Pexeva

Generic Name: paroxetine (Oral route)

par-OX-e-teen

Oral route(Tablet)

Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24, and there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. This risk must be balanced with the clinical need. Monitor patients closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Not approved for use in pediatric patients .

Oral route(Tablet;Tablet, Extended Release;Suspension)

Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies with major depressive disorder (MDD) and other psychiatric disorders. Short term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24, and there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. This risk must be balanced with the clinical need. Monitor patients closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Not approved for use in pediatric patients .

Commonly used brand name(s)

In the U.S.

• Paxil


• Paxil CR


• Pexeva

Available Dosage Forms:

• Tablet


• Tablet, Extended Release


• Suspension

Therapeutic Class: Antidepressant

Pharmacologic Class: Serotonin Reuptake Inhibitor

Uses For Pexeva

Paroxetine is used to treat mental depression, obsessive-compulsive disorder (OCD), panic disorder, generalized anxiety disorder (GAD), social anxiety disorder (also known as social phobia), premenstrual dysphoric disorder (PMDD), and posttraumatic stress disorder (PTSD).

Paroxetine belongs to a group of medicines known as selective serotonin reuptake inhibitors (SSRIs). These medicines are thought to work by increasing the activity of the chemical called serotonin in the brain.

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

Before Using Pexeva

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

Allergies

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

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of paroxetine in the pediatric population. Safety and efficacy have not been established.

Studies have shown that some children, teenagers, and young adults think about suicide or attempt suicide when taking the medicine. Talk with your doctor if you have concerns about this.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of paroxetine in the elderly. However, elderly patients may be more sensitive to the effects of this medicine than younger adults, and are more likely to have hyponatremia (low sodium in the blood) which may require caution and an adjustment in the dose for patients receiving paroxetine.

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

Studies in women suggest that this medication poses minimal risk to the infant when used during 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.

• Clorgyline


• Furazolidone


• Iproniazid


• Isocarboxazid


• Linezolid


• Methylene Blue


• Metoclopramide


• Moclobemide


• Nialamide


• Pargyline


• Phenelzine


• Pimozide


• Procarbazine


• Rasagiline


• Selegiline


• Thioridazine


• Toloxatone


• Tranylcypromine

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.

• Abciximab


• Aceclofenac


• Acemetacin


• Acenocoumarol


• Alclofenac


• Almotriptan


• Ancrod


• Anisindione


• Antithrombin III Human


• Apazone


• Ardeparin


• Aspirin


• Benoxaprofen


• Bivalirudin


• Bromfenac


• Bufexamac


• Carprofen


• Certoparin


• Cilostazol


• Citalopram


• Clometacin


• Clonixin


• Clopidogrel


• Dalteparin


• Danaparoid


• Defibrotide


• Dermatan Sulfate


• Desirudin


• Desvenlafaxine


• Dexfenfluramine


• Dexketoprofen


• Dextromethorphan


• Diclofenac


• Dicumarol


• Diflunisal


• Dipyridamole


• Dipyrone


• Droperidol


• Droxicam


• Duloxetine


• Eletriptan


• Enoxaparin


• Eptifibatide


• Escitalopram


• Etodolac


• Etofenamate


• Felbinac


• Fenbufen


• Fenfluramine


• Fenoprofen


• Fentanyl


• Fentiazac


• Floctafenine


• Flufenamic Acid


• Fluoxetine


• Flurbiprofen


• Fluvoxamine


• Fondaparinux


• Frovatriptan


• Haloperidol


• Heparin


• Ibuprofen


• Indomethacin


• Indoprofen


• Isoxicam


• Ketoprofen


• Ketorolac


• Lornoxicam


• Magnesium Salicylate


• Meclofenamate


• Mefenamic Acid


• Meloxicam


• Milnacipran


• Nabumetone


• Nadroparin


• Naproxen


• Naratriptan


• Nefazodone


• Nepafenac


• Niflumic Acid


• Nimesulide


• Oxaprozin


• Oxyphenbutazone


• Parnaparin


• Paroxetine


• Pentosan Polysulfate Sodium


• Phenindione


• Phenprocoumon


• Phenylbutazone


• Pirazolac


• Piroxicam


• Pirprofen


• Prasugrel


• Propyphenazone


• Proquazone


• Reviparin


• Rizatriptan


• Salicylic Acid


• Salsalate


• Sertraline


• Sibutramine


• St John's Wort


• Sulindac


• Sumatriptan


• Suprofen


• Tamoxifen


• Tapentadol


• Tenidap


• Tenoxicam


• Tiaprofenic Acid


• Ticlopidine


• Tinzaparin


• Tirofiban


• Tolmetin


• Tramadol


• Trazodone


• Tryptophan


• Vilazodone


• Warfarin


• Zolmitriptan


• Zomepirac

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.

• Amitriptyline


• Amoxapine


• Aprepitant


• Asenapine


• Bupropion


• Cimetidine


• Clarithromycin


• Clomipramine


• Clozapine


• Cyproheptadine


• Darunavir


• Desipramine


• Dothiepin


• Doxepin


• Encainide


• Flecainide


• Fluoxetine


• Fluphenazine


• Fosamprenavir


• Fosphenytoin


• Galantamine


• Ginkgo


• Iloperidone


• Imipramine


• Lithium


• Lofepramine


• Metoprolol


• Nortriptyline


• Paliperidone


• Perhexiline


• Perphenazine


• Phenytoin


• Procyclidine


• Propafenone


• Protriptyline


• Quinidine


• Risperidone


• Ritonavir


• Tamsulosin


• Tetrabenazine


• Trimipramine

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

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

• Bipolar disorder (mood disorder with alternating episodes of mania and depression), or risk of or


• Bleeding problems or


• Bone problems or


• Glaucoma, narrow angle or


• Hyponatremia (low sodium in the blood) or


• Mania, history of or


• Seizures, history of—Use with caution. May make these conditions worse.

• Diseases affecting metabolism or diseases involving blood circulation—Caution should be used in patients with these medical problems.

• Heart disease, unstable or


• Heart attack, recent history of—The effects of paroxetine in patients with these conditions are not known.

• Kidney disease or


• Liver disease—Use with caution. Higher blood levels of paroxetine may occur, increasing the chance of side effects.

Proper Use of paroxetine

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

Take this medicine only as directed by your doctor to benefit your condition as much as possible. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

This medicine should come with a Medication Guide. It is very important that you read and understand this information. Be sure to ask your doctor about anything you do not understand.

