Iron and Folic Acid

Pronunciation: EYE-urn/FOE-lik AS-id
Generic Name: Iron and Folic Acid
Brand Name: Examples include Proferrin-Forte and Tandem F

Accidental overdose of products that contain iron is a leading cause of fatal poisoning in children younger than 6 years old. Keep this and all medicines out of the reach of children. In case of accidental ingestion, call the poison control center or doctor at once.

Iron and Folic Acid is used for:

Treating anemia caused by low levels of iron or folate in the blood. It is used during pregnancy to prevent and treat low levels of iron in the blood and to provide a maintenance dose of folic acid. It may also be used to treat other conditions as determined by your doctor.

Iron and Folic Acid is an iron and folic acid combination. It works by replacing or adding iron and folic acid when the body does not produce enough of its own.

Do NOT use Iron and Folic Acid if:

• you are allergic to any ingredient in Iron and Folic Acid


• you have pernicious anemia or hemolytic anemia


• you have certain iron metabolism problems (eg, hemosiderosis, hemochromatosis), or you have high levels of iron in your blood

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

Before using Iron and Folic Acid:

Some medical conditions may interact with Iron and Folic Acid. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you

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


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


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


• if you have stomach or intestinal problems (eg, ulcerative colitis, Crohn disease, diverticulitis, a peptic ulcer)


• if you have had multiple blood transfusions, anemia, or a blood disorder (eg, thalassemia, porphyria)

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

• Bisphosphonates (eg, alendronate, risedronate), cephalosporins (eg, cephalexin), hydantoins (eg, phenytoin), methyldopa, penicillamine, quinolones (eg, ciprofloxacin, levofloxacin), tetracyclines (eg, doxycycline), thrombopoietin mimetics (eg, eltrombopag), or thyroid hormones (eg, levothyroxine) because the effectiveness of these medicines may be decreased


• Fluorouracil because the risk of its side effects may be increased by Iron and Folic Acid

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

How to use Iron and Folic Acid:

Use Iron and Folic Acid as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Iron and Folic Acid is absorbed better on an empty stomach but may be taken with food if it upsets your stomach.


• If you are taking a bisphosphonate (eg, alendronate), a cephalosporin (eg, cephalexin), methyldopa, penicillamine, a quinolone (eg, ciprofloxacin), a tetracycline (eg, minocycline), or a thrombopoietin mimetic (eg, eltrombopag) along with Iron and Folic Acid, you may need to space the doses several hours apart. Ask your doctor or pharmacist how much time is needed between doses of Iron and Folic Acid and your other medicines.


• Do not take Iron and Folic Acid within 1 hour before or 2 hours after antacids, eggs, whole grain breads or cereal, milk, milk products, coffee, or tea.


• Take Iron and Folic Acid with a full glass (8 oz/240 mL) of water.


• Do not lie down for 30 minutes after taking Iron and Folic Acid.


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

Ask your health care provider any questions you may have about how to use Iron and Folic Acid.

Important safety information:

• Iron and Folic Acid has iron in it. Iron overdose is a leading cause of fatal poisoning in children younger than 6 years old. In case of an overdose, call a doctor or poison control center right away. Keep Iron and Folic Acid out of the reach of children.


• Do not take large doses of vitamins (megadoses or megavitamin therapy) unless otherwise directed by your doctor.


• Do not exceed the recommended dose or take Iron and Folic Acid for longer than 6 months without checking with your doctor.


• Iron and Folic Acid may darken the stools. This is normal and not a cause for concern.


• Iron and Folic Acid may cause false test results with kits used to check for blood in the stool or blood cholesterol. Check with your doctor if you are using either kind of test kit.


• Lab tests, including blood tests and iron levels, may be performed while you use Iron and Folic Acid. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Iron and Folic Acid should not be used in CHILDREN younger than 12 years old; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: Iron and Folic Acid is intended for use during pregnancy. If you are or will be breast-feeding while you use Iron and Folic Acid, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Iron and Folic Acid:

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

Constipation; diarrhea; heartburn; loss of appetite; nausea; stomach upset; vomiting.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); black, tarry stools; blood or streaks of blood in the stools; fever; severe or persistent vomiting with continuing stomach pain.

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

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include black, bloody, or tarry stools; blue or pale skin; coma; drowsiness; nausea; vomiting.

Proper storage of Iron and Folic Acid:

Store Iron and Folic Acid at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Iron and Folic Acid out of the reach of children and away from pets.

General information:

• If you have any questions about Iron and Folic Acid, please talk with your doctor, pharmacist, or other health care provider.


• Iron and Folic Acid is to be used only by the patient for whom it is prescribed. Do not share it with other people.


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


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

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

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

Ophthalmic steroids with anti-infectives

A drug may be classified by the chemical type of the active ingredient or by the way it is used to treat a particular condition. Each drug can be classified into one or more drug classes.

Ophthalmic steroids with anti-infectives are preparations designed to be applied into the eyes. They contain steroids and anti-infectives. Steroids are effective anti-inflammatory agents and are used to treat pain and inflammation. The anti-infectives commonly present in eye drops are antibiotics that either kill or inhibit the growth of bacteria.

Steroids and antibiotics in combination are used to treat eye infections, which have pain and inflammation component or they can be used post surgery to prevent infections and to treat the inflammation.

See also

Medical conditions associated with ophthalmic steroids with anti-infectives:

• Blepharitis
• Conjunctivitis, Bacterial
• Cyclitis
• Iritis
• Keratitis
• Keratoconjunctivitis
• Uveitis

Drug List:

Fml-S-Liquifilm

Neo-Decadron

Tobradex

Zylet

Blephamide-Suspension

Ak-Cide

Ak-Neo-Dex

Ak-Trol

Blephamide-S-O-P-Ointment

Cetapred

Cortisporin-Ophthalmic

Cortisporin-Ophthalmic-Suspension-Drops-Suspension

Cortomycin-Eye-Ointment

Cortomycin-Suspension

Dexacidin

Dexacine

Dexasporin

Fml-S-Suspension

Isopto-Cetapred

Maxitrol-Drops

Methadex

Metimyd

Neo-Decadron-Ocumeter

Neo-Dex

Neo-Dexair

Neo-Poly-Bac

Neo-Poly-Dex

Neotricin-Hc

Npd-Ophthalmic-Ointment

Ocu-Cort

Ocu-Lone-C

Ocu-Trol

Ophthocort

Poly-Dex-Drops

Poly-Pred-Drops

Pred-G

Pred-G-S-O-P

Tobradex-St-Drops

Triple-Antibiotic-Hc-Ophthalmic-Ointment

Vasocidin-Drops

Bricanyl 0.3 mg / ml Syrup

1. Name Of The Medicinal Product

Bricanyl 0.3 mg/ml Syrup

2. Qualitative And Quantitative Composition

Terbutaline sulphate 0.3mg/ml.

