Pontocaine

Generic Name: tetracaine topical (TET ra kane TOP ik al)

Brand Names: Pontocaine, Viractin

What is Pontocaine (tetracaine topical)?

Tetracaine is a local anesthetic (numbing medication). It works by blocking nerve signals in your body.

Tetracaine topical cream or ointment is used to reduce pain or discomfort caused by minor skin irritations, cold sores or fever blisters, sunburn or other minor burns, insect bites or stings, and many other sources of minor pain on a surface of the body.

Tetracaine topical solution is used to numb the skin or surfaces inside the mouth, nose, and throat to lessen the pain of inserting a medical instrument such as a tube or scope. The solution may also be used to numb the surface of the eyes before a diagnostic or procedure.

Tetracaine topical may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Pontocaine (tetracaine topical)?

An overdose of numbing medications can cause fatal side effects if too much of the medicine is absorbed through your skin and into your blood. This is more likely to occur when using a numbing medicine without the advice of a medical doctor (such as during a cosmetic procedure like laser hair removal). Overdose symptoms may include uneven heartbeats, seizure (convulsions), coma, slowed breathing, or respiratory failure (breathing stops). Your body may absorb more of this medication if you use too much, if you apply it over large skin areas, or if you apply heat, bandages, or plastic wrap to treated skin areas. Skin that is cut or irritated may also absorb more topical medication than healthy skin.

Use the smallest amount of this medication needed to numb the skin or relieve pain. Do not use large amounts of tetracaine topical, or cover treated skin areas with a bandage or plastic wrap without medical advice. Be aware that many cosmetic procedures are performed without a medical doctor present.

Do not use this medication if you are allergic to tetracaine or other numbing medicines such as lidocaine, benzocaine, or prilocaine.

Call your doctor if your symptoms do not improve or if they get worse within the first 7 days of using tetracaine topical. Also call your doctor if your symptoms had cleared up but then came back.

What should I discuss with my health care provider before using Pontocaine (tetracaine topical)?

An overdose of numbing medications can cause fatal side effects if too much of the medicine is absorbed through your skin and into your blood. This is more likely to occur when using a numbing medicine without the advice of a medical doctor (such as during a cosmetic procedure like laser hair removal). Overdose symptoms may include uneven heartbeats, seizure (convulsions), coma, slowed breathing, or respiratory failure (breathing stops). Do not use this medication if you are allergic to tetracaine or similar numbing medications such as lidocaine, benzocaine, or prilocaine.

Before using tetracaine topical, tell your doctor about all of your medical conditions. You may not be able to use tetracaine topical, or you may need a dosage adjustment or special tests during treatment.

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether tetracaine topical passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I use Pontocaine (tetracaine topical)?

Use this medication exactly as directed on the label, or as it has been prescribed by your doctor. Do not use the medication in larger or smaller amounts, or use it for longer than recommended.

Your body may absorb more of this medication if you use too much, if you apply it over large skin areas, or if you apply heat, bandages, or plastic wrap to treated skin areas. Skin that is cut or irritated may also absorb more topical medication than healthy skin.

Use the smallest amount of medicine needed to numb the skin or relieve pain. Do not use large amounts of tetracaine topical, or cover treated skin areas with a bandage or plastic wrap without medical advice. Be aware that many cosmetic procedures are performed without a medical doctor present.

This medication comes with instructions for safe and effective application. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

To treat minor skin conditions, apply a thin layer of tetracaine topical to the affected area up to 4 times per day.

Do not use tetracaine topical to treat large skin areas or deep puncture wounds. Avoid using the medicine on skin that is raw or blistered, such as a severe burn or abrasion.

Call your doctor if your symptoms do not improve or if they get worse within the first 7 days of using tetracaine topical. Also call your doctor if your symptoms had cleared up but then came back.

Store tetracaine topical cream or ointment at room temperature away from moisture and heat. Tetracaine topical solution should be stored in the refrigerator and kept from freezing.

What happens if I miss a dose?

Since tetracaine topical is used as needed, you may not be on a dosing schedule. If you are using the medication regularly, use the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and wait until your next regularly scheduled dose. Do not use extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine. An overdose of tetracaine topical applied to the skin can cause life-threatening side effects such as uneven heartbeats, seizure (convulsions), coma, slowed breathing, or respiratory failure (breathing stops).

What should I avoid while taking Pontocaine (tetracaine topical)?

Tetracaine topical is for use only on the surface of your body. Avoid swallowing the medication, or getting the cream or ointment in your eyes while applying it.

If tetracaine topical solution has been used in your eyes, avoid rubbing the eyes or exposing them to irritating chemicals or pollutants. Follow your doctor's instructions about covering the eye(s) for a short period of time.

Pontocaine (tetracaine topical) 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 tetracaine topical and call your doctor at once if you have any of these serious side effects:

• 
  

  severe burning, stinging, or sensitivity where the medicine is applied;

  
  


• 
  

  swelling, warmth, or redness;

  
  


• 
  

  oozing, blistering, or any signs of infection; or

  
  


• 
  

  eye irritation, watering, or increased sensitivity to light.

  
  

Rare but serious side effects may include:

• 
  

  nervousness, dizziness, blurred vision;

  
  


• 
  

  drowsiness, feeling like you might pass out;

  
  


• 
  

  breathing problems;

  
  


• 
  

  fast or slow heart rate; and

  
  


• 
  

  weak pulse, fainting, slow breathing (breathing may stop).

  
  

Less serious side effects may include:

• 
  

  mild stinging, burning, or itching where the medicine is applied;

  
  


• 
  

  skin tenderness or redness; or

  
  


• 
  

  dry white flakes where the medicine was applied.

  
  

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Pontocaine (tetracaine topical)?

There may be other drugs that can affect tetracaine topical. Do not apply other medications to the same affected areas you treat with tetracaine topical, unless your doctor has told you otherwise.

Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Pontocaine resources

• Pontocaine Support Group
• 0 Reviews for Pontocaine - Add your own review/rating

• Pontocaine Advanced Consumer (Micromedex) - Includes Dosage Information

Compare Pontocaine with other medications

• Allergic Urticaria
• Cold Sores
• Local Anesthesia
• Skin Rash
• Urticaria

Where can I get more information?

• Your pharmacist can provide more information about tetracaine topical.

Minocin MR 100mg Modified Release Capsules (Meda Pharmaceuticals )

1. Name Of The Medicinal Product

MINOCIN MR 100mg Modified Release Capsules

2. Qualitative And Quantitative Composition

MINOCIN MR Capsules contain 100mg of the active ingredient minocycline (equivalent to 116 mg of minocycline hydrochloride as the dehydrate salt).

For a full list of excipients see 6.1

3. Pharmaceutical Form

Modified release capsule.

Two piece, hard shell, size 2 capsules with an orange opaque body and a brown opaque cap.

4. Clinical Particulars

4.1 Therapeutic Indications

MINOCIN MR Capsules are indicated for the treatment of acne.

4.2 Posology And Method Of Administration

Dosage:

Adults: One 100mg capsule every 24 hours.

Children over 12 years: One 100mg capsule every 24 hours.

