Scar PT Gel

Pentoxifylline

Pentoxifylline is a synthetic dimethylxanthine derivative that is structurally related to theophylline and caffeine. Unlike these agents, pentoxifylline has hematological effects that are useful in the symptomatic treatment of complications of peripheral vascular diseases. Pentoxifylline also has been used to manage acute and chronic cerebrovascular insufficiency, sickle cell disease^[1], and painful diabetic neuropathy.^[2] Pentoxifylline was approved by the FDA in August 1984.

Triamcinolone Acetonide

Triamcinolone is a synthetic glucocorticoid that is considered slightly more potent than prednisone when given orally. Triamcinolone has little mineralocorticoid activity and is therefore not used systemically to manage adrenal insufficiency unless a more potent mineralocorticoid is administered concomitantly. Triamcinolone is commercially available in nasal, parenteral, topical, and intravitreal injection formulations. Oral and respiratory formulations of triamcinolone were previously available but are no longer marketed in the U.S. Triamcinolone injections are commonly used for intra-articular use when such therapy is indicated. The nasal spray is used to manage symptoms of seasonal and perennial allergies. Topical preparations for corticosteroid-responsive dermatoses are considered to be of medium or high potency.

Pentoxifylline

The actions of pentoxifylline include increased erythrocyte flexibility and decreased blood viscosity. The mechanism of action for increasing erythrocyte flexibility is unknown, but the drug’s actions appear to be related to inhibition of erythrocyte phosphodiesterase, which causes an increase in erythrocyte cAMP activity. This increase allows the erythrocyte membrane to maintain its integrity and become more resistant to deformity. Pentoxifylline’s effect on blood viscosity is attributed to its reduction in plasma fibrinogen concentrations and an increase in fibrinolytic activity, as well as to its effects on erythrocytes. Improvement in blood viscosity results in increased blood flow to the microcirculation and enhanced tissue oxygenation. Unlike theophylline, pentoxifylline does not possess any bronchodilatory actions. Although pentoxifylline does not possess any direct anti-sickling properties, its actions on erythrocyte flexibility make it potentially beneficial in sickle cell disease.

Triamcinolone Acetonide

Corticosteroids exhibit anti-inflammatory, antipruritic, and vasoconstrictive properties. At the cellular level, corticosteroids induce peptides called lipocortins. Lipocortins antagonize phospholipase A2, an enzyme which causes the breakdown of leukocyte lysosomal membranes to release arachidonic acid. This action decreases the subsequent formation and release of endogenous inflammatory mediators including prostaglandins, kinins, histamine, liposomal enzymes and the complement system.^[3][4]

Early anti-inflammatory effects of topical corticosteroids include the inhibition of macrophage and leukocyte movement and activity in the inflamed area by reversing vascular dilation and permeability. Later inflammatory processes such as capillary production, collagen deposition, keloid (scar) formation also are inhibited by corticosteroids. Clinically, these actions correspond to decreased edema, erythema, pruritus, plaque formation and scaling of the affected skin.^[3]

In the treatment of asthma, corticosteroids block the late phase allergic response to allergens. Mediators involved in the pathogenesis of asthma include histamine, leukotrienes (slow releasing substance of anaphylaxis, SRS-A), eosinophil chemotactic factor of anaphylaxis (ECF-A), neutrophil chemotactic factor (NCF), cytokines, hydroxyeicosatetraenoic acids, prostaglandin-generating factor of anaphylaxis (PGF-A), prostaglandins, major basic protein, bradykinin, adenosine, peroxides, and superoxide anions. Different cell types are responsible for release of these mediators including airway epithelium, eosinophils, basophils, lung parenchyma, lymphocytes, macrophages, mast cells, neutrophils, and platelets. Corticosteroids inhibit the release of these mediators as well as inhibit IgE synthesis, attenuate mucous secretion and eicosanoid generation, up-regulate beta-receptors, promote vasoconstriction, and suppress inflammatory cell influx and inflammatory processes. Clinical effects in asthma include a reduction in bronchial hyperresponsiveness to allergens, a decreased number of asthma exacerbations, and an improvement in FEV-1, peak-flow rate, and respiratory symptoms. Since corticosteroid effects take several hours to days to become clinically noticeable, they are ineffective for primary treatment of severe acute bronchospastic attacks or for status asthmaticus. Inhaled corticosteroids have no bronchodilatory properties.^[3][5]

Pentoxifylline

Pentoxifylline is contraindicated in patients who have exhibited intolerance to pentoxifylline or methylxanthines (e.g., caffeine, theophylline, theobromine).

Pentoxifylline should be used cautiously in patients with risk factors complicated by bleeding. These patients include those with recent surgery or peptic ulcer disease. Periodic exams for bleeding including hematocrit and hemoglobin should be performed. Pentoxifylline is contraindicated in patients with intracranial bleeding or retinal bleeding.

