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Tuesday, 21 August 2012

Tylenol with Codeine

acetaminophen and codeine phosphate

Dosage Form: tablets
TYLENOL®

with Codeine

CIII

(acetaminophen and codeine phosphate) tablets

HEPATOTOXICITY

Tylenol with Codeine Description

TYLENOL® with Codeine is supplied in tablet form for oral administration.

Acetaminophen, 4'-hydroxyacetanilide, a slightly bitter, white, odorless, crystalline powder, is a non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula:

C8 H9 NO2 M.W. 151.16

Codeine phosphate, 7,8-didehydro-4, 5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol phosphate (1:1) (salt) hemihydrate, a white crystalline powder, is a narcotic analgesic and antitussive. It has the following structural formula:

C18H21NO3•H3PO4•1/2 H2O M.W. 406.37

Each tablet contains:

Acetaminophen	300 mg
No. 3 Codeine Phosphate	30 mg
(Warning: May be habit forming)

Acetaminophen	300 mg
No. 4 Codeine Phosphate	60 mg
(Warning: May be habit forming)

In addition, each tablet contains the following inactive ingredients:

TYLENOL® with Codeine No. 3 contains powdered cellulose, magnesium stearate, sodium metabisulfite1, pregelatinized starch (corn), and modified starch (corn).

TYLENOL® with Codeine No. 4 contains powdered cellulose, magnesium stearate, sodium metabisulfite1, pregelatinized starch (corn), and corn starch.

1: See WARNINGS

Tylenol with Codeine - Clinical Pharmacology

This product combines the analgesic effects of a centrally acting analgesic, codeine, with a peripherally acting analgesic, acetaminophen.

Pharmacokinetics

The behavior of the individual components is described below.

Codeine

Codeine is rapidly absorbed from the gastrointestinal tract. It is rapidly distributed from the intravascular spaces to the various body tissues, with preferential uptake by parenchymatous organs such as the liver, spleen, and kidney. Codeine crosses the blood-brain barrier and is found in fetal tissue and breast milk. The plasma concentration does not correlate with brain concentration or relief of pain; however, codeine is not bound to plasma proteins and does not accumulate in body tissues.

The plasma half-life is about 2.9 hours. The elimination of codeine is primarily via the kidneys, and about 90% of an oral dose is excreted by the kidneys within 24 hours of dosing. The urinary secretion products consist of free and glucuronide conjugated codeine (about 70%), free and conjugated norcodeine (about 10%), free and conjugated morphine (about 10%), normorphine (4%), and hydrocodone (1%). The remainder of the dose is excreted in the feces.

At therapeutic doses, the analgesic effect reaches a peak within 2 hours and persists between 4 and 6 hours.

Acetaminophen

Acetaminophen is rapidly absorbed from the gastrointestinal tract and is distributed throughout most body tissues. The plasma half-life is 1.25 to 3 hours, but may be increased by liver damage and following overdosage. Elimination of acetaminophen is principally by liver metabolism (conjugation) and subsequent renal excretion of metabolites. Approximately 85% of an oral dose appears in the urine within 24 hours of administration, most as the glucuronide conjugate, with small amounts of other conjugates and unchanged drug.

Indications and Usage for Tylenol with Codeine

TYLENOL® with Codeine (acetaminophen and codeine phosphate) Tablets are indicated for the relief of mild to moderately severe pain.

Contraindications

This product should not be administered to patients who have previously exhibited hypersensitivity to codeine or acetaminophen.

Warnings

Hepatotoxicity

Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involve more than one acetaminophen-containing product. The excessive intake of acetaminophen may be intentional to cause self-harm or unintentional as patients attempt to obtain more pain relief or unknowingly take other acetaminophen-containing products (see Boxed Warning).

The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen.

Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen. Instruct patients to seek medical attention immediately upon ingestion of more than 4,000 milligrams of acetaminophen per day, even if they feel well.

Hypersensitivity/Anaphylaxis

There have been post-marketing reports of hypersensitivity and anaphylaxis associated with the use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and vomiting. There were infrequent reports of life-threatening anaphylaxis requiring emergency medical attention. Instruct patients to discontinue TYLENOL® with Codeine immediately and seek medical care if they experience these symptoms. Do not prescribe TYLENOL® with Codeine for patients with acetaminophen allergy.

Head Injuries

In the presence of head injury or other intracranial lesions, the respiratory-depressant effects of codeine and other narcotics may be markedly enhanced, as well as their capacity for elevating cerebrospinal fluid pressure. Narcotics also produce other CNS-depressant effects, such as drowsiness, that may further obscure the clinical course of the patients with head injuries.

Acute Abdominal Conditions

Codeine or other narcotics may obscure signs on which to judge the diagnosis or clinical course of patients with acute abdominal conditions.

Abuse Potential

Codeine is habit forming and potentially abusable. Consequently, the extended use of this product is not recommended.

Sulfite Sensitivity

TYLENOL® with Codeine (acetaminophen and codeine phosphate) Tablets contain sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

Precautions

General

TYLENOL® with Codeine (acetaminophen and codeine phosphate) Tablets should be prescribed with caution in certain special-risk patients, such as the elderly or debilitated, and those with severe impairment of renal or hepatic function, head injuries, elevated intracranial pressure, acute abdominal conditions, hypothyroidism, urethral stricture, Addison's disease, or prostatic hypertrophy.

Ultra-Rapid Metabolizers of Codeine

Some individuals may be ultra-rapid metabolizers due to a specific CYP2D6*2×2 genotype. These individuals convert codeine into its active metabolite, morphine, more rapidly and completely than other people. This rapid conversion results in higher than expected serum morphine levels. Even at labeled dosage regimens, individuals who are ultra-rapid metabolizers may experience overdose symptoms such as extreme sleepiness, confusion, or shallow breathing.

The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.5% to 1% in Chinese and Japanese, 0.5% to 1% in Hispanics, 1% to 10% in Caucasians, 3% in African Americans, and 16% to 28% in North Africans, Ethiopians, and Arabs. Data are not available for other ethnic groups.

When physicians prescribe codeine-containing drugs, they should choose the lowest effective dose for the shortest period of time and inform their patients about these risks and the signs of morphine overdose (see PRECAUTIONS – Nursing Mothers).

Information for Patients/Caregivers

Do not take TYLENOL® with Codeine if you are allergic to any of its ingredients.

If you develop signs of allergy such as a rash or difficulty breathing, stop taking TYLENOL® with Codeine and contact your healthcare provider immediately.

Do not take more than 4,000 milligrams of acetaminophen per day. Call your healthcare provider if you took more than the recommended dose.

