Triamcinolone Injection

Generic Name: triamcinolone acetonide

Dosage Form: injection, suspension
Triamcinolone Acetonide Injectable Suspension, USP

NOT FOR USE IN NEONATES

CONTAINS BENZYL ALCOHOL

For Intra-articular or Intralesional Use

NOT FOR INTRAVENOUS, INTRAMUSCULAR, OR INTRAOCULAR USE

Triamcinolone Injection Description

Triamcinolone acetonide injectable suspension, USP is triamcinolone acetonide, a synthetic glucocorticoid corticosteroid with marked anti-inflammatory action, in a sterile aqueous suspension suitable for intralesional and intra-articular injection. THIS FORMULATION IS SUITABLE FOR INTRA-ARTICULAR AND INTRALESIONAL USE ONLY.

Each mL of the sterile aqueous suspension provides 10 mg triamcinolone acetonide, with sodium chloride for isotonicity, 0.94% (w/v) benzyl alcohol as a preservative, 0.75% carboxymethylcellulose sodium, and 0.04% polysorbate 80; sodium hydroxide or hydrochloric acid may have been added to adjust pH between 5 and 7.5. At the time of manufacture, the air in the container is replaced by nitrogen.

The chemical name for triamcinolone acetonide is 9-Fluoro- 11β, 16α, 17,21 -tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with acetone. Its structural formula is:

M.W. 434.5

Triamcinolone Injection - Clinical Pharmacology

Glucocorticoids, naturally occurring and synthetic, are adrenocortical steroids that are readily absorbed from the gastrointestinal tract.

Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Synthetic analogs such as triamcinolone are primarily used for their anti-inflammatory effects in disorders of many organ systems.

Indications and Usage for Triamcinolone Injection

The intra-articular or soft tissue administration of triamcinolone acetonide injectable suspension is indicated as adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in acute gouty arthritis, acute and subacute bursitis, acute nonspecific tenosynovitis, epicondylitis, rheumatoid arthritis, synovitis or osteoarthritis.

The intralesional administration of triamcinolone acetonide injectable suspension is indicated for alopecia areata; discoid lupus erythematosus; keloids; localized hypertrophic, infiltrated, inflammatory lesions of granuloma annulare, lichen planus, lichen simplex chronicus (neurodermatitis), and psoriatic plaques; necrobiosis lipoidica diabeticorum. Triamcinolone acetonide injectable suspension may also be useful in cystic tumors of an aponeurosis or tendon (ganglia).

Contraindications

Triamcinolone acetonide injectable suspension is contraindicated in patients who are hypersensitive to any components of this product.

Intramuscular corticosteroid preparations are contraindicated for idiopathic thrombocytopenic purpura.

Warnings

General

Exposure to excessive amounts of benzyl alcohol has been associated with toxicity (hypotension, metabolic acidosis), particularly in neonates, and an increased incidence of kernicterus, particularly in small preterm infants. There have been rare reports of deaths, primarily in preterm infants, associated with exposure to excessive amounts of benzyl alcohol. The amount of benzyl alcohol from medications is usually considered negligible compared to that received in flush solutions containing benzyl alcohol. Administration of high dosages of medications containing this preservative must take into account the total amount of benzyl alcohol administered. The amount of benzyl alcohol at which toxicity may occur is not known. If the patient requires more than the recommended dosages or other medications containing this preservative, the practitioner must consider the daily metabolic load of benzyl alcohol from these combined sources (see PRECAUTIONS: Pediatric Use).

Because triamcinolone acetonide injectable suspension is a suspension, it should not be administered intravenously. Strict aseptic technique is mandatory.

Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroid therapy (see ADVERSE REACTIONS).

Increased dosage of rapidly acting corticosteroids is indicated in patients on corticosteroid therapy subjected to any unusual stress before, during, and after the stressful situation.

Triamcinolone acetonide injectable suspension is a long-acting preparation, and is not suitable for use in acute stress situations.

Results from one multicenter randomized, placebo controlled study with methylprednisolone hemisuccinate, an IV corticosteroid, showed an increase in early (at 2 weeks) and late (at 6 months) mortality in patients with cranial trauma who were determined not to have other clear indications for corticosteroid treatment. High does of systemic corticosteroids, including triamcinolone acetonide injectable suspension should not be used for the treatment of traumatic brain injury.

Cardio-Renal

Average and large doses of corticosteroids can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. These effects are less likely to occur with the synthetic derivatives except when they are used in large doses. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion.

Literature reports suggest an apparent association between use of corticosteroids and left ventricular free wall rupture after a recent myocardial infarction; therefore, therapy with corticosteroids should be used with great caution in these patients.

Endocrine

Corticosteroids can produce reversible hypothalamic-pituitary adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment.

Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate adjustment in dosage.

Infections

General

Patients who are on corticosteroids are more susceptible to infections than are healthy individuals. There may be decreased resistance and inability to localize infection when corticosteroids are used. Infection with any pathogen (viral, bacterial, fungal, protozoan or helminthic) in any location of the body may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents. These infections may be mild to severe. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases. Corticosteroids may also mask some signs of current infection.

Fungal Infections

Corticosteroids may exacerbate systemic fungal infections and therefore should not be used in the presence of such infections unless they are needed to control drug reactions. There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure (see PRECAUTIONS: Drug Interactions: Amphotericin B injection and potassium-depleting agents).

Special Pathogens

Latent disease may be activated or there may be an exacerbation of intercurrent infections due to pathogens, including those caused by Amoeba, Candida, Cryptococcus, Mycobacterium, Nocardia, Pneumocystis, Toxoplasma.

It is recommended that latent amebiasis or active amebiasis be ruled out before initiating corticosteroid therapy in any patient who has spent time in the tropics or in any patient with unexplained diarrhea.

Similarly, corticosteroids should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.

Corticosteroids should not be used in cerebral malaria.

Tuberculosis

If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis.

Vaccination

Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered. However, the response to such vaccines cannot be predicted.

Immunization procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy, e.g., for Addison’s disease.

Viral Infections

Chicken pox and measles can have a more serious or even fatal course in pediatric and adult patients on corticosteroids. In pediatric and adult patients who have not had these diseases, particular care should be taken to avoid exposure. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chicken pox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chicken pox develops, treatment with antiviral agents should be considered.

Neurologic

Reports of severe medical events have been associated with the intrathecal route of administration (see ADVERSE REACTIONS: Gastrointestinal and Neurologic/Psychiatric).

Ophthalmic

Use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses. The use of oral corticosteroids is not recommended in the treatment of optic neuritis and may lead to an increase in the risk of new episodes. Corticosteroids should not be used in active ocular herpes simplex.

Adequate studies to demonstrate the safety of triamcinolone acetonide injectable suspension use by intraturbinal, subconjunctival, sub-Tenons, retrobulbar and intraocular (intravitreal) injections have not been performed. Endophthalmitis, eye inflammation, increased intraocular pressure and visual disturbances including vision loss have been reported with intravitreal administration.

Administration of triamcinolone acetonide injectable suspension, USP intraocularly or into the nasal turbinates is not recommended.

Intraocular injection of corticosteroid formulations containing benzyl alcohol such as triamcinolone acetonide injectable suspension, USP, is not recommended because of potential toxicity from the benzyl alcohol.

Precautions

General

This product, like many other steroid formulations, is sensitive to heat. Therefore, it should not be autoclaved when it is desirable to sterilize the exterior of the vial.

The lowest possible dose of corticosteroid should be used to control the condition under treatment. When reduction in dosage is possible, the reduction should be gradual.

Since complications of treatment with glucocorticoids are dependent on the size of the dose and the duration of treatment, a risk/benefit decision must be made in each individual case as to dose and duration of treatment and as to whether daily or intermittent therapy should be used.

Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement.

Cardio-Renal

As sodium retention with resultant edema and potassium loss may occur in patients receiving corticosteroids, these agents should be used with caution in patients with congestive heart failure, hypertension, or renal insufficiency.

Endocrine

Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently.

Gastrointestinal

Steroids should be used with caution in active or latent peptic ulcers, diverticulitis, fresh intestinal anastomoses, and nonspecific ulcerative colitis, since they may increase the risk of a perforation.

Signs of peritoneal irritation following gastrointestinal perforation in patients receiving corticosteroids may be minimal or absent.

There is an enhanced effect of corticosteroids in patients with cirrhosis.

Intra-Articular and Soft Tissue Administration

Intra-articularly injected corticosteroids may be systemically absorbed.

Appropriate examination of any joint fluid present is necessary to exclude a septic process.

A marked increase in pain accompanied by local swelling, further restriction of joint motion, fever, and malaise are suggestive of septic arthritis. If this complication occurs and the diagnosis of sepsis is confirmed, appropriate antimicrobial therapy should be instituted.

