Dermatitis TN Cream

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.

Niacinamide

Niacin (nicotinic acid or 3-pyridinecarboxylic acid) is a B-complex vitamin. Good dietary sources of niacin are animal proteins, beans, green vegetables, liver, mushrooms, peanuts, whole wheat, and unpolished rice. Niacin is also present in cereal grains but is largely bound to plant proteins, and thus is poorly absorbed after ingestion. Niacin is one of the substances used in the enrichment of refined flour, and our dietary intake of pre-formed niacin comes primarily from enriched grains. However, the body’s niacin requirement is also met by the biosynthesis of niacin from tryptophan, an amino acid. For example, milk and eggs do not contain niacin, but do contain large amounts of tryptophan from which niacin is derived. Each 60 mg of excess tryptophan (after protein synthesis) is converted to approximately 1 mg of niacin. Synthesis of the vitamin from tryptophan in proteins supplies roughly half the niacin requirement in man. Iron-deficiency or inadequate pyridoxine or riboflavin status will decrease the conversion of tryptophan to niacin and may contribute to deficiency, due to an interdependence of coenzymes in the niacin production pathway. A late and serious manifestation of niacin deficiency is pellagra, a clinical symptom complex principally affecting the GI tract, skin, and CNS, producing symptoms of diarrhea, dermatitis, and dementia, respectively. Pellagra may result from a niacin- and protein-deficient diet, isoniazid therapy, or certain diseases that result in poor utilization of tryptophan. Pellagra was the only vitamin-deficiency disease to ever reach epidemic proportions in the US; pellagra is rare today in industrialized countries due to the enrichment of refined flours.

Several synonyms for niacin and niacinamide exist. Synthetic niacin could be produced by the oxidation of nicotine, and the term ‘nicotinic acid’ evolved. Scientists also coined the terms ‘nicotinamide’ and ‘niacinamide’ for the amide form of nicotinic acid. The term ‘niacin’ has been used generically since the 1940’s to label foods and to avoid association of the vitamins with the nicotine alkaloid from tobacco. Thus the name ‘niacin’ has been used to denote both chemical forms, which are equivalent as vitamins on a weight basis. Both nicotinic acid and nicotinamide are synthesized for inclusion in nutritional supplements. However, since nicotinic acid and nicotinamide have different pharmacologic properties outside of their use as vitamins, it is important to distinguish between the two forms in pharmaceutical products.

In clinical medicine, nicotinic acid is used as an antilipemic, but nicotinamide (niacinamide) is not effective for this purpose. Nicotinic acid was the first hypolipidemic agent shown to decrease the incidence of secondary myocardial infarction (MI) and reduce total mortality in MI patients. However, no incremental benefit of coadministration of extended-release niacin with lovastatin or simvastatin on cardiovascular morbidity and mortality over and above that demonstrated for extended-release niacin, simvastatin, or lovastatin monotherapy has been established. In addition, the AIM-HIGH trial demonstrated that the concurrent use of extended-release niacin (1500—2000 mg/day PO) and simvastatin does not result in a greater reduction in the incidence of cardiovascular events than simvastatin alone. These results are consistent with those of the larger HPS2-THRIVE trial in which the addition of extended-release niacin to effective statin-based therapy did not result in a greater reduction in the incidence of cardiovascular events. Furthermore, there was an increased risk of serious adverse events including an increased incidence of disturbances in diabetes control and diabetes diagnoses, as well as serious gastrointestinal, musculoskeletal, dermatological, infectious, and bleeding adverse events. There was also a statistically insignificant 9% proportional increase in the incidence of death from any cause in the niacin group. The ARBITER 6-HALTS trial demonstrated that the addition of extended-release niacin 2000 mg/day to statins results in significant regression in atherosclerosis as measured by carotid intima-media thickness, and is superior to the combination of ezetimibe and a statin. In an MRI study, the addition of extended-release niacin 2000 mg/day to statin therapy resulted in a significant reduction in carotid wall area compared to placebo. However, the NIA Plaque study, which was presented at the American Heart Association (AHA) 2009 Scientific Sessions, did not find a significant reduction in the progression of atherosclerosis associated with the addition of niacin to statin therapy as compared to statin monotherapy. Additionally, nicotinic acid has been used as a therapy for tinnitus, but efficacy data are scant. Some sustained-release nicotinic acid formulations have a lower incidence of flushing but a higher incidence of hepatotoxicity when compared to immediate-release forms. Some dosage forms are available without prescription. The FDA officially approved niacin in 1938.