For excipients see Section 6.1.

3. Pharmaceutical Form

Oral Solution.

Bricanyl syrup is a clear colourless raspberry flavoured oral solution.

4. Clinical Particulars

4.1 Therapeutic Indications

For bronchodilation

Terbutaline is a selective beta₂-adrenergic agonist recommended for the relief and prevention of bronchospasm in bronchial asthma and other bronchopulmonary disorders in which bronchospasm is a complicating factor.

For the management of uncomplicated premature labour.

4.2 Posology And Method Of Administration

Use in bronchospasm

Bricanyl Syrup has a duration of action of 7 to 8 hours. The minimum recommended dosage interval is therefore 7 hours.

Adults:	The starting dose should be 2 x 5ml spoonfuls 3 times in 24 hours. The dose may then be increased to 3 x 5ml spoonfuls 3 times in 24 hours if necessary to achieve adequate bronchodilation.
Elderly:	Dosage as for Adults.
Children:	The following dosage is recommended - 0.075mg (0.25ml)/kg body weight 3 times in a 24 hour period. e.g.

Body weight (kg)	Dosage
14	3.5 ml x 3
16	4 ml x 3
18	4.5 ml x 3
20	5 ml x 3
24	6 ml x 3
28	7 ml x 3
32	8 ml x 3
36	9 ml x 3
40	10 ml x 3

Use in the management of premature labour.

Oral treatment should not be used initially in an attempt to arrest premature labour. After uterine contractions have been controlled by intravenous infusion of Bricanyl Injection, (see Bricanyl Injection Summary of Product Characteristics) or subcutaneous injections (0.25mg, 4 times in a 24 hour period for a few days) maintenance therapy can be continued with oral treatment (5mg, 3 times in a 24 hour period). Oral treatment may be continued for as long as the physician considers it desirable to prolong pregnancy.

4.3 Contraindications

Bricanyl Syrup should not be used as a tocolytic agent in patients with pre-existing ischaemic heart disease or those patients with significant risk factors for ischaemic heart disease.

Although Bricanyl Syrup is used in the management of uncomplicated premature labour, use in the following conditions is contra-indicated: -

• any condition of the mother or foetus in which prolongation of the pregnancy is hazardous, e.g. severe toxaemia, anti-partum haemorrhage, intra-uterine infection, severe pre-eclampsia, abruptio placentae, threatened abortion during the 1^st and 2^nd trimester, or cord compression.

Bricanyl Syrup should not be used in patients with a history of hypersensitivity to any of the ingredients.

4.4 Special Warnings And Precautions For Use

As for all beta₂-agonists caution should be observed in patients with thyrotoxicosis.

Cardiovascular effects may be seen with sympathomimetic drugs, including Bricanyl. There is some evidence from post-marketing data and published literature of myocardial ischaemia associated with beta agonists.

Due to the positive inotropic effect of beta₂-agonists, these drugs should not be used in patients with hypertrophic cardiomyopathy.

Tocolysis

Bricanyl should be used with caution in tocolysis and supervision of cardiorespiratory function, including ECG monitoring, should be considered. Treatment should be discontinued if signs of myocardial ischaemia (such as chest pain or ECG changes) develop. Bricanyl should not be used as a tocolytic agent in patients with significant risk factors for or pre-existing heart disease (see section 4.3, Contraindications).

During infusion treatment in pregnant women with beta₂-stimulants in combination with corticosteroids a rare complication with a pathological picture resembling pulmonary oedema, has been reported.

Increased tendency to uterine bleeding has been reported in connection with Caesarean section. However, this can be effectively stopped by propranolol 1-2 mg injected intravenously.

Respiratory indications

Patients with underlying severe heart disease (e.g. ischaemic heart disease, arrhythmia or severe heart failure) who are receiving Bricanyl should be warned to seek medical advice if they experience chest pain or other symptoms of worsening heart disease.

Attention should be paid to assessment of symptoms such as dyspnoea and chest pain, as they may be of either respiratory or cardiac origin.

Due to the hyperglycaemic effects of beta₂-agonists, additional blood glucose controls are recommended initially in diabetic patients.

Potentially serious hypokalaemia may result from beta₂-agonist therapy. Particular caution is recommended in acute severe asthma as the associated risk may be augmented by hypoxia. The hypokalaemic effect may be potentiated by concomitant treatments (see section 4.5, Interactions). It is recommended that serum potassium levels are monitored in such situations.

If a previously effective dosage regimen no longer gives the same symptomatic relief, the patient should urgently seek further medical advice. Consideration should be given to the requirements for additional therapy (including increased dosages of anti-inflammatory medication). Severe exacerbations of asthma should be treated as an emergency in the usual manner.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Beta-blocking agents (including eye drops), especially the non-selective ones such as propranolol, may partially or totally inhibit the effect of beta-stimulants. Therefore Bricanyl preparations and non-selective beta-blockers should not normally be administered concurrently. Bricanyl should be used with caution in patients receiving other sympathomimetics.

Hypokalaemia may result from beta₂-agonist therapy and may be potentiated by concomitant treatment with xanthine derivatives, corticosteroids and diuretics (see Section 4.4, Special Warnings and Precautions for use).

4.6 Pregnancy And Lactation

Although no teratogenic effects have been observed in animals or in patients, Bricanyl should only be administered with caution during the first trimester of pregnancy.

Terbutaline is secreted in breast milk, but effect on the infant is unlikely at therapeutic doses.

Transient hypoglycaemia has been reported in newborn preterm infants after maternal beta₂-agonist treatment.

4.7 Effects On Ability To Drive And Use Machines

None Known.

4.8 Undesirable Effects

The intensity of the adverse reactions depends on dosage and route of administration. Most of the adverse reactions are characteristic of sympathomimetic amines. The majority of these effects have reversed spontaneously within the first 1-2 weeks of treatment.

The frequency of side-effects is low at the recommended doses.

