Infuvite Pediatric

Dosage Form: injection, solution
Infuvite Pediatric -multiple vitamins for infusion

For intravenous infusion after dilution only.

Infuvite Pediatric Description

Infuvite Pediatric is a sterile product consisting of two vials: a 4 mL single-dose vial labeled Vial 1 and a 1 mL single-dose vial labeled Vial 2.

Each 4 mL of Vial 1 contains:

Ascorbic acid (Vitamin C) ......................................... 80 mg

Vitamin A1 (as palmitate)...................................... 2,300 IU

Vitamin D31 (cholecalciferol) ................................... 400 IU

Thiamine (Vitamin B1)

(as the hydrochloride)............................................ 1.2 mg

Riboflavin (Vitamin B2)

(as riboflavin 5-phosphate sodium) ....................... 1.4 mg

Pyridoxine HCl (Vitamin B6) ....................................... 1 mg

Niacinamide .............................................................. 17 mg

Dexpanthenol

(as d-pantothenyl alcohol) ........................................ 5 mg

Vitamin E1 (dl-α-tocopheryl acetate)........................... 7 IU

Vitamin K11.............................................................. 0.2 mg

Inactive ingredients: 50 mg polysorbate 80, sodium hydroxide and/or hydrochloric acid for pH adjustment and water for injection.

1Polysorbate 80 is used to water solubilize the oil-soluble vitamins A, D, E, and K.

Each 1 mL of Vial 2 contains:

Folic acid............................................................... 140 mcg

Biotin....................................................................... 20 mcg

Vitamin B12 (cyanocobalamin).................................. 1 mcg

Inactive ingredients: 75 mg mannitol, citric acid and/or sodium citrate for pH adjustment and water for injection.

Vitamin A 2,300 IU equals 0.7 mg

Vitamin D 400 IU equals 10 mcg

Vitamin E 7 IU equals 7 mg

Multiple vitamin preparation for intravenous infusion: Infuvite Pediatric (Multiple Vitamins for Infusion) makes available a combination of important oil-soluble and water-soluble vitamins in an aqueous solution, formulated for incorporation into intravenous solutions. The liposoluble vitamins A, D, E, and K have been solubilized in an aqueous medium with polysorbate 80, permitting intravenous administration of these vitamins.

Contains no more than 30 mcg/L of aluminum (combined vials 1 and 2).

Indications and Usage for Infuvite Pediatric

Infuvite Pediatric is indicated as a daily multivitamin maintenance dosage for infants and children up to 11 years of age receiving parenteral nutrition.

Infuvite Pediatric is also indicated in other situations where administration by the intravenous route is required. Such situations include surgery, extensive burns, fractures and other trauma, severe infectious diseases, and comatose states, which may provoke a “stress” situation with profound alterations in the body's metabolic demands and consequent tissue depletion of nutrients. The physician should not await the development of clinical signs of vitamin deficiency before initiating vitamin therapy.

Infuvite Pediatric (administered in intravenous fluids under proper dilution) contributes intake of necessary vitamins toward maintaining the body's normal resistance and repair processes.

Patients with multiple vitamin deficiencies or with markedly increased requirements may be given multiples of the daily dosage for two or more days, as indicated by the clinical status. Blood vitamin concentrations should be periodically monitored to ensure maintenance of adequate levels, particularly in patients receiving parenteral multivitamins as their sole source of vitamins for long periods of time.

Contraindications

Infuvite Pediatric is contraindicated where there is a preexisting hypervitaminosis, or a known hypersensitivity to any of the vitamins or excipients in the product.

Allergic reactions have been known to occur following intravenous administration of thiamine and vitamin K. The formulation is contraindicated prior to blood sampling for detection of megaloblastic anemia, as the folic acid and the cyanocobalamin in the vitamin solution can mask serum deficits.

Warnings

Infuvite Pediatric is administered in intravenous solutions, which may contain aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solution, which contain aluminum. Research indicates that patients with impaired kidney function, including premature neonates who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

Precautions

Caution should be exercised when administering Infuvite Pediatric to patients on warfarin sodium-type anticoagulant therapy. In such patients, vitamin K may antagonize the hypoprothrombinemic response to anticoagulant drugs. In such patients, periodic monitoring of prothrombin time/INR response is essential in determining the appropriate dosage of anticoagulant therapy.

Adequate blood levels of vitamin E are achieved when Infuvite Pediatric is given to infants at the recommended dosage. Larger doses or supplementation with oral or parenteral vitamin E are not recommended because elevated blood levels of vitamin E may result.

Studies have shown that vitamin A may adhere to plastic, resulting in inadequate vitamin A administration in the doses recommended with Infuvite Pediatric. Additional vitamin A supplementation may be required, especially in low-birth-weight infants. Long-standing specific vitamin deficiencies may require additional therapeutic amounts of specific vitamins to supplement the maintenance vitamins provided by Infuvite Pediatric.

In patients receiving parenteral multivitamins, blood vitamin concentrations should be periodically monitored to determine if vitamin deficiencies or excesses are developing.

Polysorbates have been associated with the E-Ferol syndrome (thrombocytopenia, renal dysfunction, hepatomagaly, cholestasis, ascites, hypotension and metabolic acidosis) in low-birth-weight infants. However, no such adverse reports have been associated with the use of pediatric multiple vitamins for infusion such as Infuvite Pediatric.

Infuvite Pediatric should be aseptically transferred to the infusion fluid.

Drug-Drug Interactions

Physical incompatibilities

Infuvite Pediatric (Multiple Vitamins for Infusion) is not physically compatible with alkaline solutions or moderately alkaline drugs such as acetazolamide, and chlorothiazide sodium, aminopylline or sodium bicarbonate. Infuvite Pediatric is not physically compatible with ampicillin and it may not be physically compatible with tetracycline HCl. It has also been reported that folic acid is unstable in the presence of calcium salts such as calcium gluconate. Direct addition to intravenous fat emulsions is not recommended. Consult appropriate references for listings of physical compatibility of solutions and drugs with the vitamin infusion. In such circumstances, admixture or Y-site administration with vitamin solutions should be avoided.

Some of the vitamins in Infuvite Pediatric may react with vitamin K bisulfite or sodium bisulfite; if bisulfite solutions are necessary, patients should be monitored for Vitamin A, thiamine, and ascorbic acid deficiencies.

Clinical Interactions

A number of interactions between vitamins and drugs have been reported which may affect the metabolism of either agent. The following are examples of these types of interactions.

Folic acid may lower the serum concentration of phenytoin resulting in increased seizure frequency.Conversely, phenytoin may decrease serum folic acid concentrations and, therefore, should be avoided in pregnancy. Folic acid may decrease the patient's response to methotrexate therapy.

Pyridoxine may decrease the efficacy of levodopa by increasing its metabolism. Concomitant administration of hydralazine or isoniazid may increase pyridoxine requirements.

In patients with pernicious anemia, the hematological response to vitamin B12 therapy may be inhibited by concomitant administration of chloramphenicol.

Several vitamins have been reported to decrease the activity of certain antibiotics. Thiamine, riboflavin, pyridoxine, niacinamide, and ascorbic acid have been reported to decrease the antibiotic activity of erythromycin, kanamycin, streptomycin, doxycycline, and lincomycin. Bleomycin is inactivated in vitro by ascorbic acid and riboflavin.

Vitamin K may antagonize the hypoprothrombinemic effect of oral anticoagulants (see PRECAUTIONS).

Consult appropriate references for additional specific vitamin-drug interactions.

Drug-Laboratory Test Interactions

Ascorbic acid in the urine may cause false negative urine glucose determinations.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, mutagenicity, and fertility studies have not been performed.

Adverse Reactions

There have been rare reports of anaphylactic reactions following parenteral multivitamin administration. Rare reports of anaphylactoid reactions have also been reported after large intravenous doses of thiamine. The risk, however, is negligible if thiamine is coadministered with other vitamins of the B group. There have been no reports of fatal anaphylactoid reactions associated with multivitamin preparations for infusion.

There have been rare reports of the following types of reactions:

Dermatologic – rash, erythema, pruritis

CNS – headache, dizziness, agitation, anxiety

Ophthalmic – diplopia

Allergic – urticaria, shortness of breath, wheezing and angioedema.

