Hespan

hetastarch in sodium chloride

Dosage Form: injection, solution
Hespan®

(6% hetastarch in 0.9% sodium chloride injection)

Hespan Description

Hespan® (6% hetastarch in 0.9% sodium chloride injection) is a sterile, nonpyrogenic solution for intravenous administration. Each 100 mL contains:

  Hetastarch.............................................................................................................6   g

  Sodium Chloride, USP..........................................................................................0.9 g

  Water for Injection, USP...........................................................................................qs

  pH adjusted with Sodium Hydroxide, NF if necessary

  Concentration of Electrolytes (mEq/L): Sodium 154, Chloride 154

  pH: approximately 5.9 with negligible buffering capacity

  Calc. Osmolarity: approximately 309 mOsM

Hetastarch is a synthetic colloid derived from a waxy starch composed almost entirely of amylopectin. Hydroxyethyl ether groups are introduced into the glucose units of the starch, and the resultant material is hydrolyzed to yield a product with a molecular weight suitable for use as a plasma volume expander and erythrocyte sedimenting agent. Hetastarch is characterized by its molar substitution and also by its molecular weight. The molar substitution is approximately 0.75 which means hetastarch has an average of approximately 75 hydroxyethyl groups for every 100 glucose units. The weight average molecular weight is approximately 600,000 with a range of 450,000 to 800,000 and with at least 80% of the polymers falling within the range of 20,000 to 2,600,000. Hydroxyethyl groups are attached by ether linkage primarily at C-2 of the glucose unit and to a lesser extent at C-3 and C-6. The polymer resembles glycogen, and the polymerized D-glucose units are joined primarily by α-1,4 linkages with occasional α-1,6 branching linkages. The degree of branching is approximately 1:20 which means that there is an average of approximately one α-1,6 branching point for every 20 glucose monomer units.

The chemical name for hetastarch is hydroxyethyl starch.

The structural formula is as follows:

Amylopectin derivative in which R2 and R3 are H or CH2CH2OH and R6 is H, CH2CH2OH, or a branching point in the starch polymer connected through an α-1,6 link to additional D-glucopyranosyl units.

Hespan® is a clear, pale yellow to amber solution. Exposure to prolonged adverse storage conditions may result in a change to a turbid deep brown or the formation of a crystalline precipitate. Do not use the solution if these conditions are evident.

The Excel® Container is Latex-free; PVC-free; and DEHP-free.

The plastic container is made from a multi-layered film specifically developed for parenteral drugs. It contains no plasticizers and exhibits virtually no leachables. The solution contact layer is a rubberized copolymer of ethylene and propylene. The container is nontoxic and biologically inert. The container-solution unit is a closed system and is not dependent upon entry of external air during administration. The container is overwrapped to provide protection from the physical environment and to provide an additional moisture barrier when necessary.

The closure system has two ports; the one for the administration set has a tamper evident plastic protector.

Hespan - Clinical Pharmacology

The plasma volume expansion produced by Hespan® approximates that of 5% Albumin (Human). Intravenous infusion of Hespan® results in expansion of plasma volume that decreases over the succeeding 24 to 36 hours. The degree of plasma volume expansion and improvement in hemodynamic state depend upon the patient's intravascular status.

Hetastarch molecules below 50,000 molecular weight are rapidly eliminated by renal excretion. A single dose of approximately 500 mL of Hespan® (approximately 30 g) results in elimination in the urine of approximately 33% of the dose within 24 hours. This is a variable process but generally results in an intravascular hetastarch concentration of less than 10% of the total dose injected by two weeks. A study of the biliary excretion of Hespan® in 10 healthy males accounted for less than 1% of the dose over a 14 day period. The hydroxyethyl group is not cleaved by the body but remains intact and attached to glucose units when excreted. Significant quantities of glucose are not produced as hydroxyethylation prevents complete metabolism of the smaller polymers.

The addition of hetastarch to whole blood increases the erythrocyte sedimentation rate. Therefore, Hespan® is used to improve the efficiency of granulocyte collection by centrifugal means.

In randomized, controlled, comparative studies of Hespan® (6% hetastarch in 0.9% sodium chloride injection) (n=92) and Albumin (n=85) in surgical patients, no patient in either treatment group had a bleeding complication and no significant difference was found in the amount of blood loss between the treatment groups.1–4

Indications and Usage for Hespan

Hespan® is indicated in the treatment of hypovolemia when plasma volume expansion is desired. It is not a substitute for blood or plasma.

The adjunctive use of Hespan® in leukapheresis has also been shown to be safe and efficacious in improving the harvesting and increasing the yield of granulocytes by centrifugal means.

Contraindications

Hespan® is contraindicated in patients with known hypersensitivity to hydroxyethyl starch. It is also contraindicated in clinical conditions where volume overload is a potential problem, such as, congestive heart failure or renal disease with anuria or oliguria not related to hypovolemia.

Patients with pre-existing coagulation or bleeding disorders should not be given Hespan®.

Warnings

Life threatening anaphylactic/anaphylactoid reactions have been rarely reported with Hespan®; death has occurred, but a causal relationship has not been established. Patients who develop severe anaphylactic/anaphylactoid reactions may need continued supportive care until symptoms have resolved.

Hypersensitivity reactions can occur even after Hespan® has been discontinued.

Usage in Plasma Volume Expansion

Hespan® has not been adequately evaluated to establish its safety in situations other than treatment of hypovolemia in elective surgery.

Large volumes of Hespan® may transiently alter the coagulation mechanism due to hemodilution and a direct inhibitory action on Factor VIII. Administration of volumes of Hespan® that are greater than 25% of the blood volume in less than 24 hours may cause significant hemodilution reflected by lower hematocrit and plasma protein values. Administration of packed red cells, platelets, or fresh frozen plasma should be considered if clinically indicated.

Hespan® is not recommended for use as a cardiac bypass pump prime, while the patient is on cardiopulmonary bypass, or in the immediate period after the pump has been discontinued because of the risk of increasing coagulation abnormalities and bleeding in patients whose coagulation status is already impaired. However, this risk of bleeding diminished within hours.5–6

Hematocrit may be decreased and plasma proteins diluted excessively by administration of large volumes of Hespan®. Administration of packed red cells, platelets, and fresh frozen plasma should be considered if excessive dilution occurs.

Use over extended periods: Hespan® has not been adequately evaluated to establish its safety in situations other than leukapheresis that require frequent use of colloidal solutions over extended periods. In some cases, hetastarch has been associated with coagulation abnormalities in conjunction with an acquired, reversible von Willebrand's-like syndrome and/or Factor VIII deficiency when used over a period of days. Replacement therapy should be considered if a severe Factor VIII deficiency is identified. If a coagulopathy develops, it may take several days to resolve. Certain conditions may affect the safe use of Hespan® on a chronic basis. For example, in patients with subarachnoid hemorrhage where Hespan® is used repeatedly over a period of days for the prevention of cerebral vasospasm, significant clinical bleeding may occur. Intracranial bleeding resulting in death has been reported.7

Usage in Leukapheresis

Slight declines in platelet counts and hemoglobin levels have been observed in donors undergoing repeated leukapheresis procedures using Hespan® due to the volume expanding effects of hetastarch and to the collection of platelets and erythrocytes. Hemoglobin levels usually return to normal within 24 hours. Hemodilution by Hespan® may also result in 24 hour declines of total protein, albumin, calcium, and fibrinogen levels. None of these decreases are to a degree recognized to be clinically significant risks to healthy donors.