Triamcinolone Acetonide

Corticosteroids exhibit anti-inflammatory, antipruritic, and vasoconstrictive properties. At the cellular level, corticosteroids induce peptides called lipocortin’s. Lipocortin 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.

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.

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, hydroxy eicosatetraenoic 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 bronchodilator properties.

Niacinamide

Dietary requirements for niacin can be met by the ingestion of either nicotinic acid or nicotinamide; as vitamins, both have identical biochemical functions. As pharmacologic agents, however, they differ markedly. Nicotinic acid is not directly converted into nicotinamide by the body; nicotinamide is only formed as a result of coenzyme metabolism. Nicotinic acid is incorporated into a coenzyme known as nicotinamide adenine dinucleotide (NAD) in erythrocytes and other tissues. A second coenzyme, nicotinamide adenine dinucleotide phosphate (NADP), is synthesized from NAD. These two coenzymes function in at least 200 different redox reactions in cellular metabolic pathways. Nicotinamide is released from NAD by hydrolysis in the liver and intestines and is transported to other tissues; these tissues use nicotinamide to produce more NAD as needed. Together with riboflavin and other micronutrients, the NAD and NADP coenzymes work to convert fats and proteins to glucose and assist in the oxidation of glucose.

In addition to its role as a vitamin, niacin (nicotinic acid) has other dose-related pharmacologic properties. Nicotinic acid, when used for therapeutic purposes, acts on the peripheral circulation, producing dilation of cutaneous blood vessels and increasing blood flow, mainly in the face, neck, and chest. This action produces the characteristic “niacin-flush”. Nicotinic acid-induced vasodilation may be related to release of histamine and/or prostacyclin. Histamine secretion can increase gastric motility and acid secretion. Flushing may result in concurrent pruritus, headaches, or pain. The flushing effects of nicotinic acid appear to be related to the 3-carboxyl radical on its pyridine ring. Nicotinamide (niacinamide), in contrast to nicotinic acid, does not contain a carboxyl radical in the 3 position on the pyridine ring and does not appear to produce flushing.

Nicotinic acid may be used as an antilipemic agent, but nicotinamide does not exhibit hypolipidemic activity. Niacin reduces total serum cholesterol, LDL, VLDL, and triglycerides, and increases HDL cholesterol. The mechanism of nicotinic acid’s antilipemic effect is unknown but is unrelated to its biochemical role as a vitamin. One of nicotinic acid’s primary actions is decreased hepatic synthesis of VLDL. Several mechanisms have been proposed, including inhibition of free fatty acid release from adipose tissue, increased lipoprotein lipase activity, decreased triglyceride synthesis, decreased VLDL-triglyceride transport, and an inhibition of lipolysis. This last mechanism may be due to niacin’s inhibitory action on lipolytic hormones. Nicotinic acid possibly reduces LDL secondary to decreased VLDL production or enhanced hepatic clearance of LDL precursors. Nicotinic acid elevates total HDL by an unknown mechanism, but is associated with an increase in serum levels of Apo A-I and lipoprotein A-I, and a decrease in serum levels of Apo-B. Nicotinic acid is effective at elevating HDL even in patients whose only lipid abnormality is a low-HDL value. Niacin does not appear to affect the fecal excretion of fats, sterols, or bile acids. Clinical trial data suggest that women have a greater hypolipidemic response to niacin therapy than men at equivalent doses.

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. 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. 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. 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. 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. 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. 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. Additionally, clearance of corticosteroids is decreased in patients with hypothyroidism and increased in hyperthyroidism.

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. 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.

Do not use high doses of corticosteroids such as triamcinolone hex acetonide 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 hemi succinate.

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 anti-infective 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 anti-infective 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. 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.

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.

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. 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.

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.

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

Niacinamide

Patients who have a known hypersensitivity to niacin or any product component should not be given the drug.

While steady state plasma concentrations of niacin are generally higher in women than in men, the absorption, metabolism, and excretion of niacin appears to be similar in both genders. Women have been reported to have greater response to the lipid-lowering effects of nicotinic acid (niacin) when compared to men.

No overall differences in safety and efficacy were observed between geriatric and younger individuals receiving niacin. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity for some older individuals cannot be ruled out.

