Triamcinolone

Triamcinolone belongs to the pharmacological class Corticosteroids. Triamcinolone appears to have anti-inflammatory effects. Triamcinolone inhibits phospholipase A2 on the cell membranes thereby preventing the breakdown of lysosomal membranes of leukocytes, which in turn prevents the formation of arachidonic acid, causing a decrease in expression of cyclooxygenase and lipoxygenase and inhibiting synthesis of prostaglandins and leukotrienes. Anti-inflammatory activity occurs via the reversal of vascular dilation and also by reducing permeability, which prevents the macrophage and leukocyte migration. Triamcinolone is also found to inhibit nuclear factor kappa-B, which decreases the production of signals called as pro-inflammatory signals such as interleukin-8, interleukin-6, and monocyte chemoattractant protein-1

Triamcinolone had been approved for relieving the symptoms and also for the treatment and maintenance of episodes of Alopecia areata, discoid lupus erythematosus, keloid, necrobiosis lipoidica diabeticorum, granuloma annulare, lichen planus, lichen simplex chronicus, psoriatic plaques, pruritic manifestations, gout, rheumatoid arthritis, osteoarthritis, allergic rhinitis, etc.

Triamcinolone is completely and rapidly absorbed with 25 % bioavailability after the inhalation dose of 800ucg. Triamcinolone achieved an apparent volume of distribution of 115.2±10L. There is found to be a metabolite of Triamcinolone which is 6-beta-hydroxy-triamcinolone. The route of elimination is primarily through urine.

The common side effects associated with Triamcinolone are irregular heartbeat, shortness of breath, dizziness, blurred vision, headache, acne, etc.

Triamcinolone is available in the form of systemic, topical cream, ophthalmic and nasal solutions. Triamcinolone is available in the U.S., Canada,E.U., India, Australia, and Japan.

Triamcinolone belongs to the pharmacological class Corticosteroids. Triamcinolone appears to have anti-inflammatory effects. Triamcinolone is said to inhibit phospholipase A2 on cell membranes thereby prevents the breakdown of lysosomal membranes of leukocytes, which in turn prevents the formation of arachidonic acid.This decreases the expression of lipoxygenase and cyclooxygenase , in turn inhibiting synthesis of leukotrienes and prostaglandins. Anti-inflammatory activity occurs through the reversal of vascular dilation and also reducing permeability, which prevents macrophage as well as leukocyte migration.Triamcinolone also inhibits nuclear factor kappa-B, which in turn decreases the production of pro-inflammatory signals such as interleukin-8, interleukin-6 and monocyte chemoattractant protein-1

Triamcinolone had been approved for relieving symptoms and also for the maintenance and treatment of episodes of Alopecia areata,discoid lupus erythematosus,keloid,necrobiosis lipoidica diabeticorum,granuloma annulare,lichen planus,lichen simplex chronicus,psoriatic plaques,pruritic manifestations,gout,rheumatoid arthritis,osteoarthritis,allergic rhinitis etc.

An oral dose of 16mg Triamcinolone reaches a Cmax of 5.23±0.84ng/mL while a Tmax of 2.24±0.78h is achieved.

Triamcinolone can be used in the treatment of:

• Alopecia areata
• Discoid lupus erythematosus
• Keloids
• Necrobiosis lipoidica diabeticorum
• Granuloma annulare
• Lichen planus
• Lichen simplex chronicus
• Psoriatic plaques
• Pruritic manifestations
• Gout
• Rheumatoid arthritis
• Osteoarthritis
• Allergic rhinitis

Triamcinolone is approved for use in the following clinical indications:

• Alopecia areata
• Discoid lupus erythematosus
• Keloids
• Necrobiosis lipoidica diabeticorum
• Granuloma annulare
• Lichen planus
• Lichen simplex chronicus
• Psoriatic plaques
• Pruritic manifestations
• Gout
• Rheumatoid arthritis
• Osteoarthritis
• Allergic rhinitis

Systemic

• Intramuscular to be administered on the muscle directly.
• Intraarticular is to be administered in the bone joints
• Intralesional is to be administered into the lesions through the skin

Topical

Apply the cream at the site of application

Ophthalmic

1 or 2 drops to be instilled into the eyes as directed by the physician.