Precautions

General

If administration is by pressure infusion, all air should be withdrawn or expelled from the bag through the medication port prior to infusion.

Caution should be used when administering Hespan® to patients allergic to corn because such patients can also be allergic to hetastarch.

If a hypersensitivity effect occurs, administration of the drug should be discontinued and appropriate treatment and supportive measures should be undertaken (see WARNINGS).

When using Hespan® for plasma volume expansion, caution should be taken to avoid excessive hemodilution and circulatory overload especially in those patients at risk for developing congestive heart failure and pulmonary edema. Hespan® is primarily excreted via the kidneys so caution should be exercised in patients who have impaired renal function. Although the risk of circulatory overload is largely dependent on the clinical circumstances, use of doses higher than 20 mL/kg/24h will increase the risk significantly. Increased risk of coagulation abnormalities and bleeding is also associated with higher doses. Patients vital signs and hemoglobin, hematocrit, platelet count, prothrombin time and partial thromboplastin time should be monitored closely.

Hespan® should be used with caution in patients who have been anticoagulated with other drugs that negatively influence the coagulation system.

Regular and frequent clinical evaluation and complete blood counts (CBC) are necessary for proper monitoring of Hespan® use during leukapheresis. If the frequency of leukapheresis is to exceed the guidelines for whole blood donation, you may wish to consider the following additional tests: total leukocyte and platelet counts, leukocyte differential count, hemoglobin and hematocrit, prothrombin time (PT), and partial thromboplastin time (PTT).

Indirect bilirubin levels of 8.3 mg/L (normal 0.0–7.0 mg/L) have been reported in 2 out of 20 normal subjects who received multiple infusions of Hespan® (6% hetastarch in 0.9% sodium chloride injection). Total bilirubin was within normal limits at all times; indirect bilirubin returned to normal by 96 hours following the final infusion. The significance, if any, of these elevations is not known; however, caution should be observed before administering Hespan® to patients with a history of liver disease.

Elevated serum amylase levels may be observed temporarily following administration of Hespan® although no association with pancreatitis has been demonstrated. Serum amylase levels cannot be used to assess or to evaluate for pancreatitis for 3–5 days after administration of Hespan®. Elevated serum amylase levels persist for longer periods of time in patients with renal impairment. Hetastarch has not been shown to increase serum lipase.

One report suggests that in the presence of renal glomerular damage, larger molecules of Hespan® can leak into the urine and elevate the specific gravity. The elevation of specific gravity can obscure the diagnosis of renal failure.

Hespan® is not eliminated by hemodialysis. The utility of other extracorporeal elimination techniques has not been evaluated.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies of animals have not been performed to evaluate the carcinogenic potential of hetastarch.

Teratogenic Effects

Pregnancy Category C

Hetastarch has been shown to have an embryocidal effect on New Zealand rabbits when given intravenously over the entire organogenesis period in a daily dose 1/2 times the maximum recommended therapeutic human dose (1500 mL) and on BD rats when given intraperitoneally, from the 16th to the 21st day of pregnancy, in a daily dose 2.3 times the maximum recommended therapeutic human dose. When hetastarch was administered to New Zealand rabbits, BD rats, and swiss mice with intravenous daily doses of 2 times, 1/3 times, and 1 times the maximum recommended therapeutic human dose respectively over several days during the period of gestation, no evidence of teratogenicity was evident. There are no adequate and well-controlled studies in pregnant women. Hespan® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether hetastarch is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Hespan® is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of hetastarch in pediatric patients have not been established. Adequate, well-controlled clinical trials to establish the safety and effectiveness of Hespan® in pediatric patients have not been conducted. However, in one small double-blind study, 47 infants, children, and adolescents (ages 1 year to 15.5 years) scheduled for repair of congenital heart disease with moderate hypothermia were randomized to receive either Hespan® or Albumin as a postoperative volume expander during the first 24 hours after surgery. Thirty-eight children required colloid replacement therapy, of which 20 children received Hespan®. No differences were found in the coagulation parameters or in the amount of replacement fluids required in the children receiving 20 mL/kg or less of either colloid replacement therapy. In children who received greater than 20 mL/kg of Hespan®, an increase in prothrombin time was demonstrated (p=0.006).8 There were no neonates included in this study.

Adverse Reactions

Reported adverse reactions with hetastarch include:

General

Hypersensitivity (see WARNINGS).

Death, life-threatening anaphylactic/anaphylactoid reactions, cardiac arrest, ventricular fibrillation, severe hypotension, non-cardiac pulmonary edema, laryngeal edema, bronchospasm, angioedema, wheezing, restlessness, tachypnea, stridor, fever, chest pain, bradycardia, tachycardia, shortness of breath, chills, urticaria, pruritus, facial and periorbital edema, coughing, sneezing, flushing, erythema multiforme, and rash.

Cardiovascular

Circulatory overload, congestive heart failure, and pulmonary edema (see PRECAUTIONS).

Hematologic

Intracranial bleeding, bleeding and/or anemia due to hemodilution (see WARNINGS) and/or Factor VIII deficiency, acquired von Willebrand's-like syndrome, and coagulopathy including rare cases of disseminated intravascular coagulopathy and hemolysis.

Metabolic

Metabolic acidosis.

Other

Vomiting, peripheral edema of the lower extremities, submaxillary and parotid glandular enlargement, mild influenza-like symptoms, headaches, and muscle pains.

Hydroxyethyl starch-associated pruritus has been reported in some patients with deposits of hydroxyethyl starch in peripheral nerves.

Hespan Dosage and Administration

Dosage for Acute Use in Plasma Volume Expansion

Hespan® is administered by intravenous infusion only. Total dosage and rate of infusion depend upon the amount of blood or plasma lost and the resultant hemoconcentration.

Adults

The amount usually administered is 500 to 1000 mL. Doses of more than 1500 mL per day for the typical 70 kg patient (approximately 20 mL per kg of body weight) are usually not required although higher doses have been reported in postoperative and trauma patients where severe blood loss has occurred (see WARNINGS and PRECAUTIONS).

Pediatric Patients

Adequate, well-controlled clinical trials to establish the safety and effectiveness of Hespan® in pediatric patients have not been conducted (see PRECAUTIONS, Pediatric Use).

Dosage in Leukapheresis

250 to 700 mL of Hespan® (6% hetastarch in 0.9% sodium chloride injection) to which citrate anticoagulant has been added is typically administered by aseptic addition to the input line of the centrifugation apparatus at a ratio of 1:8 to 1:13 to venous whole blood. The Hespan® and citrate should be thoroughly mixed to assure effective anticoagulation of blood as it flows through the leukapheresis machine.

When stored at room temperature, Hespan® admixtures of 500–560 mL with citrate concentrations up to 2.5% were compatible for 24 hours. The safety and compatibility of additives other than citrate have not been established.

General Recommendations

Do not use plastic container in series connection.

If administration is controlled by a pumping device, care must be taken to discontinue pumping action before the container runs dry or air embolism may result. If administration is not controlled by a pumping device, refrain from applying excessive pressure (>300mmHg) causing distortion to the container such as wringing or twisting. Such handling could result in breakage of the container.

This solution is intended for intravenous administration using sterile equipment. It is recommended that intravenous administration apparatus be replaced at least once every 24 hours.

Use only if solution is clear and container and seals are intact.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

If administration is by pressure infusion, all air should be withdrawn or expelled from the bag through the medication port prior to infusion.

The safety and compatibility of other additives have not been established.