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (>1/10), common (>1/100 and <1/10), uncommon (>1/1,000 and <1/100), rare (>1/10,000 and <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

Frequency Classification	Adverse Drug Reaction
	System Organ Class (SOC)	Preferred term (PT)
Very Common (>1/10)	Nervous System Disorders	Tremor Headache
Common (>1/100, <1/10)	Cardiac Disorders	Tachycardia Palpitations
Musculoskeletal and Connective Tissue Disorders #	Muscle spasms
Metabolism and Nutrition Disorders	Hypokalaemia (See section 4.4)
Not Known ^	Cardiac Disorders	Arrhythmias, e.g. atrial fibrillation, supraventricular tachycardia and extrasystoles Myocardial ischaemia (See section 4.4)
Vascular Disorders	Peripheral vasodilation
Immune System Disorders	Hypersensitivity reactions including angioedema, bronchospasm, hypotension and collapse
Gastrointestinal Disorders	Nausea Mouth and throat irritation
Psychiatric Disorders	Sleep disorder and Behavioural disturbances, such as agitation and restlessness
Respiratory, Thoracic and Mediastinal Disorders	Paradoxical bronchospasm *
Skin and Subcutaneous Tissue Disorders	Urticaria Rash

# A few patients feel tense; this is also due to the effects on skeletal muscle and not to direct CNS stimulation.

^ Reported spontaneously in post-marketing data and therefore frequency regarded as unknown

* In rare cases, through unspecified mechanisms, paradoxical bronchospasm may occur, with wheezing immediately after inhalation. This should be immediately treated with a rapid-onset bronchodilator. Bricanyl therapy should be discontinued and after assessment, an alternative therapy initiated.

4.9 Overdose

Possible symptoms and signs

Headache, anxiety, tremor, nausea, tonic cramp, palpitations, tachycardia, arrhythmia. A fall in blood pressure sometimes occurs.

Laboratory findings; hypokalaemia, hyperglycaemia and lactic acidosis sometimes occur.

Treatment

Mild and moderate cases: Reduce the dose.

Severe cases: Gastric lavage, administration of activated charcoal. Determination of acid-base balance, blood sugar and electrolytes, particularly serum potassium levels. Monitoring of the heart rate and rhythm and blood pressure. Metabolic changes should be corrected.

A cardioselective beta-blocker (e.g. metoprolol) is recommended for the treatment of arrhythmias causing haemodynamic deterioration. The beta₂-mediated reduction in the peripheral vascular resistance significantly contributes to the fall in blood pressure, a volume expander should be given.

Preterm labour: Pulmonary oedema: discontinue administration of Bricanyl. A normal dose of loop diuretic (e.g. frusemide) should be given intravenously.

Increased bleeding in connection with Caesarian section: propranolol, 1

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmaco-therapeutic group: selective beta₂-agonist, terbutaline ATC code:R03C C03.

Terbutaline is a selective beta₂ -adrenergic stimulant having the following pharmacological effects:-

i) In the lung: bronchodilation; increase in mucociliary clearance; suppression of oedema and anti-allergic effects.

ii) In skeletal muscle: stimulates Na⁺/K⁺transport and also causes depression of subtetanic contractions in slow-contracting muscle.

iii) In uterine muscle: inhibition of uterine contractions.

iv) In the CNS: low penetration into the blood-brain barrier at therapeutic doses, due to the highly hydrophilic nature of the molecule.

v) In the CVS: administration of terbutaline results in cardiovascular effects mediated through beta₂ -receptors in the peripheral arteries and in the heart e.g. in healthy subjects, 0.25 - 0.5mg injected s.c., is associated with an increase in cardiac output (up to 85% over controls) due to an increase in heart rate and a larger stroke volume. The increase in heart rate is probably due to a combination of a reflex tachycardia via a fall in peripheral resistance and a direct positive chronotropic effect of the drug.

5.2 Pharmacokinetic Properties

Basic parameters have been evaluated in man after i.v and oral administration of therapeutic doses, e.g.

i.v. single dose

Volume distribution (VSS):	114 L
Total body clearance (CL):	213 ml/min
Mean residence time (MRT):	9.0 h
Renal clearance (CLR):	149 ml/min (males)

Oral dose

renal clearance (CLR):	1.925/ml/min (males)
renal clearance (CLR):	2.32ml/min (females)

The plasma concentration/time curve after iv administration is characterised by a fast distribution phase, an intermediate elimination phase and a late elimination phase.

Terminal half-life T½ has been determined after single and multiple dosing (mean values varied between 16-20 h)

Bioavailability

Food reduces bioavailability following oral dosing (10% on average).

Fasting values of 14-15% have been obtained.

Metabolism

The main metabolite after oral dosing is the sulphate conjugate and also some glucoronide conjugate can be found in the urine.

5.3 Preclinical Safety Data

The major toxic effect of terbutaline, observed in toxicological studies in rats and dogs at exposures in excess of maximum human exposure, is focal myocardial necrosis. This type of cardiotoxicity is a well known pharmacological manifestation seen after the administration of high doses of beta₂-agonists.

In rats, an increase in the incidence of benign uterine leiomyomas has been observed. This effect is looked upon as a class-effect observed in rodents after long term exposure to high doses of beta₂-agonists

6. Pharmaceutical Particulars

6.1 List Of Excipients

Citric Acid, disodium edetate, ethanol, glycerol, sodium hydroxide, sorbitol, sodium benzoate, essence of raspberry, water.

6.2 Incompatibilities

None known.

6.3 Shelf Life

4 years.

6.4 Special Precautions For Storage

Do not store above 25°C.

6.5 Nature And Contents Of Container

Bottles of 100ml, 300ml and 1 litre.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

AstraZeneca UK Ltd

600 Capability Green

Luton

LU1 3LU

United Kingdom

8. Marketing Authorisation Number(S)

PL17901/0111

9. Date Of First Authorisation/Renewal Of The Authorisation

7 May 2002 / 12 May 2007

10. Date Of Revision Of The Text

15^th January 2010

Hemorrhoids Medications

Definition of Hemorrhoids: Hemorrhoids are painful, swollen veins in the lower portion of the rectum or anus.