Codeine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Avoid such tasks while taking this product.

Alcohol and other CNS depressants may produce an additive CNS depression when taken with this combination product. Avoid drinking alcohol or taking other CNS depressants when you are taking Tylenol with Codeine.

Codeine may be habit forming. Take this drug only for as long as it is prescribed, in the amounts prescribed, and no more frequently than prescribed.

Some people have a variation in a liver enzyme and change codeine into morphine more rapidly and completely than other people. These people are ultra-rapid metabolizers and are more likely to have higher-than-normal levels of morphine in their blood after taking codeine, which can result in overdose symptoms such as extreme sleepiness, confusion, or shallow breathing. In most cases, it is unknown if someone is an ultra-rapid codeine metabolizer.

Nursing mothers taking codeine can also have higher morphine levels in their breast milk if they are ultra-rapid metabolizers. These higher levels of morphine in breast milk may lead to life-threatening or fatal side effects in nursing babies. If you are a nursing mother, watch for signs of morphine toxicity in your infant, including increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness. Talk to your baby's doctor immediately if you notice these signs. If you cannot reach the doctor right away, take your baby to an emergency room or call 911 (or local emergency services).

Laboratory Tests

In patients with severe hepatic or renal disease, effects of therapy should be monitored with serial liver and/or renal function tests.

Drug Interactions

This drug may enhance the effects of other narcotic analgesics, alcohol, general anesthetics, tranquilizers such as chlordiazepoxide, sedative-hypnotics, or other CNS depressants, causing increased CNS depression.

Drug/Laboratory Test Interactions

Codeine may increase serum amylase levels.

Acetaminophen may produce false-positive test results for urinary 5-hydroxyindoleacetic acid.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No adequate studies have been conducted in animals to determine whether acetaminophen and codeine have a potential for carcinogenesis or mutagenesis. No adequate studies have been conducted in animals to determine whether acetaminophen has a potential for impairment of fertility.

Acetaminophen and codeine have been found to have no mutagenic potential using the Ames Salmonella-Microsomal Activation test, the Basc test on Drosophila germ cells, and the Micronucleus test on mouse bone marrow.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Codeine

A study in rats and rabbits reported no teratogenic effect of codeine administered during the period of organogenesis in doses ranging from 5 to 120 mg/kg. In the rat, doses at the 120 mg/kg level, in the toxic range for the adult animal, were associated with an increase in embryo resorption at the time of implantation. In another study a single 100 mg/kg dose of codeine administered to pregnant mice reportedly resulted in delayed ossification in the offspring.

There are no adequate and well-controlled studies in pregnant women. TYLENOL® with Codeine (acetaminophen and codeine phosphate) Tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Dependence has been reported in newborns whose mothers took opiates regularly during pregnancy. Withdrawal signs include irritability, excessive crying, tremors, hyperreflexia, fever, vomiting, and diarrhea. These signs usually appear during the first few days of life.

Labor and Delivery

Narcotic analgesics cross the placental barrier. The closer to delivery and the larger the dose used, the greater the possibility of respiratory depression in the newborn. Narcotic analgesics should be avoided during labor if delivery of a premature infant is anticipated. If the mother has received narcotic analgesics during labor, newborn infants should be observed closely for signs of respiratory depression. Resuscitation may be required (see OVERDOSAGE). The effect of codeine, if any, on the later growth, development, and functional maturation of the child is unknown.

Nursing Mothers

Acetaminophen is excreted in breast milk in small amounts, but the significance of its effect on nursing infants is not known. Because of the potential for serious adverse reactions in nursing infants from acetaminophen, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Codeine is secreted into human milk. In women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and dose-dependent. Despite the common use of codeine products to manage postpartum pain, reports of adverse events in infants are rare. However, some women are ultra-rapid metabolizers of codeine. These women achieve higher-than-expected serum levels of codeine's active metabolite, morphine, leading to higher-than-expected levels of morphine in breast milk and potentially dangerously high serum morphine levels in their breastfed infants. Therefore, maternal use of codeine can potentially lead to serious adverse reactions, including death, in nursing infants.

The risk of infant exposure to codeine and morphine through breast milk should be weighed against the benefits of breastfeeding for both the mother and baby. Caution should be exercised when codeine is administered to a nursing woman. If a codeine-containing product is selected, the lowest dose should be prescribed for the shortest period of time to achieve the desired clinical effect. Mothers using codeine should be informed about when to seek immediate medical care and how to identify the signs and symptoms of neonatal toxicity, such as drowsiness or sedation, difficulty breastfeeding, breathing difficulties, and decreased tone, in their baby. Nursing mothers who are ultra-rapid metabolizers may also experience overdose symptoms such as extreme sleepiness, confusion, or shallow breathing. Prescribers should closely monitor mother-infant pairs and notify treating pediatricians about the use of codeine during breastfeeding (see PRECAUTIONS – General, Ultra-Rapid Metabolizers of Codeine).

Adverse Reactions

The most frequently observed adverse reactions include drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea and vomiting. These effects seem to be more prominent in ambulatory than in nonambulatory patients, and some of these adverse reactions may be alleviated if the patient lies down.

Other adverse reactions include allergic reactions, euphoria, dysphoria, constipation, abdominal pain, pruritus, rash, thrombocytopenia, and agranulocytosis.

At higher doses, codeine has most of the disadvantages of morphine including respiratory depression.

Drug Abuse and Dependence

Controlled Substance

TYLENOL® with Codeine (acetaminophen and codeine phosphate) Tablets are classified as a Schedule III controlled substance.

Abuse and Dependence

Codeine can produce drug dependence of the morphine type and, therefore, has the potential for being abused. Psychological dependence, physical dependence, and tolerance may develop upon repeated administration and it should be prescribed and administered with the same degree of caution appropriate to the use of other oral narcotic medications.

Overdosage

Following an acute overdosage, toxicity may result from codeine or acetaminophen.

Signs and Symptoms

Toxicity from codeine poisoning includes the opioid triad of pinpoint pupils, depression of respiration, and loss of consciousness. Convulsions may occur.

In acetaminophen overdosage, dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and coagulation defects may also occur.

Early symptoms following a potentially hepatotoxic overdose may include nausea, vomiting, diaphoresis, and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion.

Treatment

A single or multiple drug overdose with acetaminophen and codeine is a potentially lethal polydrug overdose and consultation with a regional poison control center is recommended.

Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption.

Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. Assisted or controlled ventilation should also be considered. For respiratory depression due to overdosage or unusual sensitivity to codeine, parenteral naloxone is a specific and effective antagonist.

