Poly Hist PD

pyrilamine maleate, chlorpheniramine maleate and phenylephrine hydrochloride

Dosage Form: liquid
Poly Hist PD

Poly Hist PD

Antihistamine / Decongestant

Sugar Free / Alcohol Free / Dye Free


DESCRIPTION: Poly Hist PD is a sugar free, alcohol free, dye free, clear and colorless liquid with a

bubble gum odor and flavor. Each 5 mL (1 teaspoonful) contains:

Pyrilamine Maleate.................... 12.5 mg

Chlorpheniramine Maleate........... 2 mg

Phenylephrine HCl...................... 7.5 mg


Pyrilamine Maleate is an antihistamine that occurs as a white crystalline powder, usually having a faint odor.

It is very soluble in water, freely soluble in alcohol and chloroform, and slightly soluble in ether and benzene.

The chemical name is 1,2-Ethanediamine, N-[(4-methoxyphenyl)methyl]-N', N'dimethyl-N-2-pyridinyl-, (Z)-2-

butenedioate (1:1). Its structural formula is as follows:

Chlorpheniramine Maleate is an antihistaminic that occurs as a white, odorless crystalline powder. Its solutions

have a pH between 4 and 5. It is freely soluble in water, soluble in alcohol and chloroform, and slightly soluble

in ether and benzene. The chemical name is 2-Pyridinepropanamine, gamma-(4-chlorophenyl)-N,N-dimethyl-,

(Z)-2-butenedioate (1:1). Its structural formula is as follows:

Phenylephrine hydrochloride is an adrenergic that occurs as white or practically white, odorless crystals, having

a bitter taste. It is freely soluble in water and alcohol. It is affected by light. The chemical name is benzenemethanol, 3-hydroxy-alpha[(methylamino)methyl]-, hydrochloride (R)-. Its structural formula is as follows:

Inactive ingredients:

Propylene glycol, sorbitol, glycerin, sodium saccharin, purified water, and bubble gum flavoring.

CLINICAL PHARMACOLOGY:

Pyrilamine Maleate: Pyrilamine is an antihistamine belonging to the ethylenediamine class. Pyrilamine is a

highly effective H1 blocker which possesses local anesthetic activity. Pyrilamine antagonizes most of the

smooth muscle stimulating actions of histamine on the H1 receptors of the gastrointestinal tract, blood

vessels and bronchial muscle. It also antagonizes the actions of histamine that result in increased capillary

permeability and the formation of edema. Pyrilamine has a duration of action of 4 to 6 hours in clinical studies.


Chlorpheniramine Maleate:

Chlorpheniramine is an antihistamine belonging to the alkylamine class. It possesses anticholinergic and

sedative effects. Antihistamines appear to compete with histamine for H1 cell receptor sites on effector cells.

Chlorpheniramine Maleate does not prevent the release of histamine in response to injury, drugs or antigens.

Antihistamines effectively block most smooth muscle responses to histamine and acts as an antagonist of

the constrictor action of histamine on respiratory smooth muscle. Antihistamines counteract edema formation

and whealing in response to injury, antigens, or histamine-liberating drugs. Chlorpheniramine is readily absorbed

from the gastrointestinal tract and has a duration of 4 to 6 hours. Plasma half-life is approximately 22 hours.

Degradation products of chlorpheniramine's metabolic transformation by the liver are almost completely excreted

in 24 hours via the kidney. The alkylamines of which chlorpheniramine is the prototype, are among the most

potent H1 blockers. Although not so prone as others to cause drowsiness, a significant proportion of patients

do experience this effect. CNS stimulation is more common in chlorpheniramine than in other groups of H1 blockers.


Phenylephrine Hydrochloride:

Phenylephrine is a potent postsynaptic alpha-receptor agonist with little effect on beta-receptors on the heart.

Phenylephrine has no effect on beta-adrenergic receptors of the bronchi or peripheral blood vessels. A direct

action at receptors accounts for the greater part of its effects; only a small part is due to its ability to release

norepinephrine. Therapeutic doses of phenylephrine mainly cause vasoconstriction. It increases resistance,

and to a lesser extent, decreases capacitance of blood vessels. Total peripheral resistance is increased,

resulting in increased systolic and diastolic blood pressure. Pulmonary arterial pressure is usually increased,

and renal blood flow is usually decreased. Following oral administration of phenylephrine, constriction of blood

vessels in the nasal mucosa relieves nasal congestion associated with allergy or head colds. Following oral

administration of phenylephrine, nasal decongestion may occur within 15 to 20 minutes and may persist for up

to 4 hours. Phenylephrine is irregularly absorbed from and readily metabolized in the gastrointestinal tract.

Phenylephrine is metabolized in the liver and intestine by monoamine oxidase. The metabolites and their route

and rate of excretion have not been identified. The pharmacologic action of phenylephrine is terminated at least

partially by uptake of the drug into the tissues.

INDICATIONS AND USAGE:

Poly Hist PD is indicated for symptomatic relief of seasonal and perennial allergic rhinitis, and vasomotor rhinitis.

CONTRAINDICATIONS:

Hypersensitivity to any of the ingredients. Patients known to be sensitive to other sympathomimetic amines

may exhibit cross sensitivity with this drug. Poly Hist PD is contraindicated in patients with severe hypertension,

severe coronary artery disease and patients on monoamine oxidase (MAO) inhibitor therapy. It is also

contraindicated in patients with diabetes or hyperthyroidism. Antihistamines should not be administered to premature

or newborn infants or be used to treat lower respiratory tract symptoms or asthma.

WARNINGS:

Pyrilamine Maleate and Chlorpheniramine Maleate:

Antihistamines should be used with considerable caution in patients with narrow angle glaucoma, stenosing peptic

ulcer, pyloroduodenal obstruction, symptomatic prostatic hypertrophy, and bladder neck obstruction. In infants and

children especially, antihistamine overdosage may cause hallucinations, convulsions or death. As in adults,

antihistamines may diminish mental alertness in children. Chlorpheniramine Maleate has additional effects with

alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers) Patients should be warned about engaging

in activities requiring mental alertness, such as driving a car or operating appliances, machinery, etc.


Phenylephrine Hydrochloride:

Sympathomimetic amines should be used with considerable caution in patients with hypertension, ischemic heart

disease, diabetes mellitus, increased intraocular pressure, hyperthyroidism or prostatic hypertrophy.

Sympathomimetics may produce central nervous system stimulation with convulsions or cardiovascular collapse

with accompanying hypotension. DO NOT EXCEED RECOMMENDED DOSAGE. Hypertensive crisis could occur

with concurrent use of phenylephrine and monoamine oxidase (MAO) inhibitors, indomethacin or with beta blockers

and methyldopa. If a hypertensive crisis occurs, this drug should be discontinued immediately and therapy to lower

blood pressure should be instituted. Fever should be managed by means of external cooling. The elderly

(approximately sixty years or older) are more likely to have adverse reactions to sympathomimetics. Overdosage of

sympathomimetics in this age group may cause hallucinations, convulsions, CNS depression and death. Therefore,

safe use of a short-acting sympathomimetic should be demonstrated in the individual elderly patient before

considering the use of a sustained-release formulation. Discontinue use if adverse reaction(s) occur.

