Acne Keto Cream

Ketoconazole

Ketoconazole is an imidazole antifungal agent and is available as an oral tablet and various topical formulations. Oral ketoconazole has been associated with fatal hepatotoxicity, adrenal gland suppression, and harmful drug interactions. Due to the potential for severe adverse events, oral ketoconazole should only be used to treat serious blastomycosis, histomycosis, coccidioidomycosis, paracoccidioidomycosis, and chromomycosis infections when no other antifungal therapies are available. The topical formulations are indicated for the treatment of tinea corporis, tinea cruris, tinea pedis, tinea versicolor, mucocutaneous candidiasis, seborrheic dermatitis, and dandruff. Ketoconazole was FDA-approved in 1981.12345

Niacinamide

Niacin (nicotinic corrosive or 3-pyridinecarboxylic corrosive) is also vitamin B3, a B-complex vitamin. Dietary sources of niacin include animal proteins, beans, green vegetables, liver, mushrooms, peanuts, whole wheat, and unpolished rice. Niacin is additionally found in cereal grains but is generally bound to plant proteins, and poorly absorbed after ingestion. Niacin is used to enrich flour, and dietary intake of pre-formed niacin comes from enriched grains. The body’s niacin needs are met by the biosynthesis of niacin from tryptophan, an amino corrosive. Eggs, for example, don’t contain niacin, but do contain tryptophan, where niacin is derived. Each 60 mg of tryptophan (after protein union) is converted to around 1 mg of niacin. A combination of the vitamin from tryptophan in proteins supplies generally half of the body’s niacin requirements. Insufficient pyridoxine or riboflavin will slow the conversion of tryptophan to niacin and may contribute to deficiency due to interdependency of coenzymes within the niacin generation pathway. A sign of niacin deficiency is pellagra, a clinical indication influencing the GI tract, skin, and CNS, creating side effects like loose bowels, dermatitis, and dementia, independently. Pellagra may result from a niacin-and protein-deficient caloric intake, isoniazid treatment, or certain maladies that result in destitute utilization of tryptophan. Pellagra is the first vitamin-deficiency infection to ever reach scourge extents within the US; pellagra is uncommon due to the enrichment of refined flours.

A few equivalents of niacin and niacinamide exist. Synthetic niacin may be delivered by the oxidation of nicotine, hence the term ‘nicotinic acid’. Researchers coined the terms ‘nicotinamide’ and ‘niacinamide’ for the amide-like structure of nicotinic corrosive. The term ‘niacin’ has been utilized since the 1940’s to avoid affiliation of the vitamins with the nicotine alkaloid from tobacco. Thus the word ‘niacin’ has been used to represent both chemical structures. Both nicotinic corrosive and nicotinamide are synthesized for health supplements. Nicotinic corrosive and nicotinamide have distinctive pharmacologic properties outside of their role as vitamins, and it is critical to recognize between the two structures in pharmaceutical contexts.

In clinical medication, nicotinic corrosive is utilized as an antilipemic, but nicotinamide (niacinamide) isn’t successful for this reason. Nicotinic acid was the primary hypolipidemic operator appeared to diminish the rate of auxiliary myocardial localized necrosis (MI) and decrease add up to mortality in MI patients. No incremental advantage of the co-administration of extended-release niacin with lovastatin or simvastatin on cardiovascular failure and mortality repeatedly illustrated for extended-release niacin, simvastatin, or lovastatin monotherapy has been established. In expansion, the AIM-HIGH trial illustrated that the concurrent use of extended-release niacin (1500—2000 mg/day PO) and simvastatin does not result in a more prominent reduction of the rate of cardiovascular events than simvastatin alone. 6 These comes about are steady with those of the bigger HPS2-THRIVE trial in which the expansion of extended-release niacin to successful statin-based treatment did not result in a more noteworthy decrease within the frequency of cardiovascular occasions. Moreover, there was an expanded chance of genuine antagonistic occasions counting an expanded frequency of unsettling influences in diabetes control and diabetes analyze, as well as genuine gastrointestinal, musculoskeletal, dermatological, irresistible, and dying antagonistic occasions. There was too a factually insignificant 9% corresponding increment within the frequency of passing from any cause within the niacin gather. 7 The Mediator 6-HALTS trial illustrated that the expansion of extended-release niacin 2000 mg/day to statins comes about in critical relapse in atherosclerosis as measured by carotid intima-media thickness, and is predominant to the combination of ezetimibe and a statin. 8 In an MRI ponder, the expansion of extended-release niacin 2000 mg/day to statin treatment come about in a noteworthy lessening in carotid divider zone compared to fake treatment.