Niacin is contraindicated in patients who have significant or unexplained hepatic disease. Patients who consume large quantities of ethanol (alcoholism), who have risk factors for hepatic disease, or who have a past-history of gallbladder disease, jaundice, or hepatic dysfunction may receive niacin with close clinical observation. Elevations in liver function tests (LFTs) appear to be dose-related. Some sustained-release nicotinic acid (niacin) formulations have a higher incidence of hepatotoxicity when compared to immediate-release dosage forms. Extended-release nicotinic acid preparations (e.g., Niaspan, Slo-Niacin) should not be substituted for equivalent dosages of immediate-release (crystalline) niacin (e.g., Niacor and others). Follow the manufacturer-recommended initial dosage titration schedules for extended-release products, regardless of previous therapy with other niacin formulations. Monitor LFTs in all patients during therapy at roughly 6-month intervals or when clinically indicated. If transaminase levels (i.e., ALT or AST) rise to 3 times the upper limit of normal, or clinical symptoms of hepatic dysfunction are present, niacin should be discontinued.

Nicotinic acid (niacin) can stimulate histamine release, which, in turn, can stimulate gastric acid output. Niacin is contraindicated in patients with active peptic ulcer disease (PUD) because it can exacerbate PUD symptoms. Use niacin with caution in patients with a past history of peptic ulcer disease or in those on maintenance therapy to prevent PUD recurrence.

Due to its vasodilatory action, nicotinic acid (niacin) should be used with caution in those patients with uncorrected hypotension (or predisposition to orthostatic hypotension), acute myocardial infarction, or unstable angina, particularly when vasodilator medications such as nitrates, calcium channel blockers, or adrenergic blocking agents are Coad ministered (see Drug Interactions). Because the vasodilatory response to niacin may be more dramatic at the initiation of treatment, activities requiring mental alertness (e.g., driving or operating machinery) should not be undertaken until the response to niacin is known.

Niacin, especially in high doses, can cause hyperuricemia. Niacin should be prescribed cautiously to patients with gout (or predisposed to gout). These individuals should be advised not to purchase OTC forms of niacin without the guidance of a physician.

Niacin, especially in high doses, can cause hypophosphatemia. Although the reductions in phosphorus levels are usually transient, clinicians should monitor serum phosphorus periodically in those at risk for this electrolyte imbalance.

Rare cases of rhabdomyolysis have been reported in patients taking lipid-altering dosages of nicotinic acid (niacin) and statin-type agents concurrently (see Drug Interactions). Patients undergoing combined therapy should be carefully monitored for muscle pain, tenderness, or weakness, particularly in the early months of treatment or during periods of upward dose titration of either drug. While periodic CPK and potassium determinations may be considered, there is no evidence that these tests will prevent the occurrence of severe myopathy. If rhabdomyolysis occurs, the offending therapies should be discontinued.

Niacin, especially in high doses, may cause hyperglycemia. Niacin should be prescribed cautiously to patients with diabetes mellitus. These individuals should be advised not to purchase OTC forms of niacin without the guidance of a physician. Niacin has also been reported to cause false-positive results in urine glucose tests that contain cupric sulfate solution (e.g., Benedict’s reagent, Clingiest).

Niacin therapy has been used safely in children for the treatment of nutritional niacin deficiency. However, the safety and effectiveness of nicotinic acid for the treatment of dyslipidemias have not been established in neonates, infants and children <= 16 years of age. Nicotinic acid has been used for the treatment of dyslipidemia in pediatric patients under select circumstances. Children may have an increased risk of niacin-induced side effects versus adult populations. At least one pediatric study has concluded that niacin treatment should be reserved for treatment of severe hypercholesterolemia under the close-supervision of a lipid specialist. In general, the National Cholesterol Education Program (NCEP) does not recommend drug therapy for the treatment of children with dyslipidemias until the age of 10 years or older.

Since niacin is an essential nutrient, one would expect it to be safe when administered during pregnancy at doses meeting the recommended daily allowance (RDA). Niacin is categorized as pregnancy category A under these conditions. However, when used in doses greater than the RDA for dyslipidemia, or when used parenterally for the treatment of pellagra, niacin is categorized as pregnancy category C. Most manufacturers recommend against the use of niacin in dosages greater than the RDA during pregnancy. The potential benefits of high-dose niacin therapy should be weighed against risks, since toxicological studies have not been performed.

