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FINASTERIDE

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Finasteride, a synthetic 4-azasteroid compound, is a specific inhibitor of steroid 5 alpha-reductase, an intracellular enzyme that converts testosterone into androgen 5 alpha-dihydrotestosterone (DHT).

Specific Substances

    1) 4-Azaandrost-1-ene-17-caroxamide
    2) N-(1,1-dimethylethyl)-3-oxo-, (5-alpha, 17-beta)-
    3) MK-0906
    4) MK-906
    5) CAS 98319-26-7

Available Forms Sources

    A) FORMS
    1) Finasteride is available in the United States as a 1 mg(Prod Info PROSCAR(R) oral tablets, 2013) or 5 mg tablet (Prod Info PROSCAR(R) oral tablets, 2013).
    B) USES
    1) Finasteride is indicated for the treatment of symptomatic benign prostatic hyperplasia (Prod Info PROSCAR(R) oral tablets, 2013) and male pattern alopecia (Prod Info PROPECIA(R) oral tablets, 2012).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Finasteride is used for the treatment of symptomatic benign prostatic hyperplasia and male pattern alopecia.
    B) PHARMACOLOGY: Finasteride is a synthetic 4-azasteroid compound that competitively and specifically inhibits 5 alpha-reductase (type 2), an isoenzyme that metabolizes testosterone to dihydrotestosterone (DHT) in the prostate gland, liver, and skin. This inhibition blocks the peripheral conversion of testosterone to DHT, leading to a reduction in serum and tissue DHT.
    C) TOXICOLOGY: Excessive doses can lead to decreased systemic DHT concentrations.
    D) EPIDEMIOLOGY: Clinically significant toxicity from overdose has not been reported in humans.
    E) WITH THERAPEUTIC USE
    1) Adverse effects include increased risk of breast and prostate cancer, male infertility, depression, decreased libido, decreased ejaculate volume, impotence, gynecomastia, and orthostatic hypotension. Finasteride is associated with an increased risk of high grade prostate cancer. It is teratogenic and should not be taken or handled by women of child bearing age.
    F) WITH POISONING/EXPOSURE
    1) Overdoses resulting in significant toxicity have not been reported. Overdose effects are anticipated to be an extension of adverse effects following therapeutic doses, including orthostatic hypotension.
    0.2.20) REPRODUCTIVE
    A) Finasteride is classified as FDA pregnancy category X and is not indicated for use in women. Embryo-fetal toxicity (ie, decreased prostatic and seminal vesicular weights, delayed preputial separation, transient nipple development) in male offspring has been reported in animal studies. Because finasteride has the ability to inhibit the conversion of testosterone to 5 alpha-dihydrotestosterone (DHT), pregnant women should be warned of the potential risk to the male fetus.
    0.2.21) CARCINOGENICITY
    A) According to the 7-year Prostate Cancer Prevention Trial, men taking finasteride experienced an increased risk of high-grade prostate cancer compared with placebo. Male breast cancer has been reported during several studies of finasteride; however, the relationship between long-term finasteride use and the development of breast cancer is not clear.

