Cyklokapron

tranexamic acid

Dosage Form: injection, solution
Cyklokapron®

tranexamic acid injection

Antifibrinolytic agent

Cyklokapron Description

Each mL of the sterile solution for intravenous injection contains 100 mg tranexamic acid and Water for Injection to 1 mL.

FORMULATION

Chemical Name: trans-4-(aminomethyl)cyclohexanecarboxylic acid

Structural Formula:

Tranexamic acid is a white crystalline powder. The aqueous solution for injection has a pH of 6.5 to 8.0.

Cyklokapron - Clinical Pharmacology

Tranexamic acid is a competitive inhibitor of plasminogen activation, and at much higher concentrations, a noncompetitive inhibitor of plasmin, i.e., actions similar to aminocaproic acid. Tranexamic acid is about 10 times more potent in vitro than aminocaproic acid.

Tranexamic acid binds more strongly than aminocaproic acid to both the strong and weak receptor sites of the plasminogen molecule in a ratio corresponding to the difference in potency between the compounds. Tranexamic acid in a concentration of 1 mg per mL does not aggregate platelets in vitro.

Tranexamic acid in concentrations up to 10 mg per mL blood has no influence on the platelet count, the coagulation time, or various coagulation factors in whole blood or citrated blood from normal subjects. On the other hand, tranexamic acid in concentrations of 10 mg and 1 mg per mL blood prolongs the thrombin time.

The plasma protein binding of tranexamic acid is about 3% at therapeutic plasma levels and seems to be fully accounted for by its binding to plasminogen. Tranexamic acid does not bind to serum albumin.

After an intravenous dose of 1 g, the plasma concentration time curve shows a triexponential decay with a half-life of about 2 hours for the terminal elimination phase. The initial volume of distribution is about 9 to 12 liters. Urinary excretion is the main route of elimination via glomerular filtration. Overall renal clearance is equal to overall plasma clearance (110 to 116 mL/min), and more than 95% of the dose is excreted in the urine as unchanged drug. Excretion of tranexamic acid is about 90% at 24 hours after intravenous administration of 10 mg per kg body weight.

An antifibrinolytic concentration of tranexamic acid remains in different tissues for about 17 hours, and in the serum, up to seven or eight hours.

Tranexamic acid passes through the placenta. The concentration in cord blood after an intravenous injection of 10 mg per kg to pregnant women is about 30 mg per liter, as high as in the maternal blood. Tranexamic acid diffuses rapidly into joint fluid and the synovial membrane. In the joint fluid, the same concentration is obtained as in the serum. The biological half-life of tranexamic acid in the joint fluid is about three hours.

The concentration of tranexamic acid in a number of other tissues is lower than in blood. In breast milk, the concentration is about one hundredth of the serum peak concentration. Tranexamic acid concentration in cerebrospinal fluid is about one tenth of that of the plasma. The drug passes into the aqueous humor, the concentration being about one tenth of the plasma concentration.

Tranexamic acid has been detected in semen where it inhibits fibrinolytic activity but does not influence sperm migration.

Indications and Usage for Cyklokapron

Cyklokapron Injection is indicated in patients with hemophilia for short-term use (two to eight days) to reduce or prevent hemorrhage and reduce the need for replacement therapy during and following tooth extraction.

Contraindications

Cyklokapron Injection is contraindicated:

1. In patients with acquired defective color vision, since this prohibits measuring one endpoint that should be followed as a measure of toxicity (see WARNINGS).


2. In patients with subarachnoid hemorrhage. Anecdotal experience indicates that cerebral edema and cerebral infarction may be caused by Cyklokapron in such patients.


3. In patients with active intravascular clotting.


4. In patients with hypersensitivity to tranexamic acid or any of the ingredients.

Warnings

Focal areas of retinal degeneration have developed in cats, dogs, and rats following oral or intravenous tranexamic acid at doses between 250 to 1600 mg/kg/day (6 to 40 times the recommended usual human dose) from 6 days to 1 year. The incidence of such lesions has varied from 25% to 100% of animals treated and was dose-related. At lower doses, some lesions have appeared to be reversible.

Limited data in cats and rabbits showed retinal changes in some animals with doses as low as 126 mg/kg/day (only about 3 times the recommended human dose) administered for several days to two weeks.

No retinal changes have been reported or noted in eye examinations in patients treated with tranexamic acid for weeks to months in clinical trials.

However, visual abnormalities, often poorly characterized, represent the most frequently reported postmarketing adverse reaction in Sweden. For patients who are to be treated continually for longer than several days, an ophthalmological examination, including visual acuity, color vision, eye-ground, and visual fields, is advised, before commencing and at regular intervals during the course of treatment. Tranexamic acid should be discontinued if changes in examination results are found.

Convulsions have been reported in association with tranexamic acid treatment.

Precautions

General

The dose of Cyklokapron Injection should be reduced in patients with renal insufficiency because of the risk of accumulation. (See DOSAGE AND ADMINISTRATION.)

Ureteral obstruction due to clot formation in patients with upper urinary tract bleeding has been reported in patients treated with Cyklokapron.

Venous and arterial thrombosis or thromboembolism has been reported in patients treated with Cyklokapron. In addition, cases of central retinal artery and central retinal vein obstruction have been reported.

Patients with a previous history of thromboembolic disease may be at increased risk for venous or arterial thrombosis.

Cyklokapron should not be administered concomitantly with Factor IX Complex concentrates or Anti-inhibitor Coagulant concentrates, as the risk of thrombosis may be increased.

Patients with disseminated intravascular coagulation (DIC), who require treatment with Cyklokapron, must be under strict supervision of a physician experienced in treating this disorder.

Tranexamic acid may cause dizziness and therefore may influence the ability to drive or use machines.

Drug Interactions

No studies of interactions between Cyklokapron and other drugs have been conducted.

Carcinogenesis, Mutagenesis, Impairment of Fertility

An increased incidence of leukemia in male mice receiving tranexamic acid in food at a concentration of 4.8% (equivalent to doses as high as 5 g/kg/day) may have been related to treatment. Female mice were not included in this experiment.

Hyperplasia of the biliary tract and cholangioma and adenocarcinoma of the intrahepatic biliary system have been reported in one strain of rats after dietary administration of doses exceeding the maximum tolerated dose for 22 months. Hyperplastic, but not neoplastic, lesions were reported at lower doses. Subsequent long-term dietary administration studies in a different strain of rat, each with an exposure level equal to the maximum level employed in the earlier experiment, have failed to show such hyperplastic / neoplastic changes in the liver. No mutagenic activity has been demonstrated in several in vitro and in vivo test systems.

There are no clinical or nonclinical data to assess the effects of tranexamic acid on fertility.

Pregnancy (Category B)

Reproduction studies performed in mice, rats, and rabbits have not revealed any evidence of impaired fertility or adverse effects on the fetus due to tranexamic acid.

There are no adequate and well-controlled studies in pregnant women. However, tranexamic acid is known to pass the placenta and appears in cord blood at concentrations approximately equal to maternal concentration. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Labor and Delivery

See above under Pregnancy.

Nursing Mothers

Tranexamic acid is present in the mother's milk at a concentration of about a hundredth of the corresponding serum levels. Caution should be exercised when Cyklokapron is administered to a nursing woman.

Pediatric Use

The drug has had limited use in pediatric patients, principally in connection with tooth extraction. The limited data suggest that dosing instructions for adults can be used for pediatric patients needing Cyklokapron therapy.