Overdosage

The possibility of hypervitaminosis A or D should be borne in mind. Clinical manifestations of hypervitaminosis A have been reported in patients with renal failure receiving 1.5 mg/day retinol. Therefore, vitamin A supplementation of renal failure patients should be undertaken with caution.

Infuvite Pediatric Dosage and Administration

Infuvite Pediatric is ready for immediate use in infants and children up to 11 years of age when added to intravenous infusion fluids.

Infuvite Pediatric should not be given as a direct, undiluted intravenous injection as it may give rise to dizziness, faintness and possible tissue irritation.

A daily dose of Infuvite Pediatric (4 mL of Vial 1 plus 1 mL of Vial 2) should be added directly to not less than 100 mL of intravenous dextrose, saline or similar infusion solutions.

For administration to infants weighing < 1 kg:

The daily dose is 30% of the contents of Vial 1 (1.2 mL) and of Vial 2 (0.3 mL). Do not exceed this daily dose. Supplemental vitamin A may be required for low-birth-weight infants.

For administration to infants weighing ≥1 kg and < 3 kg: The daily dose is 65% of the contents of Vial 1 (2.6 mL) and of Vial 2 (0.65 mL). Do not exceed this daily dose. Supplemental vitamin A may be required for low-birth-weight infants.

For administration to infants and children weighing ≥3 kg up to 11 years of age: The daily dose is the entire contents of Vial 1 (4 mL) and of Vial 2 (1 mL), unless there is clinical or laboratory evidence for increasing or decreasing the dosage.

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

After Infuvite Pediatric is diluted in an intravenous infusion, the resulting solution is ready for immediate use. Some of the vitamins in this product, particularly A, D, and riboflavin, are light sensitive, therefore, exposure to light should be minimized. DISCARD ANY UNUSED PORTION

How is Infuvite Pediatric Supplied

Infuvite Pediatric – NDC 54643-5646-0, is available in boxes containing 2 vials – Vial 1 (4 mL) and Vial 2 (1 mL), both vials to be used for a single dose.

Infuvite Pediatric – NDC 54643-5646-1, is available in boxes containing 10 vials – 5 each of Vial 1 (4 mL) and 5 each of Vial 2 (1 mL), one Vial 1 plus one Vial 2 to be used for a single dose.

Store under refrigeration 2-8°C (36-46°F).

Rx only

Manufactured by

Sandoz Canada Inc.

145 Jules-Leger Street Boucherville, QC, Canada J4B 7K8

Distributed by

Baxter Healthcare Corporation

Clintec Nutrition Division Deerfield, IL 60015 USA

Printed in Canada

D1006224 Rev. September 2007

® INFUVITE is a registered trademark of Sandoz Canada Inc.

Infuvite Pediatric Carton

2A9008 NDC 54643-5646-1

Baxter

Infuvite Pediatric Multiple Vitamins for Infusion

For intravenous infusion after dilution only.

Sterile Rx only

Contains 5 each of Vial 1 (4 mL) and Vial 2 (1 mL).

One vial of each to be used for a single dose.

Store under refrigeration, 2-8°C (36-46°F).

PEDIATRIC INFUVITE MULTIPLE VITAMINS FOR INFUSION  asorbic acid, vitamin a palmitate, cholecalciferol, thiamine hydrochloride, riboflavin 5-phosphate sodium, pyridoxine hydrochloride, niacinamide, dexpanthenol, alpha-tocopherol acetate, vitamin k1, folic acid, biotin, cyanocobalamin  injection, solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 54643-5646 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ASCORBIC ACID (ASCORBIC ACID) ASCORBIC ACID 80 mg  in 5 mL VITAMIN A PALMITATE (VITAMIN A) VITAMIN A 2300 [iU]  in 5 mL CHOLECALCIFEROL (CHOLECALCIFEROL) CHOLECALCIFEROL 400 [iU]  in 5 mL THIAMINE HYDROCHLORIDE (THIAMINE) THIAMINE 1.2 mg  in 5 mL RIBOFLAVIN 5'-PHOSPHATE SODIUM (RIBOFLAVIN) RIBOFLAVIN 1.4 mg  in 5 mL PYRIDOXINE HYDROCHLORIDE (PYRIDOXINE) PYRIDOXINE HYDROCHLORIDE 1 mg  in 5 mL NIACINAMIDE (NIACINAMIDE) NIACINAMIDE 17 mg  in 5 mL DEXPANTHENOL (DEXPANTHENOL) DEXPANTHENOL 5 mg  in 5 mL ALPHA-TOCOPHEROL ACETATE (ALPHA-TOCOPHEROL) ALPHA-TOCOPHEROL ACETATE 7 [iU]  in 5 mL PHYTONADIONE (PHYTONADIONE) PHYTONADIONE 0.2 mg  in 5 mL FOLIC ACID (FOLIC ACID) FOLIC ACID 140 ug  in 5 mL BIOTIN (BIOTIN) BIOTIN 20 ug  in 5 mL CYANOCOBALAMIN (CYANOCOBALAMIN) CYANOCOBALAMIN 1 ug  in 5 mL

Inactive Ingredients Ingredient Name Strength POLYSORBATE 80   ANHYDROUS CITRIC ACID   SODIUM CITRATE   SODIUM HYDROXIDE   HYDROCHLORIC ACID   MANNITOL

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 54643-5646-0 2 VIAL In 1 CARTON contains a VIAL 1 5 mL In 1 VIAL This package is contained within the CARTON (54643-5646-0) 2 54643-5646-1 10 VIAL In 1 CARTON contains a VIAL 2 5 mL In 1 VIAL This package is contained within the CARTON (54643-5646-1)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA021265	02/21/2001

Labeler - Sandoz Canada Inc (244062071)

Revised: 01/2012Sandoz Canada Inc

Slo-Phyllin 60mg, 125mg, 250mg, Capsules

1. Name Of The Medicinal Product

Slo-Phyllin 60mg Capsules

Slo-Phyllin 125mg Capsules

Slo-Phyllin 250mg Capsules

2. Qualitative And Quantitative Composition

Slo-Phyllin 60mg capsules each contain theophylline (anhydrous) EP 60mg

Slo-Phyllin 125mg capsules each contain theophylline (anhydrous) EP 125mg

Slo-Phyllin 250mg capsules each contain theophylline (anhydrous) EP 250mg

3. Pharmaceutical Form

Prolonged release capsule

4. Clinical Particulars

4.1 Therapeutic Indications

As a bronchodilator in the symptomatic and prophylactic treatment of asthma and for reversible bronchoconstriction associated with chronic bronchitis and bronchial asthma.

4.2 Posology And Method Of Administration

Method of administration Oral

Dosage

Children:
2 - 6 years (10 - 20kg):	60 - 120mg twice daily
6 - 12 years (20 - 35kg)	125 - 250mg twice daily
over 12 years	250-500 mg twice daily
Adults:	250-500 mg twice daily
Elderly:	There is a tendency for theophylline clearance to decrease with age leading to higher serum levels. A reduction of the adult dosage may therefore be necessary and close monitoring is advised.

Each patient should be titrated to a suitable dosage regimen by clinical assessment. It may also be necessary to measure plasma theophylline levels.

Initially the lowest dosage for each group is recommended. This may be increased gradually if optimal bronchodilator effects are not achieved. The total dosage should not normally exceed 24 mg/kg body weight for children and 13 mg/kg for adults. However the plasma theophylline level measured 4-8 hours after dosing and at least three days after any dosage adjustment, provides a more accurate assessment of the patients' dosage need, especially as significant variations in the rate of drug elimination can occur between individuals. The following table provides a guide:

Plasma level (mcg/ml)	Result	Directions (if clinically indicated)
Below 10	Too low	Increase dose by 25%
10-20	Correct	Maintain dose
20-25	Too high	Decrease dose by 10%
25-30	Too high	Miss next dose and decrease subsequent doses by 25%
Over 30	Too high	Miss next two doses and decrease subsequent doses by 50%

It is advisable to recheck the plasma level after dose adjustment and every 6-12 months.

It is not possible to ensure bioequivalence between different sustained release theophylline products. Once titrated to an effective dose, patients should not be changed from Slo-Phyllin to another sustained release xanthine preparation without re-titration and clinical assessment.

4.3 Contraindications

Hypersensitivity to theophylline or other xanthines. Concomitant use of theophylline and ephedrine in children.