PRECAUTIONS:

General:

Antihistamines have an atropine-like action and therefore should be used with caution in patients with a

history of bronchial asthma, increased intraocular pressure, hyperthyroidism, cardiovascular disease and

hypertension. Phenylephrine should be used with caution in patients with diabetes, hypertension,

 cardiovascular disease and hyper-reactivity to ephedrine.

Information for Patients:

Antihistamines may impair the mental and physical abilities required for the performance of potentially

hazardous tasks such as driving a vehicle or operating machinery. Patients should also be warned about

possible additive effects with alcohol and other central nervous system depressants (hypnotics, sedatives

and tranquilizers).

Drug/Laboratory Test Interactions:

MAO inhibitors and tricyclic antidepressants may prolong and intensify the anticholinergic (drying) effects

of antihistamines. Beta-adrenergic blockers and MAO inhibitors may potentiate the pressor effect of

phenylephrine. Concurrent use of digitalis glycosides may increase the possibility of cardiac arrhythmias.

Sympathomimetics may reduce the antihypertensive effects of methyldopa, mecamylamine, reserpine and

veratrum alkaloids. Concurrent use of tricyclic antidepressants may antagonize the effects of phenylephrine.

Concomitant use of antihistamines with alcohol, tricyclic antidepressants, barbiturates, and other CNS

depressants may have an additive effect.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

No long-term studies have been performed using Poly Hist PD to determine the long-term potential for

carcinogenesis, mutagenesis and impairment of fertility. In a four-year evaluation of phenylephrine, no

statistically significant associated between the drug and cancer was found.

Usage in Pregnancy:

Pregnancy Category C: Moderate overexposure to phenylephrine has been found to contribute to birth defects

in rabbits. Animal reproduction studies have not been conducted with the other ingredients in Poly Hist PD.

Poly Hist PD should be used during pregnancy only if the potential benefit justifies the possible risk to the fetus.

Labor and Delivery:

Administration of phenylephrine to patients in late pregnancy or labor may cause fetal anoxia or bradycardia by

increasing contractility of the uterus and decreasing uterine blood flow.

Nursing Mothers:

Due to the possible passage of antihistamines into breast milk, and because of the higher than usual risk for

infants from sympathomimetic amines and antihistamines, a decision should be made whether to discontinue

nursing or to discontinue the drug, taking into account the importance of both.

Pediatric Use:

In infants and children especially, antihistamines in overdosage may cause hallucination, convulsions or death.

As in adults, antihistamines may diminish mental alertness in children. In the young child particularly, they may

produce excitation.

Geriatric Use:

The elderly (60 years and older) are more likely to experience adverse reactions from sympathomimetics and

antihistamines. Overdosage of sympathomimetics in this age group may cause hallucinations, convulsions,

CNS depression and death.

ADVERSE REACTIONS:

Pyrilamine Maleate and Chlorpheniramine Maleate:

Chlorpheniramine maleate may cause slight to moderate drowsiness relatively infrequently. Other possible side effects

of antihistamines in general include: urticaria, drug rash, anaphylactic shock, photosensitivity, excessive perspiration,

chills, dryness or the mouth, nose and throat; cardiovascular effects (hypotension, headache, palpitation, tachycardia,

extrasystoles); hematological effects (hemolytic anemia, thrombocytopenia, agranulocytosis); CNS disturbances (sedation,

dizziness, disturbed coordination, fatigue, confusion, restlessness, excitation, nervousness, tremor, irritability, insomnia,

euphoria, paresthesias, blurred vision, diplopia, vertigo, tinnitus, acute labyrinthitis, hysteria, neuritis, convulsions);

gastrointestinal effects (epigastric distress, anorexia, nausea, vomiting, diarrhea, constipation); genitourinary effects

(urinary frequency, difficult urination, urinary retention, early menses) and respiratory effects (thickening of bronchial

secretions, tightness of the chest, wheezing and nasal stuffiness).


Phenylephrine Hydrochloride:

Hyper-reactive individuals may display ephedrine-like reactions such as tachycardia, palpitations, headache, dizziness,

or nausea. Sympathomimetic amines have been associated with certain untoward reactions including fear, anxiety,

nervousness, restlessness, tremor, weakness, pallor, respiratory difficulty, dysuria, insomnia, hallucinations, convulsions,

CNS depression, arrhythmias, and cardiovascular collapse with hypotension. Phenylephrine may cause precordial pain,

respiratory distress, tremor, weakness, hypertension, restlessness, anxiety, nervousness and dizziness.

OVERDOSAGE:

Signs and symptoms:

Pyrilamine Maleate and Chlorpheniramine Maleate:

Manifestations of antihistamine overdosage may vary from central nervous system depression (sedation, apnea,

cardiovascular collapse) to stimulation (insomnia, hallucinations, tremors or convulsions). Other signs and

symptoms may be dizziness, tinnitus, ataxia, blurred vision and hypotension. Stimulation is particularly likely

in children, as are atropine-like signs and symptoms (dry mouth, fixed dilated pupils, flushing, hypothermia and

gastrointestinal symptoms.


Phenylephrine Hydrochloride:

May cause hypertension, headache, convulsions, cerebral hemorrhage and vomiting. Ventricular premature beats

and short paroxysms of ventricular tachycardia may also occur. Headache may be a symptom of hypertension.

Bradycardia may also be seen early in phenylephrine overdosage through stimulation of baroreceptors. Excessive

CNS stimulation may result in excitement, tremor, restlessness and insomnia. Other effects may include pallor,

mydriasis, hyperglycemia and urinary retention. Severe overdosage may cause tachypnea or hyperpnea,

hallucination, convulsions or delirium but in some individuals, there may be CNS depression with somnolence,

stupor or respiratory depression. Arrhythmias (including ventricular fibrillation) may lead to hypotension and

circulatory collapse. Severe hypokalemia can occur, probably due to compartmental shift rather than a depletion

of potassium.


Treatment:

The patient should be induced to vomit even if emesis has occurred spontaneously. Pharmacologic vomiting by

the administration of ipecac is facilitated by physical activity and by the administration of eight to twelve ounces

of water. If emesis does not occur within fifteen minutes, the dose of ipecac should be repeated.

Precautions against aspiration must be taken especially in infants and children. Following emesis, any drug remaining

in the stomach may be absorbed by activated charcoal administered as a slurry with water. If vomiting is unsuccessful

or contraindicated, gastric lavage should be performed. Isotonic and one-half isotonic saline are the lavage solution of

choice. Saline cathartics, such as milk of magnesia, draw water into the bowel by osmosis and therefore, may be

valuable for their action in rapid dilution of bowel content. After emergency treatment, the patient should continue to

be medically monitored. Treatment of the signs and symptoms of overdosage is symptomatic and supportive.

DOSAGE AND ADMINISTRATION:

Adults and Children 12 years of age and over:

1-2 teaspoonfuls every 4-6 hours.

Children 6 to under 12 years of age:

1/2 teaspoonful every 4-6 hours.

Not recommended for Children under 6 years of age.

HOW SUPPLIED:

16 fluid ounce bottles, NDC 50991-405-16 and 20 mL bottles, NDC 50991-405-20.


KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

IN CASE OF ACCIDENTAL OVERDOSE, CONTACT A POISON CONTROL

CENTER OR SEEK PROFESSIONAL ASSISTANCE IMMEDIATELY.

Storage:

Store at controlled room temperature, 15o-30oC (59o-86oF).


