Keralyt

Generic Name: salicylic acid

Dosage Form: topical gel
Rx Only

Keralyt® Gel w/applicator

(salicylic acid) 6%

FOR TOPICAL USE ONLY. NOT FOR OPHTHALMIC, ORAL OR INTRAVAGINAL USE.

DESCRIPTION: Keralyt® is a gel for topical administration containing salicylic acid 6%, in a vehicle composed of propylene glycol, SD-40 alcohol (21%), hydroxypropylcellulose and purified water. Salicylic acid is the 2 hydroxy derivative of benzoic acid having the following structure:

CLINICAL PHARMACOLOGY: Salicylic acid has been shown to produce desquamation of the horny layer of skin while not affecting qualitative or quantitative changes in structure of the viable epidermis.¹, ² The mechanism of action has been attributed to a dissolution of intercellular cement substance.³ In a study of the percutaneous absorption of salicylic acid from Keralyt GEL in four patients with extensive active psoriasis, Taylor and Halprin⁴ showed that peak serum salicylate levels never exceeded 5 mg/100 ml even though more than 60% of the applied salicylic acid was absorbed. Systemic toxic reactions are usually associated with much higher serum levels (30 to 40 mg/100 ml). Peak serum levels occurred within 5 hours of the topical application under occlusion. The sites were occluded for 10 hours over the entire body surface below the neck. Since salicylates are distributed in the extracellular space, patients with a contracted extracellular space due to dehydration or diuretics have higher salicylate levels than those with a normal extracellular space.⁵ (See PRECAUTIONS).

The major metabolites identified in the urine after topical administration are salicyluric acid (52%), salicylate glucuronides (42%), and free salicylic acid (6%).³ The urinary metabolites after percutaneous absorption differ from those after oral salicylate administration; those derived from percutaneous absorption contain more glucuronides and less salicyluric and salicylic acid. Almost 95% of a single dose of salicylate is excreted within 24 hours of its entrance into the extracellular space.⁵

Fifty to eighty percent of salicylate is protein bound to albumin. Salicylates compete with the binding of several drugs and can modify the action of these drugs. By similar competitive mechanisms other drugs can influence the serum levels of salicylate.⁵ (See PRECAUTIONS).

INDICATIONS AND USAGE - For the removal of excess keratin in hyperkeratotic disorders, including scaling associated with scalp psoriasis or thickened skin of palms and soles, corns and calluses.

CONTRAINDICATIONS: Keralyt GEL should not be used in any patient known to be sensitive to salicylic acid or any other listed ingredient. Keralyt should not be used in children under 2 years of age.

WARNINGS: Prolonged use over large areas, especially in children and those patients with significant renal or hepatic impairment, could result in salicylism. Concomitant use of other drugs which may contribute to elevated serum salicylate levels should be avoided where the potential for toxicity is present. In children under 12 years of age and those patients with renal or hepatic impairment, the area to be treated should be limited and the patient monitored closely for signs of salicylate toxicity: nausea, vomiting, dizziness, loss of hearing, tinnitus, lethargy, hyperpnoea, diarrhea, psychic disturbances. In the event of salicylic acid toxicity, the use of Keralyt GEL should be discontinued. Fluids should be administered to promote urinary excretion. Treatment with sodium bicarbonate (oral or intravenous) should be instituted as appropriate.

Considering the potential risk of developing Reye’s Syndrome, salicylate products should not be administered to children or teenagers with varicella or influenza, unless directed by a physician.

PRECAUTIONS: For external use only. Avoid contact with eyes and other mucous membranes. Mild burning or stinging may occur. Peeling of the skin may increase as the salicylic acid works to loosen excess keratin. If excessive burning, stinging or peeling occurs, discontinue use and consult your physician. Flammable. Keep away from heat and open flame. Keep this and all medications out of reach of children.

Drug Interactions. (The following interactions are from a published review⁵ and include reports concerning both oral and topical salicylate administration. The relationship of these interactions to the use of Keralyt GEL is not known.)

I. Due to the competition of salicylate with other drugs for binding to serum albumin the following drug interactions may occur:

Drug	Description of Interaction
Tolbutamide; Sulfonylureas	Hypoglycemia potentiated
Methotrexate	Decreases tubular reabsorption; clinical toxicity from methotrexate can result
Oral Anticoagulant	Increased bleeding

II. Drugs changing salicylate levels by altering renal tubular reabsorption:

Drug	Description
Corticosteroids	Decreases plasma salicylate level; Tapering doses of steroids may promote salicylism
Ammonium Sulfate	Increases plasma salicylate level

III. Drugs with complicated interactions with salicylates:

Drug	Description
Heparin	Salicylate decreases platelet adhesiveness and interferes with hemostasis in heparin-treated patients
Pyrazinamide	Inhibits pyrazinamide-induced hyperuricemia
Uricosuric Agents	Effect of probenecid, sulfinpyrazone and phenylbutazone inhibited

The following alterations of laboratory tests have been reported during salicylate therapy⁶:

Laboratory Tests	Effect of Salicylates
Thyroid Function	Decreased PBI; increased T3 uptake
Urinary Sugar	False negative with glucose oxidase; false positive with Clinitest with high-dose salicylate therapy (2-5 g qd)
5 Hydroxyindole acetic acid	False negative with fluorometric test
Acetone, Ketone Bodies	False positive FeCl3 in Gerhardt reaction; red color persists with boiling
17-OH corticosteroids	False reduced values with >4.8 g qd salicylate
Vanilmandelic Acid	False reduced values
Uric Acid	May increase or decrease depending on dose
Prothrombin	Decreased levels; slightly increased prothrombin time

Pregnancy (Category C): Salicylic acid has been shown to be teratogenic in rats and monkeys. It is difficult to extrapolate from oral doses of acetyl salicylic acid used in these studies to topical administration as the oral dose to monkeys may represent 4 times the maximum daily human dose of salicylic acid (as supplied in one tube, 40 g of Keralyt GEL) when applied topically over a large body surface. There are no adequate and well-controlled studies in pregnant women. Keralyt GEL should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

Nursing Mothers: Because of the potential for serious adverse reactions in nursing infants from the mother’s use of Keralyt GEL, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Carcinogenesis, Mutagenesis, Impairment of Fertility: No data are available concerning potential carcinogenic or reproductive effects of Keralyt GEL. It has been shown to lack mutagenic potential in the Ames Salmonella test.

ADVERSE REACTIONS: Excessive erythema and scaling conceivably could result from use on open skin lesions.