Paroxetine may be taken with or without food or on a full or empty stomach. However, if your doctor tells you to take the medicine a certain way, take it exactly as directed.

You may have to take paroxetine for several weeks before you begin to feel better. Your doctor should check your progress at regular visits during this time. Also, if you are taking paroxetine for depression, you will probably need to continue taking it for at least 6 months to help prevent the depression from returning.

If you are taking the oral suspension, shake the bottle well before measuring each dose. Use a small measuring cup or a measuring spoon to measure each dose. The teaspoons and tablespoons that are used for serving and eating food do not measure exact amounts.

Swallow the extended-release tablets or tablets whole. Do not break, crush, or chew it.

Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

Dosing

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

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

• For oral dosage form (suspension):
  
  • For depression:
    
    • Adults—At first, 20 milligrams (mg) (10 milliliters [mL]) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 50 mg (25 mL) per day.
    
    
    • Older adults—At first, 10 mg (5 mL) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 40 mg (20 mL) per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For generalized anxiety disorder:
    
    • Adults—At first, 20 milligrams (mg) (10 milliliters [mL]) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 50 mg (25 mL) per day.
    
    
    • Older adults—At first, 10 mg (5 mL) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 40 mg (20 mL) per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For obsessive-compulsive disorder:
    
    • Adults—At first, 20 milligrams (mg) (10 milliliters [mL]) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 60 mg (30 mL) per day.
    
    
    • Older adults—At first, 10 mg (5 mL) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 40 mg (20 mL) per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For panic disorder:
    
    • Adults—At first, 10 milligrams (mg) (5 milliliters [mL]) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 60 mg (30 mL) per day.
    
    
    • Older adults—At first, 10 mg (5 mL) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 40 mg (20 mL) per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For posttraumatic stress disorder:
    
    • Adults—At first, 20 milligrams (mg) (10 milliliters [mL]) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 50 mg (25 mL) per day.
    
    
    • Older adults—At first, 10 mg (5 mL) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose usually is not more than 40 mg (20 mL) per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For social anxiety disorder:
    
    • Adults—At first, 20 milligrams (mg) (10 milliliters [mL]) once a day, usually taken in the morning.
    
    
    • Older adults—At first, 10 mg (5 mL) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose usually is not more than 20 mg (10 mL) per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

• For oral dosage form (tablets):
  
  • For depression:
    
    • Adults—At first, 20 milligrams (mg) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 50 mg per day.
    
    
    • Older adults—At first, 10 mg once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 40 mg per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For generalized anxiety disorder:
    
    • Adults—At first, 20 milligrams (mg) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 50 mg per day.
    
    
    • Older adults—At first, 10 mg once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose usually is not more than 40 mg per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For obsessive-compulsive disorder:
    
    • Adults—At first, 20 milligrams (mg) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose usually is not more than 60 mg per day.
    
    
    • Older adults—At first, 10 mg once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 40 mg per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For panic disorder:
    
    • Adults—At first, 10 milligrams (mg) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 60 mg per day.
    
    
    • Older adults—At first, 10 mg once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 40 mg per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For posttraumatic stress disorder:
    
    • Adults—At first, 20 milligrams (mg) once a day, usually taken in the morning. Your doctor may increase your dose if needed. However, the dose usually is not more than 50 mg per day.
    
    
    • Older adults—At first, 10 mg once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 40 mg per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For social anxiety disorder:
    
    • Adults—At first, 20 milligrams (mg) once a day, usually taken in the morning.
    
    
    • Older adults—At first, 10 mg once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 20 mg per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

• For oral dosage form (extended-release tablets):
  
  • For depression:
    
    • Adults—At first, 25 milligrams (mg) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose usually is not more than 62.5 mg per day.
    
    
    • Older adults—At first, 12.5 mg once a day, usually taken in the morning. Your doctor may increase your dose if needed. However, the dose is usually not more than 50 mg per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For panic disorder:
    
    • Adults—At first, 12.5 milligrams (mg) once a day, usually taken in the morning. Your doctor may increase your dose if needed. However, the dose usually is not more than 75 mg per day.
    
    
    • Older adults—At first, 12.5 mg once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 50 mg per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For social anxiety disorder:
    
    • Adults—At first, 12.5 milligrams (mg) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 37.5 mg per day.
    
    
    • Older adults—At first, 12.5 mg once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 37.5 mg per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For premenstrual dysphoric disorder:
    
    • Adults—At first, 12.5 milligrams (mg) once a day, usually taken in the morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 25 mg per day.
    
    
    • Older adults and children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

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

Storage

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

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

Precautions While Using Pexeva

It is important that your doctor check your progress at regular visits to allow changes in your dose and help reduce any side effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.

Do not take paroxetine within 2 weeks of taking an monoamine oxidase (MAO) inhibitor (e.g., isocarboxazid [Marplan®], phenelzine [Nardil®], selegiline [Eldepryl®], tranylcypromine [Parnate®]), linezolid (Zyvox®), or methylthioninium chloride (methylene blue). Do not take an MAO inhibitor for at least 2 weeks after taking paroxetine. If you do, you may develop extremely high blood pressure or seizures.

Do not take thioridazine (Mellaril®) while you are taking paroxetine. You should not use pimozide (Orap®) while you are taking this medicine. Using these medicines together can cause very serious heart problems.

Do not take Pexeva® tablets if you are also using Paxil® tablets. These medicines should not be taken together because both medicines contains paroxetine. Ask your doctor if you have any questions.

This medicine may decrease the amount of sperm men make and affect their ability to have children. If you plan to have children, talk with your doctor before using this medicine.

Tell your doctor right away if you develop any allergic reactions, such as skin rash or hives, while taking paroxetine.

Paroxetine may cause some teenagers and young adults to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. Some people may have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. If you or your caregiver notice any of these unwanted effects, tell your doctor right away. Let the doctor know if you or anyone in your family has bipolar disorder (manic-depressive) or has tried to commit suicide.

Do not suddenly stop taking this medicine without checking first with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely. This is to decrease the chance of having discontinuation symptoms such as agitation, breathing problems, chest pain, confusion, diarrhea, dizziness or lightheadedness, fast heartbeat, headache, increased sweating, muscle pain, nausea, restlessness, runny nose, trouble in sleeping, trembling or shaking, unusual tiredness or weakness, vision changes, or vomiting.

