Deserila

Deserila may be available in the countries listed below.

Ingredient matches for Deserila

Methysergide

Methysergide is reported as an ingredient of Deserila in the following countries:

• Brazil

International Drug Name Search

Tham injection

tromeThamine

Dosage Form: injection

For the Prevention and Correction of Severe Metabolic Acidosis

Large Volume Glass Container

Rx Only

Tham Description

Tham Solution (tromeThamine injection) is a sterile, non-pyrogenic 0.3 M solution of tromeThamine, adjusted to a pH of approximately 8.6 with glacial acetic acid. It is administered by intravenous injection, by addition to ACD blood for priming cardiac bypass equipment and by injection into the ventricular cavity during cardiac arrest.

Each 100 mL contains tromeThamine 3.6 g (30 mEq) in water for injection. The solution is hypertonic 389 mOsmol/L (calc.). pH 8.6 (8.4-8.7).

The solution contains no bacteriostat, antimicrobial agent or added buffer (except acetic acid for pH adjustment) and is intended only for use as a single-dose injection. When smaller doses are required the unused portion should be discarded.

Tham solution is a parenteral systemic alkalizer and fluid replenisher.

TromeThamine, USP (sometimes called “tris” or “tris buffer”) is chemically designated 2-amino-2-(hydroxymethyl)-1, 3-propanediol, a solid readily soluble in water, also classified as an organic amine buffer. It has the following structural formula:

Water for Injection, USP is chemically designated H20.

Tham - Clinical Pharmacology

When administered intravenously as a 0.3 M solution, tromeThamine act as a proton acceptor and prevents or corrects acidosis by actively binding hydrogen ions (H+). It binds not only cations of fixed or metabolic acids, but also hydrogen ions of carbonic acid, thus increasing bicarbonate anion (HCO3⁻). TromeThamine also acts as an osmotic diuretic, increasing urine flow, urinary pH, and excretion of fixed acids, carbon dioxide and electrolytes. A significant fraction of tromeThamine (30% at pH 7.40) is not ionized and therefore is capable of reaching equilibrium in total body water. This portion may penetrate cells and may neutralize acidic ions of the intracellular fluid.

The drug is rapidly eliminated by the kidney; 75% or more appears in the urine after eight hours. Urinary excretion continues over a period of three days.

Water is an essential constituent of all body tissues and accounts for approximately 70% of total body weight. Average normal adult daily requirement ranges from two to three liters (1.0 to 1.5 liters each for insensible water loss by perspiration and urine production).

Water balance is maintained by various regulatory mechanisms. Water distribution depends primarily on the concentration of electrolytes in the body compartments and sodium (Na+) plays a major role in maintaining physiologic equilibrium.

Indications and Usage for Tham

Tham Solution (tromeThamine injection) is indicated for the prevention and correction of metabolic acidosis. In the following conditions it may help to sustain vital functions and thus provide time for treatment of the primary disease:

1. 
   

   Metabolic Acidosis Associated with Cardiac Bypass Surgery.

   
   

   Tham Solution has been found to be primarily beneficial in correcting metabolic acidosis which may occur during or immediately following cardiac bypass surgical procedures.

   
   


2. 
   

   Correction of Acidity of ACD Blood in Cardiac Bypass Surgery.

   
   

   It is well known that ACD blood is acidic and becomes more acidic on storage. TromeThamine effectively corrects this acidity. Tham Solution may be added directly to the blood used to prime the pump-oxygenator. When ACD blood is brought to a normal pH range the patient is spared an initial acid load. Additional tromeThamine may be indicated during cardiac bypass surgery should metabolic acidosis appear.

   
   


3. 
   

   Metabolic Acidosis Associated with Cardiac Arrest.

   
   

   Acidosis is nearly always one of the consequences of cardiac arrest and, in some instances, may even be a causative factor in arrest. It is important therefore, that the correction of acidosis should be started promptly with other resuscitative efforts. By correcting acidosis, Tham Solution (tromeThamine injection) has caused the arrested heart to respond to resuscitative efforts after standard methods alone had failed. In these cases, tromeThamine was given intraventricularly. It is to be noted, however, that such precariously ill patients often have died subsequently of causes unrelated to the administration of tromeThamine. With administration by the peripheral venous route, metabolic acidosis has been corrected in a majority of patients. The success in reinstitution of cardiac rhythm by this means probably has not been of the same order of magnitude as with the intraventricular route.

   
   

Contraindications

Tham Solution (tromeThamine injection) is contraindicated in uremia and anuria. In neonates it is also contraindicated in chronic respiratory acidosis and salicylate intoxication.

Warnings

1. 
   

   Large doses of Tham Solution may depress ventilation, as a result of increased blood pH and reduced CO2 concentration. Thus, dosage should be adjusted so that blood pH is not allowed to increase above normal. In situations in which respiratory acidosis may be present concomitantly with metabolic acidosis, the drug may be used with mechanical assistance to ventilation.

   
   


2. 
   

   Care must be exercised to prevent perivascular infiltration since this can cause inflammation, necrosis and sloughing of tissue. Venospasm and intravenous thrombosis, which may occur during infusion, can be minimized by insuring that the injection needle is well within the largest available vein and that solutions are slowly infused. Intravenous catheters are recommended. If perivascular infiltration occurs, institute appropriate countermeasures. See ADVERSE REACTIONS.

   
   


3. 
   

   Tham Solution (tromeThamine injection) should be administered slowly and in amounts sufficient only to correct the existing acidosis, and to avoid overdosage and alkalosis. Overdosage in terms of total drug and/or too rapid administration, may cause hypoglycemia of a prolonged duration (several hours). Therefore, frequent blood glucose determinations should be made during and after therapy.

   
   


4. 
   

   Extreme care should be exercised in patients with renal disease or reduced urinary output because of potential hyperkalemia and the possibility of a decreased excretion of tromeThamine. In such patients, the drug should be used cautiously with electrocardiographic monitoring and frequent serum potassium determinations.

   
   


5. 
   

   Because clinical experience has been limited generally to short-term use, the drug should not be administered for more than a period of one day except in a life-threatening situation.

   
   

The intravenous administration of Tham Solution can cause fluid and/or solute overloading resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema.

Additives may be incompatible. Consult with pharmacist, if available. When introducing additives, use aseptic technique, mix thoroughly and do not store.

Precautions

1. 
   

   Blood pH, PCO2 bicarbonate, glucose and electrolyte determinations should be performed before, during and after administration of Tham Solution.

   
   


2. 
   

   While it has not been shown that the drug increases coagulation time in humans, this possibility should be kept in mind since this has been noted experimentally in dogs.

   
   

Do not administer unless solution is clear and seal is intact. Discard unused portion.

Pregnancy Category C:

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

Nursing Mothers:

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Tham Solution is administered to a nursing mother.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Studies with Tham Solution have not been performed to evaluate carcinogenic potential, mutagenic potential or effects on fertility.

Pediatric Use:

The safety and effectiveness of Tham Solution in pediatric patients is based on over 30 years’ clinical experience documented in the literature and on safety surveillance. Tham Solution has been used to treat severe cases of metabolic acidosis with concurrent respiratory acidosis because it does not raise PCO2 as bicarbonate does in neonates and infants with respiratory failure. It has also been used in neonates and infants with hypernatremia and metabolic acidosis to avoid the additional sodium given with the bicarbonate. However, because the osmotic effects of Tham Solution are greater and large continuous doses are required, bicarbonate is preferred to Tham Solution in the treatment of acidotic neonates and infants with RDS. Hypoglycemia may occur when this product is used in premature and even full-term neonates. See WARNINGS and ADVERSE REACTIONS.

Geriatric Use:

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

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

Adverse Reactions

Generally, side effects have been infrequent.

Respiratory: Although the incidence of ventilatory depression is low, it is important to keep in mind that such depression may occur. Respiratory depression may be more likely to occur in patients who have chronic hypoventilation or those who have been treated with drugs which depress respiration. In patients with associated respiratory acidosis, tromeThamine should be administered with mechanical assistance to ventilation.

Vascular: Extreme care should be taken to avoid perivascular infiltration. Local tissue damage and subsequent sloughing may occur if extravasation occurs. Chemical phlebitis and venospasm also have been reported.

Hematologic: Transient depression of blood glucose may occur.

Hepatic: Infusion via low-lying umbilical venous catheters has been associated with hepatocellular necrosis.

Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection extravasation and hypervolemia.

If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination if deemed necessary.

Overdosage

Too rapid administration and/or excessive amounts of tromeThamine may cause alkalosis, hypoglycemia, overhydration or solute overload. In the event of overdosage, discontinue the infusion, evaluate the patient and institute appropriate countermeasures. See WARNINGS, PRECAUTIONS and ADVERSE REACTIONS.

The LD50 values for the acute intravenous toxicity of Tham are influenced by the rate of infusion of the dose administered.

Intravenous LD50 Mice = 3500 mg/kg

Intravenous LD50 Rats = 2300 mg/kg

Tham Dosage and Administration

Tham Solution (tromeThamine injection) is administered by slow intravenous infusion, by addition to pump-oxygenator ACD blood or other priming fluid or by injection into the ventricular cavity during cardiac arrest. For infusion by peripheral vein, a large needle should be used in the largest antecubital vein or an indwelling catheter placed in a large vein of an elevated limb to minimize chemical irritation of the alkaline solution during infusion. Catheters are recommended.