Injection of a steroid into an infected site is to be avoided. Local injection of a steroid into a previously infected joint is not usually recommended.

Corticosteroid injection into unstable joints is generally not recommended.

Intra-articular injection may result in damage to joint tissues (see ADVERSE REACTIONS: Musculoskeletal).

Musculoskeletal

Corticosteroids decrease bone formation and increase bone resorption both through their effect on calcium regulation (i.e., decreasing absorption and increasing excretion) and inhibition of osteoblast function. This, together with a decrease in the protein matrix of the bone secondary to an increase in protein catabolism, and reduced sex hormone production, may lead to inhibition of bone growth in pediatric patients and the development of osteoporosis at any age. Special consideration should be given to patients at increased risk of osteoporosis (i.e., postmenopausal women) before initiating corticosteroid therapy.

Neuro-Psychiatric

Although controlled clinical trials have shown corticosteroids to be effective in speeding the resolution of acute exacerbations of multiple sclerosis, they do not show that they affect the ultimate outcome or natural history of the disease. The studies do show that relatively high doses of corticosteroids are necessary to demonstrate a significant effect. (See DOSAGE AND ADMINISTRATION.)

An acute myopathy has been observed with the use of high doses of corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium). This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatinine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.

Psychic derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids.

Ophthalmic

Intraocular pressure may become elevated in some individuals. If steroid therapy is continued for more than 6 weeks, intraocular pressure should be monitored.

Information for Patients

Patients should be warned not to discontinue the use of corticosteroids abruptly or without medical supervision, to advise any medical attendants that they are taking corticosteroids and to seek medical advice at once should they develop fever or other signs of infection.

Persons who are on corticosteroids should be warned to avoid exposure to chicken pox or measles. Patients should also be advised that if they are exposed, medical advice should be sought without delay.

Drug Interactions

Aminoglutethimide

Aminoglutethimide may lead to a loss of corticosteroid-induced adrenal suppression.

Amphotericin B injection and potassium-depleting agents

When corticosteroids are administered concomitantly with potassium-depleting agents (i.e., amphotericin B, diuretics), patients should be observed closely for development of hypokalemia. There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure.

Antibiotics

Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance.

Anticholinesterases

Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy.

Anticoagulants, oral

Coadministration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, coagulation indices should be monitored frequently to maintain the desired anticoagulant effect.

Antidiabetics

Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required.

Antitubercular drugs

Serum concentrations of isoniazid may be decreased.

Cholestyramine

Cholestyramine may increase the clearance of corticosteroids.

Cyclosporine

Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with this concurrent use.

Digitalis glycosides

Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia.

Estrogens, including oral contraceptives

Estrogens may decrease the hepatic metabolism of certain corticosteroids, thereby increasing their effect.

Hepatic Enzyme Inducers (e.g., barbiturates, phenytoin, carbamazepine, rifampin)

Drugs which induce hepatic microsomal drug metabolizing enzyme activity may enhance the metabolism of corticosteroids and require that the dosage of the corticosteroid be increased.

Ketoconazole

Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to an increased risk of corticosteroid side effects.

Nonsteroidal anti-inflammatory agents (NSAIDS)

Concomitant use of aspirin (or other nonsteroidal anti-inflammatory agents) and corticosteroids increases the risk of gastrointestinal side effects. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance of salicylates may be increased with concurrent use of corticosteroids.

Skin tests

Corticosteroids may suppress reactions to skin tests.

Vaccines

Patients on prolonged corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines due to inhibition of antibody response. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines. Routine administration of vaccines or toxoids should be deferred until corticosteroid therapy is discontinued if possible (see WARNINGS: Infections: Vaccination).

Carcinogenesis, Mutagenesis, Impairment of Fertility

No adequate studies have been conducted in animals to determine whether corticosteroids have a potential for carcinogenesis or mutagenesis.

Steroids may increase or decrease motility and number of spermatozoa in some patients.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Corticosteroids have been shown to be teratogenic in many species when given in doses equivalent to the human dose. Animal studies in which corticosteroids have been given to pregnant mice, rats, and rabbits have yielded an increased incidence of cleft palate in the offspring. There are no adequate and well-controlled studies in pregnant women. Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Infants born to mothers who have received corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.

Nursing Mothers

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Caution should be exercised when corticosteroids are administered to a nursing woman.

Pediatric Use

This product contains benzyl alcohol as a preservative. Benzyl alcohol, a component of this product, has been associated with serious adverse events and death, particularly in pediatric patients. The “gasping syndrome”, (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and low-birth-weight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Although normal therapeutic doses of this product deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome”, the minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birth-weight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.

The efficacy and safety of corticosteroids in the pediatric population are based on the well-established course of effect of corticosteroids which is similar in pediatric and adult populations. Published studies provide evidence of efficacy and safety in pediatric patients for the treatment of nephrotic syndrome (>2 years of age), and aggressive lymphomas and leukemias (>1 month of age). Other indications for pediatric use of corticosteroids, e.g., severe asthma and wheezing, are based on adequate and well-controlled trials conducted in adults, on the premises that the course of the diseases and their pathophysiology are considered to be substantially similar in both populations.

The adverse effects of corticosteroids in pediatric patients are similar to those in adults (see ADVERSE REACTIONS). Like adults, pediatric patients should be carefully observed with frequent measurements of blood pressure, weight, height, intraocular pressure, and clinical evaluation for the presence of infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis. Pediatric patients who are treated with corticosteroids by any route, including systemically administered corticosteroids, may experience a decrease in their growth velocity. This negative impact of corticosteroids on growth has been observed at low systemic doses and in the absence of laboratory evidence of HPA axis suppression (i.e., cosyntropin stimulation and basal cortisol plasma levels). Growth velocity may therefore be a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The linear growth of pediatric patients treated with corticosteroids should be monitored, and the potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the availability of treatment alternatives. In order to minimize the potential growth effects of corticosteroids, pediatric patients should be titrated to the lowest effective dose.

Geriatric Use

No overall differences in safety or effectiveness were observed between elderly subjects and younger subjects, and 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.

Adverse Reactions

(listed alphabetically under each subsection)

The following adverse reactions may be associated with corticosteroid therapy

Allergic reactions

Anaphylactoid reaction, anaphylaxis, angioedema.

Cardiovascular

Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction (see WARNINGS), pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis.

Dermatologic

Acne, allergic dermatitis, cutaneous and subcutaneous atrophy, dry scaly skin, ecchymoses and petechiae, edema, erythema, hyperpigmentation, hypopigmentation, impaired wound healing, increased sweating, lupus erythematosus-like lesions, purpura, rash, sterile abscess, striae, suppressed reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria.

Endocrine

Decreased carbohydrate and glucose tolerance, development of cushingoid state, glycosuria, hirsutism, hypertrichosis, increased requirements for insulin or oral hypoglycemic agents in diabetes, manifestations of latent diabetes mellitus, menstrual irregularities, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery, or illness), suppression of growth in pediatric patients.

Fluid and electrolyte disturbances

Congestive heart failure in susceptible patients, fluid retention, hypokalemic alkalosis, potassium loss, sodium retention.

Gastrointestinal

Abdominal distention, bowel/bladder dysfunction (after intrathecal administration), elevation in serum liver enzyme levels (usually reversible upon discontinuation), hepatomegaly, increased appetite, nausea, pancreatitis, peptic ulcer with possible perforation and hemorrhage, perforation of the small and large intestine (particularly in patients with inflammatory bowel disease), ulcerative esophagitis.

Metabolic

Negative nitrogen balance due to protein catabolism.

Musculoskeletal

Aseptic necrosis of femoral and humeral heads, calcinosis (following intra-articular or intralesional use), Charcot-like arthropathy, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, post injection flare (following intra-articular use), steroid myopathy, tendon rupture, vertebral compression fractures.

Neurologic/Psychiatric

Convulsions, depression, emotional instability, euphoria, headache, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, insomnia, mood swings, neuritis, neuropathy, paresthesia, personality changes, psychic disorders, vertigo. Arachnoiditis, meningitis, paraparesis/paraplegia, and sensory disturbances have occurred after intrathecal administration (see WARNINGS: Neurologic).

Ophthalmic

Exophthalmos, glaucoma, increased intraocular pressure, posterior subcapsular cataracts, rare instances of blindness associated with periocular injections.

Other

Abnormal fat deposits, decreased resistance to infection, hiccups, increased or decreased motility and number of spermatozoa, malaise, moon face, weight gain.

Overdosage

Treatment of acute overdosage is by supportive and symptomatic therapy. For chronic overdosage in the face of severe disease requiring continuous steroid therapy, the dosage of the corticosteroid may be reduced only temporarily, or alternate day treatment may be introduced.

Triamcinolone Injection Dosage and Administration

General

NOTE: CONTAINS BENZYL ALCOHOL (see PRECAUTIONS).