Make sure your doctor knows about all the other medicines you are using. Paroxetine may cause a serious condition called serotonin syndrome and neuroleptic malignant syndrome (NMS)-like reactions when taken with certain medicines such as lithium, tryptophan, St. John's wort, or some pain medicines (e.g., tramadol [Ultram®], rizatriptan [Maxalt®], sumatriptan [Imitrex®], or zolmitriptan [Zomig®]). Check with your doctor first before taking any other medicines.

Check with your doctor right away if you develop the following symptoms during the first few weeks of treatment with paroxetine: inability to sit still, need to keep moving, or restlessness.

Paroxetine has not been shown to add to the effects of alcohol. However, use of alcohol is not recommended in patients who are taking paroxetine.

Paroxetine may cause some people to become drowsy or have blurred vision. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are not alert or able to see clearly.

Hyponatremia (low sodium in the blood) may occur with this medicine. Stop using the medicine and check with your doctor right away if you have confusion, difficulty concentrating, headaches, memory problems, weakness, and unsteadiness.

This medicine may increase your risk for bleeding problems. Make sure your doctor knows if you are also taking other medicines that thin the blood, such as aspirin, nonsteroidal anti-inflammatory agents also called NSAIDs (e.g., ibuprofen, naproxen, Advil®, Aleve®, Celebrex®, or Motrin®), or warfarin (Coumadin®).

This medicine may increase the risk of bone fractures. Tell your doctor if you have unexplained bone pain, tenderness, swelling, or bruising. Also, ask your doctor about ways to keep your bones strong to help prevent fractures.

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

Pexeva Side Effects

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

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

Less common

• Agitation


• chest congestion


• chest pain


• chills


• cold sweats


• confusion


• difficulty with breathing


• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position


• fast, pounding, or irregular heartbeat or pulse


• muscle pain or weakness


• skin rash

Rare

• Absence of or decrease in body movements


• bigger, dilated, or enlarged pupils (black part of the eye)


• difficulty with speaking


• inability to move the eyes


• incomplete, sudden, or unusual body or facial movements


• increased sensitivity of the eyes to light


• low blood sodium (confusion, convulsions [seizures], drowsiness, dryness of the mouth, increased thirst, or lack of energy)


• red or purple patches on the skin


• serotonin syndrome (confusion, diarrhea, fever, poor coordination, restlessness, shivering, sweating, talking and acting with excitement you cannot control, trembling or shaking, or twitching)


• talking, feeling, and acting with excitement and activity you cannot control

Incidence not known

• Back, leg, or stomach pains


• bleeding gums


• blindness


• blistering, peeling, or loosening of the skin


• bloated, full feeling


• bloody or black, tarry stools


• bloody urine


• blue-yellow color blindness


• blurred vision


• coma


• constipation


• cough or hoarseness


• dark urine


• decreased frequency or amount of urine


• decreased vision


• depression


• difficulty opening the mouth


• difficulty with swallowing


• electric shock sensations


• epileptic seizure that will not stop


• excessive muscle tone


• eye pain


• fainting


• fixed position of the eye


• fluid-filled skin blisters


• general body swelling


• general feeling of tiredness or weakness


• headache


• high fever


• hives


• inability to move the arms and legs


• inability to sit still


• increased blood pressure


• increased sweating


• increased thirst


• incremental or ratchet-like movement of the muscle


• indigestion


• itching skin


• joint pain


• light-colored stools


• lockjaw


• loss of appetite


• loss of bladder control


• low blood pressure


• lower back or side pain


• muscle spasm, especially of the neck and back


• muscle tension or tightness


• nausea


• need to keep moving


• nosebleeds


• painful knees and ankles


• painful or difficult urination


• painful or prolonged erection of the penis


• pale skin


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


• raised red swellings on the skin, the buttocks, legs, or ankles


• red, irritated eyes


• rigid muscles


• seizure or coma late in pregnancy


• sensitivity to the sun


• shortness of breath


• skin redness or soreness


• skin sores, welts, or blisters


• skin thinness


• slow heart rate


• slow movement


• slow reflexes


• sore throat


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


• spasms of the throat


• stiff muscles


• stomach pain


• sudden numbness and weakness in the arms and legs


• swelling of the breasts


• swelling of the face, fingers, or lower legs


• swollen or painful glands


• tightness in the chest


• unexpected or excess milk flow from the breasts


• unusual bleeding or bruising


• unusual or decreased blood cell production


• unusual tiredness or weakness


• vomiting


• weight gain


• wheezing


• yellowing of the eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

• Dizziness


• drowsiness


• flushing of the face


• irritability


• large pupils


• racing heartbeat


• trembling or shaking

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

• Acid or sour stomach


• belching


• decreased appetite


• decreased sexual ability or desire


• excess air or gas in the stomach or intestines


• heartburn


• nervousness


• pain or tenderness around the eyes and cheekbones


• passing gas


• problems in urinating


• runny or stuffy nose


• sexual problems, especially ejaculatory disturbances


• sleepiness or unusual drowsiness


• stomach discomfort, upset, or pain


• sweating


• trauma


• trouble with sleeping

Less common

• Abnormal dreams


• anxiety


• bladder pain


• body aches or pain


• change in sense of taste


• changes in vision


• cloudy urine


• confusion


• congestion


• difficulty in focusing the eyes


• difficulty with moving


• discouragement, feeling sad, or empty


• drugged feeling


• dryness of the throat


• excessive muscle tone


• fainting or loss of consciousness


• fast or irregular breathing


• feeling of unreality


• feeling of warmth or heat


• flushing or redness of the skin, especially on the face and neck


• frequent urge to urinate


• headache, severe and throbbing


• heavy bleeding


• increase in body movements


• increased appetite


• irritability


• itching of the vagina or genital area


• itching, pain, redness, or swelling of the eye or eyelid


• lack of emotion


• loss of interest or pleasure


• loss of memory


• lump in the throat


• menstrual changes


• menstrual pain or cramps


• muscle twitching or jerking


• pain during sexual intercourse


• problems with memory


• problems with tooth


• rhythmic movement of the muscles


• sense of detachment from self or body


• severe sunburn


• slow heartbeat


• sneezing


• thick, white vaginal discharge with no odor or with a mild odor


• tightness in the throat


• tingling, burning, or prickling sensations


• trouble concentrating


• voice changes


• watering of the eyes


• weight loss


• yawn

After you stop using this medicine, it may still produce some side effects that need attention. During this period of time, check with your doctor immediately if you notice the following side effects:

• Actions that are out of control


• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings


• crying


• depersonalization


• diarrhea


• dizziness or lightheadedness


• dysphoria


• electric shock sensations


• euphoria


• fear


• feeling unwell or unhappy


• increased sweating


• irritability


• muscle pain


• nervousness


• paranoia


• quick to react or overreact emotionally


• rapidly changing moods


• talking, feeling, and acting with excitement


• unusual drowsiness, dullness, or feeling of sluggishness


• unusual tiredness or weakness


• vision changes

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: Pexeva side effects (in more detail)

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

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

More Pexeva resources

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

• Pexeva MedFacts Consumer Leaflet (Wolters Kluwer)


• Pexeva Prescribing Information (FDA)


• Paroxetine Prescribing Information (FDA)


• Paroxetine MedFacts Consumer Leaflet (Wolters Kluwer)


• Paroxetine Professional Patient Advice (Wolters Kluwer)


• Paroxetine Hydrochloride Monograph (AHFS DI)


• Paxil Consumer Overview


• Paxil Prescribing Information (FDA)


• Paxil CR Controlled-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• Paxil CR Prescribing Information (FDA)

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Ferrous Fumarate 140mg / 5ml Oral Suspension

1. Name Of The Medicinal Product

Ferrous Fumarate 140mg/5ml Oral Suspension

2. Qualitative And Quantitative Composition

Each 5ml of suspension contains 140mg ferrous fumarate.

For excipients, see 6.1.

3. Pharmaceutical Form

Oral Suspension

A smooth brown suspension with an odour of elderberry.

4. Clinical Particulars

4.1 Therapeutic Indications

Prophylaxis and treatment of iron deficiency states.

For prophylaxis during pregnancy, a combination of iron and folic acid is usually recommended.

4.2 Posology And Method Of Administration

Shake the bottle before use.

Adults and the elderly: Two 5ml spoonfuls of syrup twice a day. Dose may be increased to four 5ml spoonfuls twice a day, if required.

Children: Full term infants and young children-half to one 5ml spoonful twice a day.

Premature infants: 0.6ml/kg day to 2.4 ml/kg/day.

Method of administration: Oral

4.3 Contraindications

Known hypersensitivity to any of the ingredients of the product.

Must not be used in anaemia's other than those due to iron deficiency.

Iron preparations are contra-indicated in patients with:

• Paroxysmal nocturnal haemoglobinuria. Haemosiderosis, haemochromatosis.

• In patients with active peptic ulcer, regional enteritis and ulcerative colitis.

• In patients receiving repeated blood transfusions.

• When used concomitantly with parental iron therapy.

4.4 Special Warnings And Precautions For Use

Before starting treatment, it is important to exclude any underlying cause of the anaemia (e.g. gastric erosion, colonic carcinoma).

Because anaemia due to combined iron and Vitamin B₁₂ or folate deficiencies may be microcytic in type, patients with microcytic anaemia resistant to treatment with iron alone should be screened for Vitamin B₁₂ or folate deficiency.

Duration of treatment of uncomplicated iron deficiency anaemia should not usually exceed 6 months (3 months after reversal of the anaemia has been achieved).

Oral iron, particularly modified-release preparations may exacerbate diarrhoea in patients with inflammatory bowel disease.

As with all iron preparations, ferrous fumarate should be used with care in patients with known or suspected gastrointestinal strictures or intestinal diverticular disease.

Some post-gastrectomy patients show poor absorption of iron.

Care is required when treating patients with iron deficiency anaemia who have treated or controlled peptic ulceration.

This product contains liquid glucose and sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Long-term treatment with Ferrous Fumarate 140mg/5ml Oral Suspension can increase the risk of dental caries. Adequate dental hygiene must be maintained. Since Ferrous Fumarate 140mg/5ml oral suspension contains sugar, care must be exercised when using in patients with diabetes mellitus.

Aspiration of iron preparations induces inflammatory lesions at the site of iron deposit and may cause bronchial stenosis.

This product also contains Sodium metabisulphite and parahydroxybenzoates. Sodium metabisulphite may rarely cause severe hypersensitivity reactions and bronchospasm. Parahydroxybenzoates may cause allergic reactions (possibly delayed).

The label will state

“Important warning: Contains iron. Keep out of the reach and sight of children, as overdose may be fatal.”

This will appear on the front of the pack within a rectangle, in which there is no other information.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Iron inhibits the absorption of tetracyclines from the gastrointestinal tract and tetracycline inhibits the absorption of iron. If both drugs must be given, tetracyclines should be taken three hours after or two hours before oral iron supplements.

Iron reduces the absorption of penicillamine, bisphosphonates, ciprofloxacin, entacapone, levodopa, levofloxacin, levothyroxine (thyroxine) (give at least 2 hours apart), moxifloxacin, mycophenolate, norfloxacin, ofloxacin, zinc.

Concurrent administration of oral iron preparations with tea, coffee, eggs, food or medications containing bicarbonates, carbonate, oxalates or phosphates, milk or milk products, whole grain breads and cereals and dietary fibre, may decrease iron absorption.

The absorption of ferrous fumarate is reduced by magnesium trisilicate, calcium salts, trientine and cholestyramine.

Chloramphenicol delays plasma iron clearance, incorporation of iron into red blood cells and interferes with erythropoiesis.

Avoid concomitant use of iron with dimercaprol.

Ferrous fumarate also reduces the hypotensive effect of methyldopa.

Absorption of iron salts is enhanced by ascorbic acid and meat.

4.6 Pregnancy And Lactation

Pregnancy

Ferrous fumarate suspension can be used during pregnancy if clinically indicated.

Lactation

No adverse effects of ferrous sulphate have been shown in breastfed infants of treated mothers. Ferrous fumarate suspension can be used during breast-feeding if clinically indicated.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

The commonest side effects relate to gastrointestinal irritation (nausea, epigastric pain, constipation or diarrhoea). In the event of these ADRs, it may be helpful to reduce the dose or switch to an alternative iron salt.

Darkening of stools, black discoloration of the teeth and allergic reactions (due to metabisulphite in the syrup vehicle) may also occur

4.9 Overdose

Symptoms:

Ingestion of 20 mg/kg elemental iron is potentially toxic and 200-250 mg/kg is potentially fatal. No single method of assessment is entirely satisfactory - clinical features as well as laboratory analysis must be taken into account. The serum iron taken at about 4 hours after ingestion is the best laboratory measure of severity.

