Loceryl Nail Lacquer 5%

1. Name Of The Medicinal Product

Loceryl 5% w/v Medicated Nail Lacquer

2. Qualitative And Quantitative Composition

Loceryl nail lacquer contains 5% w/v amorolfine in the form of hydrochloride. Amorolfine is chemically described as cis-4-[(RS)-3[4-(1,1-Dimethylpropyl)phenyl]-2-methylpropyl]-2,6-dimethylmorpholine.

Amorolfine hydrochloride HSE 6.40 w/w

For a full list of excipients, see section 6.1

3. Pharmaceutical Form

Medicated Nail Lacquer.

4. Clinical Particulars

4.1 Therapeutic Indications

Onychomycoses caused by dermatophytes, yeasts and moulds.

4.2 Posology And Method Of Administration

The nail lacquer should be applied to the affected finger or toe nails once weekly. Twice weekly application may prove beneficial in some cases.

The patient should apply the nail lacquer as follows:

1. Before the first application of Loceryl, it is essential that the affected areas of nail (particularly the nail surfaces) should be filed down as thoroughly as possible using the nail file supplied. The surface of the nail should then be cleansed and degreased using a cleaning pad (as supplied). Before repeat application of Loceryl, the affected nails should be filed down again as required, following cleansing with a cleaning pad to remove any remaining lacquer.

Caution: Nail files used for affected nails must not be used for healthy nails.

2. With one of the reusable applicators supplied, apply the nail lacquer to the entire surface of the affected nails and allow it to dry. After use, clean the applicator with the same cleaning pad used before for nail cleaning. Keep the bottle tightly closed.

For each nail to be treated, dip the applicator into the nail lacquer without wiping off any of the lacquer on the bottle neck.

Caution: When working with organic solvents (thinners, white spirit, etc.) wear impermeable gloves in order to protect the Loceryl lacquer on the nails.

Treatment should be continued without interruption until the nail is regenerated and the affected areas are finally cured. The required frequency and duration of treatment depends essentially on intensity and localisation of the infection. In general, it is six months (finger nails) and nine to twelve months (toe nails). A review of the treatment is recommended at intervals of approximately three months.

Co-existent tinea pedis should be treated with an appropriate antimycotic cream.

Elderly

There are no specific dosage recommendations for use in elderly patients.

Children

There are no specific dosage recommendations for children owing to the lack of clinical experience available to date.

4.3 Contraindications

Loceryl nail lacquer must not be reused by patients who have shown hypersensitivity to the active substance or to any of the excipients.

No experience exists of use during pregnancy and nursing, therefore, the use of Loceryl should be avoided during pregnancy and lactation.

4.4 Special Warnings And Precautions For Use

Avoid contact of the lacquer with eyes, ears and mucous membranes.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

There are no specific studies involving concomitant treatment with other topical medicines.

Use of nail varnish or artificial nails should be avoided during treatment.

4.6 Pregnancy And Lactation

Reproductive toxicology studies showed no evidence of teratogenicity in laboratory animals but embryotoxicity was observed at high oral doses. The systemic absorption of amorolfine during and after topical administration is very low and therefore the risk to the human foetus appears to be negligible. However, because there is no relevant experience, Loceryl should be avoided during pregnancy and breast feeding.

4.7 Effects On Ability To Drive And Use Machines

Loceryl Nail Lacquer has no influence on the ability to drive and use machines.

4.8 Undesirable Effects

Adverse drug reactions are rare. Nail disorders (e.g. nail discoloration, broken nails, brittle nails) may occur. These reactions can also be linked to the onychomycosis itself.

System Organ Class	Frequency	Adverse drug reaction
Skin and subcutaneous tissue disorders	Rare (	Nail disorder, nail discoloration, onychoclasis (broken nails), onychorrhexis (brittle nails)
Very rare ( < 1/10000)	Skin burning sensation

Contact dermatitis (unknown frequency) has been reported in spontaneous reports.

4.9 Overdose

Accidental oral ingestion

Loceryl is for topical use. In the event of accidental oral ingestion, an appropriate method of gastric emptying may be used.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic Group: Other antifungals for topical use ATC code: D01AE16

Loceryl is a topical antimycotic. Amorolfine belongs to a new chemical class, and its fungicidal action is based on an alteration of the fungal cell membrane targeted primarily on sterol biosynthesis. The ergosterol content is reduced, and at the same time unusual sterically nonplanar sterols accumulate.

Amorolfine is a broad spectrum antimycotic. It is highly active (MIC < 2mcg/ml) in vitro against

yeasts:	Candida, Cryptococcus, Malassezia
dermatophytes:	Trichophyton, Microsporum, Epidermophyton
moulds:	Hendersonula, Alternaria, Scopulariopsis
dematiacea:	Cladosporium, Fonsecaea, Wangiella
dimorphic fungi:	Coccidioides, Histoplasma, Sporothrix

With the exception of Actinomyces, bacteria are not sensitive to amorolfine. Propionibacterium acnes is only slightly sensitive.

5.2 Pharmacokinetic Properties

Amorolfine from nail lacquer penetrates into and diffuses through the nail plate and is thus able to eradicate poorly accessible fungi in the nail bed. Systemic absorption of the active ingredient is very low with this type of application.

Following prolonged use of Loceryl Nail Lacquer, there is no indication of drug accumulation in the body.

5.3 Preclinical Safety Data

None stated.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Ammonio methacrylate copolymer A

triacetin

butyl acetate

ethyl acetate

ethanol absolute.

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Loceryl nail lacquer should be stored below 30°C. Protect from heat. Keep bottle tightly closed after use.

6.5 Nature And Contents Of Container

Amber glass container with screw thread and plastic screw closure.

Pack Sizes:	2.5 ml (1 x 2.5 ml)
	5.0 ml (1 x 5.0 ml)
	7.5 ml (1 x 2.5 ml & 1 x 5.0 ml)
	10.0 ml (2 x 5.0 ml)

All packs contain cleansing swabs, spatulas and nail files.

Not all pack sizes may be marketed

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Galderma (UK) Limited

Meridien House

69-71 Clarendon Road

Watford

Herts.

WD17 1DS

UK

8. Marketing Authorisation Number(S)

PL 10590/0042

9. Date Of First Authorisation/Renewal Of The Authorisation

April 1999

10. Date Of Revision Of The Text

November 2010

Promethegan

Generic Name: promethazine (Rectal route)

proe-METH-a-zeen

Rectal route(Suppository)

Promethazine hydrochloride should not be used in pediatric patients less than 2 years of age because of the potential for fatal respiratory depression. Exercise caution when administering to pediatric patients 2 years of age and older and use at the lowest effective dose. Avoid concomitant use of other drugs with respiratory depressant effects .

Commonly used brand name(s)

In the U.S.

• Phenadoz


• Phenergan


• Promethegan

Available Dosage Forms:

• Suppository

Therapeutic Class: Gastrointestinal Agent

Pharmacologic Class: Antihistamine

Chemical Class: Aliphatic

Uses For Promethegan

Promethazine is used to relieve or prevent the symptoms of hay fever, allergic conjunctivitis (inflammation of the eye), and other types of allergy or allergic reactions. It works by preventing the effects of a substance called histamine, which is produced by the body. Histamine can cause itching, sneezing, runny nose, and watery eyes. It can sometimes close up the bronchial tubes (air passages of the lungs) and make breathing difficult .

Promethazine is also used to prevent and control motion sickness, nausea, vomiting, and dizziness. In addition, it may be used to help people go to sleep and control their pain or anxiety before or after surgery or other procedures .

Promethazine may also be used for other conditions as determined by your doctor .