Pentoxifylline and its active metabolites can accumulate in patients with renal impairment; such patients should be monitored carefully for adverse effects. Dosage adjustments are recommended in patients with renal impairment (CrCl < 50 ml/min) or renal failure (see Dosage). Dosage adjustments are recommended in patients who do not tolerate pentoxifylline (i.e., experience GI or CNS adverse effects) at usual prescribed dosages. Clinical studies of pentoxifylline did not include sufficient numbers of subjects aged 65 years or older to determine whether they respond differently from younger subjects, and other reported clinical experience has not identified differences in responses between geriatric and younger patients. Because elderly patients are more likely to have decreased hepatic, renal, or cardiac function, they are at increased risk of adverse reactions due to decreased clearance of pentoxifylline and its metabolites. Elderly patients taking this drug should be monitored carefully, and it may be useful to monitor renal function. Pentoxifylline is classified as FDA pregnancy risk category C. No controlled studies of pentoxifylline use have been conducted in women who are pregnant. Therefore, caution should be exercised when the drug is used during pregnancy.^[6] Pentoxifylline and its metabolites are excreted into human milk. According to the manufacturer, pentoxifylline has been shown to be tumorigenic in rats; therefore, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.^[6] A single dose of extended-release pentoxifylline was given to 5 women who had been breast-feeding for at least 6 weeks. Data from this study indicate an exclusively breastfed infant would receive about 2% of the maternal-adjusted dosage.^[7] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA. The safe and effective use of pentoxifylline in children has not been established.

Triamcinolone Acetonide

Prolonged administration of pharmacological doses of systemic corticosteroids or topical preparations (resulting in systemic absorption) may result in hypothalamic-pituitary-adrenal (HPA) suppression and/or manifestations of Cushing’s syndrome in some patients. Adrenal suppression and increased intracranial pressure have been reported with the use and/or withdrawal of various corticosteroid formulations in pediatric patients.^[8][9][10] Inhaled triamcinolone should be used with caution when substituting the drug for oral corticosteroid therapy; deaths due to adrenal insufficiency have been reported in asthmatic patients during and following such a transfer.^[11] Acute adrenal insufficiency and even death may occur following abrupt discontinuation of systemic therapy. In addition, a withdrawal syndrome unrelated to adrenocortical insufficiency may occur following sudden discontinuation of corticosteroid therapy.^[12] These effects are thought to be due to the sudden change in glucocorticoid concentration rather than to low corticosteroid concentrations. Withdraw prolonged systemic corticosteroid therapy (duration of treatment more than 2 weeks) gradually. HPA suppression can last for up to 12 months following cessation of systemic therapy. Recovery of HPA axis function is generally prompt and complete upon discontinuation of the topical corticosteroid. HPA-suppressed patients may need supplemental corticosteroid treatment during periods of physiologic stress, such as post-surgical stress, acute blood loss, or infectious conditions, even after the corticosteroid has been discontinued.^[12] Encourage patients currently receiving chronic corticosteroid therapy or who have had corticosteroids discontinued within the last 12 months to carry identification advising the need for administration of corticosteroids in situations of increased stress.^[13] Conditions that increase systemic absorption of topical corticosteroids include use over large surface areas, prolonged use, use in areas where the epidermal barrier is disrupted (i.e., skin abrasion), and the use of an occlusive dressing. Pediatric patients may absorb proportionally larger amounts of topical corticosteroids compared to adults due to a larger skin surface to body mass ratio and, therefore, may be at increased risk of systemic adverse reactions. Evaluate patients receiving large doses of triamcinolone applied to a large surface area periodically for evidence of HPA axis suppression and/or manifestations of Cushing’s syndrome. If these effects are noted, attempt withdrawal of the drug, a reduction in the frequency of application, or substitution of a less potent corticosteroid.^[14] Non prescription intranasal corticosteroids should not be used for greater than 2 months in pediatric patients without oversight of a healthcare provider. If signs of HPA suppression occur with the use of intranasal corticosteroids, the drug should be slowly discontinued.^[15][16] Additionally, clearance of corticosteroids is decreased in patients with hypothyroidism and increased in hyperthyroidism.^[17]

Potential adverse effects of chronic corticosteroid therapy should be weighed against the clinical benefits obtained and the availability of other treatment alternatives. Prolonged systemic corticosteroid therapy can lead to osteoporosis, vertebral compression fractures, aseptic necrosis of femoral and humoral heads, and pathologic fractures of long bones secondary to decreased bone formation, increased bone resorption, and protein catabolism in any patients.^[12] A high-protein diet may alleviate or prevent the adverse effects associated with protein catabolism. The elderly, post-menopausal, and pediatric patients may be more susceptible to the effects on bone. Chronic systemic triamcinolone therapy may cause growth inhibition in pediatric patients due to hypothalamic-pituitary-adrenal axis suppression and inhibition of bone growth. Corticosteroids should be titrated to the lowest effective dose. Because bone development is critical in pediatric patients, monitoring is warranted in patients receiving high-dose or chronic corticosteroid treatment. Growth inhibition may also occur with intranasal or topical triamcinolone due to systemic absorption, particularly in susceptible patients or when used in high doses or for prolonged periods of time. Use of the lowest effective dose is recommended to minimize the occurrence of systemic adverse effects. Monitor growth routinely.^{[15][18] [19][14][9]}

Do not use high doses of corticosteroids such as triamcinolone hexacetonide for the treatment of traumatic brain injury. An increase in early mortality (at 2 weeks) and late mortality (at 6 months) was noted in patients with head trauma who were determined not to have other clear indications for corticosteroid treatment; in the trial, patients received methylprednisolone hemisuccinate.