Geriatric Use

Clinical studies of Cyklokapron did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

Adverse Reactions

Gastrointestinal disturbances (nausea, vomiting, diarrhea) may occur but disappear when the dosage is reduced. Allergic dermatitis, giddiness, and hypotension have been reported occasionally. Hypotension has been observed when intravenous injection is too rapid. To avoid this response, the solution should not be injected more rapidly than 1 mL per minute.

Worldwide Postmarketing Reports

Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, cerebral thrombosis, acute renal cortical necrosis, and central retinal artery and vein obstruction) have been rarely reported in patients receiving tranexamic acid for indications other than hemorrhage prevention in patients with hemophilia. Convulsion, chromatopsia, and visual impairment have also been reported. However, due to the spontaneous nature of the reporting of medical events and the lack of controls, the actual incidence and causal relationship of drug and event cannot be determined.

Overdosage

Cases of overdosage of Cyklokapron have been reported. Based on these reports, symptoms of overdosage may be gastrointestinal, e.g., nausea, vomiting, diarrhea; hypotensive, e.g., orthostatic symptoms; thromboembolic, e.g., arterial, venous, embolic; visual impairment; convulsions, mental status changes; myoclonus, and rash.

Cyklokapron Dosage and Administration

Immediately before tooth extraction in patients with hemophilia, administer 10 mg per kg body weight of Cyklokapron intravenously together with replacement therapy (see PRECAUTIONS). Following tooth extraction, intravenous therapy, at a dose of 10 mg per kg body weight three to four times daily, may be used for 2 to 8 days.

Note: For patients with moderate to severe impaired renal function, the following dosages are recommended:

Serum Creatinine (µmol/L)	Tranexamic Acid I.V. Dosage
120 to 250 (1.36 to 2.83 mg/dL)	10 mg/kg BID
250 to 500 (2.83 to 5.66 mg/dL)	10 mg/kg daily
>500 (>5.66 mg/dL)	10 mg/kg every 48 hours or 5 mg/kg every 24 hours

For intravenous infusion, Cyklokapron Injection may be mixed with most solutions for infusion such as electrolyte solutions, carbohydrate solutions, amino acid solutions, and Dextran solutions. The mixture should be prepared the same day the solution is to be used. Heparin may be added to Cyklokapron Injection. Cyklokapron Injection should NOT be mixed with blood. The drug is a synthetic amino acid, and should NOT be mixed with solutions containing penicillin.

How is Cyklokapron Supplied

Cyklokapron Injection 100 mg/mL

NDC 0013-1114-10 10 × 10 mL ampules

STORAGE

Store at 25°C (77°F); excursions permitted to 15°–30°C (59°–86°F) [see USP Controlled Room Temperature].

Rx only

LAB-0258-6.0

January 2011

PRINCIPAL DISPLAY PANEL - 10 mL Ampule Carton

100 mg/mL

NDC 0013-1114-10

Contains 10 of NDC 0013-1114-01

Rx only

10 × 10 mL ampules

Cyklokapron®

tranexamic acid injection

(1000 mg/10 mL)

Solution for intravenous injection

Cyklokapron  tranexamic acid  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0013-1114 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength tranexamic acid (tranexamic acid) tranexamic acid 100 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength water

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0013-1114-10 10 AMPULE In 1 BOX contains a AMPULE 1 10 mL In 1 AMPULE This package is contained within the BOX (0013-1114-10)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA019281	12/30/1986

Labeler - Pharmacia and Upjohn Company (829076566)

Establishment
Name	Address	ID/FEI	Operations
CMIC CMO Co., Ltd.		690846636	API MANUFACTURE

Establishment
Name	Address	ID/FEI	Operations
Pfizer Manufacturing Belgium NV		370156507	MANUFACTURE

Revised: 02/2011Pharmacia and Upjohn Company

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Cystorelin

Dosage Form: FOR ANIMAL USE ONLY
Cystorelin®

(Gonadorelin Diacetate Tetrahydrate)

FOR INJECTION

For the treatment of cystic ovaries in cattle

CAUTION

Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian.

Cystorelin Description

Cystorelin® is a sterile solution containing 50 micrograms of gonadorelin (GnRH) diacetate tetrahydrate per milliliter suitable for intramuscular or intravenous administration. Gonadorelin is a decapeptide composed of the sequence of amino acids–

 

5-oxoPro-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2–

a molecular weight of 1182.32 and empirical formula C55H75N17O13. The diacetate tetrahydrate ester has a molecular weight of 1374.48 and empirical formula C59H91N17O21.

Gonadorelin is the hypothalamic releasing factor responsible for the release of gonadotropins (e.g., LH, FSH) from the anterior pituitary. Synthetic gonadorelin is physiologically and chemically identical to the endogenous bovine hypothalamic releasing factor.

PHARMACOLOGY AND TOXICOLOGY

Endogenous gonadorelin is synthesized and/or released from the hypothalamus during various stages of the bovine estrus cycle following appropriate neurogenic stimuli. It passes via the hypophyseal portal vessels, to the anterior pituitary to effect the release of gonadotropins (e.g. LH, FSH) Synthetic gonadorelin administered intravenously or intramuscularly also causes the release of endogenous LH or FSH from the anterior pituitary.

Gonadorelin diacetate tetrahydrate has been shown to be safe. The LD50 for mice and rats is greater than 60 mg/kg, and for dogs, greater than 600 mcg/kg, respectively. No untoward effects were noted among rats or dogs administered 120 mcg/kg/day or 72 mcg/kg/day intravenously for 15 days.

It has no adverse effects on heart rate, blood pressure, or EKG to unanesthetized dogs at 60 mcg/kg. In anesthetized dogs it did not produce depression of myocardial or system hemodynamics or adversely affect coronary oxygen supply or myocardial oxygen requirements.

The intravenous administration of 60 mcg/kg/day of gonadorelin diacetate tetrahydrate to pregnant rats and rabbits during organogenesis did not cause embryotoxic or teratogenic effects.

The intramuscular administration of 1000 mcg to normally cycling dairy cattle had no effect on hematology or blood chemistry.

Further, Cystorelin does not cause irritation at the site of intramuscular administration in dogs. The dosage administered was 72 mcg/kg/day for seven (7) days.

INDICATIONS AND DOSAGE

Cystorelin® is indicated for the treatment of ovarian follicular cysts in dairy cattle. Ovarian cysts are non-ovulated follicles with incomplete luteinization which result in nymphomania or irregular estrus.

Historically, cystic ovaries have responded to an exogenous source of luteinizing hormone (LH) such as human chorionic gonadotropin. Cystorelin initiates release of endogenous LH to cause ovulation and luteinization.

The recommended intravenous or intramuscular dosage of Cystorelin is 100 mcg (2 mL) per cow.

Each mL of Cystorelin contains:
Gonadorelin diacetate tetrahydrate	50 mcg
Benzyl Alcohol	9 mg
Sodium Chloride	7.47 mg
Water for Injection, U.S.P.	q.s.
pH adjusted with potassium phosphate (monobasic and dibasic).

Precautions

Not for use in humans.

Keep this and all drugs out of reach of children.

The Material Safety Data Sheet (MSDS) contains more detailed occupational safety information. To report adverse effects in users, to obtain an MSDS, or for assistance call 1-888-637-4251.

KEEP REFRIGERATED: 2–8°C (36–46°F).

Discard remaining product 90 days after first use.