Laboratory Monitoring

    A) Monitor vital signs with large overdoses or if coingestants are involved.
    B) No specific blood or serum monitoring is indicated. Monitoring should be based on the clinical effects observed.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Monitor vital signs.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Monitor vital signs. HYPOTENSION: Monitor blood pressure, administer isotonic fluids at 10 to 20 mL/kg. Administer norepinephrine or dopamine if hypotension persists. ACUTE ALLERGIC REACTION: In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required.
    C) DECONTAMINATION
    1) PREHOSPITAL: Prehospital gastrointestinal decontamination is not routinely required following a minor exposure.
    2) HOSPITAL: Finasteride has a low toxicity profile and gastric decontamination is unlikely to be necessary unless a coingestant is involved. Consider activated charcoal for a large overdose if the ingestion is recent and the patient is not vomiting and the airway can be maintained.
    D) AIRWAY MANAGEMENT
    1) Airway compromise is not expected with isolated finasteride ingestion.
    E) ANTIDOTE
    1) None.
    F) HYPOTENSION
    1) Administer IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids.
    G) ACUTE ALLERGIC REACTION
    1) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    H) ENHANCED ELIMINATION
    1) Hemodialysis and hemoperfusion are UNLIKELY to be effective because of the high degree of protein binding (90%).
    I) PATIENT DISPOSITION
    1) HOME CRITERIA: Asymptomatic patients with inadvertent ingestions can be managed at home with observation.
    2) OBSERVATION CRITERIA: Symptomatic patients and patients with deliberate overdose should be referred to a health care facility for observation and treatment.
    3) ADMISSION CRITERIA: Patients are not expected to develop toxicity requiring admission from an isolated finasteride ingestion.
    4) CONSULT CRITERIA: Finasteride is FDA pregnancy category X. Any pregnant woman exposed to finasteride should be referred to a perinatologist, obstetrician, or specialist in teratogenesis.
    J) PITFALLS
    1) When managing a suspected finasteride overdose, the possibility of multidrug involvement should be considered. Finasteride is FDA pregnancy category X, women should be counseled to avoid pregnancy after exposure and exposed pregnant women should be referred for fetal evaluation.
    K) PHARMACOKINETICS
    1) Peak plasma concentrations of finasteride occur within 1 to 2 hours of ingestion. The mean bioavailability is 63% and protein binding is 90%. The volume of distribution is 76L. Finasteride is primarily metabolized in the liver and is excreted in feces (57%) and urine (39%). The terminal half-life is 6 hours (range: 4 to 6 hours) and may increase by 15% (6 to 15 hours) in men over 70 years of age.

Range Of Toxicity

    A) TOXICITY: No cases of significant toxicity from isolated finasteride ingestion have been reported. Single doses up to 400 mg and multiple doses of finasteride up to 80 mg/day for 3 months have resulted in NO adverse effects.
    B) THERAPEUTIC DOSE: Recommended dose is 5 mg orally once daily for benign prostatic hyperplasia and 1 mg daily for male pattern alopecia.

Clinical Effects

Summary Of Exposure

    A) USES: Finasteride is used for the treatment of symptomatic benign prostatic hyperplasia and male pattern alopecia.
    B) PHARMACOLOGY: Finasteride is a synthetic 4-azasteroid compound that competitively and specifically inhibits 5 alpha-reductase (type 2), an isoenzyme that metabolizes testosterone to dihydrotestosterone (DHT) in the prostate gland, liver, and skin. This inhibition blocks the peripheral conversion of testosterone to DHT, leading to a reduction in serum and tissue DHT.
    C) TOXICOLOGY: Excessive doses can lead to decreased systemic DHT concentrations.
    D) EPIDEMIOLOGY: Clinically significant toxicity from overdose has not been reported in humans.
    E) WITH THERAPEUTIC USE
    1) Adverse effects include increased risk of breast and prostate cancer, male infertility, depression, decreased libido, decreased ejaculate volume, impotence, gynecomastia, and orthostatic hypotension. Finasteride is associated with an increased risk of high grade prostate cancer. It is teratogenic and should not be taken or handled by women of child bearing age.
    F) WITH POISONING/EXPOSURE
    1) Overdoses resulting in significant toxicity have not been reported. Overdose effects are anticipated to be an extension of adverse effects following therapeutic doses, including orthostatic hypotension.