4.4 Special Warnings And Precautions For Use

Smoking and alcohol consumption can increase the clearance of theophylline and a higher dose may be necessary.

Careful monitoring is recommended for patients with congestive heart failure, chronic alcoholism, hepatic dysfunction, or viral infections, as they may have a lower clearance of theophylline, which could lead to higher than normal plasma levels.

Caution should be exercised in patients with peptic ulcers, cardiac arrhythmias, other cardiovascular diseases, hyperthyroidism or hypertension. Slo-Phyllin should not be used concurrently with other preparations containing xanthines derivatives. If it is necessary to administer aminophylline to a patient who is already receiving Slo-Phyllin, plasma theophylline concentration should be monitored.

The use of alternative treatments is advised in patients with a history of seizures, as these may be exacerbated by theophylline.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Theophylline has been reported to interact with a number of drugs. The following increase clearance and it may therefore be necessary to increase dosage to ensure therapeutic effect: barbiturates, carbamazepine, lithium, phenytoin, rifampicin and sulphinpyrazone.

The following reduce clearance and a reduced dosage may therefore be necessary to avoid side-effects: allopurinol, cimetidine, ciprofloxacin, corticosteroids, diltiazem, erythromycin, frusemide, isoprenaline, oral contraceptives, thiabendazole and verapamil. There is some evidence of an interaction between theophylline and influenza vaccine.

Xanthines can potentiate hypokalaemia resulting from beta₂ agonist therapy, steroids, diuretics and hypoxia. Particular caution is advised in severe asthma. It is recommended that serum potassium levels are monitored in such situations.

The concomitant use of theophylline and fluvoxamine should usually be avoided. Where this is not possible, patients should have their theophylline dose halved and plasma theophylline should be monitored closely.

Plasma concentrations of theophylline can be reduced by concomitant use of the herbal remedy St John's wort (Hypericum perforatum).

4.6 Pregnancy And Lactation

Slo-Phyllin is not recommended since theophylline is known to cross the placenta and its safety in pregnancy has not been established.

Theophylline is distributed in breast milk and therefore Slo-Phyllin should be used with caution in nursing mothers.

4.7 Effects On Ability To Drive And Use Machines

None known

4.8 Undesirable Effects

Side effects usually occur when theophylline blood levels exceed 20 micrograms/ml and include gastric irritation, nausea, vomiting, abdominal discomfort, palpitations, a fall in blood pressure, headache, occasional diarrhoea and insomnia. CNS stimulation and diuresis may also occur, especially in children.

4.9 Overdose

Over 3 g could be serious in an adult (40 mg/kg in a child). The fatal dose may be as little as 4.5 g in an adult (60 mg/kg in a child), but is generally higher.

Symptoms

Warning: Serious features may develop as long as 12 hours after overdosage with sustained release formulations.

Alimentary features: Nausea, vomiting (which is often severe), epigastric pain and haematemesis. Consider pancreatitis if abdominal pain persists.

Neurological features: Restlessness, hypertonia, exaggerated limb reflexes and convulsions. Coma may develop in very severe cases.

Cardiovascular features: Sinus tachycardia is common. Ectopic beats and supraventricular and ventricular tachycardia may follow.

Metabolic features: Hypokalaemia due to shift of potassium from plasma into cells is common, can develop rapidly and may be severe. Hyperglycaemia, hypomagnesaemia and metabolic acidosis may also occur. Rhabdomyolysis may also occur.

Management

Activated charcoal or gastric lavage should be considered if a significant overdose has been ingested within 1-2 hours. Repeated doses of activated charcoal given by mouth can enhance theophylline elimination. Measure the plasma potassium concentration urgently, repeat frequently and correct hypokalaemia. BEWARE! If large amounts of potassium have been given, serious hyperkalaemia may develop during recovery. If plasma potassium is low then the plasma magnesium concentration should be measured as soon as possible.

In the treatment of ventricular arrhythmias, proconvulsant antiarrhythmic agents such as lignocaine (lidocaine) should be avoided because of the risk of causing or exacerbating seizures.

Measure the plasma theophylline concentration regularly when severe poisoning is suspected, until concentrations are falling. Vomiting should be treated with an antiemetic such as metoclopramide or ondansetron.

Tachycardia with an adequate cardiac output is best left untreated. Beta-blockers may be given in extreme cases but not if the patient is asthmatic. Control isolated convulsions with intravenous diazepam. Exclude hypokalaemia as a cause.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

The mechanism of action of theophylline is unclear although a number of pharmacological actions have been implicated. The principal of these are: -

1) Inhibition of the enzyme phosphodiesterase leading to raised cyclic AMP levels.

2) Antagonism of adenosine receptors.

3) Inhibition of the intracellular release of calcium.

4) Stimulation of catecholamine release

5) Anti-inflammatory action possible involving the inhibition of submucosal action.

5.2 Pharmacokinetic Properties

Following administration of Slo-Phyllin capsules at an appropriate twice-daily dosage, peak levels occur 4-8 hours after dosing, and steady state is achieved in three days.

5.3 Preclinical Safety Data

No adverse effects can be predicted from animal toxicology studies other than those documented from human use of theophylline.

6. Pharmaceutical Particulars

6.1 List Of Excipients

The inactive ingredients are sucrose, maize starch, refined bleached lac, talc and ethanol. The gelatine capsules contain the following shell colours: Slo-Phyllin 60mg E171; Slo-Phyllin 125mg E171 and E172; Slo-Phyllin 250mg E171, E127 and E132.

Printing ink: black iron oxide (E172), shellac glaze, propylene glycol.

6.2 Incompatibilities

None stated.

6.3 Shelf Life

Three years.

6.4 Special Precautions For Storage

Do not store above 25 degree C. Store in the original package.

6.5 Nature And Contents Of Container

PVC/Foil blister packs of 56 tablets

Sample PVC/Foil blister packs of 8 tablets

Plastic container of 100 tablets.

6.6 Special Precautions For Disposal And Other Handling

Patients should be instructed not to chew or suck the capsules or pellets as this destroys the time-release properties. However, for those who experience difficulty in swallowing capsules, the contents of a capsule may be sprinkled on to a spoonful of soft food, e.g. yoghurt.

7. Marketing Authorisation Holder

Merck Serono Ltd, Bedfont Cross, Stanwell Road, Feltham, Middlesex, TW14 8NX, UK

8. Marketing Authorisation Number(S)

Slo-Phyllin 60mg capsules PL 11648/0079

Slo-Phyllin 125mg capsules PL 11648/0080

Slo-Phyllin 250mg capsules PL 11648/0081

9. Date Of First Authorisation/Renewal Of The Authorisation

Year granted - 1977

10. Date Of Revision Of The Text

25 September 2009

Medotar Topical

Generic Name: coal tar (Topical route)

kole tar

Commonly used brand name(s)

In the U.S.

• Betatar Gel


• Cutar Emulsion


• Denorex


• DHS Tar


• Doak Tar


• Duplex T


• Fototar


• Ionil-T Plus


• Medotar


• MG 217


• Neutrogena T/Derm


• Neutrogena T/Gel

In Canada

• Estar


• Liquor Carbonis Detergens


• Psorigel


• Spectro Tar Skin Wash


• Tar Distillate

Available Dosage Forms:

• Liquid


• Shampoo


• Lotion


• Solution


• Cream


• Gel/Jelly


• Soap


• Kit


• Ointment


• Bar


• Foam


• Emulsion

Therapeutic Class: Keratolytic

Uses For Medotar

Coal tar is used to treat eczema, psoriasis, seborrheic dermatitis, and other skin disorders.

Some of these preparations are available only with your doctor's prescription.

Before Using Medotar

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

Coal tar products should not be used on infants, unless otherwise directed by your doctor. Studies on this medicine have been done only in adult patients, and there is no specific information comparing use of this medicine in children with use in other age groups.

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of this medicine in the elderly with use in other age groups.

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. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

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.

Proper Use of coal tar

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

Use this medicine only as directed. Do not use more of it and do not use it more often than recommended on the label, unless otherwise directed by your doctor. To do so may increase the chance of side effects.

After applying coal tar, protect the treated area from direct sunlight and do not use a sunlamp for 72 hours, unless otherwise directed by your doctor, since a severe reaction may occur. Also, make sure you have removed all the coal tar medicine from your skin before you go back into direct sunlight or use a sunlamp.

