Triamcinolone

Mechanism of Action

Triamcinolone is a glucocorticoid in the corticosteroid drug class. It exhibits anti-inflammatory and immunosuppressant activity via inhibiting the phospholipase A2 enzyme on the cell membrane phospholipid layer, thereby hindering the breakdown of leukocyte lysosomal membranes and preventing the formation of arachidonic acid.[7] It decreases the expression of cyclooxygenase (COX) and lipoxygenase (LOX) and thus prevents the biosynthesis of prostaglandins and leukotrienes, respectively. Corticosteroids manifest anti-inflammatory effects via inhibiting macrophage and leukocyte migration to the affected site by reversing vascular dilation and permeability. These actions lead to reduced edema, erythema, and pruritus. An important anti-inflammatory mechanism is mediated by the inhibition of nuclear factor kappa-B (NF-κB), which leads to decreased protein expression of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and COX-2.[8][9]

Pharmacokinetics

Absorption: Absorption, onset, and duration vary based on dose form.

• Injection: IV administration results in rapid and complete absorption.[10] After deep intramuscular injection, triamcinolone acetonide is absorbed slowly, though almost completely. While triamcinolone may be absorbed systemically from synovial spaces, clinically significant systemic levels after intra-articular injection are unlikely except possibly following injection to large joints with high doses. 
• Oral: The medication has a rapid absorption rate following oral intake; oral ingestion results in 90% absorption. Triamcinolone has a half-life of 18 to 36 hours, and peak triamcinolone concentrations occur within 1.5 to 2 hours following oral administration.
• Topical: Systemic absorption varies based on application area and site, occlusion, and patient-specific characteristics
• Nasal spray: This formulation exhibits minimal systemic absorption

Distribution: The duration of triamcinolone varies because it depends on the route of administration. IV administration has been shown to have a volume of distribution of 103L. Oral bioavailability was 23%.[10]

Metabolism: Systemically absorbed triamcinolone is hepatically metabolized via the CYP450 enzyme system; it is a CYP3A4 substrate.

Elimination: Elimination is via both renal and fecal pathways.

Administration

Available Dosage Forms

Triamcinolone administration can be oral (tablets or capsules), topical (spray, lotion, cream, and ointment), oral or intranasal topical (eg, spray), intramuscular, or via intravitreal injection. Triamcinolone should be taken orally with meals to avoid GI discomfort. When given topically, instructions are to apply a thin layer to the affected area and rub gently. When administered as an inhalation solution, the patient must learn the proper administration technique for the correct dose.[11]

Available Strengths

The injectable suspension formulation is available in 5, 10, 20, and 40 mg/mL strengths. The topical lotion, cream, and ointment are available in 0.025%, 0.1%, and 0.5% formulations. The topical spray is available at 0.0147%. There is also a 0.1% dental paste formulation. Triamcinolone should be stored in a cool, dry area at room temperature (68 °F to 77 °F or 20 °C to 25 °C).

Adult Dosing

A list of some regimens for conditions organized by dosage form:

Seasonal allergic rhinitis

• In adults and children ages 12 and older: 220 μg daily via intranasal spray (1 to 2 actuator sprays in each nostril; start with 2 sprays. Do not exceed 2 sprays in each nostril per day.) Discontinue in 3 weeks if there is no improvement.
• In children:
  • Ages 2 to 5: 110 μg daily via intranasal spray (1 actuation in each nostril); do not exceed 110 μg (1 actuation) daily in children younger than 6. Discontinue in 3 weeks if there is no improvement.
  • Ages 6 to 11: 110 μg to 220 μg daily via intranasal spray (1 to 2 actuator sprays in each nostril; start with 1 spray - do not exceed 2 sprays in each nostril per day.) Discontinue in 3 weeks if there is no improvement.

Allergic conditions (hay fever/pollen)

• For adults, 40 to 100 mg IM for a single dose is recommended. The lowest effective dose is used for hay fever or pollen asthma.