How is Cystorelin Supplied

Cystorelin is available in a concentration of 50 mcg/mL pH adjusted with potassium phosphate (monobasic and dibasic).

Cystorelin is supplied in multi-dose vials containing 10 mL and 30 mL of sterile solution.

Marketed by:

Merial LLC

Duluth, GA 30096-4640 U.S.A.

Technical Support 1-888-637-4251

® Cystorelin and the Cattle Head Logo are registered trademarks of Merial.

© 2010 Merial. All Rights Reserved.

Rev. 01/2010

1050-2907-00

NADA 098-379, Approved by FDA

Item No. 82830201

PRINCIPAL DISPLAY PANEL - 10 mL Carton

Cystorelin®

(Gonadorelin Diacetate Tetrahydrate)

(50 mcg/mL) Sterile Solution

FOR ANIMAL USE ONLY

NOT FOR HUMAN USE

KEEP OUT OF THE REACH OF CHILDREN

NADA 098-379, Approved by the FDA

CAUTION: Federal law

restricts this drug to use by

or on the order of a licensed

veterinarian.

Item No. 82830201

NET CONTENTS:

1 × 10 mL

MERIAL

PRINCIPAL DISPLAY PANEL - 30 mL Carton

Cystorelin®

(Gonadorelin Diacetate Tetrahydrate)

(50 mcg/mL) Sterile Solution

Item No. 72010

Carton contains 150 doses

NET CONTENTS: 10 × 30 mL

MERIAL

Cystorelin  gonadorelin diacetate tetrahydrate  injection, solution

Product Information Product Type PRESCRIPTION ANIMAL DRUG NDC Product Code (Source) 50604-8283 Route of Administration INTRAVENOUS, INTRAMUSCULAR DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength gonadorelin diacetate tetrahydrate (gonadorelin) gonadorelin diacetate tetrahydrate 50 ug  in 1 mL

Inactive Ingredients Ingredient Name Strength Benzyl Alcohol   Sodium Chloride   Water

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 50604-8283-1 1 BOTTLE In 1 CARTON contains a BOTTLE, GLASS 1 10 mL In 1 BOTTLE, GLASS This package is contained within the CARTON (50604-8283-1) 2 50604-8283-3 10 BOTTLE In 1 CARTON contains a BOTTLE, GLASS (50604-8283-2) 2 50604-8283-2 30 mL In 1 BOTTLE, GLASS This package is contained within the CARTON (50604-8283-3)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NADA	NADA098379	03/10/1978

Labeler - Merial Limited (034393582)

Revised: 09/2010Merial Limited

Cydectin Pour-On

Dosage Form: FOR ANIMAL USE ONLY
CYDECTIN®

moxidectin

Pour-On for Beef and Dairy Cattle

Antiparasitic

NADA 141-099, Approved by FDA

Contains 5 mg moxidectin/mL

For Treatment of Infections and Infestations Due to Internal and External Parasites of Beef and Dairy Cattle

Consult your veterinarian for assistance in the diagnosis, treatment and control of parasitism. If animals are likely to be reinfected following treatment, a strategic parasite control program should be established.

Mode of Action

Moxidectin is an endectocide in the milbemycin chemical class which shares the distinctive mode of action characteristic of macrocyclic lactones. CYDECTIN (moxidectin) Pour-On is specially formulated to allow moxidectin to be absorbed through the skin and distributed internally to the areas of the body affected by endo- and/or ectoparasitism. Moxidectin binds selectively and with high affinity to glutamate-gated chloride ion channels which are critical to the function of invertebrate nerve and muscle cells. This interferes with neurotransmission resulting in paralysis and elimination of the parasite.

Indications

Cydectin Pour-On when applied at the recommended dose level of 0.5 mg/2.2 lb (0.5 mg/kg) body weight is effective in the treatment and control of the following internal [adult and fourth-stage larvae (L4)] and external parasites of cattle:

Gastrointestinal Roundworms

Ostertagia ostertagi - Adult and L4 (including inhibited larvae)

Haemonchus placei - Adult and L4

Trichostrongylus axei - Adult and L4

Trichostrongylus colubriformis - Adult and L4

Cooperia oncophora - Adult and L4

Cooperia pectinata - Adult

Cooperia punctata - Adult and L4

Cooperia spatulata - Adult

Cooperia surnabada - Adult and L4

Bunostomum phlebotomum - Adult

Nematodirus helvetianus - Adult and L4

Oesophagostomum radiatum - Adult and L4

Lungworms

Dictyocaulus viviparus - Adult and L4

Cattle Grubs

Hypoderma bovis

Hypoderma lineatum

Mites

Chorioptes bovis

Psoroptes ovis (Psoroptes communis var. bovis)

Lice

Linognathus vituli

Haematopinus eurysternus

Solenopotes capillatus

Bovicola (Damalinia) bovis

Horn Flies

Haematobia irritans

Management Considerations for External Parasites

For most effective external parasite control, Cydectin Pour-On should be applied to all cattle in the herd. Cattle entering the herd following this administration should be treated prior to introduction. Consult your veterinarian or a livestock entomologist for the most appropriate time to apply Cydectin Pour-On in your location to effectively control horn flies and external parasites. Cydectin Pour-On provides seven days of persistent activity against horn flies. For optimal control of horn flies, the product should be used as part of an integrated control program utilizing other methods to provide extended control.

Persistent Activity

 Cydectin Pour-On has been proven to effectively control infections and protect from reinfection with Haemonchus placei for 14 days after treatment, Oesophagostomum radiatum and Ostertagia ostertagi for 28 days after treatment, and Dictyocaulus viviparus for 42 days after treatment. Efficacy below 90% was observed in some Ostertagia ostertagi persistent activity studies at 21 and 28 days posttreatment.

Dosage

CYDECTIN (moxidectin) Pour-On is a ready-to-use topical formulation intended for direct application to the hair and skin in a narrow strip extending along the top of the back from the withers to the tailhead (see Figure 1). Due to the angular topline characteristic of most dairy breeds, it is recommended that all pour-on products be applied slowly to dairy cows. Apply to healthy skin avoiding any mange scabs, skin lesions, mud or manure. Treated cattle can be easily recognized by the characteristic purple color, which will remain for a short period of time after treatment. The recommended rate of administration is 1 mL for each 22 lb (10 kg) body weight which provides 0.5 mg moxidectin for each 2.2 lb (0.5 mg/kg) body weight. The table below will assist in the calculation of the appropriate volume of pour-on which must be applied based on the weight of animal being treated.

Body Weight		Dose	Body Weight		Dose
Lb (kg)		mL	Lb (kg)		mL
88	(40)	4	330	(150)	15
110	(50)	5	440	(200)	20
132	(60)	6	550	(250)	25
154	(70)	7	660	(300)	30
176	(80)	8	770	(350)	35
198	(90)	9	880	(400)	40
220	(100)	10	990	(450)	45
242	(110)	11	1100	(500)	50
264	(120)	12	1210	(550)	55
286	(130)	13	1320	(600)	60
308	(140)	14	1430	(650)	65

Figure 1. Where to Apply Cydectin Pour-On

Use Conditions

Varying weather conditions, including rainfall, do not affect the efficacy of Cydectin Pour-On.