The National Institute on Aging Plaque Study (NIA Plaque), presented at the American Heart Affiliation (AHA) 2009 Scientific Sessions, did not discover a significant reduction within the movement of atherosclerosis related with the expansion of niacin to statin treatment as compared to statin monotherapy. Furthermore, nicotinic corrosive has been utilized as a treatment for tinnitus, but viability information are insufficient. A few sustained-release nicotinic corrosive definitions have a lower incidence of flushing but a better frequency of hepatotoxicity when compared to immediate-release forms.10 The FDA formally affirmed niacin in 1938.

Ketoconazole

Like other azole antifungals, ketoconazole exerts its effect by altering the fungal cell membrane. Ketoconazole inhibits ergosterol synthesis by interacting with 14-alpha demethylase, a cytochrome P-450 enzyme that is necessary for the conversion of lanosterol to ergosterol, an essential component of the membrane. In contrast, amphotericin B binds to ergosterol after it is synthesized. Inhibition of ergosterol synthesis results in increased cellular permeability, which causes leakage of cellular contents. Ketoconazole does not appear to have the same effects on human cholesterol synthesis. Other antifungal effects of azole compounds have been proposed11 and include: inhibition of endogenous respiration, interaction with membrane phospholipids, and inhibition of yeast transformation to mycelial forms. Other mechanisms may involve inhibition of purine uptake and impairment of triglyceride and/or phospholipid biosynthesis.12 At higher concentrations, ketoconazole may have a direct physiochemical effect on the fungal cell membrane, which leads to a fungicidal action.

Ketoconazole possesses actions that may make it useful in conditions other than fungal infections. Ketoconazole can inhibit sterol synthesis in humans including the synthesis of aldosterone, cortisol, and testosterone. Ketoconazole’s effects on testosterone synthesis occur at lower doses than do the effects on cortisol synthesis; doses of of 200—400 mg/day can inhibit testosterone secretion and doses of 400—600 mg/day have been shown to inhibit cortisol synthesis.1314 Ketoconazole acts at many of same steps as metyrapone and, in some sites, has been shown to be a more potent inhibitor.13Both ketoconazole and metyrapone affect multiple steps in the steroid-synthesis pathway, while finasteride appears to work at a single site. Ketoconazole has been used successfully for treating advanced prostate cancer.15 Finally, ketoconazole is a known potent inhibitor of thromboxane synthesis and has been used clinically to prevent ARDS in patients at high risk of this syndrome.

Niacinamide

Dietary necessities for niacin can be met by the ingestion of either nicotinic corrosive or nicotinamide; as vitamins, both have indistinguishable biochemical capacities. As pharmacologic operators, in any case, they vary extraordinarily. Nicotinic corrosive isn’t specifically changed over into nicotinamide by the body; nicotinamide is as it was shaped as a result of the coenzyme digestion system. Nicotinic corrosive is consolidated into a coenzyme known as nicotinamide adenine dinucleotide (NAD) in erythrocytes and other tissues. A moment coenzyme, nicotinamide adenine dinucleotide phosphate (NADP), is synthesized from NAD. These two coenzymes work in at slightest 200 distinctive redox responses in cellular metabolic pathways. Nicotinamide is discharged from NAD by hydrolysis within the liver and insides and is transported to other tissues; these tissues utilize nicotinamide to deliver more NAD as required. Along with riboflavin and other micronutrients, the NAD and NADP coenzymes work to change over fats and proteins to glucose and help with the oxidation of glucose.

Niacin (nicotinic acid) has other dose-related pharmacologic properties other than being a vitamin. Nicotinic acid, when utilized for restorative purposes, acts on the peripheral circulation, creating expansion of cutaneous blood vessels and expanding blood stream, primarily within the confront, neck, and chest. This activity produces the characteristic “niacin-flush”. Nicotinic acid-induced vasodilation may be related to the discharge 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 show to be related to the 3-carboxyl radical on its pyridine ring. Nicotinamide (niacinamide), as opposed to nicotinic acid, does not contain a carboxyl radical within the 3 positions on the pyridine ring and does not appear to produce flushing.