Corticosteroids such as triamcinolone are not recommended for use by patients with cerebral malaria. Systemic corticosteroid therapy can mask the symptoms of infection and should not be used in cases of viral infection, fungal infection, or bacterial infection that are not adequately controlled by antiinfective agents. Although the manufacturers state that systemic triamcinolone is contraindicated in patients with systemic fungal infections, most clinicians believe that systemic corticosteroids can be administered to these patients as long as appropriate antiinfective therapy is administered simultaneously.

Patients receiving immunosuppressive doses of systemic corticosteroids should be advised to avoid exposure to viral infections (i.e., measles or varicella) because these diseases may be more serious or even fatal in immunosuppressed patients. Pediatric patients dependent on systemic corticosteroids should undergo anti-varicella-zoster virus antibody testing. The incidence or course of acute viral or bacterial infection are probably minimally affected by inhaled triamcinolone.^[20] Application of topical corticosteroids to areas of infection, including dermatologic fungal infection, and cutaneous or systemic viral infection (e.g., herpes infection, measles, varicella), should be initiated or continued only if the appropriate antiinfective treatment is instituted. If the infection does not respond to the antimicrobial therapy, the concurrent use of the topical corticosteroid should be discontinued until the infection is controlled. Use ophthalmic triamcinolone acetonide injectable suspension (Triesence or Trivaris) with caution in patients with ocular herpes infection because of possible corneal perforation. Corticosteroids should not be used in active ocular herpes infection.

Topical corticosteroids, such as triamcinolone, should not be used to treat acne vulgaris, acne rosacea, or perioral dermatitis as they may exacerbate these conditions.

Topical corticosteroids may delay the healing of non-infected wounds, such as venous stasis ulcers. Use topical triamcinolone preparations with caution in patients with markedly impaired circulation or peripheral vascular disease; skin ulceration has been reported in these patients following topical corticosteroid use.

As with any long-term topical treatment of the nasal cavity, patients using triamcinolone intranasally over several months or longer should be examined periodically for possible changes in the nasal mucosa. Further, because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal septal perforation or ulcer, nasal surgery, or nasal trauma should not use a nasal corticosteroid until healing has occurred.

Topical corticosteroids should be used for brief periods, or under close medical supervision in patients with evidence of preexisting skin atrophy. Elderly patients may be more likely to have preexisting skin atrophy secondary to aging. Purpura and skin lacerations that may raise the skin and subcutaneous tissue from deep fascia may be more likely to occur with the use of topical corticosteroids in older adult patients. Use of lower potency topical corticosteroids also may be necessary in some patients.^[21][22]

Topical corticosteroids should be used with caution in patients with diabetes mellitus. Exacerbation of diabetes may occur with systemic absorption of the topical corticosteroid. Use of topical corticosteroids may further delay healing of skin ulcers in diabetic patients.

Topical use of triamcinolone during pregnancy should also be approached with caution. Topical corticosteroids, including triamcinolone, should not be used in large amounts, on large areas, or for prolonged periods of time in pregnant women. Guidelines recommend mild to moderate potency topical agents over potent corticosteroids, which should be used in short durations. Fetal growth restriction and a significantly increased risk of low birthweight has been reported with use of potent or very potent topical corticosteroids during the third trimester, particularly when using more than 300 grams. Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals.^{[21][14][10][23]}

Triamcinolone therapy usually does not contraindicate vaccination with live-virus vaccines when such therapy is of short-term (< 2 weeks); low to moderate dose; long-term alternate day treatment with short-acting preparations; maintenance physiologic doses (replacement therapy); or administration topically (skin or eye), by aerosol, or by intra-articular, bursal or tendon injection. The immunosuppressive effects of steroid treatment differ, but many clinicians consider a dose equivalent to either 2 mg/kg/day or 20 mg/day of prednisone as sufficiently immunosuppressive to raise concern about the safety of immunization with live-virus vaccines. In general, patients with severe immunosuppression due to large doses of corticosteroids should not receive vaccination with live-virus vaccines. When cancer chemotherapy or immunosuppressive therapy is being considered (e.g., for patients with Hodgkin's disease or organ transplantation), vaccination should precede the initiation of chemotherapy or immunotherapy by >= 2 weeks. Patients vaccinated while on immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated at least 3 months after discontinuation of therapy. In patients who have received high-dose, systemic corticosteroids for >= 2 weeks, it is recommended to wait at least 3 months after discontinuation of therapy before administering a live-virus vaccine.