DISPENSE IN TIGHT, LIGHT-RESISTANT CONTAINER WITH A CHILD-RESISTANT

CLOSURE AS DESCRIBED IN THE USP/NF.


CAUTION: FEDERAL LAW PROHIBITS DISPENSING WITHOUT A PRESCRIPTION.


Manufactured by:

Great Southern Laboratories,

Houston, TX 77099


Distributed by:

Poly Pharmaceuticals, Inc.,

Mobile, AL 36619


Rev. 11/09

PRODUCT PACKAGING:

The packaging below represents the labeling currently used:


Principal Display Panel and Side Panel for 473 mL Label:


NDC 50991-405-16


POLY HIST

PD


EACH TEASPOONFUL (5 mL)

FOR ORAL ADIMISTRATION CONTAINS:


PYRILAMINE MALEATE..................12.5 mg

CHLORPHENIRAMINE MALEATE...... 2 mg

PHENYLEPHRINE HCl......................7.5 mg

• SUGAR FREE


• ALCOHOL FREE


• DYE FREE

Rx Only


16 fl oz (473 mL)


DOSAGE AND ADMINISTRATION:

Adults and Children 12 years of age and over: 1-2 teaspoonfuls every 4-6 hours.

Children 6 to under 12 years of age: 1/2 teaspoonful every 4-6 hours.

Not recommended for Children under 6 years of age.


SEE LABEL FOLDOUT FOR FULL PRESCRIBING INFORMATION.


KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

IN CASE OF ACCIDENTAL OVERDOSE, SEEK PROFESSIONAL ASSISTANCE

OR CONTACT A POISON CONTROL CENTER IMMEDIATELY.


Store at controlled room temperature, 15o-30oC (59o-86oF).

Dispense in a tight, light-resistant container as defined in the USP/NF with a child-resistant closure.


This bottle is not to be dispensed to consumer.


Tamper evident by heat seal under cap. Do not use if there is evidence of tampering.


Poly Hist PD is a product of POLY PHARMACEUTICALS, INC.


Mfg. by: Great Southern Labroatories, Houston, TX 77099

Distributed by: Poly Pharmaceuticals, Inc. Mobile, AL 36619

Rev. 11/09

POLY HIST  PD pyrilamine maleate, chlorpheniramine maleate, and phenylephrine hydrochloride  liquid

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 50991-405 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Pyrilamine Maleate (Pyrilamine) Pyrilamine Maleate 12.5 mg  in 5 mL Chlorpheniramine Maleate (Chlorpheniramine) Chlorpheniramine Maleate 2 mg  in 5 mL Phenylephrine Hydrochloride (Phenylephrine) Phenylephrine Hydrochloride 7.5 mg  in 5 mL

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color      Score      Shape Size Flavor BUBBLE GUM Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 50991-405-16 473 mL In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
unapproved drug other		08/05/2004

Labeler - Poly Pharmaceuticals, Inc. (198449894)

Registrant - Great Southern Laboratories (056139553)

Establishment
Name	Address	ID/FEI	Operations
Great Southern Laboratories		056139553	manufacture

Revised: 12/2009Poly Pharmaceuticals, Inc.

More Poly Hist PD resources

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

• Poly Hist PD Concise Consumer Information (Cerner Multum)


• Chlorpheniramine/Phenylephrine/Pyrilamine MedFacts Consumer Leaflet (Wolters Kluwer)


• AllerTan Suspension MedFacts Consumer Leaflet (Wolters Kluwer)


• Phena-S Liquid MedFacts Consumer Leaflet (Wolters Kluwer)


• Ru-Hist Forte Controlled-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)

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• Cold Symptoms
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Juraclox

Juraclox may be available in the countries listed below.

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

Ingredient matches for Juraclox

Cloxacillin

Cloxacillin benzathine (a derivative of Cloxacillin) is reported as an ingredient of Juraclox in the following countries:

• Australia


• New Zealand

International Drug Name Search

Pennsaid

Generic Name: diclofenac topical (dye KLOE fen ak TOP ik al)

Brand Names: Pennsaid, Solaraze, Voltaren Topical

What is diclofenac topical?

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID). It works by reducing hormones that cause inflammation and pain in the body.

Diclofenac topical 1% gel (Voltaren Topical) is used to treat joint pain in the hands, wrists, elbows, knees, ankles, or feet caused by osteoarthritis. This medication may not be effective in treating arthritis pain elsewhere in the body.

Diclofenac topical 1.5% solution (Pennsaid) is used to treat pain in the knees caused by osteoarthritis. This medication may not be effective in treating arthritis pain elsewhere in the body.

Diclofenac topical 3% gel (Solaraze) is used to treat warty overgrowths of skin (actinic keratoses) on sun-exposed areas of the body.

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

What is the most important information I should know about diclofenac topical?

Do not use this medication if you have ever had asthma or a severe allergic reaction caused by aspirin, diclofenac (Cataflam, Voltaren), or another non-steroidal anti-inflammatory drug (NSAID). Do not use diclofenac just before or after having heart bypass surgery (also called coronary artery bypass graft, or CABG).

Before using this medication, tell your doctor if you have heart disease, congestive heart failure, high blood pressure, a history of heart attack or stroke, a history of stomach ulcer or bleeding, liver or kidney disease, a blood clotting disorder, asthma, or nasal polyps.

While the risk of absorbing diclofenac topical into your bloodstream is low, an NSAID may cause life-threatening heart or circulation problems such as heart attack or stroke, especially if you use it long term.

Get emergency medical help if you have chest pain, weakness, shortness of breath, slurred speech, or problems with vision or balance.

This medicine may also cause serious effects on the stomach or intestines, including bleeding or perforation (forming of a hole). These conditions can be fatal and can occur without warning while you are using diclofenac topical, especially in older adults.

Call your doctor at once if you have symptoms of stomach bleeding such as black, bloody, or tarry stools, or coughing up blood or vomit that looks like coffee grounds.

What should I discuss with my healthcare provider before using diclofenac topical?

While the risk of absorbing diclofenac topical into your bloodstream is low, an NSAID can cause life-threatening heart or circulation problems such as heart attack or stroke, especially if you use it long term.

This medicine may also cause serious effects on the stomach or intestines, including bleeding or perforation (forming of a hole). These conditions can be fatal and can occur without warning while you are using diclofenac topical, especially in older adults.

Do not use this medication if you have ever had asthma or a severe allergic reaction caused by aspirin, diclofenac (Cataflam, Voltaren), or another NSAID. Do not use diclofenac just before or after having heart bypass surgery (also called coronary artery bypass graft, or CABG).

To make sure you can safely use diclofenac topical, tell your doctor if you have any of these other conditions:

• 
  

  a history of drug allergies;

  
  


• 
  

  a history of heart attack, stroke, or blood clot;

  
  


• 
  

  heart disease, congestive heart failure, high blood pressure;

  
  


• 
  

  a history of stomach ulcer or bleeding;

  
  


• liver or kidney disease;


• 
  

  a bleeding or blood clotting disorder; or

  
  


• 
  

  asthma, or polyps in your nose.

  
  

This medication may be harmful to an unborn baby. If you are pregnant, ask your doctor if it is safe for you to use diclofenac topical. Tell your doctor if you become pregnant during treatment. Diclofenac topical can pass into breast milk and may harm a nursing baby. You should not breast-feed while using diclofenac topical.