IT SHOULD BE EMPHASIZED THAT DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE UNDER TREATMENT AND THE RESPONSE OF THE PATIENT.

After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. Situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient’s individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment. In this latter situation it may be necessary to increase the dosage of the corticosteroid for a period of time consistent with the patient’s condition. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.

In pediatric patients, the initial dose of triamcinolone may vary depending on the specific disease entity being treated. The range of initial doses is 0.11 to 1.6 mg/kg/day in three or four divided doses (3.2 to 48 mg/m2bsa/day).

For the purpose of comparison, the following is the equivalent milligram dosage of the various glucocorticoids:

Cortisone, 25	Triamcinolone, 4
Hydrocortisone, 20	Paramethasone, 2
Prednisolone, 5	Betamethasone, 0.75
Prednisone, 5	Dexamethasone, 0.75
Methylprednisolone, 4

These dose relationships apply only to oral or intravenous administration of these compounds. When these substances or their derivatives are injected intramuscularly or into joint spaces, their relative properties may be greatly altered.

Intra-Articular Administration

Dosage

The initial dose of triamcinolone acetonide injectable suspension for intra-articular administration may vary from 2.5 mg to 5 mg for smaller joints and from 5 to 15 mg for larger joints, depending on the specific disease entity being treated. Single injections into several joints, up to a total of 20 mg or more, have been given.

Intralesional

For intralesional administration, the initial dose per injection site will vary depending on the specific disease entity and lesion being treated. The site of injection and volume of injection should be carefully considered due to the potential for cutaneous atrophy.

Multiple sites separated by one centimeter or more may be injected, keeping in mind that the greater the total volume employed the more corticosteroid becomes available for systemic absorption and systemic effects. Such injections may be repeated, if necessary, at weekly or less frequent intervals.

Localization of Doses

The lower dosages in the initial dosage range of triamcinolone acetonide may produce the desired effect when the corticosteroid is administered to provide a localized concentration. The site and volume of the injection should be carefully considered when triamcinolone acetonide is administered for this purpose.

Administration

STRICT ASEPTIC TECHNIQUE IS MANDATORY. The vial should be shaken before use to ensure a uniform suspension. Prior to withdrawal, the suspension should be inspected for clumping or granular appearance (agglomeration). An agglomerated product results from exposure to freezing temperatures and should not be used. After withdrawal, inject without delay to prevent settling in the syringe.

Injection Technique

For treatment of joints, the usual intra-articular injection technique should be followed. If an excessive amount of synovial fluid is present in the joint, some, but not all, should be aspirated to aid in the relief of pain and to prevent undue dilution of the steroid.

With intra-articular administration, prior use of a local anesthetic may often be desirable. Care should be taken with this kind of injection, particularly in the deltoid region, to avoid injecting the suspension into the tissues surrounding the site, since this may lead to tissue atrophy.

In treating acute nonspecific tenosynovitis, care should be taken to ensure that the injection of triamcinolone acetonide injectable suspension is made into the tendon sheath rather than the tendon substance. Epicondylitis may be treated by infiltrating the preparation into the area of greatest tenderness.

Intralesional

For treatment of dermal lesions, triamcinolone acetonide injectable suspension should be injected directly into the lesion, i.e., intradermally or subcutaneously. For accuracy of dosage measurement and ease of administration, it is preferable to employ a tuberculin syringe and a small-bore needle (23 to 25 gauge). Ethyl chloride spray may be used to alleviate the discomfort of the injection.

How is Triamcinolone Injection Supplied

Triamcinolone acetonide injectable suspension, USP in multiple dose vials provides 10 mg triamcinolone acetonide per mL, and is supplied as follows:

NDC 0781-3243-75 10 mg/mL, 5 mL multiple dose vial

Storage

Store at 20°-25°C (68°-77°F) (see USP Controlled Room Temperature). Avoid freezing and protect from light.

U46037846

03-2010M

Manufactured in Canada by

Sandoz Canada Inc. for

Sandoz Inc., Princeton, NJ 08540

mg 5 mL Label

NDC 0781-3243-75

Triamcinolone

Acetonide Injectable

Suspension, USP

50 mg/5 mL (10 mg/mL)

NOT FOR IV OR IM USE

5 mL Multidose Vial

Rx only

SANDOZ

mg 5 mL Carton

NDC 0781-3243-75

Triamcinolone

Acetonide

Injectable

Suspension,

USP

50 mg/5 mL

(10 mg/mL)

NOT FOR IV OR IM USE

Rx only

1 x 5 mL

Multidose Vial

SANDOZ

TRIAMCINOLONE ACETONIDE  triamcinolone acetonide  injection, suspension

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0781-3243 Route of Administration INTRA-ARTICULAR, INTRABURSAL, INTRADERMAL, INTRALESIONAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength TRIAMCINOLONE ACETONIDE (TRIAMCINOLONE) TRIAMCINOLONE ACETONIDE 10 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength BENZYL ALCOHOL   CARBOXYMETHYLCELLULOSE SODIUM   HYDROCHLORIC ACID   POLYSORBATE 80   SODIUM CHLORIDE   SODIUM HYDROXIDE

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0781-3243-75 1 VIAL In 1 CARTON contains a VIAL, MULTI-DOSE 1 5 mL In 1 VIAL, MULTI-DOSE This package is contained within the CARTON (0781-3243-75)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA090166	05/27/2009

Labeler - Sandoz Inc (110342024)

Establishment
Name	Address	ID/FEI	Operations
Sandoz Canada Inc		244062071	MANUFACTURE

Revised: 07/2010Sandoz Inc

More Triamcinolone Injection resources

• Triamcinolone Injection Use in Pregnancy & Breastfeeding
• Drug Images
• Triamcinolone Injection Drug Interactions
• Triamcinolone Injection Support Group
• 24 Reviews for Triamcinolone Injection - Add your own review/rating

Compare Triamcinolone Injection with other medications

• Adrenocortical Insufficiency
• Allergic Reactions
• Alopecia
• Ankylosing Spondylitis
• Asthma
• Berylliosis
• Bursitis
• Chorioditis
• Chorioretinitis
• Conjunctivitis
• Dermal Necrosis, Prophylaxis
• Dermatitis
• Dermatological Disorders
• Erythroblastopenia

Voltarol 25mg, 50mg Rapid Tablets

VOLTAROL Rapid Tablets 25 and 50 mg

(diclofenac potassium)

What you need to know about Voltarol Rapid Tablets

Your doctor has decided that you need this medicine to help treat your condition.

Please read this leaflet carefully before you start to take your medicine. It contains important information. Keep the leaflet in a safe place because you may want to read it again.

If you have any other questions, or if there is something you don’t understand, please ask your doctor or pharmacist.

This medicine has been prescribed for you. Never give it to someone else. It may not be the right medicine for them even if their symptoms seem to be the same as yours.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

• 1. What Voltarol Rapid Tablets are, and what they are used for


• 2. Things to consider before you start to take Voltarol Rapid Tablets


• 3. How to take Voltarol Rapid Tablets


• 4. Possible side effects


• 5. How to store Voltarol Rapid Tablets


• 6. Further information

What Voltarol Rapid Tablets are and what they are used for

Diclofenac potassium, the active ingredient in Voltarol Rapid Tablets, is one of a group of medicines called non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs reduce pain and inflammation.

Voltarol Rapid Tablets relieve pain, reduce swelling and ease inflammation in:

• Rheumatoid arthritis, osteoarthrosis, acute gout, low back pain, ankylosing spondylitis


• Migraine


• Conditions affecting the joints and muscles such as sprains and strains, soft tissue sports injuries, frozen shoulder, dislocations, and fractures


• Conditions affecting the tendons for example, tendonitis, tenosynovitis, bursitis.

They are also used to treat pain and inflammation associated with orthopaedic, dental and other minor surgery.

Things to consider before you start to take Voltarol Rapid Tablets

Some people MUST NOT take Voltarol Rapid Tablets. Talk to your doctor if:

• you think you may be allergic to diclofenac potassium, aspirin, ibuprofen or any other NSAID, or to any of the other ingredients of Voltarol Rapid Tablets. (These are listed at the end of the leaflet.) Signs of a hypersensitivity reaction include swelling of the face and mouth (angioedema), breathing problems, runny nose, skin rash or any other
  allergic type reaction


• you have now, or have ever had, a stomach (gastric) or duodenal (peptic) ulcer, or bleeding in the digestive tract (this can include blood in vomit, bleeding when emptying bowels, fresh blood in faeces or black, tarry faeces)


• you have had stomach or bowel problems after you have taken other NSAIDs


• you have severe heart, kidney or liver failure


• you are more than six months pregnant.