According to the Beers Criteria, systemic corticosteroids are considered potentially inappropriate medications (PIMs) for use in geriatric patients with delirium or at high risk for delirium and should be avoided in these patient populations due to the possibility of new-onset delirium or exacerbation of the current condition. The Beers expert panel notes that oral and parenteral corticosteroids may be required for conditions such as exacerbation of chronic obstructive pulmonary disease (COPD) but should be prescribed in the lowest effective dose and for the shortest possible duration.^[24] The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs); the need for continued use of a glucocorticoid, with the exception of topical or inhaled formulations, should be documented, along with monitoring for and management of adverse consequences with intermediate or longer-term systemic use.^[25]

Monitor patients with renal disease or renal impairment for signs of edema, weight gain, or serum electrolyte abnormalities. Triamcinolone may increase salt and water retention and increase the excretion of potassium and calcium. Dietary salt restriction or potassium supplementation may be necessary.^[26]

Use triamcinolone with caution in patients with hepatic disease. An enhanced corticosteroid effect may occur due to increased drug metabolism in patients with cirrhosis.^[12]

Pentoxifylline

Pentoxifylline therapy is associated with adverse effects involving the GI tract and the central nervous system. Adverse events are dose-related and if they do occur a dosage reduction should be considered. If adverse events continue at a reduced dosage, pentoxifylline therapy should be discontinued.

The following gastrointestinal-related adverse reactions were reported with pentoxifylline extended-release tablets during controlled clinical trials compared to placebo: nausea (2.2% vs. 0.8%), vomiting (1.2% vs. 0%), and belching/flatulence/bloating (0.6% vs. 0%). Anorexia, cholecystitis, constipation, and xerostomia/thirst have been reported spontaneously since marketing or occurred in other clinical trials with an incidence of less than 1%; the causal relationship was uncertain.^[32]

Anxiety, confusion, depression, seizures, and aseptic meningitis have been reported spontaneously since pentoxifylline marketing or occurred in other clinical trials with an incidence of less than 1%; the causal relationship was uncertain.^[32]

Angina/ chest pain (unspecified) was reported at an incidence of 0.3% in pentoxifylline-treated patients compared to 0% of placebo-treated patients in clinical trials. Dyspnea, edema, and hypotension were reported spontaneously since marketing or occurred in other clinical trials with an incidence of less than 1%; the causal relationship was uncertain. Arrhythmia exacerbation and sinus tachycardia have been reported rarely during post-marketing experience; a causal relationship has not been established.^[32]

Epistaxis, influenza-like symptoms, laryngitis, and nasal congestion have been reported spontaneously since marketing of pentoxifylline or occurred in other clinical trials with an incidence of less than 1%; the causal relationship was uncertain.^[32]

Angioedema has been reported spontaneously during post-marketing of pentoxifylline or in other clinical trials with an incidence of less than 1%; the causal relationship was uncertain. In addition, anaphylactoid reactions, including anaphylactic shock, have been reported rarely; a causal relationship has not been established. Pentoxifylline should be discontinued at the first sign of an anaphylactic reaction.^[32]

Hepatitis, jaundice, cholestasis, and elevated hepatic enzymes have been reported rarely during post-marketing experience with pentoxifylline; a causal relationship has not been established.^[32]

Leukopenia has been reported spontaneously since marketing of pentoxifylline or occurred in other clinical trials with an incidence of less than 1%; the causal relationship was uncertain. Decreased serum fibrinogen, pancytopenia, aplastic anemia, leukemia, purpura, and thrombocytopenia have been reported rarely during post-marketing experience with pentoxifylline; a causal relationship has not been established.^[32]

Brittle fingernails, pruritus, rash (unspecified), and urticaria have been reported spontaneously since marketing pentoxifylline or in other clinical trials with an incidence of less than 1%; the causal relationship was uncertain.^[32]

Blurred vision, conjunctivitis, earache, and scotomata have been reported spontaneously since marketing of pentoxifylline or in other clinical trials with an incidence of less than 1%; the causal relationship was uncertain.^[32]

Bad taste, excessive salivation (hypersalivation), malaise, sore throat/swollen neck glands, and weight change (e.g., weight gain or weight loss) have been reported spontaneously since marketing of pentoxifylline or occurred in other clinical trials with an incidence of less than 1%; the causal relationship was uncertain.^[32]