How should I use diclofenac topical?

Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. When treating osteoarthritis, keep using any oral medications your doctor has prescribed.

Do not use diclofenac topical on an open skin wound, or on areas of eczema, infection, skin rash, or burn injury. Do not cover the treated skin with a bandage or expose it to heat from a hot tub, heating pad, sauna, or heated water bed. Heat or bandaging can increase the amount of drug you absorb through your skin and may cause harmful effects. Wash your hands after applying this medication, unless you are treating the skin on your hands. Do not wear gloves for at least 10 minutes after applying diclofenac topical to the hands.

After you apply diclofenac topical gel, wait at least 10 minutes before dressing and at least 1 hour before you bathe or shower.

To treat actinic keratosis (with Solaraze): Apply enough gel to cover each lesion and rub in gently. Do not apply Solaraze gel more than 2 times daily and never use more than your prescribed dose.

To treat osteoarthritis knee pain (with Pennsaid): Apply the solution only to clean, dry skin. Place 10 drops at a time into your hand and spread the solution over the front, back, and sides of the knee. Apply a total of 40 drops to each affected knee, 4 times per day. You may also drop the medicine directly onto the knee, spreading after every 10 drops.

Wait until the solution is completely dry before covering treated skin with clothing or applying any other skin products, including sunscreen.

To treat osteoarthritis pain (with Voltaren Topical): This medicine is supplied with dosing cards that show you how much gel to use for a 2-gram dose or a 4-gram dose. Squeeze the gel onto this card along the line for your dose. Use no more gel than will fit on the length of your dosing line. Wipe the card directly onto the treatment area and rub gently into the skin.

To treat arthritis pain in the foot, spread the gel out onto all areas of the foot including the toes and soles. When treating the hand, spread the gel out onto all areas of the hand including the fingers and palms.

Store at room temperature away from moisture and heat. Do not freeze.

What happens if I miss a dose?

Use the missed dose as soon as you remember. 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 using diclofenac topical?

Avoid drinking alcohol. It may increase your risk of stomach bleeding. Do not use cosmetics, sunscreen, lotions, insect repellant, or other medicated skin products on the same area you treat with diclofenac topical. Avoid getting this medication in your mouth, nose, or eyes. If this does happen, rinse with water. Avoid exposure to sunlight or artificial UV rays (sunlamps or tanning beds) while you are using diclofenac topical.

Avoid taking aspirin, oral (pill form) diclofenac (Cataflam, Voltaren), or other NSAIDs without your doctor's advice. This includes ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), indomethacin, piroxicam (Feldene), nabumetone (Relafen), etodolac (Lodine), and others.

Ask a doctor or pharmacist before using any cold, allergy, or pain medicine. Aspirin and other medicines similar to diclofenac are 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 aspirin, ibuprofen, ketoprofen, or naproxen.

Diclofenac 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.

Although the risk of serious side effects is low when diclofenac is applied to the skin, you should be aware of side effects that can occur if the medication is absorbed into your bloodstream.

Stop using this medicine and call your doctor at once if you have a serious side effect such as:

• 
  

  chest pain, slurred speech, problems with vision or balance, and feeling weak or short of breath;

  
  


• 
  

  bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;

  
  


• 
  

  pale or yellowed skin, dark colored urine, confusion;

  
  


• 
  

  swelling or rapid weight gain, urinating less than usual or not at all;

  
  


• 
  

  nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

  
  


• 
  

  bruising, severe tingling, numbness, pain, muscle weakness;

  
  


• 
  

  fever, sore throat, and headache with a severe blistering, peeling, and red skin rash; or

  
  


• 
  

  the first sign of any skin rash, no matter how mild.

  
  

Less serious side effects may include:

• 
  

  mild nausea, stomach pain, upset stomach;

  
  


• 
  

  diarrhea, gas; or

  
  


• 
  

  mild itching, dryness, redness, scaling, or other skin irritation where the medicine was applied.

  
  

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 diclofenac topical?

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

• 
  

  a blood thinner such as warfarin (Coumadin, Jantoven);

  
  


• 
  

  cyclosporine (Gengraf, Neoral, Sandimmune);

  
  


• 
  

  lithium (Eskalith, Lithobid);

  
  


• 
  

  methotrexate (Rheumatrex, Trexall);

  
  


• 
  

  a diuretic (water pill);

  
  


• 
  

  steroids (prednisone and others); or

  
  


• 
  

  heart or blood pressure medication such as benazepril (Lotensin), enalapril (Vasotec), lisinopril (Prinivil, Zestril), quinapril (Accupril), ramipril (Altace), and others.

  
  

It is not likely that other drugs you take orally or inject will have an effect on topically applied diclofenac. But many drugs can interact with each other. 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 Pennsaid resources

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

• Pennsaid Prescribing Information (FDA)


• Pennsaid Consumer Overview


• Pennsaid Topical Advanced Consumer (Micromedex) - Includes Dosage Information


• Pennsaid Solution MedFacts Consumer Leaflet (Wolters Kluwer)


• Solaraze Prescribing Information (FDA)


• Solaraze topical Monograph (AHFS DI)


• Solaraze Gel MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Pennsaid with other medications

• Osteoarthritis

Where can I get more information?

• Your pharmacist can provide more information about diclofenac topical.

See also: Pennsaid side effects (in more detail)

Spectracef

Pronunciation: SEF-di-TOR-en
Generic Name: Cefditoren Pivoxil
Brand Name: Spectracef

Spectracef is used for:

Treating bacterial infections.

Spectracef is a cephalosporin antibiotic. It works by killing sensitive bacteria.

Do NOT use Spectracef if:

• you are allergic to any ingredient in Spectracef or to another cephalosporin (eg, cephalexin)


• you have low levels of carnitine in your body or have a metabolic problem that may cause low levels of carnine in your body


• you are allergic to milk protein (not lactose intolerant)

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

Before using Spectracef:

Some medical conditions may interact with Spectracef. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

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


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


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


• if you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to a penicillin (eg, amoxicillin) or beta-lactam antibiotic (eg, imipenem)


• if you have stomach of bowel problems (eg, inflammation), blood clotting problems, kidney or liver problems, decreased muscle mass, or poor nutrition

Some MEDICINES MAY INTERACT with Spectracef. However, no specific interactions with Spectracef are known at this time.

Ask your health care provider if Spectracef may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Spectracef:

Use Spectracef as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Spectracef by mouth with food.


• To clear up your infection completely, continue using Spectracef for the full course of treatment even if you feel better in a few days.


• Do not take antacids or H₂ antagonists (eg, famotidine) within 2 hours before or 2 hours after taking Spectracef.


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

Ask your health care provider any questions you may have about how to use Spectracef.

Important safety information:

• Spectracef only works against bacteria; it does not treat viral infections (eg, the common cold).


• Be sure to use Spectracef for the full course of treatment. If you do not, the medicine may not clear up your infection completely. The bacteria could also become less sensitive to this or other medicines. This could make the infection harder to treat in the future.


• Long-term or repeated use of Spectracef may cause a second infection. Tell your doctor if signs of a second infection occur. Your medicine may need to be changed to treat this.


• Contact your doctor right away if stomach pain or cramps, severe diarrhea, or bloody stools occur. Do not treat diarrhea without first checking with your doctor.