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) In a large randomized study of finasteride in men with symptomatic benign hyperplasia (n=3047), 1.2% of men treated with 5 mg/day of finasteride alone (n=768) experienced hypotension compared with 0.7% of men in a placebo group (n=737). Postural hypotension was reported in 9.1% of men in the finasteride alone group compared with 8% in the placebo group (Prod Info PROSCAR(R) oral tablets, 2013).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) WITH THERAPEUTIC USE
    a) One study reported that approximately 2.7% of patients reported headache during the first 6 months of finasteride therapy; symptoms were reported less frequently with ongoing therapy (Moore et al, 1995)
    b) In clinical studies of women receiving finasteride for idiopathic hirsutism, mild and transient headache was reported in one case (Castello et al, 1996).
    B) DEPRESSIVE DISORDER
    1) WITH THERAPEUTIC USE
    a) Depression was reported in postmarketing experience with finasteride use (Prod Info PROSCAR(R) oral tablets, 2013).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) DIARRHEA
    1) WITH THERAPEUTIC USE
    a) Diarrhea (30%) was reported frequently in patients with advanced prostate carcinoma given a combination therapy of finasteride and flutamide (Staiman & Lowe, 1997).
    b) LACK OF EFFECT: Diarrhea has NOT been reported in studies where finasteride was used as a monotherapy (Mocellini et al, 1993; Moore et al, 1995; McConnell et al, 1998).
    B) CONSTIPATION
    1) WITH THERAPEUTIC USE
    a) In a 5-year review of the safety and efficacy of finasteride, 2% of patients reported constipation within the first 6 months of therapy (Moore et al, 1995).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) IMPOTENCE
    1) WITH THERAPEUTIC USE
    a) Impotence was the most commonly reported adverse effect and was rated as mild to moderate by patients with benign prostatic hyperplasia (BPH) in a large multicenter study (Mocellini et al, 1993).
    b) In a large randomized study of finasteride in men with symptomatic benign hyperplasia (n=3047), 18.5% of men treated with 5 mg/day of finasteride alone (n=768) developed impotence compared with 12.2% of men in a placebo group (n=737) (Prod Info PROSCAR(R) oral tablets, 2013).
    B) DISORDER OF EJACULATION
    1) WITH THERAPEUTIC USE
    a) In a large randomized study of finasteride in men with symptomatic benign hyperplasia (n=3047), 7.2% of men treated with 5 mg/day of finasteride alone (n=768) experienced abnormal ejaculation compared with 2.3% of men in a placebo group (n=737) (Prod Info PROSCAR(R) oral tablets, 2013).
    C) ABNORMAL SEXUAL FUNCTION
    1) WITH THERAPEUTIC USE
    a) Abnormal sexual function and decreased libido were both reported in a large randomized study of finasteride in men with symptomatic benign hyperplasia (n=3047). Study results showed that abnormal sexual function was reported by 2.5% of men treated with 5 mg/day of finasteride alone (n=768) compared with 0.9% of men in a placebo group (n=737); 10% of men in the finasteride alone group experienced decreased libido compared with 5.7% of men in the placebo group (n=737) (Prod Info PROSCAR(R) oral tablets, 2013).
    D) MALE INFERTILITY
    1) WITH POISONING/EXPOSURE
    a) Male infertility and/or poor quality of semen have been reported rarely with finasteride use. Improvement of semen quality was reported after discontinuation of finasteride (Prod Info PROSCAR(R) oral tablets, 2013).
    E) PROSTATE SPECIFIC ANTIGEN ABNORMAL
    1) WITH THERAPEUTIC USE
    a) Finasteride use can cause a decrease in serum prostate specific antigen (PSA) levels by approximately 50% in patients with benign prostatic hyperplasia (BPH), even in the presence of prostate cancer (Prod Info PROSCAR(R) oral tablets, 2013; Tenover et al, 1997).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) WITH THERAPEUTIC USE
    a) In one study, rash was reported in 1% or more of men receiving finasteride therapy (McConnell et al, 1998).
    B) VASCULITIS
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Two weeks after starting finasteride (5 mg daily) for prostatism, a 58-year-old man developed an itchy, lumpy rash on his extremities. A skin biopsy was positive for leukocytoclastic vasculitis. Therapy included drug cessation and dapsone 50 mg twice daily; symptoms resolved without sequelae (Lear & Byrne, 1996).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) DRUG-INDUCED MYOPATHY
    1) WITH THERAPEUTIC USE
    a) CHRONIC TOXICITY
    1) CASE REPORT: A 70-year-old man taking finasteride (5 mg daily) for several years developed progressive weakness of the arms and legs along with some respiratory difficulty. Drug cessation resulted in a gradual increase of muscle strength and dyspneic symptoms improved over a one month period (Haan et al, 1997).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) GYNECOMASTIA
    1) WITH THERAPEUTIC USE
    a) Gynecomastia (unilateral or bilateral) is frequently reported with therapeutic doses of finasteride (5 mg dose) (Green et al, 1996; Steiner, 1996; Fleshner & Fair, 1996; Carlin et al, 1997; Staiman & Lowe, 1997).
    b) In a large randomized study of finasteride in men with symptomatic benign hyperplasia (n=3047), 2.2% of men treated with 5 mg/day of finasteride alone (n=768) developed gynecomastia compared with 0.7% of men in a placebo group (n=737) (Prod Info PROSCAR(R) oral tablets, 2013).
    c) CASE SERIES: ONSET: Out of 214 patients reporting gynecomastia, symptoms began within a range of 14 days up to 2.5 years (median, 180 days) after receiving finasteride. Eighty percent of patients who stopped the medication had partial or complete remission; 20% reported no change (Green et al, 1996).
    d) CASE SERIES: In one study, patients with advanced prostate cancer who were treated with a combination therapy of finasteride and flutamide frequently developed gynecomastia (30%) and mastodynia (10%). Patients were treated with low dose tamoxifen with relief of pain in all cases (Staiman & Lowe, 1997)
    e) CASE STUDY: A 67-year-old man with prostatitis and epididymitis developed gynecomastia, breast tenderness, and an elevated estradiol level of 75 ng/L (normal 10 to 50) approximately 3 months after finasteride was begun (Carlin et al, 1997).
    f) ETIOLOGY: Finasteride alters the ratio of estrogen to androgen, thereby making it biologically possible for finasteride to cause gynecomastia (Green et al, 1996; Steiner, 1996). It is suggested that elevations in serum estradiol levels could precipitate gynecomastia in patients receiving finasteride (Carlin et al, 1997).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) HYPERSENSITIVITY REACTION
    1) WITH THERAPEUTIC USE
    a) In postmarketing experience, hypersensitivity reactions such as pruritus, urticaria, and swelling of the lips and face have been reported with therapeutic use of finasteride (Prod Info PROSCAR(R) oral tablets, 2013).