Gastric decontamination with activated charcoal should be administered just prior to N-acetylcysteine (NAC) to decrease systemic absorption if acetaminophen ingestion is known or suspected to have occurred within a few hours of presentation. Serum acetaminophen levels should be obtained immediately if the patient presents 4 or more hours after ingestion to assess potential risk of hepatotoxicity; acetaminophen levels drawn less than 4 hours post-ingestion may be misleading. To obtain the best possible outcome, NAC should be administered as soon as possible where impending or evolving liver injury is suspected. Intravenous NAC may be administered when circumstances preclude oral administration.

Vigorous supportive therapy is required in severe intoxication. Procedures to limit the continuing absorption of the drug must be readily performed since the hepatic injury is dose-dependent and occurs early in the course of intoxication.

Tylenol with Codeine Dosage and Administration

Dosage should be adjusted according to severity of pain and response of the patient.

The usual adult dosage is:

	Single Doses (Range)	Maximum 24-Hour Dose
Codeine Phosphate	15 mg to 60 mg	360 mg
Acetaminophen	300 mg to 1,000 mg	4,000 mg

Doses may be repeated up to every 4 hours.

The prescriber must determine the number of tablets per dose, and the maximum number of tablets per 24 hours, based upon the above dosage guidance. This information should be conveyed in the prescription.

It should be kept in mind, however, that tolerance to codeine can develop with continued use and that the incidence of untoward effects is dose related. Adult doses of codeine higher than 60 mg fail to give commensurate relief of pain but merely prolong analgesia and are associated with an appreciably increased incidence of undesirable side effects. Equivalently high doses in children would have similar effects.

How is Tylenol with Codeine Supplied

TYLENOL® with Codeine (acetaminophen and codeine phosphate) Tablets are white, round, flat-faced, beveled-edged tablet, imprinted "McNEIL" on one side and "TYLENOL CODEINE" and either "3" or "4" on the other side and are supplied as follows:

TYLENOL® with Codeine No. 3 bottle of 100 tablets – NDC 50458-513-60

TYLENOL® with Codeine No. 3 bottle of 1000 tablets – NDC 50458-513-80

TYLENOL® with Codeine No. 4 bottle of 100 tablets – NDC 50458-515-60

TYLENOL® with Codeine No. 4 bottle of 500 tablets – NDC 50458-515-70

Store TYLENOL® with Codeine Tablets at 20° to 25°C (68° to 77°F). (See USP Controlled Room Temperature.)

Dispense in tight, light-resistant container as defined in the official compendium.

Manufactured by:

Janssen Ortho, LLC

Gurabo, Puerto Rico 00778

Manufactured for:

PriCara®

Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.

Raritan, New Jersey 08869

10186601

Revised September 2011

PRINCIPAL DISPLAY PANEL - 100 Tablet Bottle Label

NDC 50458-513-60

CIII

100 tablets

Tylenol®

with codeine

ACETAMINOPHEN AND

CODEINE PHOSPHATE

TABLETS No.3

Each tablet contains:

codeine phosphate 30 mg

acetaminophen 300 mg

Rx only.

PriCara®

Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.

PRINCIPAL DISPLAY PANEL - 100 Tablet Bottle Label

NDC 50458-515-60

CIII

100 tablets

Tylenol®

with codeine

ACETAMINOPHEN AND

CODEINE PHOSPHATE

TABLETS No.4

Each tablet contains:

codeine phosphate 60 mg

acetaminophen 300 mg

Rx only.

PriCara®

Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc.

Tylenol with Codeine
acetaminophen and codeine phosphate tablet

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	NDC Product Code (Source)	50458-513
Route of Administration	ORAL	DEA Schedule	CIII

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
acetaminophen (acetaminophen)	acetaminophen	300 mg
codeine phosphate (codeine)	codeine phosphate	30 mg

Inactive Ingredients
Ingredient Name	Strength
powdered cellulose
magnesium stearate
sodium metabisulfite
starch, corn

Product Characteristics
Color	WHITE	Score	no score
Shape	ROUND	Size	11mm
Flavor		Imprint Code	McNEIL;TYLENOL;CODEINE;3
Contains

Packaging
#	NDC	Package Description	Multilevel Packaging
1	50458-513-60	100 TABLET In 1 BOTTLE	None
2	50458-513-80	1000 TABLET In 1 BOTTLE	None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA085055	08/17/1977

Tylenol with Codeine
acetaminophen and codeine phosphate tablet

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	NDC Product Code (Source)	50458-515
Route of Administration	ORAL	DEA Schedule	CIII

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
acetaminophen (acetaminophen)	acetaminophen	300 mg
codeine phosphate (codeine)	codeine phosphate	60 mg

Inactive Ingredients
Ingredient Name	Strength
powdered cellulose
magnesium stearate
sodium metabisulfite
starch, corn

Product Characteristics
Color	WHITE	Score	no score
Shape	ROUND	Size	11mm
Flavor		Imprint Code	McNEIL;TYLENOL;CODEINE;4
Contains

Packaging
#	NDC	Package Description	Multilevel Packaging
1	50458-515-60	100 TABLET In 1 BOTTLE	None
2	50458-515-70	500 TABLET In 1 BOTTLE	None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA085055	08/17/1977

Labeler - Janssen Pharmaceuticals, Inc. (063137772)

Establishment
Name	Address	ID/FEI	Operations
Janssen Ortho LLC		062191882	MANUFACTURE

Establishment
Name	Address	ID/FEI	Operations
Mallinckrodt Inc.		097722284	ANALYSIS, API MANUFACTURE

Establishment
Name	Address	ID/FEI	Operations
Noramco Inc.		166506142	API MANUFACTURE

Establishment
Name	Address	ID/FEI	Operations
Ortho-McNeil-Janssen Pharmaceuticals, Inc.		063137772	ANALYSIS

Revised: 07/2011Janssen Pharmaceuticals, Inc.

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Sunday, 19 August 2012

Trelstar

Generic Name: Triptorelin Pamoate
Class: Antineoplastic Agents
VA Class: AN500
Chemical Name: 6-d-Tryptophan luteinizing hormone-releasing factor (pig)
Molecular Formula: C₆₄H₈₂N₁₈O₁₃
CAS Number: 57773-63-4

Special Alerts:

[Posted 10/20/2010] ISSUE: Gonadotropin-Releasing Hormone (GnRH) agonists will have new safety information added to the Warnings and Precautions section of the drug labels. This new information warns about increased risk of diabetes and certain cardiovascular diseases (heart attack, sudden cardiac death, stroke) in men receiving these medications for the treatment of prostate cancer.