• Spectracef may reduce the ability of your blood to clot. Avoid activities that may cause bruising or injury. Tell your doctor if you have unusual bruising or bleeding. Tell your doctor if you have dark, tarry, or bloody stools.


• Diabetes patients - Spectracef may affect your blood sugar. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.


• Diabetes patients - Spectracef may cause the results of some tests for urine glucose to be wrong. Ask your doctor before you change your diet or the dose of your diabetes medicine.


• Spectracef may interfere with certain lab tests. Be sure your doctor and lab personnel know you are using Spectracef.


• Lab tests, including liver, kidney, or lung function, may be performed while you use Spectracef. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Spectracef with caution in the ELDERLY; they may be more sensitive to its effects.


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


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Spectracef while pregnant. It is not known if Spectracef is found in breast milk. If you are or will be breast-feeding while you use Spectracef, check with your doctor or pharmacist. Discuss any possible risks to your baby.

Possible side effects of Spectracef:

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

Headache; mild diarrhea; nausea; stomach pain or upset; vomiting.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bloody stools; decreased urination; easy bruising or bleeding; fever; hoarseness; red, swollen, or blistered skin; seizures; severe diarrhea; severe nausea or vomiting; severe stomach pain/cramping; unusual tiredness; vaginal discharge or itching; white spots in the mouth; yellowing of the skin or eyes.

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

See also: Spectracef side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include diarrhea; nausea; seizures; stomach pain; vomiting.

Proper storage of Spectracef:

Store Spectracef at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Spectracef out of the reach of children and away from pets.

General information:

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


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


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


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

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

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Spectracef resources

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

• Spectracef Prescribing Information (FDA)


• Spectracef Concise Consumer Information (Cerner Multum)


• Spectracef Monograph (AHFS DI)


• Spectracef Advanced Consumer (Micromedex) - Includes Dosage Information

Compare Spectracef with other medications

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Paracetamol 500mg Soluble Tablets / Soluble Paracetamol Tablets 500mg

1. Name Of The Medicinal Product

Paracetamol 500mg Soluble Tablets / Soluble Paracetamol Tablets 500mg

2. Qualitative And Quantitative Composition

Paracetamol 500mg Ph Eur.

3. Pharmaceutical Form

Effervescent tablet.

4. Clinical Particulars

4.1 Therapeutic Indications

Paracetamol Soluble is a mild analgesic and antipyretic. The tablets are recommended for the treatment of most painful conditions for example, headache, including migraine, toothache, sore throat, dysmenorrhoea, rheumatic pains and the symptomatic relief of colds and influenza.

4.2 Posology And Method Of Administration

Adults and children over 12 years:

1-2 tablets in at least half a tumbler full of water, up to 4 times daily as required. Do not take for more than 3 days without consulting your doctor.

These doses should not be given more frequently than every 4 hours, and not more than 4 doses should be given in any 24 hour period.

Children under 12 years:

Not recommended for children under the age of 12 years.

Route of administration: the tablets should be dissolved in water and are for oral administration only.

4.3 Contraindications

Hypersensitivity to paracetamol or any of the other constituents.

4.4 Special Warnings And Precautions For Use

Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.

Do not exceed the recommended dose.

Do not take with any other paracetamol-containing products.

If symptoms persist consult your doctor.

Keep out of the reach of children.

Immediate medical advice should be sought in the event of an overdose, even if you feel well, because of the risk of delayed, serious liver damage.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular daily use of paracetamol with increased risk of bleeding; occasional doses have no significant effect.

4.6 Pregnancy And Lactation

Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used in the recommended dosage, but patients should follow the advice of their doctor regarding its use.

Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data do not contraindicate breast feeding.

4.7 Effects On Ability To Drive And Use Machines

None.

4.8 Undesirable Effects

Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur. There have been a few reports of blood dyscrasias including thrombocytopenia and agranulocytosis but these were not necessarily causally related to paracetamol.

4.9 Overdose

Liver damage is possible in adults who have taken 10g or more of paracetamol. Ingestion of 5g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).

Risk factors

If the patient:

• is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St. John's Wort or other drugs that induce liver enzymes, or

• regularly consumes ethanol in excess of recommended amounts, or

• is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

Symptoms

Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.

Management

Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines (see BNF overdose section).

Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be used up to 24 hours after ingestion of paracetamol, however, the maximum protective effect is obtained up to 8 hours post-ingestion. The effectiveness of the antidote declines sharply after this time. If required the patient should be given intravenous N-acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside hospital. Management of patients who present with serious hepatic dysfunction beyond 24h from ingestion should be discussed with the NPIS or a liver unit.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Paracetamol is a well established analgesic.

5.2 Pharmacokinetic Properties

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Concentration of the drug in plasma reaches a peak in 30-60 minutes and the plasma half-life is 1-4 hours.

Paracetamol is relatively uniformly distributed throughout most body fluids and exhibits variable protein binding.

Excretion is almost exclusively renal, in the form of conjugated metabolites.

5.3 Preclinical Safety Data

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sodium bicarbonate,

Sorbitol powder

Saccharin sodium

Sodium lauryl sulphate

Citric acid (anhydrous)

Sodium carbonate (anhydrous)

Polyvidone

Dimeticone

Purified water

6.2 Incompatibilities

None

6.3 Shelf Life

48 months.

6.4 Special Precautions For Storage

Store below 25°C.

6.5 Nature And Contents Of Container

The tablets will be individually packed into PPFP laminate strips in cardboard cartons.

Pack size: 32, 48, 60, 100.

6.6 Special Precautions For Disposal And Other Handling

None

7. Marketing Authorisation Holder

Sterwin Medicines Limited

One Onslow Street

Guildford

Surrey

GU1 4YS

United Kingdom

Trading as: Sterwin Medicines, PO Box 611, Guildford, Surrey, GU1 4YS

8. Marketing Authorisation Number(S)

PL 17780/0162

9. Date Of First Authorisation/Renewal Of The Authorisation

17 November 2002

10. Date Of Revision Of The Text

18 August 2008

Jutadol

Jutadol may be available in the countries listed below.

Ingredient matches for Jutadol

Tramadol

Tramadol hydrochloride (a derivative of Tramadol) is reported as an ingredient of Jutadol in the following countries:

• Germany

International Drug Name Search

Actikerall 5mg / g + 100mg / g Cutaneous Solution

1. Name Of The Medicinal Product

Actikerall 5 mg/g + 100 mg/g Cutaneous Solution

2. Qualitative And Quantitative Composition

1 g of cutaneous solution contains 5 mg of fluorouracil and 100 mg of salicylic acid.

Excipient: 80 mg of dimethyl sulfoxide/g of solution.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Cutaneous solution.

Actikerall is a clear, colourless to slightly orange-white solution.

4. Clinical Particulars

4.1 Therapeutic Indications

Actikerall is indicated for the topical treatment of slightly palpable and/or moderately thick hyperkeratotic actinic keratosis (grade I/II) in immunocompetent adult patients.

Grade I/II intensity is based on the 4-point scale of Olsen et al. (1991), see section 5.1.

4.2 Posology And Method Of Administration

Cutaneous use.

In general Actikerall is applied to actinic keratoses once daily.