Directions for Use of EXCEL® Container

Caution: Before administering to the patient, review these directions:

Visual Checking

1. Do not remove the plastic infusion container from its overwrap until immediately before use.


2. While the overwrap is intact, identify the solution as Hespan®, the lot number, and the expiration date.


3. Check that the solution is clear.


4. Inspect the intact unit for signs of obvious damage. If present, the unit should not be used.

Removal of Overwrap

To open overwrap, tear at any notch located at either end of unit. After removing the overwrap, check for any leakage by squeezing container firmly. If any leaks are found, discard unit as sterility may be impaired.

Preparation for Administration (Use aseptic technique.)

1. Close flow control clamp of administration set.


2. Twist off plug from port designated "Infusion Set Port".


3. Insert spike of infusion set into port with a twisting motion until the set is firmly seated.


4. Suspend container from hanger.


5. Follow manufacturer's recommended procedures for the administration set.


6. Discontinue administration and notify physician immediately if patient exhibits signs of adverse reactions.

How is Hespan Supplied

Hespan® (6% hetastarch in 0.9% sodium chloride injection) is supplied sterile and nonpyrogenic in 500 mL EXCEL® Containers packaged 12 per case.

NDC	Cat. No.	Size
Hespan® (6% hetastarch in 0.9% sodium chloride injection)
0264-1965-10	L6511	500 mL

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. It is recommended that the product be stored at room temperature (25°C); however, brief exposure up to 40°C does not adversely affect the product.

Storage in automated dispensing machines: Brief exposure up to 2 weeks to ultraviolet or fluorescent light does not adversely affect the product labeling legibility; prolonged exposure can cause fading of the red label. Rotate stock frequently.

Revised: September 2010

References

1. Diehl J., et al., Clinical Comparison of Hetastarch and Albumin in Postoperative Cardiac Patients. The Annals of Thoracic Surgery, 1982;34(6):674–679.


2. Gold M., et al., Comparison of Hetastarch to Albumin for Perioperative Bleeding in Patients Undergoing Abdominal Aortic Aneurysm Surgery. Annals of Surgery, 1990;211(4):482–485.


3. Kirklin J., et al., Hydroxyethyl Starch versus Albumin for Colloid Infusion Following Cardiopulmonary Bypass in Patients Undergoing Myocardial Revascularization. The Annals of Thoracic Surgery, 1984;37(1):40–46.


4. Moggio RA., et al., Hemodynamic Comparison of Albumin and Hydroxyethyl Starch in Postoperative Cardiac Surgery Patients. Critical Care Medicine, 1983;11(12):943–945.


5. Knutson JE., et al., Does Intraoperative Hetastarch Administration Increase Blood Loss and Transfusion Requirements After Cardiac Surgery? Anesthesia Analg., 2000;90:801–7.


6. Cope JT., et al., Intraoperative Hetastarch Infusion Impairs Hemostasis After Cardiac Operations. The Annals of Thoracic Surgery, 1997;63:78–83.


7. Damon L., Intracranial Bleeding During Treatment with Hydroxyethyl Starch. New England Journal of Medicine, 1987;317(15):964–965.


8. Brutocao D., et al., Comparison of Hetastarch with Albumin for Postoperative Volume Expansion in Children After Cardiopulmonary Bypass. Journal of Cardiothoracic and Vascular Anesthesia, 1996;10(3):348–351.

EXCEL and Hespan are registered trademarks of B. Braun Medical Inc.

 

B. Braun Medical Inc.

Irvine, CA 92614-5895 USA

Made in USA


Y36-002-755  LD-233-1

PRINCIPAL DISPLAY PANEL - 500 mL

Hespan®

(6% hetastarch in 0.9%

sodium chloride injection)


Y94-003-110

LD-262-1

REF L6511

NDC 0264-1965-10

500 mL

EXCEL® CONTAINER

For intravenous use only.

Each 100 mL contains: Hetastarch 6 g

Sodium Chloride USP 0.9 g in Water for Injection, USP

pH adjusted with Sodium Hydroxide, NF


pH: approximately 5.9 with negligible buffering capacity

Calc. Osmolarity: approximately 309 mOsM


Electrolytes (mEq/L):    Sodium  154       Chloride  154


If administration is by pressure infusion, all air

should be withdrawn or expelled from the bag

through the medication port prior to infusion.


Sterile, nonpyrogenic. Use only if solution is clear and container

and seals are intact. Single dose container. Discard unused solution.


Recommended Storage: Store at room temperature,

25ºC (77ºF). Avoid excessive heat. Protect from freezing.


Usual Dosage: See package insert for complete information.

Rx only

EXCEL and Hespan are registered trademarks of B. Braun Medical Inc.

B. Braun Medical Inc.

Irvine, CA 92614-5895 USA

Made in USA

Y94-003-141

LD-152-3

Do not remove overwrap until ready for use. After removing the

overwrap, check for minute leaks by squeezing container firmly.

If leaks are found, discard solution as sterility may be impaired.

DO NOT INTRODUCE ADDITIVES OTHER THAN CITRATE INTO BAG.

EXP

LOT

Hespan  hetastarch in sodium chloride  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0264-1965 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength HETASTARCH (HETASTARCH) HETASTARCH 6 g  in 100 mL SODIUM CHLORIDE (SODIUM CATION) SODIUM CHLORIDE 0.9 g  in 100 mL

Inactive Ingredients Ingredient Name Strength WATER   SODIUM HYDROXIDE

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0264-1965-10 12 CONTAINER In 1 CASE contains a CONTAINER 1 500 mL In 1 CONTAINER This package is contained within the CASE (0264-1965-10)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA890105	04/04/1991

Labeler - B. Braun Medical Inc. (002397347)

Revised: 07/2011B. Braun Medical Inc.

More Hespan resources

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

• Hespan MedFacts Consumer Leaflet (Wolters Kluwer)


• Hespan Concise Consumer Information (Cerner Multum)


• Hetastarch Monograph (AHFS DI)

Compare Hespan with other medications

• Blood Disorders

Zirtek Allergy Solution 1mg / ml

Zirtek

ALLERGY SOLUTION 1 mg/ml

cetirizine hydrochloride

once-a-day

What You Should Know About Your Medicine

Please read this leaflet carefully before you start taking this medicine. It provides a summary of the information currently available on Zirtek Allergy Solution. For further information or advice ask your doctor or pharmacist.

What Is In Zirtek Allergy Solution

Each pack contains 150 or 200 ml of a banana flavoured, sugar free oral solution; each ml containing 1 mg of cetirizine hydrochloride as the active ingredient. This medicine also contains sorbitol (E420), glycerol (E422), propylene glycol, saccharin sodium, methylhydroxybenzoate (E218), propylhydroxybenzoate (E216), banana flavouring, sodium acetate (E262), acetic acid (E260) and purified water.

Product licence number: PL 00039 / 0540

This medicine is manufactured and licenced by:

UCB Pharma Ltd

208 Bath Road

Slough

Berkshire

SL1 3WE

When Is Zirtek Allergy Solution Used

Your medicine belongs to the antihistamine group of drugs.

This medicine treats adults & children aged 2 years and over: suffering from hay fever (seasonal allergic rhinitis), year round allergies such as dust or pet allergies (perennial allergic rhinitis) and urticaria (swelling, redness and itchiness of the skin).

Antihistamines like Zirtek Allergy Solution relieve the unpleasant symptoms and discomfort associated with the above conditions, such as sneezing, irritated, runny and blocked up nose, itchy, red and watering eyes and skin rashes.

Before Taking Zirtek Allergy Solution

If you are pregnant or if your doctor has told you that you have kidney problems, you should consult your doctor before taking this medicine. You should not take this medicine if you are breastfeeding or if you have ever had an allergic reaction to any of its constituents (see ‘What is in Zirtek Allergy Solution’).