BACKGROUND: GnRH agonists are approved to treat the symptoms (palliative treatment) of advanced prostate cancer. The benefits of GnRH agonist use for earlier stages of prostate cancer that have not spread (non-metastatic prostate cancer) have not been established. FDA’s notification to manufacturers of GnRH agonists to add this safety information is based on the Agency’s review of several published studies. Most of the studies reviewed by FDA reported small but statistically significant increased risks of diabetes and/or cardiovascular events in patients receiving GnRH agonists.

RECOMMENDATIONS: Healthcare professionals should evaluate patients for risk factors for these diseases and carefully weigh the benefits and risks of using GnRH agonists before determining appropriate treatment for prostate cancer. Patients who are receiving treatment with GnRH agonists should undergo periodic monitoring of blood glucose and/or glycosylated hemoglobin (HbA1c). Healthcare professionals should also monitor patients for signs and symptoms suggestive of development of cardiovascular disease and manage according to current clinical practice. For more information visit the FDA website at: and .

[Posted 05/03/2010] FDA notified healthcare professionals and patients of FDA’s preliminary and ongoing review which suggests an increase in the risk of diabetes and certain cardiovascular diseases in men treated with GnRH agonists, drugs that suppress the production of testosterone, a hormone that is involved in the growth of prostate cancer.

Most of the studies reviewed by FDA reported small, but statistically significant increased risks of diabetes and/or cardiovascular events in patients receiving GnRH agonists. FDA’s review is ongoing and the agency has not made any conclusions about GnRH agonists and whether they increase the risk of diabetes and cardiovascular disease in patients receiving these medications for prostate cancer.

Healthcare professionals and patients should be aware of these potential safety issues and carefully weigh the benefits and risks of GnRH agonists when determining treatment choices. FDA recommends that patients receiving GnRH agonists should be monitored for development of diabetes and cardiovascular disease. Patients should not stop their treatment with GnRH agonists unless told to do so by their healthcare professional.

Some GnRH agonists are also used in women and in children for other indications than those above. There are no known comparable studies that have evaluated the risk of diabetes and heart disease in women and children taking GnRH agonists. For more information visit the FDA website at: and .

Introduction

Antineoplastic agent; synthetic decapeptide analog of gonadotropin-releasing hormone (GnRH, luteinizing hormone-releasing hormone, gonadorelin);¹ ⁷ structurally related to leuprolide and goserelin.¹ ² ³ ⁴ ⁶ ⁷

Uses for Trelstar

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Prostate Cancer

Palliative treatment of advanced prostate cancer; considered alternative therapy when orchiectomy or estrogen therapy is not appropriate or is unacceptable to the patient.¹ ⁷

Trelstar Dosage and Administration

Administration

IM Administration

Administer by IM injection once monthly (every 28 days) as a depot 1-month formulation or every 84 days (12 weeks) as a long-acting 3-month formulation.¹ ⁷

Inject IM into buttock; rotate injection sites periodically.¹ ⁷

Administer under the supervision of a qualified clinician.¹ ⁷

Reconstitution

Reconstitute powder just prior to administration.¹ ⁷ Discard suspension if not used immediately after reconstitution.¹ ⁷

Using a syringe with 20-gauge needle, add 2 mL of sterile water for injection to vial containing the powder (1- or 3-month formulation); do not reconstitute with other diluents.¹ ⁷ Shake well to disperse particles and obtain a uniform, milky suspension.¹ ⁷

If using the single-dose delivery system, add contents of the prefilled syringe (2 mL of sterile water for injection) to vial containing the powder according to the manufacturer’s instructions.¹ ⁷ Mix well.¹ ⁷

Withdraw entire contents of vial and use immediately.¹ ⁷

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Available as triptorelin pamoate; dosage is expressed in terms of triptorelin.¹ ⁷

Adults

Prostate Cancer

IM

3.75 mg every 28 days (monthly) as the 1-month formulation or 11.25 mg every 84 days (12 weeks) as the 3-month formulation.¹ ⁷

Special Populations

Hepatic Impairment

Potential need for dosage adjustment not determined.¹

Renal Impairment

Potential need for dosage adjustment not determined.¹

Cautions for Trelstar

Contraindications

Known hypersensitivity to triptorelin or any other ingredient in the formulation, other GnRH agonists, or GnRH.¹ ⁷

Known or suspected pregnancy.¹ ⁷

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Endocrine Effects

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Possible worsening of signs and/or symptoms of prostate cancer and/or development of new manifestations (e.g., bone pain, neuropathy, hematuria, urethral or bladder outlet obstruction) due to increases in serum testosterone concentrations during initial weeks of therapy.¹ ² ³ ⁵ ⁷

Possible spinal cord compression contributing to paralysis; possibly fatal.¹ ² ⁵ ⁷

Increased risk of neurologic and/or genitourinary complications during initial therapy in patients with prostate cancer and metastatic vertebral lesions and/or urinary tract obstruction.¹ ⁷ Observe such patients closely during initial weeks of therapy.¹ ⁵ ⁷

If spinal cord compression or renal impairment develops, institute standard treatment of these complications; consider immediate orchiectomy in extreme cases.¹ ⁷

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactic shock and angioedema reported rarely.¹ ⁷ If such reactions occur, discontinue immediately and provide supportive and symptomatic care.¹ ⁷

Major Toxicities

Pituitary Apoplexy

Pituitary apoplexy, a clinical syndrome resulting from infarction of the pituitary gland, reported rarely.¹ ⁷ Most cases occur within 2 weeks of the first dose, sometimes within the first hour.¹ ⁷ If manifestations occur (e.g., sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, sometimes cardiovascular collapse), immediate medical attention required.¹ ⁷ In most cases, pituitary adenoma diagnosed.¹

General Precautions

Laboratory Monitoring

Periodically determine serum testosterone and prostate-specific antigen concentrations to monitor therapeutic response.¹ ⁷

Specific Populations

Pregnancy

Category X.¹ ⁷ (See Contraindications under Cautions.)

