Biotin / Finasteride Capsules

Biotin

Biotin (vitamin H; coenzyme R; classified as a B vitamin) is a dietary component that is important for the metabolism of carbohydrates, fats, and amino acids. It is found primarily in liver, kidney, and muscle. Biotin functions as an essential cofactor for five carboxylases that catalyze steps in fatty acid, glucose, and amino acid metabolism. It is also an important factor in histone modifications, gene regulation, and cell signaling. Mammals must consume biotin to replenish stores. Sources of biotin include organ meats, eggs, fish, seeds, and nuts. As a dietary supplement, biotin has been promoted to be useful in the treatment of hair and nail problems, cradle cap (seborrheic dermatitis) in phenylketonuria patients, biotinidase deficiency, diabetes, peripheral neuropathy, candida infections, and high cholesterol. It has also been used in pregnancy, hemodialysis, and peritoneal dialysis, as biotin deficiency is more likely in these situations. Biotin is found in many cosmetics products. Radiolabeled biotin is used for pretargeted radioimmunotherapy of cancerous tumors.

Finasteride

Finasteride is a 5-alpha reductase inhibitor used to treat symptomatic benign prostatic hyperplasia (BPH), a condition found in the majority of men over the age of 50. Finasteride has been shown to increase and maintain maximum urine flow rate in men with BPH, although less than 50% of men show improvement despite a reduction in prostate size. In a typical patient undergoing treatment for BPH with finasteride (>= 6 months), a 50% decrease in serum PSA concentrations can be expected; however, individual patients may experience varying decreases in PSA values. During treatment, serum PSA concentrations may decrease even in the presence of prostate cancer. If clinicians use serum PSA concentrations as an aid in the detection of prostate cancer in men receiving finasteride, values should be doubled for comparison with normal ranges in untreated men. Any increase from baseline, even if the value is within the normal range for untreated men, may signal the presence of prostate cancer. If clinicians elect to use percent free PSA (free to total PSA ratio) as a marker, no adjustment in PSA values appear to be necessary as the value is not significantly decreased by finasteride. In June 2011, a review of two large, randomized controlled trials, the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial prompted the FDA to alert healthcare professionals of the potential risk of an increased incidence of high-grade prostate cancer in patients receiving finasteride or dutasteride treatment. Results from the PCPT trial showed that men receiving finasteride had a 26% decreased risk of being diagnosed with prostate cancer overall when compared to placebo (p < 0.0001); however, the risk reduction was limited to Gleason score (GS) <= 6 cancers. There was an increased incidence of GS 8—10 prostate cancers with finasteride compared to placebo (1.8% vs. 1.1%, respectively). Finasteride is also used for treating hair loss in men and has been shown to be effective for mild to moderate hair loss of the vertex and anterior mid-scalp area; efficacy in bitemporal recession has not been established. Finasteride (Proscar) was approved by the FDA in June 1992 for the treatment of BPH. Another finasteride oral dosage form, Propecia, was approved by the FDA in December 1997 for the treatment of male pattern baldness (i.e., androgenetic alopecia). Finasteride is also used investigationally as an alternative agent for treating hirsutism.

Biotin

Biotin is a water-soluble B vitamin found naturally in some foods and used as a dietary supplement. It is important for the metabolism of carbohydrates, fats, and amino acids. It is found primarily in liver, kidney, and muscle. Biotin functions as an essential cofactor for five carboxylases that catalyze steps in fatty acid, glucose, and amino acid metabolism. It is mostly protein-bound in foods such as organ meats, eggs, nuts, and soybeans. Gastrointestinal enzymes break down ingested biotin via proteolysis. This creates biocytin, which is then cleaved by biotinidase into free biotin and lysine. Free biotin is then absorbed in the small intestine. Biotin can be used for metabolism issues such as biotinidase, holocarboxylase synthetase, and isolated carboxylase enzyme deficiencies due to its essential role in the metabolism of fatty acids, glucose, and amino acids.