Triamcinolone Acetonide

Pharmacologic doses of systemic corticosteroids, such as triamcinolone, administered for prolonged periods can result in physiological dependence due to hypothalamic-pituitary-adrenal (HPA) suppression. Generally, HPA suppression is not observed with inhaled triamcinolone alone but is theoretically possible at high doses. Additionally, use of inhaled corticosteroids with systemic corticosteroids could increase the likelihood of HPA suppression compared to a therapeutic dose of either one alone. Systemic absorption of topical corticosteroids can also produce reversible HPA suppression with possible adrenocortical insufficiency after withdrawal of treatment. Percutaneous absorption of triamcinolone is dependent on many factors including the vehicle, the integrity of the epidermal barrier, duration of use, and use of an occlusive dressing. Children may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios. Manifestations of adrenocortical insufficiency in children include low plasma cortisol concentrations and absence of response to adrenocorticotropin (ACTH) stimulation. HPA axis suppression has been reported in children receiving topical corticosteroids. Increased intracranial pressure has also been reported in children receiving topical corticosteroids. Increased intracranial pressure with glucocortiocoids usually occurs after treatment. Clinical signs of increased intracranial pressure include bulging fontanelle, head pain/ache, and bilateral papilledema (i.e., pseudotumor cerebri). Patients applying triamcinolone to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression (using the ACTH stimulation test, A.M. plasma cortisol test, and urinary free cortisol test). To minimize risk of HPA axis suppression, discontinue therapy when control is achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary. If HPA axis suppression is noted, an attempt should be made to withdraw the drug, reduce the frequency of application, or substitute a less potent corticosteroid. Recovery of HPA axis function is generally prompt and complete upon discontinuation of the topical corticosteroid. Exogenously administered corticosteroids exert a negative feedback effect on the pituitary, inhibiting the secretion of ACTH. This results in a decrease in ACTH-mediated synthesis of endogenous corticosteroids and androgens by the adrenal cortex. The severity of secondary adrenocortical insufficiency varies among individuals and is dependent on the dose, frequency, time of administration, and duration of therapy. Systemic administration drug on alternate days may help to alleviate this adverse effect. Patients with HPA suppression will require increased doses of corticosteroid therapy during periods of physiologic stress. Acute adrenal insufficiency and even death can occur with abrupt discontinuation of therapy. Discontinuation of prolonged oral corticosteroid therapy should be gradual, since HPA suppression can last for up to 12 months following cessation of therapy. Patients may continue to need supplemental corticosteroid treatment during periods of physiologic stress or infectious conditions, even after the drug has been discontinued. A withdrawal syndrome unrelated to adrenocortical insufficiency can occur following sudden discontinuance of corticosteroid therapy. This syndrome includes symptoms such as appetite loss, lethargy, nauseousness, head pain/ache, fever, joint pain, muscle pain, exfoliative dermatitis, loss of weight, and hypotension. These effects are believed to be due to the sudden change in corticosteroid concentration rather than to low corticosteroid levels.^[26]

Adverse GI effects associated with long-term triamcinolone administration include nausea, vomiting and anorexia with subsequent weight loss. Appetite stimulation with weight gain, diarrhea, constipation, abdominal pain and/or distention, esophageal ulceration, hiccups, gastritis, and pancreatitis also have been reported. Among intranasal triamcinolone recipients, diarrhea (3% vs. 1.3% with placebo), upper abdominal pain (4.7% vs. 0.8% with placebo), and dyspepsia (3.4% vs. 1% with placebo) were noted. Peptic ulcers with possible subsequent GI bleeding and GI perforation have been reported. Although it was once believed that corticosteroids contributed to the development of peptic ulcer disease, in a review of 93 studies of corticosteroid use, the incidence of peptic ulcer disease was not found to be higher in steroid recipients compared to control groups.^[33] While most of these studies did not utilize endoscopy, it is unlikely that corticosteroids contribute to the development of peptic ulcer disease.

Corticosteroid therapy including triamcinolone can mask the symptoms of infection and should generally be avoided during an acute viral, fungal, or bacterial infection. The incidence or course of acute viral or bacterial infection, however, is probably minimally affected by inhaled or nasal corticosteroids in immunocompetent individuals.^[20] The most common potentially infectious-related adverse reactions with nasal triamcinolone use (more than 2% incidence) were flu-like syndrome and bronchitis. Influenza or a flu-like syndrome was reported in 8.4% of pediatric patients treated with intranasal triamcinolone in clinical trials. Localized candidiasis of the nasal mucosa and pharynx occurs frequently with intranasal corticosteroid therapy. If such an infection develops, the corticosteroid should be discontinued and appropriate local or systemic therapy initiated. It is recommended that patients using an intranasal or inhaled corticosteroid for several months or longer be examined periodically for evidence of infection.^{[15] [11]} Leukocytosis is a common physiologic effect of systemic corticosteroid therapy and may need to be differentiated from the leukocytosis that occurs with inflammatory or infectious processes.^[3][34][35] Immunosuppression from corticosteroids is most likely to occur in patients receiving high-dose (e.g., equivalent to 1 mg/kg or more of prednisone daily), systemic corticosteroid therapy for any period of time, particularly in conjunction with corticosteroid-sparing drugs (e.g., troleandomycin) and/or concomitant immunosuppressant agents; however, patients receiving moderate dosages of systemic corticosteroids for short periods or low dosages for prolonged periods may also be at risk. Corticosteroid-induced immunosuppression may result in the activation of latent viral (e.g., herpes) or bacterial (e.g., tuberculosis) infections and should not be used in patients with an active infection except when appropriate anti-infective therapy is instituted concomitantly. Patients receiving immunosuppressive doses of corticosteroids should be advised to avoid exposure to measles or varicella (chickenpox) and, if exposed to these diseases, to seek medical advice immediately. Monitoring systemic corticosteroid recipients for signs of an opportunistic fungal infection is recommended, as cases of oropharyngeal candidiasis have been reported. Development of Kaposi’s sarcoma has also been associated with prolonged administration of corticosteroids; discontinuation of the corticosteroid may result in clinical improvement.^[36] Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects, especially if used in excessive dosage, over large body surface areas, for prolonged periods, or with occlusive dressings. In the presence of dermatological infections, institute the use of an appropriate antifungal or antibacterial agent. If a favorable response does not promptly occur, discontinue the topical corticosteroid until the infection has been adequately controlled.^[21]