Nasal

One or two sprays into the nostril as directed by the physician.

Adult and Pediatric Dosage Forms and Strengths

Injectable Solutions:5 mg/mL,10 mg/mL,20 mg/mL,40 mg/mL

Triamcinolone Acetonide

Adult: Treatment of rheumatic or arthritic disorders

60 mg intramuscularly (IM) every six weeks; might be supplemented by an additional 20-100 mg Intramuscularly as needed.

Intralesional injection (10 mg/mL suspension): 1 mg per injection site one or more times weekly and should not to exceed 30 mg/day

Intra-articular/intrasynovial/soft-tissue injection: For Large joints:15-40 mg; For small joints/tendon sheath inflammation: 2.5-10 mg

Pediatric:

• Treatment of rheumatic conditions

0.11-1.6 mg/kg/day intramuscularly divided every three-four hours

Children 6-12 years: 0.03-0.2 mg/kg Intramuscularly every one-seven days

Children aged 12 years or more: 60 mg Intramuscularly every 6 weeks; may be supplemented by additional 20-100 mg Intramuscularly as needed

Children aged 12 years or more, intralesional injection (10 mg/mL suspension): 1 mg per injection site one or more times weekly and should not to exceed 30 mg/day

Triamcinolone Hexacetonide

• Treatment of rheumatic or arthritic disorders

Intralesional injection: 0.5 mg/²; should be repeated as needed

Intra-articular injection (20 mg/mL suspension): 10-20 mg for large joints; 2-6 mg for small joints which is repeated every three-four weeks as needed

Ophthalmic: 1-4 mg

Topical: 0.025%, 0.5%,0.1%

Nasal Solution: 1 spray equal to 55 mcg dose

Systemic, Topical ointment or lotion.

Maintaining health and cessation of smoking is a must.

Caffeine should be limited to use or avoided as it may lead to the risk of nervousness, rapid heartbeat, nausea, palpitations, etc.

Patients with an underlying liver disorder or liver dysfunction must avoid drinking alcohol.

Diet containing food with high sugar content and carbohydrates should be restricted.This includes pies, cakes, honey,cookies, jams, candies,chips and bread. It is also advised to reduce or limit the intake of cholesterol and saturated fat and instead choose poultry, lean meat or fish.

The dietary restrictions need to be individualized as per the patient's requirements.

Triamcinolone may be contraindicated under the following conditions:

• Hypersensitivity to the ingredients of the medication
• Idiopathic Thrombocytopenic Purpura.

The treating physician should be closely monitoring the patients and keep pharmacovigilance as follows:

General: Rare instances of anaphylactoid reactions have been found to have occurred in patients receiving corticosteroid therapy

Cardio-renal:

At average and large doses, corticosteroids can cause elevation of salt, blood pressure and water retention, and increased excretion of potassium salt. These effects are found to occur less likely with the synthetic derivatives except when it is used in large doses. Dietary salt restriction and potassium supplementation might be necessary. All corticosteroids cause an increase in calcium excretion. Literature reports suggest an apparent association between left ventricular free wall rupture and the use of corticosteroids after a most recent myocardial infarction; therefore, the therapy with corticosteroids should be used cautiously in such patients.

As sodium retention resulting in edema and potassium loss might occur in patients who are receiving corticosteroids, these agents should be used cautiously in patients with hypertension,congestive heart failure, or renal insufficiency.

Endocrine:

Corticosteroids are said to produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression along with the potential for glucocorticosteroid insufficiency after the withdrawal of the treatment. The Metabolic clearance of corticosteroids is found to be decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient might necessitate adjustments in dosage.

Infections

General:

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

Fungal infections:

Triamcinolone may exacerbate systemic fungal infections and therefore it should not be used in the presence of such infections existing unless it is needed to control drug reactions.

