Description

Overview of Acne Onex Cream

Dosage Strength of Acne Onex Cream

Benzoyl Peroxide / Clindamycin / Niacinamide 5/1/2% 30 mL Pump

Benzoyl Peroxide

Topical benzoyl peroxide is used to treat acne. Benzoyl peroxide has antimicrobial properties. It also has drying, sebostatic, and mild skin desquamation properties. Both inflammatory and non-inflammatory acne lesions benefit from benzoyl peroxide. In mild cases of acne, benzoyl peroxide is useful as a monotherapy, while in moderate to severe cases of acne, it is used as an adjuvant. For the treatment of mild to moderate acne, research 1 in the United Kingdom found that an OTC 5 percent benzoyl peroxide topical formulation (Panoxyl Aquagel) was as effective as a topical benzoyl peroxide/erythromycin combination and the oral tetracyclines minocycline and oxytetracycline. Topical benzoyl peroxide and benzoyl peroxide/erythromycin combinations were not linked to tetracycline-induced propionibacterium antibiotic resistance. Off-label uses of benzoyl peroxide include the treatment of decubitus ulcers. Prescription and over-the-counter versions of benzoyl peroxide are available, as well as combinations with erythromycin, hydrocortisone, and sulfur (see separate monographs for each of the combination products). To guarantee uniformity with the standardized ‘Drug Facts’ layout, the FDA has amended labeling regulations for all non-prescription (over-the-counter) topical acne medications, including benzoyl peroxide. In over-the-counter topical acne medication treatments, benzoyl peroxide is generally recognized as a safe and effective (GRASE) active component.

Clindamycin Phosphate

Clindamycin as an antibiotic is structurally related to lincomycin, from which it is produced. Clindamycin has long been thought to be an effective anti-anaerobic antibiotic, but it has recently been proven to be useful in treating toxoplasmic encephalopathy in AIDS patients when combined with pyrimethamine. 2. Clindamycin was licensed by the FDA in 1970 and is available as a hydrochloride salt for oral use and a phosphate salt for parenteral, topical, and vaginal use. In November 2004, the FDA authorized ClindesseTM, a single-dose vaginal cream for bacterial vaginosis. In December 2004, the FDA authorized EvoclinTM, an aerosol topical foam containing 1% clindamycin, for the treatment of acne vulgaris.

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.3 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.4 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.5 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.6 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.7 Some dosage forms are available without prescription. The FDA officially approved niacin in 1938.

Benzoyl Peroxide

Antimicrobial activities of benzoyl peroxide against Propionibacterium acnes, the most common bacteria found in sebaceous follicles and comedones. The generation of free-radical oxygen species, which are capable of damaging bacterial proteins, is responsible for benzoyl peroxide’s antibacterial properties. Acne normally clears up within four to six weeks of starting treatment. The reduction of P. acnes, lipids, and free fatty acids in the skin follicle corresponds with resolution. Benzoyl peroxide also has keratolytic activity, which results in drying and desquamative effects that aid in the treatment of comedones. Benzoyl peroxide increases epithelial cell proliferation and granulation tissue development in the treatment of decubitus ulcers.

Clindamycin Phosphate

Clindamycin suppresses protein synthesis by binding to the 23S RNA of the bacteria’s 50S ribosomal subunit. Antibacterial efficacy is derived from the suppression of protein synthesis, similar to lincomycin. Clindamycin has bacteriostatic properties. Clindamycin’s mechanism of action in the treatment of acne vulgaris remains uncertain.

The pathogen determines the susceptibility interpretation criteria for clindamycin. The MICs for beta-hemolytic streptococci, S. aureus, have been established. S. viridans and the viridans group At 0.25 mcg/mL or less, pneumoniae is sensitive, intermediate at 0.5 mcg/mL, and resistant at 1 mcg/mL or higher. The MICs for Staphylococcus sp. have been established. At 0.5 mcg/mL or less, it’s susceptible, intermediate at 1 to 2 mcg/mL, and resistant at 4 mcg/mL or above. Anaerobes are susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or higher, according to the MICs.