Children under 12 years: MINOCIN is not recommended.

Elderly: No special dosing requirements.

Administration:

To reduce the risk of oesophageal irritation and ulceration, the capsules should be swallowed whole with plenty of fluid, while sitting or standing. Unlike earlier tetracyclines, absorption of Minocin MR is not significantly impaired by food or moderate amounts of milk.

Treatment of acne should be continued for a minimum of 6 weeks. If, after six months, there is no satisfactory response Minocin MR should be discontinued and other therapies considered. If Minocin MR is to be continued for longer than six months, patients should be monitored at least three monthly thereafter for signs and symptoms of hepatitis or SLE or unusual pigmentation (see Special Warnings and Precautions).

4.3 Contraindications

Known hypersensitivity to tetracyclines, or to any of the components of Minocin MR. Use in pregnancy, lactation, children under the age of 12 years, complete renal failure.

4.4 Special Warnings And Precautions For Use

Minocin MR should be used with caution in patients with hepatic dysfunction and in conjunction with alcohol and other hepatotoxic drugs. It is recommended that alcohol consumption should remain within the Government's recommended limits.

Rare cases of auto-immune hepatotoxicity and isolated cases of systemic lupus erythematosus (SLE) and also exacerbation of pre-existing SLE have been reported. If patients develop signs or symptoms of SLE or hepatotoxicity, or suffer exacerbation of pre-existing SLE, minocycline should be discontinued.

Clinical studies have shown that there is no significant drug accumulation in patients with renal impairment when they are treated with Minocin MR in the recommended doses. In cases of severe renal insufficiency, reduction of dosage and monitoring of renal function may be required. The anti-anabolic action of the tetracyclines may cause an increase in serum urea. In patients with significantly impaired renal function, higher serum levels of tetracyclines may lead to uraemia, hyperphosphataemia and acidosis. If renal impairment exists, even usual oral and parenteral doses may lead to excessive systemic accumulations of the drug and possible liver toxicity.

Caution is advised in patients with myasthenia gravis as tetracyclines can cause weak neuromuscular blockade.

Cross-resistance between tetracyclines may develop in micro-organisms and cross-sensitisation in patients. Minocin MR should be discontinued if there are signs/symptoms of overgrowth of resistant organisms, e.g. enteritis, glossitis, stomatitis, vaginitis, pruritus ani or Staphylococcal enteritis.

Patients taking oral contraceptives should be warned that if diarrhoea or breakthrough bleeding occur there is a possibility of contraceptive failure.

Minocycline may cause hyperpigmentation at various body sites (see Administration and 4.8 Undesirable Effects). Hyperpigmentation may present regardless of dose or duration of therapy but develops more commonly during long term treatment. Patients should be advised to report any unusual pigmentation without delay and Minocin should be discontinued.

If a photosensitivity reaction occurs, patients should be warned to avoid direct exposure to natural or artificial light and to discontinue therapy at the first signs of skin discomfort.

As with other tetracyclines, bulging fontanelleles in infants and benign intracranial hypertension in juveniles and adults have been reported. Presenting features were headache and visual disturbances including blurring of vision, scotoma and diplopia. Permanent vision loss has been reported. Treatment should cease if evidence of raised intracranial pressure develops.

Use in the elderly:

Dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Use in children:

The use of tetracyclines during tooth development in children under the age of 12 years may cause permanent discolouration. Enamel hypoplasia has also been reported.

Laboratory monitoring:

Periodic laboratory evaluations of organ system function, including haematopoietic, renal and hepatic should be conducted.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Tetracyclines depress plasma prothrombin activity and reduced doses of concomitant anticoagulants may be necessary.

Diuretics may aggravate nephrotoxicity by volume depletion.

Bacteriostatic drugs may interfere with the bactericidal action of penicillin. Avoid giving tetracycline-class drugs in conjunction with penicillin. Absorption of Minocin MR is impaired by the concomitant administration of antacids, iron, calcium, magnesium, aluminium bismuth and zinc salts (interactions with specific salts, antacids, bismuth containing ulcer – healing drugs, quinapril which contains a magnesium carbonate excipient). It is recommended that any indigestion remedies, vitamins, or other supplements containing these salts are taken at least 3 hours before or after a dose of Minocin MR. Unlike earlier tetracyclines, absorption of Minocin MR is not significantly impaired by food or moderate amounts of milk.

There is an increased risk of ergotism when ergot alkaloids or their derivatives are given with tetracyclines.

The concomitant use of tetracyclines may reduce the efficacy of oral contraceptives.

Administration of isotretinoin or other systemic retinoids or retinol should be avoided shortly before, during and shortly after minocycline therapy. Each of these agents alone has been associated with pseudotumor cerebri (benign intracranial hypertension) (see 4.4 Special warnings and precautions).

Interference with laboratory and other diagnostic tests:

False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.

4.6 Pregnancy And Lactation

Use in pregnancy:

Minocin MR should not be used in pregnancy unless considered essential.

Results of animal studies indicate that tetracyclines cross the placenta, are found in foetal tissues and can have toxic effects on the developing foetus (often related to retardation of skeletal development). Evidence of embryotoxicity has also been noted in animals treated early in pregnancy. Minocin MR therefore, should not be used in pregnancy unless considered essential

In humans, Minocin, like other tetracycline-class antibiotics, crosses the placenta and may cause foetal harm when administered to a pregnant woman. In addition, there have been post marketing reports of congenital abnormalities including limb reduction. If Minocin is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to the foetus.

The use of drugs of the tetracycline class during tooth development (last half of pregnancy) may cause permanent discolouration of the teeth (yellow-grey-brown). This adverse reaction is more common during long term use of the drugs but has been observed following repeated short term courses. Enamel hypoplasia has also been reported.

Tetracyclines administered during the last trimester form a stable calcium complex throughout the human skeleton. A decrease in fibula growth rate has been observed in premature human infants given oral tetracyclines in doses up to 25mg/kg every 6 hours. Changes in fibula growth rate were shown to be reversible when the drug was discontinued.

Use in lactation:

Tetracyclines have been found in the milk of lactating women who are taking a drug in this class. Permanent tooth discolouration may occur in the developing infant and enamel hypoplasia has been reported.

4.7 Effects On Ability To Drive And Use Machines

Headache, light-headedness, dizziness, tinnitus and vertigo (more common in women) and, rarely, impaired hearing have occurred with Minocin MR. Patients should be warned about the possible hazards of driving or operating machinery during treatment. These symptoms may disappear during therapy and usually disappear when the drug is discontinued.

4.8 Undesirable Effects

Adverse reactions are listed in the Table in CIOMS frequency categories under MedDRA system/organ classes:

Common:

Uncommon:

Rare:

Very Rare: < 0.01%

Infections and Infestations

Very Rare: Oral and anogenital candidiasis, vulvovaginitis.

Blood and Lymphatic System Disorders

Rare: Eosinophilia, leucopenia, neutropenia, thrombocytopenia.

Very Rare: Haemolytic anaemia, pancytopenia.

There are also reports of: Agranulocytosis

Immune System Disorders

Rare: Anaphylaxis /anaphylactoid reaction (including shock), including fatalities.