Do not apply this medicine to infected, blistered, raw, or oozing areas of the skin.

Keep this medicine away from the eyes. If you should accidentally get some in your eyes, flush them thoroughly with water at once.

To use the cream or ointment form of this medicine:

• Apply enough medicine to cover the affected area, and rub in gently.

To use the gel form of this medicine:

• Apply enough gel to cover the affected area, and rub in gently. Allow the gel to remain on the affected area for 5 minutes, then remove excess gel by patting with a clean tissue.

To use the shampoo form of this medicine:

• Wet the scalp and hair with lukewarm water. Apply a generous amount of shampoo and rub into the scalp, then rinse. Apply the shampoo again, working up a rich lather, and allow to remain on the scalp for 5 minutes. Then rinse thoroughly.

To use the nonshampoo liquid form of this medicine:

• Some of these preparations are to be applied directly to dry or wet skin, some are to be added to lukewarm bath water, and some may be applied directly to dry or wet skin or added to lukewarm bath water. Make sure you know exactly how you should use this medicine. If you have any questions about this, check with your health care professional.


• If this medicine is to be applied directly to the skin, apply enough to cover the affected area, and rub in gently.


• Some of these preparations contain alcohol and are flammable. Do not use near heat, near open flame, or while smoking.

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 eczema, psoriasis, seborrheic dermatitis, and other skin disorders:
  
  • For cleansing bar dosage form:
    
    • Adults—Use one or two times a day, or as directed by your doctor.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For cream dosage form:
    
    • Adults—Apply to the affected area(s) of the skin up to four times a day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For gel dosage form:
    
    • Adults—Apply to the affected area(s) of the skin one or two times a day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For lotion dosage form:
    
    • Adults—Apply directly to the affected area(s) of the skin or use as a bath, hand or foot soak, or as a hair rinse, depending on the product.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For ointment dosage form:
    
    • Adults—Apply to the affected area(s) of the skin two or three times a day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For shampoo dosage form:
    
    • Adults—Use once a day to once a week or as directed by your doctor.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For topical solution dosage form:
    
    • Adults—Apply to wet the skin or scalp, or use as a bath, depending on the product.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For topical suspension dosage form:
    
    • Adults—Use as a bath.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, apply 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.

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.

Precautions While Using Medotar

If this medicine is used on the scalp, it may temporarily discolor blond, bleached, or tinted hair.

Coal tar may stain the skin or clothing. Avoid getting it on your clothing. The stain on the skin will wear off after you stop using the medicine.

Medotar Side Effects

In animal studies, coal tar has been shown to increase the chance of skin cancer.

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 as soon as possible if any of the following side effects occur:

Rare

• Skin irritation not present before use of this medicine


• skin rash

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

• Stinging (mild)—especially for gel and solution dosage forms

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: Medotar Topical side effects (in more detail)

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More Medotar Topical resources

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

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Tamsulosin

Dosage Form: capsule
FULL PRESCRIBING INFORMATION

Indications and Usage for Tamsulosin

Tamsulosin hydrochloride capsules are indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH) [see Clinical Studies (14)]. Tamsulosin hydrochloride capsules are not indicated for the treatment of hypertension.

Tamsulosin Dosage and Administration

Tamsulosin hydrochloride capsules 0.4 mg once daily is recommended as the dose for the treatment of the signs and symptoms of BPH. It should be administered approximately one-half hour following the same meal each day.

For those patients who fail to respond to the 0.4 mg dose after 2 to 4 weeks of dosing, the dose of Tamsulosin hydrochloride capsules can be increased to 0.8 mg once daily. Tamsulosin hydrochloride capsules 0.4 mg should not be used in combination with strong inhibitors of CYP3A4 (e.g., ketoconazole) [see Warnings and Precautions (5.2)].

If Tamsulosin hydrochloride capsules administration is discontinued or interrupted for several days at either the 0.4 mg or 0.8 mg dose, therapy should be started again with the 0.4 mg once-daily dose.

Dosage Forms and Strengths

Capsule: 0.4 mg, hard-shell gelatin capsule with a blue opaque cap and a blue opaque body filled with white to off-white beads. The capsule is axially printed with MYLAN over 2500 in black ink on both the cap and the body.

Contraindications

Tamsulosin hydrochloride capsules are contraindicated in patients known to be hypersensitive to Tamsulosin hydrochloride or any component of Tamsulosin hydrochloride capsules. Reactions have included skin rash, urticaria, pruritus, angioedema and respiratory symptoms [see Adverse Reactions (6.2)].

Warnings and Precautions

Orthostasis

The signs and symptoms of orthostasis (postural hypotension, dizziness and vertigo) were detected more frequently in Tamsulosin hydrochloride capsule-treated patients than in placebo recipients. As with other alpha adrenergic blocking agents there is a potential risk of syncope [see Adverse Reactions (6.1)]. Patients beginning treatment with Tamsulosin hydrochloride capsules should be cautioned to avoid situations where injury could result should syncope occur [see Patient Counseling Information (17.1)].

Drug Interactions

Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6. Tamsulosin hydrochloride capsules 0.4 mg should not be used in combination with strong inhibitors of CYP3A4 (e.g., ketoconazole) [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)]. Tamsulosin hydrochloride capsules should be used with caution in combination with moderate inhibitors of CYP3A4 (e.g., erythromycin), in combination with strong (e.g., paroxetine) or moderate (e.g., terbinafine) inhibitors of CYP2D6, in patients known to be CYP2D6 poor metabolizers particularly at a dose higher than 0.4 mg (e.g., 0.8 mg) [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

Tamsulosin hydrochloride capsules should be used with caution in combination with cimetidine, particularly at a dose higher than 0.4 mg (e.g., 0.8 mg) [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

Tamsulosin hydrochloride capsules should not be used in combination with other alpha adrenergic blocking agents [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)].

Caution is advised when alpha adrenergic blocking agents including Tamsulosin hydrochloride capsules are coadministered with PDE5 inhibitors. Alpha-adrenergic blockers and PDE5 inhibitors are both vasodilators that can lower blood pressure. Concomitant use of these two drug classes can potentially cause symptomatic hypotension [see Drug Interactions (7.3) and Clinical Pharmacology (12.3)].

Caution should be exercised with concomitant administration of warfarin and Tamsulosin hydrochloride capsules [see Drug Interactions (7.4) and Clinical Pharmacology (12.3)].

Priapism

Rarely (probably less than 1 in 50,000 patients), Tamsulosin, like other alpha1 antagonists, has been associated with priapism (persistent painful penile erection unrelated to sexual activity). Because this condition can lead to permanent impotence if not properly treated, patients must be advised about the seriousness of the condition [see Patient Counseling Information (17.2)].

Screening for Prostate Cancer

Prostate cancer and BPH frequently coexist; therefore, patients should be screened for the presence of prostate cancer prior to treatment with Tamsulosin hydrochloride capsules and at regular intervals afterwards [see Patient Counseling Information (17.3)].

Intraoperative Floppy Iris Syndrome

 Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in some patients on or previously treated with alpha1 blockers, including Tamsulosin hydrochloride capsules [see Adverse Reactions (6.2)].

Most reports were in patients taking the alpha1 blocker when IFIS occurred, but in some cases, the alpha1 blocker had been stopped prior to surgery. In most of these cases, the alpha1 blocker had been stopped recently prior to surgery (2 to 14 days), but in a few cases, IFIS was reported after the patient had been off the alpha1 blocker for a longer period (5 weeks to 9 months). IFIS is a variant of small pupil syndrome and is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs and potential prolapse of the iris toward the phacoemulsification incisions. The patient's ophthalmologist should be prepared for possible modifications to their surgical technique, such as the utilization of iris hooks, iris dilator rings, or viscoelastic substances.

 IFIS may increase the risk of eye complications during and after the operation. The benefit of stopping alpha1 blocker therapy prior to cataract surgery has not been established. The initiation of therapy with Tamsulosin in patients for whom cataract surgery is scheduled is not recommended.

Sulfa Allergy

In patients with sulfa allergy, allergic reaction to Tamsulosin hydrochloride capsules has been rarely reported. If a patient reports a serious or life threatening sulfa allergy, caution is warranted when administering Tamsulosin hydrochloride capsules.