Nicotinic acid may be utilized as an antilipemic agent, but nicotinamide does not show hypolipidemic activity. Niacin reduces total serum cholesterol, LDL, VLDL, and triglycerides, and increments HDL cholesterol. The mechanism of nicotinic acid’s antilipemic impact is unknown but is irrelevant to its biochemical role as a vitamin. One of nicotinic acid’s essential activities is the diminished hepatic synthesis of VLDL. A few components have been proposed, counting hindrance of free greasy corrosive discharge from fat tissue, expanded lipoprotein lipase movement, diminished triglyceride blend, diminished VLDL-triglyceride transport, and restraint of lipolysis. This final component may be due to niacin’s inhibitory activity on lipolytic hormones. Nicotinic acid conceivably diminishes LDL auxiliary to diminished VLDL generation or upgraded hepatic clearance of LDL antecedents.

Nicotinic acid raises total HDL by an unknown component, but is related to an increment in serum levels of Apo A-I and lipoprotein A-I, and a diminish in serum levels of Apo-B. Nicotinic acid works at raising HDL in patients whose only lipid abnormality may be a low-HDL value. Niacin does not show up to influence the fecal excretion of fats, sterols, or bile acids. Clinical trial information proposes that women have a more prominent hypolipidemic reaction to niacin treatment than men at identical dosages.

Ketoconazole

Due to its potent inhibition of the hepatic isoenzyme CYP3A4, oral ketoconazole coadministration with other drugs metabolized by CYP3A4 should be done with extreme caution, if at all. Ketoconazole can cause elevated plasma concentrations of selected drugs metabolized via CYP3A4 which may prolong the QT interval, sometimes resulting in life-threatening ventricular arrhythmias such as torsade de pointes; use of ketoconazole with such drugs is contraindicated. Oral ketoconazole may also inhibit the metabolism of many other drugs, which could result in serious and potentially life-threatening adverse reactions, and use with selected drugs is also contraindicated.1 Due to the potential for harmful drug interactions and other serious adverse effects, oral ketoconazole should only be used to treat serious fungal infections when no other antifungal therapies are available.45 Systemic ketoconazole can prolong the QT interval. Use ketoconazole tablets with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, congenital long QT syndrome, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, older adult patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic disease may also be at increased risk for QT prolongation.

Ketoconazole oral tablets may cause adrenal insufficiency at doses of 400 mg/day and higher in adults. This effect is not shared with other azole antifungals. The recommended dose of 200 to 400 mg daily in adults should not be exceeded. Adrenal function should be monitored in patients with adrenal insufficiency or with borderline adrenal function and in patients under prolonged periods of stress (major surgery, intensive care, etc.).1 Due to the risk of adrenal insufficiency and other serious adverse effects, oral ketoconazole should only be used to treat serious fungal infections when no other antifungal therapies are available.

Ketoconazole should be used with caution in patients with known azole antifungals hypersensitivity. Hypersensitivity reactions may be due to the various vehicles present in the different ketoconazole formulations. Ketoconazole may have a cross sensitivity with other azole derivatives such as itraconazole, fluconazole, clotrimazole, and miconazole. In rare cases, patients receiving ketoconazole have reported hypersensitivity reactions and even anaphylaxis. Ketoconazole is contraindicated in patients who have previously demonstrated these reactions.

Avoid accidental ocular exposure of topical ketoconazole products. If ocular exposure occurs, treat by immediate flushing the affected eye with cool, clean water. Contact an ophthalmologist if eye irritation persists.

Some topical ketoconazole products are flammable. Due to the alcohol content of ketoconazole topical gel (e.g., Xolegel gel) and the alcohol, butane, and proprane content of ketoconazole topical foam (e.g., Extina foam), avoid fire, flame, or tobacco smoking during and immediately after the application of these ketoconazole products.

Dizziness or drowsiness occurs in some patients receiving systemic ketoconazole. Patients should be careful driving or operating machinery if they have these reactions.

Due to the risk of severe drug interactions and other serious adverse effects with ketoconazole oral tablets, ketoconazole oral tablets should not be a first-line treatment for any fungal infection in the geriatric patient.4 1 Systemic ketoconazole can prolong the QT interval. Geriatric patients may be at increased risk for QT prolongation and for serious drug-drug interactions that may increase the risk QT prolongation risk or may increase the risk for other serious side effects.1161718192021 The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, systemic azole antifungals should be used in the lowest possible dose for the shortest possible duration, particularly in patients receiving other medications known to interact with these medications. Increased monitoring may be required to identify and minimize the toxicity of warfarin, phenytoin, theophylline, or sulfonylureas when an azole antifungal is co-administered; other medications such as rifampin and cimetidine may decrease the therapeutic effect of the antifungal. Some drug-drug combinations may be contraindicated. OBRA guidelines caution that azole antifungals may cause hepatotoxicity, headaches, and GI distress.