According to a manufacturer of niacin (Niaspan), although no studies have been conducted in nursing mothers, excretion into human milk is expected. The manufacturer recommends the discontinuation of nursing or the drug due to serious adverse reactions that may occur in nursing infants from lipid-altering doses of nicotinic acid. Niacin, in the form of niacinamide, is excreted in breast milk in proportion to maternal intake. Niacin supplementation is only needed in those lactating women who do not have adequate dietary intake. The Recommended Daily Allowance (RDA) of the National Academy of Science for niacin during lactation is 20 mg. There are no safety data regarding the use of nicotinic acid in doses above the RDA during breast-feeding. 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.

Use niacin with caution in patients with renal disease (renal failure or severe renal impairment) since niacin metabolites are excreted through the kidneys. It appears that no special precautions are needed when administering niacin to meet the recommended nutritional daily allowance (RDA). Use caution when administering higher dosages.

Nicotinic acid (niacin) occasionally causes slight decreases in platelet counts or increased prothrombin times and should be used with caution in patients with thrombocytopenia, coagulopathy, or who are receiving anticoagulant therapy. Patients who will be undergoing surgery should have blood counts monitored. Nicotinic acid (niacin) is contraindicated in patients with arterial bleeding.

The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities (LTCFs). According to OBRA, glucose and liver function tests should be evaluated regularly because niacin interferes with glucose control, can aggravate diabetes, and can exacerbate active gallbladder disease and gout. Flushing is a common side effect of niacin.

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.Caution is also recommended with the use of inhaled and respiratory triamcinolone. 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. 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.

Niacinamide

Since niacin is an essential nutrient, one would expect it to be safe when administered during pregnancy at doses meeting the recommended daily allowance (RDA). Niacin is categorized as pregnancy category A under these conditions. However, when used in doses greater than the RDA for dyslipidemia, or when used parenterally for the treatment of pellagra, niacin is categorized as pregnancy category C. Most manufacturers recommend against the use of niacin in dosages greater than the RDA during pregnancy. The potential benefits of high-dose niacin therapy should be weighed against risks, since toxicological studies have not been performed.

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. Reviewers and an expert panel consider inhaled and oral corticosteroids acceptable to use during breast-feeding. 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. It is not known whether topical administration of triamcinolone could result in sufficient systemic absorption to produce detectable quantities in breast milk. However, most dermatologists stress that topical corticosteroids can be safely used during lactation and breast-feeding. 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 breastfeeding, 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.

Niacinamide

According to a manufacturer of niacin (Niaspan), although no studies have been conducted in nursing mothers, excretion into human milk is expected. The manufacturer recommends the discontinuation of nursing or the drug due to serious adverse reactions that may occur in nursing infants from lipid-altering doses of nicotinic acid. Niacin, in the form of niacinamide, is excreted in breast milk in proportion to maternal intake. Niacin supplementation is only needed in those lactating women who do not have adequate dietary intake. The Recommended Daily Allowance (RDA) of the National Academy of Science for niacin during lactation is 20 mg. There are no safety data regarding the use of nicotinic acid in doses above the RDA during breast-feeding. 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

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 of drugs 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, nausea, 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.

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. 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. 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. 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. 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. 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.

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. A rash (unspecified) was noted in 2.5% of intranasal triamcinolone recipients as compared with 1.7% of placebo recipients. 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. 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).

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. Use of intranasal triamcinolone is not recommended until healing has occurred for patients who have experienced recent nasal septal ulcers, nasal surgery, or trauma. Skin ulcer may develop in patients with markedly impaired circulation who use topical corticosteroids.

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.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. 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.

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. 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.

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.

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. 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. 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. 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 bio microscopy 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).

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.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.

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.

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.

Niacinamide

Niacin (nicotinic acid), when administered in doses equivalent to the RDA, is generally nontoxic. Niacinamide also rarely causes adverse reactions. Larger doses of nicotinic acid (i.e., >= 1 g/day PO), can cause adverse reactions more frequently. Differences in adverse reaction profiles can be explained by the fact that nicotinic acid has pharmacologic properties that are different from niacinamide.