Administration

Cydectin Pour-On is available in three convenient package styles designed for ease of administration and the number of cattle to be treated. Directions for use of each container type follow:

Squeeze-Measure-Pour System

(16.91 fl oz/500 mL and 33.81 fl oz/1 L Bottles)

Determine the weight of the animal, calculate the recommended volume of Cydectin Pour-On and locate the volume marker equivalent to this dose on the dosing chamber of the bottle. Remove the dosing chamber cap and squeeze the main chamber of bottle until the desired level of solution is present in the dosing chamber. Release pressure on the container to avoid further filling. Holding the dosing chamber as shown below, pour this measured volume of solution evenly along the backline of the animal from the withers to the tailhead (see Figure 1).

Figure 2. Squeeze-Measure-Pour System 16.91 fl oz/500 mL and 33.81 fl oz/1 L Bottles)

Large Conventional Containers (84.54 fl oz/2.5 L and 169 fl oz/5 LBottles and 338 fl oz/10 L Cubetainer)

These bottles are designed for use with the CYDECTIN (moxidectin) Pour-On applicators. Simply remove the transient cap and seal and replace with the vented cap. Attach the applicator feeder hose to the vented cap. Invert the container prior to use (2.5 L and 5 L containers only). Apply the recommended volume of Cydectin Pour-On evenly along the backline of the animal from the withers to the tailhead (see Figure 1).

Figure 3. Large Conventional Containers (84.54 fl oz/2.5 L and 169 fl oz/5 L Bottles)

Figure 4. Large Conventional Container (338 fl oz/10 L Cubetainer)

Animal Safety

Tolerance and toxicity studies have demonstrated an adequate margin of safety to allow treatment of cattle of all ages with Cydectin Pour-On. No toxic signs were seen in cattle given up to 25 times the recommended dose level. Newborn calves similarly showed no toxic signs when treated with up to three times the recommended dose level within 12 hours of birth and nursing from cows concurrently treated with the recommended dose level of Cydectin Pour-On. In breeding animals (bulls and cows in estrous and during early, mid and late pregnancy), treatment with three times the recommended dose level had no effect on breeding performance.

Warning

Not For Use In Humans. Keep this and all drugs out of the reach of children. This product can cause irritation to skin, eyes, or mucous membranes. In case of accidental skin contact and/or clothing contamination, wash skin thoroughly with soap and water and launder clothing with detergent. In case of accidental eye contact, flush eyes with copious amounts of water. When direct inhalation occurs, cleanse lungs and respiratory passages with fresh air. In case of ingestion do not induce vomiting and seek medical attention immediately. If irritation or any other symptom attributable to exposure to this product persists, consult your physician.

To obtain a copy of the material safety data sheet (MSDS) which provides more detailed occupational safety information or to report adverse reactions attributable to exposure to this product, call 1-866-638-2226.

Residue Warning

When used according to label directions, neither a pre-slaughter drug withdrawal period nor a milk discard time are required. Meat and milk from cattle treated with CYDECTIN (moxidectin) Pour-On may be used for human consumption at any time following treatment. A withdrawal period has not been established for this product in pre-ruminating calves. Do not use in calves to be processed for veal.

Precautions

For external use only. Do not apply to areas of skin with mange scabs, skin lesions, mud or manure. Cydectin Pour-On is not recommended for use in species other than cattle. This product has been formulated specifically for topical use in cattle and should not be used in other animal species or by other routes of administration as adverse reactions may occur. Cydectin Pour-On is effective against the migrating stage of cattle grubs (Hypoderma larvae). Treatment with Cydectin Pour-On during the period when grubs are migrating through vital areas may cause undesirable host-parasite reactions. Killing H. lineatum when they are located in peri-esophageal tissues may cause bloat. Killing H. bovis when they are in the vertebral canal may cause staggering or hindlimb paralysis. Cattle should be treated as soon as possible after heel fly (warble fly) season to avoid this potential problem. Cattle treated with Cydectin Pour-On at the end of fly season can be re-treated during the winter without danger of grub-related reactions. Consult your veterinarian for more information regarding these secondary grub reactions and the correct time to treat with Cydectin Pour-On.

Environmental Safety

Studies indicate that when moxidectin comes in contact with the soil it readily and tightly binds to the soil and becomes inactive. Free moxidectin may adversely affect fish and certain aquatic organisms. Do not contaminate water by direct application or by improper disposal of drug containers.

Storage

Store product at or below room temperature. Avoid prolonged exposure above 25°C (77°F). If product becomes frozen, thaw completely and shake well prior to use.

Disposal

Dispose of containers in an approved landfill or by incineration.

Package Information

Cydectin Pour-On is available in five convenient container sizes. The 16.91 fl oz/500 mL (NDC 0010-3843-01) and 33.81 fl oz/1 L (NDC 0010-3843-02) are packaged in specially-designed squeeze-measure-pour polyethylene bottles. When treating larger numbers of cattle, 84.54 fl oz/2.5 L (NDC 0010-3843-03), 169 fl oz/5 L (NDC 0010-3843-04), or 338 fl oz/10 L (NDC 0010-3843-05) conventional polyethylene containers are available for use with most commercially-available topical applicators.

U.S. Patent No. 4,916,154 and 6,514,951

Cydectin is a registered trademark of Boehringer Ingelheim Vetmedica, Inc.

© 2010 Boehringer Ingelheim Vetmedica, Inc. All Rights Reserved.

Manufactured for:

Boehringer Ingelheim Vetmedica, Inc.

St. Joseph, MO 64506 U.S.A.

10190 Revised January 2010 2680I

mL Front Label

mL Back Label

mL Carton Front and Side Panel

mL Carton Back and Side Panel

CYDECTIN  moxidectin  liquid

Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 0010-3843 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength MOXIDECTIN (MOXIDECTIN) MOXIDECTIN 5 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0010-3843-01 1 BOTTLE In 1 CARTON contains a BOTTLE, PLASTIC 1 500 mL In 1 BOTTLE, PLASTIC This package is contained within the CARTON (0010-3843-01) 2 0010-3843-02 1 BOTTLE In 1 CARTON contains a BOTTLE, PLASTIC 2 1000 mL In 1 BOTTLE, PLASTIC This package is contained within the CARTON (0010-3843-02) 3 0010-3843-03 1 BOTTLE In 1 CARTON contains a BOTTLE, PLASTIC 3 2500 mL In 1 BOTTLE, PLASTIC This package is contained within the CARTON (0010-3843-03) 4 0010-3843-04 1 BOTTLE In 1 CARTON contains a BOTTLE, PLASTIC 4 5000 mL In 1 BOTTLE, PLASTIC This package is contained within the CARTON (0010-3843-04) 5 0010-3843-05 1 BOTTLE In 1 CARTON contains a BOTTLE, PLASTIC 5 10000 mL In 1 BOTTLE, PLASTIC This package is contained within the CARTON (0010-3843-05)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NADA	NADA141099	06/21/2010

Labeler - Boehringer Ingelheim Vetmedica, Inc. (007134091)

Revised: 11/2010Boehringer Ingelheim Vetmedica, Inc.

Cystadane

betaine

Dosage Form: powder, for oral solution
HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use Cystadane safely and effectively.  See full prescribing information for Cystadane.