You should also ask yourself these questions before taking Voltarol Rapid Tablets:

• Do you suffer from any stomach or bowel disorders including ulcerative colitis or Crohn's disease?


• Do you have kidney or liver problems, or are you elderly?


• Do you have a condition called porphyria?


• Do you suffer from any blood or bleeding disorder? If you do, your doctor may ask you to go for regular check-ups while you are taking these tablets.


• Have you ever had asthma?


• Are you breast-feeding?


• Do you have heart problems, or have you had a stroke, or do you think you might be at risk of these conditions (for example, if you have high blood pressure, diabetes, or high cholesterol or are a smoker)?


• Do you have Lupus (SLE) or any similar condition?


• Do you have an intolerance to some sugars such as sucrose? (Voltarol Rapid Tablets contain sucrose.)

If the answer to any of these questions is YES, discuss your treatment with your doctor or pharmacist because Voltarol Rapid Tablets might not be the right medicine for you.

Are you taking other medicines?

Some medicines can interfere with your treatment. Tell your doctor or pharmacist if you are taking any of the following:

• Medicines to treat diabetes


• Anticoagulants (blood thinning tablets like warfarin)


• Diuretics (water tablets)


• Lithium (used to treat some mental problems)


• Methotrexate (for some inflammatory diseases and some cancers)


• Ciclosporin or tacrolimus (used to treat some inflammatory diseases and after transplants)


• Quinolone antibiotics (for infections)


• Any other NSAID or COX-2 (cyclo-oxgenase-2) inhibitor, for example aspirin or ibuprofen


• Mifepristone (a medicine used to terminate pregnancy)


• Cardiac glycosides (for example digoxin), used to treat heart problems


• Medicines known as SSRIs used to treat depression


• Oral steroids (an anti-inflammatory drug)


• Medicines used to treat heart conditions or high blood pressure, for example beta blockers or ACE inhibitors.

Always tell your doctor or pharmacist about all the medicines you are taking. This means medicines you have bought yourself as well as medicines on prescription from your doctor.

Pregnancy

• Are you pregnant or planning to become pregnant? Although not common, abnormalities have been reported in babies whose mothers have taken NSAIDs during pregnancy. You should not take Voltarol Rapid Tablets during the last 3 months of pregnancy as it may affect the baby’s circulation.


• Are you trying for a baby? Taking Voltarol Rapid Tablets may make it more difficult to conceive. You should talk to your doctor if you are planning to become pregnant, or if you have problems getting pregnant.

Will there be any problems with driving or using machinery?

Very occasionally people have reported that Voltarol Rapid Tablets have made them feel dizzy, tired or sleepy. Problems with eyesight have also been reported. If you are affected in this way, you should not drive or operate machinery.

Other special warnings

• You should take the lowest dose of Voltarol for the shortest possible time, particularly if you are underweight or elderly.


• There is a small increased risk of heart attack or stroke when you are taking any medicine like Voltarol. The risk is higher if you are taking high doses for a long time. Always follow the doctor’s instructions on how much to take and how long to take it for.


• Whilst you are taking these medicines your doctor may want to give you a check-up from time to time.


• If you have a history of stomach problems when you are taking NSAIDs, particularly if you are elderly, you must tell your doctor straight away if you notice any unusual symptoms.


• Because it is an anti-inflammatory medicine, Voltarol may reduce the symptoms of infection, for example, headache and high temperature. If you feel unwell and need to see a doctor, remember to tell him or her that you are taking Voltarol.

How to take Voltarol Rapid Tablets

The doctor will tell you how many Voltarol Rapid Tablets to take and when to take them. Always follow his/her instructions carefully. The dose will be on the pharmacist’s label. Check the label carefully. If you are not sure, ask your doctor or pharmacist. Keep taking your tablets for as long as you have been told, unless you have any problems. In that case, check with your doctor.

Take the tablets with or after food.

Voltarol Rapid Tablets are specially formulated to act quickly. Swallow the tablets whole with a drink of water. Do not crush or chew them.

The usual doses are:

Adults

75 mg to 150 mg daily divided into two or three doses. The number of tablets you take will depend on the strength the doctor has given you.

For the relief of migraine in adults:

Take 50 mg at the first signs of an attack. If the migraine has not gone after 2 hours, take another 50 mg. You can take further doses at intervals of 4 to 6 hours if necessary, but you must not take more than 200 mg in a day.

Elderly

Your doctor may advise you to take a dose that is lower than the usual adult dose if you are elderly. Your doctor may also want to check closely that the Voltarol Rapid Tablets are not affecting your stomach.

Children over 14

75 mg to 100 mg daily divided into two or three doses.

Voltarol Rapid Tablets are not recommended for children under 14. They are not recommended for the treatment of migraine in children of any age.

The doctor may also prescribe another drug to protect the stomach to be taken at the same time, particularly if you have had stomach problems before, or if you are elderly, or taking certain other drugs as well.

What if you forget to take a dose?

If you forget to take a dose, take one as soon as you remember. If it is nearly time for your next dose, though, just take the next dose and forget about the one you missed. Do not double up on the next dose to make up for the one missed. Do not take more than 150 mg (three 50 mg tablets or six 25 mg tablets) in 24 hours.

What if you take too many tablets?

If you, or anyone else, accidentally takes too much, tell your doctor or your nearest hospital casualty department. Take your medicine pack with you so that people can see what you have taken.

Possible side effects

Voltarol Rapid Tablets are suitable for most people, but, like all medicines, they can sometimes cause side effects.

Some side effects can be serious

Stop taking Voltarol Rapid Tablets and tell your doctor straight away if you notice:

• Stomach pain, indigestion, heartburn, wind, nausea (feeling sick) or vomiting (being sick)


• Any sign of bleeding in the stomach or intestine, for example, when emptying your bowels, blood in vomit or black, tarry faeces


• Allergic reactions which can include skin rash, itching, bruising, painful red areas, peeling or blistering


• Wheezing or shortness of breath (bronchospasm)


• Swollen face, lips, hands or fingers


• Yellowing of your skin or the whites of your eyes


• Persistent sore throat or high temperature


• An unexpected change in the amount of urine produced and/or its appearance.

If you notice that you are bruising more easily than usual or have frequent sore throats or infections, tell your doctor.

The side effects listed below have also been reported.

Up to 1 in 10 people have experienced:

• Stomach pain, heartburn, nausea, vomiting, diarrhoea, indigestion, wind, loss of appetite


• Headache, dizziness, vertigo


• Skin rash or spots


• Raised levels of liver enzymes in the blood.

Between 1 in 100,000 and 1 in 100 people have experienced:

• Stomach ulcers or bleeding (there have been very rare reported cases resulting in death, particularly in the elderly)


• Drowsiness, tiredness


• Hypotension (low blood pressure, symptoms of which may include faintness, giddiness or light headedness)


• Skin rash and itching


• Fluid retention, symptoms of which include swollen ankles


• Liver function disorders, including hepatitis and jaundice.

Isolated side-effects, reported in less than 1 in 100,000 people include:

Effects on the nervous system:

Tingling or numbness in the fingers, tremor, blurred or double vision, hearing loss or impairment, tinnitus (ringing in the ears), sleeplessness, nightmares, mood changes, depression, anxiety, mental disorders, confusion, hallucinations, malaise, disorientation and loss of memory, fits, headaches together with a dislike of bright lights, fever and a stiff neck, disturbances in sensation.

Effects on the stomach and digestive system:

Constipation, inflammation of the tongue, mouth ulcers, taste changes, lower gut disorders (including inflammation of the colon).

Effects on the heart, chest or blood:

Palpitations (fast or irregular heart beat), chest pain, hypertension (high blood pressure), inflammation of blood vessels (vasculitis), inflammation of the lung (pneumonitis), congestive heart failure, blood disorders (including anaemia), heart attack, stroke.

Effects on the liver or kidneys:

Kidney or liver disorders, presence of blood or protein in the urine.

Effects on skin or hair:

Serious skin rashes including Stevens-Johnson syndrome and Lyell’s syndrome and other skin rashes which may be made worse by exposure to sunlight.

Hair loss.

Other effects:

Inflammation of the pancreas, impotence.

Medicines such as diclofenac may be associated with a small increased risk of heart attack or stroke.

Do not be alarmed by this list - most people take Voltarol Rapid Tablets without any problems.

If any of the symptoms become troublesome, or if you notice anything else not mentioned here, please go and see your doctor. He/she may want to give you a different medicine.

How to store Voltarol Rapid Tablets

Store in a dry place, below 30°C. Keep the tablets in their original pack.

Keep out of the reach and sight of children.

Do not take Voltarol Rapid Tablets after the expiry date which is printed on the outside of the pack.

If your doctor tells you to stop taking the tablets, please take any unused tablets back to your pharmacist to be destroyed. Do not throw them away with your normal household water or waste. This will help to protect the environment.