OVERDOSAGE - See WARNINGS

DOSAGE AND ADMINISTRATION - The preferable method of use is to apply Keralyt GEL thoroughly to the affected area and occlude the area at night. Preferably, the skin should be hydrated for at least five minutes prior to application. The medication is washed off in the morning and if excessive drying and/or irritation is observed a bland cream or lotion may be applied. Once clearing is apparent, the occasional use of Keralyt GEL will usually maintain the remission. In those areas where occlusion is difficult or impossible, application may be made more frequently; hydration by wet packs or baths prior to application apparently enhances the effect. Unless hands are being treated, hands should be rinsed thoroughly after application. For use as a scalp treatment: Keralyt GEL should be applied directly to the affected areas of the scalp on a frequency directed by your physician. The applicator tip will provide accurate application, avoiding contact with normal hair or skin. The gel should be washed off after 10 to 20 minutes initially, but it can be left on for up to an hour as treatment progresses. The gel can be washed off using Keralyt SHAMPOO or warm water in a bath or shower.

HOW SUPPLIED: 60 g Plastic bottle NDC 11086-030-60

Store at controlled room temperature 59° to 86° F (15° to 30° C)

REFERENCES:

1. Davies M, Marks R: Br J Dermatol 95: 187-192,1976.


2. Marks R, Davies M, Cattel A: J Invest Dermatol 64: 283, 1975.


3. Huber C, Christophers E: Arch Derm Res 257: 293-297, 1977.


4. Taylor JR, Halprin KM: Arch Dermatol 111: 740-743, 1975.


5. Goldsmith LA: Int J Dermatol 18: 32-36.


6. Wilson JG, Ritter EJ, Scott WJ, Fradlein R: Tox Appl Pharmacol 41: 67-78, 1977.

SUMMERS

LABORATORIES INC

Manufactured by:

EMS Contract Packaging, Hatfield, PA 19440

Distributed by:

Summers Laboratories, Inc. Collegeville, PA 19426

1-800-533-SKIN (7546) • www.sumlab.com

Keralyt is a trademark of Summers Laboratories, Inc.

Package Label - Principal Display Panel – 60 g Plastic bottle

Package Label - Principal Display Panel – 8 g Tube

Keralyt  salicylic acid  gel

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 11086-030 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength SALICYLIC ACID (SALICYLIC ACID) SALICYLIC ACID 6 g  in 100 g

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 11086-030-60 60 g In 1 BOTTLE, WITH APPLICATOR None 2 11086-030-99 8 g In 1 TUBE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
Unapproved drug other		11/01/2009

Labeler - Summers Laboratories Inc (002382612)

Revised: 10/2009Summers Laboratories Inc

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Bisoprolol Fumarate 3.75 mg Film-coated Tablets

1. Name Of The Medicinal Product

Bisoprolol Fumarate 3.75 mg Film-coated Tablets

2. Qualitative And Quantitative Composition

Each tablet contains 3.75 mg bisoprolol fumarate

Excipients:

Each tablet contains lactose (as lactose monohydrate 1.26 mg)

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Film-coated tablet

yellow-white, round tablet with a score and encoded "BIS 3.75" on one side

The tablet can be divided into equal thirds.

4. Clinical Particulars

4.1 Therapeutic Indications

Treatment of stable chronic heart failure with reduced systolic left ventricular function in addition to ACE inhibitors, and diuretics, and optionally cardiac glycosides (For additional information see section 5.1).

4.2 Posology And Method Of Administration

Method of administration

Bisoprolol tablets should be taken in the morning and can be taken with food. They should be swallowed with liquid and should not be chewed.

Treatment of stable chronic heart failure

Standard treatment of CHF consists of an ACE inhibitor (or an angiotensin receptor blocker in case of intolerance to ACE inhibitors), a beta-blocking agent, diuretics, and when appropriate cardiac glycosides. Patients should be stable (without acute failure) when bisoprolol treatment is initiated.

It is recommended that the treating physician should be experienced in the management of chronic heart failure.

Transient worsening of heart failure, hypotension, or bradycardia may occur during the titration period and thereafter.

Titration phase

The treatment of stable chronic heart failure with bisoprolol requires a titration phase.

The treatment with bisoprolol is to be started with a gradual up titration according to the following steps:

1.25 mg once daily for 1 week, if well tolerated increase to

2.5 mg once daily for a further week, if well tolerated increase to

3.75 mg once daily for a further week, if well tolerated increase to

5 mg once daily for the 4 following weeks, if well tolerated increase to

7.5 mg once daily for the 4 following weeks, if well tolerated increase to

10 mg once daily for the maintenance therapy.

The maximum recommended dose is 10 mg once daily.

Close monitoring of vital signs (heart rate, blood pressure) and symptoms of worsening heart failure is recommended during the titration phase. Symptoms may already occur within the first day after initiating the therapy.

Treatment modification

If the maximum recommended dose is not well tolerated, gradual dose reduction may be considered.

In case of transient worsening of heart failure, hypotension, or bradycardia reconsideration of the dosage of the concomitant medication is recommended. It may also be necessary to temporarily lower the dose of bisoprolol or to consider discontinuation.

The reintroduction and/or uptitration of bisoprolol should always be considered when the patient becomes stable again.

Duration of treatment

Treatment of stable chronic heart failure with bisoprolol is generally a long-term treatment.

The treatment with bisoprolol must not be stopped abruptly since this might lead to a transitory worsening of condition. Especially in patients with ischaemic heart disease, treatment must not be discontinued suddenly. Gradual reduction of the daily dose is recommended.

Renal or liver impairment

There is no information regarding pharmacokinetics of bisoprolol in patients with chronic heart failure and with impaired liver or renal function. Uptitration of the dose in these populations should therefore be made with additional caution.

Elderly

No dosage adjustment is required.

Children and adolescents

There is no experience with bisoprolol in children and adolescents, therefore its use cannot be recommended for children.

4.3 Contraindications

Bisoprolol is contra-indicated in:

• hypersensitivity to bisoprolol or to any of the excipients

• acute heart failure or during episodes of heart failure decompensation requiring i.v. inotropic therapy

• cardiogenic shock

• AV block of second or third degree (without a pacemaker)

• sick sinus syndrome

• sinoatrial block

• symptomatic bradycardia

• symptomatic hypotension

• severe bronchial asthma or severe chronic obstructive pulmonary disease

• severe forms of peripheral arterial occlusive disease or severe forms of Raynaud's syndrome

• untreated phaeochromocytoma (see section4.4)

• metabolic acidosis

• combinations with floctafenin and sultopride

4.4 Special Warnings And Precautions For Use

The treatment of stable chronic heart failure with bisoprolol has to be initiated with a special titration phase (see section 4.2).

Especially in patients with ischaemic heart disease the cessation of therapy with bisoprolol must not be done abruptly unless clearly indicated, because this may lead to transitional worsening of heart condition (see section 4.2).