Acute exacerbations of multiple sclerosis

• In adults, the recommended dose is 160 to 100 mg IM daily for 1 week, then 64 mg every other day for 1 month. Use the lowest effective dose for the shortest effective treatment duration and taper the dose to discontinue therapy.

Various skin conditions

Treatment for atopic dermatitis, contact dermatitis, dermatitis herpetiformis, psoriasis, eczema, or lichen planus:

• Topical cream or ointment:
  • For adults: apply 0.1% triamcinolone paste 2 or 3 times daily to the affected area after meals.

Dermatomyositis or symptomatic sarcoidosis

• IM:
  • For adults, the dose ranges between 40 and 80 mg IM daily. Start with 60 mg for 1 dose; use the lowest effective dose. The frequency will vary based on the condition and severity.
  • The dose ranges from 0.11 to 1.6 mg/kg/d for children, divided into 3 or 4 doses.

• Topical cream or ointment:
  • In adults, apply 0.025% to 0.05% lotion/cream/ointment or 0.1% to 0.5% cream/ointment 2 or 3 times daily to the affected area.

Steroid responsive dermatoses (including atopic and contact dermatitis)

• Topical cream or ointment:
  • Apply a thin film of 0.025% cream or ointment to the affected areas 2 to 4 times daily.
  • Injection: Inject intralesionally or sub-lesional up to 0.5 mg/in² of affected skin.

Symptomatic relief of rheumatoid arthritis, gouty arthritis, osteoarthritis

• IM:
  • For adults, the dose ranges between 40 and 80 mg IM; repeat every 4 weeks.
  • For children, the dose is 40 mg IM; repeat every 4 weeks.

Intra-articular injection and tendon sheaths (including gout)

• Large joints: inject 5 to 15 mg intraarticular once; may need up to 40 mg.
• Small joints: inject 2.5 to 5 mg intraarticular once; may require up to 10 mg.
• Tendon sheaths: inject 2.5 to 10 mg along the sheath 1 time.

Special Patient Population

Hepatic impairment: Renal dose adjustments, including for patients on dialysis, are undefined. Caution is advised.

Renal impairment: Dosing for hepatic impairment is undefined.

Pregnant considerations: Clinicians must weigh the risks and benefits, especially in the first trimester or with long-term use. Conflicting human data shows a risk of orofacial cleft, possible low birth weight, and premature birth based on limited data from other corticosteroids.

Breastfeeding considerations: No human data is available. However, the risk of infant harm is not expected based on limited data from other similar drugs and triamcinolone's properties. However, there is a potential risk of suppressed infant growth and reduced endogenous steroid production. Based on data from high-dose steroid injections, there is a potential risk of reduced milk production.

Pediatric patients: See pediatric dosing above.

Older patients: To date, no studies have demonstrated specific problems affecting older patients that would limit the use of triamcinolone injection in this patient population. However, older patients are more sensitive to triamcinolone's effects than younger adults, especially osteoporosis. A higher incidence of skin atrophy is noted with glucocorticoid use in older patients.

Adverse Effects

Common adverse effects associated with the initial use of topical triamcinolone involve itchiness, burning, irritation, or skin drying.[12] These symptoms resolve on their own within a few days of use. Other adverse effects may include headaches, dizziness, edema of the ankles or feet, or changes in urination or vision.

Chronic use of glucocorticoids such as triamcinolone may cause Cushing syndrome or Cushingoid appearance. Other effects include hypertension, weight gain, acne, striae, thinning of the dermal skin layer, osteoporosis, hyperglycemia, amenorrhea, immunosuppression, and steroid psychosis (eg, depression or mania).[13][14][15] Other adverse effects include those associated with all corticosteroids, including emotional lability, weight gain, sodium retention, hypokalemia, acne, and increased intraocular pressure. Long-term use can result in oral candidiasis (thrush), osteoporosis, and muscle weakness. Adverse effects from intraarticular use include post-injection flare and joint swelling.

Patients with congestive heart failure or severe hypertension may experience a higher incidence of edema and weight gain when taking systemically administered triamcinolone. Glucocorticoid drugs must be slowly tapered off with chronic use to prevent the occurrence of adrenal insufficiency (high risk if the drug is abruptly discontinued, especially in very ill patients).