Finasteride

Finasteride is a synthetic 4-aza analog of testosterone that acts as a competitive, specific inhibitor of type II 5-alpha-reductase, an intracellular enzyme that converts testosterone to the potent androgen 5-alpha-dihydrotestosterone (DHT). The type II 5alpha-reductase isozyme is primarily found in prostate, seminal vesicles, epididymides, and hair follicles, as well as liver. The type II isozyme is responsible for two-thirds of circulating DHT. DHT is the primary androgen that stimulates the development of prostate tissue. When used for the treatment of benign prostatic hyperplasia, as the enzymatic conversion from testosterone to DHT is inhibited, a desirable reduction in prostate hypertrophy is achieved, and urine flow should be improved. In male pattern hair loss, the balding scalp contains miniaturized hair follicles and increased amounts of DHT compared with hairy scalp. Finasteride decreases scalp and serum DHT concentrations, thus interrupting a key factor in the development of androgenetic alopecia in those patients genetically predisposed. Finasteride does not appear to affect circulating concentrations of cortisol, estradiol, prolactin, thyroid-stimulating hormone, thyroxine or cholesterol. Research to date also suggests that finasteride does not affect the hypothalamic-pituitary-testicular-axis.

Biotin

Biotin in blood or other samples taken from patients who are ingesting higher biotin dosages (i.e., doses of 10 to 300 mg biotin/day) in dietary supplements, including multivitamins, prenatal vitamins, and supplements for hair, skin, and nail growth, can cause clinically significant incorrect lab test results (falsely high or falsely low results) in assays that use biotin-streptavidin technology. Adverse events, including one death, related to biotin interference with lab tests have been reported. Specifically, biotin lab interference has caused falsely low troponin results, which may lead to missed diagnosis and potentially serious clinical implications. One patient taking high levels of biotin died following falsely low troponin test results when a troponin test known to have biotin interference was used. Some lab test developers have been successful at mitigating the biotin interference in their assays, while others may have not addressed this. Health care providers should be aware that many lab tests, including but not limited to, cardiovascular diagnostic tests and hormone tests that use biotin technology, may be affected. Discuss dietary supplement intake, particularly those that may contain biotin, with patients and communicate to the lab conducting testing if the patient reports taking biotin containing supplements. Consider laboratory test interference from biotin as a possible source of error if the lab test result does not match the clinical presentation of the patient and report any adverse events thought to be due to biotin interference to the lab test manufacturer and the FDA. One patient reportedly had abnormal thyroid function tests (TFTs) that did not match the clinical context after starting biotin. Within 3 days of stopping supplementation with biotin, repeated TFTs were normal. Then, biotin was reintroduced to the same patient, and TFTs taken 16 hours after the last dose and after an overnight fast showed further evidence of biotin immunoassay interference.

Biotin during pregnancy at the recommended adequate intake (AI) is recommended. Supplementation outside of dietary intake is usually not necessary if a healthy diet is consumed and no deficiency has been diagnosed.

Breastfeeding females may consume biotin within the recommended adequate intake (AI) parameters. Supplementation outside of dietary intake is usually not necessary if a healthy diet is consumed and no deficiency has been diagnosed.

Finasteride

Finasteride is not FDA-approved for use in females of childbearing potential and is contraindicated during pregnancy. Finasteride may cause fetal harm. Finasteride and other 5-alpha-reductase inhibitors, by inhibiting the conversion of testosterone to DHT, have the ability to cause abnormalities in the external genitalia of the male fetus. Pregnant women or females trying to conceive should not handle crushed or broken finasteride tablets. The distribution of finasteride into human semen has been assessed and appears to be well below the threshold concentration associated with fetal anomalies in animals.

Finasteride is not FDA-approved for use in females of childbearing potential and is recommended to be avoided during breastfeeding. It is not known whether finasteride is excreted in human milk. Therefore, the effects of finasteride on breastfeeding or a nursing infant cannot be determined.

Finasteride is not indicated for use in adolescents, children, or infants. Safety and effectiveness have not been established in pediatric patients under 18 years of age.

Finasteride should be used with caution in patients with hepatic disease, since finasteride is metabolized extensively in the liver. Data are lacking regarding the incidence of adverse effects or drug accumulation in patients with hepatic impairment.