Peripheral vasodilation is a well-known adverse reaction to niacin. It is characterized by flushing; warmth; and burning or tingling of the skin, especially in the face, neck, and chest. Hypotension can be caused by this vasodilation. Patients should avoid sudden changes in posture to prevent symptomatic or orthostatic hypotension. Dizziness and/or headache, including migraine, can occur. Cutaneous flushing is more likely to occur with immediate-release preparations as opposed to sustained-release ones and also increases in incidence with higher doses. Following 4-weeks of maintenance therapy of 1500 mg daily, patients receiving immediate release niacin averaged 8.6 flushing events compared to 1.9 events in the Niaspan group. In placebo-controlled studies of Niaspan, flushing occurred in 55—69% of patients compared to 19% of patients receiving placebo. Flushing was described as the reason for discontinuing therapy for 6% of patients receiving Niaspan in pivotal studies. These reactions usually improve after the initial 2 weeks of therapy. Some patients develop generalized pruritus as a result of peripheral flushing. In placebo controlled trials, pruritus was reported in 0—8% of patients receiving Niaspan compared to 2% of patients taking placebo. Rash (unspecified) was reported in 0—5% of patients in the Niaspan group compared to no patients in the placebo group. Patients should avoid ethanol or hot drinks that can precipitate flushing. Flushing can be minimized by taking niacin with meals, using low initial doses, and increasing doses gradually. If necessary, taking one aspirin (e.g., 325 mg) 30 minutes before each dose can help prevent or reduce flushing. Spontaneous reports with niacin suggest that flushing may also be accompanied by symptoms of dizziness or syncope, sinus tachycardia, palpitations, atrial fibrillation, dyspnea, diaphoresis, chills, edema, or exacerbations of angina. On rare occasions, cardiac arrhythmias or syncope has occurred. Hypersensitivity or anaphylactoid reactions have been reported rarely during niacin therapy; episodes have included one or more of the following features: anaphylaxis, angioedema, urticaria, flushing, dyspnea, tongue edema, laryngeal edema, face edema, peripheral edema, laryngospasm, maculopapular rash, and vesiculobullous rash (vesicular rash, bullous rash).

Niacin can produce a variety of GI effects, such as nausea/vomiting, abdominal pain, diarrhea, bloating, dyspepsia, or flatulence, when taken in large doses. Eructation and peptic ulcer has been reported with post-marketing experience of Niaspan. Compared to placebo, diarrhea was reported in 7—14% (vs. 13%), nausea in 4—11% (vs. 7%), and vomiting in 0—9% (vs. 4%) of patients receiving Niaspan. These effects are attributed to increased GI motility and may disappear after the first 2 weeks of therapy. Administering niacin with meals can reduce these adverse reactions.

Jaundice can result from chronic liver damage caused by niacin. It has been shown that elevated hepatic enzymes occur more frequently with some sustained-release niacin than with immediate-release products. However, in a study of 245 patients receiving Niaspan (doses ranging from 500—3000 mg/day for a mean of 17 weeks) no patients with normal serum transaminases at baseline experienced elevations to > 3x the upper limit of normal. Sustained-release products have been associated with post-marketing reports of hepatitis and jaundice, including Niaspan. Regular liver-function tests should be performed periodically. The changes in liver function induced by niacin are typically reversible with drug discontinuation. However, rare cases of fulminant hepatic necrosis and hepatic failure have been reported. Some cases have occurred after the substitution of sustained-release dosage forms for immediate-release products at directly equivalent doses; these dosage forms are not bioequivalent. Dosage titration schedules must be observed for any patient switched to a sustained-release niacin product, even if the patient was previously taking immediate-release therapy.

Niacin interferes with glucose metabolism and can result in hyperglycemia. This effect is dose-related. During clinical anti-lipemic trials, increases in fasting blood glucose above normal occurred frequently (e.g., 50%) during niacin therapy. Some patients have required drug discontinuation due to hyperglycemia or exacerbation of diabetes. In the AIM-HIGH trial of patients with stable cardiovascular disease, the incidence of hyperglycemia (6.4% vs. 4.5%) and diabetes mellitus (3.6% vs. 2.2%) was higher in niacin plus simvastatin-treated patients compared to the simvastatin plus placebo group. Close blood glucose monitoring is advised for diabetic or potentially diabetic patients during treatment with niacin; adjustment of diet and/or antidiabetic therapy may be necessary.

Niacin, especially in high doses, can cause hyperuricemia. Gout has been reported in post-marketing surveillance of Niaspan. Therefore, patients predisposed to gout should be treated with caution.