Your medicine contains methylhydroxybenzoate (E218) and propylhydroxybenzoate (E216) which may cause allergic reactions (possibly delayed) and glycerol (E422) which may cause headache, stomach upset and diarrhoea. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking Zirtek Allergy Solution.

As with all antihistamines, you should avoid excessive alcohol consumption when taking this medicine.

If you have ever had a reaction to an antihistamine in the past consult your doctor or pharmacist before taking this solution.

How To Take Your Medicine

Adults, and children aged 12 years and over: Two 5 ml spoonfuls once a day.

Children aged between 6 - 11 years: One 5 ml spoonful in the morning and another 5 ml spoonful in the evening. Alternatively two 5ml spoonfuls can be taken once a day.

Children aged between 2 – 5 years: One 2.5 ml spoonful in the morning and another 2.5 ml spoonful in the evening. Alternatively one 5 ml dose can be taken once a day.

You may feel drowsy or dizzy, taking half your dose twice a day may reduce this. If you accidentally take more than the recommended dose consult your doctor immediately.

This solution should not be given to children under 2 years of age.

REMEMBER... If you forget to take a dose, you should take one as soon as you remember, but wait at least 24 hours before taking the next dose.

DO NOT EXCEED THE STATED DOSE

If symptoms persist consult your doctor or pharmacist.

After Taking Zirtek Allergy Solution

This medicine does not cause side-effects in most people. However, as with all medicines, some people can react differently. If you:

• have frequent headaches


• have an upset stomach


• become agitated


• have diarrhoea


• get a dry mouth


• feel weak and/or unwell


• experience unusual touch sensation


• experience fatigue, dizziness or drowsiness


• experience itchiness and skin rash

Stop taking the solution and tell your doctor.

Other rare side effects have been reported such as bleeding and bruising easily, rapid heart beat, difficulty focussing, blurred vision, swelling, allergic reaction/ shock, changes in liver function, fits, confusion, depression, aggression, weight increase, unusual limb movements, experience a bad taste in the mouth, fainting, hallucination, insomnia, bed wetting, pain and/or difficulty passing water, red and/or blotchy skin rash.

If you notice anything unusual or have these or any other unexpected effects stop taking the solution and tell your doctor.

This solution does not normally cause drowsiness. However, individuals can react differently to treatment. If you are affected you should not drive or operate machinery, but should persist with the solution as any drowsiness doesn’t usually last very long.

Storing Your Medicine.

Keep this medicine out of reach and sight of children.

Store the solution below 30°C

Do not use after the expiry date shown under Exp on the end panel of the carton.

LEGAL STATUS: P.

Date of preparation of this leaflet: October 2005

© UCB 2004

Cod. I 31456/6

Fortical Parenteral

Generic Name: calcitonin (Parenteral route)

kal-si-TOE-nin

Uses For Fortical

Calcitonin is used to treat Paget's disease of bone. It also may be used to prevent continuing bone loss in women with postmenopausal osteoporosis and to treat hypercalcemia (too much calcium in the blood). This medicine may be used to treat other conditions as determined by your doctor.

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

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

• Osteoporosis caused by hormone problems, certain drugs, and other causes

Before Using Fortical

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group 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 this medicine have been done only in adult patients, and there is no specific information comparing the use of calcitonin in children with use in other age groups. Therefore, be sure to discuss with your doctor the use of this medicine in children.

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. Although there is no specific information comparing the use of calcitonin in the elderly with use in other age groups, this medicine is not expected to cause different side effects or problems in older people than it does in younger adults. Calcitonin is often used in elderly patients.

Pregnancy

Calcitonin has not been studied in pregnant women. However, in animal studies, calcitonin has been shown to lower the birth weight of the baby when the mother was given a dose of calcitonin many times the human dose.

Breast Feeding

Calcitonin has not been reported to cause problems in nursing babies. However, studies in animals have shown that calcitonin may decrease the flow of breast milk.

Interactions with Medicines

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

Interactions with Food/Tobacco/Alcohol

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

Proper Use of calcitonin

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

Make certain your health care professional knows if your diet includes large amounts of calcium-containing foods and/or vitamin D-containing foods, such as milk or other dairy products. Calcium and vitamin D may cause the calcitonin to be less effective in treating a high blood calcium. Also let your health care professional know if you are on any special diet, such as low-sodium or low-sugar diet.

This medicine is for injection only. If you will be giving yourself the injections, make sure you understand exactly how to give them, including how to fill the syringe before injection. If you have any questions about this, check with your doctor.

Use the calcitonin only when the contents of the syringe are clear and colorless. Do not use it if it looks grainy or discolored.

Dosing

The dose medicines in this class 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 these medicines. 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 calcitonin-human


• For injection dosage form:
  
  • For Paget's disease of bone:
    
    • Adults—To start, 500 micrograms (mcg) injected under the skin once a day. Your doctor may reduce your dose or increase the time between doses. Or, your doctor may give you a smaller dose to start and increase your dose over two weeks.
    
    
    • Children—Dose must be determined by your doctor.
    
    
  
  

• For calcitonin-salmon


• For injection dosage form:
  
  • For Paget's disease of bone:
    
    • Adults—To start, 100 Units injected into a muscle or under the skin once a day, once every other day, or three times a week. Your doctor may reduce your dose or increase the time between doses.
    
    
    • Children—Dose must be determined by your doctor.
    
    
  
  
  • For hypercalcemia (too much calcium in the blood):
    
    • Adults—To start, 4 Units per kilogram (kg) (1.8 Units per pound) of body weight injected into a muscle or under the skin every twelve hours. Your doctor may increase your dose or increase the time between doses.
    
    
    • Children—Dose must be determined by your doctor.
    
    
  
  
  • For postmenopausal osteoporosis:
    
    • Adults—100 Units injected into a muscle or under the skin once a day, once every other day, or three times a week. Or, your doctor may give you a smaller dose to start and increase your dose over two weeks.
    
    
    • Children—Dose must be determined by your doctor.
    
    
  
  

Missed Dose

Call your doctor or pharmacist for instructions.

If you miss a dose of this medicine and your dosing schedule is:

• Two doses a day—If you remember within 2 hours of the missed dose, give it right away. Then go back to your regular dosing schedule. But if you do not remember the missed dose until later, skip it and go back to your regular dosing schedule. Do not double doses.


• One dose a day—Give the missed dose as soon as possible. Then go back to your regular dosing schedule. If you do not remember the missed dose until the next day, skip it and go back to your regular dosing schedule. Do not double doses.


• One dose every other day—;Give the missed dose as soon as possible if you remember it on the day it should be given. Then go back to your regular dosing schedule. If you do not remember the missed dose until the next day, give it at that time. Then skip a day and start your dosing schedule again.


• One dose three times a week—Give the missed dose the next day. Then set each injection back a day for the rest of the week. Go back to your regular Monday-Wednesday-Friday schedule the following week. Do not double doses.

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

Storage

Keep out of the reach of children.

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

Do not keep outdated medicine or medicine no longer needed.

Store calcitonin-human at a temperature below 77 °F. Do not refrigerate. Use prepared solution within 6 hours.

Store calcitonin-salmon in the refrigerator. However, keep it from freezing.

Precautions While Using Fortical

Your doctor should check your progress at regular visits to make sure that this medicine does not cause unwanted effects.

If you are using this medicine for hypercalcemia (too much calcium in the blood), your doctor may want you to follow a low-calcium diet. If you have any questions about this, check with your doctor.