Serum Iron	Severity
< 3 mg/L (55 micromol/L)	Mild toxicity
3-5 mg/L (55-90 micromol/L)	Moderate toxicity
> 5 mg/L (90 micromol/L)	Severe toxicity

Early signs and symptoms include nausea, vomiting, abdominal pain and diarrhoea. The vomit and stools may be grey or black. In mild cases early features improve but in more serious cases there may be evidence of hypoperfusion (cool peripheries and hypotension), metabolic acidosis and systemic toxicity. In serious cases there can be recurrence of vomiting and gastrointestinal bleeding, 12 hours after ingestion. Shock can result from hypovolaemia or direct cardiotoxicity.

Evidence of hepatocellular necrosis appears at this stage with jaundice, bleeding, hypoglycaemia, encephalopathy and positive anion gap metabolic acidosis. Poor tissue perfusion may lead to renal failure. Rarely, gastric scarring causing stricture or pyloric stenosis (alone or in combination) may lead to partial or complete bowel obstruction 2-5 weeks after ingestion.

Management:

Supportive and symptomatic measures include ensuring a clear airway, monitor cardiac rhythm, BP and urine output, establishing IV access and administering sufficient fluids to ensure adequate hydration. Consider whole bowel irrigation. If metabolic acidosis persists despite correction of hypoxia and adequate fluid resuscitation, an initial dose of 50 mmol sodium bicarbonate may be given and repeated as necessary, for adults guided by arterial blood gas monitoring (aim for a pH of 7.4). Consider the use of desferrioxamine, if /the patient is symptomatic (other than nausea), serum iron concentration is between 3-5 mg/L (55-90 micromol/L) and still rising. Haemodialysis does not remove iron effectively but should be considered on a supportive basis for acute renal failure as this will facilitate removal of the iron-desferrioxamine complex.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

ATC code: B03A A02 Iron bivalent, oral preparations

Iron is an essential constituent of the body, and is necessary for haemoglobin formation and for the oxidative processes of living tissues. Iron and iron salts should be given for the treatment or prophylaxis of iron deficiency anaemias.

Preparations of iron are administered by mouth, by intramuscular or intravenous injection.

Soluble ferrous salts are most effective by mouth. Ferrous fumarate is an easily absorbed source of iron for replacement therapy. It is a salt of ferrous iron with an organic acid and is less irritant to the gastrointestinal tract than salts with inorganic acids.

5.2 Pharmacokinetic Properties

In the acid conditions of the gastric contents, ferrous fumarate is dissociated and ferrous ions are liberated. These ions are absorbed in the proximal portion of the duodenum.

The ferrous iron absorbed by the mucosal cells of the duodenum is oxidised to the ferric form, and this is bound to protein to form Ferritin.

Ferritin in the mucosal cells release's iron into the blood, where it is bound to transferrin and passed into the iron stores - liver, spleen, and bone marrow.

These stores are a reserve of iron for synthesis of haemoglobin, myoglobin, and iron containing enzymes.

Iron is lost from the body through loss of cells in urine, faeces, hair, skin, sputum, nails, and mucosal cells, and through blood loss.

Ferrous fumarate has the same pattern of absorption and excretion as dietary iron.

5.3 Preclinical Safety Data

No further data.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Nipastat GL 75

Methylcellulose

Glucose Liquid

Sucrose

Granular Lecithin

Elderberry flavour

Sodium metabisulphite

Purified water

6.2 Incompatibilities

None.

6.3 Shelf Life

24 months

6.4 Special Precautions For Storage

Keep the bottle in the outer carton in order to protect from light.

Do not store above 25°C.

6.5 Nature And Contents Of Container

Amber glass bottle with polypropylene cap and melinex/pulpboard/aluminium wad containing 200 ml of oral suspension.

6.6 Special Precautions For Disposal And Other Handling

Shake the bottle before use.

No Data Held

7. Marketing Authorisation Holder

Goldshield Pharmaceutical Ltd

NLA Tower, 12-16 Addiscombe Road

Croydon, Surrey CR0 0XT

United Kingdom

8. Marketing Authorisation Number(S)

PL 12762/0083

9. Date Of First Authorisation/Renewal Of The Authorisation

17^th June 2005

10. Date Of Revision Of The Text

05/11/2010

Flebogamma

human immunoglobulin g

Dosage Form: injection
Immune Globulin Intravenous (Human)

Flebogamma® 5%

Rx only

DESCRIPTION

Immune Globulin Intravenous (Human), Flebogamma® 5% (IGIV) is a sterile, clear or slightly opalescent and colorless to pale yellow, liquid, pasteurized preparation of highly purified immunoglobulin (IgG) obtained from human plasma pools. The purification process includes cold alcohol fractionation, polyethylene glycol precipitation, and ion exchange chromatography.

Flebogamma® 5% is a highly purified (≥ 99% IgG), unmodified, human IgG that contains the antibody specificities found in the donor population. IgG subclasses are fully represented with the following approximate percents of total IgG: IgG1, is 70.3%, IgG2, 24.7%, IgG3, 3.1%, and IgG4, 1.9% (1). The IgA content is < 0.05 mg/mL, and IgM is present in trace amounts.

In the final formulation, Flebogamma® 5% contains 50 mg IgG per mL, 50 mg D-sorbitol per mL, and ≤ 6 mg/mL polyethylene glycol. There is no preservative in the formulation. The pH of the solution ranges from 5 to 6 and the osmolarity from 240 to 350 mOsm/L.

All Source Plasma used in the manufacture of this product was tested by FDA-licensed serological tests for HBsAg, antibodies to HCV and HIV and Nucleic Acid Test (NAT) for HCV and HIV-1 and found to be nonreactive (negative).

Virus elimination experiments have been performed on 2 steps of the production process. Residual viral titers were determined by infectivity assays. When no residual virus was detected, the Poisson distribution was used to give the minimum detectable level (MDL) based on the assay sensitivity and the sample volume used (1).

The viral reduction data (in log10) from these experiments are summarized in Table 1.