Adverse Reactions

Clinical Trials Experience

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

The incidence of treatment-emergent adverse events has been ascertained from six short-term U.S. and European placebo-controlled clinical trials in which daily doses of 0.1 to 0.8 mg Tamsulosin hydrochloride capsules were used. These studies evaluated safety in 1,783 patients treated with Tamsulosin hydrochloride capsules and 798 patients administered placebo. Table 1 summarizes the treatment-emergent adverse events that occurred in ≥ 2% of patients receiving either Tamsulosin hydrochloride capsules 0.4 mg or 0.8 mg and at an incidence numerically higher than that in the placebo group during two 13-week U.S. trials (US92-03A and US93-01) conducted in 1,487 men.

Table 1: Treatment Emergent* Adverse Events Occurring in ≥ 2% of Tamsulosin Hydrochloride Capsules or Placebo Patients in Two U.S. Short-Term Placebo-Controlled Clinical Studies

* A treatment-emergent adverse event was defined as any event satisfying one of the following criteria: The adverse event occurred for the first time after initial dosing with double-blind study medication. The adverse event was present prior to or at the time of initial dosing with double-blind study medication and subsequently increased in severity during double-blind treatment; or The adverse event was present prior to or at the time of initial dosing with double-blind study medication, disappeared completely, and then reappeared during double-blind treatment. † Coding preferred terms also include cold, common cold, head cold, flu, and flu-like symptoms. ‡ Coding preferred terms also include nasal congestion, stuffy nose, runny nose, sinus congestion, and hay fever.
Body System/ Adverse Event	Tamsulosin Hydrochloride Capsules Groups		Placebo
	0.4 mg n = 502	0.8 mg n = 492	n = 493
Body As Whole
Headache	97 (19.3%)	104 (21.1%)	99 (20.1%)
Infection†	45 (9%)	53 (10.8%)	37 (7.5%)
Asthenia	39 (7.8%)	42 (8.5%)	27 (5.5%)
Back Pain	35 (7%)	41 (8.3%)	27 (5.5%)
Chest Pain	20 (4%)	20 (4.1%)	18 (3.7%)
Nervous System
Dizziness	75 (14.9%)	84 (17.1%)	50 (10.1%)
Somnolence	15 (3%)	21 (4.3%)	8 (1.6%)
Insomnia	12 (2.4%)	7 (1.4%)	3 (0.6%)
Libido Decreased	5 (1%)	10 (2%)	6 (1.2%)
Respiratory System
Rhinitis‡	66 (13.1%)	88 (17.9%)	41 (8.3%)
Pharyngitis	29 (5.8%)	25 (5.1%)	23 (4.7%)
Cough Increased	17 (3.4%)	22 (4.5%)	12 (2.4%)
Sinusitis	11 (2.2%)	18 (3.7%)	8 (1.6%)
Digestive System
Diarrhea	31 (6.2%)	21 (4.3%)	22 (4.5%)
Nausea	13 (2.6%)	19 (3.9%)	16 (3.2%)
Tooth Disorder	6 (1.2%)	10 (2%)	7 (1.4%)
Urogenital System
Abnormal Ejaculation	42 (8.4%)	89 (18.1%)	1 (0.2%)
Special Senses
Blurred Vision	1 (0.2%)	10 (2%)	2 (0.4%)

Signs and Symptoms of Orthostasis

In the two U.S. studies, symptomatic postural hypotension was reported by 0.2% of patients (1 of 502) in the 0.4 mg group, 0.4% of patients (2 of 492) in the 0.8 mg group, and by no patients in the placebo group. Syncope was reported by 0.2% of patients (1 of 502) in the 0.4 mg group, 0.4% of patients (2 of 492) in the 0.8 mg group and 0.6% of patients (3 of 493) in the placebo group. Dizziness was reported by 15% of patients (75 of 502) in the 0.4 mg group, 17% of patients (84 of 492) in the 0.8 mg group, and 10% of patients (50 of 493) in the placebo group. Vertigo was reported by 0.6% of patients (3 of 502) in the 0.4 mg group, 1% of patients (5 of 492) in the 0.8 mg group and by 0.6% of patients (3 of 493) in the placebo group.

Multiple testing for orthostatic hypotension was conducted in a number of studies. Such a test was considered positive if it met one or more of the following criteria: (1) a decrease in systolic blood pressure of ≥ 20 mmHg upon standing from the supine position during the orthostatic tests; (2) a decrease in diastolic blood pressure ≥ 10 mmHg upon standing, with the standing diastolic blood pressure < 65 mmHg during the orthostatic test; (3) an increase in pulse rate of ≥ 20 bpm upon standing with a standing pulse rate ≥ 100 bpm during the orthostatic test; and (4) the presence of clinical symptoms (faintness, lightheadedness/lightheaded, dizziness, spinning sensation, vertigo, or postural hypotension) upon standing during the orthostatic test.

Following the first dose of double-blind medication in Study 1, a positive orthostatic test result at 4 hours post-dose was observed in 7% of patients (37 of 498) who received Tamsulosin hydrochloride capsules 0.4 mg once daily and in 3% of the patients (8 of 253) who received placebo. At 8 hours post-dose, a positive orthostatic test result was observed for 6% of the patients (31 of 498) who received Tamsulosin hydrochloride capsules 0.4 mg once daily and 4% (9 of 250) who received placebo (Note: patients in the 0.8 mg group received 0.4 mg once daily for the first week of Study 1).

In Studies 1 and 2, at least one positive orthostatic test result was observed during the course of these studies for 81 of the 502 patients (16%) in the Tamsulosin hydrochloride capsules 0.4 mg once-daily group, 92 of the 491 patients (19%) in the Tamsulosin hydrochloride capsules 0.8 mg once-daily group, and 54 of the 493 patients (11%) in the placebo group.

Because orthostasis was detected more frequently in Tamsulosin hydrochloride capsule-treated patients than in placebo recipients, there is a potential risk of syncope [see Warnings and Precautions (5.1)].

Abnormal Ejaculation

Abnormal ejaculation includes ejaculation failure, ejaculation disorder, retrograde ejaculation and ejaculation decrease. As shown in Table 1, abnormal ejaculation was associated with Tamsulosin hydrochloride capsules administration and was dose related in the U.S. studies. Withdrawal from these clinical studies of Tamsulosin hydrochloride capsules because of abnormal ejaculation was also dose-dependent with 8 of 492 patients (1.6%) in the 0.8 mg group and no patients in the 0.4 mg or placebo groups discontinuing treatment due to abnormal ejaculation.

Laboratory Tests

No laboratory test interactions with Tamsulosin hydrochloride capsules are known. Treatment with Tamsulosin hydrochloride capsules for up to 12 months had no significant effect on prostate-specific antigen (PSA).

Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of Tamsulosin hydrochloride capsules. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to Tamsulosin hydrochloride capsules.

Allergic-type reactions such as skin rash, urticaria, pruritus, angioedema and respiratory symptoms have been reported with positive rechallenge in some cases. Priapism has been reported rarely. Infrequent reports of dyspnea, palpitations, hypotension, atrial fibrillation, arrhythmia, tachycardia, skin desquamation including reports of Stevens-Johnson Syndrome, constipation and vomiting have been received during the post-marketing period.

During cataract surgery, a variant of small pupil syndrome known as Intraoperative Floppy Iris Syndrome (IFIS) has been reported in association with alpha1 blocker therapy [see Warnings and Precautions (5.5)].

Drug Interactions

Cytochrome P450 Inhibition

Strong and Moderate Inhibitors of CYP3A4 or CYP2D6

Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6.