Response can be seen as early as in six weeks. Response increases over time and data are available for treatment up to 12 weeks. Complete healing of the lesion(s) or optimal therapeutic effect may not be evident for up to eight weeks after treatment cessation.

Paediatric population

Actinic keratosis is not a disease of a paediatric population. Therefore, the safety and efficacy of Actikerall in this population has not been established.

Method of administration

Multiple actinic keratoses can be treated simultaneously. There is experience in treating up to ten lesions at the same time. The total area of skin being treated with Actikerall at any one time should not exceed 25 cm² (5 cm x 5 cm).

Actikerall should only come into contact with the actinic keratosis and a rim of max. 0.5 cm of the healthy skin surrounding the lesion. To avoid overloading the brush with solution, the brush should be wiped off on the neck of the bottle before application.

The treated area should not be covered after application and the solution should be left to dry to form a film over the applied area.

Each time Actikerall is reapplied the existing film coating should be removed beforehand by simply peeling it off.

4.3 Contraindications

Hypersensitivity to the active ingredients or to any other excipients.

Actikerall must not be used during the lactation period, an existing pregnancy or by women for whom pregnancy cannot be excluded with certainty.

Actikerall must not be used to treat patients with renal insufficiency.

Actikerall must not be used in conjunction with brivudine, sorivudine and analogues. Brivudine, sorivudine and analogues are potent inhibitors of the fluorouracil-degrading enzyme dihydropyrimidine dehydrogenase (DPD) (see also sections 4.4 and 4.5).

Actikerall must not be allowed to come into contact with the eyes or mucous membranes.

4.4 Special Warnings And Precautions For Use

Actikerall contains the cytostatic agent 5-fluorouracil.

The enzyme dihydropyrimidine dehydrogenase (DPD) plays an important role in the breakdown of fluorouracil. Inhibition, deficiency or decreased activity of this enzyme can result in accumulation of fluorouracil.

If applicable, the determination of DPD enzyme activity is indicated before starting treatment with fluorouracil or other fluoropyrimidines.

Patients who take phenytoin concomitantly with fluorouracil should be regularly tested for elevated plasma levels of phenytoin.

In patients with sensory disturbances (e.g. those with diabetes mellitus) close medical monitoring of the treatment area is required.

There is currently no data available on Actikerall treatment of other body areas apart from the face, forehead and bald scalp.

If areas of skin with a thin epidermis are treated, the solution should be applied less frequently and the course of the therapy monitored more often.

This medicinal product contains dimethyl sulfoxide. May be irritant to the skin.

The bottle should be closed tightly after use or the solution will dry up quickly and can no longer be used correctly.

The solution should not be used if crystals occur.

Actikerall solution should not come into contact with textiles or acrylics (e.g. acrylic bathtubs) as the solution may cause permanent stains.

Caution flammable: keep away from fire or flames.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

The enzyme dihydropyrimidine dehydrogenase (DPD) plays an important role in the breakdown of fluorouracil. Nucleoside analogues such as brivudine and sorivudine may lead to a drastic increase in plasma concentrations of fluorouracil or other fluoropyrimidines and thus an associated increase in toxicity. For this reason, an interval of at least 4 weeks between the use of fluorouracil and brivudine, sorivudine and analogues should be observed.

In case of accidental administration of nucleoside analogues such as brivudine and sorivudine to patients who are being treated with fluorouracil, effective measures for reducing fluorouracil toxicity should be taken. Admission to a hospital may be indicated. All necessary measures for protection from systemic infections and dehydration should be introduced.

Elevated plasma levels of phenytoin leading to symptoms of phenytoin intoxication have been reported with the concomitant administration of phenytoin and fluorouracil (see 4.4).

There is no evidence for relevant systemic absorption of salicylic acid, however absorbed salicylic acid may interact with methotrexate and sulphonylureas.

4.6 Pregnancy And Lactation

Animal studies are insufficient with respect to fertility. However, because of the very limited absorption after cutaneous administration, any such effect is very unlikely to be of relevance in man.

There are no data from the use of topical fluorouracil in pregnant women. It is unknown whether fluorouracil or its metabolites are excreted in human milk after topical application. A risk to the suckling child cannot be excluded.

Despite the evidence that salicylic acid can adversely influence the outcome of pregnancy in rodents it can be concluded after many years of widespread clinical usage that the molecule has no teratogenic potential in humans whatever routes of clinical exposure are considered.

Actikerall is contraindicated in pregnancy and lactation (see section 4.3).

4.7 Effects On Ability To Drive And Use Machines

Actikerall has no influence on the ability to drive and use machines.

4.8 Undesirable Effects

The following categories of frequencies underlie the evaluation of side effects:

Very common	(
Common	(
Uncommon	(
Rare	(
Very rare	(< 1/10,000)
Not known	(cannot be estimated from the available data).

Application site reactions:

Very common: erythema, inflammation, irritation (including burning), pain, pruritus.

Common: bleeding, erosion, scab.

Uncommon: dermatitis, oedema, ulcer.

Skin and subcutaneous tissue disorders:

Common: skin exfoliation.

Nervous system disorders:

Common: headache.

Eye disorders:

Uncommon: dry eye, eye pruritus, increased lacrimation.

Mild to moderate irritation and inflammation at the application site occurred in the majority of patients treated with the solution for actinic keratosis. In case of severe reactions frequency of treatment may be reduced.

As the medicinal product has a very strong softening effect on the corneal layer, whitish discolorations and scaling of the skin may occur, particularly in the area surrounding the actinic keratosis.

Due to its salicylic acid content, use of this medicinal product may cause slight signs of irritation, such as dermatitis and contact allergic reactions, in patients of a corresponding disposition. Such contact allergy reactions may be manifested in the form of itching, reddening and small blisters even outside the area of application.

4.9 Overdose

When applied on the skin as recommended, systemic intoxications with either actives is unlikely. Significantly more applications than recommended result in an increase of frequency of reactions at the application site and their severity.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: fluorouracil, combinations, ATC code: L01BC52

Fluorouracil:

The active substance fluorouracil (FU) is a cytostatic agent that has an antimetabolite effect. Due to its structural similarity with the thymine (5-methyluracil) occurring in nucleic acids, FU prevents its formation and utilisation and in this way inhibits both DNA and RNA synthesis. The result is growth inhibition of those cells in particular which - as in the case of actinic keratosis - are at a stage of accelerated growth and therefore absorb FU in increased quantities. As a consequence also the growth of viruses, which can be involved in actinic keratosis development, is inhibited.

Thymine	Fluorouracil

Salicylic acid:

Topical salicylic acid has a keratolytic effect and reduces the hyperkeratosis associated with actinic keratosis. Salicylic acid is considered to be a phenolic aromatic acid and is lipid soluble. Its mechanism of action as a keratolytic and corneolytic agent is thought to be related to its interference with corneocyte adhesion, its solubilising effect on intercellular cement, and its loosening and detachment of corneocytes. By acting as an organic solvent, salicylic acid may remove intercellular lipids covalently linked to the cornified envelope surrounding cornified cells.