Table 1. Viral Log Reductions

Target Virus	HIVa	HBV, Herpesvirus		HCV		HAV	Parvovirus B19
Model	HIV-1	IBR	PRV	BVDV	Sindbis	EMC	PPV
a Abbreviations: HIV = Human immunodeficiency virus; HBV = Hepatitis B virus; HCV = Hepatitis C virus; HAV = Hepatitis A virus; IBR = Infectious Bovine Rhinotracheitis virus; PRV = Pseudorabies virus; BVDV = Bovine Viral Diarrhoea virus; EMC = Encephalomyocarditis virus; PPV = Porcine Parvovirus.
Pasteurization (60°C, 10 h)	> 5.9	5.8	≥ 4.3	≥ 5.1	≥ 6.6	5.0	2.3
PEG precipitation	3.7	4.3	4.2	≥ 5.3	4.2	3.8	3.9
Cumulative	≥ 9.6	10.1	≥ 8.5	≥ 10.4	≥ 10.8	8.8	6.2

CLINICAL PHARMACOLOGY

Flebogamma® 5% was administered as an IV infusion (300 to 600 mg/kg) to subjects with primary humoral immunodeficiency disease (PID) every 3 (n = 11) or 4 (n = 10) weeks for 12 months. The pharmacokinetics of total IgG was determined after the 7th infusion for the 3-week dosing interval and after the 5th infusion for the 4-week dosing interval (Table 2).

Table 2. Pharmacokinetic Variables of Total IgG in Patients with PID

Variable	3-Week Dosing Interval		4-Week Dosing Interval
	Mean	SD	Mean	SD
a The numbers in brackets are the minimum and maximum values.
b For a subject on the 3-week schedule, the average of the trough levels from Infusion 7 to the end of the study was calculated; for those on a 4-week schedule, the average of the trough levels from Infusion 5 to the end of the study was calculated. The means of the subject means are presented in this table.
Cmax (mg/dL)	1845	389	1900	277
	[1340 - 2430]a		[1490 - 2430]
AUC0 - ∞ (day·mg/dL)	63388	29583	91337	35915
	[18570 - 119909]		[48360 - 161073]
Clearance (mL/day)	70	58	40	21
	[23 - 177]		[20 - 78]
Half-life (days)	30	12	45	17
	[13 - 54]		[23 - 75]
Trough IgG level (mg/dL)b	832.7	822.2	870.4	856.3
	[317.4 - 1207.5]		[660.0 - 1111.0]

Pharmacokinetic data for antibodies to specific antigens are in Table 3.

Table 3. Summary of Pharmacokinetic Data for Antibodies to Specific Antigens

Test (unit)	Statistic	3-Week Dosing Interval			4-Week Dosing Interval
		Cmax (mg/dL)	Trough (mg/dL)	Half-life (days)	Cmax (mg/dL)	Trough (mg/dL)	Half-life (days
CMV IgG (IV)	Mean (SD)	30 (36)	11 (16)	22 (9)	30 (10)	12 (8)	30 (8)
	Min - Max	14 - 138	3 - 58	13 - 38	18 - 48	5 - 25	21 - 45
S. pneumoniae	Mean (SD)	12 (4)	6 (4)	23 (8)	13 (4)	6 (2)	29 (4)
Type 14 (μg/mL)	Min – Max	7 - 21	2 - 18	14 - 33	9 - 22	3 - 10	22 - 33
S. pneumoniae	Mean (SD)	14 (12)	5 (7)	41 (39)	9 (2)	4 (1)	25 (6)
Type 19F (μg/mL)	Min – Max	6 - 43	1 - 25	11 - 132	7 - 13	2 - 6	16 - 36
S. pneumoniae	Mean (SD)	2 (0.5)	1 (0.4)	50 (77)	2 (1)	1 (1)	43 (24)
Type 4 (μg/mL)	Min – Max	1 - 2	0 - 2	10 - 254	1 - 4	0 - 2	21 - 82
S. pneumoniae	Mean (SD)	9 (2)	4 (2)	29 (21)	9 (3)	4 (1)	36 (22)
Type 6B (μg/mL)	Min – Max	6 - 13	1 - 9	13 - 73	7 - 15	2 - 7	21 - 86
S. pneumoniae	Mean (SD)	12 (6)	4 (2)	45 (60)	11 (4)	4 (1)	42 (42)
Type 9V (μg/mL)	Min – Max	6 - 25	1 - 8	11 - 170	8 - 18	2 - 6	17 - 143
Tetanus Antitoxoid	Mean (SD)	12 (2)	5 (2)	23 (11)	14 (3)	5 (1)	28 (11)
Antibody (IU/mL)	Min - Max	9 - 16	2 - 8	11 - 45	10 - 18	3 - 6	13 - 41

There is evidence that the half-life of IgG can vary considerable among patients (2-5).

There were 2 adolescent (≤ 16 years of age) subjects who underwent pharmacokinetic testing, and both of them were on the 3-week infusion schedule. There were no clinically relevant differences among the adults and adolescents that were tested.

Clinical:

Grifols-04-I was a multicenter, open-label, historically controlled study conducted in the United States. A total of 51 subjects were enrolled, and their data were analyzed for safety and efficacy. The primary efficacy variable was the number of episodes of the following serious infections: bacterial pneumonia, bacteremia or sepsis, osteomyelitis/septic arthritis, visceral abscesses and bacterial meningitis. The secondary efficacy variables were the number of days of work/school missed, the number of hospitalizations and the number of days of each hospitalization, the number of visits to physicians or emergency rooms, and the number of other infections documented by positive radiographic findings and fever.

The results showed that subjects had a serious infection rate of 0.061 infections/subject/year (98% confidence interval = 0.011 to 0.183), a rate that is much less than 1 infection/subject/year. With regard to the secondary efficacy variables, the mean rate was less than 10 days or visits/subject/year (Table 4), and there were no other infections documented by positive radiographic findings and fever.

Table 4. Summary of Secondary Efficacy Variables

Variable	Subjects		Total Days or Visits	Total Subject Years	Days or Visits/Subject/Year
	N	%			Estimatea	95% C. I.b
a Estimate = Total days or visits/total subject years.
b The 95% confidence intervals were obtained by using a generalized linear model procedure for Poisson distribution.
Work/School Days Missed	22	43	328	50.8	6.46	5.69, 7.29
Days in Hospital	9	18	54	50.9	1.1	0.77, 1.42
Visits to Physician/ER	40	78	201	50.9	3.95	3.36, 4.61

The dosing statistics for this study are in Table 5.