Lactation

Not known whether distributed into milk; not recommended for use in nursing women.¹ ⁷

Pediatric Use

Safety and efficacy not established in children.¹ ⁷

Geriatric Use

Studies conducted principally in patients ≥65 years of age, since prostate cancer occurs mainly in an older patient population.¹ ⁷

Common Adverse Effects

Temporary worsening of disease manifestations, hot flushes (flashes), skeletal pain, impotence, headache, pain at injection site, leg pain and edema, dysuria, hypertension.¹ ⁷

Also observed with 3-month formulation: decreased hemoglobin and erythrocyte counts, increased BUN, increased serum concentrations of glucose, AST, ALT, and alkaline phosphatase.⁷

Interactions for Trelstar

Metabolism unlikely to involve CYP enzymes; effect of triptorelin on other drug-metabolizing enzymes unknown.⁷

Drugs That Induce Hyperprolactinemia

Potential pharmacologic interaction (possible decrease in triptorelin efficacy due to decreased number of GnRH receptors) with drugs such as antipsychotic agents, methyldopa, metoclopramide, and reserpine.¹ ⁶ ⁷

Trelstar Pharmacokinetics

Absorption

Bioavailability

Not active when administered orally.¹ ⁷

Following IM administration as Trelstar Depot or Trelstar LA, peak plasma concentrations usually are attained within 1 or 3 hours, respectively.¹ ⁷

Duration

Following IM injection of Trelstar Depot or Trelstar LA in males, therapeutic plasma concentrations persist for 1 or 3 months, respectively.¹ ⁷

Distribution

Extent

Not known whether triptorelin is distributed into milk.¹ ⁷

Plasma Protein Binding

No evidence that triptorelin binds to plasma proteins.¹ ⁷

Elimination

Metabolism

Metabolism is unknown; involvement of CYP enzymes is unlikely.¹ ⁷ No metabolites identified to date.¹ ⁷

Elimination Route

Hepatic and renal elimination.¹ ⁷

Half-life

Approximately 3 hours.¹ ⁷

Special Populations

In males with hepatic impairment or moderate or severe renal impairment, AUC increased 2- to 4-fold compared with healthy males.¹ ⁷

Stability

Storage

Parenteral

Powder for Injection

20–25°C (may be exposed to 15–30°C).¹ ⁷ Do not freeze.⁷

Discard suspension if not used immediately after reconstitution.¹ ⁷

ActionsActions

Potent inhibitor of gonadotropin secretion when given continuously in therapeutic doses; greater activity than naturally occurring GnRH.¹ ⁷

Transient surge in circulating levels of LH, FSH, testosterone, and estradiol observed after initial administration.¹ ⁷ Sustained decreases in LH and FSH secretion and reduced testicular and ovarian steroidogenesis observed following chronic, continuous administration (generally 2–4 weeks after initiation of therapy).¹ ⁴ ⁷

Reduction of serum testosterone in males comparable to effects achieved after surgical castration; results in inactivation of physiologic functions and tissues dependent on testosterone.¹ ² ⁴ ⁷ These effects usually are reversible after cessation of therapy.¹ ⁷

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Risk of worsening manifestations of prostate cancer during initial weeks of therapy.¹ ⁷

Importance of promptly reporting weakness or paresthesia of lower limbs and/or worsening of urinary signs and symptoms to clinicians.⁶

Importance of promptly reporting sudden onset of headache, vomiting, or visual changes to clinicians.¹ ⁷

Risk of anaphylactoid and other sensitivity reactions.¹ ⁷

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹ ⁷

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹ ⁷ If used during pregnancy, apprise of potential fetal hazard.⁷

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

Preparations

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

Triptorelin Pamoate
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for IM use only	3.75 mg (of triptorelin)	Trelstar Depot	Watson
			Trelstar Depot Clip’n’Ject	Watson
		11.25 mg (of triptorelin)	Trelstar LA	Watson
			Trelstar LA Clip’n’Ject	Watson

Disclaimer

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

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

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions November 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Watson Pharma. Trelstar Depot 3.75 mg (triptorelin pamoate for injectable suspension) prescribing information. Corona, CA; 2006 Aug.

2. Parmar H, Phillips RH, Lightman SL et al. Randomised controlled study of orchidectomy vs long-acting D-Trp-6-LHRH microcapsules in advanced prostatic carcinoma. Lancet. 1985; 2:1201-5. [PubMed 2866289]

3. Mahler C. Is disease flare a problem? Cancer. 1993; 72:3799-802.

4. Rolandi E, Martorana G, Franceschini R et al. Treatment of prostatic cancer with a depot preparation of an LHRH analogue: endocrine effects. Curr Ther Res. 1985; 38:670-5.

5. Kahan A, Delrieu F, Amor B et al. Disease flare induced by D-Trp⁶-LHRH analogue in patients with metastatic prostatic cancer. Lancet. 1984; 1:971-2. [IDIS 184509] [PubMed 6143912]

6. Pharmacia & Upjohn, Kalomazoo, MI: Personal communication.

7. Watson Pharma. Trelstar LA 11.25 mg (triptorelin pamoate for injectable suspension) prescribing information. Corona, CA: 2006 Aug.

8. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; 1:41-52.

More Trelstar resources

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

Compare Trelstar with other medications

Prostate Cancer

Tequin Suspension

Generic Name: Gatifloxacin (ga-ti-FLOKS-a-sin)
Brand Name: Tequin

Tequin Suspension is used for:

Treating infections caused by certain bacteria.

Tequin Suspension is a fluoroquinolone antibiotic. It works by stopping the production of proteins that bacteria need to survive.

Do NOT use Tequin Suspension if:

you are allergic to any ingredient in Tequin Suspension or to similar medicines (eg, ciprofloxacin)

you have low blood potassium or diabetes

you or a family member have a rare heart condition known as congenital prolongation of the QTc interval

you are taking medicines for heart rhythm disturbances (eg, quinidine, procainamide, amiodarone, sotalol), cisapride, ketolides (eg, telithromycin), a macrolide antibiotic (eg, erythromycin), pimozide, or ziprasidone

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

Before using Tequin Suspension:

Some medical conditions may interact with Tequin Suspension. Tell your health care provider 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 heart problems, including a slow heartbeat, a history of lack of blood supply to your heart, or hardening of the arteries

if you have a history of low blood potassium levels, diabetes, or kidney or liver problems

if you have Alzheimer disease, tendonitis, or a history of seizures

if you have a central nervous system disease or increased pressure in the head

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

Antidepressants (eg, amitriptyline), antihistamines (eg, diphenhydramine, loratadine), arsenic, azole antifungals (eg, ketoconazole), certain medicines for heart rhythm disturbances (eg, quinidine, procainamide, amiodarone, sotalol), cisapride, diuretics (eg, hydrochlorothiazide, furosemide), droperidol, ketolides (eg, telithromycin, macrolide antibiotics (eg, erythromycin), phenothiazines (eg, chlorpromazine), pimozide , or ziprasidone because side effects, such as racing heartbeat, dizziness, fainting, life-threatening irregular heartbeat leading to unconsciousness, may be increased by Tequin Suspension

Probenecid because the actions and side effects of Tequin Suspension may be increased

Digoxin because the side effects may be increased by Tequin Suspension

Anticoagulants (eg, warfarin) because side effects, including risk of bleeding, may be increased by Tequin Suspension

Insulin, sulfonylureas (eg, glyburide), or other medicines for diabetes because the risk of blood sugar changes may be increased

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

How to use Tequin Suspension:

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

Tequin Suspension may be taken with or without food.