The initiation of treatment of stable chronic heart failure with bisoprolol necessitates regular monitoring. For the posology and method of administration please refer to section 4.2.

Bisoprolol must be used with caution in:

• bronchospasm (bronchial asthma, obstructive airways diseases)

• diabetes mellitus with large fluctuations in blood glucose values. Symptoms of hypoglycaemia (e.g. tachycardia, palpitations or sweating) can be masked

• strict fasting

• ongoing desensitisation therapy. As with other beta-blockers, bisoprolol may increase both the sensitivity towards allergens and the severity of anaphylactic reactions. Epinephrine treatment may not always yield the expected therapeutic effect.

• AV block of first degree

• Prinzmetal's angina

• peripheral arterial occlusive disease (intensification of complaints might happen especially during the start of therapy)

• General anaesthesia

In patients undergoing general anaesthesia beta-blockade reduces the incidence of arrhythmias and myocardial ischemia during induction and intubation, and the post-operative period. It is currently recommended that maintenance beta-blockade be continued peri-operatively. The anaesthesist must be aware of beta-blockade because of the potential for interactions with other medicinal products, resulting in bradyarrhythmias, attenuation of the reflex tachycardia and the decreased reflex ability to compensate for blood loss. If it is thought necessary to withdraw beta-blocking agent therapy before surgery, this should be done gradually and completed about 48 hours before anaesthesia.

There is no therapeutic experience of bisoprolol treatment of heart failure in patients with the following diseases and conditions:

• insulin dependent diabetes mellitus (type I)

• severely impaired renal function

• severely impaired liver function

• restrictive cardiomyopathy

• congenital heart disease

• haemodynamically significant organic valvular disease

• myocardial infarction within 3 months

Combination of bisoprolol with calcium antagonists of the verapamil and diltiazem type, with Class I antiarrhytmic medicinal products and with centrally acting antihypertensive medicinal products is generally not recommended, for details please refer to section 4.5.

In bronchial asthma or other chronic obstructive lung diseases, which may cause symptoms, bronchodilating therapy should be given concomitantly. Occasionally an increase of the airway resistance may occur in patients with asthma, therefore the dose of beta₂-stimulants may have to be increased.

Patients with psoriasis or with a history of psoriasis should only be given beta-blocking agents (e.g. bisoprolol) after carefully balancing the benefits against the risks.

In patients with phaeochromocytoma bisoprolol must not be administered until after alpha-receptor blockade.

Under treatment with bisoprolol the symptoms of a thyrotoxicosis may be masked.

Lactose

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Combinations contra-indicated:

floctafenine: Beta blocking agents may impede the compensatory cardiovascular reactions associated with hypotension or shock that may be induced by floctafenine.

sultopride: Bisoprolol should not be concomitantly administered with sultopride since there is an increase risk of ventricular arrhythmia.

Combinations not recommended

Calcium antagonists of the verapamil type and to a lesser extent of the diltiazem type: Negative influence on contractility and atrio-ventricular conduction. Intravenous administration of verapamil in patients on β-blocker treatment may lead to severe hypotension and atrioventricular block.

Class I antiarrhythmic medicinal products (e.g. quinidine, disopyramide; lidocaine, phenytoin; flecainide, propafenone): Effect on atrio-ventricular conduction time may be potentiated and negative inotropic effect increased.

Centrally acting antihypertensive medicinal products such as clonidine and others (e.g. methyldopa, moxonodine, rilmenidine): Concomitant use of centrally acting antihypertensive medicinal products may worsen heart failure by a decrease in the central sympathetic tonus (reduction of heart rate and cardiac output, vasodilation). Abrupt withdrawal, particularly if prior to beta-blocking agent discontinuation, may increase risk of “rebound hypertension”.

Combinations to be used with caution

Calcium antagonists of the dihydropyridine type such as felodipine and amlodipine: Concomitant use may increase the risk of hypotension, and an increase in the risk of a further deterioration of the ventricular pump function in patients with heart failure cannot be excluded.

Class-III antiarrhythmic medicinal product (e.g. amiodarone): Effect on atrio-ventricular conduction time may be potentiated.

Topical beta-blocking agents (e.g. eye drops for glaucoma treatment) may add to the systemic effects of bisoprolol.

Parasympathomimetic medicinal products: Concomitant use may increase atrio-ventricular conduction time and the risk of bradycardia.

Insulin and oral antidiabetic medicinal products: Intensification of blood sugar lowering effect. Blockade of beta-adrenoreceptors may mask symptoms of hypoglycaemia.

Anaesthetic agents: Attenuation of the reflex tachycardia and increase of the risk of hypotension (for further information on general anaesthesia see also section 4.4.).

Digitalis glycosides: Reduction of heart rate, increase of atrio-ventricular conduction time.

Non-steroidal anti-inflammatory medicinal products (NSAIDs): NSAIDs may reduce the hypotensive effect of bisoprolol.

β-Sympathomimetic agents (e.g. isoprenaline, dobutamine): Combination with bisoprolol may reduce the effect of both agents.

Sympathomimetics that activate both β- and α-adrenoceptors (e.g. noradrenaline, adrenaline): Combination with bisoprolol may unmask the α-adrenoceptor-mediated vasoconstrictor effects of these agents leading to blood pressure increase and exacerbated intermittent claudication. Such interactions are considered to be more likely with nonselective

β-blockers.

Concomitant use with antihypertensive agents as well as with other medicinal products with blood pressure lowering potential (e.g. tricyclic antidepressants, barbiturates, phenothiazines) may increase the risk of hypotension.

Combinations to be considered

Mefloquine: increased risk of bradycardia

Monoamine oxidase inhibitors (except MAO-B inhibitors): Enhanced hypotensive effect of the beta-blocking agents but also risk for hypertensive crisis.

4.6 Pregnancy And Lactation

Pregnancy:

Bisoprolol has pharmacological effects that may cause harmful effects on pregnancy and/or the foetus/newborn. In general, beta-adrenoceptor blocking agents reduce placental perfusion, which has been associated with growth retardation, intrauterine death, abortion or early labour. Adverse effects (e.g. hypoglycaemia and bradycardia) may occur in the foetus and newborn infant. If treatment with beta-adrenoceptor blocking agents is necessary, beta₁-selective adrenoceptor blocking agents are preferable.

Bisoprolol is not recommended during pregnancy unless clearly necessary. If treatment with bisoprolol is considered necessary, monitoring of the uteroplacental blood flow and the foetal growth is recommended. In case of harmful effects on pregnancy or the foetus concideration of alternative treatment is recommended. The newborn infant must be closely monitored. Symptoms of hypoglycaemia and bradycardia are generally to be expected within the first 3 days.

Lactation:

There are no data on the excretion of bisoprolol in human breast milk or the safety of bisoprolol exposure in infants. Therefore, breastfeeding is not recommended during administration of bisoprolol.