Table 5. Statistical Summary of the Mean Total Dose (mg/kg) of Flebogamma® 5% Administered Per Infusion

Statistic	3-Week Dosing Interval	4-Week Dosing Interval	Total
a Q1 is the 25th percentile, and Q3 is the 75th percentile.
n	15	36	51
Mean (SD)	437.5 (92.07)	427.0 (78.44)	430.1 (81.88)
Median	442.8	432.3	436.2
Q1, Q3a	378.8, 480.8	367.9, 498.4	375.5, 497.0
Min, Max	307.0, 609.4	248.4, 572.4	248.4, 609.4

INDICATIONS AND USAGE

Flebogamma® 5% is indicated for replacement therapy in primary (inherited) humoral immunodeficiency disorders, such as common variable immunodeficiency, x-linked agammaglobulinemia, severe combined immunodeficiency, and Wiskott-Aldrich Syndrome. Flebogamma® 5% is especially useful when rapid replacement of IgG or the attainment of high serum levels of IgG is desired.

Some clinical trials conducted with Flebogamma® 5% included infants, children, and adolescents with primary and secondary immunodeficiency diseases to assess clinical efficacy. Data have also been obtained from postmarketing studies and postmarketing surveillance. Clinical trials with Flebogamma® 5% enrolled a very limited number of children and adolescents with primary humoral immune deficiency, a number insufficient to fully characterize the efficacy and safety in pediatric patients [See PRECAUTIONS, Pediatric Use].

CONTRAINDICATIONS

Flebogamma® 5% should not be administered to individuals with a history of severe or anaphylactic reactions to blood or blood-derived products. Individuals with selective IgA deficiency and demonstrable antibodies to IgA should not receive Flebogamma® 5%. If patients are known to be intolerant to any component of Flebogamma® 5%, such as sorbitol (i.e., intolerance to fructose), they should not receive the product.

WARNINGS

Immune Globulin Intravenous (Human) (IGIV) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death (6). Patients predisposed to acute renal failure include patients with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Especially in such patients, IGIV products should be administered at the minimum concentration available and the minimum rate of infusion practicable. While these reports of renal dysfunction and acute renal failure have been associated with the use of many of the licensed IGIV products, those containing sucrose as a stabilizer accounted for a disproportionate share of the total number. Flebogamma® 5% does not contain sucrose.

See PRECAUTIONS and DOSAGE AND ADMINISTRATION sections for important information intended to reduce the risk of acute renal failure.

Flebogamma® 5% is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, and theoretically, the Creutzfeldt-Jakob (CJD) agent that can cause disease. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses. (See DESCRIPTION section). Plasma pools for manufacture are screened using Nucleic Acid Testing with polymerase chain reaction technology for HIV-1 and HCV. Two steps in the manufacturing process, Pasteurization for 10 hours at 60 degrees centigrade and Polyethylene Glycol precipitation, have been evaluated and demonstrated to provide cumulative log reductions exceeding 6 logs for all the tested viruses. Despite these measures, such IGIV products can still potentially transmit disease. ALL infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Grifols Biologicals at 888-GRIFOLS (888-474-3657). Physicians should discuss the potential risks and benefits of the use of this product with the patient.

All patients, but especially individuals receiving Flebogamma® 5% for the first time or being restarted on the product after a treatment hiatus of more than 8 weeks, may be at risk for the development of inflammatory reactions characterized by fever, chills, nausea, and vomiting. Careful monitoring of recipients and adherence to recommendations regarding information in the DOSAGE AND ADMINISTRATION section may reduce the risk of these types of events.

Appropriate supportive care, including immediate access to epinephrine injection, should be available for the management of acute anaphylactic reactions.

PRECAUTIONS

General:

Any vial that has been entered should be used promptly. Partially used vials should be discarded and not saved for future use because the solution contains no preservative. Do not use if turbid. Solution that has been frozen should not be used.

Ensure that patients are not volume-depleted before the initiation of the infusion of IGIV.

Renal Function:

Periodic monitoring of renal function and urine output is particularly important in patients judged to have a potential increased risk for developing acute renal failure (6). Renal function, including measurement of blood urea nitrogen (BUN)/serum creatinine, should be assessed before the initial infusion of Flebogamma® 5% and again at appropriate intervals thereafter. If renal function deteriorates, discontinuation of the product should be considered.

For patients judged to be at risk for developing renal dysfunction, it may be prudent to reduce the amount of product infused per unit time by infusing Flebogamma® 5% at a maximum rate less than 0.06 mL/kg (3 mg/kg) body weight/minute.

Aseptic Meningitis Syndrome:

An aseptic meningitis syndrome (AMS) has been reported to occur infrequently in association with IGIV treatment. The syndrome usually begins within several hours to 2 days following IGIV treatment. It is characterized by symptoms and signs including severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, and nausea and vomiting. Cerebrospinal fluid (CSF) studies are frequently positive with pleocytosis up to several thousand cells per cubic milliliter, predominantly from the granulocytic series, and with elevated protein levels up to several hundred mg/dL. Patients exhibiting such symptoms and signs should receive a thorough neurological examination, including CSF studies, to rule out other causes of meningitis. AMS may occur more frequently in association with high-dose (e.g., >1.0 g/kg body weight) and/or rapid-infusion IGIV treatment. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae (7-10).

Hemolysis:

Immune Globulin Intravenous (Human) (IGIV) products can contain blood group antibodies which may act as hemolysins and induce in vivo coating of red blood cells with immunoglobulin, causing a positive direct antiglobulin reaction and, rarely, hemolysis (11-13). Hemolytic anemia can develop subsequent to IGIV therapy due to enhanced RBC sequestration (14) [See ADVERSE REACTIONS]. IGIV recipients should be monitored for clinical signs and symptoms of hemolysis [See PRECAUTIONS: Laboratory Tests].

Thrombotic Events:

Thrombotic events have been reported in association with IGIV (15-17) (See ADVERSE REACTIONS). Patients at risk may include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, and/or known or suspected hyperviscosity. The potential risks and benefits of IGIV should be weighed against those of alternative therapies for all patients for whom IGIV administration is being considered. Baseline assessment of blood viscosity should be considered in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies [See PRECAUTIONS: Laboratory Tests].

Transfusion-Related Acute Lung Injury (TRALI):

There have been reports of noncardiogenic pulmonary edema [Transfusion-Related Acute Lung Injury (TRALI)] in patients administered IGIV (18). TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever and typically occurs within 1 to 6 hours after transfusion. Patients with TRALI may be managed by using oxygen therapy with adequate ventilatory support.

IGIV recipients should be monitored for pulmonary adverse reactions. If TRALI is suspected, appropriate tests should be performed for the presence of antineutrophil antibodies in both the product and patient serum [See PRECAUTIONS: Laboratory Tests].

Information for Patients:

Patients should be instructed to immediately report symptoms of decreased urine output, sudden weight gain, fluid retention/edema, and/or shortness of breath (which may suggest kidney damage) to their physicians.