Reproductive

    3.20.1) SUMMARY
    A) Finasteride is classified as FDA pregnancy category X and is not indicated for use in women. Embryo-fetal toxicity (ie, decreased prostatic and seminal vesicular weights, delayed preputial separation, transient nipple development) in male offspring has been reported in animal studies. Because finasteride has the ability to inhibit the conversion of testosterone to 5 alpha-dihydrotestosterone (DHT), pregnant women should be warned of the potential risk to the male fetus.
    3.20.2) TERATOGENICITY
    A) CASE REPORT
    1) A male infant was born with bladder exstrophy, severe epispadius, undescended right testicle, bilateral indirect inguinal hernias, and diastasis of the pubic symphysis. His father had taken finasteride 5 mg/day for two years. His mother was diagnosed with autoimmune hypothyroidism at 30 weeks gestation (treated with levothyroxine 50 mcg/day) and developed gestational diabetes that did not require medication. It is unclear if the infant's urogenital abnormalities were related to the finasteride exposure (Lechuga Sancho et al, 2004).
    B) ANIMAL STUDIES
    1) LACK OF EFFECT: No developmental abnormalities were observed in male or female offspring resulting from mating male rats treated with finasteride 80 mg/kg/day (61 times the human exposure of 5 mg/day) with untreated females (Prod Info PROSCAR(R) oral tablets, 2007).
    2) LACK OF EFFECT: In rabbit fetuses exposed to finasteride in utero from days 6 to 18 of gestation at maternal doses up to 100 mg/kg/day (1000 times the recommended human dose), there was no evidence of fetal abnormalities. Because the dosing did not occur during the critical period of genital development in male rats, the absence of fetal abnormalities would be expected.
    3) Dose-dependent development of hypospadia was observed in 3.6 to 100% of male offspring when pregnant rats were administered finasteride doses of 100 mcg/kg/day to 100 mg/kg/day (1 to 1000 times the recommended human dose of 5 mg/day). When pregnant rats were treated with finasteride 30 mcg/kg/day or greater (3/10 or more of the recommended human dose), decreased prostatic and seminal vesicular weights, delayed preputial separation, and transient nipple development in male offspring. With finasteride 3 mcg/kg/day or greater (3/100 or more of the recommended human dose), decreased anogenital distance was observed in male rats. There was a slight decrease in fertility of F1 male offspring when finasteride 3 mg/kg/day (30 times the human dose) was administered during late gestation and the lactation period. Days 16 to 17 of gestation is the critical period during which these effects may be induced in male rat offspring.(Prod Info PROSCAR(R) oral tablets, 2007). Following administration of finasteride 0.01 to 100 mg/kg/day to pregnant rats, decreased distance, nipple retention, hypospadias, prostate malformations, and ectopic testes were observed in male offspring (Bowman et al, 2003). These effects are expected with 5-alpha reductase inhibitors in male offspring (Prod Info PROSCAR(R) oral tablets, 2007).
    4) Pregnant rhesus monkeys were given intravenous administration of finasteride at 800 ng/day (60 to 120 times the highest estimated exposure to finasteride from semen of men taking finasteride 5 mg/day) resulted in no abnormalities in male fetuses; however, oral administration of finasteride at 2 mg/kg/day (20 times the human estimated exposure) resulted in genital abnormalities in male fetuses (Prod Info PROSCAR(R) oral tablets, 2007).