Shake well before using.

Tequin Suspension works best if it is taken at the same time each day.

Tequin Suspension should be taken 4 hours before any other medicines or dietary supplements that contain aluminum, buffered didanosine, calcium, iron, magnesium, sucralfate, or zinc.

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

To clear up your infection completely, continue using Tequin Suspension for the full course of treatment even if you feel better in a few days.

Do not miss any doses of Tequin Suspension. If you miss a dose, 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 Tequin Suspension.

Important safety information:

Tequin Suspension may cause dizziness, drowsiness, or changes in vision. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Tequin Suspension. Using Tequin Suspension alone, with certain other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.

Tequin Suspension is effective only against bacteria. It is not effective for treating viral infections (eg, the common cold).

It is important to use Tequin Suspension for the full course of treatment. Failure to do so may decrease the effectiveness of Tequin Suspension and may increase the risk that the bacteria will no longer be sensitive to Tequin Suspension and will not be able to be treated by this or certain other antibiotics in the future.

Long-term or repeated use of Tequin Suspension may cause a second infection. Your doctor may want to change your medicine to treat the second infection. Contact your doctor if signs of a second infection occur.

If severe diarrhea, stomach pain/cramps or bloody stools occur, contact your doctor immediately. This could be a symptom of a serious side effect requiring immediate medical attention. Do not treat diarrhea without consulting your doctor.

Tequin Suspension may cause increased sensitivity to the sun. Avoid exposure to the sun, sunlamps, or tanning booths until you know how you react to Tequin Suspension. Use a sunscreen or protective clothing if you must be outside for a prolonged period.

Phenylketonuria patients - Tequin Suspension contains phenylalanine.

Tequin Suspension may cause low blood sugar (eg, increased heartbeat, headache, chills, sweating, tremor, increased hunger, changes in vision, nervousness, weakness, dizziness, drowsiness, fainting) or high blood sugar (eg, thirst, increased urination, confusion, drowsiness, flushing, rapid breathing, fruity breath odor). If these symptoms occur, tell your doctor immediately.

Use Tequin Suspension with caution in the ELDERLY because they may be more sensitive to its effects, especially blood sugar changes.

Tequin Suspension is not recommended for use in CHILDREN younger than 18 years of age. Safety and effectiveness in this age group have not been confirmed.

PREGNANCY and BREAST-FEEDING: If you become pregnant, discuss with your doctor the benefits and risks of using Tequin Suspension during pregnancy. It is unknown if Tequin Suspension is excreted in breast milk. If you are or will be breast-feeding while you are using Tequin Suspension, check with your doctor or pharmacist to discuss the risks to your baby.

Possible side effects of Tequin Suspension:

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

Diarrhea; dizziness; drowsiness; headache; mild diarrhea; nausea; stomachache; vaginal irritation; vomiting.

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

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody stools; changes in mood or behavior; chest pain or pounding in the chest; confusion; convulsions; depression; excessive hunger, thirst, or urination; fainting; fast or irregular heartbeat; "fruity"-smelling breath; hallucinations; hoarseness; lightheadedness; loss of consciousness; nervousness; nightmares; pale skin; paranoia; restlessness; seizures; severe or continuous diarrhea; sleeplessness; stomach pain/cramps; sweating; tendon or joint pain or swelling; tremors; unusual or severe drowsiness or dizziness; vision changes.

This is not a complete list of all side effects that may occur. If you have questions or need medical advice about side effects, contact your doctor or health care provider. You may report side effects to the FDA at 1-800-FDA-1088 (1-800-332-1088) or at http://www.fda.gov/medwatch.

See also: Tequin 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 (http://www.aapcc.org/DNN/), or emergency room immediately.

Proper storage of Tequin Suspension:

Before mixing, store Tequin Suspension at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. After mixing, store the suspension in the tightly closed bottle in the refrigerator (36 to 46 degrees F; 2 to 8 degrees C) for up to 14 days. Keep Tequin Suspension out of the reach of children and away from pets.

General information:

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

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

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

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

Issue Date: February 1, 2012

Database Edition 12.1.1.002

More Tequin resources

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

Compare Tequin with other medications

Anthrax
Anthrax Prophylaxis
Bladder Infection
Bronchitis
Gonococcal Infection, Uncomplicated
Kidney Infections
Otitis Media
Pneumonia
Sinusitis
Skin Infection
Tuberculosis, Active
Urinary Tract Infection

Friday, 17 August 2012

Idursulfase

Class: Enzymes
Chemical Name: α-L-iduronate sulfate sulfatase
Molecular Formula: C₂₆₈₉H₄₀₅₇N₆₉₉O₇₉₂S₁₄
CAS Number: 50936-59-9
Brands: Elaprase

Risk of Anaphylaxis

Life-threatening anaphylactic reactions observed in some patients during idursulfase infusions. Appropriate medical support should be readily available.

Biphasic anaphylactic reactions also observed after administration. Patients who experienced anaphylactic reactions may require prolonged observation.

Patients with compromised respiratory function or acute respiratory disease may be at risk of serious acute exacerbation of their respiratory compromise due to infusion reactions; may require additional monitoring.

Introduction

Biosynthetic (recombinant DNA origin) form of human iduronate-2-sulfatase; lysosomal enzyme that catalyzes the hydrolysis of the 2-sulfate esters of terminal iduronate sulfate residues from the glycosaminoglycans dermatan sulfate and heparan sulfate.¹ ² ⁴ ⁵ ⁶ ⁷

Uses for Idursulfase

Hunter Syndrome

Management of Hunter syndrome (mucopolysaccharidosis II, MPS II);¹ ² ⁴ ⁵ ⁶ designated an orphan drug by FDA for use in this condition.³

Hunter syndrome is an X-linked recessive disease characterized by a deficiency of the lysosomal enzyme iduronate-2-sulfatase.¹ ² ⁴ ⁴ ⁵ ⁶

In patients with Hunter disease, reduced or absent iduronate-2-sulfatase activity results in progressive accumulation of glycosaminoglycans in the lysosomes of various cells, leading to cellular engorgement, organomegaly, tissue destruction, and organ system dysfunction.¹ ⁵ ⁶

Idursulfase improves endurance (measured by increases in walking distance) in patients with Hunter syndrome.¹ ² ⁴ ⁵ ⁶

Idursulfase Dosage and Administration

Administration

Administer by IV infusion.¹

IV Administration

For solution compatibility and storage information, see Stability.