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

Before Using Promethegan

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

Allergies

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

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of promethazine in the pediatric population. Safety and efficacy have not been established in children below 2 years of age. Caution should be used when this medicine is given to children 2 years of age and older .

Geriatric

Insufficient information is available on the relationship of age to the effects of promethazine in geriatric patients. However, elderly patients may be more sensitive to the side effects of this medicine (such as confusion and severe drowsiness) than in younger adults, and are more likely to have age-related heart or blood vessel disease, liver problems, and kidney disease, which may require adjustment of dosage in patients receiving promethazine .

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

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Cisapride


• Dronedarone


• Grepafloxacin


• Mesoridazine


• Metoclopramide


• Pimozide


• Sparfloxacin


• Thioridazine

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.

• Alfuzosin


• Amiodarone


• Amitriptyline


• Amoxapine


• Apomorphine


• Arsenic Trioxide


• Asenapine


• Astemizole


• Azithromycin


• Chloroquine


• Chlorpromazine


• Ciprofloxacin


• Citalopram


• Clarithromycin


• Clomipramine


• Clozapine


• Crizotinib


• Dasatinib


• Desipramine


• Disopyramide


• Dofetilide


• Dolasetron


• Droperidol


• Erythromycin


• Fentanyl


• Flecainide


• Fluconazole


• Gatifloxacin


• Gemifloxacin


• Granisetron


• Halofantrine


• Haloperidol


• Hydromorphone


• Ibutilide


• Iloperidone


• Imipramine


• Isradipine


• Lapatinib


• Levofloxacin


• Levorphanol


• Lithium


• Lopinavir


• Lumefantrine


• Mefloquine


• Methadone


• Metrizamide


• Morphine


• Morphine Sulfate Liposome


• Moxifloxacin


• Nilotinib


• Norfloxacin


• Nortriptyline


• Octreotide


• Ofloxacin


• Ondansetron


• Oxycodone


• Paliperidone


• Pazopanib


• Pentamidine


• Perflutren Lipid Microsphere


• Posaconazole


• Procainamide


• Procarbazine


• Prochlorperazine


• Propafenone


• Protriptyline


• Quetiapine


• Quinine


• Ranolazine


• Salmeterol


• Saquinavir


• Sodium Phosphate


• Sodium Phosphate, Dibasic


• Sodium Phosphate, Monobasic


• Solifenacin


• Sorafenib


• Sotalol


• Sunitinib


• Tapentadol


• Telavancin


• Telithromycin


• Terfenadine


• Tetrabenazine


• Toremifene


• Tramadol


• Trifluoperazine


• Trimipramine


• Vandetanib


• Vardenafil


• Vemurafenib


• Voriconazole


• Ziprasidone


• Zolpidem

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.

• Belladonna


• Belladonna Alkaloids


• Betel Nut


• Evening Primrose


• Meperidine


• Midodrine


• Phenylalanine

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:

• Brain disease or injury or


• Breathing or lung problems (e.g., asthma) or


• Comatose state (unconscious) or


• Reye's syndrome or


• Sleep apnea, history of—Promethazine should NOT be used in patients with any of these conditions .

• Bone marrow disease or


• Enlarged prostate or


• Glaucoma or


• Heart or blood vessel disease or


• Intestinal tract obstruction or


• Jaundice or


• Liver disease or


• Neuroleptic malignant syndrome, or history of, or


• Stomach ulcer or


• Urinary tract blockage or difficult urination—Use with caution. This medicine may make these conditions worse .

• Seizure disorders—This medicine may increase the chance of seizures especially in patients who are also using narcotic or anesthetic medicines .

Proper Use of promethazine

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

Never take rectal suppositories by mouth.

Wash your hands with soap and water before and after using this medicine.

To insert suppository: First remove the foil wrapper and moisten the suppository with cold water. Lie down on your side and use your finger to push the suppository well up into the rectum. If the suppository is too soft to insert, chill the suppository in the refrigerator for 30 minutes or run cold water over it before removing the foil wrapper.

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 rectal dosage form (suppositories):
  
  • For allergy symptoms:
    
    • Adults and teenagers—12.5 milligrams (mg) before meals and at bedtime; or 25 mg at bedtime as needed.
    
    
    • Children 2 years of age and older—Your doctor will determine dose based on the weight and/or size of the child. The dose is usually 6.25 to 12.5 mg three times a day; or 25 mg at bedtime as needed.
    
    
    • Children younger than 2 years of age—Use and dose must be determined by your doctor .
    
    
  
  
  • For prevention of motion sickness:
    
    • Adults and teenagers—25 mg twice daily; this initial dose should be taken one-half to one hour before traveling. The dose may be repeated eight to twelve hours later if needed. On other days of travel, 25 mg may be taken on arising and again before the evening meal.
    
    
    • Children 2 years of age and older—Your doctor will determine dose based on the weight and/or size of the child. The dose is usually 12.5 to 25 mg one-half to one hour before traveling. The dose may be repeated eight to twelve hours later if needed.
    
    
    • Children younger than 2 years of age—Use and dose must be determined by your doctor .
    
    
  
  
  • For nausea and vomiting:
    
    • Adults and teenagers—25 mg for the first dose, then 12.5 to 25 mg every four to six hours if needed.
    
    
    • Children 2 years of age and older—Your doctor will determine dose based on the weight and/or size of the child. The dose is usually 0.5 mg per pound of body weight (1.1 mg per kg) or 12.5 to 25 mg every four to six hours as needed.
    
    
    • Children younger than 2 years of age—Use and dose must be determined by your doctor .
    
    
  
  
  • For sedation:
    
    • Adults and teenagers—25 to 50 mg.
    
    
    • Children 2 years of age and older—Your doctor will determine dose based on the weight and/or size of the child. The dose is usually 12.5 to 25 mg.
    
    
    • Children younger than 2 years of age—Use and dose must be determined by your doctor .
    
    
  
  
  • For control of pain or anxiety before or after surgery:
    
    • Adults and teenagers—50 mg the night before surgery; 25 to 50 mg after surgery.
    
    
    • Children 2 years of age and older—Your doctor will determine dose based on the weight and/or size of the child. The dose is usually 0.5 mg per pound of body weight (1.1 mg per kg) or 12.5 to 25 mg the night before surgery or after the surgery.
    
    
    • Children younger than 2 years of age—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.

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

Do not keep outdated medicine or medicine no longer needed.

Keep out of the reach of children.

Precautions While Using Promethegan

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests may be needed to check for unwanted effects .

This medicine may affect blood sugar levels. If you notice a change in the results of your blood or urine sugar tests or if you have any questions, check with your doctor .

This medicine may cause some people to become dizzy, lightheaded, drowsy, or less alert than they are normally. Even if taken at bedtime, it may cause some people to feel drowsy or less alert on arising. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are not alert .

This medicine will add to the effects of alcohol and other CNS depressants (medicines that make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds; sedatives, tranquilizers, antidepressants, or sleeping medicine; prescription pain medicine or narcotics; barbiturates; medicine for seizures; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your medical doctor or dentist before taking any of the above while you are taking this medicine.

Check with your doctor right away if you have symptoms of pale or blue lips, fingernails, or skin; difficult or troubled breathing; irregular, fast, slow, or shallow breathing; or shortness of breath. These could be signs of a condition called respiratory depression .

Check with your doctor right away and stop taking your medicine (if directed by your doctor) if you have muscle stiffness, fever, difficult or fast breathing, seizures, fast heartbeat, increased sweating, loss of bladder control, unusually pale skin, or tiredness or weakness. These may be symptoms of a serious condition called neuroleptic malignant syndrome (NMS) .