4.7 Effects On Ability To Drive And Use Machines

No studies on the effects on the ability to drive and use machines have been performed. In a study with coronary heart disease patients bisoprolol did not impair driving performance. However, due to individual variations in reactions to the medicinal product, the ability to drive a vehicle or to operate machinery may be impaired. This should be considered particularly at start of treatment and upon change of medication as well as in conjunction with alcohol.

4.8 Undesirable Effects

The following definitions apply to the frequency terminology used hereafter:

Very common (

Cardiac disorders

Very common: bradycardia in patients with chronic heart failure

Common: worsening of pre-exsisting heart failure in patients with chronic heart failure

Uncommon: AV-conduction disturbances

Very rare: chest pain

Investigations

Rare: increased triglycerides, increased liver enzymes (ALAT, ASAT)

Nervous system disorders

Common: dizziness, headache

Rare: syncope

Eye disorders

Rare: reduced tear flow (to be considered if the patient uses lenses)

Very rare: conjunctivitis

Ear and labyrinth disorders

Rare: hearing disorders

Respiratory, thoracic and mediastinal disorders

Uncommon: bronchospasm in patients with bronchial asthma or a history of obstructive airways disease

Rare: allergic rhinitis

Gastrointestinal disorders

Common: gastrointestinal complaints such as nausea, vomiting, diarrhoea, constipation

Skin and subcutaneous tissue disorders

Rare: hypersensitivity reactions (itching, flush, rash)

Very rare: beta-blocking agents may provoke or worsen psoriasis or induce psoriasis-like rash, alopecia

Musculoskeletal and connective tissue disorders

Uncommon: muscular weakness and cramps

Vascular disorders

Common: feeling of coldness or numbness in the extremities, hypotension (especially in patients with heart failure)

Uncommon: orthostatic hypotension

General disorders

Common: asthenia, fatigue

Hepatobiliary disorders

Rare: hepatitis

Reproductive system and breast disorders

Rare: potency disorders

Psychiatric disorders

Uncommon: sleep disorders, depression

Rare: nightmares, hallucinations

4.9 Overdose

With overdose (e.g. daily dose of 15 mg instead of 7.5 mg) third degree AV-block, bradycardia, and dizziness have been reported. In general the most common signs expected with overdose of a beta-blocking agent are bradycardia, hypotension, bronchospasm, acute cardiac insufficiency and hypoglycaemia. To date a few cases of overdose (maximum: 2000 mg) with bisoprolol have been reported in patients suffering from hypertension and/or coronary heart disease showing bradycardia and/or hypotension; all patients recovered. There is a wide interindividual variation in sensitivity to one single high dose of bisoprolol and patients with heart failure are probably very sensitive. Therefore it is mandatory to initiate the treatment of these patients with a gradual uptitration according to the scheme given in section 4.2.

If overdose occurs, bisoprolol treatment should be stopped and supportive and symptomatic treatment should be provided. Limited data suggest that bisoprolol is hardly dialysable. Based on the expected pharmacologic actions and recommendations for other beta-blocking agents, the following general measures should be considered when clinically warranted.

Bradycardia: Administer intravenous atropine. If the response is inadequate, isoprenaline or another agent with positive chronotropic properties may be given cautiously. Under some circumstances, transvenous pacemaker insertion may be necessary.

Hypotension: Intravenous fluids and vasopressors should be administered. Intravenous glucagon may be useful.

AV block (second or third degree): Patients should be carefully monitored and treated with isoprenaline infusion or transvenous cardiac pacemaker insertion.

Acute worsening of heart failure: Administer i.v. diuretics, inotropic agents, vasodilating agents.

Bronchospasm: Administer bronchodilator therapy such as isoprenaline, beta₂-sympathomimetic medicinal products and/or aminophylline.

Hypoglycaemia: Administer i.v. glucose.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Beta blocking agents, selective. ATC Code: C07AB07

Bisoprolol is a highly beta₁-selective-adrenoceptor blocking agent, lacking intrinsic sympathomimetic and relevant membrane stabilising activity. It only shows low affinity to the beta₂-receptor of the smooth muscles of bronchi and vessels as well as to the beta₂-receptors concerned with metabolic regulation. Therefore, bisoprolol is generally not to be expected to influence the airway resistance and beta₂-mediated metabolic effects. Its beta₁-selectivity extends beyond the therapeutic dose range.

Bisoprolol is used for the treatment of hypertension, angina pectoris and heart failure. As with other Beta-1-blocking agents, the method of acting in hypertension is unclear. However, it is known that Bisoprolol reduces plasma renin activity markedly.

Antianginal mechanism: Bisoprolol by inhibiting the cardiac beta receptors inhibits the response given to sympathetic activation. That results in the decrease of heart rate and contractility this way decreasing the oxygen demand of the cardiac muscle.

The indication heart failure was investigated in the CIBIS II trial. In total 2647 patients were included, 83% (N = 2202) were in NYHA class III and 17% (N = 445) were in NYHA class IV. They had stable symptomatic systolic heart failure (ejection fraction <35%, based on echocardiography). Total mortality was reduced from 17.3% to 11.8% (relative reduction 34%). A decrease in sudden death (3.6% vs 6.3%, relative reduction 44%) and a reduced number of heart failure episodes requiring hospital admission (12% vs 17.6%, relative reduction 36%) was observed. Finally, a significant improvement of the functional status according to NYHA classification has been shown. During the initiation and titration of bisoprolol hospital admission due to bradycardia (0.53%), hypotension (0.23%), and acute decompensation (4.97%) were observed, but they were not more frequent than in the placebo-group (0%, 0.3% and 6.74%). The numbers of fatal and disabling strokes during the total study period were 20 in the bisoprolol group and 15 in the placebo group.

The CIBIS III trial investigated 1010 patients aged

There was a trend toward higher frequency of chronic heart failure worsening when bisoprolol was used as the initial 6 months treatment. Non inferiority of bisoprolol-first versus enalapril-first treatment was not proven in the per-protocol analysis, although the two strategies for initiation of CHF treatment showed a similar rate of the primary combined endpoint death and hospitalization at study end (32.4% in the bisoprolol-first group vs. 33.1 % in the enalapril-first group, per-protocol population). The study shows that bisoprolol can also be used in elderly chronic heart failure patients with mild to moderate disease.

In acute administration in patients with coronary heart disease without chronic heart failure bisoprolol reduces the heart rate and stroke volume and thus the cardiac output and oxygen consumption. In chronic administration the initially elevated peripheral resistance decreases.