There are also reports of: Hypersensitivity, pulmonary infiltrates, anaphylactoid purpura.

Endocrine Disorders

Very Rare: Abnormal thyroid function, brown-black discolouration of the thyroid.

Metabolism and Nutrition Disorders

Rare: Anorexia.

Nervous System Disorders

Common: Dizziness (light-headedness).

Rare: Headache, hypaesthesia, paraesthesia, intracranial hypertension, vertigo.

Very Rare: Bulging fontanelle.

There are also reports of: convulsions, sedation.

Ear and Labyrinth Disorders

Rare: Impaired hearing, tinnitus.

Cardiac Disorders

Rare: Myocarditis, pericarditis.

Respiratory, Thoracic and Mediastinal Disorders

Rare: Cough, dyspnoea.

Very Rare: Bronchospasm, exacerbation of asthma, pulmonary eosinophilia.

There are also reports of: Pneumonitis.

Gastrointestinal Disorders

Rare: Diarrhoea, nausea, stomatitis, discolouration of teeth (including adult tooth discolouration), vomiting.

Very Rare: Dyspepsia, dysphagia, enamel hypoplasia, enterocolitis, oesophagitis, oesophageal ulceration, glossitis, pancreatitis, pseudomembranous colitis.

There are also reports of: Oral cavity discolouration (including tongue, lip and gum).

Hepatobiliary Disorders

Rare: Increased liver enzymes, hepatitis, autoimmune hepatoxicity. (See Section 4.4 Special warnings and precautions for use).

Very Rare: Hepatic cholestatis, hepatic failure (including fatalities), hyperbilirubinaemia, jaundice.

There are also reports of: Autoimmune hepatitis.

Skin and Subcutaneous Tissue Disorders

Rare: Alopecia, erythema multiforme, erythema nodosum, fixed drug eruption, hyperpigmentation of skin, photosensitivity, pruritis, rash, urticaria, vasculitis.

Very Rare: Angioedema, exfoliative dermatitis, hyperpigmentation of nails, Stevens-Johnson Syndrome, toxic epidermal necrolysis.

Musculoskeletal, Connective Tissue and Bone Disorders

Rare: Arthralgia, lupus-like syndrome, myalgia.

Very Rare: Arthritis, bone discolouration, cases of or exacerbation of systemic lupus erythematosus (SLE) (See Section 4.4 Special warnings and precautions for use), joint stiffness, joint swelling.

Renal and Urinary Disorders

Rare: Increased serum urea, acute renal failure, interstitial nephritis.

Reproductive System and Breast Disorders

Very Rare: Balanitis.

General Disorders and Administration Site Conditions

Uncommon: Fever.

Very Rare: Discolouration of secretions.

The following syndromes have been reported. In some cases involving these syndromes, death has been reported. As with other serious adverse reactions, if any of these syndromes are recognised, the drug should be discontinued immediately:

• Hypersensitivity syndrome consisting of cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, and one or more of the following: hepatitis, pneumonitis, nephritis, myocarditis, pericarditis. Fever and lymphadenopathy may be present.

• Lupus-like syndrome consisting of positive antinuclear antibody, arthralgia, arthritis, joint stiffness or joint swelling, and one or more of the following: fever, myalgia, hepatitis, rash, vasculitis.

• Serum sickness-like syndrome consisting of fever, urticaria or rash, and arthralgia, arthritis, joint stiffness or joint swelling. Eosinophilia may be present.

Hyperpigmentation of various body sites including the skin, nails, teeth, oral mucosa, bones, thyroid, eyes (including sclera and conjunctiva), breast milk, lacrimal secretions and perspiration has been reported. This blue/black/grey or muddy-brown discolouration may be localised or diffuse. The most frequently reported site is in the skin. Pigmentation is often reversible on discontinuation of the drug, although it may take several months or may persist in some cases. The generalised muddy-brown skin pigmentation may persist, particularly in areas exposed to the sun.

4.9 Overdose

Dizziness, nausea and vomiting are the adverse effects most commonly seen with overdose. There is no specific antidote. In cases of overdose, discontinue medication, treat symptomatically with appropriate supportive measures. Minocin is not removed in significant quantities by haemodialysis or peritoneal dialysis.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

MINOCIN MR Capsules contain the active ingredient minocycline as minocycline hydrochloride, a semi-synthetic derivative of tetracycline.

5.2 Pharmacokinetic Properties

MINOCIN MR Capsules have been formulated as a "double pulse" delivery system in which a portion of the minocycline dose is delivered in the stomach, and a second portion of the dose is available for absorption in the duodenum and upper GI tract.

5.3 Preclinical Safety Data

None stated.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Pellets:	Microcrystalline cellulose
	Croscarmellose sodium
	Hypromellose phthalate 50
	Hypromellose (E464)
	Light liquid paraffin
	Methylene Chloride
	Methanol
	Purified Water
	Opaspray K-1-7000 (white), (containing:	Titanium dioxide
		Hydroxypropylcellulose)
Capsule shells:	Titanium dioxide (E171)
	Iron oxide yellow (E172)
	Iron oxide red (E172)
	Iron oxide black (E172)
	Gelatin
Capsule Cap:	Titaniurn Dioxide
	Iron Oxide red (E172)
	Iron Oxide black (E172)
	Iron Oxide yellow (E172)
	Gelatin

6.2 Incompatibilities

None known.

6.3 Shelf Life

18 months.

6.4 Special Precautions For Storage

Do not store above 25°C.

Blisters: Store in the original package

Keep the container in the outer carton

Bottles: Store in the original container

Keep the container tightly closed

6.5 Nature And Contents Of Container

PVC/PVDC aluminium blister packs containing 2, 49 and 56 capsules.

Polypropylene bottle with urea cap containing 100 capsules.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Meda Pharmaceuticals Ltd

249 West George Street

Glasgow

G2 4RB

Trading as:

Meda Pharmaceuticals Ltd

Skyway House

Parsonage Road

Takeley

Bishop's Stortford

CM22 6PU

8. Marketing Authorisation Number(S)

PL 15142/0101

9. Date Of First Authorisation/Renewal Of The Authorisation

14^th February 2005

10. Date Of Revision Of The Text

11^th August 2010

Chlor-Trimeton

Generic Name: chlorpheniramine (KLOR fen IR a meen)

Brand Names: AHist, Aller-Chlor, Allergy Relief, C.P.M., Chlo-Amine, Chlor-Mal, Chlor-Trimeton, Chlor-Trimeton Allergy SR, Chlorphen, ChlorTan, Ed Chlor-Tan, Ed ChlorPed, PediaTan, TanaHist-PD, Triaminic Allergy, Wal-finate

What is Chlor-Trimeton (chlorpheniramine)?

Chlorpheniramine is an antihistamine that reduces the natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Chlorpheniramine is used to treat sneezing, itching, watery eyes, and runny nose caused by allergies or the common cold.

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

What is the most important information I should know about Chlor-Trimeton (chlorpheniramine)?

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Do not take chlorpheniramine if you are allergic to it.