Before you have any medical tests, tell the medical doctor in charge that you are taking this medicine. The results of some tests may be affected by this medicine .

This medicine may cause dryness of the mouth. For temporary relief, use sugarless candy or gum, melt bits of ice in your mouth, or use a saliva substitute. However, if your mouth continues to feel dry for more than 2 weeks, check with your medical doctor or dentist. Continuing dryness of the mouth may increase the chance of dental disease, including tooth decay, gum disease, and fungus infections .

This medicine may make your skin more sensitive to sunlight. Use a sunscreen when you are outdoors. Avoid sunlamps and tanning beds .

This medicine controls nausea and vomiting. For this reason, it may cover up some of the signs of overdose caused by other medicines or the symptoms of encephalopathy or Reye's syndrome. This will make it difficult for your doctor to diagnose these conditions. Make sure your doctor knows that you are using this medicine .

Promethegan 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:

Stop taking this medicine and get emergency help immediately if any of the following effects occur:

Rare - Symptoms of neuroleptic malignant syndrome; two or more occur together; most of these effects do not require emergency medical attention if they occur alone

• Convulsions (seizures)


• difficult or unusually fast breathing


• fast heartbeat or irregular pulse


• high fever


• high or low (irregular) blood pressure


• increased sweating


• loss of bladder control


• severe muscle stiffness


• unusually pale skin


• unusual tiredness or weakness

Incidence not known

• Abdominal or stomach pain


• black, tarry stools


• bleeding gums


• blood in urine or stools


• bloody nose


• blurred vision


• chest pain or discomfort


• chills


• clay-colored stools


• confusion as to time, place, or person


• cough or hoarseness


• dark urine


• decreased awareness or responsiveness


• difficulty or troubled breathing


• double vision


• fast, pounding, or irregular heartbeat or pulse


• fever with or without chills


• fixed position of eye


• headache


• heavier menstrual periods


• high fever


• holding false beliefs that cannot be changed by fact


• hyperexcitability


• increased or decreased blood pressure


• increased sweating


• irregular, fast or slow, or shallow breathing


• itching


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


• lightheadedness, dizziness, or fainting


• loss of appetite


• loss of bladder control


• lower back or side pain


• mimicry of speech or movements


• mutism


• nasal stuffiness


• nausea


• negativism


• nightmares


• noisy breathing


• not breathing


• painful or difficult urination


• pale or blue lips, fingernails, or skin


• peculiar postures or movements, mannerisms or grimacing


• pinpoint red spots on skin


• seeing double


• seeing, hearing, or feeling things that are not there


• seizures


• severe muscle stiffness


• severe sleepiness


• shortness of breath


• skin rash


• slow or irregular heartbeat


• sore throat


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


• sticking out of tongue


• swollen glands


• tightness in chest


• tremors


• uncontrolled twisting movements of neck


• unpleasant breath odor


• unusual bleeding or bruising


• unusual excitement, nervousness, or restlessness


• unusual tiredness or weakness


• vomiting of blood


• wheezing


• yellow eyes or skin

Symptoms of overdose

• Discouragement


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


• dry mouth


• excessive muscle tone


• feeling of warmth


• feeling sad or empty


• irritability


• lack of appetite


• loss of interest or pleasure


• muscle tension or tightness


• overactive reflexes


• pupils of eyes large and not moving or responding to light


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


• shakiness and unsteady walk


• sudden death


• trouble concentrating


• trouble sleeping


• unconsciousness


• unsteadiness, trembling, or other problems with muscle control or coordination


• unusual paleness

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:

Incidence not known

• blistering, crusting, irritation, itching, or reddening of skin


• continuing ringing or buzzing or other unexplained noise in ears


• cracked, dry, scaly skin


• dizziness


• drowsiness


• excitation


• false or unusual sense of well-being


• hearing loss


• hives or welts


• increased sensitivity of skin to sunlight


• lack of coordination


• loss of strength or energy


• muscle pain or weakness


• redness or other discoloration of skin


• relaxed and calm


• sunburn


• swelling


• unable to sleep


• vomiting

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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

See also: Promethegan side effects (in more detail)

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More Promethegan resources

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

• Promethegan Prescribing Information (FDA)


• Promethazine Prescribing Information (FDA)


• Phenadoz Prescribing Information (FDA)


• Phenergan MedFacts Consumer Leaflet (Wolters Kluwer)


• Phenergan Prescribing Information (FDA)


• Phenergan Consumer Overview


• Promethazine Hydrochloride Monograph (AHFS DI)

Compare Promethegan with other medications

• Allergic Reactions
• Anaphylaxis
• Hay Fever
• Light Sedation
• Motion Sickness
• Nausea/Vomiting
• Opiate Adjunct
• Sedation
• Urticaria
• Vertigo

Carbatab-12 Sustained-Release Tablets

Pronunciation: car-beta-PEN-tane/gwye-FEN-e-sin/FEN-il-EF-rin
Generic Name: Carbetapentane/Guaifenesin/Phenylephrine
Brand Name: Examples include Carbatab-12 and Oratuss 12

Carbatab-12 Sustained-Release Tablets are used for:

Relieving congestion, cough, and throat and airway irritation due to colds, flu, or hay fever. It may also be used for other conditions as determined by your doctor.

Carbatab-12 Sustained-Release Tablets are a decongestant, cough suppressant, and expectorant combination. It works by constricting blood vessels and reducing swelling in the nasal passages, loosening mucus and lung secretions in the chest, and making coughs more productive. The cough suppressant works in the brain to help decrease the cough reflex to reduce a dry cough.

Do NOT use Carbatab-12 Sustained-Release Tablets if:

• you are allergic to any ingredient in Carbatab-12 Sustained-Release Tablets


• you have an overactive thyroid, uncontrolled high blood pressure, rapid heartbeat, or other severe heart problems (eg, heart blood vessel disease)


• you take droxidopa or have taken furazolidone a monoamine oxidase inhibitor (MAOI) (eg, phenelzine) within the last 14 days

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

Before using Carbatab-12 Sustained-Release Tablets:

Some medical conditions may interact with Carbatab-12 Sustained-Release Tablets. 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 a history of glaucoma or increased pressure in the eye, an enlarged prostate gland or other prostate problems, heart problems, diabetes, high blood pressure, blood vessel problems, adrenal gland problems (eg, pheochromocytoma), mental or mood problems (eg, depression), trouble sleeping, an overactive thyroid, seizures, or stroke


• if you have a chronic cough, chronic obstructive pulmonary disease (COPD), or other lung problems (eg, asthma, chronic bronchitis, emphysema), or if your cough produces large amounts of mucus


• if you are in poor health or are very overweight

Some MEDICINES MAY INTERACT with Carbatab-12 Sustained-Release Tablets. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Beta-blockers (eg, propranolol), catechol-o-methyltransferase (COMT) inhibitors (eg, tolcapone), furazolidone, indomethacin, MAOIs (eg, phenelzine), or tricyclic antidepressants (eg, amitriptyline) because they may increase the risk of Carbatab-12 Sustained-Release Tablets's side effects


• Digoxin or droxidopa because the risk of irregular heartbeat or heart attack may be increased


• Alpha-blockers (eg, prazosin) or bromocriptine because the risk of its side effects may be increased by Carbatab-12 Sustained-Release Tablets


• Guanadrel, guanethidine, mecamylamine, medicines for high blood pressure, methyldopa, or reserpine because their effectiveness may be decreased by Carbatab-12 Sustained-Release Tablets

This may not be a complete list of all interactions that may occur. Ask your health care provider if Carbatab-12 Sustained-Release Tablets 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 Carbatab-12 Sustained-Release Tablets:

Use Carbatab-12 Sustained-Release Tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Carbatab-12 Sustained-Release Tablets by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation.