Modification of particular nucleotides of the 23S ribosomal RNA is the most common cause of clindamycin resistance. Clindamycin and lincomycin have 100% cross-resistance. Cross-resistance can occur between lincosamides, macrolides, and streptogramin B due to overlapping binding sites. Inducible clindamycin resistance has been discovered in macrolide-resistant organisms; consequently, the D-zone test should be used to screen macrolide-resistant and clindamycin-susceptible bacteria for inducible clindamycin resistance.

Clindamycin resistance is a well-known cause of pseudomembranous colitis, which is assumed to be caused by Clostridia difficile overgrowth. Clindamycin resistance affects 10% to 20% of Clostridia perfringens strains. 8 Some strains of B. fragilis have also shown increased resistance.13 Clindamycin treatment for bacterial vaginosis resulted in considerable antibiotic resistance, according to one study, which remained for up to 90 days after treatment.

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.

Benzoyl Peroxide

Individuals who have a known intolerance to benzoyl peroxide or any of the other specified chemicals should avoid using it.

The use of benzoyl peroxide products in individuals with skin illnesses like dermatitis, seborrhea, and eczema, as well as skin abrasion or inflammation, as well as denuded skin, such as sunburn or windburn, may increase the risk of skin irritation. The use of benzoyl peroxide should be avoided until the skin irritation has subsided. To reduce the risk of skin irritation, patients should restrict their UV exposure and apply sunscreen while taking benzoyl peroxide treatments.

Due to significant irritation, avoid accidentally exposing benzoyl peroxide products to the eyes, lips, mucous membranes, and inflammatory or raw skin. If a mucus membrane or ocular exposure occurs unintentionally, thoroughly rinse the affected regions with water.

The safety and efficacy of benzoyl peroxide products in children has yet to be determined.

Products containing benzoyl peroxide are classified as pregnancy risk category C by the FDA. It’s unclear whether benzoyl peroxide can harm a fetus or affect reproductive potential. Topical use, on the other hand, is typically regarded as safe during pregnancy.

It is unknown if benzoyl peroxide is secreted in breastmilk. However, because only a little amount of benzoic acid is absorbed systemically when benzoyl peroxide is applied topically, there is no risk to the infant. 16 Because ointments may expose the newborn to excessive quantities of mineral paraffins, only water-miscible cream products should be administered to the breast. 17 Consider the advantages of breastfeeding, the risk of baby drug exposure, and the risk of an illness that is ignored or inadequately treated. If a breastfeeding newborn has an adverse reaction to a medicine given to her by her mother, healthcare providers are advised to report the reaction to the FDA.

Clindamycin Phosphate

Clindamycin is not suggested for anyone who have had a clindamycin hypersensitivity reaction in the past. Because of the risk of cross-sensitivity, clindamycin usage is also prohibited in cases of lincomycin hypersensitivity. Use the drug with caution in patients who have asthma or a history of allergies (atopy). Several oral capsule formulations contain tartrazine dye, which can cause bronchial asthma or other allergic reactions in persons with tartrazine dye hypersensitivity. 18 Serious rash events such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), and drug response with eosinophilia and systemic symptoms (DRESS), some fatal, have been recorded with systemic clindamycin treatment. Clindamycin should be discontinued permanently if major skin or hypersensitivity problems arise.

Clindamycin can cause nonsusceptible bacteria to overgrow, leading to superinfection, which is particularly common in yeast and fungal diseases. Take the required precautions if superinfection occurs.

Clindamycin has been related to severe colitis more than any other antibacterial. Patients with a history of pseudomembranous colitis should avoid topical (topical solution, gel, and lotion) and vaginal (cream, ovules) clindamycin preparations; additional product formulations warn against usage in patients with pseudomembranous colitis. 91819 Antibiotics have been linked to pseudomembranous colitis (antibiotic-associated colitis), which can range in severity from mild to life-threatening. When natural flora is disrupted as a result of antimicrobial treatment, Clostridia overgrowth can occur in the colon. Pseudomembranous colitis is caused by a toxin generated by Clostridium difficile. Carriage rates for C. difficile are 37 percent in neonates, 30 percent in newborns 1 to 6 months, and 14 percent in infants 6 to 12 months; however, nursing reduces carriage rates dramatically.20 Carriage rates are comparable to those of non-hospitalized individuals by the age of three (3 percent or less). Consider pseudomembranous colitis as a possible diagnosis in people who develop diarrhea after taking antibiotics. Patients with inflammatory bowel illness, such as ulcerative colitis or other GI diseases, should be given systemic antibiotics with caution. If diarrhea develops during treatment, the medicine should be stopped. Implement therapeutic steps after a diagnosis of pseudomembranous colitis. Antibiotic-associated colitis can develop up to 2 months after systemic antibiotic therapy is stopped; a thorough medical history should be collected.