Administer by IV infusion using a 0.2-mcm filter.¹

Do not infuse idursulfase infusions simultaneously through the same IV line with other drugs.¹

Dilution

Prior to infusion, dilute the appropriate dose of commercially available idursulfase concentrated solution (2 mg of the drug per mL) in 100 mL of 0.9% sodium chloride for injection according to the manufacturer’s instructions.¹ Vials are for single use only; discard partially used vials of idursulfase solution.¹

Withdraw the calculated volume providing the appropriate dose of idursulfase from the appropriate number of vials and dilute in 100 mL of 0.9% sodium chloride injection.¹ Gently mix the solution in the infusion bag; do not shake.¹ Consult the manufacturer’s labeling for additional information on dilution and administration of idursulfase.¹

Rate of Administration

Administer by IV infusion at an initial infusion rate of 8 mL/hour for the first 15 minutes.¹ May increase infusion rate in increments of 8 mL/hour every 15 minutes in order to administer the entire volume within the desired time, up to a maximum rate of 100 mL/hour.¹ May administer the total volume of infusion in 1–3 hours; do not exceed 8 hours.¹ May decrease infusion rate, temporarily discontinue infusion, or stop the infusion for the particular visit if infusion-related reactions occur.¹

Dosage

The specific activity of idursulfase is 41–77 units/mg, with 1 unit defined as the amount of activity that results in the hydrolysis of 1 mcmol of heparin disaccharide substrate per hour under specified assay conditions.¹

Pediatric Patients

Hunter Syndrome

IV

Children ≥5 years of age: 0.5 mg/kg by IV infusion once weekly.¹

Adults

Hunter Syndrome

IV

0.5 mg/kg by IV infusion once weekly.¹

Prescribing Limits

Pediatric Patients

Hunter Syndrome

IV

Maximum infusion rate: 100 mL/hour.¹

Adults

Hunter Syndrome

IV

Maximum infusion rate: 100 mL/hour.¹

Special Populations

No special population dosage recommendations at this time.¹

Cautions for Idursulfase

Contraindications

The manufacturer states that there are no known contraindications to the use of idursulfase.¹

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Life-threatening hypersensitivity reactions (e.g., anaphylaxis, respiratory distress, hypoxia, hypotension, seizure, loss of consciousness, urticaria, angioedema of the throat and tongue) reported during and after idursulfase infusion in patients receiving the drug.¹ ⁵ Ensure that appropriate medical support measures are readily available during administration.¹

Consider prolonged observation in patients who experience initial severe or refractory reactions, since biphasic anaphylactic reactions occurring up to approximately 24 hours after treatment and recovery from an initial anaphylactic reaction have been reported.¹

Provide additional monitoring in patients with compromised respiratory function or acute respiratory disease, who may be at risk of serious acute exacerbation of their respiratory compromise secondary to infusion reactions.¹ Consider delaying idursulfase infusion in patients with concomitant acute respiratory and/or febrile illness.¹

If anaphylactic reactions or other severe allergic reaction occurs, immediately discontinue administration of the drug, and initiate appropriate medical treatment.¹ In clinical studies, treatment included hospitalization, epinephrine, inhaled β-adrenergic agonists, and corticosteroids.¹ ⁴ ⁵ Consider resuming the infusion at a slower rate or discontinuing the idursulfase infusion for that visit.¹ May consider use of antihistamines and/or corticosteroids prior to and during subsequent infusions in patients who have experienced severe infusion reactions.¹ ⁴ ⁵

General Precautions

Antibody Formation

Possible formation of antibodies to idursulfase.¹ ² ⁴ ⁶ Increased incidence of infusion reactions, including allergic reactions, reported in patients who developed IgG antibodies to idursulfase; in addition, decreased reduction of urinary glycosaminoglycan excretion reported in patients who developed antibodies to idursulfase.¹ The relationship between the development of antibodies to idursulfase and clinical efficacy outcome is not fully known.¹

Specific Populations

Pregnancy

Category C.¹

Lactation

Not known whether idursulfase is distributed into milk.¹ Use with caution.¹

Pediatric Use

Patients ≥5 years of age have received idursulfase in clinical trials.¹ Clinical response to idursulfase was similar in children, adolescents, and adults.¹ Safety and efficacy of idursulfase in pediatric patients <5 years of age have not been established.¹

Geriatric Use

No experience in patients ≥65 years of age; unknown whether geriatric patients respond differently than younger individuals.¹

Common Adverse Effects

Pyrexia,¹ ² headache,¹ ² arthralgia,¹ limb pain,¹ pruritus,¹ ² hypertension,¹ malaise,¹ visual disturbance,¹ wheezing,¹ abscess,¹ chest wall musculoskeletal pain,¹ ² musculoskeletal dysfunction,¹ urticaria, ¹ anxiety/irritability,¹ ² atrial abnormality,¹ dyspepsia,¹ ² infusion site edema, injury,¹ pruritic rash,¹ ² skin disorder,¹ superficial injury.¹

In clinical studies, the most frequent serious adverse effects related to idursulfase were hypoxic episodes.¹ The most common infusion-related reactions were headache, fever, cutaneous reactions, and hypertension.¹ ⁵

Interactions for Idursulfase

No formal drug interaction studies to date.¹

Idursulfase Pharmacokinetics

Absorption

Plasma Concentrations

AUC values increased in a greater than dose proportional manner following single 1-hour IV infusion of idursulfase dosages ranging from 0.15–1.5 mg/kg.¹

Distribution

Extent

Not known whether idursulfase is distributed into milk.¹

Elimination

Half-life

44–48 minutes.¹

Stability

Storage

Parenteral

Solution for IV Infusion

2–8°C; protect from light and do not shake or freeze.¹ Vials are for single use only; discard any unused product.¹

Administer diluted solution without delay; if not used immediately, diluted solution is stable at 2–8°C ≤48 hours.¹ If held at room temperature, administer diluted solution within 8 hours.¹

ActionsActions

Biosynthetic (recombinant DNA origin) form of human iduronate-2-sulfatase, a lysosomal enzyme that catalyzes the hydrolysis of the 2-sulfate esters of terminal iduronate sulfate residues from the glycosaminoglycans dermatan sulfate and heparan sulfate in the lysosomes of various cell types.¹ ² ⁴ ⁵ ⁶ ⁷