• Swallow Carbatab-12 Sustained-Release Tablets whole. Do not break, crush, or chew before swallowing. Some brands of Carbatab-12 Sustained-Release Tablets may be broken in half before taking. If you have difficulty swallowing the whole tablet, ask your pharmacist if your brand of medicine may be broken in half.


• Take Carbatab-12 Sustained-Release Tablets with a full glass of water (8 oz/240 mL).


• Drink plenty of water while taking Carbatab-12 Sustained-Release Tablets.


• If you miss a dose of Carbatab-12 Sustained-Release Tablets, take it as soon as possible. If it is almost time for your next dose, skip the missed dose. 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 Carbatab-12 Sustained-Release Tablets.

Important safety information:

• Carbatab-12 Sustained-Release Tablets may cause dizziness or drowsiness. These effects may be worse if you take it with alcohol or certain medicines. Use Carbatab-12 Sustained-Release Tablets with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Do not use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using Carbatab-12 Sustained-Release Tablets; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.


• Do not take appetite suppressants while you are taking Carbatab-12 Sustained-Release Tablets without checking with your doctor.


• Carbatab-12 Sustained-Release Tablets has phenylephrine, carbetapentane, and guaifenesin in it. Before you start any new medicine, check the label to see if it has phenylephrine, carbetapentane, or guaifenesin in it too. If it does or if you are not sure, check with your doctor or pharmacist.


• Do not use Carbatab-12 Sustained-Release Tablets for a cough with a lot of mucus. Do not use it for a long-term cough (eg, caused by asthma, emphysema, smoking). However, you may use it for these conditions if your doctor tells you to.


• Do NOT take more than the recommended dose or use for longer than prescribed without checking with your doctor.


• If your symptoms do not get better within 5 to 7 days or if they get worse, check with your doctor.


• If cough persists for more than 1 week or is accompanied by a fever, rash, headache, or sore throat, contact your heath care provider. A persistent cough could be a sign of a serious condition.


• Carbatab-12 Sustained-Release Tablets may interfere with certain lab tests. Be sure your doctors and lab personnel know that you are taking Carbatab-12 Sustained-Release Tablets.


• Tell your doctor or dentist that you take Carbatab-12 Sustained-Release Tablets before you receive any medical or dental care, emergency care, or surgery.


• Use Carbatab-12 Sustained-Release Tablets with caution in the ELDERLY; they may be more sensitive to its effects.


• Caution is advised when using Carbatab-12 Sustained-Release Tablets in CHILDREN; they may be more sensitive to its effects.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Carbatab-12 Sustained-Release Tablets while you are pregnant. It is not known if Carbatab-12 Sustained-Release Tablets are found in breast milk. Do not breast-feed while taking Carbatab-12 Sustained-Release Tablets.

Possible side effects of Carbatab-12 Sustained-Release Tablets:

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:

Diarrhea; dizziness; drowsiness; excitability; headache; irritability; nausea; stomach upset; trouble sleeping.

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); difficulty urinating; fast, slow, or irregular heartbeat; fever; hallucinations; mental or mood changes (eg, anxiety, nervousness); paleness; seizures; severe or persistent dizziness, lightheadedness, or headache; tremor.

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: Carbatab-12 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 bizarre behavior; blurred vision; confusion; difficulty urinating; fast or shallow breathing; hallucinations; paleness; restlessness; seizures; severe dizziness, lightheadedness, or headache; severe drowsiness; tremor; unusually fast, slow, or irregular heartbeat; vomiting.

Proper storage of Carbatab-12 Sustained-Release Tablets:

Store Carbatab-12 Sustained-Release Tablets at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Carbatab-12 Sustained-Release Tablets out of the reach of children and away from pets.

General information:

• If you have any questions about Carbatab-12 Sustained-Release Tablets, please talk with your doctor, pharmacist, or other health care provider.


• Carbatab-12 Sustained-Release Tablets are 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 Carbatab-12 Sustained-Release Tablets. 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 Carbatab-12 resources

• Carbatab-12 Side Effects (in more detail)
• Carbatab-12 Use in Pregnancy & Breastfeeding
• Carbatab-12 Drug Interactions
• Carbatab-12 Support Group
• 0 Reviews for Carbatab-12 - Add your own review/rating

Compare Carbatab-12 with other medications

• Cough and Nasal Congestion

Clove Oil BP

1. Name Of The Medicinal Product

Clove Oil BP.

2. Qualitative And Quantitative Composition

Clove Oil BP 100% v/v.

3. Pharmaceutical Form

Dental Solution

4. Clinical Particulars

4.1 Therapeutic Indications

For the temporary relief of toothache.

4.2 Posology And Method Of Administration

Local.

Adults, the elderly and children:

Apply on cotton wool to the tooth cavity as required.

4.3 Contraindications

Contra-indicated in patients hypersensitive to clove oil or eugenol.

4.4 Special Warnings And Precautions For Use

Use with caution in the mouth or if sensitive to clove oil.

Avoid contact with the skin.

Repeated use may cause gum damage.

Seek dental attention as soon as possible.

Use with caution in children under 2 years.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

May enhance inhibition of platelet activity in patients receiving anti-coagulant therapy.

4.6 Pregnancy And Lactation

As for all medicines, use only with caution during pregnancy and lactation.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

Contact with skin or soft tissue may cause transient irritation, contact dermatitis, inflammation of the lips, and inflammation or ulceration of the mouth.

Patients may become sensitive to clove oil.

4.9 Overdose

Accidental oral ingestion of clove oil may lead to CNS depression, urinary abnormalities, anion-gap acidosis, deterioration of liver function, coma, seizure and low blood glucose levels.

Treatment should be supportive and symptomatic; there have been reports in the literature that N-acetylcysteine has been successfully used as an antidote.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Clove Oil has local anaesthetic, antiseptic and antihistaminic properties, and is used as an anodyne in toothache.

5.2 Pharmacokinetic Properties

Clove Oil acts at the site of application.

No data exists on the human pharmacokinetics of Eugenol the principle ingredient of Clove Oil.

In the rat 20-30% of Eugenol is metabolised to homovanillic acid and 4-hydroxy-3-methoxymandelic acid.

5.3 Preclinical Safety Data

None.

6. Pharmaceutical Particulars

6.1 List Of Excipients

None.

6.2 Incompatibilities

None known.

6.3 Shelf Life

10ml:	36 months unopened.
50ml:	36 months unopened.

6.4 Special Precautions For Storage

Store below 25°C.

Keep container tightly closed and protect from light.

6.5 Nature And Contents Of Container

10ml & 50ml: amber glass bottle with plastic cap or white plastic child resistant cap with EPE/Saranex liner or white 28mm polypropylene cap with Tamper Evident band and EPE/ Saranex liner.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

L.C.M. Ltd.

Linthwaite Laboratories

Huddersfield

HD7 5QH

England.

8. Marketing Authorisation Number(S)

PL: 12965/0006

9. Date Of First Authorisation/Renewal Of The Authorisation

25.08.93 / 11.11.98/

10. Date Of Revision Of The Text

10.11.2008

11 DOSIMETRY (IF APPLICABLE)

Not Applicable

12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS (IF APPLICABLE)

Not Applicable

Nalfon

Generic Name: fenoprofen (fen oh PROE fen)

Brand Names: Nalfon

What is Nalfon (fenoprofen)?

Fenoprofen is in a group of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). Fenoprofen works by reducing hormones that cause inflammation and pain in the body.