Dosage and rate of administration should be carefully supervised to avoid overtreatment (alkalosis). Pretreatment and subsequent determinations of blood values (e.g. pH, PCO2, PO2, glucose and electrolytes) and urinary output should be made as necessary to monitor dosage and progress of treatment. In general, dosage should be limited to an amount sufficient to increase blood pH to normal limits (7.35 to 7.45) and to correct acid-base derangements. The total quantity to be administered during the period of illness will depend upon the severity and progression of the acidosis. The possibility of some retention of tromeThamine, especially in patients with impaired renal function, should be kept in mind.

The intravenous dosage of Tham Solution (tromeThamine injection) may be estimated from the buffer base deficit of the extracellular fluid in mEq/liter determined by means of the Siggaard-Andersen nomogram. The following formula is intended as a general guide:

Tham Solution (mL of 0.3 M) Required =

Body Weight (kg) X

Base Deficit (mEq/liter) X 1.1*

Thus, a 70 kg patient with a buffer base deficit (“negative base excess”) of 5 mEq/liter would require 70 x 5 x 1.1 = 385 mL of Tham Solution containing 13.9 g (115 mEq) of tromeThamine. The need for administration of additional Tham Solution is determined by serial determinations of the existing base deficit.

* Factor of 1.1 accounts for an approximate reduction of 10% in buffering capacity due to the presence of sufficient acetic acid to lower pH of the 0.3 M solution to approximately 8.6.

Correction of Metabolic Acidosis Associated with Cardiac Bypass Surgery: An adverse dose of approximately 9.0 mL/kg (324 mg/kg) has been used in clinical studies with Tham Solution (tromeThamine injection). This is equivalent to a total dose of 630 mL (189 mEq) for 70 kg patient. A total single dose of 500 mL (150 mEq) is considered adequate for most adults. Larger single doses (up to 1000 mL) may be required in unusually severe cases.

It is recommended that individual doses should not exceed 500 mg/kg (227 mg/lb) over a period of not less than one hour. Thus, for a 70 kg (154 pound) patient the dose should not exceed a maximum of 35 g per hour (1078 mL of a 0.3 M solution). Repeated determinations of pH and other clinical observations should be used as a guide to the need for repeat doses.

Correction of Acidity of ACD Blood in Cardiac Bypass Surgery:The pH of stored blood ranges from 6.80 to 6.22 depending upon the duration of storage. The amount of Tham Solution used to correct this acidity ranges from 0.5 to 2.5 g (15 to 77 mL of a 0.3 M solution) added to each 500 mL of ACD blood used for priming the pump-oxygenator. Clinical experience indicates that 2 g (62 mL of a 0.3 M solution) added to 500 mL of ACD blood is usually adequate.

Correction of Metabolic Acidosis Associated with Cardiac Arrest: In the treatment of cardiac arrest, Tham Solution should be given at the same time that other standard resuscitative measures, including manual systole, are being applied. If the chest is open, Tham Solution is injected directly into the ventricular cavity. From 2 to 6 g (62 to 185 mL of a 0.3 M solution) should be injected immediately. Do not inject into the cardiac muscle.

If the chest is not open, from 3.6 to 10.8 g (111 to 333 mL of a 0.3 M solution) should be injected immediately into a larger peripheral vein. Additional amounts may be required to control acidosis persisting after cardiac arrest is reversed.

Correction of Metabolic Acidosis Associated with RDS in Neonates and Infants: The initial dose of Tham Solution should be based on initial pH and birthweight amounting to approximately 1 mL per kg for each pH unit below 7.4. Further doses have been given according to changes in PaO2, pH and PCO2.

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

How is Tham Supplied

Tham Solution (tromeThamine injection) is supplied in a single-dose 500 mL large volume glass container (List No. 1593).

Protect from freezing and extreme heat.

©Hospira 2004	EN-0044	Printed in USA

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

Tham  tromeThamine  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0409-1593 Route of Administration INTRAVENOUS DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength tromeThamine (tromeThamine) Active 3.6 GRAM  In 100 MILLILITER Water Inactive   Glacial Acetic Acid Inactive

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0409-1593-04 6 BOTTLE In 1 CASE contains a BOTTLE, GLASS 1 500 mL (MILLILITER) In 1 BOTTLE, GLASS This package is contained within the CASE (0409-1593-04)

Revised: 04/2006Hospira

More Tham resources

• Tham Side Effects (in more detail)
• Tham Dosage
• Tham Drug Interactions
• Tham Support Group
• 0 Reviews for Tham - Add your own review/rating

Compare Tham with other medications

• Metabolic Acidosis

dienogest and estradiol

Generic Name: dienogest and estradiol (dye EN oh jest and ESS tra DYE ole)

Brand Names: Natazia

What is dienogest and estradiol?

Dienogest and estradiol is a combination of female hormones that prevent ovulation (the release of an egg from an ovary). This medication also causes changes in your cervical mucus and uterine lining, making it harder for sperm to reach the uterus and harder for a fertilized egg to attach to the uterus.

Dienogest and estradiol is used as contraception to prevent pregnancy.

Dienogest and estradiol may also be used for purposes not listed in this medication guide.

What is the most important information I should know about dienogest and estradiol?

Smoking can increase your risk of blood clots, stroke, or heart attack caused by birth control pills, especially if you are older than 35. This medication can harm an unborn baby or cause birth defects. Do not use dienogest and estradiol if you are pregnant. Do not use this medication if you have a history of heart attack or stroke, a history of blood clot or coronary artery disease, circulation problems (especially if caused by diabetes), a blood clotting disorder, breast or uterine cancer, abnormal vaginal bleeding, eye problems or kidney problems caused by diabetes, liver disease or liver cancer, uncontrolled high blood pressure, severe migraine headaches, a heart valve or heart rhythm disorder, or if you smoke and you are over 35 years old.

Some drugs can make birth control pills less effective, which may result in pregnancy. Tell your doctor about all medications you use.

What should I discuss with my healthcare provider before using dienogest and estradiol?

This medication can harm an unborn baby or cause birth defects. Do not use if you are pregnant. Tell your doctor right away if you become pregnant, or if you miss two menstrual periods in a row. If you have recently had a baby, wait at least 4 weeks before taking birth control pills. Do not use this medication if you are allergic to dienogest or estradiol, or if you have:

• 
  

  a history of heart attack, stroke, blood clot, or coronary artery disease;

  
  


• 
  

  a blood-clotting disorder, untreated or uncontrolled high blood pressure;

  
  


• 
  

  a hormone related cancer such as breast or uterine cancer;

  
  


• 
  

  abnormal vaginal bleeding;

  
  


• 
  

  problems with your eyes, kidneys, or circulation caused by diabetes;

  
  


• 
  

  liver disease or liver cancer;

  
  


• 
  

  severe migraine headaches;

  
  


• 
  

  a heart valve or heart rhythm disorder; or

  
  


• 
  

  if you smoke and you are over 35 years old.

  
  

To make sure you can safely take this medicine, tell your doctor if you have any of these other conditions:

• 
  

  high blood pressure, heart disease, congestive heart failure, high cholesterol or triglycerides;

  
  


• 
  

  a history of depression;

  
  


• 
  

  diabetes;

  
  


• 
  

  underactive thyroid; or

  
  


• 
  

  a history of jaundice caused by birth control pills.

  
  

The hormones in this medication can pass into breast milk and may harm a nursing baby. This medication may also slow breast milk production. Do not use if you are breast feeding a baby.

How should I take dienogest and estradiol?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Take your first pill on the first day of your period or on the first Sunday after your period begins. Follow the directions on your prescription label. The 28 day birth control pack contains five different colors of pills. Take one pill each day in the exact order directed on the blister pack.

Take one pill every day, no more than 24 hours apart. When the pills run out, start a new pack the following day. Get your prescription refilled before you run out of pills completely.

You may need to use back up birth control, such as condoms or a spermicide, when you first start using this medication. Follow your doctor's instructions. Do not take two different kinds of birth control pills at the same time.

If you are switching to this medication from another birth control pill, start taking dienogest and estradiol on the first day of your withdrawal bleeding and stop taking the other birth control pills. If you were taking progestin only pills before, start taking dienogest and estradiol on the day you would have taken your next pill.

If you are switching from a birth control implant, intrauterine device (IUD), vaginal ring, or skin patch, start taking dienogest and estradiol on the day the other birth control device is removed.

If you are switching from a birth control injection, start taking dienogest and estradiol on the day you would have received your next scheduled injection.

You may have breakthrough bleeding. Tell your doctor if this bleeding continues or is very heavy.

Use a back up birth control if you are sick with severe vomiting or diarrhea. Vomiting within 4 hours after your dose is the same as missing a pill.

If you need surgery or medical tests or if you will be on bed rest, you may need to stop using this medication for a short time. Any doctor or surgeon who treats you should know that you are using birth control pills. Store at room temperature away from moisture and heat.

See also: Dienogest and estradiol dosage (in more detail)

What happens if I miss a dose?

If you are less than 12 hours late in taking your pill, take the missed dose as soon as you remember. Take the next pill at the usual time, then take one pill per day in the order directed on the pack. Missing a pill by more than 12 hours increases your risk of becoming pregnant.