Cystadane (betaine anhydrous for oral solution) powder

Initial U.S. Approval: 1996

Indications and Usage for Cystadane

Cystadane is a methylating agent indicated for the treatment of homocystinuria to decrease elevated homocysteine blood levels.  Included within the category of homocystinuria are (1):

• Cystathionine beta-synthase (CBS) deficiency


• 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency


• Cobalamin cofactor metabolism (cbl) defect
  

Cystadane Dosage and Administration

• Usual dose in adult and pediatric patients is 6 grams per day, administered orally in divided doses of 3 grams two times a day.(2)


• In children less than 3 years of age, may initiate dosing at 100 mg/kg/day, divided in twice daily doses, and then increased weekly by 50 mg/kg increments.(2)


• Dose can be gradually increased until plasma total homocysteine is undetectable or present only in small amounts.(2)


• Monitor patient response by plasma homocysteine levels.(2)


• Prescribed amount of Cystadane should be measured with the measuring scoop provided and then dissolved in 4 to 6 ounces of water, juice, milk, or formula, or mixed with food for immediate ingestion.(2)
  

Dosage Forms and Strengths

Powder for oral solution available in bottles containing 180 grams of betaine anhydrous.(3)

Contraindications

• None (4)
  

Warnings and Precautions

• Hypermethioninemia:  Cystadane may worsen elevated plasma methionine concentrations in patients with CBS deficiency.  Cerebral edema has been reported in patients receiving Cystadane.( 5.1)


• Monitoring:  Monitor plasma methionine concentrations in patients with CBS deficiency.  Keep plasma methionine concentrations below 1,000 mmol/L through dietary medication and, if necessary, a reduction of Cystadane dose. ( 5.1)

Adverse Reactions

Most common adverse reactions (incidence > 2%) were nausea and gastrointestinal distress, based on physician survey.


To report SUSPECTED ADVERSE REACTIONS, contact Rare Disease Therapeutics at 1-615-399-0700, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

USE IN SPECIFIC POPULATIONS

• Pregnancy: Animal reproduction studies have not been conducted with Cystadane.  Use only if clearly needed.(8.1)


• Nursing women: It is not known whether Cystadane is excreted in human milk.  Use only if clearly needed.(8.3)


• Pediatrics: Pediatric patients ranging in age from 24 days to 17 years have been treated with Cystadane.  Children younger than 3 years of age may benefit from dose titration. 

See 17 for PATIENT COUNSELING INFORMATION.


                Revised: April 2010

FULL PRESCRIBING INFORMATION: CONTENTS*


1    INDICATIONS AND USAGE

2    DOSAGE AND ADMINISTRATION

      2.1    Dosage               

      2.2    Administration

3    DOSAGE FORMS AND STRENGTHS

4    CONTRAINDICATIONS

5    WARNINGS AND PRECAUTIONS

      5.1    Hypermethioninemia

6    ADVERSE REACTIONS

      6.1   Adverse Reactions in Clinical Studies

      6.2    Postmarketing Experience

8    USE IN SPECIFIC POPULATIONS

      8.1    Pregnancy

      8.3    Nursing Mothers

      8.4    Pediatric Use     

10    OVERDOSAGE

11    DESCRIPTION

12    CLINICAL PHARMACOLOGY

        12.1    Mechanism of Action

        12.2    Pharmacodynamics

        12.3    Pharmacokinetics

13    NONCLINICAL TOXICOLOGY

        13.1    Carcinogenesis, Mutagenesis, Impairment of Fertility

14    CLINICAL STUDIES

16    HOW SUPPLIED/STORAGE AND HANDLING

        16.1  Storage

17    PATIENT COUNSELING INFORMATION

        17.1   Dosing and Administration


*Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION

Indications and Usage for Cystadane

Cystadane® (betaine anhydrous for oral solution) is indicated for the treatment of homocystinuria to decrease elevated homocysteine blood levels.  Included within the category of homocystinuria are:  

• Cystathionine beta-synthase (CBS) deficiency


• 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency


• Cobalamin cofactor metabolism (cbl) defect
  

Cystadane Dosage and Administration

2.1 Dosage

The usual dosage in adult and pediatric patients is 6 grams per day administered orally in divided doses of 3 grams twice daily.  In pediatric patients less than 3 years of age, dosage may be started at 100 mg/kg/day divided in twice daily doses, and then increased weekly by 50 mg/kg increments. 

Therapy with Cystadane should be directed by physicians knowledgeable in the management of patients with homocystinuria.  Patient response to Cystadane can be monitored by homocysteine plasma levels.  Dosage in all patients can be gradually increased until plasma total homocysteine is undetectable or present only in small amounts.  Response (by homocysteine plasma levels) usually occurs within several days and steady state within a month.  Plasma methionine concentrations should be monitored in patients with CBS deficiency [See Warnings and Precautions (15.2)].

Dosages of up to 20 grams per day have been necessary to control homocysteine levels in some patients.  However, one pharmacokinetic and pharmacodynamic in vitro simulation study indicated minimal benefit from exceeding a twice-daily dosing schedule and a 150 mg/kg/day dosage for Cystadane.

2.2 Administration

The prescribed amount of Cystadane should be measured with the measuring scoop provided (one level 1.7 mL scoop is equal to 1 gram of betaine anhydrous powder) and then dissolved in 4 to 6 ounces (120 to 180 mL) of water, juice, milk, or formula, or mixed with food for immediate ingestion.

Dosage Forms and Strengths

Cystadane is a white, granular, hygroscopic powder for oral solution available in bottles containing 180 grams of betaine anhydrous.

Contraindications

None.

Warnings and Precautions

5.1    Risk of Hypermethioninemia in Patients with CBS Deficiency

Patients with homocystinuria due to cystathionine beta-synthase (CBS) deficiency may also have elevated plasma methionine concentrations.  Treatment with Cystadane may further increase methionine concentrations due to the remethylation of homocysteine to methionine.  Cerebral edema has been reported in patients with hypermethioninemia, including patients treated with Cystadane.  Plasma methionine concentrations should be monitored in patients with CBS deficiency.  Plasma methionine concentrations should be kept below 1,000 µmol/L through dietary modification and, if necessary, a reduction of Cystadane dose.

Adverse Reactions

 6.1    Adverse Reactions in Clinical Studies

The most serious adverse reaction reported with Cystadane treatment is the development of hypermethioninemia and cerebral edema in patients with CBS Deficiency [see Warnings and Precautions (5.1)].


The assessment of clinical adverse reactions is based on a survey study of 41 physicians, who treated a total of 111 homocystinuria patients with Cystadane.  Adverse reactions were retrospectively recalled and were not collected systematically in this open-label, uncontrolled, physician survey.  Thus, this list may not encompass all types of potential adverse reactions, reliably estimate their frequency, or establish a causal relationship to drug exposure.  The following adverse reactions were reported (Table 1):

Table 1: Number of Patients with Adverse Reactions to Cystadane by Physician Survey

Adverse Reactions	Number of Patients
Nausea	2
Gastrointestinal distress	2
Diarrhea	1
"Bad Taste"	1
"Caused Odor"	1
Questionable psychological changes	1
“Aspirated the powder”	1

6.2    Postmarketing Experience

The following adverse reactions have been identified during post approval use of Cystadane.  Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. 

   

In postmarketing experience with Cystadane, severe cerebral edema and hypermethioninemia have been reported within 2 weeks to 6 months of starting betaine therapy, with complete recovery after discontinuation of Cystadane.  All patients who developed cerebral edema had homocystinuria due to CBS deficiency and had severe elevation in plasma methionine levels (range 1,000 to 3,000 mM).  As cerebral edema has also been reported in patients with hypermethioninemia, secondary hypermethioninemia due to betaine therapy has been postulated as a possible mechanism of action.


The following adverse reactions have been reported in patients during postmarketing use of Cystadane: anorexia, agitation, depression, irritability, personality disorder, sleep disturbed, dental disorders, diarrhea, glossitis, nausea, stomach discomfort, vomiting, hair loss, hives, skin odor abnormalities, and urinary incontinence.

