dark urine


• decrease in frequency of urination


• decrease in urine volume


• diarrhea


• difficult or labored breathing


• difficulty in moving


• difficulty in passing urine (dribbling)


• difficulty with concentration


• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly


• dry mouth


• ear congestion


• environment seems unreal


• fainting


• fear or nervousness


• feeling of unreality


• feeling warm


• fever


• general feeling of discomfort or illness


• headache


• hyperventilation


• inability to move eyes


• inability to sit still


• increased blinking or spasms of the eyelid


• irregular heartbeats


• itching


• joint pain


• lack or loss of self-control


• loss of bladder control


• loss of coordination


• loss of memory


• loss of voice


• mood or mental changes


• muscle aching or cramping


• muscle pain or stiffness


• muscle weakness


• nasal congestion


• nausea


• need to keep moving


• painful urination


• problems with memory


• rash


• restlessness


• runny nose


• seeing, hearing, or feeling things that are not there


• seizures


• sense of detachment from self or body


• shaking


• shivering


• shortness of breath


• sneezing


• sore throat


• sticking out of the tongue


• sweating


• swollen joints


• talkativeness


• tightness in the chest


• trouble in breathing, speaking, or swallowing


• trouble with balance


• twitching, twisting, or uncontrolled repetitive movements of the tongue, lips, face, arms, or legs


• uncontrolled twisting movements of the neck, trunk, arms, or legs


• unpleasant breath odor


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


• unusual facial expressions


• unusually deep sleep


• unusually long duration of sleep


• vomiting of blood


• wheezing


• yellow eyes or skin

Rare

• Actions that are out of control


• attack, assault, or force


• chest pain


• continuing ringing or buzzing or other unexplained noise in ears


• decreased awareness or responsiveness


• deep or fast breathing with dizziness


• ear pain


• false or unusual sense of well-being


• fast, irregular, pounding, or racing heartbeat or pulse


• feeling jittery


• feeling unusually cold


• generalized slowing of mental and physical activity


• hearing loss


• hoarseness


• lack of feeling or emotion


• loss of control of the legs


• loss of strength or energy


• nightmares


• numbness of the feet, hands, and around mouth


• severe sleepiness


• shakiness in the legs, arms, hands, or feet


• sleep talking


• sleeplessness


• swelling


• talking, feeling, and acting with excitement


• thoughts of killing oneself


• unable to sleep


• uncaring


• unusual weak feeling


• voice changes

Incidence not known

• General tiredness and weakness


• light-colored stools


• stomach pain, continuing


• upper right abdominal pain

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

More common

• Absent, missed, or irregular menstrual periods


• decreased appetite


• decreased interest in sexual intercourse


• decreased sexual performance or desire abnormal ejaculation


• difficulty having a bowel movement (stool)


• inability to have or keep an erection


• increased appetite


• increased in sexual ability, desire, drive, or performance


• increased interest in sexual intercourse


• increased weight


• loss in sexual ability, desire, drive, or performance


• stopping of menstrual bleeding


• watering of mouth


• weight loss

Less common

• Abdominal bloating and cramping


• blistering, crusting, irritation, itching, or reddening of the skin


• change in taste bad unusual or unpleasant (after) taste


• cracked, dry, or scaly skin


• cramps


• double vision


• feeling of warmth


• heavy bleeding


• menstrual changes


• pain


• pelvic pain


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


• seeing double


• sudden sweating


• unexplained runny nose or sneezing

Rare

• Acid or sour stomach


• belching


• bigger, dilated, or enlarged pupils (black part of eye)


• change in color vision


• difficulty seeing at night


• feeling of constant movement of self or surroundings


• feeling of relaxation


• heartburn


• hives or welts


• increased sensitivity of eyes to sunlight


• indigestion


• redness of skin


• runny nose


• sensation of spinning


• stomach discomfort, upset, or pain


• stuffy nose

Incidence not known

• Blistering, peeling, or loosening of the skin


• red, irritated eyes


• red skin lesions, often with a purple center


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


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


• unexpected or excess milk flow from breasts

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: alprazolam side effects (in more detail)

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