If you miss one pill:

• 
  

  During Days 1 through 17, take the missed pill as soon as you remember, then take your next pill at the usual time. Use back-up birth control for at least 9 days.

  
  


• 
  

  During Days 18 through 24, throw out the pack and start a new one the same day. Take the Day 1 pill from the new pack and then take one pill per day in the order directed on the pack. Use back-up birth control for at least 9 days.

  
  


• 
  

  During Days 25 through 28, take the missed pill as soon as you remember, then take your next pill at the usual time. You do not need back-up birth control if you miss one pill during Days 25 through 28.

  
  

If you miss two pills:

• 
  

  During Days 1 through 16, skip the missed pills and start with the pill that corresponds to the day you remember you missed your doses. Then take one pill per day in the order directed on the pack. Use your back up birth control for at least 9 days.

  
  


• 
  

  During Days 17 through 24, throw out the rest of the pack and start a new on the same day. Take the Day 3 pill from the new pack and then take one pill per day in the order directed on the pack. Use your back up birth control for at least 9 days.

  
  


• 
  

  During Days 25 through 28, throw out the rest of the pack. Start a new pack on the same day or on the day you would normally start a new pack. Take one pill per day in the order directed on the pack. No back up birth control is needed.

  
  

Your risk of getting pregnant will increase with the number of pills you miss. If you miss a period for two months in a row, call your doctor because you might be pregnant. Use back-up birth control if you are not sure how many pills you have missed.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Overdose symptoms may include nausea, vomiting, or vaginal bleeding.

What should I avoid while using dienogest and estradiol?

Do not smoke while using this medication, especially if you are older than 35. Smoking can increase your risk of blood clots, stroke, or heart attack caused by birth control pills.

Birth control pills will not protect you from sexually transmitted diseases, including HIV and AIDS. Using a condom is the only way to protect yourself from these diseases.

Dienogest and estradiol side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using this medication and call your doctor at once if you have a serious side effect such as:

• 
  

  sudden numbness or weakness, especially on one side of the body;

  
  


• 
  

  sudden severe headache, confusion, problems with vision, speech, or balance;

  
  


• 
  

  sudden cough, wheezing, rapid breathing, coughing up blood;

  
  


• 
  

  pain, swelling, warmth, or redness in one or both legs;

  
  


• 
  

  chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;

  
  


• 
  

  jaundice (yellowing of the skin or eyes);

  
  


• 
  

  a change in the pattern or severity of migraine headaches;

  
  


• 
  

  swelling in your hands, ankles, or feet;

  
  


• 
  

  a breast lump; or

  
  


• 
  

  symptoms of depression (sleep problems, weakness, mood changes).

  
  

Less serious side effects may include:

• 
  

  mild nausea or vomiting, appetite or weight changes;

  
  


• 
  

  breast swelling or tenderness;

  
  


• 
  

  headache, nervousness, dizziness;

  
  


• 
  

  problems with contact lenses;

  
  


• 
  

  freckles or darkening of facial skin, loss of scalp hair; or

  
  


• 
  

  vaginal itching or discharge.

  
  

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

Dienogest and estradiol Dosing Information

Usual Adult Dose for Contraception:

One tablet taken orally, once a day, consecutively in the order directed on the package for 28 days with the next pack to be started the day after the last pack.

Dienogest-estradiol products are packaged in 28 day dosage preparations.

The cycle length for oral contraceptives is generally considered to be 28 days. (The first day of menstrual bleeding is counted as day 1).

Initiation of Oral Contraceptive Therapy:

This product can be started one of the following ways:

1. No preceding hormonal contraceptive use in the past month: Start on day 1 of the woman's natural cycle;

2. For postpartum women who do not breastfeed or after a second trimester abortion: Start on day 28 after delivery or abortion. The patient should be advised to use additional barrier methods for the first 9 days of tablet taking. However, if intercourse has already taken place, pregnancy should be excluded before use or the patient should wait until the first menstrual cycle.

3. Changing from a combined oral contraceptive, vaginal ring, or transdermal patch: Instruct her to take the first dark yellow pill on the first day of her withdrawal bleed. She should not continue taking the pills from her previous birth control pack. If she does not have a withdrawal bleed, rule out pregnancy before starting dienogest-estradiol. If she previously used a vaginal ring or transdermal patch, she should start using dienogest-estradiol on the day the ring or patch is removed. Instruct the patient to use a non-hormonal backup method such as a condom or spermicide for the first 9 days.

4. Changing from a progesterone-only method: Instruct her to take the first dark yellow pill on the day she would have taken her next progestin-only pill or on the day of removal of her implant or intrauterine system or on the day when she would have had her next injection. Instruct the patient to use a non-hormonal backup method such as a condom or spermicide for the first 9 days.

Missed Doses:

If a woman is less than 12 hours late for an active tablet, the missed dose should be taken as soon as it is remembered and the normal schedule should be resumed.

If a woman is more than 12 hours late for an active tablet, please follow the following principles:

Day 1 to 17: Take the missed tablet immediately and the rest as usual. Use backup contraception for the next 9 days.
Day 18 to 24: Discard the current cycle, start a new cycle immediately. Use backup contraception for the next 9 days.
Day 25 to 28: Take the missed tablet immediately and following tablets as usual. No backup contraception is required.

If a woman misses TWO PILLS in a row, please follow the following principles:

Days 1-17 (if she misses the pills for Days 17 and 18, follow the instructions for Days 17-25 instead):
Do not take the missed pills. Instead, take the pill for the day on which you first noticed you had missed pills. Use backup contraception for the next 9 days. Continue taking one pill each day at the same time for the rest of the cycle.
Days 17-25 (if she misses the pills for Days 25 and 26, follow the instructions for Days 25-28 instead):
Do not take any pills from the current blister pack and throw the pack away. Take Day 3 pill from a new blister pack. Use backup contraception for the next 9 days. Continue taking one pill from the new blister pack at the same time each day.
Days 25-28:
Do not take any pills from the current blister pack and throw the pack away. Start a new pack on the same day or start a new pack on the day you usually start a new pack. No backup contraception is needed. Continue taking one pill from the new pack at the same time each day, for the rest of the cycle.

What other drugs will affect dienogest and estradiol?

Many drugs can make birth control pills less effective, which may result in pregnancy. Below is just a partial list:

• 
  

  antifungal medication (Sporanox, Extina, Ketozole, Nizoral, Vfend, and others);

  
  


• 
  

  certain antibiotics (especially Biaxin, Ery-Tab, Erythrocin, Ketek, and others);

  
  


• 
  

  certain antidepressants, or St. John's wort;

  
  


• 
  

  certain HIV medications;

  
  


• 
  

  certain seizure medications;

  
  


• 
  

  St. John's wort;

  
  


• 
  

  isoniazid (for treating tuberculosis);

  
  


• 
  

  rifabutin (Mycobutin), rifampin (Rifadin, Rifater, Rifamate), or rifapentine (Priftin);

  
  


• 
  

  thyroid replacement (Synthroid, Levothroid, and others);

  
  


• 
  

  phenobarbital or other barbiturates; or

  
  


• 
  

  heart or blood pressure medication (especially Cartia, Cardizem, Cardene, Procardia, Calan, Covera, Isoptin, Verelan, and others).

  
  

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

More dienogest and estradiol resources

• Dienogest and estradiol Dosage
• Dienogest and estradiol Use in Pregnancy & Breastfeeding
• Dienogest and estradiol Drug Interactions
• Dienogest and estradiol Support Group
• 9 Reviews for Dienogest and estradiol - Add your own review/rating

Compare dienogest and estradiol with other medications

• Birth Control

Where can I get more information?

• Your pharmacist can provide more information about dienogest and estradiol.

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Nozevet

Nozevet may be available in the countries listed below.

In some countries, this medicine may only be approved for veterinary use.

Ingredient matches for Nozevet

Dimenhydrinate

Dimenhydrinate is reported as an ingredient of Nozevet in the following countries:

• France

International Drug Name Search

Docosavit

ascorbic acid, pyridoxine hydrochloride, folic acid, ferrous fumarate and iron

Dosage Form: tablet
Docosavit

INGREDIENTS:

Ferrous Fumarate: Provides about 15 mg of elemental iron per dose. Ferrous Fumarate is an anhydrous salt of a combination of ferrous iron and fumaric acid containing 33% or iron by weight. The acute toxicity in experimental animals is low and Ferrous Fumarate is well tolerated clinically. As a ferrous salt, it is more efficiently absorbed in the duodenum. Ferrous Fumarate contrasts very favorably with the availability of the 20% of elemental iron of ferrous sulfate and the 13% of elemental iron of Ferrous Gluconate.