Drugs associated with Hemorrhoids

The following drugs and medications are in some way related to, or used in the treatment of Hemorrhoids. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Learn more about Hemorrhoids

Micromedex Care Notes:

• Hemorrhoids
• Rectal Bleeding

Medical Encyclopedia:

• Hemorrhoids

Harvard Health Guide:

• Symptoms and treatment for Hemorrhoids

Drug List:

Americaine-Ointment

Americaine-Anesthetic-Lubricant

Americaine-Hemorrhoidal

Analpram-Advanced

Analpram-E

Analpram-Hc-Cream

Anamantle-Hc-Cream

Anecream

Anecream-With-Tegaderm

Anest-Hemor

Anestacon

Anucort-Hc-Cream-Ointment-Suppository

Anumed-Hc-Cream-Ointment-Suppository

Anusert-Rectal

Anusol

Anusol-Suppositories-Rectal

Anusol-Hc-Cream

Anusol-Hc-Suppository

Bactine-Liquid

Benzo-Jel

Cepacol-Fizzlers

Cortalo-With-Aloe

Curasore

Dent-O-Kain

Enzone

Epifoam-Foam

Fleet-Relief-Ointment

Hc-Pram-Cream

Hc-Pramoxine

Hemorrhoidal-Hygiene-Pads

Hemorrhoidal-Suppositories-Rectal

Hydrocortisone-1-In-Absorbase

Hydrocortisone-With-Aloe-Cream

Hydropram

Hygenic-Cleansing-Pad

Lidamantle-Cream

Lidamantle-Hc-Cream

Lidamantle-Hc-Relief

Lidocort

Lidocream

Lidoderm

Lidosense-5-Cream

L-M-X4-Cream

Lmx-4-With-Tegaderm

Lmx-5-Cream

Lta-Ii-Kit

Lta-Pediatric-Kit

Lta-Preattached-360-Kit

Md-Hydrocortisone

Medi-Pad

Medi-Quik-Spray

Novacort

Nucort-With-Aloe

Nupercainal-Ointment

Orabase

Pediaderm-Hc-Lotion

Peranex-Hc-Pad

Pramasone-Cream

Pramasone-E-Cream

Preparation-H-Cream

Procto-Kit-1-Cream-Ointment-Suppository

Procto-Kit-2-5-Cream-Ointment-Suppository

Procto-Pak-1-Cream-Ointment-Suppository

Proctocare-Hc-Cream

Proctocort-Cream-Ointment-Suppository

Proctocream-Hc-Cream-Ointment-Suppository

Proctofoam-Foam

Proctofoam-Hc-Foam

Proctosert-Hc-Cream-Ointment-Suppository

Proctosol-Hc-Cream-Ointment-Suppository

Proctozone-Hc-Cream-Ointment-Suppository

Proctozone-H-Cream-Ointment-Suppository

Proctozone-P

Rectacreme-Hc-Cream

Rectagel-Hc-Cream

Rectasol-Hc-Cream-Ointment-Suppository

Rectocort-Hc

Sani-Clens

Sani-Pads-With-Aloe

Sarna-Sensitive-Eczema-Itch-Relief

Scalacort

Senatec

Soothe-It-Plus-Hemmorhoidal-Pad

Super-Dent-Topical-Anesthetic-Gel

Topicaine-Topical-Application

Topical-Anesthetic-Dental-Gel

Tronolane

Tronolane-Anesthetic-For-Hemorrhoids

Tucks

Tucks-Hemorrhoidal

Tucks-Suppositories-Rectal

Uro-Jet

Uro-Jet-Ac

Venastat

Xylocaine-Jelly-Gel

Xylocaine-Topical

Xyralid

Xyralid-Rc-Cream

Zone-A

Zone-A-Forte

Zypram-Cream

Soltamox

Generic Name: tamoxifen (Oral route)

ta-MOX-i-fen

Oral route(Tablet)

Serious and life-threatening uterine malignancies, stroke, and pulmonary embolism have been associated with tamoxifen use in the risk reduction setting (women with Ductal Carcinoma in Situ (DCIS) and women at high risk for breast cancer). Some of these adverse events were fatal. Health care providers should discuss the potential benefits versus the potential risks of these serious events with women at high risk of breast cancer and women with DCIS considering tamoxifen to reduce their risk of developing breast cancer. The benefits of tamoxifen outweigh its risks in women already diagnosed with breast cancer .

Commonly used brand name(s)

In the U.S.

• Nolvadex


• Soltamox

Available Dosage Forms:

• Solution


• Tablet

Therapeutic Class: Antiestrogen

Uses For Soltamox

Tamoxifen is a medicine that blocks the effects of the estrogen hormone in the body. It is used to treat breast cancer in women or men. It may also be used to treat other kinds of cancer, as determined by your doctor.

Tamoxifen also may be used to reduce the risk of developing breast cancer in women who have a high risk of developing breast cancer. Women at high risk for developing breast cancer are at least 35 years of age and have a combination of risk factors that make their chance of developing breast cancer 1.67% or more over the next 5 years. Your doctor will help to determine your risk of developing breast cancer.

• The following are risk factors that may increase your chance of developing breast cancer:


• If you have close family members (mother, sister, or daughter) with breast cancer.


• If you have ever had a breast biopsy or if high-risk changes in your breast(s) have been found from a breast biopsy.


• If you have never been pregnant or if your first pregnancy occurred at a late age.


• If your first menstrual period occurred at an early age.

The exact way that tamoxifen works against cancer is not known, but it may be related to the way it blocks the effects of estrogen on the body.

Before you begin treatment with tamoxifen, you and your doctor should talk about the good this medicine will do as well as the risks of using it.

Tamoxifen 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 these uses are not included in product labeling, tamoxifen is used in certain patients with the following medical conditions:

• Breast cancer, neoadjuvant treatment for hormone receptor-positive disease in postmenopausal women.


• Cancer of the endometrium (lining of the uterus).


• Malignant melanoma (a certain type of skin cancer).

Before Using Soltamox

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.

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 use of tamoxifen 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.

Pregnancy

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

Breast Feeding

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.

• Warfarin

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.

• Acenocoumarol


• Cyclophosphamide


• Dicumarol


• Fluorouracil


• Fluoxetine


• Genistein


• Ipriflavone


• Methotrexate


• Mitomycin


• Paroxetine


• Phenprocoumon


• Red Clover


• Ritonavir


• Sertraline


• St John's Wort

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.

• Aldesleukin


• Aminoglutethimide


• Anastrozole


• Bexarotene


• Letrozole


• Rifampin

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 this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• For all patients


• Blood problems or


• Cataracts or other eye problems—Tamoxifen may also cause these problems.

• High cholesterol levels in the blood—Tamoxifen can increase cholesterol levels.

• When used for reducing the risk for developing breast cancer in high-risk women or in women with Ductal Carcinoma in Situ (DCIS)


• Blood clots (or history of) or


• Pulmonary embolism (or history of) or


• Stroke or


• Uterine (womb) cancer—May increase risk of serious side effects from tamoxifen.

Proper Use of tamoxifen

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

Use this medicine only as directed by your doctor. Do not use more or less of it, and do not use it more often than your doctor ordered. The exact amount of medicine you need has been carefully worked out. Taking too much may increase the chance of side effects, while taking too little may not improve your condition.