USE IN SPECIFIC POPULATIONS

8.1    Pregnancy

Pregnancy Category C: Animal reproduction studies have not been conducted with Cystadane.  It is also not known whether Cystadane can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.  Cystadane should be given to a pregnant woman only if clearly needed.

8.3    Nursing Mothers

It is not known whether Cystadane is excreted in human milk.  Use only if clearly needed.

8.4    Pediatric Use

The majority of case studies of homocystinuria patients treated with Cystadane have been pediatric patients, including patients ranging in age from 24 days to 17 years [see Clinical Studies (14)].  Children younger than 3 years of age may benefit from dose titration [see Dosage and Administration (2)].

Overdosage

In an acute toxicology study in rats, death occurred frequently at doses equal to or greater than 10 g/kg.

Cystadane Description

Cystadane (betaine anhydrous for oral solution) is an agent for the treatment of homocystinuria.  It contains no ingredients other than anhydrous betaine. Cystadane is a white, granular, hygroscopic powder, which is diluted in water and administered orally.  The chemical name of betaine anhydrous powder is trimethylglycine.  It has a molecular weight of 117.15.  The structural formula is:

Cystadane - Clinical Pharmacology

12.1 Mechanism of Action

Cystadane acts as a methyl group donor in the remethylation of homocysteine to methionine in patients with homocystinuria.  Cystadane occurs naturally in the body.  It is a metabolite of choline and is present in small amounts in foods such as beets, spinach, cereals, and seafood.

12.2 Pharmacodynamics

Cystadane was observed to lower plasma homocysteine levels in three types of homocystinuria, including CBS deficiency; MTHFR deficiency; and cbl defect.  Patients have taken Cystadane for many years without evidence of tolerance.  There has been no demonstrated correlation between Cystadane levels and homocysteine levels.

In CBS-deficient patients, large increases in methionine levels over baseline have been observed.  Cystadane has also been demonstrated to increase low plasma methionine and S-adenosylmethionine (SAM) levels in patients with MTHFR deficiency and cbl defect.

12.3 Pharmacokinetics

Pharmacokinetic studies of Cystadane are not available.  Plasma levels of Cystadane have not been measured in patients and have not been correlated to homocysteine levels.

Nonclinical Toxicology

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term carcinogenicity and fertility studies have not been conducted with Cystadane.  No evidence of genotoxicity was demonstrated in the following tests: metaphase analysis of human lymphocytes; bacterial reverse mutation assay; and mouse micronucleus test.

Clinical Studies

Cystadane was studied in a double-blind, placebo-controlled, crossover study in 6 patients with CBS deficiency, ages 7 to 32 years at enrollment.  Cystadane was administered at a dosage of 3 grams twice daily, for 12 months. Plasma homocystine levels were significantly reduced (p<0.01) compared to placebo. Plasma methionine levels were variable and not significantly different compared to placebo. No adverse events were reported in any patient.

Cystadane has also been evaluated in observational studies without concurrent controls in patients with homocystinuria due to CBS deficiency, MTHFR deficiency, or cbl defect.A review of 16 case studies and the randomized controlled trial previously described was also conducted, and the data available for each study were summarized; however, no formal statistical analyses were performed. The studies included a total of 78 male and female patients with homocystinuria who were treated with Cystadane. This included 48 patients with CBS deficiency, 13 with MTHFR deficiency, and 11 with cbl defect, ranging in age from 24 days to 53 years. The majority of patients (n=48) received 6 gm/day, 3 patients received less than 6 gm/day, 12 patients received doses from 6 to 15 gm/day, and 5 patients received doses over 15 gm/day. Most patients were treated for more than 3 months (n=57) and 30 patients were treated for 1 year or longer (range 1 month to 11 years). Homocystine is formed nonenzymatically from two molecules of homocysteine, and both have be used to evaluate the effect of Cystadane in patients with homocystinuria. Plasma homocystine or homocysteine levels were reported numerically for 62 patients, and 61 of these patients showed decreases with Cystadane treatment. Homocystine decreased by 83-88% regardless of pre-treatment level, and homocysteine decreased by 71-83%, regardless of the pre-treatment level. Clinical improvement, such as improvement in seizures, or behavioral and cognitive functioning, was reported by the treating physicians in about three-fourths of patients. Many of these patients were also taking other therapies such as vitamin B6 (pyridoxine), vitamin B12 (cobalamin), and folate with variable biochemical responses. In most cases, adding Cystadane resulted in a further reduction of either homocystine or homocysteine.

How Supplied/Storage and Handling

Cystadane is available in plastic bottles containing 180 grams of betaine anhydrous.  Each bottle is equipped with a plastic child-resistant cap and is supplied with a polystyrene measuring scoop.  One level scoop (1.7 mL) is equal to 1 gram of betaine anhydrous powder.

NDC 66621-4000-1    180 g/bottle

Cystadane can be ordered by calling Accredo Health Group, Inc., Customer service at 1-888-454-8860

16.1    Storage

Store at room temperature, 15 – 30 ˚C (59 – 86 ˚F).  Protect from moisture.

Patient Counseling Information

Patients should be advised of the following information before beginning treatment with Cystadane:

17.1    Dosing and Administration

• Instruct patients and caregivers that Cystadane should only be taken as directed by their healthcare professional.


• Instruct patients and caregivers to administer Cystadane as follows:


• Shake bottle lightly before removing cap.


• Measure with the scoop provided.


• Measure the number of scoops as prescribed by their healthcare professional. One level scoop (1.7 mL) is equivalent to 1 gram of betaine anhydrous powder.


• Mix powder with 4 to 6 ounces (120 to 180 mL) of water, juice, milk, or formula until completely dissolved, or mix with food, then ingest mixture immediately.


• Always replace the cap tightly after using, and protect powder from moisture.
  

Distributed in the U.S. by:

Rare Disease Therapeutics, Inc.

2550 Meridian Blvd., Suite 150

Franklin, TN 37067


Part No.:    RDT C PI003

Cystadane  betaine  powder, for solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 66621-4000 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength betaine (betaine) betaine 6 g

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color white (none) Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 66621-4000-1 180 SCOOPFUL In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA020576	10/25/1996

Labeler - Rare Disease Therapeutics, Inc. (966133100)

Registrant - Rare Disease Therapeutics, Inc. (966133100)

Establishment
Name	Address	ID/FEI	Operations
Rare Disease Therapeutics, Inc.		966133100	label

Establishment
Name	Address	ID/FEI	Operations
Orphan Europe, SARL		767598352	manufacture

Revised: 06/2010Rare Disease Therapeutics, Inc.

More Cystadane resources

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

• Cystadane Concise Consumer Information (Cerner Multum)


• Cystadane Advanced Consumer (Micromedex) - Includes Dosage Information


• Cystadane Powder MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Cystadane with other medications

• Nonalcoholic Fatty Liver Disease

cyproterone Oral, Intramuscular

sye-PROE-ter-one

Available Dosage Forms:

• Injectable


• Tablet

Uses For cyproterone

Cyproterone is used to treat cancer of the prostate gland. The prostate gland is present only in males; therefore, females do not get prostate cancer.

cyproterone blocks the effect of the male hormone testosterone in the body. This decreases the amount of testosterone produced in the body and is one way of treating this type of cancer.

cyproterone is available only with your doctor's prescription.