Concomitant treatment with ketoconazole (a strong inhibitor of CYP3A4) resulted in an increase in the Cmax and AUC of Tamsulosin by a factor of 2.2 and 2.8, respectively [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)]. The effects of concomitant administration of a moderate CYP3A4 inhibitor (e.g., erythromycin) on the pharmacokinetics of Tamsulosin hydrochloride have not been evaluated [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

Concomitant treatment with paroxetine (a strong inhibitor of CYP2D6) resulted in an increase in the Cmax and AUC of Tamsulosin by a factor of 1.3 and 1.6, respectively [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)]. A similar increase in exposure is expected in CYP2D6 poor metabolizers (PM) as compared to extensive metabolizers (EM). Since CYP2D6 PMs cannot be readily identified and the potential for significant increase in Tamsulosin exposure exists when Tamsulosin hydrochloride capsules 0.4 mg is coadministered with strong CYP3A4 inhibitors in CYP2D6 PMs, Tamsulosin hydrochloride 0.4 mg capsules should not be used in combination with strong inhibitors of CYP3A4 (e.g., ketoconazole) [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

The effects of concomitant administration of a moderate CYP2D6 inhibitor (e.g., terbinafine) on the pharmacokinetics of Tamsulosin hydrochloride have not been evaluated [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

The effects of coadministration of both a CYP3A4 and a CYP2D6 inhibitor with Tamsulosin hydrochloride capsules have not been evaluated. However, there is a potential for significant increase in Tamsulosin exposure when Tamsulosin hydrochloride capsules 0.4 mg is coadministered with a combination of both CYP3A4 and CYP2D6 inhibitors [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

Cimetidine

Treatment with cimetidine resulted in a significant decrease (26%) in the clearance of Tamsulosin hydrochloride, which resulted in a moderate increase in Tamsulosin hydrochloride AUC (44%) [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

Other Alpha Adrenergic Blocking Agents

The pharmacokinetic and pharmacodynamic interactions between Tamsulosin hydrochloride capsules and other alpha adrenergic blocking agents have not been determined; however, interactions between Tamsulosin hydrochloride capsules and other alpha adrenergic blocking agents may be expected [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

PDE5 Inhibitors

Caution is advised when alpha adrenergic blocking agents including Tamsulosin hydrochloride are coadministered with PDE5 inhibitors. Alpha adrenergic blockers and PDE5 inhibitors are both vasodilators that can lower blood pressure. Concomitant use of these two drug classes can potentially cause symptomatic hypotension [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

Warfarin

A definitive drug-drug interaction study between Tamsulosin hydrochloride and warfarin was not conducted. Results from limited in vitro and in vivo studies are inconclusive. Caution should be exercised with concomitant administration of warfarin and Tamsulosin hydrochloride capsules [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

Nifedipine, Atenolol, Enalapril

Dosage adjustments are not necessary when Tamsulosin hydrochloride capsules are administered concomitantly with nifedipine, atenolol, or enalapril [see Clinical Pharmacology (12.3)].

Digoxin and Theophylline

Dosage adjustments are not necessary when a Tamsulosin hydrochloride capsule is administered concomitantly with digoxin or theophylline [see Clinical Pharmacology (12.3)].

Furosemide

Tamsulosin hydrochloride capsules had no effect on the pharmacodynamics (excretion of electrolytes) of furosemide. While furosemide produced an 11% to 12% reduction in Tamsulosin hydrochloride Cmax and AUC, these changes are expected to be clinically insignificant and do not require adjustment of the Tamsulosin hydrochloride capsules dosage [see Clinical Pharmacology (12.3)].

USE IN SPECIFIC POPULATIONS

Pregnancy

Teratogenic Effects. Pregnancy Category B

Administration of Tamsulosin hydrochloride to pregnant female rats at dose levels up to approximately 50 times the human therapeutic AUC exposure (300 mg/kg/day) revealed no evidence of harm to the fetus. Administration of Tamsulosin hydrochloride to pregnant rabbits at dose levels up to 50 mg/kg/day produced no evidence of fetal harm. Tamsulosin hydrochloride capsules are not indicated for use in women.

Nursing Mothers

Tamsulosin hydrochloride capsules are not indicated for use in women.

Pediatric Use

Tamsulosin hydrochloride capsules are not indicated for use in pediatric populations.

A description of the data from pediatric studies of Tamsulosin hydrochloride capsules is contained in the approved labeling for Boehringer Ingelheim’s Flomax® capsules. However, due to Boehringer Ingelheim’s marketing exclusivity rights, a description of these pediatric studies is not contained in the approved labeling for this Tamsulosin hydrochloride capsules.

Geriatric Use

Of the total number of subjects (1,783) in clinical studies of Tamsulosin, 36% were 65 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and the other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.3)].

Renal Impairment

Patients with renal impairment do not require an adjustment in Tamsulosin hydrochloride capsules dosing. However, patients with end-stage renal disease (CLcr < 10 mL/min/1.73 m2) have not been studied [see Clinical Pharmacology (12.3)].

Hepatic Impairment

Patients with moderate hepatic impairment do not require an adjustment in Tamsulosin hydrochloride capsules dosage. Tamsulosin hydrochloride has not been studied in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)].

Overdosage

Should overdosage of Tamsulosin hydrochloride capsules lead to hypotension [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)], support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by keeping the patient in the supine position. If this measure is inadequate, then administration of intravenous fluids should be considered. If necessary, vasopressors should then be used and renal function should be monitored and supported as needed. Laboratory data indicate that Tamsulosin hydrochloride is 94% to 99% protein bound; therefore, dialysis is unlikely to be of benefit.

Tamsulosin Description

Tamsulosin hydrochloride is an antagonist of alpha1A adrenoceptors in the prostate.

Tamsulosin hydrochloride is (-)-(R)-5-[2-[[2-(o-Ethoxyphenoxy)ethyl]amino]propyl]-2-methoxybenzenesulfonamide, monohydrochloride. Tamsulosin hydrochloride, USP is a white to off-white powder that melts with decomposition at approximately 230°C. It is sparingly soluble in water and methanol, slightly soluble in glacial acetic acid and ethanol, and practically insoluble in ether.

The molecular formula of Tamsulosin hydrochloride is C20H28N2O5S • HCl. The molecular weight of Tamsulosin hydrochloride is 444.97. Its structural formula is:

Each Tamsulosin hydrochloride capsule, USP for oral administration contains Tamsulosin hydrochloride 0.4 mg, and the following inactive ingredients: calcium stearate, D&C Red No. 28, FD&C Blue No. 1, gelatin, methacrylic acid copolymer, microcrystalline cellulose, polysorbate 80, sodium hydroxide, sodium lauryl sulfate, talc, titanium dioxide and triethyl citrate.

The imprinting ink contains the following: black iron oxide, D&C Yellow No. 10 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake, FD&C Red No. 40 Aluminum Lake, propylene glycol and shellac glaze.

Meets Dissolution Test 5.

Tamsulosin - Clinical Pharmacology

Mechanism of Action

The symptoms associated with benign prostatic hyperplasia (BPH) are related to bladder outlet obstruction, which is comprised of two underlying components: static and dynamic. The static component is related to an increase in prostate size caused, in part, by a proliferation of smooth muscle cells in the prostatic stroma. However, the severity of BPH symptoms and the degree of urethral obstruction do not correlate well with the size of the prostate. The dynamic component is a function of an increase in smooth muscle tone in the prostate and bladder neck leading to constriction of the bladder outlet. Smooth muscle tone is mediated by the sympathetic nervous stimulation of alpha1 adrenoceptors, which are abundant in the prostate, prostatic capsule, prostatic urethra, and bladder neck. Blockade of these adrenoceptors can cause smooth muscles in the bladder neck and prostate to relax, resulting in an improvement in urine flow rate and a reduction in symptoms of BPH.

Tamsulosin, an alpha1 adrenoceptor blocking agent, exhibits selectivity for alpha1 receptors in the human prostate. At least three discrete alpha1 adrenoceptor subtypes have been identified: alpha1A, alpha1B, and alpha1D; their distribution differs between human organs and tissue. Approximately 70% of the alpha1 receptors in the human prostate are of the alpha1A subtype.

Tamsulosin hydrochloride capsules are not intended for use as an antihypertensive drug.

Pharmacodynamics

Urologic pharmacodynamic effects have been evaluated in neurologically impaired pediatric patients and in adults with BPH [see Use in Specific Populations (8.4) and Clinical Studies (14)].

Pharmacokinetics

The pharmacokinetics of Tamsulosin hydrochloride have been evaluated in adult healthy volunteers and patients with BPH after single and/or multiple administration with doses ranging from 0.1 mg to 1 mg.

Absorption

Absorption of Tamsulosin hydrochloride from Tamsulosin hydrochloride capsules 0.4 mg is essentially complete (> 90%) following oral administration under fasting conditions. Tamsulosin hydrochloride exhibits linear kinetics following single and multiple dosing, with achievement of steady-state concentrations by the fifth day of once-a-day dosing.