Special pathogens:

Latent disease might be activated or there might be an exacerbation of intercurrent infections due to pathogens, including those caused by Mycobacterium, Nocardia, Pneumocystis, Amoeba, Candida, Cryptococcus, Toxoplasma. It is recommended that latent amebiasis or active amebiasis should be ruled out before initiating Triamcinolone therapy in any patient who spent time in the tropics or in any patient with episodes of unexplained diarrhea.

Triamcinolone should not be used in cerebral malaria.

Tuberculosis:

The use of Triamcinolone in the case of active tuberculosis should be restricted to those cases of tuberculosis in which the Triamcinolone might be used for the management of the disease along with the appropriate anti tuberculosis regimen.

If corticosteroids are being indicated in patients with tuberculin reactivity or latent tuberculosis or a close observation is necessary or suggested as reactivation of the disease might occur.

Vaccination:

The administration of vaccines, such as live or live, is attenuated , is contraindicated or inhibited in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines might be administered. However, the response to such vaccines is unpredictable. Immunization procedures might be undertaken in patients who are being administered corticosteroids as replacement therapy, such as, for Addison's disease.

Viral infections:

Chicken pox and measles might have a more serious or even fatal effect in pediatric and adult patients on corticosteroids. In adult and pediatric patients who have not been exposed to such diseases, specific care should be taken to avoid exposure.The effect of the underlying disease and/or prior corticosteroid treatment associated with the risk is also not known. If a patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) might be indicated. If a patient is exposed to measles, prophylaxis with immunoglobulin (IG) might be indicated. If chicken pox develops, the treatment with antiviral agents should be considered and opted

Ophthalmic:

Use of Triamcinolone might produce glaucoma with possible damage to the optic nerves, posterior subcapsular cataracts and might increase the establishment of secondary ocular infections due to various fungi, bacteria or viruses. The use of oral corticosteroids is not found to be recommended in the treatment of optic neuritis and might lead to an increase in the risk of the new episodes.

Triamcinolone should not be used in the condition of active ocular herpes simplex.Intraocular pressure might be elevated in some individuals. If Triamcinolone therapy is continued for more than six weeks, intraocular pressure should be monitored.

Avoid alcohol usage while on Triamcinolone medication as alcohol can worsen the effects of any other underlying disease condition, including conditions such as blurred vision, dizziness, etc.

Systemically administered corticosteroids appears in human milk and might suppress growth, also interfere with endogenous corticosteroid production, or cause other unwanted effects. Hence ,caution should be exercised when corticosteroids are administered to the nursing women.

Teratogenic Effects: Pregnancy Category C

Corticosteroids had been shown to be teratogenic in many species when given in the doses equivalent to that of the human dose. Animal studies in which corticosteroids had been given to rats, pregnant mice, and rabbits had yielded an increased incidence of cleft palate in the offspring. There are found to be well-controlled and no adequate studies in pregnant women.

The Corticosteroids should be used during pregnancy only if the potential benefits outweigh the potential risks associated with the fetus. Infants born to mothers who had received corticosteroids during pregnancy should be carefully observed for the signs of hypoadrenalism.

There has been found to be no sufficient scientific evidence traceable regarding the use and safety of Triamcinolone in concurrent use with any particular food.

The adverse reactions related to Triamcinolone can be categorized as:

Common

• Pounding in the ears
• Aggression
• Dizziness
• Irregular heartbeat or pulse
• Headache
• Irritability
• Mood changes
• Nervousness
• Noisy
• Rattling breathing
• Mental depression
• Shortness of breath
• Troubled breathing at rest
• Weight gain
• Agitation
• Anxiety
• Blurred vision
• Decrease in the amount of urine