Before Using cyproterone

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 cyproterone, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to cyproterone 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

Studies on cyproterone have been done only in adult patients, and there is no specific information comparing use of cyproterone in children with use in other age groups.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of cyproterone in the elderly with use in other age groups.

Breast Feeding

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

Interactions with Medicines

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

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

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

• Blood clots (or history of) or


• Circulation disease (or history of) or


• Stroke (or history of)—If these conditions already are already present, cyproterone may have a greater chance of causing blood clotting problems.

• Cardiac disease—May make the condition worse.

• Depressive tendencies—May cause depression to occur.

• Type 2 diabetes mellitus—May cause a loss of control of diabetes by increasing blood and urine sugar.

• Liver disease—Effects of cyproterone may be increased because of its slower removal from the body.

Proper Use of cyproterone

At first, cyproterone often causes loss of strength and energy or tiredness. However, these effects are lessened after about the third month of treatment and it is very important that you continue to receive this medication.

This medication should not be discontinued even if improvement of the disease occurs.

Dosing

The dose of cyproterone 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 cyproterone. 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 oral dosage form (tablets):
  
  • For treating prostate cancer:
    
    • Adults—100 to 200 milligrams (mg) per day divided into 2 to 3 doses. Take after meals.
    
    
  
  

• For injection dosage form:
  
  • For treating prostate cancer:
    
    • Adult—300 milligrams (mg) injected into a muscle once a week.
    
    
  
  

Missed Dose

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

Storage

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

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

Precautions While Using cyproterone

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it.

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

Cyproterone may cause your skin to be more sensitive to sunlight than it is normally. Exposure to sunlight, even for brief periods of time, may cause a skin rash, itching, redness or other discoloration of the skin, or a severe sunburn. When you begin taking cyproterone:

• Stay out of direct sunlight, especially between the hours of 10:00 a.m. and 3:00 p.m., if possible.


• Wear protective clothing, including a hat. Also, wear sunglasses.


• Apply a sun block product that has a skin protection factor (SPF) of at least 15. Some patients may require a product with a higher SPF number, especially if they have a fair complexion. If you have any questions about this, check with your health care professional.


• Apply a sun block lipstick that has an SPF of at least 15 to protect your lips.


• Do not use a sunlamp or tanning bed or booth.

If you have a severe reaction from the sun, check with your doctor.

While you are taking cyproterone, be careful to limit the amount of alcohol you drink.

cyproterone 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 as soon as possible if any of the following side effects occur:

Less common

• Abdominal pain or tenderness


• agitation


• back pain


• black, tarry stools


• blisters on the skin


• bloody urine


• blurred vision


• chest pain


• chills


• clay-colored stools


• confusion


• cough


• dark urine


• decreased appetite


• decreased urine output


• difficulty swallowing


• dilated neck veins


• dizziness


• drowsiness


• dry mouth


• fainting or light-headedness when getting up from a lying or sitting position suddenly


• fast heartbeat


• fatigue


• fever


• flushed, dry skin


• fruit-like breath odor


• general feeling of discomfort or illness


• hallucinations


• headache, sudden and severe


• hives


• inability to speak


• increased blood pressure


• increased hunger


• increased thirst


• increased urination


• irregular breathing


• irregular heartbeat


• itching


• loss of consciousness


• lower back or side pain


• mood or mental changes


• nausea and vomiting


• painful or difficult urination


• pains in the chest, groin, or legs, especially the calves of legs


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


• red, thickened, or scaly skin


• seizures


• shortness of breath


• skin rash


• slurred speech


• sore throat


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


• stiff neck


• stomachache


• sudden loss of coordination


• sweating


• swelling of the feet or lower legs


• swollen and/or painful glands


• temporary blindness


• tightness in the chest


• unexplained weight loss


• unusual bleeding or bruising


• vision changes


• weakness in the arm and/or leg on one side of the body, sudden and severe


• wheezing


• yellow eyes or skin

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

• Decreased interest in sexual intercourse


• inability to have or keep an erection


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


• increased interest in sexual intercourse


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


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


• unexpected or excess milk flow from breasts

Less common

• Bleeding, blistering, burning, coldness, or discoloration of the skin


• change in walking and balance


• clumsiness or unsteadiness


• hair loss


• inability to move legs or arms


• increased sensitivity of skin to sunlight


• increase in bowel movements


• loose stools


• loss of strength or energy


• muscle pain or weakness


• paralysis of one side of the body


• redness or other discoloration of the skin


• severe sunburn


• soft stools


• tiredness or weakness


• unusual increase in hair growth


• weight gain

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.

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

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

cytarabine

Generic Name: cytarabine (sye TAR a been)

Brand names: Cytosar-U, Tarabine PFS, Cytosar

What is cytarabine?

Cytarabine is a cancer medication that interferes with the growth and spread of cancer cells in the body.

Cytarabine is used to treat certain types of leukemia (blood cancers). Cytarabine is also used to treat leukemia associated with meningitis.

Cytarabine will not treat an active meningitis infection that has already developed in the body.

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

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

Cytarabine can cause serious side effects on your brain or central nervous system that may not be reversible. Cytarabine is usually given together with a steroid medication to help lessen these side effects. Talk with your doctor about the risks and benefits of using this medication. Do not use cytarabine if you are pregnant. It could harm the unborn baby.

Before you receive cytarabine, tell your doctor if you have a seizure disorder or a history of head injury or brain tumor.

Cytarabine can lower blood cells that help your body fight infections. Your blood may need to be tested often. Avoid being near people who are sick or have infections. Avoid activities that may increase your risk of bleeding injury. Tell your doctor at once if you develop signs of infection. Do not receive a "live" vaccine while you are being treated with cytarabine. The live vaccine may not work as well during this time, and may not fully protect you from disease.

What should I discuss with my healthcare provider before receiving cytarabine?

Cytarabine can cause serious side effects on your brain or central nervous system that may not be reversible. Cytarabine is usually given together with a steroid medication to help lessen these side effects. Talk with your doctor about the risks and benefits of using this medication. You should not receive this medication if you are allergic to cytarabine.

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

• 
  

  epilepsy or other seizure disorder; or

  
  


• 
  

  a history of head injury or brain tumor.

  
  

FDA pregnancy category D. Do not receive cytarabine if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment. It is not known whether cytarabine passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are receiving cytarabine.

How is cytarabine given?

Cytarabine is given as an injection through a needle placed into a vein, under the skin, or into the space around the spinal cord. You will receive this injection in a clinic or hospital setting.

Cytarabine is usually given once every 2 to 4 weeks. Follow your doctor's dosing instructions very carefully.

Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when cytarabine is injected.

After receiving an injection in the space around your spinal cord, you will need to lie flat for at least 1 hour. You will be watched closely during this time to make sure you do not have serious side effects.

Cytarabine can lower blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood may need to be tested often. Visit your doctor regularly.

What happens if I miss a dose?

Call your doctor for instructions if you miss an appointment for your cytarabine injection.

What happens if I overdose?

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

Overdose symptoms may include severe forms of some of the side effects listed in this medication guide.

What should I avoid while receiving cytarabine?

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Do not receive a "live" vaccine while receiving cytarabine. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), Bacillus Calmette-Guérin (BCG), oral polio, rotavirus, smallpox, typhoid, yellow fever, varicella (chickenpox), H1N1 influenza, and nasal flu vaccine.