Fortical 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:

Rare

• Skin rash or hives

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

• Diarrhea


• flushing or redness of face, ears, hands, or feet


• loss of appetite


• nausea or vomiting


• pain, redness, soreness, or swelling at place of injection


• stomach pain

Less common

• Increased frequency of urination

Rare

• Chills


• dizziness


• headache


• pressure in chest


• stuffy nose


• tenderness or tingling of hands or feet


• trouble in breathing


• weakness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Fortical Parenteral side effects (in more detail)

The information contained in the Thomson Healthcare (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 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 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 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 HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Healthcare does not assume any responsibility or risk for your use of the Thomson Healthcare products.

More Fortical Parenteral resources

• Fortical Parenteral Side Effects (in more detail)
• Fortical Parenteral Use in Pregnancy & Breastfeeding
• Fortical Parenteral Drug Interactions
• Fortical Parenteral Support Group
• 1 Review for Fortical Parenteral - Add your own review/rating

Compare Fortical Parenteral with other medications

• Hypercalcemia
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• Osteoporosis
• Paget's Disease

Urelle

Generic Name: hyoscyamine, methenamine, methylene blue, phenyl salicylate, and sodium phosphate (Oral route)

hye-oh-SYE-a-meen SUL-fate, meth-EN-a-meen, METH-i-leen BLOO, FEN-il sal-I-si-late, SOE-dee-um FOS-fate, mono-BAY-sik

Commonly used brand name(s)

In the U.S.

• Phosphasal


• Urelle


• Uretron D/S


• Uribel


• Urimar-T


• UR N-C


• Ustell


• Uticap


• Utira-C


• Utrona-C

Available Dosage Forms:

• Tablet


• Capsule


• Tablet, Enteric Coated


• Tablet, Extended Release

Therapeutic Class: Urinary Antispasmodic

Pharmacologic Class: Hyoscyamine

Chemical Class: Salicylate, Non-Aspirin

Uses For Urelle

Urelle® is a combination of five medicines: hyoscyamine, methenamine, methylene blue, phenyl salicylate, and sodium phosphate. It is used to relieve discomfort, swelling, pain, frequent urge to urinate, and cramps or spasms of the urinary tract caused by an infection or a diagnostic procedure.

Hyoscyamine is an antispasmodic drug, which relieves muscle cramps or spasms. Methenamine and methylene blue are antiseptic drugs, which help clear a urinary tract infection. Phenyl salicylate is a pain reliever. Sodium phosphate makes the urine more acidic, which helps methenamine work better.

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

Before Using Urelle

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of Urelle® in children. However, use is not recommended in children 6 years of age and younger.

Geriatric

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

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. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amitriptyline


• Amoxapine


• Bupropion


• Cisapride


• Citalopram


• Clomipramine


• Desipramine


• Desvenlafaxine


• Doxepin


• Duloxetine


• Escitalopram


• Fluoxetine


• Fluvoxamine


• Imipramine


• Isocarboxazid


• Linezolid


• Maprotiline


• Mesoridazine


• Mirtazapine


• Nortriptyline


• Paroxetine


• Phenelzine


• Pimozide


• Potassium


• Protriptyline


• Selegiline


• Sertraline


• Sparfloxacin


• Thioridazine


• Tranylcypromine


• Trimipramine


• Venlafaxine


• Vilazodone

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

• Alfuzosin


• Amiodarone


• Amitriptyline


• Amoxapine


• Apomorphine


• Arsenic Trioxide


• Asenapine


• Astemizole


• Azithromycin


• Buspirone


• Chloroquine


• Chlorpromazine


• Ciprofloxacin


• Citalopram


• Clarithromycin


• Clomipramine


• Clozapine


• Crizotinib


• Dasatinib


• Desipramine


• Disopyramide


• Dofetilide


• Dolasetron


• Droperidol


• Erythromycin


• Flecainide


• Fluconazole


• Gatifloxacin


• Gemifloxacin


• Granisetron


• Halofantrine


• Haloperidol


• Ibutilide


• Iloperidone


• Imipramine


• Lapatinib


• Levofloxacin


• Lopinavir


• Lumefantrine


• Mefloquine


• Methadone


• Moxifloxacin


• Nefazodone


• Nilotinib


• Norfloxacin


• Nortriptyline


• Octreotide


• Ofloxacin


• Ondansetron


• Paliperidone


• Pazopanib


• Perflutren Lipid Microsphere


• Posaconazole


• Procainamide


• Prochlorperazine


• Promethazine


• Propafenone


• Protriptyline


• Quetiapine


• Quinidine


• Quinine


• Ranolazine


• Salmeterol


• Saquinavir


• Solifenacin


• Sorafenib


• Sotalol


• Sunitinib


• Telavancin


• Telithromycin


• Terfenadine


• Tetrabenazine


• Trazodone


• Trimipramine


• Vandetanib


• Vardenafil


• Vemurafenib


• Voriconazole


• Ziprasidone

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

• Aluminum Carbonate, Basic


• Aluminum Hydroxide


• Aluminum Phosphate


• Calcium Acetate


• Calcium Carbonate


• Calcium Citrate


• Dihydroxyaluminum Aminoacetate


• Dihydroxyaluminum Sodium Carbonate


• Magaldrate


• Magnesium Carbonate


• Magnesium Hydroxide


• Magnesium Oxide


• Magnesium Trisilicate

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

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

• Congestive heart failure or


• Coronary heart disease or


• Glaucoma or


• Heart disease (e.g., mitral stenosis) or


• Heart rhythm problems (e.g., arrhythmia) or


• Myasthenia gravis (severe muscle weakness) or


• Stomach or intestinal (bowel) blockage or


• Stomach ulcers or


• Urinary problems (e.g., bladder blockage due to an enlarged prostate)—Use with caution. May make these conditions worse.

• Allergy or intolerance to belladonna or salicylates—Use with caution. May be sensitive to this medicine also.

Proper Use of hyoscyamine, methenamine, methylene blue, phenyl salicylate, and sodium phosphate

This section provides information on the proper use of a number of products that contain hyoscyamine, methenamine, methylene blue, phenyl salicylate, and sodium phosphate. It may not be specific to Urelle. Please read with care.

Take this medicine for the full time of treatment, even if you begin to feel better. Also, keep your appointments with your doctor for check-ups so that your doctor will be better able to tell you when to stop taking this medicine.

Drink extra fluids after you take this medicine so you will pass more urine.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  
  • For treatment of symptoms of urinary tract infection or diagnostic procedure:
    
    • Adults—One tablet four times a day
    
    
    • Children 7 years of age and older—Use and dose must be determined by your doctor.
    
    
    • Children 6 years of age and younger—Use is not recommended.
    
    
  
  

Missed Dose

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

Storage

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 Urelle

It is very important that your doctor check the progress of you or your child 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.

If your or your child's symptoms do not improve or if they get worse, call your doctor.

Stop using this medicine and check with your doctor right away if you or your child have blurred vision, dizziness, or rapid pulse.

This medicine will make your urine to be colored blue. This is normal and is nothing to worry about.

This medicine will not cure a serious urinary tract infection and will only work to relieve symptoms as long as you continue to take it.

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

Urelle Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Incidence not known

• Blurred vision


• dizziness


• rapid pulse

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:

Incidence not known

• Blue-colored urine

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.

Medigesic

Generic Name: butalbital and acetaminophen combination (Oral route)

Commonly used brand name(s)

In the U.S.