Tamoxifen sometimes causes mild nausea and vomiting. However, it may have to be taken for several weeks or months to be effective. Even if you begin to feel ill, do not stop using this medicine without first checking with your doctor. Ask your health care professional for ways to lessen these effects.

Swallow the tablets whole with a drink of water. You can take the tablets with or without food.

If you vomit shortly after taking a dose of tamoxifen, check with your doctor. You will be told whether to take the dose again or to wait until the next scheduled dose.

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 breast cancer in women or men:
    
    • Adults—20 to 40 milligrams (mg) daily.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For reducing the risk of developing breast cancer in high-risk women:
    
    • Adults—20 milligrams (mg) a day for five years.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For reducing the risk of developing invasive breast cancer in women with ductal carcinoma in situ:
    
    • Adults—20 milligrams (mg) a day for five years.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Call your doctor or pharmacist for instructions.

Storage

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

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

Precautions While Using Soltamox

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly and to check for unwanted effects.

A woman should contact her doctor right away if she develops:

• Changes in vaginal discharge or


• Changes in vision or


• Coughing up blood or


• Leg swelling or tenderness or


• Menstrual irregularities or


• New breast lumps or


• Pelvic pain or pressure or


• Sudden chest pain or


• Unexplained shortness of breath or


• Vaginal bleeding

If you seek medical attention for any reason, be sure to tell your doctor that you take tamoxifen or have taken tamoxifen.

For women: Tamoxifen may make you more fertile. It is best to use some type of birth control while you are taking it. However, do not use oral contraceptives (“the Pill”) since they may change the effects of tamoxifen. Tell your doctor right away if you think you have become pregnant while taking this medicine.

Soltamox Side Effects

Because of the way this medicine acts on the body, there is a chance that it might cause unwanted effects that may not occur until months or years after the medicine is used. Tamoxifen increases the chance of cancer of the uterus (womb) in some women taking it. Tamoxifen may cause blockages to form in a vein, lung, or brain. In women, tamoxifen may cause cancer or other problems of the uterus (womb). It also causes liver cancer in rats. In addition, tamoxifen has been reported to cause cataracts and other eye problems. Discuss these possible effects with your doctor.

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:

Less common or rare

• Anxiety


• blistering, peeling, or loosening of the skin and mucous membranes


• blurred vision


• cataracts in the eyes or other eye problems


• change in vaginal discharge


• chest pain


• chills


• confusion


• cough


• dizziness


• fainting


• fast heartbeat


• fever


• hoarseness


• lightheadedness


• lower back or side pain


• pain or feeling of pressure in the pelvis


• pain or swelling in the legs


• pain, redness, or swelling in your arm or leg


• painful or difficult urination


• rapid shallow breathing


• shortness of breath or trouble with breathing


• skin rash or itching over the entire body


• sweating


• weakness or sleepiness


• wheezing


• vaginal bleeding


• yellow eyes or skin

Incidence not known

• Bloating


• constipation


• darkened urine


• diarrhea


• difficulty with breathing


• indigestion


• itching


• joint or muscle pain


• large, hard skin blisters


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


• loss of appetite


• nausea


• pain in the stomach or side, possibly radiating to the back


• red, irritated eyes


• red skin lesions, often with a purple center


• sore throat


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


• unusual tiredness or weakness


• vomiting

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

More common

• Absent, missed, or irregular periods


• decrease in the amount of urine


• feeling of warmth


• menstrual changes


• noisy, rattling breathing


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


• skin changes


• stopping of menstrual bleeding


• swelling of the fingers, hands, feet, or lower legs


• troubled breathing at rest


• weight gain or loss


• white or brownish vaginal discharge

Less common or rare

• Abdominal or stomach cramps


• black, tarry stools


• bleeding gums


• blood in the urine or stools


• bluish color changes in skin color


• bone pain


• decreased interest in sexual intercourse


• discouragement


• feeling sad or empty


• hair loss or thinning of the hair


• headache


• inability to have or keep an erection


• irritability


• itching in the genital area


• loss of interest or pleasure


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


• nausea or vomiting (mild)


• pain


• pinpoint red spots on the skin


• skin rash or dryness


• stomach or pelvic discomfort, aching, or heaviness


• swelling


• trouble concentrating


• trouble with sleeping


• unusual bleeding or bruising

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: Soltamox side effects (in more detail)

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

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

More Soltamox resources

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

• Soltamox Prescribing Information (FDA)


• Soltamox Concise Consumer Information (Cerner Multum)


• Soltamox Solution MedFacts Consumer Leaflet (Wolters Kluwer)


• Tamoxifen Prescribing Information (FDA)


• Nolvadex Prescribing Information (FDA)


• Nolvadex MedFacts Consumer Leaflet (Wolters Kluwer)


• Nolvadex Monograph (AHFS DI)

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Zorbtive

somatropin (rDNA origin)

Dosage Form: injection
Zorbtive®

[somatropin (rDNA origin) for injection]

Zorbtive Description

Zorbtive® [somatropin (rDNA origin) for injection] is a human growth hormone (hGH) produced by recombinant DNA technology. Zorbtive® has 191 amino acid residues and a molecular weight of 22,125 daltons. Its amino acid sequence and structure are identical to the dominant form of human pituitary GH. Zorbtive® is produced by a mammalian cell line (mouse C127) that has been modified by the addition of the hGH gene. Zorbtive® is secreted directly through the cell membrane into the cell-culture medium for collection and purification.

Zorbtive® is a highly purified preparation. Biological potency is determined by measuring the increase in the body weight induced in hypophysectomized rats.

Zorbtive® is available in 8.8 mg vials for multi-dose administration. Each 8.8 mg vial contains 8.8 mg (approximately 26.4 IU) somatropin, 60.19 mg sucrose and 2.05 mg phosphoric acid. The pH is adjusted with sodium hydroxide or phosphoric acid to give a pH of 7.4 to 8.5 after reconstitution.

Zorbtive - Clinical Pharmacology

Zorbtive® [somatropin (rDNA origin) for injection] is an anabolic and anticatabolic agent which exerts its influence by interacting with specific receptors on a variety of cell types including myocytes, hepatocytes, adipocytes, lymphocytes, and hematopoietic cells. Some, but not all of its effects, are mediated by insulin-like growth factor-1 (IGF-1).

MECHANISM OF ACTION IN SHORT BOWEL SYNDROME (SBS) PATIENTS

Intestinal mucosa contains receptors for growth hormone and for insulin-like growth factor-1 (IGF-1), which is known to mediate many of the cellular actions of growth hormone. Thus, the actions of growth hormone on the gut may be direct or mediated via the local or systemic production of IGF-1.