Effect of Food

The time to maximum concentration (Tmax) is reached by 4 to 5 hours under fasting conditions and by 6 to 7 hours when Tamsulosin hydrochloride capsules are administered with food. Taking Tamsulosin hydrochloride capsules under fasted conditions results in a 30% increase in bioavailability (AUC) and 40% to 70% increase in peak concentrations (Cmax) compared to fed conditions (Figure 1).

Figure 1: Mean Plasma Tamsulosin Hydrochloride Concentrations Following Single-Dose Administration of Tamsulosin Hydrochloride Capsules 0.4 mg Under Fasted and Fed Conditions (n = 8)

The effects of food on the pharmacokinetics of Tamsulosin hydrochloride are consistent regardless of whether a Tamsulosin hydrochloride capsule is taken with a light breakfast or a high-fat breakfast (Table 2).

Table 2: Mean (± S.D.) Pharmacokinetic Parameters Following Tamsulosin Hydrochloride Capsules 0.4 mg Once Daily or 0.8 mg Once Daily with a Light Breakfast, High-Fat Breakfast or Fasted

Pharmacokinetic Parameter	0.4 mg QD to healthy volunteers; n = 23 (age range 18 to 32 years)		0.8 mg QD to healthy volunteers; n = 22 (age range 55 to 75 years)
	Light Breakfast	Fasted	Light Breakfast	High-Fat Breakfast	Fasted
Cmin (ng/mL)	4 ± 2.6	3.8 ± 2.5	12.3 ± 6.7	13.5 ± 7.6	13.3 ± 13.3
Cmax (ng/mL)	10.1 ± 4.8	17.1 ± 17.1	29.8 ± 10.3	29.1 ± 11	41.6 ± 15.6
Cmax/Cmin Ratio	3.1 ± 1	5.3 ± 2.2	2.7 ± 0.7	2.5 ± 0.8	3.6 ± 1.1
Tmax (hours)	6	4	7	6.6	5
T1/2 (hours)	-	-	-	-	14.9 ± 3.9
AUCτ (ng•hr/mL)	151 ± 81.5	199 ± 94.1	440 ± 195	449 ± 217	557 ± 257
Cmin = observed minimum concentration Cmax = observed maximum Tamsulosin hydrochloride plasma concentration Tmax = median time-to-maximum concentration T1/2 = observed half-life AUCτ = area under the Tamsulosin hydrochloride plasma time curve over the dosing interval

Distribution

The mean steady-state apparent volume of distribution of Tamsulosin hydrochloride after intravenous administration to ten healthy male adults was 16 L, which is suggestive of distribution into extracellular fluids in the body.

Tamsulosin hydrochloride is extensively bound to human plasma proteins (94% to 99%), primarily alpha1 acid glycoprotein (AAG), with linear binding over a wide concentration range (20 to 600 ng/mL). The results of two-way in vitro studies indicate that the binding of Tamsulosin hydrochloride to human plasma proteins is not affected by amitriptyline, diclofenac, glyburide, simvastatin plus simvastatin-hydroxy acid metabolite, warfarin, diazepam, propranolol, trichlormethiazide, or chlormadinone. Likewise, Tamsulosin hydrochloride had no effect on the extent of binding of these drugs.

Metabolism

There is no enantiomeric bioconversion from Tamsulosin hydrochloride [R(-) isomer] to the S(+) isomer in humans. Tamsulosin hydrochloride is extensively metabolized by cytochrome P450 enzymes in the liver and less than 10% of the dose is excreted in urine unchanged. However, the pharmacokinetic profile of the metabolites in humans has not been established. Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6 as well as via some minor participation of other CYP isoenzymes. Inhibition of hepatic drug-metabolizing enzymes may lead to increased exposure to Tamsulosin [see Warnings and Precautions (5.2) and Drug Interactions (7.1)]. The metabolites of Tamsulosin hydrochloride undergo extensive conjugation to glucuronide or sulfate prior to renal excretion.

Incubations with human liver microsomes showed no evidence of clinically significant metabolic interactions between Tamsulosin hydrochloride and amitriptyline, albuterol (beta agonist), glyburide (glibenclamide) and finasteride (5alpha-reductase inhibitor for treatment of BPH). However, results of the in vitro testing of the Tamsulosin hydrochloride interaction with diclofenac and warfarin were equivocal.

Excretion

On administration of the radiolabeled dose of Tamsulosin hydrochloride to four healthy volunteers, 97% of the administered radioactivity was recovered, with urine (76%) representing the primary route of excretion compared to feces (21%) over 168 hours.

Following intravenous or oral administration of an immediate-release formulation, the elimination half-life of Tamsulosin hydrochloride in plasma ranged from 5 to 7 hours. Because of absorption rate-controlled pharmacokinetics with Tamsulosin hydrochloride capsules, the apparent half-life of Tamsulosin hydrochloride is approximately 9 to 13 hours in healthy volunteers and 14 to 15 hours in the target population.

Tamsulosin hydrochloride undergoes restrictive clearance in humans, with a relatively low systemic clearance (2.88 L/h).

Specific Populations

Pediatric Use

Tamsulosin hydrochloride capsules are not indicated for use in pediatric populations [see Use in Specific Populations (8.4)].

Geriatric (Age) Use

Cross-study comparison of Tamsulosin hydrochloride capsules overall exposure (AUC) and half-life indicates that the pharmacokinetic disposition of Tamsulosin hydrochloride may be slightly prolonged in geriatric males compared to young, healthy male volunteers. Intrinsic clearance is independent of Tamsulosin hydrochloride binding to AAG, but diminishes with age, resulting in a 40% overall higher exposure (AUC) in subjects of age 55 to 75 years compared to subjects of age 20 to 32 years [see Use in Specific Populations (8.5)].

Renal Impairment

The pharmacokinetics of Tamsulosin hydrochloride have been compared in six subjects with mild-moderate (30 ≤ CLcr < 70 mL/min/1.73 m2) or moderate-severe (10 ≤ CLcr < 30 mL/min/1.73 m2) renal impairment and six normal subjects (CLcr > 90 mL/min/1.73 m2). While a change in the overall plasma concentration of Tamsulosin hydrochloride was observed as the result of altered binding to AAG, the unbound (active) concentration of Tamsulosin hydrochloride, as well as the intrinsic clearance, remained relatively constant. Therefore, patients with renal impairment do not require an adjustment in Tamsulosin hydrochloride capsules dosing. However, patients with end-stage renal disease (CLcr < 10 mL/min/1.73 m2) have not been studied [see Use in Specific Populations (8.6)].

Hepatic Impairment

The pharmacokinetics of Tamsulosin hydrochloride have been compared in eight subjects with moderate hepatic impairment (Child-Pugh’s classification: Grades A and B) and eight normal subjects. While a change in the overall plasma concentration of Tamsulosin hydrochloride was observed as the result of altered binding to AAG, the unbound (active) concentration of Tamsulosin hydrochloride does not change significantly, with only a modest (32%) change in intrinsic clearance of unbound Tamsulosin hydrochloride. Therefore, patients with moderate hepatic impairment do not require an adjustment in Tamsulosin hydrochloride capsules dosage. Tamsulosin hydrochloride has not been studied in patients with severe hepatic impairment [see Use in Specific Populations (8.7)].

Drug Interactions

Cytochrome P450 Inhibition

Strong and Moderate Inhibitors of CYP3A4 or CYP2D6

The effects of ketoconazole (a strong inhibitor of CYP3A4) at 400 mg once daily for 5 days on the pharmacokinetics of a single Tamsulosin hydrochloride capsule 0.4 mg dose was investigated in 24 healthy volunteers (age range 23 to 47 years). Concomitant treatment with ketoconazole resulted in an increase in the Cmax and AUC of Tamsulosin by a factor of 2.2 and 2.8, respectively [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)]. The effects of concomitant administration of a moderate CYP3A4 inhibitor (e.g., erythromycin) on the pharmacokinetics of Tamsulosin hydrochloride have not been evaluated [see Warnings and Precautions (5.2) and Drug Interactions (7.1)].