    5) None of the animal studies reported abnormalities in the female offspring with in utero exposure to finasteride (Prod Info PROSCAR(R) oral tablets, 2007).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) The manufacturer has classified finasteride as FDA Pregnancy Category X (Prod Info PROSCAR(R) oral tablets, 2007).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Finasteride is not indicated for use in women; it is not known whether it is excreted in human milk (Prod Info PROSCAR(R) oral tablets, 2007).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) According to the 7-year Prostate Cancer Prevention Trial, men taking finasteride experienced an increased risk of high-grade prostate cancer compared with placebo. Male breast cancer has been reported during several studies of finasteride; however, the relationship between long-term finasteride use and the development of breast cancer is not clear.
    3.21.3) HUMAN STUDIES
    A) PROSTATE CARCINOMA
    1) According to the 7-year Prostate Cancer Prevention Trial, men taking finasteride experienced an increased risk of high-grade prostate cancer compared with placebo. Men 55 years of age or older taking 5 mg of finasteride daily who had a normal digital rectal examination and a PSA level less than or equal to 3 nanograms/mL at baseline were compared with men treated with placebo. A 1.8% increased risk of Gleason score 8 to 10 prostate cancer was reported in the finasteride group compared with a 1.1% increase in the placebo group. In a 4-year, placebo-controlled, clinical trial of dutasteride, another 5 alpha-reductase inhibitor, the dutasteride-treated group also had an increased risk of prostate cancer compared with the placebo-treated group (1% vs 0.5%). In these studies, whether the effect of 5 alpha-reductase inhibitors or study-related factors impacted prostate volume has not been established (Prod Info PROSCAR(R) oral tablets, 2013).
    B) MALE BREAST CANCER
    1) Male breast cancer was reported during several long-term studies of finasteride; however, the association between finasteride use and the development of breast cancer is not clear. Four cases of breast cancer were reported in men treated with finasteride during a large 4 to-6-year randomized controlled study involving 3047 men. During a placebo-controlled study conducted over 4 years and involving 3040 men, 2 cases of breast cancer were reported. One case of breast cancer was reported in a patient treated with finasteride during a 7-year placebo-controlled trial involving 18,882 men; however, one case was also reported in the placebo group (Prod Info PROSCAR(R) oral tablets, 2013).
    3.21.4) ANIMAL STUDIES
    A) LEYDIG CELL ADENOMAS
    1) In carcinogenicity studies with CD-1 mice, a significant increase in the incidence of testicular Leydig cell adenomas was observed at a dose of 250 mg/kg/day (228 times the prescribed human dose). In addition, an increased incidence of Leydig hyperplasia was seen in mice at a dose of 25 mg/kg/day (approximately, 23 times human exposure) and in rats at 40 mg/kg/day (approximately 39 times human exposure). In both rodent species treated at high doses, a positive correlation between proliferative changes in the Leydig cells and an increase in serum luteinizing hormone (LH) levels (2- to 3-fold above control) was observed (Prod Info PROSCAR(R) oral tablets, 2013).
    B) LACK OF EFFECT
    1) No tumorigenic effects were observed in a two year study of Sprague Dawley rats receiving doses of finasteride up to 160 mg/kg/day in males and 320 mg/kg/day in females (111 and 274 times, respectively the human recommended dose of 5 mg/day) (Prod Info PROSCAR(R) oral tablets, 2013).
    2) No drug-related Leydig cell changes were observed in rats or dogs given finasteride at 20 mg/kg/day (30 times the human exposure) and 45 mg/kg/day (350 times the human exposure), respectively for 1 year. Similarly, no drug-related effects were reported in mice given approximately 2.5 mg/kg/day (2.3 times the human exposure) for 19 months (Prod Info PROSCAR(R) oral tablets, 2013).