The safety and efficacy of oral ketoconazole have not been established in neonates, infants, or children under 2 years of age.1 Topical products (e.g., shampoo, cream) have been used in pediatric patients off-label but are not FDA-approved for use in pediatric patients; the safety and efficacy of ketoconazole topical foam and gel products have not been established in pediatric patients less than 12 years old.

Niacinamide

Patients who have a known excessive sensitivity to niacin or any component should not be given the medication.

While steady-state plasma concentrations of niacin are for the most part higher in women than in men, the retention, digestion, and discharge of niacin has all the earmarks of being comparative in the two. Females have been accounted for to have more prominent reaction to the lipid-lowering impacts of nicotinic acid (niacin) when contrasted with men.

No general distinctions in safety and efficacy were seen among geriatric and more youthful people receiving niacin. Other announced clinical experience has not recognized contrasts in reactions between the old and more youthful patients, however more noteworthy awareness for a few more seasoned people can’t be precluded.

Niacin is contraindicated in patients who have a significant or unexplained hepatic illness. Patients who consume large amounts of ethanol (alcohol abuse), who have risk factors for hepatic infection, or who have a previous history of gallbladder sickness, jaundice, or hepatic dysfunction might receive niacin with close clinical observation. Rises in liver function tests (LFTs) have all the earmarks of being dose-related. Some sustainable release nicotinic acid (niacin) formulations have a higher rate of hepatotoxicity when compared with immediate-release dosage forms. Expanded discharge nicotinic corrosive arrangements (e.g., Niaspan, Slo-Niacin) ought not be substituted for comparable measurements of immediate-release (crystalline) niacin (e.g., Niacor and others). Follow the manufacturer-recommended initial dosage titration plans for broadened discharge items, paying little heed to past treatment with other niacin details. Screen LFTs in all patients during treatment at approximately 6-month stretches or when clinically indicated. Assuming 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 ought to be ended.

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 coadministered (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, particularly in high dosages, can cause hypophosphatemia. Albeit the decreases in phosphorus levels are normally transient, clinicians ought to screen serum phosphorus occasionally in those in danger for this electrolyte irregularity.

Uncommon instances of rhabdomyolysis have been accounted for in patients taking lipid-modifying measurements of nicotinic acid (niacin) and statin-type specialists simultaneously (see Drug Interactions). Patients going through joined treatment ought to be painstakingly checked for muscle pain, tenderness, or weakness, especially in the early long stretches of treatment or during times of upward dose titration of one or the other medication. While occasional CPK and potassium conclusions might be thought of, there is no proof that these tests will forestall the event of extreme myopathy. In the event that rhabdomyolysis happens, the offending therapies ought to be stopped.

Niacin, particularly in high portions, may cause hyperglycemia. Niacin ought to be recommended carefully to patients with diabetes mellitus. These people ought to be instructed not to buy OTC structures regarding niacin without the direction of a doctor. Niacin has likewise been accounted for to cause bogus positive outcomes in pee glucose tests that contain cupric sulfate arrangement (e.g., Benedict’s reagent, Clinitest).

Niacin treatment has been utilized securely in children for the treatment of nutritional niacin deficiency. Nonetheless, the safety and effectiveness of nicotinic acid for the treatment of dyslipidemias have not been laid out in youngsters, babies and kids <= 16 years old. Nicotinic acid has been utilized for the treatment of dyslipidemia in pediatric patients under select conditions. Kids might have an increased risk of niacin-induced side effects versus adult populations. At least one pediatric study has reasoned that niacin treatment ought to be held for treatment of extreme hypercholesterolemia under the close-supervision of a lipid specialist.26 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.6 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.28 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.

Ketoconazole

There are no adequate and well-controlled studies of ketoconazole use during human pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Use ketoconazole in pregnant women only if the potential benefit justifies the potential risk to the fetus.1252 Guidelines recommend against starting oral azole antifungals, including ketoconazole, during pregnancy and to discontinue these agents in HIV-positive women who become pregnant.29 Embryotoxic and teratogenic effects (syndactylia and oligodactylia) have been demonstrated in animals receiving oral ketoconazole doses at 10-times the maximum recommended human dose. In addition, dystocia was observed in animals administered oral ketoconazole during the third trimester of gestation at doses approximately one-fourth the maximum human dose, based on body surface area comparisons. Ketoconazole is not detected in human plasma after chronic shampooing of the scalp.