• Anolor 300


• Cephadyn


• Dolgic LQ


• Esgic


• Esgic-Plus


• Ezol


• Fioricet


• Geone


• Margesic


• Medigesic


• Phrenilin


• Phrenilin Forte

Available Dosage Forms:

• Tablet


• Capsule


• Solution

Uses For Medigesic

Butalbital and acetaminophen combination is a pain reliever and relaxant. It is used to treat tension headaches. Butalbital belongs to the group of medicines called barbiturates. Barbiturates act in the central nervous system (CNS) to produce their effects.

When you take butalbital for a long time, your body may get used to it so that larger amounts are needed to produce the same effects. This is called tolerance to the medicine. Also, butalbital may become habit-forming (causing mental or physical dependence) when it is used for a long time or in large doses. Physical dependence may lead to withdrawal side effects when you stop taking the medicine. In patients who get headaches, the first symptom of withdrawal may be new (rebound) headaches.

Some butalbital and acetaminophen combinations also contain caffeine. Caffeine may help to relieve headaches. However, caffeine can also cause physical dependence when it is used for a long time. This may lead to withdrawal (rebound) headaches when you stop taking it.

Butalbital and acetaminophen combination may also be used for other kinds of headaches or other kinds of pain as determined by your doctor.

These medicines are available only with your doctor's prescription.

Before Using Medigesic

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group 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

For butalbital:

• Although barbiturates such as butalbital often cause drowsiness, some children become excited after taking them.

For acetaminophen:

• Acetaminophen has been tested in children and, in effective doses, has not been shown to cause different side effects or problems than it does in adults.

For caffeine:

• There is no specific information comparing use of caffeine in children up to 12 years of age with use in other age groups. However, caffeine is not expected to cause different side effects or problems in children than it does in adults.

Geriatric

For butalbital:

• Certain side effects, such as confusion, excitement, or mental depression, may be especially likely to occur in elderly patients, who are usually more sensitive than younger adults to the effects of the butalbital in this combination medicine.

For acetaminophen:

• Acetaminophen has been tested and has not been shown to cause different side effects or problems in older people than it does in younger adults.

For caffeine:

• 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 caffeine in the elderly with use in other age groups.

Pregnancy

For butalbital:

• Barbiturates such as butalbital have been shown to increase the chance of birth defects in humans. Also, one study in humans has suggested that barbiturates taken during pregnancy may increase the chance of brain tumors in the baby.


• Butalbital may cause breathing problems in the newborn baby if taken just before or during delivery.

For acetaminophen:

• Although studies on birth defects with acetaminophen have not been done in pregnant women, it has not been reported to cause birth defects or other problems.

For caffeine:

• Studies in humans have not shown that caffeine (contained in some of these combination medicines) causes birth defects. However, use of large amounts of caffeine during pregnancy may cause problems with the heart rhythm and the growth of the fetus. Also, studies in animals have shown that caffeine causes birth defects when given in very large doses (amounts equal to those present in 12 to 24 cups of coffee a day).

Breast Feeding

For butalbital:

• Barbiturates such as butalbital pass into the breast milk and may cause drowsiness, unusually slow heartbeat, shortness of breath, or troubled breathing in nursing babies.

For acetaminophen:

• Although acetaminophen has not been shown to cause problems in nursing babies, it passes into the breast milk in small amounts.

For caffeine:

• Caffeine (present in some butalbital and acetaminophen combinations) passes into the breast milk in small amounts. Taking caffeine in the amounts present in these medicines has not been shown to cause problems in nursing babies. However, studies have shown that nursing babies may appear jittery and have trouble in sleeping when their mothers drink large amounts of caffeine-containing beverages. Therefore, breast-feeding mothers who use caffeine-containing medicines should probably limit the amount of caffeine they take in from other medicines or from beverages.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking any of these medicines, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

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

• Adinazolam


• Alfentanil


• Alprazolam


• Amobarbital


• Anileridine


• Anisindione


• Aprobarbital


• Bromazepam


• Brotizolam


• Butabarbital


• Butalbital


• Carisoprodol


• Chloral Hydrate


• Chlordiazepoxide


• Chlorzoxazone


• Clobazam


• Clonazepam


• Clorazepate


• Codeine


• Dantrolene


• Diazepam


• Dicumarol


• Estazolam


• Ethchlorvynol


• Fentanyl


• Flunitrazepam


• Flurazepam


• Halazepam


• Hydrocodone


• Hydromorphone


• Ketazolam


• Levorphanol


• Lorazepam


• Lormetazepam


• Medazepam


• Meperidine


• Mephenesin


• Mephobarbital


• Meprobamate


• Metaxalone


• Methocarbamol


• Methohexital


• Midazolam


• Morphine


• Morphine Sulfate Liposome


• Nitrazepam


• Nordazepam


• Oxazepam


• Oxycodone


• Oxymorphone


• Pentobarbital


• Phenindione


• Phenobarbital


• Phenprocoumon


• Prazepam


• Primidone


• Propoxyphene


• Quazepam


• Quetiapine


• Remifentanil


• Secobarbital


• Sodium Oxybate


• Sufentanil


• Temazepam


• Thiopental


• Triazolam

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.

Using medicines in this class with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use your medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other Medical Problems

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

• Alcohol abuse (or history of) or


• Drug abuse or dependence (or history of)—Dependence on butalbital may develop. Also, acetaminophen may cause liver damage in people who abuse alcohol.

• Asthma (or history of), emphysema, or other chronic lung disease or


• Hepatitis or other liver disease or


• Hyperactivity (in children) or


• Kidney disease—The chance of serious side effects may be increased.

• Type 2 diabetes mellitus or


• Mental depression or


• Overactive thyroid or


• Porphyria (or history of)—Butalbital can make these conditions worse.

• Heart disease (severe)—The caffeine in some butalbital and acetaminophen combinations can make some kinds of heart disease worse.

Proper Use of butalbital and acetaminophen combination

This section provides information on the proper use of a number of products that contain butalbital and acetaminophen combination. It may not be specific to Medigesic. Please read with care.

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. If butalbital and acetaminophen combination is taken regularly (for example, every day), it may become habit-forming (causing mental or physical dependence). The caffeine in some butalbital and acetaminophen combinations can also increase the chance of dependence. Dependence is especially likely to occur in patients who take these medicines to relieve frequent headaches. Taking too much of this medicine may also lead to liver damage or other medical problems.

This medicine will relieve a headache best if you take it as soon as the headache begins. If you get warning signs of a migraine, take this medicine as soon as you are sure that the migraine is coming. This may even stop the headache pain from occurring. Lying down in a quiet, dark room for a while after taking the medicine also helps to relieve headaches.

People who get a lot of headaches may need to take a different medicine to help prevent headaches. It is important that you follow your doctor's directions about taking the other medicine, even if your headaches continue to occur. Headache-preventing medicines may take several weeks to start working. Even after they do start working, your headaches may not go away completely. However, your headaches should occur less often, and they should be less severe and easier to relieve than before. This will reduce the amount of headache relievers that you need. If you do not notice any improvement after several weeks of headache-preventing treatment, check with your doctor.

Dosing

The dose medicines in this class 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 these medicines. 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 forms (capsules or tablets):
  
  • For tension headaches:
    
    • Adults—One or 2 capsules or tablets every four hours as needed. If your medicine contains 325 or 500 milligrams (mg) of acetaminophen in each capsule or tablet, you should not take more than six capsules or tablets a day. If your medicine contains 650 mg of acetaminophen in each capsule or tablet, you should not take more than four capsules or tablets a day.
    
    
    • Children—Dose must be determined by your doctor.
    