The following adverse reactions (listed in decreasing order of occurrence) are reported with topical corticosteroids such as triamcinolone and may occur more often when used with an occlusive dressing: skin irritation (including burning), pruritus, xerosis (dry skin), folliculitis, hypertrichosis, acneiform rash/eruptions, skin hypopigmentation, perioral dermatitis, maceration of the skin or oral mucosa, secondary infection, skin atrophy, atrophy of the oral mucosa, striae, and miliaria. Erythema, telangiectasia, purpura, and maculopapular rash may also occur.^[21] A rash (unspecified) was noted in 2.5% of intranasal triamcinolone recipients as compared with 1.7% of placebo recipients.^[15] Although skin atrophy usually occurs after prolonged use of topical corticosteroids, this effect may occur even with short-term use on intertriginous or flexor areas, or on the face. If irritation develops, discontinue topical corticosteroids and institute appropriate therapy. The anti-inflammatory activity of topical corticosteroids may also mask manifestations of infection. In the presence of dermatological infections, institute the use of an appropriate antifungal or antibacterial agent. If a favorable response does not promptly occur, discontinue the corticosteroid until the infection has been adequately controlled.^[21] Various adverse dermatologic effects reported during systemic corticosteroid therapy include skin atrophy, diaphoresis, acne vulgaris, striae, hirsutism, acneiform rash, alopecia, xerosis, lupus-like symptoms, perineal pain and irritation, purpura, rash (unspecified), telangiectasia, facial erythema, petechiae, ecchymosis, and easy bruising. Hypersensitivity reactions may manifest as allergic dermatitis, urticaria, anaphylactoid reactions, and/or angioedema. Post-marketing reports of anaphylactoid reactions have been rarely associated with the use of triamcinolone inhalation aerosol. Burning or tingling in the perineal area may occur following IV injection of corticosteroids. Parenteral corticosteroid therapy has also produced skin hypopigmentation, skin hyperpigmentation, scarring, and other types of injection site reaction (e.g., induration, delayed pain or soreness, subcutaneous and cutaneous atrophy, and sterile abscesses).^[26]

In general, excessive use of systemic or topical corticosteroids can lead to impaired wound healing. Triamcinolone should not be applied directly on or near healing wounds.^[17]Use of intranasal triamcinolone is not recommended until healing has occurred for patients who have experienced recent nasal septal ulcers, nasal surgery, or trauma.^[15] Skin ulcer may develop in patients with markedly impaired circulation who use topical corticosteroids.^[21]

Prolonged administration of triamcinolone can result in edema and fluid retention due to sodium retention; electrolyte disturbances (hypokalemia, hypokalemic metabolic alkalosis, hypernatremia, hypocalcemia); and hypertension.^[17]In a review of 93 studies of corticosteroid use, hypertension was found to develop 4 times as often in steroid recipients compared to control groups.^[33] Congestive heart failure can occur in susceptible patients. In a study, an increased risk of heart failure was observed for medium-dose glucocorticoid use as compared with nonuse. At the beginning of the study, patients were at least 40 years of age and had not been hospitalized for cardiovascular disease. Medium exposure was defined as less than 7.5 mg daily of prednisolone or the equivalent given orally, rectally, or parenterally.^[37]

Prolonged triamcinolone therapy can result in hyperglycemia, glucosuria (glycosuria), and aggravation of diabetes mellitus in susceptible patients. In a review of 93 studies of corticosteroid use, the development of diabetes mellitus was determined to occur 4 times more frequently in steroid recipients compared to control groups.^[33] Systemic absorption of topical corticosteroids has produced hyperglycemia and glucosuria in some patients. Percutaneous absorption of hydrocortisone is dependent on many factors including the vehicle, the integrity of the epidermal barrier, duration of use, and use of an occlusive dressing. Children may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios. Insulin or oral hypoglycemic dosages may require adjustment.^[21]