Fenoprofen is used to treat pain or inflammation caused by arthritis.

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

What is the most important information I should know about Nalfon (fenoprofen)?

This medicine can increase your risk of life-threatening heart or circulation problems, including heart attack or stroke. Do not use this medicine just before or after having heart bypass surgery (also called coronary artery bypass graft, or CABG).

Seek emergency medical help if you have symptoms of heart or circulation problems, such as chest pain, weakness, shortness of breath, slurred speech, or problems with vision or balance.

This medicine can also increase your risk of serious effects on the stomach or intestines, including bleeding or perforation (forming of a hole). These conditions can be fatal and gastrointestinal effects can occur without warning at any time while you are taking fenoprofen. Older adults may have an even greater risk of these serious gastrointestinal side effects.

Call your doctor at once if you have symptoms of bleeding in your stomach or intestines. This includes 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 taking Nalfon (fenoprofen)?

Taking an NSAID can increase your risk of life-threatening heart or circulation problems, including heart attack or stroke. This risk will increase the longer you use an NSAID. Do not use this medicine just before or after having heart bypass surgery (also called coronary artery bypass graft, or CABG).

NSAIDs can also increase your risk of serious effects on the stomach or intestines, including bleeding or perforation (forming of a hole). These conditions can be fatal and gastrointestinal effects can occur without warning at any time while you are taking an NSAID. Older adults may have an even greater risk of these serious gastrointestinal side effects.

Do not use this medication if you are allergic to fenoprofen, or if you have:

• 
  

  severe kidney disease;

  
  


• 
  

  a stomach ulcer or inflammatory bowel disease; or

  
  


• 
  

  a history of allergic reaction to aspirin or other NSAIDs.

  
  

If you have any of these other conditions, you may need a dose adjustment or special tests to safely take fenoprofen:

• 
  

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

  
  


• 
  

  heart disease, congestive heart failure, high blood pressure;

  
  


• 
  

  a history of stomach ulcers or bleeding, bowel problems, diverticulosis;

  
  


• liver or kidney disease;


• 
  

  asthma;

  
  


• 
  

  polyps in your nose; or

  
  


• 
  

  if you smoke.

  
  

FDA pregnancy category C. It is not known whether fenoprofen is harmful to an unborn baby. Before taking this medication, tell your doctor if you are pregnant or plan to become pregnant during treatment. Taking fenoprofen during the last 3 months of pregnancy may result in birth defects. Do not take fenoprofen during pregnancy unless your doctor has told you to. Fenoprofen 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. Do not give this medicine to a child younger than 14 years old without the advice of a doctor.

How should I take Nalfon (fenoprofen)?

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label. The maximum amount of fenoprofen for adults is 3 grams (3000 mg) per day. Know the amount of fenoprofen in the specific product you are taking.

If you take fenoprofen for a long period of time, your doctor may want to check you on a regular basis to make sure this medication is not causing harmful effects. Do not miss any scheduled visits to your doctor.

This medication can cause you to have unusual results with certain medical tests. Tell any doctor who treats you that you are using fenoprofen.

Store fenoprofen at room temperature, away from moisture, heat, and light.

What happens if I miss a dose?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at your next regularly scheduled time. Do not take 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.

Overdose symptoms may include nausea, vomiting, confusion, dizziness, drowsiness, black or bloody stools, coughing up blood, fever, urinating less than usual or not at all, shallow breathing, fainting, or coma.

What should I avoid while taking Nalfon (fenoprofen)?

Do not use any other over-the-counter cold, allergy, or pain medication without first asking your doctor or pharmacist. Many medicines available over the counter contain medicines similar to fenoprofen (such as aspirin, ibuprofen, ketoprofen, or naproxen). If you take certain products together you may accidentally take too much of this type of medication. Read the label of any other medicine you are using to see if it contains aspirin, ibuprofen, ketoprofen, or naproxen. Do not drink alcohol while taking fenoprofen. Alcohol can increase the risk of stomach bleeding. Fenoprofen can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Nalfon (fenoprofen) 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 taking fenoprofen and seek medical attention or call your doctor at once if you have any of these serious side effects:

• 
  

  chest pain, weakness, shortness of breath, slurred speech, problems with vision or balance;

  
  


• 
  

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

  
  


• 
  

  confusion, tremors or shaking;

  
  


• 
  

  urinating less than usual or not at all;

  
  


• 
  

  pain, burning, or bleeding when you urinate;

  
  


• 
  

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

  
  


• 
  

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

  
  


• 
  

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

  
  

Less serious side effects may include:

• 
  

  upset stomach, mild heartburn or stomach pain, diarrhea, constipation; bloating, gas;

  
  


• 
  

  dizziness, headache, nervousness;

  
  


• 
  

  skin itching or rash;

  
  


• 
  

  dry mouth;

  
  


• 
  

  increased sweating, runny nose;

  
  


• 
  

  blurred vision; or

  
  


• 
  

  ringing in your ears.

  
  

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 Nalfon (fenoprofen)?

Tell your doctor if you are taking an antidepressant such as citalopram (Celexa), duloxetine (Cymbalta), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, Symbyax), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft), or venlafaxine (Effexor). Taking any of these drugs with fenoprofen may cause you to bruise or bleed easily.

Before taking fenoprofen, tell your doctor if you are taking:

• 
  

  cyclosporine (Gengraf, Neoral, Sandimmune);

  
  


• 
  

  lithium (Eskalith, Lithobid);

  
  


• 
  

  diuretics (water pills) such as furosemide (Lasix);

  
  


• 
  

  aspirin or salicylates such as Doan's Pills, Dolobid, and others;

  
  


• 
  

  a blood thinner such as warfarin (Coumadin);

  
  


• 
  

  steroids (prednisone and others);

  
  


• 
  

  seizure medication such as phenobarbital (Luminal, Solfoton) or phenytoin (Dilantin);

  
  


• 
  

  a sulfa drug such as Bactrim or Septra;

  
  


• 
  

  oral diabetes medications such as glipizide (Glucotrol), glimepiride (Amaryl, Duetact, Avandaryl), and others; or

  
  


• 
  

  aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) such as ibuprofen (Motrin, Advil), diclofenac (Cataflam, Voltaren), etodolac (Lodine), indomethacin (Indocin), nabumetone (Relafen), naproxen (Aleve, Naprosyn), meloxicam (Mobic), piroxicam (Feldene), and others.

  
  

This list is not complete and there may be other drugs that can interact with fenoprofen. 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 Nalfon resources

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

• Nalfon Prescribing Information (FDA)


• Nalfon Monograph (AHFS DI)


• Nalfon Advanced Consumer (Micromedex) - Includes Dosage Information


• Nalfon MedFacts Consumer Leaflet (Wolters Kluwer)


• Fenoprofen Prescribing Information (FDA)


• Fenoprofen MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Nalfon with other medications

• Gout, Acute
• Osteoarthritis
• Pain
• Rheumatoid Arthritis

Where can I get more information?

• Your pharmacist can provide more information about fenoprofen.

See also: Nalfon side effects (in more detail)

Noxafil

posaconazole

Dosage Form: oral suspension
FULL PRESCRIBING INFORMATION

1. INDICATIONS AND USAGE

Prophylaxis of Invasive Fungal Infection

Noxafil Oral Suspension is indicated for prophylaxis of invasive Aspergillus and Candida infections in patients, 13 years of age and older, who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) or those with hematologic malignancies with prolonged neutropenia from chemotherapy.

Treatment of Oropharyngeal Candidiasis Including Oropharyngeal Candidiasis Refractory to Itraconazole and/or Fluconazole

Noxafil is indicated for the treatment of oropharyngeal candidiasis, including oropharyngeal candidiasis refractory to itraconazole and/or fluconazole.