Ask a doctor or pharmacist before taking chlorpheniramine if you have glaucoma, a stomach ulcer, severe constipation, kidney disease, urination problems, an enlarged prostate, or a thyroid disorder.

Ask a doctor or pharmacist before using any other cold, cough, or allergy medicine. Chlorpheniramine is contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains an antihistamine.

Chlorpheniramine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of chlorpheniramine.

What should I discuss with my healthcare provider before taking Chlor-Trimeton (chlorpheniramine)?

Do not take this medication if you are allergic to chlorpheniramine. Do not use chlorpheniramine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

Ask a doctor or pharmacist if it is safe for you to take this medicine if you have:

• 
  

  glaucoma;

  
  


• 
  

  a stomach ulcer;

  
  


• 
  

  severe constipation;

  
  


• 
  

  kidney disease;

  
  


• 
  

  urination problems or an enlarged prostate; or

  
  


• 
  

  a thyroid disorder.

  
  

FDA pregnancy category B. Chlorpheniramine is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Chlorpheniramine can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. Older adults may be more likely to have side effects from this medication.

How should I take Chlor-Trimeton (chlorpheniramine)?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Cold or allergy medicine is usually taken only for a short time until your symptoms clear up.

Take this medication with a full glass of water. Take chlorpheniramine with food or milk if it upsets your stomach. Do not crush, chew, break, or open an extended-release tablet or capsule. Swallow it whole. Breaking or opening the pill may cause too much of the drug to be released at one time.

Measure liquid medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

This medication can cause unusual results with allergy skin tests. Tell any doctor who treats you that you are taking an antihistamine.

Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Since cold or allergy medicine is taken when needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

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

Overdose symptoms may include feeling restless or nervous, nausea, vomiting, stomach pain, dizziness, drowsiness, dry mouth, warmth or tingly feeling, or seizure (convulsions).

What should I avoid while taking Chlor-Trimeton (chlorpheniramine)?

Ask a doctor or pharmacist before using any other cold, cough, or allergy medicine. Chlorpheniramine is contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains an antihistamine.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Chlorpheniramine can decrease perspiration and you may be more prone to heat stroke.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of chlorpheniramine.

Chlor-Trimeton (chlorpheniramine) side effects

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

• 
  

  urinating less than usual or not at all;

  
  


• 
  

  confusion, extreme drowsiness;

  
  


• 
  

  severe dizziness, anxiety, restless feeling, nervousness; or

  
  


• 
  

  weak or shallow breathing.

  
  

Less serious side effects may include:

• 
  

  mild dizziness, drowsiness;

  
  


• 
  

  blurred vision;

  
  


• 
  

  dry mouth;

  
  


• 
  

  nausea, stomach pain, constipation;

  
  


• 
  

  problems with memory or concentration; or

  
  


• 
  

  feeling restless or excited (especially in children).

  
  

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.

What other drugs will affect Chlor-Trimeton (chlorpheniramine)?

Other cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by chlorpheniramine. Tell your doctor if you regularly use any of these medicines.

Tell your doctor about all other medicines you use, especially:

• 
  

  glycopyrrolate (Robinul);

  
  


• 
  

  mepenzolate (Cantil);

  
  


• 
  

  probenecid (Benemid, Probalan);

  
  


• 
  

  rifampin (Rifadin, Rifater, Rifamate, Rimactane);

  
  


• 
  

  zidovudine (Retrovir, AZT);

  
  


• 
  

  a diuretic (water pill);

  
  


• 
  

  atropine (Atreza, Sal-Tropine), belladonna (Donnatal, and others), benztropine (Cogentin), dimenhydrinate (Dramamine), methscopolamine (Pamine), or scopolamine (Transderm-Scop);

  
  


• 
  

  bladder or urinary medications such as darifenacin (Enablex), flavoxate (Urispas), oxybutynin (Ditropan, Oxytrol), tolterodine (Detrol), or solifenacin (Vesicare);

  
  


• 
  

  bronchodilators such as ipratropium (Atrovent) or tiotropium (Spiriva);

  
  


• 
  

  irritable bowel medications such as dicyclomine (Bentyl), hyoscyamine (Hyomax), or propantheline (Pro-Banthine); or

  
  


• 
  

  salicylates such as aspirin, Backache Relief Extra Strength, Novasal, Nuprin Backache Caplet, Doan's Pills Extra Strength, Pepto-Bismol, Tricosal, and others;

  
  

This list is not complete and other drugs may interact with chlorpheniramine. 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 Chlor-Trimeton resources

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

• Chlor-Trimeton MedFacts Consumer Leaflet (Wolters Kluwer)


• Aller-Chlor Syrup MedFacts Consumer Leaflet (Wolters Kluwer)


• Chlorpheniramine Maleate/Tannate, Dexchlorpheniramine Maleate Monograph (AHFS DI)


• Ed ChlorPed Suspension Drops MedFacts Consumer Leaflet (Wolters Kluwer)


• Pediox-S Suspension MedFacts Consumer Leaflet (Wolters Kluwer)


• QDALL AR Sustained-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Chlor-Trimeton with other medications

• Allergic Reactions
• Cold Symptoms
• Hay Fever
• Urticaria

Where can I get more information?

• Your pharmacist can provide more information about chlorpheniramine.

See also: Chlor-Trimeton side effects (in more detail)

CRM

Generic Name: chromium picolinate (KROME ee um pi KOE li nate)

Brand Names: Cr-GTF, CRM

What is CRM (chromium picolinate)?

Chromium is a mineral found in certain foods. The body needs only trace amounts of chromium, and deficiency of this mineral in humans is rare.

Chromium picolinate works together with insulin produced by the pancreas to metabolize carbohydrates.

Chromium picolinate has been used in alternative medicine as an aid to lowering cholesterol or improving the body's use of glucose (sugar). It is also commonly touted as a weight-loss supplement that aids in reducing body fat and increasing lean muscle.

Not all uses for chromium picolinate have been approved by the FDA. Chromium picolinate should not be substituted for prescription medications.

Chromium picolinate is often sold as an herbal supplement. There are no regulated manufacturing standards in place for many herbal compounds and some marketed supplements have been found to be contaminated with toxic metals or other drugs. Herbal/health supplements should be purchased from a reliable source to minimize the risk of contamination.

Chromium picolinate may also be used for other purposes not listed in chromium picolinate guide.

What is the most important information I should know about CRM (chromium picolinate)?

Not all uses for chromium picolinate have been approved by the FDA. Chromium picolinate should not be substituted for prescription medications.

Chromium picolinate is often sold as an herbal supplement. There are no regulated manufacturing standards in place for many herbal compounds and some marketed supplements have been found to be contaminated with toxic metals or other drugs. Herbal/health supplements should be purchased from a reliable source to minimize the risk of contamination.

Use chromium picolinate as directed on the label, or as your doctor has prescribed. Do not use this product in larger amounts or for longer than recommended.

Your healthcare provider may occasionally change your dose to make sure you get the best results from chromium picolinate. The recommended dietary allowance of chromium increases with age. Follow your healthcare provider's instructions.