Adverse neurologic effects have been reported during prolonged triamcinolone administration and include insomnia, vertigo, restlessness, amnesia and memory impairment, increased motor activity, impaired cognition, paresthesias, ischemic peripheral neuropathy, malaise, ischemic peripheral neuropathy, seizures, neuritis, and EEG changes. Mental disturbances, including depression, anxiety, euphoria, personality changes, emotional lability, delirium, dementia, hallucinations, irritability, mania, mood swings, schizophrenic reactions, withdrawn behavior, and psychosis have also been reported; emotional lability and psychotic problems can be exacerbated by corticosteroid therapy. Arachnoiditis, meningitis, paresis, paraplegia, and sensory disturbances have occurred after intrathecal administration. Spinal cord infarction has been reported after epidural administration.^[17]

Ocular effects such as corneal perforation, posterior subcapsular cataracts, retinopathy, or ocular hypertension can result from prolonged use of systemic corticosteroids and could result in glaucoma or ocular nerve damage including optic neuritis. Temporary or permanent visual impairment including blurred vision and blindness has been reported with corticosteroid administration by several routes of administration. If injectable systemic steroid therapy is continued for more than 6 weeks, monitor intraocular pressure.^[38] Evaluate any patient who develops visual impairment or changes in vision during corticosteroid therapy for ocular hypertension or other ocular adverse effects. Postmarketing reports of cataracts and glaucoma have been rarely associated with the use of triamcinolone inhalation aerosol or intranasal sprays. The risk of cataracts increases with long-term and high-dose inhaled corticosteroid use.^[11][15] The mechanism of corticosteroid-induced cataract formation is uncertain but may involve disruption of sodium-potassium pumps in the lens epithelium leading to accumulation of water in lens fibers and agglutination of lens proteins.^[39] Ocular hypertension and cataracts have also occurred following prolonged application of topical corticosteroids to the skin around the eye. Triamcinolone use may reduce host resistance to infection. Secondary fungal and viral infections of the eye (ocular infection) can be masked or exacerbated by corticosteroid therapy. Investigate the possibility of fungal infection if patients have persistent corneal ulceration. After intravitreal injection with triamcinolone acetonide injectable suspension (Triesence or Trivaris), monitor patients for ocular hypertension and endophthalmitis. Increases in intraocular pressure, lasting up to 6 months, and cataract progression have been observed in 20% to 60% of patients after treatment. Appropriate monitoring and management of intraocular pressure and optic nerve head perfusion are needed. Monitoring may consist of a check for perfusion of the optic nerve head immediately after the injection, tonometry within 30 minutes following the injection, and biomicroscopy between 2 and 7 days after the injection. The increased intraocular pressure caused by triamcinolone is usually managed by topical glaucoma therapy, but patients may require aggressive non-topical treatment. After intravitreal injection, infectious culture-positive endophthalmitis was reported at a rate of 0.5%, and infectious and noninfectious endophthalmitis was present in less than 2%. Instruct patients to immediately report any symptoms suggestive of endophthalmitis. Less common reactions occurring in up to 2% of patients receiving intravitreal triamcinolone include exophthalmos, hypopyon (leukocytosis in the anterior chamber of the eye), blurring and transient discomfort upon injection, retinal detachment, optic disc vascular disorder, ocular inflammation, ocular hemorrhage, and visual impairment (including vitreous floaters).^{[22] [40]}

Hypercholesterolemia, atherosclerosis, fat embolism, sinus tachycardia, palpitations, bradycardia, syncope, vasculitis, necrotizing angiitis, thrombosis, thromboembolism, and phlebitis, specifically, thrombophlebitis have been associated with triamcinolone therapy. Glucocorticoid use appears to increase the risk of cardiovascular events such as myocardial infarction, left ventricular rupture (in persons who recently experienced a myocardial infarction), angina, angioplasty, coronary revascularization, stroke, transient ischemic attack, cardiomegaly, arrhythmia exacerbation and ECG changes, hypertrophic cardiomyopathy (in premature infants), congestive heart failure and pulmonary edema, cardiac arrest or cardiovascular death.^[17]As determined from observational data, the rate of cardiovascular events was 17 per 1,000 person-years among 82,202 non-users of glucocorticoids. In contrast, the rate was 23.9 per 1,000 person-years among 68,781 glucocorticoid users. Furthermore, the rate of cardiovascular events was 76.5 per 1,000 person-years for high exposure patients. After adjustment for known covariates by multivariate analysis, high-dose glucocorticoid use was associated with a 2.56-fold increased risk of cardiovascular events as compared with nonuse. At the beginning of the study, patients were at least 40 years of age and had not been hospitalized for cardiovascular disease. High glucocorticoid exposure was defined as at least 7.5 mg daily of prednisolone (or equivalent) given orally, rectally, or parenterally whereas medium exposure was defined as less than the above dosage by any of the 3 routes. Low-dose exposure was defined as inhaled, topical, or nasal usage only.^[37]

Tolerance may occur with the prolonged use of topical triamcinolone formulations. Tolerance is usually described as a decreased acute vasoconstrictive response to the agent after a period of days to weeks. This may explain the dramatic responses noted initially by patients early in topical corticosteroid treatment and an apparent diminished response with time. Tolerance is reversible and may be attenuated by interrupted or cyclic schedules of application of triamcinolone creams or ointments for chronic dermatologic conditions.