    
  
  

Missed Dose

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

Storage

Keep out of the reach of children.

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

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Medigesic

Check with your doctor:

• If the medicine stops working as well as it did when you first started using it. This may mean that you are in danger of becoming dependent on the medicine. Do not try to get better pain relief by increasing the dose.


• If you are having headaches more often than you did before you started taking this medicine. This is especially important if a new headache occurs within 1 day after you took your last dose of this medicine, headaches begin to occur every day, or a headache continues for several days in a row. This may mean that you are dependent on the medicine. Continuing to take this medicine will cause even more headaches later on. Your doctor can give you advice on how to relieve the headaches.

Check the labels of all nonprescription (over-the-counter [OTC]) or prescription medicines you now take. If any contain a barbiturate or acetaminophen, check with your health care professional. Taking them together with this medicine may cause an overdose.

The butalbital in this medicine will add to the effects of alcohol and other CNS depressants (medicines that slow down the nervous system, possibly causing drowsiness). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds; sedatives, tranquilizers, or sleeping medicine; other prescription pain medicine; narcotics; other barbiturates; medicine for seizures; muscle relaxants; or anesthetics, including some dental anesthetics. Also, drinking large amounts of alcoholic beverages regularly while taking this medicine may increase the chance of liver damage, especially if you take more of this medicine than your doctor ordered or if you take it regularly for a long time. Therefore, do not drink alcoholic beverages, and check with your doctor before taking any of the medicines listed above, while you are using this medicine.

This medicine may cause some people to become drowsy, dizzy, or lightheaded. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or are not alert and clearheaded.

Before you have any medical tests, tell the person in charge that you are taking this medicine. Caffeine (present in some butalbital and acetaminophen combinations) interferes with the results of certain tests that use dipyridamole (e.g., Persantine) to help show how well blood is flowing to your heart. Caffeine should not be taken for 8 to 12 hours before the test. The results of other tests may also be affected by butalbital and acetaminophen combinations.

Before having any kind of surgery (including dental surgery) or emergency treatment, tell the medical doctor or dentist in charge that you are taking this medicine. Serious side effects can occur if your medical doctor or dentist gives you certain medicines without knowing that you have taken butalbital.

If you have been taking large amounts of this medicine, or if you have been taking it regularly for several weeks or more, do not suddenly stop taking it without first checking with your doctor. Your doctor may want you to reduce gradually the amount you are taking before stopping completely in order to lessen the chance of withdrawal side effects.

If you think you or anyone else may have taken an overdose of this medicine, get emergency help at once. Taking an overdose of this medicine or taking alcohol or CNS depressants with this medicine may lead to unconsciousness or possibly death. Signs of butalbital overdose include severe drowsiness, confusion, severe weakness, shortness of breath or unusually slow or troubled breathing, slurred speech, staggering, and unusually slow heartbeat. Signs of severe acetaminophen poisoning may not occur until 2 to 4 days after the overdose is taken, but treatment to prevent liver damage or death must be started within 24 hours or less after the overdose is taken.

Medigesic Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Rare

• Bleeding or crusting sores on lips


• chest pain


• fever with or without chills


• hive-like swellings (large) on eyelids, face, lips, and/or tongue


• muscle cramps or pain


• red, thickened, or scaly skin


• shortness of breath, troubled breathing, tightness in chest, or wheezing


• skin rash, itching, or hives


• sores, ulcers, or white spots in mouth (painful)

Symptoms of overdose

• Anxiety, confusion, excitement, irritability, nervousness, restlessness, or trouble in sleeping (severe, especially with products containing caffeine)


• convulsions (seizures) (for products containing caffeine)


• diarrhea, especially if occurring together with increased sweating, loss of appetite, and stomach cramps or pain


• dizziness, lightheadedness, drowsiness, or weakness, (severe)


• frequent urination (for products containing caffeine)


• hallucinations (seeing, hearing, or feeling things that are not there)


• increased sensitivity to touch or pain (for products containing caffeine)


• muscle trembling or twitching (for products containing caffeine)


• nausea or vomiting, sometimes with blood


• ringing or other sounds in ears (for products containing caffeine)


• seeing flashes of "zig-zag" lights (for products containing caffeine)


• shortness of breath or unusually slow or troubled breathing


• slow, fast, or irregular heartbeat


• slurred speech


• staggering


• swelling, pain, or tenderness in the upper abdomen or stomach area


• unusual movements of the eyes

Check with your doctor as soon as possible if any of the following side effects occur:

Less common

• Confusion (mild)


• mental depression


• unusual excitement (mild)

Rare

• Bloody or black, tarry stools


• bloody urine


• pinpoint red spots on skin


• swollen or painful glands


• unusual bleeding or bruising


• unusual tiredness or weakness (mild

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

• Bloated or "gassy" feeling


• dizziness or lightheadedness (mild)


• drowsiness (mild)


• nausea, vomiting, or stomach pain (occurring without other symptoms of overdose)

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.

SANDIMMUN Concentrate for Solution for infusion 50mg / ml

SANDIMMUN

Concentrate for Solution for Infusion 50 mg/ml

(ciclosporin)

This product will be called Sandimmun in this leaflet.

What you need to know about Sandimmun

Your doctor has decided that you need this medicine to help treat your condition.

Please read this leaflet carefully before you start your treatment. It contains important information. Keep the leaflet in a safe place because you may want to read it again.

If you have any other questions, or if there is something you don’t understand, please ask your doctor or pharmacist.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or nurse.

In this leaflet:

• 1. What Sandimmun is and what it’s used for


• 2. Things to consider before you have Sandimmun


• 3. Administering Sandimmun


• 4. Possible side effects


• 5. How to store Sandimmun


• 6. Further information

What Sandimmun is and what it’s used for

Sandimmun is a clear, brown/yellow oily liquid containing 50 mg/ml of the active ingredient, ciclosporin. It is used to prepare a solution which is administered by intravenous infusion.

Ciclosporin is one of a group of drugs known as immunosuppressive agents. These drugs are used to dampen down the body's immune reactions.

Sandimmun can be used to prevent rejection after a kidney, liver, heart, heart/lung, lung, pancreas or bone marrow transplant.

Although you may have had a series of tests before your organ or bone marrow transplant to ensure that the match between your body and the transplanted organ or bone marrow is as close as possible, the donor tissue will still not be identical to your tissue. As a result, your body's immune system will try to reject the donor tissue. Sandimmun helps to stop this rejection response by blocking the development of special cells which would normally attack the transplanted tissue.

Things to consider before you have Sandimmun

Some people MUST NOT have Sandimmun. Talk to your doctor if:

• you think you may be allergic to ciclosporin, or to any of the other ingredients of Sandimmun. (These are listed at the end of the leaflet.)


• You are taking a drug called tacrolimus.


• You are taking a drug called rosuvastatin.


• You are breastfeeding.

You should also ask yourself these questions before having Sandimmun. If the answer to any of these questions is YES, discuss your treatment with the doctor or nurse because Sandimmun might not be the right medicine for you.

• Have you previously had an injection or infusion containing polyethoxylated castor oil (see Important information about some of the ingredients of Sandimmun, below)?


• Are you allergic to many things?


• Have you been told that you have high levels of potassium in your blood? Are you taking potassium supplements or is your diet particularly rich in potassium? (Fruit and vegetables are rich sources of potassium.)


• Do you have gout or other conditions caused by high levels of uric acid in your blood?


• Are you worried about any unusual spots, moles or warts on your skin?


• Are you out in the sun a lot, or do you use a sun bed?