Rare

• Tarry stools
• Cough or hoarseness
• Darkening of skin
• Decreased vision
• Diarrhea
• Dry mouth
• Eye pain
• Eye tearing
• Facial hair growth in females
• Fainting
• Fatigue
• Fever or chills
• Flushed, dry skin
• Fractures
• Fruit-like breath odor
• Full or round face, neck, or trunk
• Loss of appetite
• Increased hunger
• Increased thirst
• Increased urination
• Unusual tiredness or weakness
• Trouble healing
• Trouble sleeping
• Unexplained weight loss
• Vision changes
• Vomiting
• Loss of sexual desire or ability
• Lower back or side pain
• Menstrual irregularities
• Muscle pain or tenderness
• Muscle wasting or weakness
• Nausea
• Pain in back, ribs, arms, or legs
• Painful or difficult urination
• Skin rash
• Sleeplessness
• Sweating
• Abdominal cramping and/or burning (severe)
• Abdominal pain
• Backache
• Heartburn and/or indigestion (severe and continuous)

The clinically relevant drug interactions of Triamcinolone is briefly summarized here:

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

Amphotericin B injection and potassium-depleting agents: When corticosteroids are administered along with potassium-depleting agents such as diuretics, and amphotericin-B, patients should be monitored closely for the development of conditions of hypokalemia. There have been reported cases in which concomitant use of amphotericin B and hydrocortisone resulted in cardiac enlargement and congestive heart failure.

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

Anticholinesterases: The concomitant use of anticholinesterase agents and corticosteroids might produce severe weakness in patients suffering from myasthenia gravis. If it is possible, anticholinesterase agents should be withdrawn at least 24 hours prior to initiation of corticosteroid therapy.

Anticoagulants, oral: The coadministration of corticosteroids and warfarin has usually resulted in the inhibition of response to warfarin, although there have been some conflicting reports. Therefore, the coagulation indices should be observed and monitored frequently to maintain the desired anticoagulant effect.

Antidiabetics: As corticosteroids might increase blood glucose concentrations, hence dosage adjustments of antidiabetic agents might be required.

Antitubercular drugs: The Serum concentrations of isoniazid might be decreased. Cholestyramine: Cholestyramine might increase the clearance of corticosteroids.

Cyclosporine: The increased activity of both cyclosporine and corticosteroids might occur when the two are used concomitantly. Convulsions have been found to be reported with this concurrent use.

Digitalis glycosides: Patients on digitalis glycosides might be at an increased risk of arrhythmias due to hypokalemia. Estrogens, including oral contraceptives, might decrease the hepatic metabolism of certain corticosteroids, thereby increasing their effects.

Hepatic Enzyme Inducers such as phenytoin, barbiturates, carbamazepine, rifampin: The said drugs which induce hepatic microsomal drug metabolizing enzyme activity might enhance the metabolism of corticosteroids and hence require that the dosage of the corticosteroid be increased.

Ketoconazole: Ketoconazole has been found to decrease the metabolism of certain corticosteroids by around 60%, leading to an increased risk of corticosteroid related side effects.

Nonsteroidal anti-inflammatory agents (NSAIDs): Concomitant use of aspirin or any other nonsteroidal anti-inflammatory agents and corticosteroids might increase the risk of gastrointestinal side effects. Aspirin should be taken cautiously along with corticosteroids in hypoprothrombinemia. The clearance of salicylates might be increased with concurrent use of corticosteroids.

Skin tests: Corticosteroids might lead to suppression reactions to skin tests.

Vaccines: Patients who are on prolonged corticosteroid therapy might exhibit a diminished response to toxoids and to live or inactivated vaccines due to inhibition of antibody response. Corticosteroids might also increase the replication of some organisms contained in the live attenuated vaccines. The Routine administration of vaccines or toxoids should be deferred until the therapy with corticosteroid is discontinued if possible.

The common side effects of Triamcinolone include the following:

• Small white or red bumps on the skin
• Severe mood changes or depression
• Bloody or black, tarry stools
• Muscle weakness
• Confusion
• Very high blood pressure
• Fast heart rate
• Burning, itching, irritation, stinging, redness, or drying of the skin
• Acne
• Change in skin color
• Unwanted hair growth
• Tiny red bumps or rash around the mouth
• Shortness of breath
• Blurred vision
• Severe headache
• Seizure
• Pancreatitis

Pregnancy

Teratogenic Effects: Pregnancy Category C

Corticosteroids had been shown to be teratogenic in many species when given in doses equivalent to that of the human dose. Animal studies in which corticosteroids had been given to rats, pregnant mice, and rabbits had yielded an increased incidence of cleft palate in the newborn offspring. There are found to be well-controlled and no adequate studies in pregnant women.