5.2 Pharmacokinetic Properties

Bisoprolol is absorbed and has a biological availability of about 90% after oral administration. The plasma protein binding of bisoprolol is about 30%. The distribution volume is 3.5 l/kg. Total clearance is approximately 15 l/h. The half-life in plasma of 10-12 hours gives a 24 hour effect after dosing once daily.

Bisoprolol is excreted from the body by two routes. 50% is metabolised by the liver to inactive metabolites which are then excreted by the kidneys. The remaining 50% is excreted by the kidneys in an unmetabolised form. Since the elimination takes place in the kidneys and the liver to the same extent a dosage adjustment is not required for patients with impaired liver function or renal insufficiency. The pharmacokinetics in patients with stable chronic heart failure and with impaired liver or renal function has not been studied.

The kinetics of bisoprolol are linear and independent of age.

In patients with chronic heart failure (NYHA stage III) the plasma levels of bisoprolol are higher and the half-life is prolonged compared to healthy volunteers. Maximum plasma concentration at steady state is 64+21 ng/ml at a daily dose of 10 mg and the half-life is 17+5 hours.

5.3 Preclinical Safety Data

Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity or carcinogenicity. Like other beta-blocking agents, bisoprolol caused maternal (decreased food intake and decreased body weight) and embryo/fetal toxicity (increased incidence of resorptions, reduced birth weight of the offspring, retarded physical development) at high doses but was not teratogenic.

6. Pharmaceutical Particulars

6.1 List Of Excipients

calcium hydrogen phosphate, anhydrous

cellulose, microcrystalline

maize starch, pregelatinised

croscarmellose sodium

silica, colloidal anhydrous

magnesium stearate

lactose monohydrate

hypromellose

macrogol 4000

titanium dioxide (E171)

iron oxide, yellow (E172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

Blister:

5 years

HDPE bottles:

1 year

6.4 Special Precautions For Storage

This medicinal product does not require any special storage conditions.

6.5 Nature And Contents Of Container

Blister, which is made of an aluminium bottom and cover foil (OPA-Al-PVC/Al)..

Pack sizes: 7, 10, 20, 28, 30, 50, 56, 60, 90, 98, 100, 10x20, 10x30 film-coated tablets

HDPE bottles containing 10,20,30,50,60,100,250,500 film-coated tablets.

<Not all pack sizes may be marketed.>

6.6 Special Precautions For Disposal And Other Handling

The film-coated tablet can be divided by placing it on a solid surface with the score pointing upward. The film-coated tablet is divided by exerting a slight pressure with the thumb.

No special requirements.

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

7. Marketing Authorisation Holder

Sandoz Limited

Frimley Business Park,

Frimley,

Camberley,

Surrey,

GU16 7SR.

United Kingdom

8. Marketing Authorisation Number(S)

PL 04416/0925

9. Date Of First Authorisation/Renewal Of The Authorisation

20/01/2009

10. Date Of Revision Of The Text

09/2011

Triaderm Regular Ointment

Generic Name: triamcinolone (Topical application route)

trye-am-SIN-oh-lone a-SEET-oh-nide

Commonly used brand name(s)

In the U.S.

• Aristocort A


• Cinolar


• Kenalog


• Pediaderm TA


• Triacet


• Triamcot


• Triderm


• Zytopic

In Canada

• Aristocort C Concentrate


• Aristocort D Dilute


• Aristocort R Ointment Regular


• Aristocort R Regular


• Kenalog Cream


• Kenalog Ointment


• Kenalog Spray


• Triaderm Mild Cream


• Triaderm Mild Ointment


• Triaderm Regular Cream


• Triaderm Regular Ointment


• Trianide Mild-Cream

Available Dosage Forms:

• Cream


• Lotion


• Spray


• Ointment

Therapeutic Class: Corticosteroid, Intermediate

Pharmacologic Class: Triamcinolone

Uses For Triaderm Regular Ointment

Triamcinolone topical is used to help relieve redness, itching, swelling, or other discomfort caused by skin conditions. This medicine is a corticosteroid (cortisone-like medicine or steroid).

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

Before Using Triaderm Regular Ointment

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

Allergies

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

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of triamcinolone topical in the pediatric population. However, because of this medicine's toxicity, it should be used with caution. Children may absorb large amounts through the skin, which can cause serious side effects. If your child is using this medicine, follow your doctor's instructions very carefully.

Geriatric

No information is available on the relationship of age to the effects of triamcinolone topical in geriatric patients.

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.

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:

• Cushing's syndrome (adrenal gland disorder) or


• Diabetes or


• Hyperglycemia (high blood sugar) or


• Intracranial hypertension (increased pressure in the head)—Use with caution. May make these conditions worse.

• Infection of the skin at or near the place of application or


• Large sores, broken skin, or severe skin injury at the place of application—The chance of side effects may be increased.

Proper Use of triamcinolone

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

It is very important that you use this medicine only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. To do so may cause unwanted side effects or skin irritation.

This medicine is for use on the skin only. Do not get it in your eyes. Do not use it on skin areas that have cuts, scrapes, or burns. If it does get on these areas, rinse it off right away with water.

If you or your child are using the spray form on or near the face, protect your nose to avoid breathing it in and make sure that your eyes are covered.

This medicine should only be used for skin conditions that your doctor is treating. Check with your doctor before using it for other conditions, especially if you think that a skin infection may be present. This medicine should not be used to treat certain kinds of skin infections or conditions, such as severe burns.

Do not use the spray on the groin or underarms unless directed to do so by your doctor.

To use:

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


• Apply a thin layer of this medicine to the affected area of the skin. Rub it in gently.


• Do not bandage or otherwise wrap the skin being treated unless directed to do so by your doctor.


• If the medicine is applied to the diaper area of an infant, do not use tight-fitting diapers or plastic pants unless directed to do so by your doctor.


• If your doctor ordered an occlusive dressing or airtight covering to be applied over the medicine, make sure you know how to apply it. Occlusive dressings increase the amount of medicine absorbed through your skin, so use them only as directed. If you have any questions about this, check with your doctor.

The spray form is flammable until it dries on the skin. Do not use it near heat, an open flame, or while smoking. Do not puncture, break, or burn the aerosol can.

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 redness, itching, and swelling of the skin:
  
  • For topical dosage forms (cream, lotion, and ointment):
    
    • Adults—Apply to the affected area of the skin two to four times per day.
    
    
    • Children—Apply to the affected area of the skin two to four times per day.
    
    
  
  
  • For topical dosage form (aerosol spray):
    
    • Adults—Spray to the affected area of the skin three to four times per day.
    
    
    • Children—Spray to the affected area of the skin three to four times per day.
    
    
  
  

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.