Further information

The sugar-coated tablets come in two strengths containing either 25 mg or 50 mg of the active ingredient, diclofenac potassium.

The tablets also contain the inactive ingredients silica, calcium phosphate, magnesium stearate, maize starch, sodium starch glycollate, povidone, microcrystalline cellulose, red iron oxide (E172), macrogol, sucrose, talc and titanium dioxide (E171).

The tablets come in blister packs containing 2, 3, 28 or 30 tablets. Some of the pack sizes may not be marketed.

The Product licence holder is

Novartis Pharmaceuticals UK Limited

trading as Geigy Pharmaceuticals

Frimley Business Park

Frimley

Camberley

Surrey

GU16 7SR

England

Voltarol Rapid Tablets are released on to the market by

Novartis Pharmaceuticals UK Ltd

Wimblehurst Road

West Sussex

RH12 5AB

England

This leaflet was revised in March 2009.

If you would like any more information, or would like the leaflet in a different format, please contact Medical Information at Novartis Pharmaceuticals UK Ltd, telephone number 01276 698370.

VOLTAROL is a registered trade mark

Copyright Novartis Pharmaceuticals UK Limited

Flixotide Diskhaler 100 mcg

1. Name Of The Medicinal Product

Flixotide_TM Diskhaler_TM100 Micrograms

2. Qualitative And Quantitative Composition

Fluticasone Propionate (micronised) 100 micrograms

3. Pharmaceutical Form

Inhalation Powder.

4. Clinical Particulars

4.1 Therapeutic Indications

Fluticasone propionate given by inhalation offers preventative treatment for asthma. At recommended doses it has a potent glucocorticoid anti-inflammatory action within the lungs, with a lower incidence and severity of adverse effects than those observed when corticosteroids are administered systemically.

Prophylactic management in: -

Adults

Mild asthma:

Patients requiring intermittent symptomatic bronchodilator asthma medication on a regular daily basis.

Moderate asthma:

Patients with unstable or worsening asthma despite prophylactic therapy or bronchodilator alone.

Severe asthma:

Patients with severe chronic asthma and those who are dependent on systemic corticosteroids for adequate control of symptoms. On introduction of inhaled fluticasone propionate many of these patients may be able to reduce significantly, or to eliminate, their requirement for oral corticosteroids.

Children:

Any child who requires prophylactic medication, including patients not controlled on currently available prophylactic medication.

Route of administration: by inhalation.

4.2 Posology And Method Of Administration

The onset of therapeutic effect is within 4 to 7 days.

Adults and children over 16 years: 100 to 1,000 micrograms twice daily.

Patients should be given a starting dose of inhaled fluticasone propionate, which is appropriate to the severity of their disease.

Prescribers should be aware that fluticasone propionate is as effective as other inhaled steroids approximately at half the microgram daily dose. For example, a 100mcg of fluticasone propionate is approximately equivalent to 200mcg dose of beclometasone dipropionate (CFC containing) or budesonide

Due to the risk of systemic effects, doses above 500 micrograms twice daily should be prescribed only for adult patients with severe asthma where additional clinical benefit is expected, demonstrated by either an improvement in pulmonary function and/or symptom control, or by a reduction in oral corticosteroid therapy (see 4.4 Special Warnings and Precautions for Use and 4.8 Undesirable Effects).

Typical Adult Starting Doses:

For patients with mild asthma, a typical starting dose is 100 micrograms twice daily. In moderate and more severe asthma, starting doses may need to be 250 to 500 micrograms twice daily. Where additional clinical benefit is expected, doses of up to 1000 micrograms twice daily may be used. Initiation of such doses should be prescribed only by a specialist in the management of asthma (such as a consultant physician or general practitioner with appropriate experience).

The dose should be titrated down to the lowest dose at which effective control of asthma is maintained.

Typical starting doses for children over 4years of age:

50 to 100 micrograms twice daily .

Many children's asthma will be well controlled using the 50 to 100 microgram twice daily dosing regime. For those patients whose asthma is not sufficiently controlled, additional benefit may be obtained by increasing the dose up to 200 micrograms twice daily. The maximum licensed dose in children is 200 micrograms twice daily.

The starting dose should be appropriate to the severity of the disease. The dose should be titrated down to the lowest dose at which effective control of asthma is maintained.

Special patient groups:

There is no need to adjust the dose in elderly patients or those with hepatic or renal impairment.

4.3 Contraindications

Flixotide preparations are contra-indicated in patients with a history of hypersensitivity to any of their components.

4.4 Special Warnings And Precautions For Use

Flixotide Diskhalers are not designed to relieve acute symptoms for which an inhaled short acting bronchodilator is required. Patients should be advised to have such rescue medication available.

Severe asthma requires regular medical assessment, including lung-function testing, as patients are at risk of severe attacks and even death. Increasing use of short-acting inhaled β₂-agonists to relieve symptoms indicates deterioration of asthma control. If patients find that short-acting relief bronchodilator treatment becomes less effective, or they need more inhalations than usual, medical attention must be sought.

In this situation patients should be reassessed and consideration given to the need for increased anti-inflammatory therapy (e.g. higher doses of inhaled corticosteroids or a course of oral corticosteroids). Severe exacerbations of asthma must be treated in the normal way.

There have been very rare reports of increases in blood glucose levels, in patients with or without a history of diabetes mellitus (See 4.8 'Undesirable Effects'). This should be considered in particular when prescribing to patients with a history of diabetes mellitus.

As with other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. Flixotide Diskhaler should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary.

Systemic effects of inhaled corticosteroids may occur, particularly at high doses prescribed for prolonged periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). It is important therefore that the dose of inhaled corticosteroid is reviewed regularly and reduced to the lowest dose at which effective control of asthma is maintained.

Prolonged treatment with high doses of inhaled corticosteroids may result in adrenal suppression and acute adrenal crisis. Children aged < 16 years taking higher than licensed doses of fluticasone (typically

It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is regularly monitored. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of inhaled corticosteroid, if possible, to the lowest dose at which effective control of asthma is maintained. In addition, consideration should be given to referring the patient to a paediatric respiratory specialist.

When changing from a dry powder inhaler to a metered dose inhaler, administration of high doses, above 1000 mcg daily, is recommended through a spacer to reduce side effects in the mouth and throat. However, this may increase drug delivery to the lungs. As systemic absorption is largely through the lungs, there may be an increase in the risk of systemic adverse effects. A lower dose may be required.

The benefits of inhaled fluticasone propionate should minimise the need for oral steroids. However, patients transferred from oral steroids, remain at risk of impaired adrenal reserve for a considerable time after transferring to inhaled fluticasone propionate. The possibility of adverse effects may persist for some time.

These patients may require specialised advice to determine the extent of adrenal impairment before elective procedures. The possibility of residual impaired adrenal response should always be considered in emergency (medical or surgical) and elective situations likely to produce stress, and appropriate corticosteroid treatment considered.

Lack of response or severe exacerbations of asthma should be treated by increasing the dose of inhaled fluticasone propionate and, if necessary, by giving a systemic steroid and/or an antibiotic if there is an infection.

For the transfer of patients being treated with oral corticosteroids:

The transfer of oral steroid-dependent patients to Flixotide and their subsequent management needs special care as recovery from impaired adrenocortical function, caused by prolonged systemic steroid therapy, may take a considerable time.

Patients who have been treated with systemic steroids for long periods of time or at a high dose may have adrenocortical suppression. With these patients adrenocortical function should be monitored regularly and their dose of systemic steroid reduced cautiously.

After approximately a week, gradual withdrawal of the systemic steroid is started by reducing the daily dose by one milligram prednisolone, or its equivalent. For maintenance doses of prednisolone in excess of 10mg daily, it may be appropriate to cautiously use larger reductions in dose at weekly intervals.

Some patients feel unwell in a non-specific way during the withdrawal phase despite maintenance or even improvement of the respiratory function. They should be encouraged to persevere with inhaled fluticasone propionate and to continue withdrawal of systemic steroid, unless there are objective signs of adrenal insufficiency.

Patients transferred from oral steroids whose adrenocortical function is still impaired should carry a steroid warning card indicating that they need supplementary systemic steroid during periods of stress, e.g. worsening asthma attacks, chest infections, major intercurrent illness, surgery, trauma, etc.

Replacement of systemic steroid treatment with inhaled therapy sometimes unmasks allergies such as allergic rhinitis or eczema previously controlled by the systemic drug. These allergies should be symptomatically treated with antihistamine and/or topical preparations, including topical steroids.

Treatment with Flixotide Diskhalers should not be stopped abruptly.

Special care is necessary in patients with active or quiescent pulmonary tuberculosis.