Provides an exogenous source of iduronate-2-sulfatase in patients with Hunter syndrome.¹

Binds to mannose-6-phosphate receptors on the cell surface via mannose-6-phosphate residues on the oligosaccharide chains of the idursulfase molecule, which is then internalized and transported into lysosomes.¹

Enzymatic activity of idursulfase, which results in catabolism of accumulated glycosaminoglycans, is dependent on the posttranslational modification of a specific cysteine to formylglycine.¹

Advice to Patients

Importance of encouraging patients to participate in the Hunter Outcome Survey (http://www.elaprase.com or 866-888-0660) to understand the variability and progression of the disease and to continue to monitor and evaluate long-term treatment effects of idursulfase.¹

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹

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

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

Preparations

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

Idursulfase
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, concentrate, for IV infusion	6 mg	Elaprase	Shire

Disclaimer

References

1. Shire Human Genetic Therapies, Inc. Elaprase (idursulfase) solution for intravenous infusion prescribing information. Cambridge, MA; 2007 Oct.

2. Muenzer J, Wraith JE, Beck M et al. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006; 8:465-73. [PubMed 16912578]

3. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD; 2007 Feb 26. From FDA website. Accessed 2007 Mar 13.

4. Muenzer J, Gucsavas-Calikoglu M, McCandless SE et al. A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome). Mol Genet Metab. 2007; 90:329-37. [PubMed 17185020]

5. Muenzer J, Beck M, Eng CM et al. Multidisciplinary management of Hunter syndrome. Pediatrics.2009; 124 (suppl e):1228-39.

6. Okuyama T, Tanaka A, Suzuki Y et al. Japan Elaprase treatment (JET) study: idursulfase enzyme replacement therapy in adult patients with attenuated Hunter syndrome (Mucopolysaccharidosis II, MPS II). Mol Genet Metab. 2010; 99:18-25. [PubMed 19773189]

7. Manara R, Rampazzo A, Cananzi M et al. Hunter syndrome in an 11-year old girl on enzyme replacement therapy with idursulfase: brain magnetic resonance imaging features and evolution.J inherit Metab Dis. 2010 Jan 6. (Epub ahead of print)

More Idursulfase resources

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

Idursulfase MedFacts Consumer Leaflet (Wolters Kluwer)

Idursulfase Professional Patient Advice (Wolters Kluwer)

idursulfase Intravenous Advanced Consumer (Micromedex) - Includes Dosage Information

Elaprase Prescribing Information (FDA)

Elaprase Consumer Overview

Compare Idursulfase with other medications

Mucopolysaccharidosis Type II

Wednesday, 15 August 2012

Cromolyn Nebulizer Solution

Pronunciation: KROE-moe-lin
Generic Name: Cromolyn
Brand Name: Intal

Cromolyn Nebulizer Solution is used for:

Preventing bronchial asthma and decreasing the severity of asthma attacks. It is not used to treat sudden asthma attacks. It may also be used to treat other conditions as determined by your doctor.

Cromolyn Nebulizer Solution is a mast cell stabilizer. It works by stabilizing mast cells and preventing them from releasing their irritating chemicals. Some forms of recurrent or chronic asthma are due to the release of irritating chemicals from mast cells located in the breathing tubes (bronchial tubes of the lung).

Do NOT use Cromolyn Nebulizer Solution if:

you are allergic to any ingredient in Cromolyn Nebulizer Solution

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

Before using Cromolyn Nebulizer Solution:

Some medical conditions may interact with Cromolyn Nebulizer Solution. 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 liver or kidney problems

Some MEDICINES MAY INTERACT with Cromolyn Nebulizer Solution. However, no specific interactions with Cromolyn Nebulizer Solution are known at this time.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Cromolyn Nebulizer Solution 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 Cromolyn Nebulizer Solution:

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

Cromolyn Nebulizer Solution is for inhalation only.

This medication should be used in a power-driven nebulizer with an adequate airflow rate equipped with a suitable face mask or mouthpiece. Do not mix with other medicines in the nebulizer.

Squeeze the contents of the ampule into the solution container in your nebulizer. Once the nebulizer has been assembled and contains cromolyn inhalation solution, hold the mask close to the face and switch on the device. Breathe through the mouth and out through the nose in a normal, relaxed manner. Nebulization should take 5 to 10 minutes.

Any solution remaining in the nebulizer after treatment needs to be discarded.

Continue to use Cromolyn Nebulizer Solution even if you feel well. Do not miss any doses.

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

Ask your health care provider any questions you may have about how to use Cromolyn Nebulizer Solution.

Important safety information:

Cromolyn Nebulizer Solution may cause drowsiness. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Cromolyn Nebulizer Solution.

It may take up to 4 weeks for the benefits of this medication to be noticeable.

Before you have any medical or dental treatments, emergency care, or surgery, tell the doctor or dentist that you are using Cromolyn Nebulizer Solution.

Carry an identification card at all times that says you are taking Cromolyn Nebulizer Solution.

Cromolyn Nebulizer Solution is not recommended for use in CHILDREN younger than 2 years of age. Safety and effectiveness in this age group have not been confirmed.

PREGNANCY and BREAST-FEEDING: If you are pregnant or plan on becoming pregnant, discuss with your doctor the benefits and risks of using Cromolyn Nebulizer Solution during pregnancy. It is unknown if Cromolyn Nebulizer Solution is excreted in breast milk. If you are or will be breast-feeding, check with your doctor to discuss the benefits and risks to your baby.

Possible side effects of Cromolyn Nebulizer Solution:

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:

Bad taste; cough; drowsiness; hoarseness; nausea; sneezing; throat irritation; tightness in the lungs; wheezing.

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

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); breathing problems; severe nasal congestion.

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.

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. Cromolyn Nebulizer Solution may be harmful if swallowed.

Proper storage of Cromolyn Nebulizer Solution:

Store at controlled room temperature between 68 and 77 degrees F (20 and 25 degrees C), away from heat, moisture, and light. Do not store in the bathroom. Do not use the solution if it is discolored or contains particles. Store ampules in foil pouch until ready for use. Keep Cromolyn Nebulizer Solution out of the reach of children and away from pets.

General information:

If you have any questions about Cromolyn Nebulizer Solution, please talk with your doctor, pharmacist, or other health care provider.

Cromolyn Nebulizer Solution 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 Cromolyn Nebulizer Solution. 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

More Cromolyn resources

Cromolyn Use in Pregnancy & Breastfeeding
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