In human clinical studies the administration of growth hormone has been shown to enhance the transmucosal transport of water, electrolytes, and nutrients.

PHARMACOKINETICS

Subcutaneous Absorption:  The absolute bioavailability of Zorbtive® [somatropin (rDNA origin) for injection] after subcutaneous administration of a formulation not equivalent to the marketed formulation was determined to be 70-90%. The t½ (Mean ± SD) after subcutaneous administration is significantly longer than that seen after intravenous administration in normal male volunteers down-regulated with somatostatin (3.94 ± 3.44 hrs. vs. 0.58 ± 0.08 hrs.), indicating that the subcutaneous absorption of the clinically tested formulation of the compound is slow and rate-limiting.

Distribution:  The steady-state volume of distribution (Mean ± SD) following IV administration of Zorbtive® in healthy volunteers is 12.0 ± 1.08 L.

Metabolism:  Although the liver plays a role in the metabolism of GH, GH is primarily cleaved in the kidney. GH undergoes glomerular filtration and, after cleavage within the renal cells, the peptides and amino acids are returned to the systemic circulation.

Elimination:  The t½ (Mean ± SD) in nine patients with HIV-associated wasting with an average weight of 56.7 ± 6.8 kg, given a fixed dose of 6.0 mg recombinant hGH (r-hGH) subcutaneously was 4.28 ± 2.15 hrs. The renal clearance of r-hGH after subcutaneous administration in nine patients with HIV-associated wasting was 0.0015 ± 0.0037 L/h. No significant accumulation of r-hGH appears to occur after 6 weeks of dosing as indicated.

Special Populations:

Pediatric:  Available evidence suggests that r-hGH clearances are similar in adults and children, but no pharmacokinetic studies have been conducted in children with short bowel syndrome.

Gender:  Biomedical literature indicates that a gender-related difference in the mean clearance of r-hGH could exist (clearance of r-hGH in males > clearance of r-hGH in females). However, no gender-based analysis is available in normal volunteers or patients with short bowel syndrome.

Race:  No data are available.

Renal Insufficiency:  It has been reported that individuals with chronic renal failure tend to have decreased r-hGH clearance compared to normals, but there are no data on Zorbtive® use in the presence of renal insufficiency.

Hepatic Insufficiency:  A reduction in r-hGH clearance has been noted in patients with severe liver dysfunction. However, the clinical significance of this in short bowel syndrome patients is unknown.

CLINICAL STUDIES

A randomized, double-blind, controlled, parallel-group Phase III clinical study evaluated the efficacy and safety of the administration of Zorbtive® in subjects with Short Bowel Syndrome (SBS) who were dependent on intravenous parenteral nutrition (IPN) for nutritional support. The primary endpoint was the change in weekly total IPN volume defined as the sum of the volumes of IPN, supplemental lipid emulsion (SLE), and intravenous hydration fluid. The secondary endpoints were the change in weekly IPN caloric content and the change in the frequency of IPN administration per week. Subjects received either Zorbtive® placebo with the nutritional supplement, glutamine (n=9), Zorbtive® without glutamine (n=16) or Zorbtive® with glutamine (n=16). All 3 groups received a specialized diet. Following a two-week equilibration period, treatment was administered in a double-blind manner over a further period of four weeks. The dosing of Zorbtive® was approximately 0.1 mg/kg/day for 4 weeks. During the double-blind treatment portion of the trial, the glutamine was given at a daily dose of 30 g. The mean baseline IPN volume, mean IPN caloric content, and mean frequency of IPN administration are provided in Table 1. Mean reductions in IPN volume, IPN caloric content and the frequency of IPN administration in each patient group were significantly greater in both Zorbtive®-treated groups than in the group treated with Zorbtive® placebo. These changes are tabulated in Table 1.

Table 1:  Results for Endpoints after 4 weeks of Treatment

	SOD[GLN] 1	r-hGH + SOD 1	r-hGH + SOD[GLN] 1
1 SOD[GLN] = Specialized Oral Diet supplemented with Glutamine ; r-hGH + SOD = Human Growth Hormone plus Specialized Oral Diet; r-hGH + SOD[GLN] = Human Growth Hormone plus Specialized Oral Diet supplemented with Glutamine
*   p = 0.043, treatment comparison between r-hGH + SOD versus SOD[GLN]
** p <0.001, treatment comparison between r-hGH + SOD[GLN] versus SOD[GLN]
Total IPN volume (L/wk)
Mean at Baseline	13.5	10.3	10.5
Mean Change	-3.8	-5.9	-7.7
Treatment Differences (with GLN)		-2.1*	-3.9**
Total IPN Calories (kcal/wk)
Mean at Baseline	8570.4	7634.7	7895.0
Mean Change	-2633.3	-4338.3	-5751.2
Treatment Differences (with GLN)		-1705.0	-3117.9
Frequency of IPN or SLE (days/wk)
Mean at Baseline	5.9	5.1	5.4
Mean Change	-2.0	-3.0	-4.2
Treatment Differences (with GLN)		-1.0	-2.2

Indications and Usage for Zorbtive

Zorbtive® [somatropin (rDNA origin) for injection] is indicated for the treatment of Short Bowel Syndrome in patients receiving specialized nutritional support. Zorbtive® therapy should be used in conjunction with optimal management of Short Bowel Syndrome.

Specialized nutritional support may consist of a high carbohydrate, low-fat diet, adjusted for individual patient requirements and preferences. Nutritional supplements may be added according to the discretion of the treating physician. Optimal management of Short Bowel Syndrome may include dietary adjustments, enteral feedings, parenteral nutrition, fluid and micronutrient supplements, as needed.

Contraindications

Growth hormone therapy should not be initiated in patients with acute critical illness due to complications following open heart or abdominal surgery, multiple accidental trauma or acute respiratory failure. Two placebo-controlled clinical trials in non-growth hormone deficient adult patients (n=522) with these conditions revealed a significant increase in mortality (41.9% vs. 19.3%) among somatropin-treated patients (doses 5.3-8 mg/day) compared to those receiving placebo (See “WARNINGS”).

Zorbtive® is contraindicated in patients with active neoplasia (either newly diagnosed or recurrent). Any anti-tumor therapy should be completed prior to starting therapy with Zorbtive®. Zorbtive® [somatropin (rDNA origin) for injection] reconstituted with Bacteriostatic Water for Injection, USP (0.9% Benzyl Alcohol) should not be administered to patients with a known sensitivity to Benzyl Alcohol.  (See “WARNINGS”)

Zorbtive® is contraindicated in patients with a known hypersensitivity to growth hormone.