Ritonavir can greatly increase the concentration of fluticasone propionate in plasma. Therefore, concomitant use should be avoided, unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side-effects. There is also an increased risk of systemic side effects when combining fluticasone propionate with other potent CYP3A inhibitors (see 4.5 Interaction with Other Medicinal Products and Other Forms of Interaction).

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Under normal circumstances, low plasma concentrations of fluticasone propionate are achieved after inhaled dosing, due to extensive first pass metabolism and high systemic clearance mediated by cytochrome P450 3A4 in the gut and liver. Hence, clinically significant drug interactions mediated by fluticasone propionate are unlikely.

In an interaction study in healthy subjects with intranasal fluticasone propionate, ritonavir (a highly potent cytochrome P450 3A4 inhibitor) 100 mg b.i.d. increased the fluticasone propionate plasma concentrations several hundred fold, resulting in markedly reduced serum cortisol concentrations. Information about this interaction is lacking for inhaled fluticasone propionate, but a marked increase in fluticasone propionate plasma levels is expected. Cases of Cushing's syndrome and adrenal suppression have been reported. The combination should be avoided unless the benefit outweighs the increased risk of systemic glucocorticoid side-effects.

In a small study in healthy volunteers, the slightly less potent CYP3A inhibitor ketoconazole increased the exposure of fluticasone propionate after a single inhalation by 150%. This resulted in a greater reduction of plasma cortisol as compared with fluticasone propionate alone. Co-treatment with other potent CYP3A inhibitors, such as itraconazole, is also expected to increase the systemic fluticasone propionate exposure and the risk of systemic side-effects. Caution is recommended and long-term treatment with such drugs should if possible be avoided.

4.6 Pregnancy And Lactation

There is inadequate evidence of safety of fluticasone propionate in human pregnancy. Administration of corticosteroids to pregnant animals can cause abnormalities of fetal development, including cleft palate and intra-uterine growth retardation. There may therefore be a very small risk of such effects in the human fetus. It should be noted, however, that the fetal changes in animals occur after relatively high systemic exposure. Because fluticasone propionate is delivered directly to the lungs by the inhaled route it avoids the high level of exposure that occurs when corticosteroids are given by systemic routes.

Administration of fluticasone propionate during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the fetus.

The secretion of fluticasone propionate in human breast milk has not been investigated. Subcutaneous administration of fluticasone propionate to lactating laboratory rats produced measurable plasma levels and evidence of fluticasone propionate in the milk. However, plasma levels in humans after inhalation at recommended doses are likely to be low.

When fluticasone propionate is used in breast feeding mothers the therapeutic benefits must be weighed against the potential hazards to mother and baby.

4.7 Effects On Ability To Drive And Use Machines

Fluticasone propionate is unlikely to produce an effect.

4.8 Undesirable Effects

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (

System Organ Class	Adverse Event	Frequency
Infections & Infestations	Candidiasis of the mouth and throat Pneumonia (in COPD patients)	Very Common Common
Immune System Disorders	Hypersensitivity reactions with the following manifestations: Cutaneous hypersensitivity reactions Angioedema (mainly facial and oropharyngeal oedema), Respiratory symptoms (dyspnoea and/or bronchospasm), Anaphylactic reactions	Uncommon Very Rare Very Rare Very Rare
Endocrine Disorders	Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataract, glaucoma	Very Rare
Metabolism & Nutrition Disorders	Hyperglycaemia (see 4.4 'Special Warnings and Precautions for Use')	Very Rare
Gastrointestinal Disorders	Dyspepsia	Very Rare
Musculoskeletal & Connective Tissue Disorders	Arthralgia	Very Rare
Psychiatric Disorders	Anxiety, sleep disorders, behavioural changes, including hyperactivity and irritability (predominantly in children) Depression, aggression (predominantly in children)	Very Rare Not known
Respiratory, Thoracic & Mediastinal Disorders	Hoarseness/dysphonia Paradoxical bronchospasm	Common Very Rare
Skin & Subcutaneous Tissue Disorders	Contusions	Common

Hoarseness and candidiasis of the mouth and throat (thrush) occurs in some patients. Such patients may find it helpful to rinse out their mouth with water after using the Diskhaler. Symptomatic candidiasis can be treated with topical anti-fungal therapy whilst still continuing with the Flixotide Diskhaler.

Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation, decreased bone mineral density, cataract, glaucoma.(see 4.4 Special Warnings and Special Precautions for Use).

As with other inhalation therapy, paradoxical bronchospasm may occur (see 4.4 'Special Warnings and Precautions for Use'). This should be treated immediately with a fast-acting inhaled bronchodilator. Flixotide Diskhaler should be discontinued immediately, the patient assessed, and if necessary alternative therapy instituted.

There was an increased reporting of pneumonia in studies of patients with COPD receiving FLIXOTIDE 500 micrograms. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbation frequently overlap.

4.9 Overdose

Acute: Inhalation of the drug in doses in excess of those recommended may lead to temporary suppression of adrenal function. This does not necessitate emergency action being taken.

In these patients treatment with fluticasone propionate by inhalation should be continued at a dose sufficient to control asthma adrenal function recovers in a few days and can be verified by measuring plasma cortisol.

Chronic: refer to section 4.4: risk of adrenal suppression.

Monitoring of adrenal reserve may be indicated. Treatment with inhaled fluticasone propionate should be continued at a dose sufficient to control asthma.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Fluticasone propionate given by inhalation at recommended doses has a potent glucocorticoid anti-inflammatory action within the lungs, with a lower incidence and severity of adverse effects than those observed when corticosteroids are administered systemically.

5.2 Pharmacokinetic Properties

Systemic absolute bioavailability of fluticasone propionate is estimated at 12-26% of an inhaled dose, dependent on presentation. Systemic absorption occurs mainly through the lungs and is initially rapid then prolonged. The remainder of the dose may be swallowed.

Absolute oral bioavailability is negligible (<1%) due to a combination of incomplete absorption from the GI tract and extensive first-pass metabolism. 87-100% of an oral dose is excreted in the faeces, up to 75% as parent compound. There is also a non-active major metabolite.

After an intravenous dose, fluticasone propionate is extensively distributed in the body. The very high clearance rate indicates extensive hepatic clearance.

5.3 Preclinical Safety Data

No clinically relevant findings were observed in preclinical studies.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactose Ph Eur

6.2 Incompatibilities

None known

6.3 Shelf Life

24 months

6.4 Special Precautions For Storage

Whilst the disks provide good protection to the blister contents from the effects of the atmosphere, they should not be exposed to extremes of temperature and should not be stored above 30^oC. A disk may be kept in the diskhaler at all times but a blister should only be pierced immediately prior to use. Failure to observe this instruction will affect the operation of the diskhaler.

6.5 Nature And Contents Of Container

A circular double-foil (PVC/Aluminium) disk with four blisters, containing a mixture of fluticasone propionate and lactose. The foil disk is inserted into the Diskhaler device.

The following packs are registered: 5, 7, 10, 14 or 15 disks with or without a diskhaler. Refill packs of 5, 7, 10, 14 or 15 disks. A starter pack consisting of diskhaler pre-loaded with one disk (with or without a peak flow meter and diary card). A starter pack plus a spare disk (with or without a peak flow meter and diary card).

The following packs are marketed: cartons containing 14 disks (14x4 blisters), together with a Diskhaler inhaler. Cartons containing 5 disks (5x4 blisters) together with a Diskhaler inhaler (250 micrograms and 500 micrograms hospital packs only). Refill packs containing 14 disks (14x4 blisters).

6.6 Special Precautions For Disposal And Other Handling

See Patient Information Leaflet for detailed instructions.

Administrative Data

7. Marketing Authorisation Holder

Glaxo Wellcome UK Ltd

trading as Allen & Hanburys

Stockley Park West

Uxbridge,

Middlesex

UB11 1BT

8. Marketing Authorisation Number(S)

PL 10949/0006

9. Date Of First Authorisation/Renewal Of The Authorisation

25 February 1993

10. Date Of Revision Of The Text

23 August 2011

11. LEGAL STATUS

POM.

DOLPIN Haloperidol Oral Solution BP 5 mg / 5 ml

1. Name Of The Medicinal Product

DOLPIN Haloperidol Oral Solution BP 5 mg/5 ml

2. Qualitative And Quantitative Composition

Each 5 ml contains 5 mg of Haloperidol

3. Pharmaceutical Form

Oral Solution

4. Clinical Particulars

4.1 Therapeutic Indications

Psychotic disorders - schizophrenia, mania and hypomania, especially paranoid psychoses. Mental or behavioural problems such as aggression, hyperactivity and self - mutilation in the mentally retarded. As an adjunct to the short term management of moderate to severe psychomotor agitation, excitement, violent or dangerously impulsive behaviour. Gilles de la Tourette syndrome, intractable hiccup and severe tics. Childhood behaviour disorders, especially when associated with hyperactivity and aggression. Restlessness and agitation in the elderly. Nausea and vomiting.