Niacinamide

Niacin should be safe to consume during pregnancy in amounts that satisfy the recommended daily allowance (RDA), as it is an essential nutrient. In these conditions, niacin is designated as pregnancy category A. Niacin is classified as pregnancy category C when used in doses over the RDA for dyslipidemia or when administered parenterally for the treatment of pellagra. The majority of manufacturers advise against using niacin during pregnancy in amounts greater than the RDA. Since toxicological tests have not been done, the benefits and hazards of high-portion niacin treatment should be compared.

Ketoconazole

Systemic ketoconazole is excreted in breast milk. In a case report of a mother prescribed 200 mg PO daily for 10 days, ketoconazole milk concentrations of 0.22 mcg/mL (peak) were observed 3.25 hours post-dose and were undetectable at 24 hours post-dose. Assuming a milk intake of 150 mL/kg/day, the daily ketoconazole dose of an exclusively breastfed infant was calculated as 0.01 mg/kg/day or 0.4% of the mother’s weight-adjusted dose. There are no data on the effects of ketoconazole on the breast-fed infant or its effects on milk production. The manufacturer recommends mothers refrain from breastfeeding their infants during oral therapy; however, previous American Academy of Pediatrics (AAP) recommendations considered ketoconazole compatible with breastfeeding. After topical application, ketoconazole concentrations in plasma are low; therefore, concentrations in human breast milk are likely to be low. Advise breastfeeding women not to apply topical ketoconazole directly to the nipple and areola to avoid direct infant exposure. Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for topical ketoconazole and any potential adverse effects on the breast-fed infant from ketoconazole or the underlying maternal condition. Fluconazole may be a potential alternative to consider during breastfeeding.

Niacinamide

As per a producer of niacin (Niaspan), albeit no studies have been conducted in nursing moms, discharge into human milk is normal. The producer suggests the end of nursing or the medication because of serious adverse reactions that might happen in nursing babies from lipid-altering dosages of nicotinic acid.6 Niacin, in the form of niacinamide, is excreted in breastmilk 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.28 There are no safety data regarding the use of nicotinic acid in doses above the RDA during breastfeeding. 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.

Ketoconazole

Approximately 3% of patients receiving oral ketoconazole experience episodes of nausea and vomiting. This usually is transient and may improve when ketoconazole is given with food, which also can increase oral bioavailability. Other ketoconazole-associated gastrointestinal adverse reactions include abdominal pain and diarrhea which were reported in 1.2% and less than 1% of patients, respectively.1 Cases of cheilitis have been noted during postmarketing use of ketoconazole topical foam. Due to the voluntary nature of postmarketing reports, neither a frequency nor definitive causal relationship can be established.

Ketoconazole can inhibit testosterone secretion at doses of 200—400 mg/day13and can inhibit cortisol synthesis in doses of 400—600 mg/day.14 Inhibition of testosterone synthesis has led to cases of gynecomastia and impotence (erectile dysfunction) in < 1% of men. Serum testosterone concentrations return to baseline and gynecomastia and impotence usually abate after ketoconazole therapy is stopped. Oligospermia has been reported in patients receiving systemic ketoconazole in investigational studies. This was mainly at doses above those approved. Oligospermia was not reported at doses up to 400 mg/day; however, sperm counts are not frequently obtained at these doses.

Rare cases of anaphylactoid reactions have been reported following the first dose of oral ketoconazole and during post-marketing use of the 2% shampoo. Several cases of hypersensitivity reactions including urticaria and angioedema have also been reported.2 Fever and chills have been reported in < 1% of patients receiving systemic ketoconazole.1 Facial swelling has been reported in < 1% of patients using the topical gel formulation.

Dizziness, drowsiness (somnolence), and headache have been reported in < 1% of patients receiving treatment with oral ketoconazole. Neuropsychiatric events have also been reported rarely and include suicidal ideation and severe depression.1 Headache and dizziness were also reported in < 1% of patients using the topical gel formulation.

Photophobia occurs in < 1% of patients receiving treatment with oral ketoconazole. To minimize discomfort, the patient should wear sunglasses while outside and avoid bright light when possible.1 Treatment-related ophthalmic adverse events reported in < 1% of patients using the topical gel include ocular irritation, ocular swelling, and keratoconjunctivitis sicca.