Your dose needs may change if you have an injury, illness, or infection, if you are pregnant, if you are under stress, or if you exercise more than usual.

Chromium picolinate is only part of a complete program of treatment that may also include diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely.

Tell your healthcare provider about all other medications you use, especially insulin or diabetes medications you take by mouth, steroid medications, nicotinic acid, stomach acid reducers, asthma or blood pressure medications, aspirin, or an NSAID (non-steroidal anti-inflammatory drug).

What should I discuss with my health care provider before taking CRM (chromium picolinate)?

Before using chromium picolinate, talk to your doctor, pharmacist, herbalist, or other healthcare provider. You may not be able to use this product if you have:

• 
  

  liver disease;

  
  


• 
  

  diabetes;

  
  


• 
  

  cancer; or

  
  


• 
  

  a weak immune system.

  
  

Chromium picolinate may be harmful to an unborn baby. Do not use this product without talking to a healthcare provider if you are pregnant or plan to become pregnant during treatment. Chromium picolinate may pass into breast milk and may harm a nursing baby. Ask your healthcare provider before using this product if you are breast-feeding a baby. Do not give any herbal/health supplement to a child without the advice of a doctor.

How should I take CRM (chromium picolinate)?

When considering the use of herbal supplements, seek the advice of your doctor. You may also consider consulting a practitioner who is trained in the use of herbal/health supplements.

If you choose to take chromium picolinate, use it as directed on the package or as directed by your doctor, pharmacist, or other healthcare provider. Do not use more of this product than is recommended on the label.

Your healthcare provider may occasionally change your dose to make sure you get the best results from chromium picolinate. The recommended dietary allowance of chromium increases with age. Follow your healthcare provider's instructions. You may also consult the National Academy of Sciences "Dietary Reference Intake" or the U.S. Department of Agriculture's "Dietary Reference Intake" (formerly "Recommended Daily Allowances" or RDA) listings for more information.

Your dose needs may change if you have an injury, illness, or infection, if you are pregnant, if you are under stress, or if you exercise more than usual.

Chromium picolinate is only part of a complete program of treatment that may also include diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely.

Store chromium picolinate at room temperature away from moisture and heat.

What happens if I miss a dose?

Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

What happens if I overdose?

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

What should I avoid while taking CRM (chromium picolinate)?

Avoid a diet that is high in sugar. It may interfere with the effectiveness of chromium picolinate.

Avoid using antacids without your healthcare provider's advice. Use only the specific type of antacid your healthcare provider recommends. Antacids contain different medicines and some types can make it harder for your body to absorb chromium picolinate.

CRM (chromium picolinate) 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.

Less serious side effects are more likely to occur, and you may have none at all.

Tell your doctor, pharmacist, or healthcare provider about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect CRM (chromium picolinate)?

Do not take chromium picolinate without the advice of a doctor if you are using any of the following medications:

• 
  

  insulin or diabetes medications you take by mouth;

  
  


• 
  

  steroid medications (prednisolone and others);

  
  


• 
  

  nicotinic acid (niacin, Niaspan, Niacor, Advicor, and others);

  
  


• 
  

  stomach acid reducers such as cimetidine (Tagamet), ranitidine (Zantac), famotidine (Pepcid), or nizatidine (Axid);

  
  


• 
  

  proton-pump inhibitor acid reducers such as esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), or rabeprazole (Aciphex);

  
  


• 
  

  a beta-blocker such as acebutolol (Sectral), atenolol (Tenormin), betaxolol (Kerlone), bisoprolol (Zebeta, Ziac), carteolol (Cartrol), carvedilol (Coreg), esmolol (Brevibloc), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol), nadolol (Corgard), penbutolol (Levatol), pindolol (Visken), propranolol (Inderal, InnoPran), sotalol (Betapace), or timolol (Blocadren); or

  
  


• 
  

  aspirin or an NSAID (non-steroidal anti-inflammatory drug) such as ibuprofen (Motrin, Advil), naproxen (Aleve, Naprosyn), indomethacin (Indocin), piroxicam (Feldene), and others.

  
  

This list is not complete and other drugs may interact with chromium picolinate. Tell your healthcare provider 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 CRM resources

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

• Chromium Picolinate MedFacts Consumer Leaflet (Wolters Kluwer)

Compare CRM with other medications

• Diabetes, Type 2
• Vitamin/Mineral Supplementation and Deficiency

Where can I get more information?

• Consult with a licensed healthcare professional before using any herbal/health supplement. Whether you are treated by a medical doctor or a practitioner trained in the use of natural medicines/supplements, make sure all your healthcare providers know about all of your medical conditions and treatments.

Tysabri

natalizumab

Dosage Form: injection
FULL PRESCRIBING INFORMATION

WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

Tysabri increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability. Cases of PML have been reported in patients taking Tysabri who were recently or concomitantly treated with immunomodulators or immunosuppressants, as well as in patients receiving Tysabri as monotherapy [seeWarnings and Precautions (5.1)].

• Because of the risk of PML, Tysabri is available only through a special restricted distribution program called the TOUCH® Prescribing Program. Under the TOUCH® Prescribing Program, only prescribers, infusion centers, and pharmacies associated with infusion centers registered with the program are able to prescribe, distribute, or infuse the product. In addition, Tysabri must be administered only to patients who are enrolled in and meet all the conditions of the TOUCH® Prescribing Program [see Warnings and Precautions (5.1, 5.2)].


• Healthcare professionals should monitor patients on Tysabri for any new sign or symptom that may be suggestive of PML. Tysabri dosing should be withheld immediately at the first sign or symptom suggestive of PML. For diagnosis, an evaluation that includes a gadolinium-enhanced magnetic resonance imaging (MRI) scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended [see Contraindications (4), Warnings and Precautions (5.1)].

Indications and Usage for Tysabri

Multiple Sclerosis (MS)

 Tysabri is indicated as monotherapy for the treatment of patients with relapsing forms of multiple sclerosis to delay the accumulation of physical disability and reduce the frequency of clinical exacerbations. The efficacy of Tysabri beyond two years is unknown.

Because Tysabri increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability, Tysabri is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate multiple sclerosis therapy [see Boxed Warning, Warnings and Precautions (5.1)].

Safety and efficacy in patients with chronic progressive multiple sclerosis have not been studied.

Crohn's Disease (CD)

Tysabri is indicated for inducing and maintaining clinical response and remission in adult patients with moderately to severely active Crohn's disease with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional CD therapies and inhibitors of TNF-α. Tysabri should not be used in combination with immunosuppressants (e.g., 6-mercaptopurine, azathioprine, cyclosporine, or methotrexate) or inhibitors of TNF-α [see Boxed Warning, Warnings and Precautions (5.1)].

Tysabri Dosage and Administration

Multiple Sclerosis (MS)

Only prescribers registered in the MS TOUCH® Prescribing Program may prescribe Tysabri for multiple sclerosis [see Boxed Warning, Warnings and Precautions (5.2)]. The recommended dose of Tysabri for multiple sclerosis is 300 mg intravenous infusion over one hour every four weeks.