Polysaccharide Iron Complex: Provides about 15 mg elemental iron, as a cell0contracted akageneite. It is a product of ferric iron complexed to a low molecular weight polysaccharide. This polysaccharide is produced by the extensive hydrolysis of starch and is a dark brown powder that dissolves in water to form a very dark brown solution, which is virtually odorless and tasteless. The most frequent cause of anemia in pregnant women is iron deficiency. Because of the continuous loss of iron due to monthly menstruation, most women enter pregnancy with less than optimal iron stores. Supplementation of iron must suffice to meet the needs for maternal and fetal erythropoiesis and account for daily maternal gastrointestinal losses and obligate fetal transfer and growth. Iron requirement during pregnancy usually cannot be met with the average diet.(1)(2) Docosavit does not contain calcium, as calcium may inhibit iron absorption because of the binding or conversion of ferrous salts by calcium and other minerals. Calcium salts can always be prescribed separately for women at high nutritional risk, including those who do not eat adequate amounts of dairy products. The recommendation of the National Academy of Sciences suggests the supplementation of 1,200 mg of calcium for pregnant and lactating women for the prevention of calcium deficiency.(3)

Folic Acid: Neural tube defects occur in approximately 0.6 of 1,000 live births in the United States (i.e., approximately 6 of 10,000 live births; about 2,500 cases among 4 million live births annually). Neural tube defects are believed to be caused by many factors. The single greatest risk factor for a neural tube defect-affected pregnancy is a personal or family history of a pregnancy affected with such a defect. However, about 90 percent of infants with a neural tube defect are born to women who do not have a family history of these defects. The available evidence shows that diets adequate in folate (folic acid) may reduce the risk of neural tube defects but not of other birth defects.(4)

Vitamin C: An extra 15 mg of vitamin C is recommended daily for pregnant women (60 mg daily). While vitamin C deficiency has not been shown to affect the course or outcome of pregnancy in humans, questions have arisen about its possible association with low plasma levels of vitamin C, which have been reported to be associated with premature rupture of the membranes and preeclampsia.

Vitamin B6: Vitamin B6 may help for the treatment of nausea and vomiting during pregnancy. According to one clinical trial, thirty-one patients receiving vitamin B6 at 25 mg experienced significant reductions of severe nausea. (5)

Omega 3 Fatty Acids: The omega-3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are considered essential fatty acids because they must be supplied from the diet. The essential fatty acid (EFA) status of the developing fetus depends on that of its mother. Pregnancy is associated with a decrease in the biochemical EFA status and normalization after delivery is slow. This is particularly true for DHA because, on the basis of the current habitual diet, birth spacing appears to be insufficient for the maternal DHA status to normalize completely. Because of the decrease in EFA status during pregnancy, the neonatal EFA status may not be optimal. The neonatal EFA status can be increased by maternal EFA supplementation during pregnancy. (6)

INDICATIONS AND USAGE:

Docosavit is a prescription prenatal vitamin-mineral-nutrient preparation formulated to provide dietary supplementation for women throughout pregnancy and during the postnatal period (during lactation). Docosavit can also be used to improve the nutritional status of women prior to conception.

DOSAGE AND ADMINISTARTION:

Adult women (over 12 years of age), take one (1) softgel daily (orally), between meals or as prescribed by a physician. Do not exceed the recommended dosage. Do not administer to children under 12 years of age, or persons age 65 or older.

CONTRAINDICATIONS:

Docosavit is contraindicated in patients with known hypersensitivity to any of the ingredients including fish oil and soy. Iron is contraindicated in patients with hemosiderosis, hemochromatosis, or hemolytic anemias. This product is contraindicated for persons with pernicious anemia, as folic acid may obscure its signs and symptoms.

WARNING:

Folic acid alone is improper therapy in the treatment of pernicious anemia in that hematological remission can occur while neurological manifestations remain progressive.

Ingestion of omega-3 fatty acids of more than 3 grams per day may present antithrombotic effects, including increased bleeding time. Omega-3 fatty acids including DHA and EPA should be avoided in patients with inherited or acquired bleeding diatheses. Patients taking anticoagulant drug products should consult with their physician prior to ingesting omega-3 fatty acids.

PRECAUTIONS:

Folic acid in dosages above 400 mcg daily may obscure pernicious anemia in that hematological remission can occur while neurological manifestations remain progressive.

ADVERSE REACTIONS:

Ferrous Fumarate: Gastrointestinal disturbances (anorexia, nausea, diarrhea, constipation) can occur but are usually mild and can subside with continuation of therapy. Although the absorption of iron is best when taken between meals, Docosavit, when taken after meals, may control occasional G.I. disturbances. Docosavit is best absorbed when taken at bedtime.

Folic Acid: Allergic sensitizations have been reported following both oral and parenteral administration of folic acid.

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

USE IN SPECIFIC POPULATIONS:

Docosavit is not advocated for pediatric or geriatric use.

OVERDOSE:

Iron: Signs and Symptoms: Iron is toxic. Acute overdosage of iron may cause nausea and vomiting. In severe cases, iron overdose can cause cardiovascular collapse and death. Other symptoms include pallor and cyanosis, melena, shock, drowsiness and coma. The estimated overdose of orally ingested iron is 300/mg/kg body weight. When overdoses are ingested by children, server reactions, including fatalities have resulted. Docosavit should be stored beyond the reach of children to prevent against accidental iron poisoning. Keep this and all other drugs out of the reach of children.

Treatment: For specific therapy, exchange transfusion and chelating agents should be used. For general management, perform gastric lavage with sodium bicarbonate solution or milk. Administer intravenous fluids and electrolytes and use oxygen.

HOW SUPPLIED:

Docosavit is available as a dark brown softgel capsule: bottles of 90 softgels NDC 68032-280-90. Dispense in a tight, light-resistant container as defined in the USP/NF with a child resistant closure. Store at controlled room temperature 15 – 30 C (59 – 86 F). Keep in a cool, dry place.

CAUTION:

Rx Only

RESERVED FOR PROFESSIONAL RECOMMENDATION: Made in the USA excelusively for River’s Ege Pharmaceuticals, LLC, Suwanee, GA 30024. All rights reserved. Copyright by River’s Edge Pharmaceuticals.

REFERENCES

(1) Worthington-Roberts BS, Williams SR. Nutrition in Pregnancy and Lactation, 6th Edition, Pg 168. 1977.

(2) Bothwell TH. Iron requirements in pregnancy and strategies to meet them. Am Jour Clin Tutr; 2000: 72(1), 257S-264S.

(3) National Academy of Science, 11th Edition, National Academy Press, Wash, D.C., 1997

(4) 21 CFR 101.79 Health claims: Folate and neural tube defects.

(5) Sahakian V et al Vitamin B6 is effective therapy for nausea and vomiting in pregnancy: a randomized double-blind placebo-controlled study. Obstet Gynecol 78:33. 1991.

(6) Hornstra B. Essential fatty acids in mothers and their neonates. Am Jour Clin Nutr. 2000;71(suppl):1262S-9S.

PACKAGING:

Docosavit   ascorbic acid, pyridoxine hydrochloride, folic acid, ferrous fumarate, iron  tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 68032-280 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ASCORBIC ACID (ASCORBIC ACID) ASCORBIC ACID 20 mg PYRIDOXINE HYDROCHLORIDE (PYRIDOXINE) PYRIDOXINE HYDROCHLORIDE 25 mg FOLIC ACID (FOLIC ACID) FOLIC ACID 1 mg FERROUS FUMARATE (IRON) FERROUS FUMARATE 15 mg IRON (IRON) IRON 15 mg DOCONEXENT (DOCONEXENT) DOCONEXENT 215.12 mg ICOSAPENT (ICOSAPENT) ICOSAPENT 53.46 mg

Inactive Ingredients Ingredient Name Strength GELATIN   WATER   GLYCERIN   POLYSORBATE 80   YELLOW WAX   LECITHIN, SOYBEAN

Product Characteristics Color brown Score no score Shape OVAL Size 20mm Flavor Imprint Code RE;280 Contains

Packaging # NDC Package Description Multilevel Packaging 1 68032-280-90 90 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
unapproved drug other		09/16/2008	10/31/2012

Labeler - River's Edge Pharmaceuticals, LLC (133879135)

Revised: 04/2011River's Edge Pharmaceuticals, LLC

More Docosavit resources

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

• Docosavit Concise Consumer Information (Cerner Multum)


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• Prenate Elite tablets


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• PrimaCare Advantage MedFacts Consumer Leaflet (Wolters Kluwer)


• PrimaCare ONE capsules


• PrimaCare One MedFacts Consumer Leaflet (Wolters Kluwer)


• Se-Natal 19 Chewable Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


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• Vitamin/Mineral Supplementation during Pregnancy/Lactation

Mogifen

Mogifen may be available in the countries listed below.

Ingredient matches for Mogifen

Ibuprofen

Ibuprofen is reported as an ingredient of Mogifen in the following countries:

• Japan

International Drug Name Search

Docefrez

Generic Name: docetaxel (Intravenous route)

doe-se-TAX-el

Intravenous route(Solution)

Treatment-related mortality increases with abnormal liver function, at higher doses, and in patients with non-small cell lung carcinoma and a history of prior treatment with platinum-based therapy receiving docetaxel at 100 mg/m(2). Docetaxel should generally not be given to patients with bilirubin greater than the ULN, or to patients with SGOT and/or SGPT greater than 1.5 x ULN concomitant with alkaline phosphatase greater than 2.5 x ULN. These patients are at increased risk for developing severe or life-threatening toxicities. Monitor LFTs prior to each treatment cycle. Docetaxel therapy should not be given to patients with neutrophil counts of less than 1500 cells/mm(3); obtain frequent blood counts to monitor for neutropenia. Severe hypersensitivity reactions, including fatal anaphylaxis, has been reported in patients who received dexamethasone premedication. Use is contraindicated in patients with a severe hypersensitivity to docetaxel or polysorbate 80. Severe fluid retention may occur .

Commonly used brand name(s)

In the U.S.