Cytarabine side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Tell your caregivers at once if you have a serious side effect such as:

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  fever with nausea, vomiting, and headache;

  
  


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  problems with your vision or hearing;

  
  


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  loss of movement in any part of your body;

  
  


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  loss of bowel or bladder control;

  
  


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  fever, chills, body aches, flu symptoms, sores in your mouth and throat;

  
  


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

  
  


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  confusion, unusual thoughts or behavior;

  
  


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  trouble standing or walking,

  
  


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  seizure (convulsions);

  
  


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  pain or burning when you urinate;

  
  


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  feeling like you might pass out; or

  
  


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  feeling very thirsty or hot, being unable to urinate, heavy sweating, or hot and dry skin.

  
  

Less serious side effects may include:

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  drowsiness, dizziness, weakness, memory problems;

  
  


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  constipation, diarrhea, mild nausea;

  
  


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  back pain, pain in your arms or legs;

  
  


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  headache; or

  
  


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  trouble sleeping (insomnia).

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Cytarabine Dosing Information

Usual Adult Dose for Acute Nonlymphocytic Leukemia:

As a part of a combination chemotherapy:
100 mg/m2/day by continuous IV infusion (days 1 to 7) or 100 mg/m2 IV every 12 hours (days 1 to 7) with an anthracycline.

Usual Adult Dose for non-Hodgkin's Lymphoma:

Acute Leukemia Induction:
100 to 200 mg/m2/day or 2 to 6 mg/kg/day as a continuous IV infusion over 24 hours or in divided doses by rapid injection for 5 to 10 days. This course may be repeated approximately every 2 weeks.


For refractory non-Hodgkin's lymphomas and acute myeloid leukemia:
2 to 3 g/m2 IV every twelve hours for up to 12 doses. The IV infusion generally takes place over 1 to 3 hours. The dose of cytarabine should be suspended or modified if the ANC is below 1000/mm3 or the platelet count is below 50,000/mm3.


For chronic granulocytic leukemia / chronic myelogenous leukemia:
20 mg/m2 subcutaneously for 10 days per month for 6 months with interferon alfa.

Usual Adult Dose for Chronic Myelogenous Leukemia:

Acute Leukemia Induction:
100 to 200 mg/m2/day or 2 to 6 mg/kg/day as a continuous IV infusion over 24 hours or in divided doses by rapid injection for 5 to 10 days. This course may be repeated approximately every 2 weeks.


For refractory non-Hodgkin's lymphomas and acute myeloid leukemia:
2 to 3 g/m2 IV every twelve hours for up to 12 doses. The IV infusion generally takes place over 1 to 3 hours. The dose of cytarabine should be suspended or modified if the ANC is below 1000/mm3 or the platelet count is below 50,000/mm3.


For chronic granulocytic leukemia / chronic myelogenous leukemia:
20 mg/m2 subcutaneously for 10 days per month for 6 months with interferon alfa.

Usual Adult Dose for Acute Myeloid Leukemia:

Acute Leukemia Induction:
100 to 200 mg/m2/day or 2 to 6 mg/kg/day as a continuous IV infusion over 24 hours or in divided doses by rapid injection for 5 to 10 days. This course may be repeated approximately every 2 weeks.


For refractory non-Hodgkin's lymphomas and acute myeloid leukemia:
2 to 3 g/m2 IV every twelve hours for up to 12 doses. The IV infusion generally takes place over 1 to 3 hours. The dose of cytarabine should be suspended or modified if the ANC is below 1000/mm3 or the platelet count is below 50,000/mm3.


For chronic granulocytic leukemia / chronic myelogenous leukemia:
20 mg/m2 subcutaneously for 10 days per month for 6 months with interferon alfa.

Usual Adult Dose for Leukemia:

Acute Leukemia Induction:
100 to 200 mg/m2/day or 2 to 6 mg/kg/day as a continuous IV infusion over 24 hours or in divided doses by rapid injection for 5 to 10 days. This course may be repeated approximately every 2 weeks.


For refractory non-Hodgkin's lymphomas and acute myeloid leukemia:
2 to 3 g/m2 IV every twelve hours for up to 12 doses. The IV infusion generally takes place over 1 to 3 hours. The dose of cytarabine should be suspended or modified if the ANC is below 1000/mm3 or the platelet count is below 50,000/mm3.


For chronic granulocytic leukemia / chronic myelogenous leukemia:
20 mg/m2 subcutaneously for 10 days per month for 6 months with interferon alfa.

Usual Adult Dose for Meningeal Leukemia:

The manufacturer has stated that doses ranging from 5 mg/m2 to 75 mg/m2 has been used intrathecally and the frequency of administration has varied from once a day for 4 days to once every 4 days. The manufacturer has further stated that 30 mg/m2 every 4 days until cerebrospinal fluid findings were normal, followed by one additional treatment was the therapy most frequently used.

Some clinicians today recommend 10 to 30 mg intrathecally up to 3 times a week.

Usual Pediatric Dose for Acute Nonlymphocytic Leukemia:

As a part of a combination chemotherapy:
100 mg/m2/day by continuous IV infusion (days 1 to 7) or 100 mg/m2 IV every 12 hours (days 1 to 7) with an anthracycline.

Usual Pediatric Dose for non-Hodgkin's Lymphoma:

For refractory non-Hodgkin's lymphomas and acute myeloid leukemia:
1 to 3 g/m2 IV every twelve hours for up to 12 doses The IV infusion generally takes place over 1 to 3 hours. The dose of cytarabine should be suspended or modified if the ANC is below 1000/mm3 or the platelet count is below 50,000/mm3.

Usual Pediatric Dose for Acute Myeloid Leukemia:

For refractory non-Hodgkin's lymphomas and acute myeloid leukemia:
1 to 3 g/m2 IV every twelve hours for up to 12 doses The IV infusion generally takes place over 1 to 3 hours. The dose of cytarabine should be suspended or modified if the ANC is below 1000/mm3 or the platelet count is below 50,000/mm3.

Usual Pediatric Dose for Meningeal Leukemia:

The manufacturer has stated that doses ranging from 5 mg/m2 to 75 mg/m2 has been used intrathecally and the frequency of administration has varied from once a day for 4 days to once every 4 days. The manufacturer has further stated that 30 mg/m2 every 4 days until cerebrospinal fluid findings were normal, followed by one additional treatment was the therapy most frequently used.

However, some clinicians recommend the following age based dosing:
1 to 2 years: 30 mg
2 to 3 years: 50 mg
>3 years: 70 to 75 mg

What other drugs will affect cytarabine?

Tell your doctor if you take digoxin (Lanoxin).

This list is not complete and other drugs may interact with cytarabine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More cytarabine resources

• Cytarabine Use in Pregnancy & Breastfeeding
• Cytarabine Drug Interactions
• Cytarabine Support Group
• 0 Reviews for Cytarabine - Add your own review/rating

• cytarabine Advanced Consumer (Micromedex) - Includes Dosage Information


• Cytarabine Prescribing Information (FDA)


• Cytarabine Professional Patient Advice (Wolters Kluwer)


• Cytarabine Monograph (AHFS DI)


• Cytarabine MedFacts Consumer Leaflet (Wolters Kluwer)

Compare cytarabine with other medications

• Acute Myeloid Leukemia
• Acute Nonlymphocytic Leukemia
• Chronic Myelogenous Leukemia
• Leukemia
• Meningeal Leukemia
• Non-Hodgkin's Lymphoma

Where can I get more information?

• Your pharmacist can provide more information about cytarabine.