It is recommended that the lot number of the vials used be recorded when Flebogamma® 5% is administered.

Laboratory Tests:

Renal function, including measurement of blood urea nitrogen (BUN)/serum creatinine, should be assessed before the initial infusion of Flebogamma® 5% in patients judged to have a potential increased risk for developing acute renal failure and again at appropriate intervals thereafter.

Following infusion of Flebogamma® 5%, there may be a transitory rise of various antibody titers that may result in misleading positive results in serological testing.

Baseline assessment of blood viscosity should be considered in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies.

If TRALI is suspected, appropriate tests should be performed for the presence of antineutrophil antibodies in both the product and patient serum.

Pregnancy Category C:

Animal reproduction studies have not been performed with Flebogamma® 5%. It is also not known whether Flebogamma® 5% can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Flebogamma® 5% should be given to a pregnant woman only if clearly needed.

Drug Interactions:

Antibodies in Flebogamma® 5% may interfere with the response to live viral vaccines, such as measles, mumps, and rubella. Physicians should be informed of recent therapy with Immune Globulin Intravenous (Human) so that administration of live viral vaccines, if indicated, can be appropriately delayed 3 or more months from the time of IGIV administration.

Pediatric Use:

Ninety-four pediatric subjects, including 15 who were diagnosed with primary humoral immunodeficiency, have received Flebogamma® 5% in the course of clinical studies or postmarketing studies over a 14-year period. Although preliminary safety data in children and adolescents with primary humoral immune deficiency who received Flebogamma® 5% or other Immune Globulin Intravenous (Human) products produced by the same manufacturing method in different manufacturing facilities from that used for the production of Flebogamma® 5% has not revealed differences between the safety profiles of the product(s) in pediatric and adult patients, the experience has been too limited to consider the safety and efficacy of Flebogamma® 5% to be established in children and adolescents.

Geriatric Use:

Subjects over 65 are at increased risk of renal failure with IGIV treatment. For these subjects, and for any other subjects at risk of renal failure, the infusion rate of Flebogamma® 5% should be limited to < 0.06 mL/kg/min (3 mg/kg/min).

Adverse Reactions

Increases of creatinine and blood urea nitrogen (BUN) have been observed as soon as 1 to 2 days following infusion of IGIV. Progression to oliguria and anuria requiring dialysis has been observed, although some patients have improved spontaneously following cessation of treatment (19). Types of severe renal adverse reactions that have been seen following IGIV therapy include: acute renal failure, acute tubular necrosis (20), proximal tubular nephropathy, and osmotic nephrosis (6).

Certain severe adverse reactions may be related to the rate of infusion. The recommended infusion rate [See DOSAGE AND ADMINISTRATION] must be closely followed. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period. Adverse reactions may occur more frequently when a high infusion rate is used, the treatment is the initial exposure to immunoglobulin, the immunoglobulin product has been changed to that of a different manufacturer, or there has been a long interval (more than 8 weeks) since the previous infusion. Slowing or stopping an infusion usually results in the prompt disappearance of symptoms.

Postmarketing:

The following adverse reactions have been identified and reported during the post-approval use of IGIV products (21).

Respiratory	Apnea, Acute Respiratory Distress Syndrome (ARDS), Transfusion-Related Acute Lung Injury (TRALI), cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm
Cardiovascular	Cardiac arrest, thromboembolism, vascular collapse, hypotension
Neurological	Coma, loss of consciousness, seizures, tremor
Integumentary	Stevens-Johnson Syndrome, epidermolysis, erythema multiformae, bullous dermatitis
Hematologic	Pancytopenia, leukopenia, hemolysis, positive direct antiglobulin (Coombs) test
General/Body as a Whole	Pyrexia, rigors
Musculoskeletal	Back pain
Gastrointestinal	Hepatic dysfunction, abdominal pain

Because postmarketing reporting of these reactions is voluntary and the at-risk populations are of uncertain size, it is not always possible to reliably estimate the frequency of the reaction or establish a causal relationship to exposure to the product. Such is also the case with literature reports authored independently.

Adverse events were reported in a study of 51 individuals with primary humoral immunodeficiency diseases receiving infusions every 3 to 4 weeks of 300 to 600 mg/kg body weight. Forty-nine (96%) subjects experienced at least 1 adverse event irrespective of the relationship with the product, and these subjects reported a total of 784 adverse events. None of the 51 subjects who participated in this study discontinued the study prematurely due to an adverse experience.

Adverse events that occurred with an incidence of > 15% on a per subject basis are summarized in Table 6. No adverse events occurred with an incidence of > 2% on a per infusion basis.

Table 6. Adverse Events Occurring with an Incidence of > 15%

Adverse Event	Number of AEs	Number of Subjects with AE	Percent of Subjects with AE
a NOS = not otherwise specified.
Bronchitis	17	10	20
Cough and productive cough	26	13	25
Diarrhoea NOSa	16	10	20
Headache NOS and sinus headache	61	27	53
Nasal congestion	22	11	21
Pain NOS	14	8	16
Pyrexia	31	14	27
Rhinorrhoea	16	10	20
Sinusitis NOS	43	20	39
Sore throat NOS	13	10	20
Upper Respiratory tract infection	22	17	33
Wheezing and asthma aggravated	24	9	18

Forty-six (90%) subjects had 331 adverse events that occurred during an infusion or within 72 hours after the completion of the infusion. Therefore 42% of all adverse events, regardless of assessed causality, were temporally associated with the infusion of Flebogamma® 5%.

Overall, 217 of 746 infusions (29%) were temporally associated with 1 or more adverse events occurring within 72 hours after an infusion, regardless of assessed relationship to treatment; the 1-sided, 95%, upper-bound confidence interval was 34%.

A summary of infusions with mild, moderate, and severe treatment-related adverse events is in Table 7.

Table 7. Summary of Infusions with Mild, Moderate, and Severe Treatment-Related Adverse Events

Severity of AE	No. Infusions with AE	Adjusted %a	Confidence Intervalb
a Adjusted % = average of the % of infusions with a treatment-related adverse event for each individual subject.
b The 95% upper bound for the adjusted % of infusions for which at least 1 treatment-related adverse event was reported was derived by using the t-statistic.
Mild	49	6.2	8.4
Moderate	12	1.5	2.3
Severe	3	0.4	0.8

The number and percent of subjects with treatment-emergent rises in AST or ALT are in Table 8.

Table 8. Number (%) of