Crohn's Disease (CD)

Only prescribers registered in the CD TOUCH® Prescribing Program may prescribe Tysabri for Crohn's disease [see Boxed Warning, Warnings and Precautions (5.1)].

The recommended dose of Tysabri for Crohn's disease is 300 mg intravenous infusion over one hour every four weeks. Tysabri should not be used with concomitant immunosuppressants (e.g., 6-mercaptopurine, azathioprine, cyclosporine, or methotrexate) or concomitant inhibitors of TNF-α. Aminosalicylates may be continued during treatment with Tysabri.

If the patient with Crohn's disease has not experienced therapeutic benefit by 12 weeks of induction therapy, discontinue Tysabri. For patients with Crohn's disease that start Tysabri while on chronic oral corticosteroids, commence steroid tapering as soon as a therapeutic benefit of Tysabri has occurred; if the patient with Crohn's disease cannot be tapered off of oral corticosteroids within six months of starting Tysabri, discontinue Tysabri. Other than the initial six-month taper, prescribers should consider discontinuing Tysabri for patients who require additional steroid use that exceeds three months in a calendar year to control their Crohn's disease.

Dilution Instructions

1. Use aseptic technique when preparing Tysabri solution for intravenous infusion. Each vial is intended for single use only.


2. Tysabri is a colorless, clear to slightly opalescent concentrate. Inspect the Tysabri vial for particulate material and discoloration prior to dilution and administration. If visible particulates are observed and/or the liquid in the vial is discolored, the vial must not be used.


3. To prepare the solution, withdraw 15 mL of Tysabri concentrate from the vial using a sterile needle and syringe. Inject the concentrate into 100 mL 0.9% Sodium Chloride Injection, USP. No other IV diluents may be used to prepare the Tysabri solution.


4. Gently invert the Tysabri solution to mix completely. Do not shake. Inspect the solution visually for particulate material prior to administration.


5. The final dosage solution has a concentration of 2.6 mg/mL.


6. Following dilution, infuse Tysabri solution immediately, or refrigerate solution at 2 to 8°C, and use within 8 hours. If stored at 2 to 8°C, allow the solution to warm to room temperature prior to infusion. DO NOT FREEZE.

Administration Instructions

• Infuse Tysabri 300 mg in 100 mL 0.9% Sodium Chloride Injection, USP, over approximately one hour (infusion rate approximately 5 mg per minute). Do not administer Tysabri as an intravenous push or bolus injection. After the infusion is complete, flush with 0.9% Sodium Chloride Injection, USP.


• Observe patients during the infusion and for one hour after the infusion is complete. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity-type reaction [see Warnings and Precautions (5.3)].


• Use of filtration devices during administration has not been evaluated. Other medications should not be injected into infusion set side ports or mixed with Tysabri.

Dosage Forms and Strengths

Tysabri is a concentrated solution that must be diluted prior to intravenous infusion. Tysabri injection is supplied as 300 mg natalizumab in 15 mL (20 mg/mL) in a sterile, single-use vial free of preservatives.

Contraindications

• Tysabri is contraindicated in patients who have or have had progressive multifocal leukoencephalopathy (PML) [see Boxed Warning, Warnings and Precautions (5.1)].


• Tysabri should not be administered to a patient who has had a hypersensitivity reaction to Tysabri. Observed reactions range from urticaria to anaphylaxis [see Warnings and Precautions (5.3)].

Warnings and Precautions

Progressive Multifocal Leukoencephalopathy (PML)

Progressive multifocal leukoencephalopathy, an opportunistic infection caused by the JC virus, that typically only occurs in patients who are immunocompromised, developed in three patients who received Tysabri in clinical trials [see Boxed Warning]. Two cases of PML were observed among 1869 patients with multiple sclerosis treated for a median of 120 weeks. The third case occurred among 1043 patients with Crohn's disease after the patient received eight doses. Both multiple sclerosis patients were receiving concomitant immunomodulatory therapy and the Crohn's disease patient had been treated in the past with immunosuppressive therapy.

 In the postmarketing setting, additional cases of PML have been reported in multiple sclerosis patients who were receiving no concomitant immunomodulatory therapy. In patients treated with Tysabri, the risk of developing PML increases with longer treatment duration, and for patients treated for 24 to 36 months is generally similar to the rates seen in clinical trials. There is limited experience beyond 3 years of treatment. There are no known interventions that can reliably prevent PML or adequately treat PML if it occurs. It is not known whether early detection of PML and discontinuation of Tysabri will mitigate the disease.

 Ordinarily, patients receiving chronic immunosuppressant or immunomodulatory therapy or who have systemic medical conditions resulting in significantly compromised immune system function should not be treated with Tysabri.

Because of the risk of PML, Tysabri is available only under a special restricted distribution program, the TOUCH® Prescribing Program.

In multiple sclerosis patients, an MRI scan should be obtained prior to initiating therapy withTysabri. This MRI may be helpful in differentiating subsequent multiple sclerosis symptomsfrom PML.

In Crohn's disease patients, a baseline brain MRI may also be helpful to distinguish preexistentlesions from newly developed lesions, but brain lesions at baseline that could causediagnostic difficulty while on Tysabri therapy are uncommon.

Healthcare professionals should monitor patients on Tysabri for any new sign orsymptom suggestive of PML. Typical symptoms associated with PML are diverse, progress overdays to weeks, and include progressive weakness on one side of the body or clumsiness of limbs,disturbance of vision, and changes in thinking, memory, and orientation leading to confusion andpersonality changes. The progression of deficits usually leads to death or severe disability overweeks or months. Withhold Tysabri dosing immediately at the first sign or symptom suggestiveof PML.

 For diagnosis of PML, an evaluation including a gadolinium-enhanced MRI scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended. There are no known interventions that can adequately treat PML if it occurs. Three sessions of plasma exchange over 5 to 8 days were shown to accelerate Tysabri clearance in a study of 12 patients with MS who did not have PML, although in the majority of patients alpha-4 integrin receptor binding remained high. Adverse events which may occur during plasma exchange include clearance of other medications and volume shifts, which have the potential to lead to hypotension or pulmonary edema. Although plasma exchange has not been studied in Tysabri treated patients with PML, it has been used in such patients in the postmarketing setting to remove Tysabri more quickly from the circulation.

 Immune reconstitution inflammatory syndrome (IRIS) has been reported in Tysabri treated patients who developed PML and subsequently discontinued Tysabri. In almost all cases, IRIS occurred after plasma exchange was used to eliminate circulating Tysabri. It presents as an unanticipated clinical decline in the patient's condition after return of immune function (and in some cases after apparent clinical improvement) and, in the case of PML, is often followed by characteristic changes in the MRI. Tysabri has not been associated with IRIS in patients discontinuing treatment with Tysabri for reasons unrelated to PML. In Tysabri treated patients with PML, IRIS has been reported within days to several weeks after plasma exchange. Monitoring for development of IRIS and appropriate treatment of the associated inflammation should be undertaken.