Niacin, especially in high doses (>= 2 g/day PO), can cause hypophosphatemia (mean decrease 13%). Serum phosphorus concentrations should be monitored periodically in patients at risk for hypophosphatemia.

Nicotinic acid (niacin) occasionally causes slight decreases in platelet counts (mean reduction 11%) or increased prothrombin times (mean increase 4%), especially in high doses (>= 2 g/day PO). Rarely do these reactions result in coagulopathy or thrombocytopenia, but clinically significant effects might occur in patients with other risk factors or who are predisposed to these conditions.

Asthenia, nervousness, insomnia, and paresthesia have been reported during niacin therapy. Rare cases of rhabdomyolysis have been reported in patients taking niacin (nicotinic acid) in doses >=1 g/day PO and HMG-CoA reductase inhibitors (i.e., ‘statins’) concurrently. In the AIM-HIGH trial, 4 cases (0.2%) of rhabdomyolysis were reported in the niacin; simvastatin group compared with 1 case in the simvastatin plus placebo group. Rhabdomyolysis may present as myopathy (myalgia, myasthenia, muscle cramps, muscle weakness, muscle tenderness, fatigue), elevations in creatinine phosphokinase (CPK), or renal dysfunction (renal tubular obstruction). Toxicity to the skeletal muscle occurs infrequently but can be a serious adverse reaction. This toxicity appears to be reversible after discontinuation of therapy.

Niacin also has been associated with a variety of ophthalmic adverse effects including blurred vision and macular edema.

Although uncommon, niacin may be associated with skin hyperpigmentation or acanthosis nigricans. Dry skin (xerosis) also has been reported during post-marketing surveillance of Niaspan.

During clinical trials, increased cough was reported in <2—8% (vs. 6%) of patients receiving Niaspan compared to placebo.

Store this medication 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.