Store the canister at room temperature, away from heat and direct light. Do not freeze. Do not keep this medicine inside a car where it could be exposed to extreme heat or cold. Do not poke holes in the canister or throw it into a fire, even if the canister is empty.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

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

Precautions While Using Triaderm Regular Ointment

It is very important that your doctor check the progress of you or your child at regular visits for any problems that may be caused by this medicine. Blood and urine tests may be needed to check for unwanted effects.

If your or your child's symptoms do not improve within a few weeks, or if they become worse, check with your doctor.

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

Stop using this medicine and check with your doctor right away if you or your child have a skin rash, burning, stinging, swelling, or irritation on the skin.

Do not use this medication with other corticosteroid (eg, hydrocortisone) containing products without checking with your doctor first. .

Do not use cosmetics or other skin care products on the treated areas.

Triaderm Regular Ointment 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:

Incidence not known

• Blistering, burning, crusting, dryness, or flaking of the skin


• irritation


• itching, scaling, severe redness, soreness, or swelling of the skin


• redness and scaling around the mouth


• thinning of the skin with easy bruising, especially when used on the face or where the skin folds together (e.g. between the fingers)

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

• Acne or pimples


• burning and itching of the skin with pinhead-sized red blisters


• burning, itching, and pain in hairy areas, or pus at the root of the hair


• increased hair growth on the forehead, back, arms, and legs


• lightening of normal skin color


• lightening of treated areas of dark skin


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


• softening of the skin

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.

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

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

More Triaderm Regular Ointment resources

• Triaderm Regular Ointment Use in Pregnancy & Breastfeeding
• Triaderm Regular Ointment Drug Interactions
• Triaderm Regular Ointment Support Group
• 22 Reviews for Triaderm Regular - Add your own review/rating

Compare Triaderm Regular Ointment with other medications

• Aphthous Ulcer
• Atopic Dermatitis
• Dermatitis
• Lichen Planus
• Psoriasis

Prevalite

Generic Name: cholestyramine (Oral route)

koe-le-STYE-ra-meen

Commonly used brand name(s)

In the U.S.

• Prevalite


• Questran


• Questran Light

In Canada

• Novo-Cholamine


• Novo-Cholamine Light

Available Dosage Forms:

• Powder for Suspension


• Tablet

Therapeutic Class: Antihyperlipidemic

Pharmacologic Class: Bile Acid Sequestrant

Uses For Prevalite

Cholestyramine is used to lower high cholesterol levels in the blood. This may help prevent medical problems caused by cholesterol clogging the blood vessels. Cholestyramine is also used to remove substances called bile acids from your body. With some liver problems, there is too much bile acid in your body and this can cause severe itching.

Cholestyramine works by attaching to certain substances in the intestine. Since cholestyramine is not absorbed into the body, these substances also pass out of the body without being absorbed.

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

Cholestyramine is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, cholestyramine is used in certain patients with the following medical conditions:

• Digitalis glycoside overdose


• Excess oxalate in the urine

Before Using Prevalite

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

This medicine has been tested in a limited number of children. In effective doses, the medicine has not been shown to cause different side effects or problems than it does in adults.

Geriatric

Side effects may be more likely to occur in patients over 60 years of age, who are usually more sensitive to the effects of cholestyramine.

Pregnancy

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

Breast Feeding

Studies suggest that this medication may alter milk production or composition. If an alternative to this medication is not prescribed, you should monitor the infant for side effects and adequate milk intake.

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 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.

• Mycophenolate Mofetil


• Mycophenolic Acid

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.

• Amiodarone


• Anisindione


• Cephalexin


• Cerivastatin


• Deferasirox


• Diclofenac


• Dicumarol


• Digitoxin


• Digoxin


• Ezetimibe


• Furosemide


• Hydrochlorothiazide


• Leflunomide


• Levothyroxine


• Meloxicam


• Metronidazole


• Phenprocoumon


• Valproic Acid


• Warfarin

Interactions with Food/Tobacco/Alcohol

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

Other Medical Problems

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

• Bleeding problems or


• Constipation or


• Gallstones or


• Heart or blood vessel disease or


• Hemorrhoids or


• Stomach ulcer or other stomach problems or


• Underactive thyroid—Cholestyramine may make these conditions worse

• Kidney disease—There is an increased risk of developing electrolyte problems (problems in the blood)

• Phenylketonuria—Phenylalanine in aspartame is included in the sugar-free brand of cholestyramine and should be avoided. Aspartame can cause problems in people with phenylketonuria. Therefore, it is best if you avoid using the sugar-free product.

Proper Use of cholestyramine

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

Take this medicine exactly as directed by your doctor. Try not to miss any doses and do not take more medicine than your doctor ordered.

This medicine should never be taken in its dry form, since it could cause you to choke. Instead, always mix as follows:

• Place the medicine in 2 ounces of any beverage and mix thoroughly. Then add an additional 2 to 4 ounces of beverage and again mix thoroughly (it will not dissolve) before drinking. After drinking all the liquid containing the medicine, rinse the glass with a little more liquid and drink that also, to make sure you get all the medicine.


• You may also mix this medicine with milk in hot or regular breakfast cereals, or in thin soups such as tomato or chicken noodle soup. Or you may add it to some pulpy fruits such as crushed pineapple, pears, peaches, or fruit cocktail.

For patients taking this medicine for high cholesterol :

• Importance of diet—Before prescribing medicine for your condition, your doctor will probably try to control your condition by prescribing a personal diet for you. Such a diet may be low in fats, sugars, and/or cholesterol. Many people are able to control their condition by carefully following their doctor's orders for proper diet and exercise. Medicine is prescribed only when additional help is needed. Follow carefully the special diet your doctor gave you, since the medicine is effective only when a schedule of diet and exercise is properly followed.


• Also, this medicine is less effective if you are greatly overweight. It may be very important for you to go on a reducing diet. However, check with your doctor before going on any diet.


• Remember that this medicine will not cure your cholesterol problem but it will help control it. Therefore, you must continue to take it as directed if you expect to lower your cholesterol level.

Dosing

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

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

• For oral dosage form (powder for oral suspension):
  
  • For high cholesterol or pruritus (itching) related to biliary obstruction:
    
    • Adults—At first, 4 grams one or two times a day before meals. Then, your doctor may increase your dose to 8 to 24 grams a day. This is divided into two to six doses.
    
    
    • Children—At first, 4 grams a day. This is divided into two doses and taken before meals. Then, your doctor may increase your dose to 8 to 24 grams a day. This is divided into two or more doses.
    
    
  
  

Missed Dose

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

Storage

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Prevalite

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it.

Do not take any other medicine unless prescribed by your doctor since cholestyramine may change the effect of other medicines.

Do not stop taking this medicine without first checking with your doctor. When you stop taking this medicine, your blood cholesterol levels may increase again. Your doctor may want you to follow a special diet to help prevent this from happening.