4.2 Posology And Method Of Administration

For all indications dosage should be individually determined, depending on the patient's response. The initiation and titration of treatment should be under close clinical supervision.

The minimum clinically effective dose should be used.

The initial dose should be determined with consideration of the patient's age, severity of symptoms and previous response to neuroleptics. In the elderly and debilitated and those with previously reported adverse reactions to neuroleptic drugs, the recommended starting dose given below should be halved. This can be gradually titrated to achieve an optimal response.

Higher doses than those recommended should only be considered in patients who have responded poorly at a lower dose.

All patients should, once control has been achieved, have their doses gradually reduced and the minimal effective maintenance dose determined.

An oral syringe is included in the pack to assist with administering the correct dose.

IN ADULTS

For the treatment of; -Schizophrenia, mania and hypomania, as an adjunct to the short term management of moderate to severe psychomotor agitation, excitement, violent or dangerously impulsive behaviour, mental and behavioural problems, restlessness and agitation in the elderly.

Initial Dose;- Moderate Symptomatology - 1.5-3.0mg (1.5-3.0ml) bd or tds.

Severe Symptomatology- 3.0-5.0mg (3.0-5.0ml) bd or tds.

For elderly or debilitated patients half the initial adult dose is recommended.

Adolescents should receive the same doses though may in exceptional circumstance require up to a maximum of 30mg(30ml, 6 x 5ml spoonfuls) daily

Maintenance Dose;-

Once the control of symptoms has been achieved the dose should be gradually reduced to the lowest effective maintenance dose, typically 1-2mg (1-2ml) three to four times daily.

A rapid reduction in dose should be avoided.

For the treatment of;-

Gilles de la Tourette Syndrome, severe tic and intractable hiccup

Initial Dose:- 1.5mg (1.5ml) tds adjusted according to response

Maintenance Dose:-

Once the control of symptoms has been achieved the dose should be gradually reduced to the lowest effective maintenance dose. In Gilles de la Tourette Syndrome a daily maintenance dose of 10 ml may be required.

In general for all conditions the maximum daily dose is 30 mg.

IN CHILDREN

For the treatment of;-

Childhood behavioural disorders

A total daily maintenance dose of 0.025-0.05 mg/kg/day, up to a maximum of 10ml daily. Half the total dose should be given in the morning, the remaining half in the evening.

AGE	IDEAL BODY WEIGHT (kg)	DAILY DOSE (ml) 0.025 - 0.05 mg/kg body weight/day	TWICE DAILY DOSAGE (ml) Morning & Evening
New born	3.4	0.09 - 0.17	0.04 - 0.09
1 month	4.2	0.11 - 0.21	0.05 - 0.11
3 month	5.6	0.14 - 0.28	0.07 - 0.14
6 month	7.7	0.19 - 0.39	0.10 - 0.19
1 year	10	0.25 - 0.50	0.13 - 0.25
3 year	14	0.35 - 0.70	0.18 - 0.35
5 year	18	0.45 - 0.90	0.23 - 0.45
7 year	23	0.58 - 1.15	0.29 - 0.58
12 year	37	0.93 - 1.85	0.46 - 0.93

For the treatment of;-

Gilles de la Tourette Syndrome

Daily maintenance doses of up to 10 ml are required in most patients.

4.3 Contraindications

- Comatose states

- Patients with Parkinson's disease

- Patients with a known sensitivity to haloperidol or any of the product's ingredients

- Use during breast feeding

- CNS depression.

- Clinically significant cardiac disorders

- QTc interval prolongation

- History of ventricular arrhythmia or Torsades de pointes

- Bradycardia or 2/3° heart block

- Uncorrected hypokalemia

- Other QT prolonging drugs

4.4 Special Warnings And Precautions For Use

Please also refer to section 4.5 Interactions with other Medicaments and other forms of Interaction.

Caution is advised in patients with liver disease, renal failure and phaechromocytoma, prostatic hypertrophy, closed angle glaucoma, epilepsy and conditions predisposing to epilepsy or convulsions (e.g. alcohol withdrawl and brain damage). As severe neurotoxicity may result, haloperidol should only be used with great caution in patients with disturbed thyroid function. Antipsychotic therapy in these patients must always be accompanied by adequate management of the underlying thyroid dysfunction.

The risk-benefit of Haloperidol treatment should be fully assessed before treatment is commenced and patients with risk factors for ventricular arrhythmias such as cardiac disease, family history of sudden death and/or QT prolongation; uncorrected electrolyte disturbances; should be monitored carefully (ECGs and potassium levels), particularly during the initial phase of treatment to obtain steady plasma levels. Haloperidol should be used with caution in patients known to be slow metabolisers of CYP2D6, and during the use of cytochrome P450 inhbitors.

Baseline ECG recommended prior to treatment in all patients especially in the elderly and patients with a positive personal or family history of cardiac disease or abnormal findings on cardiac clinical examination. During therapy, the need for ECG monitoring e.g. at dose escalation should be assessed on an individual patient basis. Whilst on therapy, the dose should be reduced if QT is prolonged, and Haloperidol injection should be discontinued if the QTc exceeds 500 ms.

Periodic electrolyte monitoring is recommended, particularly if on diuretics or during inter-current illness.

For Patients at increased risk of arrhythmias, (those with hypokalaemia or a prolonged QT interval), and/or with severe cardiovascular disorders. The possibility of transient hypotension exists. Should hypotension occur and a vasopressor be required, adrenaline should not be used. Haloperidol may block adrenalin's vasopressor activity and cause a further paradoxical lowering of blood pressure.

Depression, unless psychotic or part of the effective component of schizophrenia. As with all antipyschotic agents, haloperidol should not be used alone where depression is predominant. Where depression and psychosis co-exist, haloperidol may be combined with an antidepressant.

Concomitant use of antipsychotics should be avoided.

Please note:-

Haloperidol may impair the metabolism of tricyclic antidepressants, (clinical significance unknown.)

-Parkinsonism, the syndrome is exacerbated by haloperidol's blockade of dopamine receptors.

-Caution should be taken in extremely hot or cold weather, the drug interfering with the crucial role of dopamine in hypothalamic thermoregulation.

Urinary retention may be exacerbated.

Haloperidol may impair alertness, especially at the start of treatment.

These effects may be potentiated by alcohol.

-Doses higher than those recommended, (an oral daily dose of 30 mg), should be considered carefully.

-A gradual reduction in dose is recommended. An acute withdrawal should be avoided.

Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with Haloperidol and preventative measures undertaken.

Increased Mortality in Elderly people with Dementia

Data from two large observational studies showed that elderly people with dementia who are treated with antipsychotics are at a small increased risk of death compared with those who are not treated. There are insufficient data to give a firm estimate of the precise magnitude of the risk and the cause of the increased risk is not known.

Haloperidol is not licenced for the treatment of dementia-related behavioural disturbances.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Adrenaline: concurrent use may block the alpha-adrenergic effects of adrenaline, severe hypotension and tachycardia may result.

Alcohol: concurrent use may potentiate alcohol intoxication.

Amphetamines: concurrent use may decrease stimulant effects of amphetamines due to alpha-adrenergic blockade, the antipsychotic effects of haloperidol may be reduced.

Anticholinergics (or other medication with anticholinergic activity): concurrent use may intensify anticholinergic effects such as confusion, hallucinations, nightmares, and intraocular pressure. Paralytic ileus may also occur and the efficacy of haloperidol may be decreased because of reduced gastrointestinal absorption.

Anticonvulsants (including barbiturates and carbamazepine): concurrent use may cause a change in the pattern and/or frequency of epileptiform seizures. Dose adjustments of anticonvulsants may be necessary. Serum concentrations of haloperidol may be significantly reduced, (by up to 50% in the case of carbamazepine)

Antidepressants (including tricyclic antidepressants, 5HT reuptake inhibitors, MAO inhibitors, trazodone, maprotiline, Nefazodone): concurrent use may prolong and intensity the sedative and anticholinergic effects of these medications or of haloperidol.

Bromocriptine: haloperidol may increase serum prolactin concentrations and therefore concurrent use with bromocriptine may limit the effects of bromocriptine.

CNS depression producing medications (including sedatives, hypnotics, opiates): concurrent use may result in increased CNS and respiratory depression and increased hypotensive effects.

Diazoxide: concurrent use antagonises the inhibition of insulin release by diazoxide.

Dopamine: concurrent use may antagonise peripheral vasoconstriction produced by high doses of dopamine because of the alpha-adrenergic blocking action of haloperidol.

Ephedrine: concurrent use may decrease the pressor response to ephedrine.

Guanethidine and guanadrel: concurrent use may decrease the hypotensive effects of these agents because of displacement from and inhibition of uptake into alpha-adrenergic neurons.