• Docefrez


• Taxotere

Available Dosage Forms:

• Solution


• Powder for Solution

Therapeutic Class: Antineoplastic Agent

Pharmacologic Class: Mitotic Inhibitor

Uses For Docefrez

Docetaxel belongs to the group of medicines called antineoplastics. It is used to treat breast cancer, non-small cell lung cancer, head and neck cancer , gastrointestinal (stomach) and prostate cancer. Docetaxel is sometimes used in combination with other medicines for certain types of cancer.

Docetaxel interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by docetaxel, other effects will also occur. Some of these may be serious and must be reported to your doctor. Other effects may not be serious but may cause concern. Some effects may not occur for months or years after the medicine is used.

Docetaxel may also be used to treat other conditions as determined by your doctor.

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

Docetaxel is to be administered only by or under the immediate supervision of your doctor.

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 the product labeling, docetaxel is used in certain patients with the following medical conditions:

• Bladder cancer


• Esophageal cancer


• Lung cancer, small cell


• Ovarian cancer

Before Using Docefrez

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

Docetaxel has been studied in a limited number of children. The study showed that children are especially sensitive to the effects of docetaxel and cannot be given usual doses of the medicine.

Geriatric

Elderly people are especially sensitive to the effects of docetaxel. This may increase the chance of side effects during treatment.

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.

• Rotavirus Vaccine, Live

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.

• Adenovirus Vaccine Type 4, Live


• Adenovirus Vaccine Type 7, Live


• Atazanavir


• Bacillus of Calmette and Guerin Vaccine, Live


• Clarithromycin


• Doxorubicin Hydrochloride


• Indinavir


• Influenza Virus Vaccine, Live


• Itraconazole


• Ketoconazole


• Measles Virus Vaccine, Live


• Mumps Virus Vaccine, Live


• Nefazodone


• Nelfinavir


• Ritonavir


• Rotavirus Vaccine, Live


• Rubella Virus Vaccine, Live


• Saquinavir


• Smallpox Vaccine


• Telithromycin


• Thalidomide


• Typhoid Vaccine


• Varicella Virus Vaccine


• Voriconazole


• Yellow Fever Vaccine

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.

• Cisplatin


• Dalfopristin


• Quinupristin


• Sorafenib

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:

• Alcohol abuse or history of—The risk of some side effects affecting the muscles and nerves may be increased.

• Chickenpox (including recent exposure) or


• Herpes zoster (shingles)—The risk of severe disease affecting other parts of the body may be increased.

• Fluid in lungs—Docetaxel may make your condition worse.

• Infection—Docetaxel may decrease your body's ability to fight infection.

• Liver disease—The chance of serious side effects is greatly increased.

Proper Use of docetaxel

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

This medicine often causes nausea and vomiting, which is usually mild. However, it is very important that you continue to receive the medicine even if you begin to feel ill. Ask your health care professional for ways to lessen these effects.

Your doctor may direct you to take a corticosteroid medicine such as dexamethasone (e.g., Decadron), starting the day before you receive an injection of docetaxel and may continue for a few days after a docetaxel treatment. This other medicine decreases the chance of an allergic reaction to docetaxel and certain other side effects. It is very important that you take each dose of the corticosteroid medicine as directed.

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.

Precautions While Using Docefrez

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.

While you are being treated with docetaxel, and after you stop treatment with it, do not have any immunizations (vaccinations) without your doctor's approval. Docetaxel may lower your body's resistance and there is a chance you might get the infection the immunization is meant to prevent. In addition, other persons living in your household should not take oral polio vaccine since there is a chance they could pass the polio virus on to you. Also, avoid persons who have taken oral polio vaccine within the past several months. Do not get close to them and do not stay in the same room with them for very long. If you cannot take these precautions, you should consider wearing a protective face mask that covers the nose and mouth.

Docetaxel can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.


• Check with your doctor immediately if you notice any unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on your skin.


• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.


• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.


• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.


• Avoid contact sports or other situations where bruising or injury could occur.

Docefrez Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Some side effects will have signs or symptoms that you can see or feel. Your doctor may watch for others by doing certain tests.

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

Less common

• Black, tarry stools


• blood in urine or stools


• cough or hoarseness (accompanied by fever or chills)


• difficult or labored breathing


• difficult or painful urination (accompanied by fever or chills)


• difficulty swallowing


• dizziness


• fast heartbeat


• fever or chills


• heart problems


• hives


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


• lower back or side pain (accompanied by fever or chills)


• noisy, rattling breathing


• pinpoint red spots on skin


• shortness of breath


• skin rash


• tightness in chest


• troubled breathing while at rest


• unusual bleeding or bruising


• unusual tiredness or weakness


• wheezing

Rare

• Chest pain or discomfort


• fast or irregular heartbeat


• shortness of breath

Docetaxel sometimes causes allergic reactions, especially during the first few treatments. Tell your doctor or nurse right away if you notice back pain or itching during an injection. Your doctor or nurse will be watching out for other signs of an allergic reaction while you are receiving this medicine, and will be ready to treat any serious effects right away.

A kind of leukemia called acute myeloid leukemia [AML] can occur if you are taking a combination of docetaxel and cyclophosphamide to treat your breast cancer. Tell your doctor right away if you develop a lot of infections, experience bone or joint pain, or have a fever.

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

More common

• Swelling of abdomen, face, fingers, hands, feet, or lower legs


• unusual tiredness or weakness


• weight gain

Less common

• Red, scaly, swollen, or peeling areas of skin (severe)

Rare

• Decrease in blood pressure, sometimes with dizziness or fainting


• increase in blood pressure, sometimes with dizziness or headaches

This medicine may also cause the following side effects that your doctor will watch out for:

More common

• Anemia


• low white blood cell count

Less common

• High or low blood pressure


• low platelet count in blood

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

• Burning, numbness, tingling, or pain in arms, hands, legs, or feet


• congestion


• diarrhea


• dryness or soreness of throat


• nausea


• skin rash or redness (mild)


• sores or ulcers on the lips or tongue or inside the mouth


• weakness in arms, hands, legs, or feet

Less common

• Bloody nose


• body aches or pain


• change in color of fingernails or toenails


• congestion


• dry, red, hot, or irritated skin at place of injection


• headache


• hoarseness


• loosening or loss of fingernails or toenails, sometimes painful


• pain in joints or muscles


• pain, swelling, or lump under the skin at place of injection


• runny nose


• tender, swollen glands in neck


• trouble in swallowing


• voice changes


• vomiting

incidence not known

• Burning, dry or itching eyes


• burning upper abdominal pain


• confusion


• difficulty having a bowel movement [stool]


• discharge from eyes


• excessive tearing


• mood or mental changes


• pain all over body


• pain and redness of skin at place of earlier radiation treatment


• rapid breathing


• redness, pain, swelling of eye, eyelid, or inner lining of eyelid


• stomach pain


• sunken eyes


• tearing of the eyes


• wrinkled skin

This medicine usually causes a temporary loss of hair. After treatment with docetaxel has ended, normal hair growth should return.

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: Docefrez 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.

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More Docefrez resources

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

• Docefrez Prescribing Information (FDA)


• Docetaxel Prescribing Information (FDA)


• Docetaxel Professional Patient Advice (Wolters Kluwer)


• Docetaxel MedFacts Consumer Leaflet (Wolters Kluwer)


• Docetaxel Monograph (AHFS DI)


• Taxotere Prescribing Information (FDA)


• Taxotere Consumer Overview

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Akten

Besivance

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Ciloxan-Drops

Iquix-Drops

Navstel

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Zymar-Drops

Deprex Leciva

Deprex Leciva may be available in the countries listed below.

Ingredient matches for Deprex Leciva

Fluoxetine

Fluoxetine hydrochloride (a derivative of Fluoxetine) is reported as an ingredient of Deprex Leciva in the following countries:

• Czech Republic

International Drug Name Search

Simponi

Generic Name: Golimumab
Class: Disease-modifying Antirheumatic Agents
VA Class: MS190
Chemical Name: Disulfide with human monoclonal CNTO 148 k-chain anti-(human tumor necrosis factor a) (human monoclonal CNTO 148 g1-chain) immunoglobulin G1 dimer.
Molecular Formula: C₆₅₃₀H₁₀₀₆₈N₁₇₅₂O₂₀₂₆S₄₄
CAS Number: 476187-74-5

Special Alerts:

[Posted 09/07/2011] ISSUE: FDA notified healthcare professionals that the Boxed Warning for the entire class of Tumor Necrosis Factor-alpha (TNF) blockers has been updated to include the risk of infection from two bacterial pathogens, Legionella and Listeria. In addition, the Boxed Warning and Warnings and Precautions sections of the labels for all of the TNF blockers have been revised so that they contain consistent information about the risk for serious infections and the associated disease-causing pathogens.

Patients treated with TNF blockers are at increased risk for developing serious infections involving multiple organ systems and sites that may lead to hospitalization or death due to bacterial, mycobacterial, fungal, viral, parasitic, and other opportunistic pathogens.

BACKGROUND: The class of TNF blockers are used to treat Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, and/or juvenile idiopathic arthritis.

RECOMMENDATION: The risks and the benefits of TNF blockers should be considered prior to initiating therapy in patients with chronic or recurrent infection and patients with underlying conditions that may predispose them to infection. See the Drug Safety Communication for a listing of recommendations for healthcare professionals and patients, as well as a data summary. For more information visit the FDA website at: and .