2. DOSAGE AND ADMINISTRATION

Dosage

Indication	Dose and Duration of Therapy
Prophylaxis of Invasive Fungal Infections	200 mg (5 mL) three times a day. The duration of therapy is based on recovery from neutropenia or immunosuppression.
Oropharyngeal Candidiasis	Loading dose of 100 mg (2.5 mL) twice a day on the first day, then 100 mg (2.5 mL) once a day for 13 days.
Oropharyngeal Candidiasis Refractory to itraconazole and/or fluconazole	400 mg (10 mL) twice a day. Duration of therapy should be based on the severity of the patient's underlying disease and clinical response.

Administration Instructions

Shake Noxafil Oral Suspension well before use.

Figure 1: A measured dosing spoon is provided, marked for doses of 2.5 mL and 5 mL.

It is recommended that the spoon is rinsed with water after each administration and before storage.

Each dose of Noxafil should be administered with a full meal or with a liquid nutritional supplement or an acidic carbonated beverage (e.g. ginger ale) in patients who cannot eat a full meal.

To enhance the oral absorption of posaconazole and optimize plasma concentrations:

• Each dose of Noxafil should be administered during or immediately (i.e. within 20 minutes) following a full meal. In patients who cannot eat a full meal, each dose of Noxafil should be administered with a liquid nutritional supplement or an acidic carbonated beverage. For patients who cannot eat a full meal or tolerate an oral nutritional supplement or an acidic carbonated beverage, alternative antifungal therapy should be considered or patients should be monitored closely for breakthrough fungal infections.


• Patients who have severe diarrhea or vomiting should be monitored closely for breakthrough fungal infections.


• Co-administration of drugs that can decrease the plasma concentrations of posaconazole should generally be avoided unless the benefit outweighs the risk. If such drugs are necessary, patients should be monitored closely for breakthrough fungal infections [See Drug Interactions (7.6, 7.7, 7.8, 7.9, 7.13)].

3. DOSAGE FORMS AND STRENGTHS

Noxafil Oral Suspension is available in 4-ounce (123 mL) amber glass bottles with child-resistant closures (NDC 0085-1328-01) containing 105 mL of suspension (40 mg of posaconazole per mL).

4. CONTRAINDICATIONS

Hypersensitivity

 Noxafil is contraindicated in persons with known hypersensitivity to posaconazole, any component of Noxafil, or other azole antifungal agents.

Use With Sirolimus

Noxafil is contraindicated with sirolimus. Concomitant administration of Noxafil with sirolimus increases the sirolimus blood concentrations by approximately 9 fold and can result in sirolimus toxicity [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

QT Prolongation With Concomitant Use With CYP3A4 Substrates

Noxafil is contraindicated with CYP3A4 substrates that prolong the QT interval. Concomitant administration of Noxafil with the CYP3A4 substrates, pimozide and quinidine may result in increased plasma concentrations of these drugs, leading to QTc prolongation and rare occurrences of torsades de pointes [see Warnings and Precautions (5.2) and Drug Interactions (7.2)].

Use With Simvastatin

 Concomitant administration of Noxafil with simvastatin increases the simvastatin plasma concentrations by approximately 10 fold. Increased plasma statin concentrations can be associated with rhabdomyolysis [see Drug Interactions (7.3) and Clinical Pharmacology (12.3)].

Use With Ergot Alkaloids

Posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism [see Drug Interactions (7.4)].

5. WARNINGS AND PRECAUTIONS

Calcineurin-Inhibitor Drug Interactions

Concomitant administration of Noxafil with cyclosporine or tacrolimus increases the whole blood trough concentrations of these calcineurin-inhibitors [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)]. Nephrotoxicity and leukoencephalopathy (including isolated deaths) have been reported in clinical efficacy studies in patients with elevated cyclosporine concentrations. Frequent monitoring of tacrolimus or cyclosporine whole blood trough concentrations should be performed during and at discontinuation of posaconazole treatment and the tacrolimus or cyclosporine dose adjusted accordingly.

Arrhythmias and QT Prolongation

Some azoles, including posaconazole, have been associated with prolongation of the QT interval on the electrocardiogram. In addition, rare cases of torsades de pointes have been reported in patients taking posaconazole.

Results from a multiple time-matched ECG analysis in healthy volunteers did not show any increase in the mean of the QTc interval. Multiple, time-matched ECGs collected over a 12-hour period were recorded at baseline and steady-state from 173 healthy male and female volunteers (18–85 years of age) administered posaconazole 400 mg BID with a high-fat meal. In this pooled analysis, the mean QTc (Fridericia) interval change from baseline was –5 msec following administration of the recommended clinical dose. A decrease in the QTc (F) interval (–3 msec) was also observed in a small number of subjects (n=16) administered placebo. The placebo-adjusted mean maximum QTc (F) interval change from baseline was <0 msec (–8 msec). No healthy subject administered posaconazole had a QTc (F) interval ≥500 msec or an increase ≥60 msec in their QTc (F) interval from baseline.

Posaconazole should be administered with caution to patients with potentially proarrhythmic conditions. Do not administer with drugs that are known to prolong the QTc interval and are metabolized through CYP3A4 [see Contraindications (4.3) and Drug Interactions (7.2)]. Rigorous attempts to correct potassium, magnesium, and calcium should be made before starting posaconazole.

Hepatic Toxicity

Hepatic reactions (e.g., mild to moderate elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin, and/or clinical hepatitis) have been reported in clinical trials. The elevations in liver function tests were generally reversible on discontinuation of therapy, and in some instances these tests normalized without drug interruption and rarely required drug discontinuation. Isolated cases of more severe hepatic reactions including cholestasis or hepatic failure including deaths have been reported in patients with serious underlying medical conditions (e.g., hematologic malignancy) during treatment with posaconazole. These severe hepatic reactions were seen primarily in subjects receiving the 800 mg daily (400 mg BID or 200 mg QID) in clinical trials.

Liver function tests should be evaluated at the start of and during the course of posaconazole therapy. Patients who develop abnormal liver function tests during posaconazole therapy should be monitored for the development of more severe hepatic injury. Patient management should include laboratory evaluation of hepatic function (particularly liver function tests and bilirubin). Discontinuation of posaconazole must be considered if clinical signs and symptoms consistent with liver disease develop that may be attributable to posaconazole.

Use with Midazolam

 Concomitant administration of Noxafil with midazolam increases the midazolam plasma concentrations by approximately 5 fold. Increased plasma midazolam concentrations could potentiate and prolong hypnotic and sedative effects. Patients must be monitored closely for adverse effects associated with high plasma concentrations of midazolam and benzodiazepine receptor antagonists must be available to reverse these effects [see Drug Interactions (7.5) and Clinical Pharmacology (12.3)].

6. ADVERSE REACTIONS

Serious and Otherwise Important Adverse Reactions

The following serious and otherwise important adverse reactions are discussed in detail in another section of the labeling:

• Hypersensitivity [see Contraindications (4.1)]


• Arrhythmias and QT Prolongation [see Warnings and Precautions (5.2)]


• Hepatic Toxicity [see Warnings and Precautions (5.3)]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of Noxafil cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of posaconazole therapy has been assessed in 1844 patients in clinical trials. This includes 605 patients in the active-controlled prophylaxis studies, 557 patients in the active-controlled OPC studies, 239 patients in refractory OPC studies, and 443 patients from other indications. This represents a heterogeneous population, including immunocompromised patients, e.g., patients with hematological malignancy, neutropenia post-chemotherapy, graft vs. host disease post hematopoietic stem cell transplant, and HIV infection, as well as non-neutropenic patients. This patient population was 71% male, had a mean age of 42 years (range 8–84 years, 6% of patients were ≥65 years of age and 1% was <18 years of age), and were 64% white, 16% Hispanic, and 36% non-white (including 14% black). Posaconazole therapy was given to 171 patients for ≥6 months, with 58 patients receiving posaconazole therapy for ≥12 months. Table 1 presents treatment-emergent adverse reactions observed at an incidence of >10% in posaconazole prophylaxis studies. Table 2 presents treatment-emergent adverse reactions observed at an incidence of at least 10% in the OPC/rOPC studies.