Post-marketing worldwide reports in patients receiving oral ketoconazole have included rare cases of paresthesias, and signs of increased intracranial pressure including bulging fontanelles and papilledema. Hypertriglyceridemia has also been reported with the oral formulation but a causal relationship with ketoconazole has not been determined.1 Paresthesias have also been reported in <= 1% of patients using the topical foam and in < 1% of patients using the topical gel.

Dermatologic reactions were reported with systemic and topical ketoconazole formulations. Pruritus has been reported in 1.5% of patients receiving oral ketoconazole; it has also been reported following application of the topical cream, topical foam (up to 1%), topical gel (less than 1%), and the shampoo. Alopecia has been reported with the shampoo and with worldwide postmarketing reports in patients receiving the oral formulation. Skin irritation has been reported with topical use, specifically with the cream (as pruritus, burning, and stinging), the foam (up to 1%), the gel (less than 1%), and the shampoo. Contact dermatitis was reported with use of the shampoo and postmarketing with the cream; application site dermatitis was reported with use of the gel (less than 1%). The topical foam (Extina) was associated with an increased incidence of contact sensitization, including photosensitivity in dermal safety studies. Application site reaction (6%) and burning (10%) were reported with ketoconazole foam, burning was also reported with the gel (4%) and the shampoo. Skin dryness or xerosis was reported with use of the foam (up to 1%), the gel (less than 1%), and the shampoo. Erythema was reported with use of the foam (up to 1%) and the gel (less than 1%). Rash (unspecified) was reported with use of the foam (up to 1%) and the shampoo. Warmth at the application site was noted in up to 1% of patients using the foam. Pustules were noted on the skin with application of the gel (less than 1%) and on the scalp with application of the shampoo. Other reactions noted in less than 1% of patients who used the topical gel include discharge, pain, impetigo, pyogenic granuloma, acne vulgaris, and nail discoloration. Adverse reactions specifically noted with use of the shampoo include hair discoloration, abnormal hair texture and removal of curl, rash (unspecified), and application site reactions.

Systemic ketoconazole can prolong the QT interval. Serious cardiovascular events, QT prolongation, ventricular arrhythmias, and torsade de pointes, have been observed in patients receiving ketoconazole oral tablets in combination with other QT-prolonging drugs.

Ketoconazole alters vitamin D metabolism and may lead to vitamin D deficiency. Patients should be monitored and supplemented with vitamin D if necessary.

Niacinamide

Niacin (nicotinic acid), when administered in portions comparable to the RDA, is by and large nontoxic. Niacinamide likewise seldom causes adverse reactions. Bigger dosages of nicotinic acid (i.e., >= 1 g/day PO), can cause adverse reactions all the more frequently. Contrasts in unfavorable response profiles can be made sense of by the way that nicotinic corrosive has pharmacologic properties that are not the same as niacinamide.

Peripheral vasodilation is a notable adverse reaction to niacin. It is portrayed by flushing; warmth; and burning or tingling of the skin, particularly in the face, neck, and chest. Hypotension can be brought about by this vasodilation. Patients ought to keep away from abrupt changes in posture to forestall symptomatic or orthostatic hypotension. Unsteadiness as well as cerebral pain, including headache, can happen. Cutaneous flushing is bound to happen with quick delivery arrangements rather than supported discharge ones and furthermore increments in frequency with higher portions. 10 Following 4-weeks of maintenance therapy of 1500 mg day to day, patients receiving immediate-release niacin averaged 8.6 flushing events in contrast with 1.9 occasions in the Niaspan bunch. In placebo-controlled investigations of Niaspan, flushing happened in 55 — 69% of patients contrasted with 19% of patients getting a placebo. Flushing was portrayed as the justification for ending treatment for 6% of patients getting Niaspan in pivotal studies.6 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.6 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 create different GI results, like queasiness/heaving, stomach torment, diarrhea, bloating, dyspepsia, or flatulence, when taken in huge dosages. Eructation and peptic ulcer has been accounted for with the post-marketing experience of Niaspan. Contrasted with placebo, looseness of the bowels was accounted for in 7 — 14% (versus 13%), queasiness in 4 — 11% (versus 7%), and heaving in 0 — 9% (versus 4%) of patients getting Niaspan. 6 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 constant liver harm brought about by niacin. It has been shown that raised hepatic catalysts happen more much of the time with some supported delivery niacin than with prompt delivery items.10 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.6 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.6 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 paresthesias 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.

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