[Posted 04/14/2011] ISSUE: FDA continues to receive reports of a rare cancer of white blood cells (known as Hepatosplenic T-Cell Lymphoma or HSTCL, primarily in adolescents and young adults being treated for Crohn’s disease and ulcerative colitis with medicines known as tumor necrosis factors (TNF) blockers, as well as with azathioprine, and/or mercaptopurine. TNF blockers include infliximab (Remicade), etancercept (Enbrel), adalimumab (Humira), certolizumab pegol (Cimzia) and golimumab (Simponi).

BACKGROUND: HSTCL is an aggressive (fast-growing) cancer and is usually fatal. The majority of cases reported were in patients being treated for Crohn’s disease or ulcerative colitis, but also included a patient being treated for psoriasis and two patients being treated for rheumatoid arthritis. FDA is now updating the number of reported cases of HSTCL.

Although most reported cases of HSTCL occurred in patients treated with a combination of medicines known to suppress the immune system, including the TNF blockers, azathioprine, and/or mercaptopurine, there have been cases reported in patients receiving azathioprine or mercaptopurine alone.

• 
  

  Educate patients and caregivers about the signs and symptoms of malignancies such as HSTCL so that they are aware of and can seek evaluation and treatment of any signs or symptoms. These may include splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss.

  
  


• 
  

  Monitor for the emergence of malignancies when a patient has been treated with TNF blockers, azathioprine, and/or mercaptopurine.

  
  


• 
  

  Know that people with rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis and plaque psoriasis may be more likely to develop lymphoma than the general U.S. population. Therefore, it may be difficult to measure the added risk of TNF blockers, azathioprine, and/or meracaptopurine.

  
  

Read the Drug Safety Communications for other specific recommendations for Healthcare Professionals and Patients and the Data Summary for additional information. For more information visit the FDA website at: and .

REMS:

FDA approved a REMS for golimumab to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

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

• Serious Infections


• 
  

  Serious, sometimes fatal infections including tuberculosis (frequently disseminated or extrapulmonary), bacterial and viral infections, invasive fungal infections (may be disseminated), and other opportunistic infections reported.¹ (See Infectious Complications under Cautions.)

  
  


• 
  

  Carefully consider risks and benefits prior to initiating golimumab therapy in patients with chronic or recurring infections.¹

  
  


• 
  

  Evaluate patients for latent tuberculosis infection prior to and periodically during golimumab therapy; if indicated, initiate appropriate antimycobacterial regimen prior to initiating golimumab therapy.¹

  
  


• 
  

  Closely monitor patients for infection, including active tuberculosis in those with a negative tuberculin skin test, during and after treatment.¹ Discontinue golimumab if serious infection occurs.¹ Consider empiric antifungal therapy if serious systemic illness occurs in a patient at risk for invasive fungal infections.¹

  
  

• Malignancy


• 
  

  Lymphoma and other malignancies (some fatal) reported in children and adolescents receiving TNF blocking agents.¹ (See Malignancies and Lymphoproliferative Disorders under Cautions.)

  
  

Introduction

Biologic response modifier and disease-modifying antirheumatic drug (DMARD); a human immunoglobulin G₁ kappa (IgG₁) monoclonal antibody specific for human tumor necrosis factor (TNF; TNF-α).^{1 2 3 4 5 6 13 14 15}

Uses for Simponi

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

Rheumatoid Arthritis in Adults

Used in conjunction with methotrexate for the management of moderately to severely active rheumatoid arthritis in adults.^{1 2 3 4 17}

Psoriatic Arthritis

Used alone or in conjunction with methotrexate for the management of active psoriatic arthritis in adults.^{1 5}

Ankylosing Spondylitis

Used for the management of ankylosing spondylitis in adults with active disease.^{1 6}

Simponi Dosage and Administration

General

Concomitant Therapy

• 
  

  Used in conjunction with methotrexate for the management of moderately to severely active rheumatoid arthritis in adults; may be used with or without methotrexate for management of psoriatic arthritis or ankylosing spondylitis in adults.¹

  
  


• 
  

  Corticosteroids, other nonbiologic DMARDs, and NSAIAs may be continued in adults receiving golimumab for the management of rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.¹

  
  

REMS Program

• 
  

  FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for golimumab.¹²

  
  


• 
  

  The program consists of a medication guide that must be provided to patients (see Advice to Patients) and a communication plan that includes initial communications targeting selected groups of clinicians.¹²

  
  


• 
  

  The goals are to inform patients about the serious risks associated with the drug and to inform clinicians about invasive fungal infections associated with use of TNF blocking agents (see Warnings/Precautions under Cautions).¹²

  
  

Administration

Sub-Q Administration

Administer by sub-Q injection into the thigh, lower abdomen, or upper arm; do not make abdominal injections within 2 inches of the umbilicus.¹ Use thigh (the preferred site) or abdomen for self-administration; may use upper arm if not self-administered.¹ Rotate injection sites.¹ Do not make injections into areas where the skin is tender, bruised, red, or hard or into scars or stretch marks.¹

Allow golimumab prefilled syringe or auto-injector to sit at room temperature outside of the carton for 30 minutes prior to injection; do not warm the drug in any other way (e.g., microwave, hot water).¹ Do not remove the syringe needle cover or auto-injector cap while the drug is warming to room temperature.¹

Intended for use under the guidance and supervision of a clinician, but may be self-administered if the clinician determines that the patient and/or their caregiver is competent to safely administer the drug after appropriate training.¹

Dosage

Adults

Rheumatoid Arthritis

Sub-Q

50 mg once monthly.¹

Psoriatic Arthritis

Sub-Q

50 mg once monthly.¹

Ankylosing Spondylitis

Sub-Q

50 mg once monthly.¹

Special Populations

Dosage adjustment based on weight or gender not necessary.^{1 15} (See Special Populations under Pharmacokinetics.)

Hepatic Impairment

Manufacturer makes no specific dosage recommendations.^{1 15} (See Special Populations under Pharmacokinetics.)

Renal Impairment

Manufacturer makes no specific dosage recommendations.^{1 15} (See Special Populations under Pharmacokinetics.)

Geriatric Patients

Manufacturer makes no specific dosage recommendations.^{1 15} (See Special Populations under Pharmacokinetics.)

Cautions for Simponi

Contraindications

• 
  

  Manufacturer states none known.¹

  
  

Warnings/Precautions

Warnings

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

Infectious Complications

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

Serious, sometimes fatal infections (including bacterial, mycobacterial, invasive fungal, viral, protozoal, and other opportunistic infections) reported with golimumab or other TNF blocking agents, particularly in patients receiving concomitant therapy with other immunosuppressive agents (e.g., methotrexate, corticosteroids).^{1 9} The most common opportunistic infections include tuberculosis, histoplasmosis, aspergillosis, candidiasis, coccidioidomycosis, listeriosis, and pneumocystosis.¹ Infections frequently are disseminated.¹

Do not initiate golimumab in patients with active infections, including clinically important localized infections.¹ Consider potential risks and benefits of the drug prior to initiating therapy in patients with a history of chronic, recurring, or opportunistic infections; patients with underlying conditions that may predispose them to infections; and patients who have been exposed to tuberculosis or who have resided or traveled in regions where tuberculosis or mycoses such as histoplasmosis, coccidioidomycosis, and blastomycosis are endemic.¹

Closely monitor patients during and after golimumab therapy for signs or symptoms of infection (e.g., fever, malaise, weight loss, sweats, cough, dyspnea, pulmonary infiltrates, serious systemic illness including shock).^{1 9}

If new infection occurs during therapy, perform thorough diagnostic evaluation (appropriate for immunocompromised patient), initiate appropriate anti-infective therapy, and closely monitor patient.^{1 9} Discontinue golimumab if serious infection, opportunistic infection, or sepsis develops.^{1 9}

Evaluate all patients for active or latent tuberculosis and for risk factors for tuberculosis prior to and periodically during therapy.¹ When indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis infection prior to golimumab therapy.¹ Also consider antimycobacterial therapy prior to golimumab therapy for individuals with a history of latent or active tuberculosis in whom an adequate course of antimycobacterial treatment cannot be confirmed and for individuals with a negative tuberculin skin test who have risk factors for tuberculosis.¹ Consultation with a tuberculosis specialist is recommended when deciding whether to initiate antimycobacterial therapy.¹

Monitor all patients, including those with negative tuberculin skin tests, for active tuberculosis.¹ Strongly consider tuberculosis in patients who develop new infections while receiving golimumab, especially if they previously have traveled to countries where tuberculosis is highly prevalent or have been in close contact with an individual with active tuberculosis.¹

Invasive fungal infections often not recognized in patients receiving TNF blocking agents; this has led to delays in appropriate treatment.⁹

Consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.^{1 9} Whenever feasible, consult specialist in fungal infections when making decisions regarding initiation and duration of antifungal therapy.^{1 9}

When deciding whether to reinitiate TNF blocking agent therapy following resolution of an invasive fungal infection, reevaluate risks and benefits, particularly in patients who reside in regions where mycoses are endemic.⁹ Whenever feasible, consult specialist in fungal infections.⁹

Increased incidence of serious infection and neutropenia observed with concomitant use of etanercept (another TNF blocking agent) and anakinra (a human interleukin-1 receptor antagonist).^{1 10} (See Specific Drugs under Interactions.)