Distribution Program for Tysabri

Tysabri is available only under a special restricted distribution program called the TOUCH® Prescribing Program. Under the TOUCH® Prescribing Program, only prescribers, infusion centers, and pharmacies associated with infusion centers registered with the program are able to prescribe, distribute, or infuse the product. For prescribers and patients, the TOUCH® Prescribing Program has two components: MS TOUCH® (for patients with multiple sclerosis) and CD TOUCH® (for patients with Crohn's disease). Tysabri must be administered only to patients who are enrolled in and meet all the conditions of the MS or CD TOUCH® Prescribing Program. Contact the TOUCH® Prescribing Program at 1-800-456-2255 [see Boxed Warning].

To enroll in the TOUCH® Prescribing Program, prescribers and patients are required to understand the risks of treatment with Tysabri, including PML and other opportunistic infections. Prescribers are required to understand the information in the Prescribing Information and to be able to:

• Educate patients on the benefits and risks of treatment with Tysabri, ensure that the patient receives the Medication Guide, instruct them to read it, and encourage them to ask questions when considering Tysabri. Patients may be educated by the enrolled prescriber or a healthcare provider under that prescriber's direction.


• Review the TOUCH® Prescriber/Patient Enrollment form for Tysabri with the patient and answer all questions.


• As part of the initial prescription process for Tysabri, obtain the patient's signature and initials on the TOUCH® program enrollment form, sign it, place the original signed form in the patient's medical record, send a copy to Biogen Idec, and give a copy to the patient.


• Report serious opportunistic and atypical infections with Tysabri to Biogen Idec or Elan at 1-800-456-2255 and to the Food and Drug Administration's MedWatch Program at 1-800-FDA-1088.


• Evaluate the patient three months after the first infusion, six months after the first infusion, and every six months thereafter.


• Determine every six months whether patients should continue on treatment and if so reauthorize treatment every six months.


• Submit to Biogen Idec the Tysabri Patient Status Report and Reauthorization Questionnaire six months after initiating treatment and every six months thereafter.

Hypersensitivity/Antibody Formation

Hypersensitivity reactions have occurred in patients receiving Tysabri, including serious systemic reactions (e.g., anaphylaxis) which occurred at an incidence of <1%. These reactions usually occur within two hours of the start of the infusion. Symptoms associated with these reactions can include urticaria, dizziness, fever, rash, rigors, pruritus, nausea, flushing, hypotension, dyspnea, and chest pain. Generally, these reactions are associated with antibodies to Tysabri.

If a hypersensitivity reaction occurs, discontinue administration of Tysabri and initiate appropriate therapy. Patients who experience a hypersensitivity reaction should not be re-treated with Tysabri. Hypersensitivity reactions were more frequent in patients with antibodies to Tysabri compared to patients who did not develop antibodies to Tysabri in both MS and CD studies. Therefore, the possibility of antibodies to Tysabri should be considered in patients who have hypersensitivity reactions [see Adverse Reactions (6.2)].

Antibody testing: If the presence of persistent antibodies is suspected, antibody testing should be performed. Antibodies may be detected and confirmed with sequential serum antibody tests. Antibodies detected early in the treatment course (e.g., within the first six months) may be transient and disappear with continued dosing. Repeat testing at three months after the initial positive result is recommended in patients in whom antibodies are detected to confirm that antibodies are persistent. Prescribers should consider the overall benefits and risks of Tysabri in a patient with persistent antibodies.

Experience with monoclonal antibodies, including Tysabri, suggests that patients who receive therapeutic monoclonal antibodies after an extended period without treatment may be at higher risk of hypersensitivity reactions than patients who received regularly scheduled treatment. Given that patients with persistent antibodies to Tysabri experience reduced efficacy, and that hypersensitivity reactions are more common in such patients, consideration should be given to testing for the presence of antibodies in patients who wish to recommence therapy following a dose interruption. Following a period of dose interruption, patients testing negative for antibodies prior to re-dosing have a risk of antibody development with re-treatment that is similar to Tysabri naïve patients [see Adverse Reactions (6.2)].

Immunosuppression/Infections

The immune system effects of Tysabri may increase the risk for infections. In Study MS1 [see Clinical Studies (14.1)], certain types of infections, including pneumonias and urinary tract infections (including serious cases), gastroenteritis, vaginal infections, tooth infections, tonsillitis, and herpes infections, occurred more often in Tysabri-treated patients than in placebo-treated patients [see Warnings and Precautions (5.1), Adverse Reactions (6.1)]. One opportunistic infection, a cryptosporidial gastroenteritis with a prolonged course, was observed in a patient who received Tysabri in Study MS1.

In Studies MS1 and MS2, an increase in infections was seen in patients concurrently receiving short courses of corticosteroids. However, the increase in infections in Tysabri-treated patients who received steroids was similar to the increase in placebo-treated patients who received steroids.

In CD clinical studies, opportunistic infections (pneumocystis carinii pneumonia, pulmonary mycobacterium avium intracellulare, bronchopulmonary aspergillosis, and burkholderia cepacia) have been observed in <1% of Tysabri-treated patients; some of these patients were receiving concurrent immunosuppressants [see Boxed Warning, Warnings and Precautions (5.1, 5.4), Adverse Reactions (6.1)].

In Studies CD1 and CD2, an increase in infections was seen in patients concurrently receiving corticosteroids. However, the increase in infections was similar in placebo-treated and Tysabri-treated patients who received steroids.

Concurrent use of antineoplastic, immunosuppressant, or immunomodulating agents may further increase the risk of infections, including PML and other opportunistic infections, over the risk observed with use of Tysabri alone [see Boxed Warning, Warnings and Precautions (5.1), Adverse Reactions (6.1)]. The safety and efficacy of Tysabri in combination with antineoplastic, immunosuppressant, or immunomodulating agents have not been established. Patients receiving chronic immunosuppressant or immunomodulatory therapy or who have systemic medical conditions resulting in significantly compromised immune system function should not ordinarily be treated with Tysabri.

For patients with Crohn's disease who start Tysabri while on chronic corticosteroids, commence steroid withdrawal as soon as a therapeutic benefit has occurred. If the patient cannot discontinue systemic corticosteroids within six months, discontinue Tysabri.

Hepatotoxicity

Clinically significant liver injury has been reported in patients treated with Tysabri in the postmarketing setting. Signs of liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, occurred as early as six days after the first dose; signs of liver injury have also been reported for the first time after multiple doses. In some patients, liver injury recurred upon rechallenge, providing evidence that Tysabri caused the injury. The combination of transaminase elevations and elevated bilirubin without evidence of obstruction is generally recognized as an important predictor of severe liver injury that may lead to death or the need for a liver transplant in some patients.

Tysabri should be discontinued in patients with jaundice or other evidence of significant liver injury (e.g., laboratory evidence).

Laboratory Test Abnormalities

Tysabri induces increases in circulating lymphocytes, monocytes, eosinophils, basophils, and nucleated red blood cells. Observed changes persist during Tysabri exposure, but are reversible, returning to baseline levels usually within 16 weeks after the last dose. Elevations of neutrophils are not observed. Tysabri induces mild decreases in hemoglobin levels that are frequently transient.

Immunizations

No data are available on the effects of vaccination in patients receiving Tysabri. No data are available on the secondary transmission of infection by live vaccines in patients receiving Tysabri.