Corticosteroids should be used during pregnancy only if the potential benefits outweigh the potential risks associated with the fetus. Infants born to mothers who had received corticosteroids during pregnancy should be carefully observed for the signs of hypoadrenalism.

Nursing Mothers

Systemically administered corticosteroids appear in human milk and might suppress growth, also interfere with endogenous corticosteroid production, or cause other unwanted effects. Hence, caution should be exercised when corticosteroids are administered to nursing women.

Pediatric Use

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

The adverse effects of Triamcinolone in pediatric patients have been found similar to those in adults. Like adults, it is advised pediatric patients should be carefully observed with frequent measurements of height, intraocular pressure, blood pressure, weight, and clinical evaluation for the presence of infection, peptic ulcers, cataracts, psychosocial disturbances, thromboembolism, and osteoporosis. Pediatric patients who are treated with corticosteroids by any route which includes systemically administered corticosteroids, might experience a decrease in their growth velocity. This negative impact of corticosteroids on growth has been observed at low systemic doses and also in the absence of laboratory evidence of HPA axis suppression i.e.,basal cortisol plasma and cosyntropin stimulation levels.

Geriatric Use

There has been found to be no overall differences in effectiveness and safety had been observed between older and younger subjects, and other reported clinical trials experience had not identified differences in responses between the older and younger patients.

Physicians should be vigilant and knowledgeable about the treatment pertaining to the treatment and identification of overdosage of Triamcinolone.

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

Pharmacodynamics

Triamcinolone is said to be a corticosteroid with anti-inflammatory properties. These properties have been found to treat inflammation in conditions that is said to affect various organs and tissues. It is advised that Triamcinolone should not be administered as an epidural injection.

Pharmacokinetics

• Absorption

A 16mg oral dose of Triamcinolone is said to reach a Cmax of 5.23±0.84ng/mL and the Tmax achieved to be 2.24±0.78h and an AUC of about 36.0±6.2ng*h/mL.

A intravenous dose of 2mg triamcinolone acetonide has foudn to have achieved an AUC of 57.7ng*h/mL.The bioavailability of 800µg of inhaled triamcinolone acetonide is found to be 25%, with around 10.4% coming from pulmonary absorption while the rest being accounted for by the deposition on the oral mucosa and other underlying factors. An inhaled dose of triamcinolone acetonide is said to reach a Cmax of about 0.92ng/mL with a Tmax of 1.74h and an AUC of 5.12ng*h/mL. The fraction of an inhaled dose of Triamcinolone that is actually absorbed via the pulmonary route is said to reach a Cmax of 0.55ng/mL which achieved a Tmax of 0.66h and an AUC of 2.15ng*h/mL.

A oral dose of 16mg triamcinolone diacetate is said to reach a Cmax of 5.33±1.55ng/mL while the Tmax of 1.86±0.47h and an AUC of 32.7±9.9ng*h/mL.

• Distribution

The apparent volume of distribution of Triamcinolone alone is found to be 115.2±10L. The mean apparent volume of distribution of triamcinolone acetonide has been reported to be 1.96L/kg and the apparent volume of distribution of triamcinolone diacetate is reported to be 119.7±33.14L.

• Metabolism

6-beta-hydroxy-triamcinolone is the major metabolite of Triamcinolone .

• Elimination

About 20% of a dose of Triamcinolone is found to be recovered in the urine in the form of unchanged drug, 25% is recovered in the form of 6-beta-hydroxy-triamcinolone, and 5% is recovered as unidentified metabolites.

• Goldstein DA, Do D, Noronha G, Kissner JM, Srivastava SK, Nguyen QD. Suprachoroidal Corticosteroid Administration: A Novel Route for Local Treatment of Noninfectious Uveitis. Transl Vis Sci Technol. 2016 Dec 14;5(6):14. doi: 10.1167/tvst.5.6.14. eCollection 2016 Dec.

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