1.Niaspan (niacin extended-release) tablet package insert. North Chicago, IL: Abbott Laboratories; 2015 Apr.
2.HPS2-THRIVE Collaborative Group. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med 2014;371:203-12.
3.Taylor AJ, Villines TC, Stanck EJ, et al. Extended-release niacin or ezetimibe and carotid intima-media thickness. N Engl J Med 2009. Epub ahead of print, doi:10.1056/NEJMoa907569.
4.Lee JMS, Robson MD, Yu LM, et al. Effects of high-dose modified-release nicotinic acid on atherosclerosis and vascular function: A randomized, placebo-controlled, magnetic resonance imaging study. J Am Coll Cardiol 2009;54:1787—94.
5.McKenney JM, et al. A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients. JAMA 1994;271:672-7.
6.Schimmer B, Parker K. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limbird LE, Molinoff PB, et al., eds. Goodman and Gilman’s the Pharmacological Basis of Therapeutics, 10th edition. New York: McGraw Hill, 2001;1649-1674.
7.Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci (Lond). 1998;94(6):557-572.
8.National Asthma Education and Prevention Program Expert Panel 3. Expert panel report 3: guidelines for the diagnosis and management of asthma. Bethesda (MD): National Institutes of Health. National Heart, Lung, and Blood Institute; 2007 Aug. NIH Publication No. 07-4051.
9.Bond DW, Charlton CPJ. Benign intracranial hypertension secondary to nasal fluticasone propionate. BMJ 2001;322 (7291):987.
10.Patradoon-Ho P, Gunasekera H, Ryan MM. Inhaled corticosteroids, adrenal suppression and benign intracranial hypertension. Med J Aust 2006;185:279-280
11.Triamcinolone acetonide ointment package insert. Melville, NY: E. Fougera & Co., 2011 Oct.
12.Azmacort (triamcinolone acetonide) package insert. North Chicago, IL: Abbott Laboratories; 2007 Sept.
13.Kenalog-40 (triamcinolone acetonide) injection package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2018 Mar.
14.Shulman DI, Palmert MR, Kemp SF. Adrenal insufficiency: still a cause of morbidity and death in childhood. Pediatrics 2007;119(2):e484-494.
15.Triamcinolone acetonide cream package insert. Melville, NY: E. Fougera & Co.; 2011 Sept
16.Nasacort AQ (triamcinolone acetonide) nasal spray package insert. Bridgewater, NJ: Sanofi-aventis U.S. LLC; 2013 July.
17.Nasacort Allergy 24HR (triamcinolone acetonide) OTC nasal spray package insert. Chattanooga, TN: Chattem, Inc., a wholly-owned subsidiary of Sanofi-Aventis; 2016 Sept.
18.Zilretta (triamcinolone acetonide extended-release injectable suspension). Burlington, MA: Flexion Therapeutics, Inc.; 2019 Dec.
19.Hengge UR, Ruzicka T, Schwartz RA. Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol 2006;54:1-15.
20.Morley KW, Dinulos JG. Update on topical glucocorticoid use in children. Curr Opin Pediatr 2012;24(1):121-128
21.Hanania NA, Chapman KR, Kesten S. Adverse effects of inhaled corticosteroids. Am J Med 1995;98:196-207.
22.Kenalog (triamcinolone acetonide) topical aerosol package insert. Jacksonville, FL: Ranbaxy; 2011 July.
23.Triesence (triamcinolone acetonide injection for ophthalmic use) package insert. Fort Worth, TX: Alcon Laboratories, Inc.; 2018 Dec.
24.Murase JE, Heller MM, Butler DC. Safety of dermatologic medications in pregnancy and lactation: Part I. Pregnancy. J Am Acad Dermatol. 2014;70:401.e1-14. Review.
25.The American Geriatrics Society 2019 Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019;00:1-21.
26.Health Care Financing Administration. Interpretive Guidelines for Long-term Care Facilities. Title 42 CFR 483.25(l) F329: Unnecessary Drugs. Revised 2015.
27.Zilretta (triamcinolone acetonide extended-release injectable suspension). Burlington, MA: Flexion Therapeutics, Inc.; 2019 Dec.
28.Colletti RB, Neufeld EJ, Roff NK, et al. Niacin treatment of hypercholesterolemia in children. Pediatrics 1993;92:78-82.
29.Expert Panel: National Cholesterol Education Program. Report of the expert panel on blood cholesterol levels in children and adolescents. Pediatrics 1992;89(suppl 2):525-84.
30.Niacinamide. In: Drugs in Pregnancy and Lactation. A Reference Guide to Fetal and Neonatal Risk. Briggs GG, Freeman RK, Yaffe SJ, (eds.) 7th ed., Philadelphia PA: Lippincott Williams and Wilkins; 2005:1140-1
31.Aristospan (triamcinolone hexacetonide) 5 mg/ml injection package insert. Princeton, NJ: Sandoz Inc.; 2014 Apr.
32.NAEPP Working Group Report on Managing Asthma During Pregnancy. Recommendations for Pharmacologic Treatment-Update 2004. NIH Publication No. 05-3279. Bethesda, MD: U.S. Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute, 2004
33.Greenberger PA, Patterson R. The management of asthma during pregnancy and lactation. Clin Rev Allergy 1987;5:317-24.
34.Ellsworth A. Pharmacotherapy of asthma while breastfeeding. J Hum Lact 1994;10:39-41.
35.Butler DC, Heller MM, Murase JE. Safety of dermatologic medications in pregnancy and lactation: Part II. Lactation. J Am Acad Dermatol. 2014;70:417.e1-10. Review.
36.Conn HO, Poynard T. Corticosteroids and peptic ulcer: meta-analysis of adverse events during steroid therapy. J Intern Med 1994;236:619-32.
37.Abramson N, Melton B. Leukocytosis: basic of clinical assessment. Am Fam Physician 2000;62:2053-60.
38.Shoenfeld Y, Gurewich Y, Gallant LA, et al. Prednisone-induced leukocytosis. Influenced of dosage, method and duration of administration on the degree of leukocytosis. Am J Med 1981;71:773-8.
39.Prednisone tablet package insert. Salisbury, MD: Cadista Pharmaceuticals Inc.; 2016 Mar.
40.Wei L, MacDonald TM, Walker BR. Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease. Ann Intern Med 2004;141:764-70.
41.Kenalog-10 (triamcinolone acetonide) injection package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2018 Jun.
42.Cumming RG, Mitchell P, Leeder SR, et al. Use of inhaled corticosteroids and the risk of cataracts. N Engl J Med 1997;337:8-14.
43.Trivaris (triamcinolone acetonide injectable suspension) package insert. Irvine, CA: Allergan, Inc.; 2008 Jun.
44.Niacor (Niacin tablets) package insert. Minneapolis, MN: Upsher-Smith Laboratories, Inc.; 2000 Feb.