Finasteride reduces total serum prostate specific antigen (PSA). In a typical patient undergoing treatment for BPH with finasteride (>= 6 months), a 50% decrease in serum PSA concentrations can be expected; however, individual patients may experience varying decreases in PSA values. During treatment, serum PSA concentrations may decrease even in the presence of prostate cancer. If clinicians use serum PSA concentrations as an aid in the detection of prostate cancer in men receiving finasteride, values should be doubled for comparison with normal ranges in untreated men. Any increase from baseline, even if the value is within the normal range for untreated men, may signal the presence of prostate cancer. If clinicians elect to use percent free PSA (free to total PSA ratio) as a marker, no adjustment in PSA values appear to be necessary as the value is not significantly decreased by finasteride. In June 2011, a review of two large, randomized controlled trials, the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial prompted the FDA to alert healthcare professionals of the potential risk of an increased incidence of high-grade prostate cancer in patients receiving finasteride or dutasteride treatment. Results from the PCPT trial showed that men receiving finasteride had a 26% decreased risk of being diagnosed with prostate cancer when compared to placebo (p < 0.0001); however, the risk reduction was limited to Gleason score (GS) <= 6 cancers. There was an increased incidence of GS 8—10 prostate cancers with finasteride compared to placebo (1.8% vs. 1.1%, respectively). Therefore, in initiating or continuing treatment with finasteride, clinicians should weigh the known benefits of treatment against the potential risk and be aware that finasteride may increase the risk of high-grade prostate cancer. Further, lower urinary tract symptoms of BPH can be indicative of other urological diseases, including prostate cancer. Patients should be assessed to rule out other urological diseases prior to treatment with finasteride. Patients with a large residual urinary volume and/or severely diminished urinary flow may not be good candidates for 5-alpha-reductase inhibitor therapy and should be carefully monitored for urinary tract obstruction.

Men treated with finasteride should refrain from blood donation while taking finasteride. The purpose of this is to prevent administration of finasteride to a pregnant female transfusion recipient.

Clinical efficacy studies of finasteride for hair loss did not include subjects aged 65 and over. Based on the pharmacokinetics of finasteride 5 mg, no dosage adjustment is necessary in the geriatric patient. However, the efficacy of finasteride for hair loss in the elderly has not been established.

The clinical significance of finasteride’s effect on semen characteristics for an individual male patient’s fertility is not known; consider the potential effects on semen when assessing a male with infertility. Finasteride may cause spermatogenesis inhibition or oligospermia, decreased sperm motility, or decreased semen volume. In a 52-week, randomized, double-blind, placebo-controlled study in healthy men, finasteride (5 mg PO once daily) significantly decreased total sperm count (-34.3%) compared to baseline at 26 weeks but not at 52 weeks or at the 24-week follow-up. Semen volume was decreased at 52 weeks for finasteride (-14.5%), but the effect was not statistically significant. Sperm concentration was decreased by finasteride (-7.4%) but was not significant for either drug. Significant reductions of 6 to 12% in sperm motility were observed during treatment. Sperm morphology was not affected. One subject taking finasteride had decreases in sperm count of more than 90% of baseline values at 52 weeks; partial recovery was noted at the 24-week follow-up. During post marketing surveillance, male infertility and/or poor seminal quality following treatment discontinuation have been reported. It should be noted that normalization or improvement of seminal quality has also been reported after discontinuation of finasteride.

Biotin

Biotin during pregnancy at the recommended adequate intake (AI) is recommended. Supplementation outside of dietary intake is usually not necessary if a healthy diet is consumed and no deficiency has been diagnosed.

Finasteride

Finasteride is not FDA-approved for use in females of childbearing potential and is contraindicated during pregnancy. Finasteride may cause fetal harm. Finasteride and other 5-alpha-reductase inhibitors, by inhibiting the conversion of testosterone to DHT, have the ability to cause abnormalities in the external genitalia of the male fetus. Pregnant women or females trying to conceive should not handle crushed or broken finasteride tablets. The distribution of finasteride into human semen has been assessed and appears to be well below the threshold concentration associated with fetal anomalies in animals.

Biotin

Breastfeeding females may consume biotin within the recommended adequate intake (AI) parameters. Supplementation outside of dietary intake is usually not necessary if a healthy diet is consumed and no deficiency has been diagnosed.

Finasteride

Finasteride is not FDA-approved for use in females of childbearing potential and is recommended to be avoided during breastfeeding. It is not known whether finasteride is excreted in human milk. Therefore, the effects of finasteride on breastfeeding or a nursing infant cannot be determined.