• Do you have any skin infections, including herpes (cold sores)?


• Are you pregnant?

Are you taking other medicines?

Ciclosporin interacts with a large number of other medicines and this can interfere with your treatment. Tell your doctor or nurse if you are taking any of the following:

• Medicines to treat heart problems or high blood pressure such as bosentan, diltiazem, nicardipine and verapamil.


• Drugs containing potassium (your doctor will know which these are).


• Medicines called NSAIDs used to treat pain and inflammation. (Some of these can be bought over-the-counter).


• Medicines to treat infections including antibiotics (especially erythromycin and clarithromycin) and antifungal medicines (especially terbinafine and voriconazole).


• Oral contraceptives.


• Medicines for epilepsy.


• Cholesterol lowering medicines (including statins).


• Sleeping tablets.


• Potassium supplements.


• Diuretics or “water tablets” that affect the amount of urine you produce and might also affect the level of potassium in your blood.


• Danazol (used to treat menstrual disorders, endometriosis or breast problems).


• St John’s Wort: The herbal remedy St John’s Wort (Hypericum perforatum) should not be taken at the same time as this medicine. If you are already taking St John’s Wort consult your doctor before stopping the St John’s Wort preparation.


• Octreotide (known as Sandostatin).


• Medicines to treat tuberculosis.


• Medicines to treat gout.


• Metoclopramide (used to stop sickness).


• Melphalan (used to treat lymphomas or tumours).


• Imatinib (used to treat leukaemia or tumours).


• Orlistat (used to help weight loss).


• Ticlopidine (used after a stroke).


• Corticosteroids (used to treat conditions such as asthma, allergic conditions, inflammatory
  conditions including inflammatory bowel disease, adrenocortical insufficiency and rheumatic disease).


• Ursodeoxycholic acid (used to treat gallstones).


• Protease inhibitors (used to treat Human Immunodeficiency Virus (HIV)).


• Tacrolimus, sirolimus and everolimus (other immunosuppressants).


• Methotrexate (used to treat tumours, severe psoriasis and rheumatoid arthritis).


• Etoposide (used to treat cancer).


• Repaglinide (used to treat diabetes).

Always tell your doctor or pharmacist about all the medicines you are taking. This means medicines you have bought yourself as well as medicines on prescription from your doctor.

Will there be any problems with driving or using machinery?

Not applicable.

Other special warnings

• Ciclosporin can affect how the liver and kidneys work. It can also affect blood pressure, and the composition of the blood. Your doctor will monitor you closely while you are being treated.


• Because ciclosporin dampens down the immune system you are more prone to catch infections and they can become very serious. If you experience vision changes, loss of coordination, clumsiness, memory loss, difficulty speaking or understanding what others say, and muscle weakness, these can be the signs and symptoms of an infection of the brain called progressive multifocal leukoencephalopathy. Make sure your doctor or nurse knows if you are feeling unwell.


• There have been very rare reports of people developing a condition called Benign Intracranial Hypertension when they are being treated with ciclosporin. Tell your doctor as soon as possible if you start to feel nauseous, develop tinnitus (ringing in your ears), or get pains in your head, neck or back, or problems with your sight, balance or memory.


• You must not eat a fatty meal or grapefruit, or drink grapefruit juice, before your infusion.


• If you have recently had a vaccination or are planning to have any vaccinations make sure the doctor or nurse knows you are being treated with Sandimmun.


• You must visit the dentist regularly while you are being treated with Sandimmun to make sure that your gums remain healthy.

Important information about some of the ingredients of Sandimmun

Sandimmun contains:

• Polyethoxylated castor oil which may cause severe allergic reactions.


• 34.4% ethanol (alcohol). A 100mg dose of Sandimmun contains 556 mg of ethanol equivalent to nearly three teaspoons of beer or one teaspoon of wine. This may be harmful if you are suffering from alcoholism and should be taken into account if you are pregnant or breast feeding, have liver disease, epilepsy or if this medicine is being given to a child.

Administering Sandimmun

Your doctor will work out the correct dose of Sandimmun for you depending on your body weight and your condition.

The usual dose is from 3 to 5 mg/kg body weight per day starting on the day before your transplant operation and continuing for up to two weeks after the operation. You will be started on oral ciclosporin (capsules or liquid) as soon as possible after the operation.

You will be given Sandimmun by slow intravenous infusion over a period of 2 to 6 hours. Sandimmun will be diluted with normal saline or 5% glucose before use.

If you think you have been given too much tell the doctor or nurse as soon as possible.

Possible side effects

Most people who are treated with Sandimmun benefit. Like all medicines though, it can sometimes cause side effects in some people.

If you develop a sore throat, any infections, or begin to feel generally unwell, tell the doctor or nurse immediately.

The following side effects have been reported:

More than 10% of people have experienced:

Kidney problems, high blood pressure, headache, tremor and increased levels of lipids (for example cholesterol) in the blood.

Up to 1 in 10 people have experienced:

Numbness or tingling, loss of appetite, feeling or being sick, stomach pain, diarrhoea, swollen gums, liver problems, high level of uric acid or potassium in the blood, low levels of magnesium in the blood, muscle pain or cramp, increased hair growth on the body and tiredness.

Up to 1 in 100 people have experienced:

Seizures, confusion, disorientation, decreased responsiveness, agitation, sleeplessness, visual disturbances, blindness, coma, partial paralysis, loss of co-ordination, changes in blood (for example anaemia), allergic rash, water retention which may cause swelling and weight increase.

Up to 1 in 1,000 people have experienced:

Problems with the nerves that control muscles, inflammation of the pancreas, high levels of glucose in the blood, muscle weakness, wasting of muscles, destruction of red blood cells which may be associated with kidney problems, changes in the menstrual cycle in women and slight enlarging of the breasts in men.

Up to 1 in 10,000 people have experienced:

Swelling at the back of the eye which may be associated with an increase in pressure inside the head (benign intracranial hypertension) and visual disturbances.

Like other medicines that dampen down the immune system, ciclosporin may cause tumours or other malignancies, particularly of the skin. It may also make you more likely to get infections which may be serious. If you experience vision changes, loss of coordination, clumsiness, memory loss, difficulty speaking or understanding what others say, and muscle weakness, these can be the signs and symptoms of an infection of the brain called progressive multifocal leukoencephalopathy.

Tell your doctor or pharmacist if you suffer from any of these effects, or from any other side effects not mentioned in this leaflet.

How to store Sandimmun

Keep out of the reach and sight of children.

Store below 30°C.

Do not use Sandimmun after the expiry date which is printed on the outside of the pack.

Further information

SANDIMMUN Concentrate for Solution for Infusion is a clear, brown-yellow, oily liquid containing 50 mg ciclosporin per ml. It also contains the inactive ingredients absolute ethanol and polyethoxylated castor oil.

SANDIMMUN Concentrate for Solution for Infusion is available in 1 ml and 5 ml ampoules. Some of these pack sizes may not be marketed.

The product licence holder is

Novartis Pharmaceuticals UK Limited

trading as Sandoz Pharmaceuticals

Frimley Business Park

Frimley

Camberley

Surrey

GU16 7SR

England

Released onto the market by

Novartis Pharmaceuticals UK Limited

Wimblehurst Road

Horsham

West Sussex

RH12 5AB

England

This leaflet was revised in November 2009.

If you would like any more information, or would like the leaflet in a different format, please contact Medical Information at Novartis Pharmaceuticals UK Ltd, telephone number 01276 698370.

SANDIMMUN is a registered trade mark

Copyright Novartis Pharmaceuticals UK Limited