Warnings

Benzyl Alcohol as a preservative in Bacteriostatic Water for Injection, USP has been associated with toxicity in newborns. If sensitivity to the diluent occurs, Zorbtive® [somatropin (rDNA origin) for injection] may be reconstituted with Sterile Water for Injection, USP. When Zorbtive® is reconstituted in this manner, the reconstituted solution should be used immediately and any unused portion should be discarded.

See “CONTRAINDICATIONS” for information regarding increased mortality in growth hormone-treated patients with acute critical illnesses in intensive care units due to complications following open heart or abdominal surgery, multiple accidental trauma or acute respiratory failure. The safety of continuing growth hormone treatment in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established. Therefore, the potential benefit of treatment continuation with growth hormone in patients developing acute critical illnesses should be weighed against the potential risk.

Precautions

General

Zorbtive® [somatropin (rDNA origin) for injection] therapy should be carried out under the regular guidance of a physician who is experienced in the diagnosis and management of short bowel syndrome.

Patients should be informed that allergic reactions are possible and that prompt medical attention should be sought if an allergic reaction occurs.

Recombinant human growth hormone (r-hGH) has been associated with acute pancreatitis. The use of somatropin has been associated with cases of new onset impaired glucose intolerance, new onset type 2 diabetes mellitus and exacerbation of preexisting diabetes mellitus have been reported in patients receiving somatropin. Some patients developed diabetic ketoacidosis and diabetic coma. In some patients, these conditions improved when somatropin was discontinued, while in others the glucose intolerance persisted. Some patients necessitated initiation or adjustment of antidiabetic treatment while on somatropin. Patients with other risk factors for glucose intolerance should be monitored closely during Zorbtive® therapy.

No cases of intracranial hypertension (IH) have been observed among patients with short bowel syndrome treated with Zorbtive®. The syndrome of IH, with papilledema, visual changes, headache, and nausea and/or vomiting has been reported in a small number of children with growth failure treated with growth hormone products. Nevertheless, funduscopic evaluation of patients is recommended at the initiation and periodically during the course of Zorbtive® therapy.

Increased tissue turgor (swelling, particularly in the hands and feet) and musculoskeletal discomfort (pain, swelling and/or stiffness) may occur during treatment with Zorbtive®, but may resolve spontaneously, with analgesic therapy, or after reducing the frequency of dosing (see “DOSAGE AND ADMINISTRATION”).

Carpal tunnel syndrome may occur during treatment with somatropin. If the symptoms of carpal tunnel syndrome do not resolve by decreasing the dose or frequency of somatropin, it is recommended that treatment be discontinued.

Information for Patients

Patients being treated with Zorbtive® should be informed of the potential benefits and risks associated with treatment. Patients should be instructed to contact their physician should they experience any side effects or discomfort during treatment with Zorbtive®.

It is recommended that Zorbtive® be administered using sterile, disposable syringes and needles. Patients should be thoroughly instructed in the importance of proper disposal and cautioned against any reuse of needles and syringes. An appropriate container for the disposal of used syringes and needles should be employed.

Patients should be instructed to rotate injection sites to avoid localized tissue atrophy.

Drug Interactions

Formal drug interaction studies have not been conducted. Somatropin inhibits 11ß-hydroxysteroid dehydrogenase type 1 (11 ßHSD-1) in adipose/ hepatic tissue and may significantly impact the metabolism of cortisol and cortisone. As a consequence, in patients treated with somatropin, previously undiagnosed primary (and secondary) hypoadrenalism may be unmasked requiring glucocorticoid replacement therapy. In addition, patients treated with glucocorticoid replacement therapy for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses; this may be especially true for patients treated with cortisone acetate and prednisone since conversion of these drugs to their biologically active metabolites is dependent on the activity of the 11 ßHSD-1 enzyme.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies for carcinogenicity have not been performed with Zorbtive®. There is no evidence from animal studies to date of Zorbtive®-induced mutagenicity or impairment of fertility.

Pregnancy

Pregnancy Category B. Reproduction studies have been performed in rats and rabbits. Doses up to 5 to 10 times the human dose, based on body surface area, have revealed no evidence of impaired fertility or harm to the fetus due to Zorbtive®. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Women

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

Pediatric Use

There are no formal studies in pediatric patients with short bowel syndrome.

Geriatric Use

Clinical studies with Zorbtive® did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Elderly patients may be more sensitive to growth hormone action, and may be more prone to develop adverse reactions. Thus, dose selection for an elderly patient should be cautious, usually starting at a lower dose.

Adverse Reactions

Table 2 summarizes the number of subjects by system-organ class who experienced an adverse event during the 4-week treatment period of the Phase III SBS study. To be listed in Table 2, an adverse event must have occurred in more than 10% of subjects in any treatment group.