Biotin

Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Phenobarbital use for greater than one year while taking biotin can lead to decreased concentrations of biotin. Anticonvulsants that are potent CYP3A4 inducers, like phenobarbital, are thought to increase biotin metabolism, leading to reduced biotin status and inhibition of intestinal biotin absorption. This can result in decreased efficacy of biotin. Discuss biotin status with patients taking these medications concomitantly.

Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Phenobarbital use for greater than one year while taking biotin can lead to decreased concentrations of biotin. Anticonvulsants that are potent CYP3A4 inducers, like phenobarbital, are thought to increase biotin metabolism, leading to reduced biotin status and inhibition of intestinal biotin absorption. This can result in decreased efficacy of biotin. Discuss biotin status with patients taking these medications concomitantly.

Carbamazepine: (Moderate) Carbamazepine use for greater than one year while taking biotin can lead to decreased concentrations of biotin. Anticonvulsants that are potent CYP3A4 inducers, like carbamazepine, are thought to increase biotin metabolism, leading to reduced biotin status and inhibition of intestinal biotin absorption. This can result in decreased efficacy of biotin. Discuss biotin status with patients taking these medications concomitantly.

Ethanol: (Moderate) Excessive ethanol (e.g., alcoholism) may result in increased urinary excretion of magnesium. Avoid high intakes of ethanol while taking magnesium salts.

Food: (Minor) Dietary avidin, a glycoprotein in raw egg whites (food), binds tightly to dietary biotin and prevents its absorption in the gastrointestinal tract. Cooking denatures the avidin, disabling it from interfering with biotin absorption.

Fosphenytoin: (Moderate) Fosphenytoin use for greater than one year while taking biotin can lead to decreased concentrations of biotin. Anticonvulsants that are potent CYP3A4 inducers, like fosphenytoin, are thought to increase biotin metabolism, leading to reduced biotin status and inhibition of intestinal biotin absorption. This can result in decreased efficacy of biotin. Discuss biotin status with patients taking these medications concomitantly.

Phenobarbital: (Moderate) Phenobarbital use for greater than one year while taking biotin can lead to decreased concentrations of biotin. Anticonvulsants that are potent CYP3A4 inducers, like phenobarbital, are thought to increase biotin metabolism, leading to reduced biotin status and inhibition of intestinal biotin absorption. This can result in decreased efficacy of biotin. Discuss biotin status with patients taking these medications concomitantly.

Phenytoin: (Moderate) Phenytoin use for greater than one year while taking biotin can lead to decreased concentrations of biotin. Anticonvulsants that are potent CYP3A4 inducers, like phenytoin, are thought to increase biotin metabolism, leading to reduced biotin status and inhibition of intestinal biotin absorption. This can result in decreased efficacy of biotin. Discuss biotin status with patients taking these medications concomitantly.

Primidone: (Moderate) Primidone use for greater than one year while taking biotin can lead to decreased concentrations of biotin. Anticonvulsants that are potent CYP3A4 inducers, like primidone, are thought to increase biotin metabolism, leading to reduced biotin status and inhibition of intestinal biotin absorption. This can result in decreased efficacy of biotin. Discuss biotin status with patients taking these medications concomitantly.

Finasteride

Saw Palmetto, Serenoa repens: (Moderate) Saw palmetto may inhibit 5 alpha-reductase, preventing the conversion of testosterone to dihydrotestosterone. This action is similar to the action of 5-alpha reductase inhibitors, such as dutasteride and finasteride. Co-use is likely to be common by patients, but the effects of co-use are not known. In theory, the effects could be additive, but it is not known if the added effects would be beneficial or harmful. Clinicians should be alert for any unusual effects if patients ingest saw palmetto supplements while taking 5-alpha reductase inhibitors.

Soy Isoflavones: (Minor) Theoretically, because the soy isoflavones appear to inhibit type II 5-alpha-reductase, the soy isoflavones may have additive effects with other 5-alpha reductase inhibitors.

Terazosin: (Minor) Terazosin has been reported to increase peak concentrations of finasteride by 16% and AUC by 31% when the two agents are coadministered. The interaction is of minor importance.