Adverse Reactions

Clinical Trials Experience

The most serious adverse reactions were [see Warnings and Precautions (5)]:

• Progressive Multifocal Leukoencephalopathy (PML)


• Hypersensitivity


• Immunosuppression/Infections

The most common adverse reactions (incidence ≥ 10%) were headache and fatigue in both the multiple sclerosis (MS) and Crohn's disease (CD) studies. Other common adverse reactions (incidence ≥ 10%) in the MS population were arthralgia, urinary tract infection, lower respiratory tract infection, gastroenteritis, vaginitis, depression, pain in extremity, abdominal discomfort, diarrhea NOS, and rash. Other common adverse reactions (incidence ≥ 10%) in the CD population were upper respiratory tract infections and nausea.

The most frequently reported adverse reactions resulting in clinical intervention (i.e., discontinuation of Tysabri), in the MS studies were urticaria (1%) and other hypersensitivity reactions (1%), and in the CD studies (Studies CD1 and CD2) were the exacerbation of Crohn's disease (4.2%) and acute hypersensitivity reactions (1.5%) [see Warnings and Precautions (5.3)].

A total of 1617 multiple sclerosis patients in controlled studies received Tysabri, with a median duration of exposure of 28 months. A total of 1563 patients received Tysabri in all CD studies for a median exposure of 5 months; of these patients, 33% (n=518) received at least one year of treatment and 19% (n=297) received at least two years of treatment.

Because clinical trials are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical trials of Tysabri cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice. The adverse reaction information does, however, provide a basis for identifying the adverse events that appear to be related to drug use and a basis for approximating rates.

Multiple Sclerosis Clinical Studies

The most frequently reported serious adverse reactions in Study MS1 [see Clinical Studies (14.1)] with Tysabri were infections (3.2% versus 2.6% in placebo, including urinary tract infection [0.8% versus 0.3%] and pneumonia [0.6% versus 0%]), acute hypersensitivity reactions (1.1% versus 0.3%, including anaphylaxis/anaphylactoid reaction [0.8% versus 0%]), depression (1.0% versus 1.0%, including suicidal ideation or attempt [0.6% versus 0.3%]), and cholelithiasis (1.0% versus 0.3%). In Study MS2, serious adverse reactions of appendicitis were also more common in patients who received Tysabri (0.8% versus 0.2% in placebo) [see Warnings and Precautions (5.4), Adverse Reactions - Infections].

Table 1 enumerates adverse reactions and selected laboratory abnormalities that occurred in Study MS1 at an incidence of at least 1 percentage point higher in Tysabri-treated patients than was observed in placebo-treated patients.

Table 1. Adverse Reactions in Study MS1 (Monotherapy Study)

*Percentage based on female patients only.
**Acute versus other hypersensitivity reactions are defined as occurring within 2 hours post-infusion versus more than 2 hours.
Adverse Reactions (Preferred Term)	Tysabri n=627 Percentage	Placebo n=312 Percentage
General
Headache	38%	33%
Fatigue	27%	21%
Arthralgia	19%	14%
Chest discomfort	5%	3%
Acute hypersensitivity reactions**	4%	<1%
Other hypersensitivity reactions**	5%	2%
Seasonal allergy	3%	2%
Rigors	3%	<1%
Weight increased	2%	<1%
Weight decreased	2%	<1%
Infection
Urinary tract infection	21%	17%
Lower respiratory tract infection	17%	16%
Gastroenteritis	11%	9%
Vaginitis*	10%	6%
Tooth infections	9%	7%
Herpes	8%	7%
Tonsillitis	7%	5%
Psychiatric
Depression	19%	16%
Musculoskeletal/Connective Tissue Disorders
Pain in extremity	16%	14%
Muscle cramp	5%	3%
Joint swelling	2%	1%
Gastrointestinal
Abdominal discomfort	11%	10%
Diarrhea NOS	10%	9%
Abnormal liver function test	5%	4%
Skin
Rash	12%	9%
Dermatitis	7%	4%
Pruritus	4%	2%
Night sweats	1%	0%
Menstrual Disorders*
Irregular menstruation	5%	4%
Dysmenorrhea	3%	<1%
Amenorrhea	2%	1%
Ovarian cyst	2%	<1%
Neurologic Disorders
Somnolence	2%	<1%
Vertigo	6%	5%
Renal and Urinary Disorders
Urinary incontinence	4%	3%
Urinary urgency/frequency	9%	7%
Injury
Limb injury NOS	3%	2%
Skin laceration	2%	<1%
Thermal burn	1%	<1%

In Study MS2, peripheral edema was more common in patients who received Tysabri (5% versus 1% in placebo).

Crohn's Disease Clinical Studies

The following serious adverse events in the induction Studies CD1 and CD2 [see Clinical Studies (14.2)] were reported more commonly with Tysabri than placebo and occurred at an incidence of at least 0.3%: intestinal obstruction or stenosis (2% vs. 1% in placebo), acute hypersensitivity reactions (0.5% vs. 0%), abdominal adhesions (0.3% vs. 0%), and cholelithiasis (0.3% vs. 0%). Similar serious adverse events were seen in the maintenance Study CD3. Table 2 enumerates adverse drug reactions that occurred in Studies CD1 and CD2 (median exposure of 2.8 months). Table 3 enumerates adverse drug reactions that occurred in Study CD3 (median exposure of 11.0 months).

Table 2. Adverse Reactions in Studies CD1 and CD2 (Induction Studies)

*Occurred at an incidence of at least 1% higher in Tysabri-treated patients than placebo-treated patients.
**Percentage based on female patients only.
Adverse Reactions*	Tysabri n=983 Percentage	Placebo n=431 Percentage
General
Headache	32%	23%
Fatigue	10%	8%
Arthralgia	8%	6%
Influenza-like illness	5%	4%
Acute hypersensitivity reactions	2%	<1%
Tremor	1%	<1%
Infection
Upper respiratory tract infection	22%	16%
Vaginal infections**	4%	2%
Viral infection	3%	2%
Urinary tract infection	3%	1%
Respiratory
Pharyngolaryngeal pain	6%	4%
Cough	3%	<1%
Gastrointestinal
Nausea	17%	15%
Dyspepsia	5%	3%
Constipation	4%	2%
Flatulence	3%	2%
Aphthous stomatitis	2%	<1%
Skin
Rash	6%	4%
Dry skin	1%	0%
Menstrual Disorder
Dysmenorrhea**	2%	<1%

Table 3. Adverse Reactions in Study CD3 (Maintenance Study)

*Occurred at an incidence of at least 2% higher in Tysabri-treated patients than placebo-treated patients.
**Percentage based on female patients only.
Adverse Reactions*	Tysabri n=214 Percentage	Placebo n=214 Percentage
General
Headache	37%	31%
Influenza-like illness	11%	6%
Toothache	4%	<1%
Peripheral edema	6%	3%
Infection
Influenza	12%	5%
Sinusitis	8%	4%
Viral infection	7%	3%
Vaginal infections**	8%	<1%
Respiratory