Prevalite Side Effects

In some animal studies, cholestyramine was found to cause tumors. It is not known whether cholestyramine causes tumors in humans.

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:

Rare

• Black, tarry stools


• stomach pain (severe) with nausea and vomiting

Check with your doctor as soon as possible if any of the following side effects occur:

More common

• Constipation

Rare

• Loss of weight (sudden)

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

• Heartburn or indigestion


• nausea or vomiting


• stomach pain

Less common

• Belching


• bloating


• diarrhea


• dizziness


• headache

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: Prevalite side effects (in more detail)

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

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

More Prevalite resources

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

• Prevalite Powder MedFacts Consumer Leaflet (Wolters Kluwer)


• Prevalite Concise Consumer Information (Cerner Multum)


• Prevalite Prescribing Information (FDA)


• Cholestyramine Prescribing Information (FDA)


• Cholestyramine Professional Patient Advice (Wolters Kluwer)


• Cholestyramine Light Prescribing Information (FDA)


• Cholestyramine Resin Monograph (AHFS DI)


• Questran Prescribing Information (FDA)

Compare Prevalite with other medications

• Crohn's Disease
• Hyperlipoproteinemia
• Hyperlipoproteinemia Type IIa, Elevated LDL
• Hyperlipoproteinemia Type IIb, Elevated LDL VLDL
• Irritable Bowel Syndrome
• Pruritus of Partial Biliary Obstruction

Ciclopirox Shampoo

CICLOPIROX

SHAMPOO, 1%

FOR TOPICAL USE ONLY.

NOT FOR OPHTHALMIC, ORAL, OR INTRAVAGINAL USE.

KEEP OUT OF REACH OF CHILDREN.

Ciclopirox Shampoo Description

Ciclopirox Shampoo, 1%, contains the synthetic antifungal agent, ciclopirox.

Each gram (equivalent to 0.96 mL) of Ciclopirox Shampoo, 1% contains 10 mg ciclopirox in a shampoo base consisting of purified water USP, sodium laureth sulfate, disodium laureth sulfosuccinate, sodium chloride USP, and laureth-2.

Ciclopirox Shampoo, 1% is a colorless, translucent solution. The chemical name for ciclopirox is 6-cyclohexyl-1-hydroxy-4-methyl-2(1H)-pyridone, with the empirical formula C12H17NO2and a molecular weight of 207.27. The CAS Registry Number is [29342-05-0]. The chemical structure is:

Ciclopirox Shampoo - Clinical Pharmacology

Mechanism of Action

Ciclopirox is a hydroxypyridone antifungal agent although the relevance of this property for the indication of seborrheic dermatitis is not known. Ciclopirox acts by chelation of polyvalent cations (Fe3+or Al3+), resulting in the inhibition of the metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell.

Pharmacokinetics and Pharmacodynamics

In a study in patients with seborrheic dermatitis of the scalp, application of 5 mL Ciclopirox Shampoo, 1% twice weekly for 4 weeks, with an exposure time of 3 minutes per application, resulted in detectable serum concentrations of ciclopirox in 6 out of 18 patients. The serum concentrations measured throughout the dosing interval on Days 1 and 29 ranged from 10.3 ng/mL to 13.2 ng/mL. Total urinary excretion of ciclopirox was less than 0.5 % of the administered dose.

Clinical Studies

In two randomized, double-blind clinical trials, patients 16 years and older with seborrheic dermatitis of the scalp applied Ciclopirox Shampoo, 1% or its vehicle two times per week for 4 weeks. Patients who were immunocompromised, those with psoriasis or atopic dermatitis, women of childbearing potential not using adequate contraception, and pregnant or lactating women were excluded from the clinical studies. An evaluation of the overall status of the seborrheic dermatitis, and the presence and severity of erythema or inflammation, and scaling, was made at week 4, using a scale of 0 = none, 1 = slight, 2 = mild, 3 = moderate, 4 = pronounced, and 5 = severe. Effective treatment was defined as achieving a score of 0 (or a score of 1 if the baseline score was ≥3) simultaneously for status of the seborrheic dermatitis, erythema or inflammation, and scaling at Week 4. Ciclopirox Shampoo, 1% was shown to be statistically significantly more effective than vehicle in both studies. Efficacy results for the two studies are presented in the following table.

Effective Treatment Rates at Week 4 in Studies 1 and 2

	Ciclopirox Shampoo, 1%	Vehicle
Study 1	220/380 (58%)	60/192 (31%)
Study 2	62/250 (26%)	32/249 (13%)

Efficacy for black patients was not demonstrated, although only 53 black patients were enrolled in the two pivotal studies.

Microbiology

Ciclopirox is fungicidalin vitroagainstMalassezia furfur (Pityrosporumspp.), P. ovale,andP. orbiculare.Ciclopirox acts by chelation of polyvalent cations (Fe3+or Al3+), resulting in the inhibition of the metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell.

The clinical significance of antifungal activity in the treatment of seborrheic dermatitis is not known.

Indications and Usage for Ciclopirox Shampoo

Ciclopirox Shampoo, 1% is indicated for the topical treatment of seborrheic dermatitis of the scalp in adults.

Contraindications

Ciclopirox Shampoo, 1% is contraindicated in individuals who have shown hypersensitivity to any of its components.

Warnings

Ciclopirox Shampoo, 1% is not for ophthalmic, oral, or intravaginal use.

Keep out of reach of children.

Precautions

General

If a reaction suggesting sensitivity or irritation should occur with the use of Ciclopirox Shampoo, 1%, treatment should be discontinued and appropriate therapy instituted.

Contact of Ciclopirox Shampoo, 1% with the eyes should be avoided. If contact occurs, rinse thoroughly with water.

Seborrheic dermatitis may appear at puberty, however, no clinical studies have been done in patients younger than 16 years.

In patients with lighter hair color, hair discoloration has rarely been reported.

There is no relevant clinical experience with patients who have a history of immunosuppression (e.g., extensive, persistent, or unusual distribution of dermatomycoses, recent or recurring herpes zoster, or persistent herpes simplex), who are immunocompromised (e.g., HIV-infected patients and transplant patients), or who have a diabetic neuropathy.

Information for Patients

The patient should be instructed to:

1. Use Ciclopirox Shampoo, 1% as directed by the physician. Avoid contact with the eyes and mucous membranes. If contact occurs, rinse thoroughly with water. Ciclopirox Shampoo, 1% is for external use on the scalp only. Do not swallow.


2. Use the medication for seborrheic dermatitis for the full treatment time even though symptoms may have improved. Notify the physician if there is no improvement after 4 weeks.


3. Inform the physician if the area of application shows signs of increased irritation (redness, itching, burning, blistering, swelling, or oozing) indicative of possible allergic reaction.