Prophylaxis of Aspergillus and Candida: In the 2 randomized, comparative prophylaxis studies, the safety of posaconazole 200 mg three times a day was compared to fluconazole 400 mg once daily or itraconazole 200 mg twice a day in severely immunocompromised patients.

The most frequently reported adverse reactions (>30%) in the prophylaxis clinical trials were fever, diarrhea and nausea.

The most common adverse reactions leading to discontinuation of posaconazole in the prophylaxis studies were associated with GI disorders, specifically, nausea (2%), vomiting (2%), and hepatic enzymes increased (2%).

TABLE 1: Study 1 and Study 2. Number (%) of Randomized Subjects Reporting Treatment-Emergent Adverse Reactions: Frequency of at Least 10% in the Posaconazole or Fluconazole Treatment Groups (Pooled Prophylaxis Safety Analysis)

Body System   Preferred Term	Posaconazole (n=605)		Fluconazole (n=539)		Itraconazole (n=58)
Subjects Reporting any Adverse Reaction	595	(98)	531	(99)	58	(100)
NOS = not otherwise specified.
* Percentages of sex-specific adverse reactions are based on the number of males/females.
Body as a Whole - General Disorders
Fever	274	(45)	254	(47)	32	(55)
Headache	171	(28)	141	(26)	23	(40)
Rigors	122	(20)	87	(16)	17	(29)
Fatigue	101	(17)	98	(18)	5	(9)
Edema Legs	93	(15)	67	(12)	11	(19)
Anorexia	92	(15)	94	(17)	16	(28)
Dizziness	64	(11)	56	(10)	5	(9)
Edema	54	(9)	68	(13)	8	(14)
Weakness	51	(8)	52	(10)	2	(3)
Cardiovascular Disorders, General
Hypertension	106	(18)	88	(16)	3	(5)
Hypotension	83	(14)	79	(15)	10	(17)
Disorders of Blood and Lymphatic System
Anemia	149	(25)	124	(23)	16	(28)
Neutropenia	141	(23)	122	(23)	23	(40)
Febrile Neutropenia	118	(20)	85	(16)	23	(40)
Disorders of the Reproductive System and Breast
Vaginal Hemorrhage*	24	(10)	20	(9)	3	(12)
Gastrointestinal System Disorders
Diarrhea	256	(42)	212	(39)	35	(60)
Nausea	232	(38)	198	(37)	30	(52)
Vomiting	174	(29)	173	(32)	24	(41)
Abdominal Pain	161	(27)	147	(27)	21	(36)
Constipation	126	(21)	94	(17)	10	(17)
Mucositis NOS	105	(17)	68	(13)	15	(26)
Dyspepsia	61	(10)	50	(9)	6	(10)
Heart Rate and Rhythm Disorders
Tachycardia	72	(12)	75	(14)	3	(5)
Infection and Infestations
Bacteremia	107	(18)	98	(18)	16	(28)
Herpes Simplex	88	(15)	61	(11)	10	(17)
Cytomegalovirus Infection	82	(14)	69	(13)	0
Pharyngitis	71	(12)	60	(11)	12	(21)
Upper Respiratory Tract Infection	44	(7)	54	(10)	5	(9)
Liver and Biliary System Disorders
Bilirubinemia	59	(10)	51	(9)	11	(19)
Metabolic and Nutritional Disorders
Hypokalemia	181	(30)	142	(26)	30	(52)
Hypomagnesemia	110	(18)	84	(16)	11	(19)
Hyperglycemia	68	(11)	76	(14)	2	(3)
Hypocalcemia	56	(9)	55	(10)	5	(9)
Musculoskeletal System Disorders
Musculoskeletal Pain	95	(16)	82	(15)	9	(16)
Arthralgia	69	(11)	67	(12)	5	(9)
Back Pain	63	(10)	66	(12)	4	(7)
Platelet, Bleeding and Clotting Disorders
Thrombocytopenia	175	(29)	146	(27)	20	(34)
Petechiae	64	(11)	54	(10)	9	(16)
Psychiatric Disorders
Insomnia	103	(17)	92	(17)	11	(19)
Anxiety	52	(9)	61	(11)	9	(16)
Respiratory System Disorders
Coughing	146	(24)	130	(24)	14	(24)
Dyspnea	121	(20)	116	(22)	15	(26)
Epistaxis	82	(14)	73	(14)	12	(21)
Skin and Subcutaneous Tissue Disorders
Rash	113	(19)	96	(18)	25	(43)
Pruritus	69	(11)	62	(12)	11	(19)

HIV Infected Subjects With OPC: In 2 randomized comparative studies in OPC, the safety of posaconazole at a dose of ≤400 mg QD in 557 HIV-infected patients was compared to the safety of fluconazole in 262 HIV-infected patients at a dose of 100 mg QD.

An additional 239 HIV-infected patients with refractory OPC received posaconazole in 2 non-comparative trials for refractory OPC (rOPC).

Of these subjects, 149 received the 800-mg/day dose and the remainder received the ≤400-mg QD dose.

In the OPC/rOPC studies, the most common adverse reactions were fever, diarrhea, nausea, headache, and vomiting.

The most common adverse reactions that led to treatment discontinuation of posaconazole in the Controlled OPC Pool included respiratory insufficiency (1%) and pneumonia (1%). In the refractory OPC pool, the most common adverse reactions that led to treatment discontinuation of posaconazole were AIDS (7%) and respiratory insufficiency (3%).

TABLE 2: Treatment-Emergent Adverse Reactions With Frequency of at Least 10% in OPC Studies (Treated Population)

	Number (%) of Subjects
	Controlled OPC Pool		Refractory OPC Pool
	Posaconazole	Fluconazole	Posaconazole
Body System
Preferred Term	n=557	n=262	n=239
Subjects Reporting any Adverse Reaction*	356 (64)	175 (67)	221 (92)
OPC=oropharyngeal candidiasis; SGOT=serum glutamic oxaloacetic transaminase (same as AST); SGPT=serum glutamic pyruvic transaminase (same as ALT).
* Number of subjects reporting treatment-emergent adverse reactions at least once during the study, without regard to relationship to treatment. Subjects may have reported more than 1 event.
Body as a Whole – General Disorders
Fever	34 (6)	22 (8)	82 (34)
Headache	44 (8)	23 (9)	47 (20)
Anorexia	10 (2)	4 (2)	46 (19)
Fatigue	18 (3)	12 (5)	31 (13)
Asthenia	9 (2)	5 (2)	31 (13)
Rigors	2 (<1)	4 (2)	29 (12)
Pain	4 (1)	2 (1)	27 (11)
Disorders of Blood and Lymphatic System
Neutropenia	21 (4)	8 (3)	39 (16)
Anemia	11 (2)	5 (2)	34 (14)
Gastrointestinal System Disorders
Diarrhea	58 (10)	34 (13)	70 (29)
Nausea	48 (9)	30 (11)	70 (29)
Vomiting	37 (7)	18 (7)	67 (28)
Abdominal Pain	27 (5)	17 (6)	43 (18)
Infection and Infestations
Candidiasis, Oral	3 (1)	1 (<1)	28 (12)
Herpes Simplex	16 (3)	8 (3)	26 (11)
Pneumonia	17 (3)	6 (2)	25 (10)
Metabolic and Nutritional Disorders
Weight Decrease	4 (1)	2 (1)	33 (14)
Dehydration	4 (1)	7 (3)	27 (11)
Psychiatric Disorders
Insomnia	8 (1)	3 (1)	39 (16)
Respiratory System Disorders
Coughing	18 (3)	11 (4)	60 (25)
Dyspnea	8 (1)	8 (3)	28 (12)
Skin and Subcutaneous Tissue Disorders
Rash	15 (3)	10 (4)	36 (15)
Sweating Increased	13 (2)	5 (2)	23 (10)

Adverse reactions were reported more frequently in the pool of patients with refractory OPC. Among these highly immunocompromised patients with advanced HIV disease, serious adverse reactions (SARs) were reported in 55% (132/239). The most commonly reported SARs were fever (13%) and neutropenia (10%).