Cases of elevated hepatic enzymes (usually reversible upon discontinuation) and hepatomegaly have been associated with corticosteroid receipt such as triamcinolone.^[26]

Allergic contact dermatitis with topical corticosteroids such as triamcinolone is usually diagnosed by observing a failure to heal. Appropriate diagnostic patch testing may help with the diagnosis.

Dizziness and anemia have been reported with corticosteroid use such as triamcinolone. Corticosteroids may decrease serum concentrations of vitamin C (ascorbic acid) and vitamin A, which may rarely produce symptoms of vitamin A deficiency or vitamin C deficiency. Some loss of folic acid may also be caused by corticosteroid use; glossitis may be noted.

Pentoxifylline

Pentoxifylline is classified as FDA pregnancy risk category C. No controlled studies of pentoxifylline use have been conducted in women who are pregnant. Therefore, caution should be exercised when the drug is used during pregnancy.^[6]

Triamcinolone Acetonide

Systemic triamcinolone use should be approached with caution during pregnancy and should be used during pregnancy only when the anticipated benefit outweighs the potential fetal risk. Complications, including cleft palate, still birth, and premature abortion, have been reported when systemic corticosteroids, including triamcinolone, were administered during pregnancy in animal studies. If systemic triamcinolone must be used chronically during pregnancy, the potential risks should be discussed with the patient. Infants born to women receiving large doses of systemic corticosteroids during pregnancy should be monitored for signs of adrenal insufficiency, and appropriate therapy should be initiated, if necessary.^{[27][12][22] [26]}Caution is also recommended with the use of inhaled and respiratory triamcinolone.^[11][15] Low-dose inhaled corticosteroids are considered first line therapy for control of mild persistent asthma during pregnancy. Data on the use of medium to high dose inhaled corticosteroid use during pregnancy are limited. However, dose titration may be considered for those with moderate to severe persistent asthma, preferably using budesonide. Budesonide is preferred over other inhaled corticosteroids due to availability of more safety information during pregnancy. However, there are no data to indicate safety concerns with other inhaled corticosteroids, and maintaining a previously established treatment regimen may be more beneficial to the patient.^[28] Selection of any pharmacologic treatment for asthma control during pregnancy should include the specific needs of the patient, based on an individual evaluation, and consideration of the potential benefits or risks to the fetus. Topical use of triamcinolone during pregnancy should also be approached with caution. Topical corticosteroids, including triamcinolone, should not be used in large amounts, on large areas, or for prolonged periods of time in pregnant women. Guidelines recommend mild to moderate potency topical agents over potent corticosteroids, which should be used in short durations. Fetal growth restriction and a significantly increased risk of low birthweight has been reported with use of potent or very potent topical corticosteroids during the third trimester, particularly when using more than 300 grams. Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals.^{[21][14][10][23]}

Pentoxifylline

Pentoxifylline and its metabolites are excreted into human milk. According to the manufacturer, pentoxifylline has been shown to be tumorigenic in rats; therefore, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.^[6] A single dose of extended-release pentoxifylline was given to 5 women who had been breast-feeding for at least 6 weeks. Data from this study indicate an exclusively breastfed infant would receive about 2% of the maternal-adjusted dosage.^[7] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

Triamcinolone Acetonide

There are no available data on the presence of triamcinolone in human milk following systemic, inhaled, or nasal administration, the effects on the breast-fed infant, or the effects on milk production.^{[27][12][22][17][11][15]} Reviewers and an expert panel consider inhaled and oral corticosteroids acceptable to use during breast-feeding.^[29][30][28] Low-dose inhaled corticosteroids are considered first line therapy for control of mild persistent asthma during lactation. Due to greater availability of data, budesonide is the preferred agent in this population. However, there are no data to indicate safety concerns with other inhaled corticosteroids and maintaining a previously established treatment regimen may be more beneficial to the patient.^[28] It is not known whether topical administration of triamcinolone could result in sufficient systemic absorption to produce detectable quantities in breast milk.^{[21] [14][10]} However, most dermatologists stress that topical corticosteroids can be safely used during lactation and breast-feeding.^[31] If applied topically, care should be used to ensure the infant will not come into direct contact with the area of application, such as the breast. Increased blood pressure has been reported in an infant whose mother applied a high potency topical corticosteroid ointment directly to the nipples. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breastfeeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

Store this medication in its original container at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.

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