4. Not use the medication for any disorder other than that for which it is prescribed.

Carcinogenesis, Mutagenesis, and Impairment of Fertility:

Long-term animal studies have not been performed to evaluate the carcinogenic potential of Ciclopirox Shampoo, 1% or ciclopirox.

The followingin vitrogenotoxicity tests have been conducted with ciclopirox: evaluation of gene mutation in the AmesSalmonellaandE. coliassays (negative); chromosome aberration assays in V79 Chinese hamster lung fibroblast cells, with and without metabolic activation (positive); chromosome aberration assays in V79 Chinese hamster lung fibroblast cells in the presence of supplemental Fe3+, with and without metabolic activation (negative); gene mutation assays in the HGPRT-test with V79 Chinese hamster lung fibroblast cells (negative); and a primary DNA damage assay (i.e., unscheduled DNA synthesis assay in A549 human cells) (negative). Anin vitrocell transformation assay in BALB/c 3T3 cells was negative for cell transformation. In anin vivoChinese hamster bone marrow cytogenetic assay, ciclopirox was negative for chromosome aberrations at a dosage of 5000 mg/kg body weight.

A combined oral fertility and embryofetal developmental study was conducted in rats with ciclopirox olamine. No effect on fertility or reproductive performance was noted at the highest dose tested of 3.85 mg/kg/day ciclopirox (approximately 1.3 times the maximum recommended human dose based on body surface area comparisons).

Pregnancy:

Teratogenic effects:

Pregnancy Category B

Oral embryofetal developmental studies were conducted in mice, rats, rabbits and monkeys. Ciclopirox or ciclopirox olamine was orally administered during the period of organogenesis. No maternal toxicity, embryotoxicity or teratogenicity were noted at the highest doses of 77, 125, 80 and 38.5 mg/kg/day ciclopirox in mice, rats, rabbits and monkeys, respectively (approximately 13, 42, 54 and 26 times the maximum recommended human dose based on body surface area comparisons, respectively).

Dermal embryofetal developmental studies were conducted in rats and rabbits with ciclopirox olamine dissolved in PEG 400. Ciclopirox olamine was topically administered during the period of organogenesis. No maternal toxicity, embryotoxicity or teratogenicity were noted at the highest doses of 92 mg/kg/day and 77 mg/kg/day ciclopirox in rats and rabbits, respectively (approximately 31 and 54 times the maximum recommended human dose based on body surface area comparisons, respectively).

There are no adequate or well-controlled studies of topically applied ciclopirox in pregnant women. Because animal reproduction studies are not always predictive of human response, Ciclopirox Shampoo, 1% should be used during pregnancy only if clearly needed.

Nursing Mothers:

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Ciclopirox Shampoo, 1% is administered to a nursing woman.

Pediatric Use:

Seborrheic dermatitis may appear at puberty, however, no clinical studies have been done in patients younger than 16 years.

Geriatric Use:

In clinical studies, the safety and tolerability of Ciclopirox Shampoo, 1% in the population 65 years and older was comparable to that of younger subjects. Results of the efficacy analysis in those patients 65 years and older showed effectiveness in 25 of 85 (29%) patients treated with Ciclopirox Shampoo, 1%, and in 15 of 61 (25%) patients treated with the vehicle; due to the small sample size, a statistically significant difference was not demonstrated. Other reported clinical experience has not identified differences in responses between the elderly and younger subjects, but greater sensitivity to adverse effects in some older individuals cannot be ruled out.

Adverse Reactions

In 626 patients treated with Ciclopirox Shampoo, 1% twice weekly in the two pivotal clinical studies, the most frequent adverse events were increased itching in 1% of patients, and application site reactions, such as burning, erythema, and itching, also in 1% of patients. Other adverse events occurred in individual patients only.

Adverse events that led to early study medication termination in clinical trials occurred in 1.5% (26/1738) of patients treated with Ciclopirox Shampoo, 1% and 2.0% (12/661) of patients treated with shampoo vehicle. The most common adverse event leading to termination of study medication in either group was seborrhea. In the Ciclopirox Shampoo, 1% group, other adverse events included rash, pruritus, headache, ventricular tachycardia, and skin disorder. In the shampoo vehicle group, other adverse events included skin disorder and rash.

Ciclopirox Shampoo Dosage and Administration

Wet hair and apply approximately 1 teaspoon (5 mL) of Ciclopirox Shampoo, 1% to the scalp. Up to 2 teaspoons (10 mL) may be used for long hair. Lather and leave on hair and scalp for 3 minutes. A timer may be used. Avoid contact with eyes. Rinse off. Treatment should be repeated twice per week for 4 weeks, with a minimum of 3 days between applications.

If a patient with seborrheic dermatitis shows no clinical improvement after 4 weeks of treatment with Ciclopirox Shampoo, 1%, the diagnosis should be reviewed.

How is Ciclopirox Shampoo Supplied

Ciclopirox Shampoo, 1% is supplied in 120 mL plastic bottles (NDC 0574-2059-12). Discard unused product after initial treatment duration.

Store at 20 - 25 C (68 - 77 F) [see USP Controlled Room Temperature]

Paddock Laboratories, Inc.

Minneapolis, MN 55427

(10-08)

PRINCIPAL DISPLAY PANEL - 120 mL Label

NDC 0574-2059-12

CICLOPIROX

SHAMPOO, 1%

Rx ONLY

For topical use only.

Not for ophthalmic, oral, or

intravaginal use.

Keep out of reach of children.

This package is not child resistant.

NET CONTENTS

120 mL

Paddock

Laboratories, Inc.

2202135 (10-08)

PRINCIPAL DISPLAY PANEL - 120 mL Carton

NDC 0574-2059-12

CICLOPIROX

SHAMPOO, 1%

Rx ONLY

For topical use only.

Not for ophthalmic, oral, or

intravaginal use.

Keep out of reach of children.

This package is not child resistant.

120 mL BOTTLE

Paddock

Laboratories, Inc.

CICLOPIROX  ciclopirox  shampoo

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0574-2059 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Ciclopirox (Ciclopirox) Ciclopirox 10 mg  in 0.96 mL

Inactive Ingredients Ingredient Name Strength Water   Sodium Laureth Sulfate   Disodium Laureth Sulfosuccinate   Sodium Chloride

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0574-2059-12 1 BOTTLE In 1 CARTON contains a BOTTLE, PLASTIC 1 120 mL In 1 BOTTLE, PLASTIC This package is contained within the CARTON (0574-2059-12)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA090490	11/24/2009	01/20/2014

Labeler - Paddock Laboratories, LLC (967694121)

Establishment
Name	Address	ID/FEI	Operations
Paddock Laboratories, LLC		967694121	MANUFACTURE

Revised: 01/2012Paddock Laboratories, LLC