Clindamycin topical solution contains an alcohol component that can cause eye irritation and burning; prevent ocular exposure. Bathe with water if you come into contact with sensitive surfaces (eye, abraded skin, mucous membranes). 9

Clindamycin is a drug that can be used to treat a variety of sexually transmitted illnesses (STD). At the time of diagnosis, all patients with a diagnosed or suspected STD should be tested for other STDs, such as HIV, syphilis, chlamydia, and gonorrhea. Following a sexually transmitted disease diagnosis, start appropriate therapy and get follow-up tests as needed. 21

Antibiotic-associated colitis and diarrhea (due to Clostridium difficile) found in connection with most systemic antibiotics, such as clindamycin, are more common in senior adults (60 years or older) and may be more severe, according to reported clinical experience. The onset of diarrhea in these patients should be closely monitored. 818 The federal Omnibus Budget Reconciliation Act (OBRA) governs medicine use in long-term care facility residents (e.g., elderly individuals) (LTCFs). Antibiotics should only be used for confirmed or suspected bacterial illnesses, according to OBRA. Antibiotics are non-selective and may cause secondary infections such as oral thrush, colitis, or vaginitis by eradicating beneficial microbes while stimulating the growth of undesirable ones. Diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions are all possible side effects of antibiotics.

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 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, 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, Clinitest).

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.23 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.3 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.25 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.

Benzoyl Peroxide

Products containing benzoyl peroxide are classified as pregnancy risk category C by the FDA. It’s unclear whether benzoyl peroxide can harm a fetus or affect reproductive potential. Topical use, on the other hand, is typically regarded safe during pregnancy.

Clindamycin Phosphate

No congenital malformations have been linked to systemic clindamycin therapy throughout the second or third trimester in clinical trials with pregnant women. 18 However, in a large population-based cohort study (n = 139,938 live births) assessing antibiotic exposure during the first trimester of pregnancy (n = 15,469 exposures) and the risk of major birth defects, clindamycin was associated with an increased risk of major congenital malformations (adjusted odds ratio (aOR) 1.34; 95% CI: 1.02 to 1.77; 60 exposed cases). Clindamycin exposure increased the risk of musculoskeletal system malformations (aOR 1.67; 95% CI: 1.12 to 2.48; 29 exposed cases) and ventricular/atrial septal defect (aOR 1.81; 95% CI: 1.04 to 3.16; 13 exposed cases).26 Use clindamycin during the first trimester of pregnancy only if clearly needed and the benefits outweigh the risks.18 Placental concentrations are roughly 50% of maternal serum concentrations.2728 Benzyl alcohol, which can pass the placenta, is also present in parenteral clindamycin; benzyl alcohol has been linked to a fatal ‘gasping syndrome’ in neonates. 891818 During pregnancy, clindamycin vaginal cream was examined to decrease premature birth and treat asymptomatic bacterial vaginosis. Women who were treated with 2% clindamycin vaginal cream prior to 20 weeks of pregnancy had a lower risk of preterm birth than those who were given a placebo (p less than 0.03). 29 In three previous studies, intravaginal clindamycin cream was given to pregnant women between 16 and 32 weeks of pregnancy, and neonates experienced an increase in adverse outcomes such as low birthweight, preterm delivery, early rupture of the membranes, and neonatal infections. 303132 No adequate, well-controlled studies of topical clindamycin in pregnant women have been conducted.

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.

Benzoyl Peroxide

Products containing benzoyl peroxide are classified as pregnancy risk category C by the FDA. It’s unclear whether benzoyl peroxide can harm a fetus or affect reproductive potential. Topical use, on the other hand, is typically regarded safe during pregnancy.16 Because ointments may expose the newborn to excessive quantities of mineral paraffins, only water-miscible cream products should be administered to the breast. 17 Consider the advantages of breastfeeding, the risk of baby drug exposure, and the risk of an illness that is ignored or inadequately treated. If a breastfeeding newborn has an adverse reaction to a medicine given to her by her mother, healthcare providers are advised to report the reaction to the FDA.