Biotin

Biotin has been very rarely associated with any adverse effects, even with high doses. There is one case report of life-threatening eosinophilic pleuro-pericardial effusion in an elderly woman who took a combination of 10 mg/day of biotin and 300 mg/day of pantothenic acid for two months.

Finasteride

Adverse reactions to finasteride are generally mild and transient. In a long-term (4 years) clinical trial in men with benign prostatic hypertrophy (BPH) , the most frequently reported adverse reactions to finasteride were related to sexual function. At 1 year, the adverse reactions reported to be drug-related were impotence (erectile dysfunction), decreased libido, decreased ejaculate volume, ejaculation dysfunction, breast enlargement, breast tenderness (mastalgia), and rash (unspecified). There was no significant difference between finasteride and placebo in the incidences of impotence, decreased libido, and ejaculation dysfunction in years 2 to 4 of the study. However, during post marketing surveillance, continued erectile dysfunction, orgasm dysfunction or other orgasm disorders, and ejaculation dysfunction following treatment discontinuation have been reported. From June 1992, when finasteride was approved, until February 1995, the FDA received reports of gynecomastia in 214 men (median age: 71 yrs). Most were taking a dose of 5 mg/day PO. Gynecomastia has been the most frequently reported adverse effect of this drug since it was marketed. The onset of gynecomastia ranged from 14 days to 2.5 years (median: 180 days). Thirty percent had unilateral gynecomastia, 25% had bilateral involvement, and, in the remainder of reports, this information was not specified. Twenty-seven percent of patients were also taking other medications that are known to cause gynecomastia. Gynecomastia resolved either completely or partially in 80% of subjects after finasteride was discontinued, however, in at least 2 cases, a new primary malignancy of primary intraductal breast cancer subsequently developed.[24660] In a 4 to 6 year trial where patients were randomized to receive finasteride 5 mg/day, doxazosin 4 or 8 mg/day, a combination of the two drugs, or placebo, four patients reported breast cancer as an adverse experience; three of the patients were receiving finasteride therapy and one patient was receiving combination therapy. In addition, male breast cancer has been reported during post-marketing experience. Other post-marketing adverse reactions have included depression, testicular pain that continued after discontinuation of treatment, and hypersensitivity reactions including pruritus, urticaria, and angioedema (including swelling of the lips, tongue, throat, and face).

In controlled trials of finasteride for the treatment of male pattern hair loss, 1.4% of patients discontinued therapy due to adverse events, compared with 1.6% of placebo-treated patients. Discontinuation of therapy because of a drug-related sexual adverse experience occurred in 1.2% of patients on finasteride and 0.9% of patients on placebo. The following adverse events were reported as at least possibly drug-related in finasteride-treated patients: libido decrease (1.8%), impotence (1.3%), and ejaculation disorder (1.2%), primarily decreased ejaculate volume. The incidence of each of the above adverse effects decreased to <= 0.3% by the fifth year of treatment. During post marketing surveillance, decreased libido and libido disorders that continued after discontinuation of treatment was reported.

Finasteride may cause spermatogenesis inhibition or oligospermia, decreased sperm motility, or decreased semen volume. The clinical significance of finasteride’s effect on semen characteristics for an individual male patient’s fertility is not known; consider the potential effects on semen when assessing a male with infertility. In a 52-week, randomized, double-blind, placebo-controlled study in healthy men, finasteride (5 mg PO once daily) significantly decreased total sperm count (-34.3%) compared to baseline at 26 weeks but not at 52 weeks or at the 24-week follow-up. Semen volume was decreased at 52 weeks for finasteride (-14.5%), but the effect was not statistically significant. Sperm concentration was decreased by finasteride (-7.4%) but was not significant for either drug. Significant reductions of 6 to 12% in sperm motility were observed during treatment. Sperm morphology was not affected. One subject taking finasteride had decreases in sperm count of more than 90% of baseline values at 52 weeks; partial recovery was noted at the 24-week follow-up. During post marketing surveillance, male infertility and/or poor seminal quality following treatment discontinuation have been reported. It should be noted that normalization or improvement of seminal quality has also been reported after discontinuation of finasteride.

By inhibiting the conversion of testosterone to DHT, finasteride and other 5-alpha-reductase inhibitors have the ability to cause teratogenesis, specifically abnormalities in the external genitalia of the male fetus (e.g., hypospadias).

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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