In a pivotal randomized, placebo-controlled, double-blind, three-armed, parallel group, multi-center Phase III trial 470 patients with actinic keratosis grade I to II were treated with either a solution of fluorouracil (5 mg/g) and salicylic acid (100 mg/g) (5-FU-SA) or placebo or a diclofenac gel (30 mg/g) (DG). 187 patients were exposed to the fixed combination 5-FU-SA for up to 12 weeks. Primary endpoint was the histological clearance of a lesion 8 weeks post end of treatment. Topical treatment with 5-FU-SA showed superiority to placebo treatment and to DG treatment. Secondary efficacy endpoints, like total lesion count, total AK lesion size, lesion response, physician's global assessment and subject's overall assessment of efficacy confirmed the results of the primary endpoint. In 72.0 % of the subjects in the 5-FU-SA group actinic keratosis could no longer be detected in the biopsy taken, whereas clearance rates in the DG and placebo groups were 59.1 % and 44.8 % respectively (per protocol analysis). The most frequent adverse reactions to 5-FU-SA were application and site irritation (including burning) (86.1 %) and application site inflammation (73.3 %). Also, application site pruritus (44.9 %) and application site pain (25.1%) occurred at a high frequency. Other adverse reactions were site erythema and site erosion. Discontinuation due to skin and application site reactions was low (0.5 %).

There is only clinical experience on the use of Actikerall on the face, forehead and bald scalp. When deciding on treatment of other parts of the body the epidermal thickness in different areas may be taken into consideration:

Average epidermal thickness of different body parts
Body part	Mean thickness (micrometer)
Face	49.4
Forehead	50.3
Upper trunk front (décolleté)	42.2
Arms/ legs	60.1
Source: Koehler et al. 2010 (Skin Res Technol 2010; 16:259-264); Sandby-Moller et al. 2003 (Acta Derm Venereol 2003; 83(6):410-3); Whitton et Everall 1973 (Br J Dermatol 1973; 89(5):467-76)

Actinic keratosis lesion intensity was graded according to the 4-point scale based on Olsen et al.,1991 (J Am Acad Dermatol 1991; 24: 738-743):

Grade	Clinical description of intensity grading
0	none	no AK lesion present, neither visible nor palpable
I	mild	flat, pink maculae without signs of hyperkeratosis and erythema, slight palpability, with AK felt better than seen
II	moderate	pink to reddish papules and erythematous plaques with hyperkeratotic surface, moderately thick AK that are easily seen and felt
III	severe	very thick and / or obvious AK

5.2 Pharmacokinetic Properties

In an absorption study carried out on pigs no fluorouracil was detected in the serum after the cutaneous application - even in large quantities - i.e. the active substance was not absorbed in quantities which could be detected with standard analytical methods (HPLC).

No fluorouracil concentration above 0.05 µg/ml could be identified in actinic keratosis patients (n=12).

According to a pharmacokinetic study analysing the absorption rate of fluorouracil in humans after the application in warts with the same formulation is markedly below 0.1 %.

After application on the skin Actikerall forms a solid film which appears white after the solvent has evaporated. This produces an occlusive effect which promotes penetration of the active substances into the epidermis, where actinic keratoses are located.

Salicylic acid has been added due to its keratolytic properties in order to improve penetration of the active substance, which is particularly difficult in the case of hyperkeratotic actinic keratoses. The same effect is achieved by the excipient dimethyl sulfoxide, which acts as a solubiliser for the active ingredient fluorouracil.

The keratolytic effect of salicylic acid is based on its direct action on the intracellular cement substances or desmosomes, which promote the cornification process.

Experiments on animals and human pharmacokinetic trials have shown that salicylic acid penetrates the surface rapidly, depending on the substrate and other factors influencing penetration, such as the condition of the skin.

Salicylic acid is metabolised by conjugation with glycine to form salicyluric acid, with glucuronic acid on the phenolic OH group to form ether glucuronide and on the COOH group to form ester glucuronide, or by hydroxylation to gentisic acid and dihydroxybenzoic acid. In the normal dose range the half-life of salicylic acid is between 2 and 3 hours, but may increase to 15 to 30 hours in the case of high dosages as a result of the limited capacity of the liver to conjugate salicylic acid.

No toxic side effects are generally to be expected from the topical application of salicylic acid (but see the contraindications), as serum levels above 5 mg/dl are hardly ever reached. Early symptoms of salicylate intoxication can only occur at serum values of more than 30 mg/dl.

5.3 Preclinical Safety Data

No experimental data on the acute and subchronic toxicity of fluorouracil after topical application are available. The results from repeat-dose toxicity studies in rats with daily dermal doses of fluorouracil between 5 and 50 mg/kg body weight (approximately 10,000 fold above the human doses) indicate that a dose-dependent systemic bioavailability occurs, resulting in severe local reactions and fatal systemic effects due to the antimetabolite actions of fluorouracil at higher doses. Such high doses are not reached with Actikerall when used as recommended.

A teratogenic effect of fluorouracil can be inferred from various experiments. Although the risk of mutagenesis in patients receiving fluorouracil cannot be clearly estimated, the possibility of a mutagenic effect must nevertheless be considered. Due to the small amount potentially absorbed from the externally applied Actikerall, mutagenicity by fluorouracil after systemic distribution e.g. on the gonads is very improbable. Data on the reproduction toxicity of fluorouracil do not show an influence of the compound on fertility and general reproduction performance. However, because of the very limited absorption after cutaneous administration, any such effect is very unlikely to be of relevance in man.

Salicylic acid has a low acute toxicity but may induce skin reactions after topical application at higher concentrations. Salicylic acid is not known to have any mutagenic, genotoxic, carcinogenic or teratogenic effects.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Dimethyl sulfoxide

Ethanol

Ethyl acetate

Pyroxyline

Poly(butyl methacrylate, methyl methacrylate)

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

2 years

Shelf life after opening: 3 months

6.4 Special Precautions For Storage

Do not store above 25 °C.

Do not refrigerate or freeze.

Keep the bottle tightly closed.

6.5 Nature And Contents Of Container

This medicinal product is packed in a brown glass bottle with a child resistant closure of white polypropylene in a cardboard carton. The closure of the bottle is connected to a brush to apply the solution. The brush applicator (CE mark) consists of polyethylene (HDPE and LDPE 1:1) with brush hairs of nylon secured in shaft with stainless steel (V2A).

Pack size: 25 ml solution.

6.6 Special Precautions For Disposal And Other Handling

Any unused product or waste material should be disposed of in accordance with local requirements.

7. Marketing Authorisation Holder

Almirall Hermal GmbH

Scholtzstrasse 3

21465 Reinbek

Germany

8. Marketing Authorisation Number(S)

PL 33016/0015

9. Date Of First Authorisation/Renewal Of The Authorisation

3 June 2011

10. Date Of Revision Of The Text

18 August 2011

Prednisone Intensol

Generic Name: prednisone (Oral route)

PRED-ni-sone

Commonly used brand name(s)

In the U.S.

• Deltasone


• Prednicot


• Prednisone Intensol


• Sterapred


• Sterapred DS

Available Dosage Forms:

• Tablet


• Syrup


• Solution

Therapeutic Class: Endocrine-Metabolic Agent

Pharmacologic Class: Adrenal Glucocorticoid

Uses For Prednisone Intensol

Prednisone provides relief for inflamed areas of the body. It is used to treat a number of different conditions, such as inflammation (swelling), severe allergies, adrenal problems, arthritis, asthma, blood or bone marrow problems, eye or vision problems, lupus, skin conditions, kidney problems, ulcerative colitis, and flare-ups of multiple sclerosis. Prednisone is a corticosteroid (cortisone-like medicine or steroid). It works on the immune system to help relieve swelling, redness, itching, and allergic reactions.