Drug-Drug Interactions

Contraindicated drugs include several vaccines, including adenovirus BCG live intravesical, live cholera vaccine, live dengue vaccine, live nasal influenza vaccine, live MMR, live rotavirus vaccine, live smallpox vaccine, live typhoid vaccine, live varicella vaccine, and live yellow fever vaccine. Desmopressin and mifepristone are also contraindicated for concurrent use. Other drugs (eg, thiazide and loop diuretics) can have additive effects resulting in hypokalemia.

Contraindications

Warnings and Precautions

Triamcinolone injections are strongly contraindicated for epidural administration due to serious medical adverse effects, including paralysis, cortical blindness, and death. Additionally, prolonged use of glucocorticoids may lead to hypothalamic-pituitary-adrenal (HPA) suppression.[16][17] High doses of corticosteroids are not recommended in patients with head trauma due to the risk of early mortality. Systemic corticosteroids are not indicated in patients with fungal or viral infections. Contraindications to triamcinolone include patients with tuberculosis due to the risk of reactivation. 

Patients diagnosed with diabetes mellitus should use caution when systemically dosing triamcinolone (as with all corticosteroids) due to its hyperglycemic adverse effect. Patients diagnosed with psychosis should also use extreme caution, as triamcinolone may exacerbate related symptoms.

Corticosteroids are known to exacerbate glaucoma; thus, primary care physician supervision is necessary.[18] Due to its potency, pregnant patients should not use triamcinolone for prolonged durations. Corticosteroid use is contraindicated in children younger than 2. Injectable triamcinolone often contains benzyl alcohol, so its use in neonates should be avoided to prevent potential gasping syndrome.

Monitoring

Patients taking triamcinolone should undergo monitoring to relieve symptoms and any adverse effects. Monitoring parameters include body weight, blood pressure, electrolytes, 2-hour postprandial glucose, chest radiograph with extended therapy duration, and bone mineral density with prolonged use or in patients older than 65.[19][20] It is essential to monitor the cardiac function in patients with a medical history of congestive heart failure or arrhythmias. 

Toxicity

Glucocorticoids such as triamcinolone can cause variable neuropsychiatric symptoms to develop. Examples of these symptoms include mania, depression, delirium, and psychosis.[21] These symptoms and other cognitive issues resulting from taking triamcinolone can be reversible after discontinuing the medication. An increased risk of suicide in patients on chronic glucocorticoid therapy has been recorded, so triamcinolone use warrants caution.

Cardiovascular effects can also be seen in patients using triamcinolone. Premature atherosclerosis, hypertension, fluid retention, and arrhythmias can occur in these patients, especially when prescribing a higher drug dosage. Many of these cardiovascular issues are likely to disappear upon discontinuation of triamcinolone.

Enhancing Healthcare Team Outcomes

Managing the administration of triamcinolone requires an interprofessional team that may include physicians, advanced practice practitioners, nurses, pharmacists, and specialty clinicians such as an allergist or dermatologist. An immunologist may also be called upon to evaluate immune system processes affected by the administration of triamcinolone. The interprofessional team must instruct patients on the proper technique for applying topical triamcinolone. Nurses will most likely administer drug injections and need to keep the team informed of any adverse events and document the dosing. 

The healthcare team should be vigilant regarding adverse effects and therapeutic outcomes of triamcinolone. Nursing staff can verify patient adherence, answer questions, provide counsel, and monitor for adverse events and treatment effectiveness, informing the clinician of any concerns. Pharmacists should be involved with recommendations regarding dosing and drug storage. Additionally, a clinical pharmacologist consult is necessary if the patient is experiencing toxicity symptoms. Regular follow-up with the patient is prudent to assess for abnormalities and drug efficacy.

Triamcinolone therapy requires a collaborative interprofessional team approach to achieve optimal patient outcomes. Open communication and meticulous documentation are also vital components of successful medical teamwork.