Clindamycin Phosphate

Clindamycin is excreted in human breast milk at quantities of less than 0.5 to 3.8 mcg/mL after dosing via oral or parenteral methods. Because clindamycin might induce major gastrointestinal side effects in breastfed babies, an alternate medicine to clindamycin may be preferable during breastfeeding. Consider the developmental and health benefits of breastfeeding, as well as the mother’s clinical requirement for clindamycin and any potential clindamycin or underlying maternal disease side effects on the breast-fed infant. If you’re using clindamycin while breastfeeding, keep an eye on your baby for gastrointestinal side effects like diarrhea, candidiasis (thrush, diaper rash), or, in rare cases, blood in the stool, which could indicate antibiotic-associated colitis. 818 Diarrhea and bloody stools were reported in a 5-day-old infant whose mother was receiving intravenous clindamycin and gentamicin for suspected endometriosis. Previous American Academy of Pediatrics recommendations considered clindamycin as usually compatible with breastfeeding.35 It is unknown if clindamycin is excreted into human breast milk after the use of vaginally or topically administered clindamycin.91833 If clindamycin is topically applied to the chest, care should be taken to avoid accidental ingestion by the infant.

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.3 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.25 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.

Benzoyl Peroxide

Xerosis is the most common side effect of benzoyl peroxide products (drying of skin). Marked peeling, erythema, and skin irritation are all symptoms of xerosis. After a few days, the skin will begin to peel. When using benzoyl peroxide products, patients with skin irritation may suffer moderate stinging, warmth, or erythema. Some patients may develop contact dermatitis, which manifests itself as a rash, pruritus, blistering, crusting, or swelling of the skin.15 Discontinue benzoyl peroxide in individuals who have severe symptoms and consider using emollients, cool compresses, or topical corticosteroids (if appropriate) to relieve symptoms and speed healing.

Topical over-the-counter (OTC) acne medications, such as benzoyl peroxide, have been linked to uncommon but acute hypersensitivity responses, which can be fatal. These reactions might happen anywhere from minutes to a day or more after using the product. Instruct patients to discontinue using topical acne products if they develop throat tightness, difficulty breathing, faintness, or swelling of the eyes, face, lips, or tongue, which are all signs of anaphylactoid reactions. Patients who experience urticaria or pruritus should stop using the medication. It’s unclear if the responses are caused by the active chemicals benzoyl peroxide or salicylic acid, the inert substances, or a mix of both, according to the information provided to the FDA. When starting treatment with an over-the-counter topical acne remedy, tell patients to apply a modest amount to one or two minor afflicted areas for three days and watch for signs of hypersensitivity. If no discomfort occurs, follow the directions on the Drug Facts label.

Clindamycin Phosphate

Systemic clindamycin therapy is more usually associated with gastrointestinal (GI) adverse effects; nevertheless, GI disturbances have also been documented in connection with topical and vaginal formulations. Diarrhea has been documented in up to 20% of patients getting systemic medication, and it is more common with the oral formulation; it has also been reported in less than 1% of patients using vaginal preparations, and it has happened with topical products. Abdominal pain/cramps, halitosis, nausea, vomiting, dyspepsia, flatulence, and gastrointestinal problem have all been recorded in fewer than 1% of patients using vaginal products and other formulations. Constipation has been noted in only 2% of individuals who have used the vaginal product. Administration of oral formulations with food can reduce minor gastric distress. Esophagitis may occur with the oral formulations of clindamycin.893318121819373839 Dysphagia, odynophagia, and retrosternal discomfort are all symptoms of esophagitis. The majority of symptoms go away within a few days to weeks after the medicine is stopped. Clindamycin has been linked to pseudomembranous colitis (Clostridium difficile-associated diarrhea, CDAD). CDAD was first reported at a rate of 0.01 percent to 10%, but it has since become more common and severe. CDAD can occur during treatment or after it has been stopped, and it can cause minor diarrhea or deadly colitis. Although systemic therapy is more usually connected with CDAD, topical and vaginal products do have some systemic absorption, and CDAD can develop. 893318121819373839 A metallic taste (dysgeusia) has been reported with the administration of the intravenous and oral clindamycin products and taste perversion has been reported in less than 1% of patients receiving the vaginal cream.81818 Hematochezia was noted in postmarketing reports with the vaginal cream.