Table 2:  Controlled Trial Adverse Events – 4 Week Treatment Period

Adverse Experiences	SOD[GLN]1 n=9 n (%)	r-hGH+SOD1 n=16 n (%)	r-hGH+SOD[GLN]1 n=16 n (%)
1 SOD[GLN] = Specialized Oral Diet supplemented with Glutamine; r-hGH + SOD = Human Growth Hormone plus Specialized Oral Diet; r-hGH + SOD[GLN] = Human Growth Hormone plus Specialized Oral Diet supplemented with Glutamine
Total Number of Subjects with At Least One AE	8 (89)	16 (100)	16 (100)
Body as a Whole, General Disorders	4 (44)	15 (94)	15 (94)
Edema, Peripheral	1 (11)	11 (69)	13 (81)
Edema, Facial	0 (0)	8 (50)	7 (44)
Pain	1 (11)	3 (19)	1 (6)
Chest Pain	0 (0)	3 (19)	0 (0)
Fever	2 (22)	0 (0)	1 (6)
Back Pain	1 (11)	1 (6)	0 (0)
Flu-like Disorder	1 (11)	0 (0)	1 (6)
Malaise	0 (0)	2 (13)	0 (0)
Edema, Generalized	0 (0)	2 (13)	0 (0)
Abdomen Enlarged	1 (11)	0 (0)	0 (0)
Allergic Reaction	1 (11)	0 (0)	0 (0)
Rigors (Chills)	1 (11)	0 (0)	0 (0)
Gastrointestinal System Disorders	6 (67)	12 (75)	12 (75)
Flatulence	2 (22)	4 (25)	4 (25)
Abdominal Pain	1 (11)	4 (25)	2 (13)
Nausea	0 (0)	2 (13)	5 (31)
Tenesmus	3 (33)	1 (6)	3 (19)
Vomiting	1 (11)	3 (19)	3 (19)
Hemorrhoids	1 (11)	1 (6)	0 (0)
Mouth Dry	1(11)	1 (6)	0 (0)
Musculoskeletal System Disorders	1 (11)	7 (44)	7 (44)
Arthralgia	0 (0)	7 (44)	5 (31)
Myalgia	1 (11)	2 (13)	0 (0)
Resistance Mechanism Disorders	4 (44)	6 (38)	3 (19)
Infection	3 (33)	0 (0)	1 (6)
Infection Bacterial	1 (11)	3 (19)	0 (0)
Infection Viral	0 (0)	1 (6)	2 (13)
Moniliasis	0 (0)	2 (13)	0 (0)
Application Site Disorders	1 (11)	5 (31)	4 (25)
Injection Site Reaction	1 (11)	3 (19)	4 (25)
Injection Site Pain	0 (0)	5 (31)	0 (0)
Central and Peripheral Nervous System Disorders	2 (22)	4 (25)	4 (25)
Dizziness	0 (0)	1 (6)	2 (13)
Headache	1 (11)	1 (6)	1 (6)
Hypoasthesia	1 (11)	1 (6)	1 (6)
Skin and Appendages Disorders	2 (22)	4 (25)	4 (25)
Rash	0 (0)	1 (6)	2 (13)
Pruritis	1 (11)	0 (0)	1 (6)
Sweating Increased	0 (0)	2 (13)	0 (0)
Nail Disorder	1 (11)	0 (0)	0 (0)
Respiratory System Disorders	1 (11)	1 (6)	5 (31)
Rhinitis	1 (11)	0 (0)	3 (19)
Metabolic and Nutritional Disorders	1 (11)	3 (19)	1 (6)
Dehydration	1 (11)	3 (19)	0 (0)
Thirst	1 (11)	0 (0)	0 (0)
Urinary System Disorders	1 (11)	2 (13)	1 (6)
Pyelonephritis	1 (11)	0 (0)	0 (0)
Psychiatric Disorders	2 (22)	1 (6)	0 (0)
Depression	2 (22)	0 (0)	0 (0)
Reproductive Disorders, Female	1 (11)	2 (13)	0 (0)
Breast Pain Female	1 (11)	1 (6)	0 (0)
Hearing and Vestibular Disorders	0 (0)	0 (0)	2 (13)
Ear or Hearing Symptoms	0 (0)	0 (0)	2 (13)

Table 3 summarizes the number of subjects by system-organ class who experienced an adverse event during the 12-week follow-up period of the Phase III SBS study. To be listed in Table 3, an adverse event must have occurred in more than 10% of subjects in any treatment group.

Table 3:  Controlled Trial Adverse Events – 12 Week Follow-Up Period

Adverse Experiences	SOD[GLN]1 n=9 n (%)	r-hGH+SOD1 n=15 n (%)	r-hGH+SOD[GLN]1 n=16 n (%)
1 SOD[GLN] = Specialized Oral Diet supplemented with Glutamine ;r-hGH + SOD = Human Growth Hormone plus Specialized Oral Diet; r-hGH + SOD[GLN] = Human Growth Hormone plus Specialized Oral Diet supplemented with Glutamine
Total Number of Subjects with At Least One AE	7 (78)	12 (80)	13 (81)
Gastrointestinal System Disorders	3 (33)	7 (47)	7 (44)
Nausea	2 (22)	3 (20)	0 (0)
Vomiting	0 (0)	2 (13)	3 (19)
Abdominal Pain	0 (0)	3 (20)	1 (6)
Tenesmus	1 (11)	0 (0)	3 (19)
Pancreatitis	1 (11)	0 (0)	1 (6)
Constipation	1 (11)	0 (0)	0 (0)
Crohn's Disease Aggravated	1 (11)	0 (0)	0 (0)
Gastric Ulcer	1 (11)	0 (0)	0 (0)
Gastrointestinal Fistula	1 (11)	0 (0)	0 (0)
Resistance Mechanism Disorders	5 (56)	6 (40)	5 (31)
Infection Bacterial	3 (33)	0 (0)	2 (13)
Infection Viral	1 (11)	3 (20)	1 (6)
Infection	1 (11)	1 (7)	2 (13)
Sepsis	0 (0)	3 (20)	1 (6)
Body as a Whole, General Disorders	1 (11)	4 (27)	2 (13)
Fever	1 (11)	2 (13)	1 (6)
Fatigue	0 (0)	2 (13)	0 (0)
Respiratory System Disorders	1 (11)	2 (13)	4 (25)
Rhinitis	0 (0)	1 (7)	3 (19)
Laryngitis	1 (11)	0 (0)	0 (0)
Pharyngitis	1 (11)	0 (0)	0 (0)
Reproductive Disorders, Female	1 (11)	0 (0)	4 (25)
Vaginal Fungal Infection	1 (11)	0 (0)	0 (0)
Skin and Appendages Disorders	1 (11)	2 (13)	2 (13)
Rash	1 (11)	1 (7)	0 (0)
Musculoskeletal System Disorders	0 (0)	2 (13)	2 (13)
Arthralgia	0 (0)	2 (13)	2 (13)
Psychiatric Disorders	1 (11)	0 (0)	1 (6)
Depression	1 (11)	0 (0)	0 (0)
Insomnia	1 (11)	0 (0)	0 (0)
Urinary System Disorders	2 (22)	0 (0)	0 (0)
Pyelonephritis	1 (11)	0 (0)	0 (0)
Renal Calculus	1 (11)	0 (0)	0 (0)
Application Site Disorders	1 (11)	0 (0)	0 (0)
Injection Site Reaction	1 (11)	0 (0)	0 (0)
Liver and Biliary System Disorders	1 (11)	0 (0)	0 (0)
Hepatic Function Abnormal	1 (11)	0 (0)	0 (0)
Vascular Extracardiac Disorders	1 (11)	0 (0)	0 (0)
Vascular Disorder	1 (11)	0 (0)	0 (0)

Adverse events that occurred in 1% to less than 10% of study participants receiving Zorbtive® in the placebo-controlled clinical efficacy trial are listed below by body system. The list of adverse events has been compiled regardless of casual relationship to Zorbtive®.

Body as a Whole, General:  edema, periorbital edema

Gastrointestinal System:  melena, rectal hemorrhage, mouth disorder, steatorrhea

Musculoskeletal System:  arthritis, arthropathy, bursitis, cramps

Resistance Mechanism Disorders:  fungal infection

Application Site Disorders:  reaction pain, inflammation at injection sites

Central