The effects of paroxetine (a strong inhibitor of CYP2D6) at 20 mg once daily for 9 days on the pharmacokinetics of a single Tamsulosin hydrochloride capsule 0.4 mg dose was investigated in 24 healthy volunteers (age range 23 to 47 years). Concomitant treatment with paroxetine resulted in an increase in the Cmax and AUC of Tamsulosin by a factor of 1.3 and 1.6, respectively [see Warnings and Precautions (5.2) and Drug Interactions (7.1)]. A similar increase in exposure is expected in CYP2D6 poor metabolizers (PM) as compared to extensive metabolizers (EM). A fraction of the population (about 7% of Caucasians and 2% of African Americans) are CYP2D6 PMs. Since CYP2D6 PMs cannot be readily identified and the potential for significant increase in Tamsulosin exposure exists when Tamsulosin hydrochloride 0.4 mg capsules

Cyanoplex

Dosage Form: injection
Cyanoplex

INDICATIONS

For use as a supplement source of B complex vitamins in cattle, swine and sheep.

Precautions

Hypersensitivity reactions to the parenteral administration of products containing thiamine have been reported. Administer with caution and keep treated animals under close observation.

Cyanoplex Dosage and Administration

Subcutaneous or Intramuscular injection is recommended. May be administered intravenously at the discretion of a veterinarian. The following are suggested dosages, depending on the condition of the animal and the desired response.


Adult Cattle-1 to 2 mL per 500 pounds of body weight.

Calves, Swine and Sheep-1 to 2 mL.

May be repeated once or twice weekly.

COMPOSITION

Each mL of sterile aqueous solution contains:

Thiamine Hydrochloride (B1) . . . . . . . . 1.25 mg

Niacinamide . . . . . . . . . . . . . . . . . . . .12.5 mg

Pyridoxine Hydrochloride (B6) . . . . . . . . 5.0 mg

d-Panthenol . . . . . . . . . . . . . . . . . . . . . 5.0 mg

Riboflavin (B2) . . . . . . . . . . . . . . . . . . . 2.0 mg

    (as Riboflavin 5' phosphate sodium)

Cyanocobalamin (B12) . . . . . . . . . . . 1000 mcg

With Benzyl Alcohol 1.5% v/v as a preservative, Ammonium Sulfate 0.1%.

Store at controlled room temperature between 15o and 30oC (59o-86oF)

Protect from light

TAKE TIME OBSERVE LABEL DIRECTIONS

Cyanoplex  cyanocobalamin, niacinamide, dexpanthenol, p yridoxine hydrochloride, riboflavin 5 phosphate sodium, thiamine hydrochloride  injection

Product Information Product Type OTC ANIMAL DRUG NDC Product Code (Source) 58005-610 Route of Administration INTRAMUSCULAR, SUBCUTANEOUS, INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CYANOCOBALAMIN (CYANOCOBALAMIN) CYANOCOBALAMIN 1000 ug  in 1 mL NIACINAMIDE (NIACINAMIDE) NIACINAMIDE 12.5 mg  in 1 mL DEXPANTHENOL (DEXPANTHENOL) DEXPANTHENOL 5.0 mg  in 1 mL PYRIDOXINE HYDROCHLORIDE (PYRIDOXINE) PYRIDOXINE HYDROCHLORIDE 5.0 mg  in 1 mL RIBOFLAVIN 5'-PHOSPHATE SODIUM (RIBOFLAVIN) RIBOFLAVIN 5'-PHOSPHATE SODIUM 2.0 mg  in 1 mL THIAMINE HYDROCHLORIDE (THIAMINE) THIAMINE HYDROCHLORIDE 1.25 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 58005-610-04 100 mL In 1 VIAL None 2 58005-610-05 250 mL In 1 VIAL None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
unapproved drug other		06/01/1997

Labeler - Sparhawk Laboratories, Inc. (958829558)

Revised: 08/2010Sparhawk Laboratories, Inc.

Histone deacetylase inhibitors

A drug may be classified by the chemical type of the active ingredient or by the way it is used to treat a particular condition. Each drug can be classified into one or more drug classes.

Histone deacetylase (HDAC) inhibitors are a group of agents that inhibit the histone deactylase enzymes. During gene expression DNA coils and uncoils around histones. Histone acetylases, acetylate the lysine residues in core histones and histone deactylases remove the acetyl groups from the lysine residues. These actions are important in the regulation of gene expression.

Histone deacetylase inhibitors prevent the deactylation, affect gene expression and causes apoptosis of tumor cells. Histone deacetylase inhibitors are used to treat cutaneous T-cell lymphoma.

See also

Medical conditions associated with histone deacetylase inhibitors:

• Cutaneous T-cell Lymphoma
• Peripheral T-cell Lymphoma

Drug List:

Istodax

Zolinza

Canesten Solution

1. Name Of The Medicinal Product

Canesten Solution

2. Qualitative And Quantitative Composition

Clotrimazole 1.0% w/v.

For excipients, see 6.1.

3. Pharmaceutical Form

A clear solution.

4. Clinical Particulars

4.1 Therapeutic Indications

Canesten Solution should be used to treat all fungal skin infections due to dermatophytes, yeasts, moulds and other fungi.

It is particularly suitable for use on hairy skin and in fungal infections of the outer ear (otitis externa) and middle ear (otomycoses).

4.2 Posology And Method Of Administration

Canesten Solution should be thinly and evenly applied to the affected area 2 or 3 times daily. To prevent relapse, treatment should be continued for at least two weeks after the disappearance of all signs of infection.

There is no separate dosage schedule for the elderly or the young.

4.3 Contraindications

Hypersensitivity to clotrimazole or macrogol 400.

4.4 Special Warnings And Precautions For Use

None known.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

There have been reports of a heat reaction when Canesten Solution is used concomitantly with Sofradex drops in the ear.

4.6 Pregnancy And Lactation

Data on a large number of exposed pregnancies indicate no adverse effects of Clotrimazole on pregnancy or on the health of the foetus/newborn child. To date, no relevant epidemiological data are available.

Clotrimazole can be used during pregnancy, but only under the supervision of a physician or midwife.

4.7 Effects On Ability To Drive And Use Machines

Not applicable.

4.8 Undesirable Effects

As the listed undesirable effects are based on spontaneous reports, assigning accurate frequency of occurrence for each is not possible

Immune system disorder: allergic reaction (syncope, hypotension, dyspnea, urticaria)

Skin and subcutaneous tissue disorders: blisters, discomfort/pain, oedema, irritation, peeling/exfoliation, pruritus, rash, stinging/burning

4.9 Overdose

In the event of accidental oral ingestion, routine measures such as gastric lavage should be performed only if clinical symptoms of overdose become apparent (e.g. dizziness, nausea or vomiting). It should be carried out only if the airway can be protected adequately.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

ATC Code: D01A C01

Clotrimazole is an imidazole derivative with a broad spectrum of antimycotic activity.

Mechanism of Action

Clotrimazole acts against fungi by inhibiting ergosterol synthesis. Inhibition of ergosterol synthesis leads to structural and functional impairment of the cytoplasmic membrane.

Pharmacodynamic Effects

Clotrimazole has a broad antimycotic spectrum of action in vitro and in vivo, which includes dermatophytes, yeasts, moulds, etc.

The mode of action of clotrimazole is fungistatic or fungicidal depending on the concentration of clotrimazole at the site of infection. In-vitro activity is limited to proliferating fungal elements; fungal spores are only slightly sensitive.

Primarily resistant variants of sensitive fungal species are very rare; the development of secondary resistance by sensitive fungi has so far only been observed in very isolated cases under therapeutic conditions.

5.2 Pharmacokinetic Properties

Pharmacokinetic investigations after dermal application have shown that clotrimazole is minimally absorbed from the intact or inflamed skin into the human blood circulation. The resulting peak serum concentrations of clotrimazole were below the detection limit of 0.001 μg/ml, suggesting that clotrimazole applied topically is unlikely to lead to measurable systemic effects or side effects.

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to the information included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Macrogol 400.

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

24 months.

6.4 Special Precautions For Storage

Do not store above 25^oC.

6.5 Nature And Contents Of Container

HDPE bottles with dropper insert and screw-on cap.

Pack size: 20 ml

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Bayer plc

Bayer House

Strawberry Hill

Newbury, Berkshire

RG14 1JA

Trading as Bayer plc, Consumer Care Division

8. Marketing Authorisation Number(S)

PL 0010/0082

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of the first authorisation:	12 June 1981
Date of last renewal of authorisation:	28 May 2002

10. Date Of Revision Of The Text

2 July 2010

Legal Category

P