Less Common Adverse Reactions: Clinically significant adverse reactions reported during clinical trials in prophylaxis, OPC/rOPC or other trials with posaconazole which occurred in less than 5% of patients are listed below:

• Blood and lymphatic system disorders: hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, neutropenia aggravated


• Endocrine disorders: adrenal insufficiency


• Nervous system disorders: paresthesia


• Immune system disorders: allergic reaction [see Contraindications (4.1)]


• Cardiac disorders: Torsades de pointes [see Warnings and Precautions (5.2)]


• Vascular disorders: pulmonary embolism


• Liver and Biliary System Disorders: bilirubinemia, hepatic enzymes increased, hepatic function abnormal, hepatitis, hepatomegaly, jaundice, SGOT Increased, SGPT Increased


• Metabolic and Nutritional Disorders: Hypokalemia


• Platelet, Bleeding, and Clotting Disorders: Thrombocytopenia


• Renal & Urinary System Disorders: Renal Failure Acute

Clinical Laboratory Values: In healthy volunteers and patients, elevation of liver function test values did not appear to be associated with higher plasma concentrations of posaconazole. The majority of abnormal liver function tests were minor, transient, and did not lead to discontinuation of therapy.

For the prophylaxis studies, the number of patients with changes in liver function tests from Common Toxicity Criteria (CTC) Grade 0, 1, or 2 at baseline to Grade 3 or 4 during the study is presented in Table 3.

TABLE 3: Study 1 and Study 2. Changes in Liver Function Test Results From CTC Grade 0, 1, or 2 at Baseline to Grade 3 or 4

Number (%) of Patients With Change*
CTC = Common Toxicity Criteria; AST= Aspartate Aminotransferase; ALT= Alanine Aminotransferase.
* Change from Grade 0 to 2 at baseline to Grade 3 or 4 during the study. These data are presented in the form X/Y, where X represents the number of patients who met the criterion as indicated, and Y represents the number of patients who had a baseline observation and at least one post-baseline observation.
Study 1
Laboratory Parameter	Posaconazole n=301	Fluconazole n=299
AST	11/266 (4)	13/266 (5)
ALT	47/271 (17)	39/272 (14)
Bilirubin	24/271 (9)	20/275 (7)
Alkaline Phosphatase	9/271 (3)	8/271 (3)
Study 2
Laboratory Parameter	Posaconazole (n=304)	Fluconazole/Itraconazole (n=298)
AST	9/286 (3)	5/280 (2)
ALT	18/289 (6)	13/284 (5)
Bilirubin	20/290 (7)	25/285 (9)
Alkaline Phosphatase	4/281 (1)	1/276 (<1)

The number of patients treated for OPC with clinically significant liver function test (LFT) abnormalities at any time during the studies is provided in Table 4. (LFT abnormalities were present in some of these patients prior to initiation of the study drug).

TABLE 4: Clinically Significant Laboratory Test Abnormalities Without Regard to Baseline Value

	Controlled		Refractory
	Posaconazole	Fluconazole	Posaconazole
Laboratory Test	n= 557(%)	n=262(%)	n=239(%)
ALT= Alanine Aminotransferase; AST= Aspartate Aminotransferase.
ALT > 3.0 × ULN	16/537 (3)	13/254 (5)	25/226 (11)
AST > 3.0 × ULN	33/537 (6)	26/254 (10)	39/223 (17)
Total Bilirubin > 1.5 × ULN	15/536 (3)	5/254 (2)	9/197 (5)
Alkaline Phosphatase > 3.0 × ULN	17/535 (3)	15/253 (6)	24/190 (13)

Postmarketing Experience

No clinically significant postmarketing adverse reactions were identified that have not previously been reported during clinical trials experience.

7. DRUG INTERACTIONS

Posaconazole is primarily metabolized via UDP glucuronidation and is a substrate of p-glycoprotein efflux. Therefore, inhibitors or inducers of these clearance pathways may affect posaconazole plasma concentrations. Posaconazole is also a strong inhibitor of CYP3A4. Therefore, plasma concentrations of drugs predominantly metabolized by CYP3A4 may be increased by posaconazole [see Clinical Pharmacology (12.3)].

Immunosuppressants Metabolized by CYP3A4

Sirolimus: Concomitant administration of posaconazole with sirolimus increases the sirolimus blood concentrations by approximately 9 fold and can result in sirolimus toxicity. Therefore, posaconazole is contraindicated with sirolimus [see Contraindications (4.2) and Clinical Pharmacology (12.3)].

Tacrolimus: Posaconazole has been shown to significantly increase the Cmax and AUC of tacrolimus. At initiation of posaconazole treatment, reduce the tacrolimus dose to approximately one-third of the original dose. Frequent monitoring of tacrolimus whole blood trough concentrations should be performed during and at discontinuation of posaconazole treatment and the tacrolimus dose adjusted accordingly [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].

Cyclosporine: Posaconazole has been shown to increase cyclosporine whole blood concentrations in heart transplant patients upon initiation of posaconazole treatment. It is recommended to reduce cyclosporine dose to approximately three-fourths of the original dose upon initiation of posaconazole treatment. Frequent monitoring of cyclosporine whole blood trough concentrations should be performed during and at discontinuation of posaconazole treatment and the cyclosporine dose adjusted accordingly [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].

CYP3A4 Substrates

Concomitant administration of posaconazole with CYP3A4 substrates such as pimozide and quinidine may result in increased plasma concentrations of these drugs, leading to QTc prolongation and rare occurrences of torsades de pointes. Therefore, posaconazole is contraindicated with these drugs. [see Contraindications (4.3), and Warnings and Precautions (5.2)].

HMG-CoA reductase Inhibitors (Statins) Metabolized Through CYP3A4

Concomitant administration of posaconazole with simvastatin increases the simvastatin plasma concentrations by approximately 10 fold. Therefore, posaconazole is contraindicated with HMG-CoA reductase inhibitor simvastatin [see Contraindications (4.4) and Clinical Pharmacology (12.3)].

Although not studied clinically with statins other than simvastatin, posaconazole may increase the plasma concentrations of statins that are metabolized by CYP3A4. Increased plasma statin concentrations can be associated with rhabdomyolysis. It is recommended that patients be monitored for adverse events and dose reduction of the statin be considered during co-administration with posaconazole.

Ergot Alkaloids

Most of the ergot alkaloids are substrates of CYP3A4. Posaconazole may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism. Therefore, posaconazole is contraindicated with ergot alkaloids [see Contraindications (4.5)].