Increased incidence of infection and serious infection reported with concomitant use of a TNF blocking agent and abatacept.^{1 11} (See Specific Drugs under Interactions.)

Hepatitis B Virus (HBV) Reactivation

Increased risk of reactivation of HBV infection in patients who are chronic carriers of this virus (i.e., hepatitis B surface antigen-positive [HBsAg-positive]).¹ Death reported in a few individuals.¹ Use of multiple immunosuppressive agents may contribute to HBV reactivation.¹

Screen at-risk patients prior to initiation of therapy.¹ Evaluate and monitor HBV carriers before, during, and for up to several months after therapy.¹ Safety and efficacy of antiviral therapy for prevention of HBV reactivation not established.¹ Discontinue golimumab and initiate appropriate treatment (e.g., antiviral therapy) if HBV reactivation occurs.¹ Not known whether golimumab can be readministered once control of a reactivated HBV infection is achieved; caution advised in this situation.¹

Malignancies and Lymphoproliferative Disorders

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

Lymphoma and other malignancies (some fatal) reported during postmarketing surveillance in children and adolescents receiving TNF blocking agents, particularly in those receiving other immunosuppressive agents (e.g., azathioprine, methotrexate) concomitantly.^{1 8} Malignancies included lymphomas (about 50% of the cases) (e.g., Hodgkin’s disease, non-Hodgkin’s lymphoma) and various other malignancies (e.g., leukemia, melanoma, solid organ cancers), including rare malignancies usually associated with immunosuppression and malignancies not usually observed in children and adolescents (e.g., leiomyosarcoma, hepatic malignancies, renal cell carcinoma).^{1 8} Median time to occurrence was 30 months (range: 1–84 months) after the initial TNF blocking agent dose.¹ FDA has concluded that there is an increased risk of malignancy with TNF blocking agents in children and adolescents; however, the strength of the association is not fully characterized.⁸

In controlled studies, lymphoma was reported more frequently in patients receiving golimumab or other TNF blocking agents than in control patients.¹ Patients with rheumatoid arthritis and other chronic inflammatory diseases, especially those with highly active disease and/or chronic exposure to immunosuppressive therapies, may be at increased risk of lymphoma.¹

In clinical studies of golimumab, the rate of malignancies other than lymphoma was not increased in golimumab-treated patients compared with placebo recipients; the rate was similar to the expected rate in the general US population.¹

However, acute and chronic leukemias (some fatal) reported during postmarketing surveillance of TNF blocking agents in adults and pediatric patients, particularly in those receiving other immunosuppressive agents concomitantly.^{1 8} Leukemia (most commonly acute myeloid leukemia, chronic lymphocytic leukemia, and chronic myeloid leukemia) generally occurred during first 2 years of therapy.⁸ FDA has concluded that there is a possible association between TNF blocking agents and development of leukemia; interpretation of findings is complicated because patients with rheumatoid arthritis may be at increased risk for leukemia independent of any treatment with TNF blocking agents.^{1 8}

In other populations at increased risk for malignancies (e.g., patients with COPD, patients with Wegener’s granulomatosis receiving concomitant cyclophosphamide), a greater proportion of malignancies occurred in patients receiving TNF blocking agents compared with control patients.¹

Malignancies also reported in a limited number of patients with uncontrolled, severe persistent asthma† who received golimumab; not reported in control patients.^{1 16}

Consider possibility of and monitor for occurrence of malignancies during and following treatment with TNF blocking agents.⁸ Consider risks and benefits of TNF blocking agents, including golimumab, before initiating therapy in patients with a known malignancy (other than successfully treated nonmelanoma skin cancer) or when considering whether to continue therapy in patients who develop a malignancy.¹

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactic reactions not reported in patients who received golimumab in clinical studies.¹

Latex Sensitivity

The needle cover of the prefilled syringe and the syringe in the auto-injector contain dry natural rubber and should not be handled by individuals sensitive to latex.¹

Other Warnings/Precautions

Cardiovascular Effects

Worsening CHF and new-onset CHF reported in patients receiving TNF blocking agents; golimumab not studied in patients with history of CHF.¹ If used in patients with CHF, caution and careful monitoring recommended.¹ Discontinue therapy if new or worsening symptoms of heart failure occur.¹

Nervous System Effects

New onset or exacerbation of CNS demyelinating disorders, including multiple sclerosis, reported in patients receiving TNF blocking agents; golimumab not studied in patients with multiple sclerosis.¹

Exercise caution when considering golimumab therapy in patients with CNS demyelinating disorders, including multiple sclerosis.¹

Hematologic Effects

Pancytopenia, leukopenia, neutropenia, aplastic anemia, and thrombocytopenia reported during postmarketing surveillance in patients receiving TNF blocking agents.¹ Severe cytopenias not observed in clinical studies of golimumab; however, use with caution in patients who have substantial cytopenias.¹

Immunization

Patients may receive inactivated vaccines.¹ Avoid live vaccines.¹ (See Interactions.)

Immunologic Reactions and Antibody Formation

Formation of autoimmue antibodies and, rarely, development of a lupus-like syndrome reported with TNF blocking agents.¹ Golimumab not associated with development of antibodies to double-stranded DNA (anti-dsDNA) in clinical studies to date in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.¹

Antibodies to golimumab may develop.¹ However, the relationship between antibodies to the drug and efficacy or safety is not fully elucidated.¹

Psoriasis

New-onset psoriasis, including pustular and palmoplantar psoriasis, and exacerbation of existing psoriasis reported with TNF blocking agents, including golimumab, particularly in patients receiving other immunosuppressive agents (e.g., corticosteroids, methotrexate) concomitantly.^{1 8} Onset of new cases observed weeks to years following initiation of drug.⁸ Some patients required hospitalization.^{1 8} Most patients experienced improvement following discontinuance of the TNF blocking agent.^{1 8} Recurrences reported upon rechallenge with a different TNF blocking agent.¹ FDA has concluded that there is a possible association between use of TNF blocking agents and development of psoriasis.⁸

Consider possibility of and monitor for manifestations (e.g., new rash) of new or worsening psoriasis, particularly pustular and palmoplantar psoriasis.⁸ Consider discontinuance of golimumab if psoriasis is severe or if it worsens or does not improve despite topical treatment.¹

Hepatic Effects

Severe hepatic reactions, including acute liver failure, reported in patients receiving TNF blocking agents.¹

Increased serum ALT and AST concentrations reported in patients receiving golimumab.¹ Relationship between golimumab and increased liver enzyme concentrations not clear because many patients received concomitant therapy with drugs that increase liver enzyme concentrations (e.g., methotrexate, NSAIAs).¹

Specific Populations

Pregnancy

Category B.¹

Lactation

Distributed into milk in cynomolgus monkeys.¹ Not known whether golimumab is distributed into human milk or absorbed systemically following ingestion.¹ Discontinue nursing or drug.¹

Pediatric Use

Safety and efficacy not established in children <18 years of age.¹

Malignancies, some fatal, reported in children and adolescents who received TNF blocking agents.^{1 8} (See Malignancies and Lymphoproliferative Disorders under Cautions.)

Geriatric Use

No overall differences in serious adverse events, serious infections, and adverse events in those ≥65 years of age compared with younger adults.¹ (See Special Populations under Pharmacokinetics.)

Overall incidence of infection is higher in the geriatric population than in younger adults; use with caution.¹

Common Adverse Effects

Upper respiratory infection,¹ nasopharyngitis.¹

Interactions for Simponi

Administered concomitantly with methotrexate, hydroxychloroquine, sulfasalazine, corticosteroids, and/or NSAIAs in clinical studies.¹

Drugs Metabolized by Hepatic Microsomal Enzymes

Because increased levels of TNF-α during chronic inflammation may suppress formation of CYP isoenzymes, antagonism of TNF-α activity by golimumab may normalize formation of CYP enzymes.^{1 15}

Drugs metabolized by CYP isoenzymes that have a low therapeutic index: Monitor therapeutic effect and serum concentrations following initiation or discontinuance of golimumab; adjust dosage as needed.^{1 15}

Biologic Antirheumatic Agents

For abatacept, anakinra, rituximab, and other TNF blocking agents, see Specific Drugs under Interactions. Insufficient data available to provide recommendations regarding concomitant use of golimumab and other biologic agents used in the management of rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.¹

Vaccines

Patients may receive inactivated vaccines.¹

Avoid live vaccines.¹ No data available on response to immunization, risk of infection, or secondary transmission of infection by live vaccines in golimumab-treated patients.¹