Levodopa and pergolide: concurrent use may decrease the therapeutic effects of these drugs because of blockade of dopamine receptors by haloperidol

Lithium: at high doses of lithium concurrent use has been reported to be associated with irreversible neurological toxicity and brain damage, as well as neuromuscular symptoms and fever. If an unexplained pyrexia occurs in the presence of extrapyramidal side-effects, both lithium and haloperidol should be stopped immediately.

Methoxamine: prior administration of haloperidol may decrease the pressor effect and duration of action of methoxamine because of the alpha-adrenergic blocking action of haloperidol.

Methyldopa: concurrent use may cause unwanted mental effects such as disorientation and slowed or difficult thought processes.

Phenindione: concurrent use has been reported to interfere with the anticoagulant properties of phenindione in an isolated case. Caution is recommended for use with other anticoagulants.

Phenylephrine: prior administration of haloperidol may decrease the pressor effect of phenylephrine because of the alpha-adrenergic blocking action of haloperidol.

Use of haloperidol with concomitant QT prolonging drugs may result in additional QT prolongation and is not recommended (please refer to Section 4.3 – Contraindications).

Use of drugs that cause electrolyte imbalance may increase the risk of ventricular arrhythmias during concomitant use of haloperidol (please refer to Section 4.4 – Special Warnings and Special Precautions for Use).

Metabolic inhibitors of cytochrome P450, and specifically CYP2D6 may increase haloperidol levels.

4.6 Pregnancy And Lactation

Haloperidol's safe use in pregnancy and lactation has not been established. Reports exist of limb malformations in the first trimester, following the concurrent maternal use of haloperidol with other drugs of suspected teratogenicity. Animal studies have shown reduced fertility, delayed delivery, cleft palate and an increase in the number of stillbirths and newborn deaths at very high doses. Haloperidol is excreted in breast milk. Animal studies have shown that haloperidol in breast milk causes drowsiness and unusual muscle movements in nursing offspring. If the use of haloperidol is considered essential, breast feeding should be discontinued.

4.7 Effects On Ability To Drive And Use Machines

Haloperidol may impair alertness, especially at the start of treatment. The effects may be potentiated by alcohol. Patients should be warned of the risks of sedation and advised not to drive or operate machinery during treatment until their susceptibility is known.

4.8 Undesirable Effects

Extrapyramidal Effects (e.g. neuromuscular (extrapyramidal) effects such as Parkinson like symptoms, akathisia, dyskinesia, dystonia, hyperreflexia, rigidity, opisthotonus and occasionally oculogyric crisis). Rarely dystonia has been reported to produce laryngeal/pharyngeal spasm associated with gagging, respiratory distress and asphyxia. Anti-Parkinson agents should not be prescribed routinely, to prevent or reverse the neuromuscular reactions associated with haloperidol. If prescribed, the administration of anti-Parkinson drugs should be based on the likelihood of the patient developing extrapyramidal effects as well as the risk of adverse reactions resulting from the agents extended use. Frequent re-evaluation of anti-Parkinson therapy is recommended.

Tardive dyskinesias and tardive dystonia. Tardive dyskinesias may develop in some patients on long term therapy, possibly in relation to total cumulative dose or following the drug's withdrawal. The condition is characterised by rhythmical involuntary movements of the tongue, face or jaw, but such movements may be generalised. Its incidence in haloperidol users is reported as being approximately 15%, the elderly and those treated concurrently with anti-Parkinson drugs being at greatest risk. Symptoms may persist for several months to years, and in some patients appear permanent. On condition first being diagnosed consideration should be given to reducing or discontinuing antipyschotic medication. If withdrawal is undertaken this should be gradual, with gradual, with careful observation of both the dyskinesia and psychotic symptoms. In schizophrenia a recurrence of symptoms may not become apparent for several weeks or months.

Behavioural (e.g. motivational, emotional and behavioural changes, insomnia, depressive reactions and toxic confusional states, drowsiness, lethargy, stupor and catalepsy, confusion, restlessness, agitation, anxiety, euphoria and exacerbation of psychotic symptoms including hallucinations, alteration of sleep patterns).

Cardiovascular system: tachycardia and dose related hypotension are uncommon, but can occur, particularly in the elderly, who are more susceptible to the sedative and hypotensive effects. Less commonly, hypertension has been reported.

Cardiac effects such as QT-prolongation, Torsade de Pointes, ventricular arrhythmias, including ventricular fibrillation and ventricular tachycardia), and cardiac arrest have been reported rarely. Cases of sudden unexplained death have also occurred. These effects may occur more frequently with high doses, intravenous administration and in predisposed patients (see 4.4 Special Warnings and Special Precautions for Use).

Autonomic (e.g. nasal stuffiness, dry mouth, constipation, blurred vision, urinary retention and incontinence)

Endocrine (e.g. hyperprolactinaemia leading to oligo/amenorrhoea, gynaecomastia galactorrhoea, infertility (in the female) and impotence (in the male)

Gastrointestinal (e.g. heartburn, nausea, vomiting, weight loss, weight gain, constipation and diarrhoea).

Liver dysfunction with jaundice and eosinophilia. Additionally there may be a possible transient abnormality in liver function tests in the absence of jaundice.

Hyperpyrexia, heat stroke, headache, vertigo and cerebral seizures.

Dermatological (e.g. exfoliative dermatitis, erythema multiforme, and rarely photosensitisation.

Neuroleptic malignant syndrome (e.g. hyperthermia, muscle rigidity, autonomic instability, an altered level consciousness and coma.

i) Symptoms such as tachycardia, a labile arterial pressure and sweating may precede hyperthermia, and act as early warning of the condition.

ii) Recovery usually occurs within five to seven days of antipsychotic withdrawal.

Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs – Frequency unknown

4.9 Overdose

In general haloperidol overdosage manifests as an extension of its pharmacological action, the most prominent of which are severe extrapyramidal symptoms, hypotension, respiratory difficulty and sedation possibility leading to impaired consciousness. A patient may appear comatose with respiratory depression and hypotension, possibly severe enough to produce a shock-like state. The risk of ECG changes associated with torsades de points should be considered. Unexpected reactions, such as bradycardia and an episode of severe delayed hypertension have been reported.

Haloperidol has no specific antidote. A patent airway should be established and mechanically assisted ventilation supplied if necessary. ECG monitoring is strongly advised in view of isolated reports of haloperidol's arrythmigenic action. Hypotension and circulatory collapse should be treated by plasma volume expansion and other appropriate measures.

ADRENALINE SHOULD NOT BE USED

Body temperature and adequate fluid intake should be maintained.

Severe extrapyramidal symptoms may merit the administration of appropriate anti-Parkinson medication.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Haloperidol is a butyrophenone derivative, it has antagonist action on a variety of receptors including muscarinic cholinergic, α-adrenergic and serotonin, (5HT1a/5HT2), and pronounced extrapyramidal reactions and a low incidence of autonomic side-effects result from the compound's pharmacological profile. Haloperidol is known to produce a selective effect on the central nervous system, by competitive blockade of postsynaptic dopamine (D2) receptors in the mesolimbic dopaminergic system and an increased turnover of brain dopamine to produce its tranquillizing effects.

5.2 Pharmacokinetic Properties

Steady state serum levels of haloperidol are normally achieved within 6 days on a fixed oral dosage. Total elimination takes approximately 28 days. Haloperidol is readily absorbed from the gastrointestinal tract. It is metabolised in the liver and is excreted in the urine, and via the bile, in the faeces: there is evidence of enterohepatic recycling. Haloperidol has been reported to have a plasma half life ranging from about 13 to 40 hours. Haloperidol is about 92% bound to plasma proteins. It is widely distributed in the body and crosses the blood brain barrier. Haloperidol is excreted in breast milk.

5.3 Preclinical Safety Data

There is no preclinical safety data of relevance to the prescriber.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactic acid

Methylhydroxybenzoate

Propylhydroxybenzoate

Propylene Glycol

Purified Water

6.2 Incompatibilities

None known

6.3 Shelf Life

36 months

6.4 Special Precautions For Storage

Do not store above 25°C. Store in the original container.

6.5 Nature And Contents Of Container

100 ml, 200 ml and 500 ml type III amber glass bottle with 28 x 18 ROPP LDPE plain white or aluminium cap with EPE (expanded polyethylene) wads and epoxy phenolic lacquer or child resistant closures with expanded polyethylene liners.

100 ml, 200 ml and 500 ml high density polyethylene bottle with 28 mm white polypropylene closure.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Pinewood Laboratories Limited, Ballymacarbry, Clonmel, Co. Tipperary, Ireland

8. Marketing Authorisation Number(S)

PL 04917/0023

9. Date Of First Authorisation/Renewal Of The Authorisation

27/02/2007

10. Date Of Revision Of The Text

25/02/2010