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

Before Using Prednisone Intensol

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

Allergies

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

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of prednisone in children. However, pediatric patients are more likely to have slower growth and bone problems if prednisone is used for a long time. Recommended doses should not be exceeded, and the patient should be carefully monitored during therapy.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of prednisone in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for elderly patients receiving prednisone.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

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.

• Rotavirus Vaccine, Live

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

• Aldesleukin


• Asparaginase


• Bupropion


• Gatifloxacin


• Quetiapine


• Telaprevir

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.

• Alatrofloxacin


• Alcuronium


• Alfalfa


• Amobarbital


• Aprobarbital


• Aspirin


• Atracurium


• Balofloxacin


• Butabarbital


• Butalbital


• Cinoxacin


• Ciprofloxacin


• Clarithromycin


• Clinafloxacin


• Enoxacin


• Fleroxacin


• Fluconazole


• Flumequine


• Fosphenytoin


• Gallamine


• Gemifloxacin


• Grepafloxacin


• Hexafluorenium


• Itraconazole


• Ketoconazole


• Levofloxacin


• Licorice


• Lomefloxacin


• Mephobarbital


• Metocurine


• Montelukast


• Moxifloxacin


• Norfloxacin


• Ofloxacin


• Pancuronium


• Pefloxacin


• Phenobarbital


• Phenytoin


• Primidone


• Prulifloxacin


• Rifampin


• Rifapentine


• Ritonavir


• Rosoxacin


• Rufloxacin


• Saiboku-To


• Secobarbital


• Sparfloxacin


• Temafloxacin


• Tosufloxacin


• Trovafloxacin Mesylate


• Vecuronium


• Warfarin

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

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

• Cataracts or


• Congestive heart failure or


• Cushing's syndrome (adrenal gland problem) or


• Diabetes or


• Eye infection or


• Glaucoma or


• Hyperglycemia (high blood sugar) or


• Hypertension (high blood pressure) or


• Infection (e.g., bacterial, virus, or fungus) or


• Mood changes, including depression or


• Myasthenia gravis (severe muscle weakness) or


• Osteoporosis (weak bones) or


• Peptic ulcer, active or history of or


• Personality changes or


• Stomach or intestinal problems (e.g., diverticulitis, ulcerative colitis) or


• Tuberculosis, inactive—Use with caution. May make these conditions worse.

• Fungal infections or


• Herpes simplex eye infection—Should not be used in patients with these conditions.

Proper Use of prednisone

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

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance for unwanted effects.

Take this medicine with food or milk to avoid stomach irritation.

Measure the oral liquid with a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid.

Prednisone Intensol™ solution is a concentrated liquid. Measure the concentrated liquid with the special oral dropper that comes with the package.

If you use this medicine for a long time, do not suddenly stop using it without checking first with your doctor. You may need to slowly decrease your dose before stopping it completely.

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 forms (concentrated solution, solution, and tablets):
  
  • Dose depends on medical condition:
    
    • Adults—At first, 5 to 60 milligrams (mg) per day. Your doctor may adjust your dose as needed.
    
    
    • 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.

Throw away any unused Prednisone Intensol™ solution 90 days after the bottle is opened for the first time.

Precautions While Using Prednisone Intensol

If you will be taking this medicine for a long time, it is very important that your doctor check you at regular visits for any unwanted effects that may be caused by this medicine. Blood or urine tests may be needed to check for unwanted 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 this medicine, tell your doctor right away.

If you are using this medicine for a long time, tell your doctor about any extra stress or anxiety in your life, including other health concerns and emotional stress. Your dose of this medicine might need to be changed for a short time while you have extra stress.

Using too much of this medicine or using it for a long time may increase your risk of having adrenal gland problems. Talk to your doctor right away if you have more than one of these symptoms while you are using this medicine: blurred vision; dizziness or fainting; a fast, irregular, or pounding heartbeat; increased thirst or urination; irritability; or unusual tiredness or weakness.

This medicine may cause you to get more infections than usual. Avoid people who are sick or have infections and wash your hands often. If you are exposed to chickenpox or measles, tell your doctor right away. If you start to have a fever, chills, sore throat, or any other sign of an infection, call your doctor right away.

Check with your doctor right away if blurred vision, difficulty in reading, eye pain, or any other change in vision occurs during or after treatment. Your doctor may want you to have your eyes checked by an ophthalmologist (eye doctor).

While you are being treated with prednisone, do not have any immunizations (vaccines) without your doctor's approval. Prednisone may lower your body's resistance and the vaccine may not work as well or you might get the infection the vaccine is meant to prevent. In addition, you should not be around other persons living in your household who receive live virus vaccines because there is a chance they could pass the virus on to you. Some examples of live vaccines include measles, mumps, influenza (nasal flu vaccine), poliovirus (oral form), rotavirus, and rubella. Do not get close to them and do not stay in the same room with them for very long. If you have questions about this, talk to your doctor.

This medicine may cause changes in mood or behavior for some patients. Tell your doctor right away if you have depression; mood swings; a false or unusual sense of well-being; trouble with sleeping; or personality changes while taking this medicine.

This medicine might cause thinning of the bones (osteoporosis) or slow growth in children if used for a long time. Tell your doctor if you have any bone pain or if you have an increased risk for osteoporosis. If your child is using this medicine, tell the doctor if you think your child is not growing properly.

Make sure any doctor or dentist who treats you knows that you are using this medicine. This medicine may affect the results of certain skin tests.

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

Prednisone Intensol 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:

More common

• Aggression


• agitation


• anxiety


• blurred vision


• decrease in the amount of urine


• dizziness


• fast, slow, pounding, or irregular heartbeat or pulse


• headache


• irritability


• mental depression


• mood changes


• nervousness


• noisy, rattling breathing


• numbness or tingling in the arms or legs


• pounding in the ears


• shortness of breath


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


• trouble thinking, speaking, or walking


• troubled breathing at rest


• weight gain

Incidence not known

• Abdominal cramping and/or burning (severe)


• abdominal pain


• backache


• bloody, black, or tarry stools


• cough or hoarseness


• darkening of skin


• decrease in height


• decreased vision


• diarrhea


• dry mouth


• eye pain


• eye tearing


• facial hair growth in females


• fainting


• fatigue


• fever or chills


• flushed, dry skin


• fractures


• fruit-like breath odor


• full or round face, neck, or trunk


• heartburn and/or indigestion (severe and continuous)


• increased hunger


• increased thirst


• increased urination


• loss of appetite


• loss of sexual desire or ability


• lower back or side pain


• menstrual irregularities


• muscle pain or tenderness


• muscle wasting or weakness


• nausea


• pain in back, ribs, arms, or legs


• painful or difficult urination


• skin rash


• sleeplessness


• sweating


• trouble healing


• trouble sleeping


• unexplained weight loss


• unusual tiredness or weakness


• vision changes


• vomiting


• vomiting of material that looks like coffee grounds

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

• Increased appetite

Incidence not known

• Abnormal fat deposits on the face, neck, and trunk


• acne


• dry scalp


• lightening of normal skin color


• red face


• reddish purple lines on the arms, face, legs, trunk, or groin


• swelling of the stomach area


• thinning of the scalp hair

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.

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