Specific Drugs

Drug	Interaction	Comments
Abatacept	Increased incidence of infection and serious infection, without additional clinical benefit, reported with abatacept and TNF blocking agents in rheumatoid arthritis1 11	Concomitant use not recommended1 11 15
Anakinra	Increased incidence of serious infections and neutropenia, without additional clinical benefit, reported with anakinra and etanercept (another TNF blocking agent) in rheumatoid arthritis1 10	Concomitant use not recommended1 15
Corticosteroids, oral	Concomitant use does not appear to alter golimumab clearance1
Cyclosporine	Possible effect on cyclosporine metabolism; because increased levels of TNF-α during chronic inflammation may suppress formation of CYP isoenzymes, antagonism of TNF-α activity by golimumab may normalize formation of CYP enzymes1 15	Monitor therapeutic effect and serum concentrations of cyclosporine following initiation or discontinuance of golimumab; adjust dosage as needed1 15
Methotrexate	Concomitant use or nonuse of methotrexate does not appear to influence efficacy or safety of golimumab for management of psoriatic arthritis or ankylosing spondylitis1 Decreased incidence of antibodies to golimumab reported with concomitant use1 Increased mean steady-state trough concentrations of golimumab reported with concomitant use1	Use golimumab in conjunction with methotrexate for management of rheumatoid arthritis1 Golimumab may be used with or without methotrexate for management of psoriatic arthritis or ankylosing spondylitis1
NSAIAs	Concomitant use does not appear to alter golimumab clearance1
Pneumococcal polysaccharide vaccine	Study data suggest that golimumab does not suppress the humoral immune response to pneumococcal vaccine1
Rituximab	Increased risk of serious infection reported in patients who received rituximab and subsequently received a TNF blocking agent1
Sulfasalazine	Concomitant use does not appear to alter golimumab clearance1
Theophylline	Possible effect on theophylline metabolism; because increased levels of TNF-α during chronic inflammation may suppress formation of CYP isoenzymes, antagonism of TNF-α activity by golimumab may normalize formation of CYP enzymes1 15	Monitor therapeutic effect and serum concentrations of theophylline following initiation or discontinuance of golimumab; adjust dosage as needed1 15
TNF blocking agents		Avoid concomitant use of golimumab and other TNF blocking agents1
Warfarin	Possible effect on warfarin metabolism; because increased levels of TNF-α during chronic inflammation may suppress formation of CYP isoenzymes, antagonism of TNF-α activity by golimumab may normalize formation of CYP enzymes1 15	Monitor therapeutic effect of warfarin following initiation or discontinuance of golimumab; adjust dosage as needed1 15

Simponi Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is approximately 53% following sub-Q administration.¹

Peak serum concentrations achieved in a median of 2–6 days following sub-Q administration.¹

Steady-state concentrations achieved within 12 weeks following sub-Q administration of golimumab 50 mg once monthly in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.^{1 18}

Patients who developed antibodies to golimumab generally had lower steady-state trough serum concentrations of golimumab.¹

Distribution

Extent

Distributed mainly into the circulatory system with limited extravascular distribution.¹

Distributed into milk in cynomolgus monkeys; not known whether golimumab is distributed into human milk.¹

Elimination

Half-life

2 weeks in healthy individuals and patients with active rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.¹

Special Populations

Pharmacokinetics not formally studied in renal or hepatic impairment.¹

Among adults, age does not appear to influence pharmacokinetics.¹ Clearance appears to be similar in patients ≥65 years of age and younger adults.¹ (See Geriatric Use under Cautions.)

With increasing body weight, there is a trend toward higher clearance; however, no clinically important weight-related differences in efficacy observed in psoriatic arthritis or ankylosing spondylitis populations.^{1 18} Reduction in clinical efficacy with increasing body weight observed with both 50- and 100-mg doses in 1 study in rheumatoid arthritis.¹ (See Special Populations under Dosage and Administration.)

No gender-related pharmacokinetic differences apparent in patients with rheumatoid arthritis or psoriatic arthritis; in patients with ankylosing spondylitis, apparent clearance was approximately 13% higher in females than in males.¹ However, both genders achieved clinically important responses at the proposed clinical dose.¹ (See Special Populations under Dosage and Administration.)

Ethnicity-related pharmacokinetic differences not observed between Caucasian and Asian patients; limited number of patients of other races available to assess for pharmacokinetic differences.¹

Stability

Storage

Parenteral

Injection

2–8°C.¹ Protect from light; store in original carton until administration.¹ Do not freeze or shake.¹ Discard unused portions.¹

Actions

• 
  

  Potent antagonist of TNF biologic activity.^{1 2 3 4 5 6 14 15 18}

  
  


• 
  

  Has high specificity and affinity for soluble and transmembrane TNF (TNF-α); does not bind to or neutralize human lymphotoxin.^{1 3 4 5 6 14 15 18} Prevents the binding of TNF to its receptors, thereby blocking the biologic activity of TNF.^{1 15 18}

  
  


• 
  

  Does not appear to bind to other TNF superfamily ligands.¹

  
  


• 
  

  Does not lyse human monocytes expressing transmembrane TNF in the presence of complement or effector cells.¹

  
  


• 
  

  An immunoglobulin G₁ kappa (IgG₁) created using genetically engineered mice immunized with human TNF, resulting in an antibody with human-derived antibody variable and constant regions.¹

  
  


• 
  

  Produced by a recombinant cell line cultured by continuous perfusion; purified by a process that includes specific viral inactivation and removal steps.¹

  
  

Advice to Patients

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

• 
  

  A copy of the manufacturer’s patient information (medication guide) for golimumab must be provided to all patients with each prescription of the drug. (See REMS Program under Dosage and Administration.)^{1 8} Importance of advising patients about potential benefits and risks of golimumab.^{1 8} Importance of patients reading the medication guide prior to initiation of therapy and each time the prescription is refilled.¹

  
  


• 
  

  Importance of instructing patient and/or caregiver regarding proper dosage and administration of golimumab, including the use of aseptic technique, and proper disposal of needles and syringes if it is determined that the patient and/or caregiver is competent to safely administer the drug.¹

  
  


• 
  

  Risk of increased susceptibility to infection.¹ Importance of promptly informing clinicians if any signs or symptoms of infection (e.g., persistent fever, sweating, cough, dyspnea, fatigue, diarrhea, burning upon urination, warm, red, or painful skin) develop.^{1 9}

  
  


• 
  

  Risk of lymphoma, leukemia, and other malignancies with TNF blocking agents.^{1 8} Importance of informing patients and families about the increased risk of cancer development in children and adolescents, taking into account the clinical utility of TNF blocking agents, the benefits and risks of other immunosuppressive drugs, and the risks associated with untreated disease.⁸ Importance of promptly informing clinicians if signs and symptoms of cancer occur (e.g., unexplained weight loss; fatigue; swollen lymph nodes in the neck, underarm, or groin; easy bruising or bleeding).⁸

  
  


• 
  

  Risk of new-onset psoriasis or worsening of existing psoriasis with TNF blocking agents.^{1 8} Importance of informing clinicians of any manifestations of new or worsening psoriasis (e.g., new rash).^{1 8}

  
  


• 
  

  Importance of alerting clinician if allergy to latex exists.¹

  
  


• 
  

  Importance of informing clinician of any new or worsening medical conditions (e.g., CHF, demyelinating disorders, autoimmune disorders, liver disease, cytopenias, psoriasis).¹

  
  


• 
  

  Importance of taking the drug as prescribed and of not altering or discontinuing therapy without first consulting with a clinician.⁸

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses or any history of tuberculosis, hepatitis B virus infection, or other chronic or recurring infections.¹

  
  


• 
  

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

  
  


• 
  

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

  
  

Preparations

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

Golimumab

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for subcutaneous use	50 mg/0.5 mL	Simponi (available as disposable prefilled syringes and prefilled auto-injectors [SmartJect])	Centocor Ortho Biotech

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Simponi 50MG/0.5ML Solution (JANSSEN BIOTECH): 1/$1,946.93 or 2/$5,838.00

Disclaimer

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

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

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Centocor Ortho Biotech Inc. Simponi (golimumab) injection prescribing information. Horsham, PA; 2009 Nov.

2. Smolen JS, Kay J, Doyle MK et al. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet. 2009; 374:210-21. [PubMed 19560810]

3. Keystone EC, Genovese MC, Klareskog L et al. Golimumab, a human antibody to tumour necrosis factor alpha given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study. Ann Rheum Dis. 2009; 68:789-96. [PubMed 19066176]

4. Emery P, Fleischmann RM, Moreland LW et al. Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis. Arthritis Rheum. 2009; 60:2272-83. [PubMed 19644849]

5. Kavanaugh A, McInnes I, Mease P et al. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum. 2009; 60:976-86. [PubMed 19333944]

6. Inman RD, Davis JC, Heijde D et al. Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum. 2008; 58:3402-12. [PubMed 18975305]

7. Anderson JJ, Baron G, van der Heijde D et al. Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis Rheum. 2001; 44:1876-86. [PubMed 11508441]

8. Food and Drug Administration, Center for Drug Evaluation and Research. Information for healthcare professionals: Tumor necrosis factor (TNF) blockers (marketed as Remicade, Enbrel, Humira, Cimzia, and Simponi). FDA alert. Rockville MD; 2009 Aug 4. Available from FDA website. Accessed 2009 Nov 3.

9. Food and Drug Administration, Center for Drug Evaluation and Research. FDA alert: Information for healthcare professionals Cimzia (certolizumab pegol), Enbrel (etanercept), Humira (adalimumab), and Remicade (infliximab). Rockville MD: Food and Drug Administration; 2008 Sep 4. Available from FDA website. Accessed 2010 May 25.

10. Immunex. Enbrel (etanercept) for subcutaneous injection prescribing information. Thousand Oaks, CA: 2010 Jun.

11. Bristol-Myers Squibb. Orencia (abatacept) lyophilized powder for intravenous infusion prescribing information. Princeton, NJ; 2009 Aug.

12. Simponi (golimumab) risk evaluation and mitigation stra