Transient neutropenia (leukopenia) and eosinophilia have been reported during clindamycin therapy. Reports of agranulocytosis and thrombocytopenia have been made. No direct relationship to concurrent clindamycin therapy has been made.

Rashes including rash (unspecified), maculopapular rash, vesicular rash, or bullous rash as well as urticaria have been observed during systemic clindamycin therapy and may be associated with hypersensitivity. Severe skin reactions, such as toxic epidermal necrolysis and Stevens-Johnson syndrome, have been reported and some cases have been fatal. Clindamycin should be permanently discontinued if severe skin or hypersensitivity reactions occur. Acute generalized exanthematous pustulosis (AGEP), angioedema, drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme, and exfoliative dermatitis have also been reported with systemic clindamycin.18 Pruritus/itching has also been noted with topical (1% to 11%), vaginal (less than 1% to 1.1%), and systemic therapy. Topical application has been associated with burning (6% to 11%), xerosis (dry skin) (1% to 23%), erythema (7% to 16%), oiliness/oily skin (1% to 18%), peeling (7% to 11%), seborrhea, application site rash, folliculitis, and application site pain. Xerosis may be attributed to the solvent used in the topical preparation. Alcohol in some topical formulations may cause ocular irritation or ocular pain or irritate the mucous membranes or abraded skin resulting in contact dermatitis.

Intramuscular injection of clindamycin can cause an injection site reaction consisting of pain, induration, and sterile abscess. Thrombo-phlebitis has been reported after intravenous infusion.

Renal impairment shown by azotemia, oliguria, and/or proteinuria has been found in rare cases with clindamycin medication, despite the lack of a causal link. Only about 1% of patients using vaginal clindamycin experienced dysuria.

Clindamycin has been linked to allergic responses including anaphylactic shock. If anaphylaxis or severe hypersensitivity responses develop, clindamycin should be stopped immediately. Because certain oral capsule preparations contain tartrazine color, patients with a tartrazine dye allergy should be treated with caution.

Vaginal irritation (3.4 percent), vulvovaginitis (6% or less), vaginal pain (1.9 percent), vulvovaginal disorder (3.2 percent to 6.7 percent), trichomonal vaginitis (0.2 percent), vaginal erythema, vulvovaginal pruritus, vaginal discharge, vaginal swelling, and vaginal bleeding were all reported in women who received vaginal clindamycin preparations. Menstrual disorder, vaginal discharge, vaginal infection, dysfunctional uterine bleeding, dysmenorrhea, intermenstrual bleeding, pelvic pain, vaginal burning, vaginal irritation, vulvar erythema, vulvitis, vulvovaginal discomfort, vulvovaginal dryness, vaginal pain, metrorrhagia, endometriosis, and menstrual disorder are other adverse events reported in less than 1% of patients. Abnormal labor was noted in 1.1% of pregnant patients. Vaginitis has also been reported with vaginal products (3.6% or less) and with systemic use of clindamycin.

During clindamycin treatment, jaundice and abnormal/elevated liver enzymes have been reported.

The use of topical clindamycin foam as well as vaginal products was associated with headache (7 percent or less) and dizziness (less than 1%). The vaginal preparations were also linked to vertigo (less than 1%).

Back pain has been described as a side effect of vaginal clindamycin use (5%).838 Cases of polyarthritis have been reported with systemic therapy.

Clindamycin use may result in infection from nonsusceptible organisms overgrowing or superinfection. Fungal infections, such as candidiasis, can be systemic or localized. Vaginal candidiasis has been documented in 1.5 percent to 14 percent of patients who get vaginal clindamycin, and systemic candidiasis in 1.7 percent or less of those who receive vaginal clindamycin. Pyelonephritis was reported in less than 1% of patients who used vaginal clindamycin, while urinary tract infection was reported in less than 2% of patients. In less than 1% of individuals who used the vaginal product, upper respiratory tract infection and an unidentified bacterial illness were also recorded.

Inflammatory swelling, hyperthyroidism, epistaxis, fever, generalized pain, localized edema, and exhaustion have all been observed in less than 1% of individuals who have used clindamycin vaginal preparations. 401938

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.7 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.3 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.3 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.3 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.7 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.3 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.3 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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