Genotoxicity

    A) There was no evidence of mutagenicity in the following tests: an in vitro bacterial mutagenesis assay, a mammalian cell mutagenesis assay, and an in vitro alkaline elution assay. Finasteride did produce a slight increase in chromosome aberration in an in vitro chromosome aberration assay using Chinese hamster ovary cells at concentrations corresponding to 4000 to 5000 times the peak plasma levels in humans given a total dose of 5 mg. However, no treatment-related increase in chromosome aberration was seen in mice at the maximum tolerated dose of 250 mg/kg/day (228 times the human exposure) (Prod Info PROSCAR(R) oral tablets, 2013).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs with large overdoses or if coingestants are involved.
    B) No specific blood or serum monitoring is indicated. Monitoring should be based on the clinical effects observed.
    4.1.2) SERUM/BLOOD
    A) SUMMARY
    1) No specific blood or serum monitoring is indicated. Monitoring should be based on the clinical effects observed.
    2) Estradiol levels may be elevated in men with complaints of gynecomastia or mastodynia.
    3) Finasteride lowers serum prostate specific antigen (PSA) levels; PSA levels may not be a reliable screening test for prostate cancer in patients ingesting finasteride.
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Monitor vital signs with large overdoses or if coingestants are involved.

Methods

    A) CHROMATOGRAPHY
    1) One report described a high-performance liquid chromatographic (HPLC) method with ultraviolet detection for the determination of finasteride in human plasma. The lowest limit of quantification was found to be a 1 ng/mL and allowed pharmacokinetic evaluation of finasteride at doses down to 5 mg (therapeutic dose). (Constanzer et al, 1991).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients are not expected to develop toxicity requiring admission from an isolated finasteride ingestion.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Asymptomatic patients with inadvertent ingestions can be managed at home with observation.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Finasteride is FDA pregnancy category X. Any pregnant woman exposed to finasteride should be referred to a perinatologist, obstetrician, or specialist in teratogenesis.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Symptomatic patients and patients with deliberate overdose should be referred to a health care facility for observation and treatment.

Monitoring

    A) Monitor vital signs with large overdoses or if coingestants are involved.
    B) No specific blood or serum monitoring is indicated. Monitoring should be based on the clinical effects observed.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Prehospital gastrointestinal decontamination is not routinely required following a minor exposure.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Finasteride has a low toxicity profile and gastric decontamination is unlikely to be necessary unless a coingestant is involved. Consider activated charcoal for a large overdose if the ingestion is recent and the patient is not vomiting and the airway can be maintained.
    2) ACTIVATED CHARCOAL
    a) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    1) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    a) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    b) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    b) CHARCOAL DOSE
    1) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    a) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    2) ADVERSE EFFECTS/CONTRAINDICATIONS
    a) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    b) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY: Treatment is symptomatic and supportive. Monitor vital signs.
    2) SEVERE TOXICITY: Treatment is symptomatic and supportive. Monitor vital signs. HYPOTENSION: Monitor blood pressure, administer isotonic fluids at 10 to 20 mL/kg. Administer norepinephrine or dopamine if hypotension persists. ACUTE ALLERGIC REACTION: In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required.
    B) MONITORING OF PATIENT
    1) Monitor vital signs with large overdoses or if coingestants are involved.
    2) No specific blood or serum monitoring is indicated. Monitoring should be based on the clinical effects observed.
    3) Estradiol levels may be elevated in men with complaints of gynecomastia or mastodynia.
    4) Finasteride lowers serum prostate specific antigen (PSA) levels; PSA levels may not be a reliable screening test for prostate cancer in patients ingesting finasteride.
    C) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    D) ACUTE ALLERGIC REACTION
    1) Hypersensitivity reactions to finasteride have been reported infrequently, but can include rash and swelling of the lips and face.
    2) SUMMARY
    a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    3) BRONCHOSPASM
    a) ALBUTEROL
    1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    4) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm.
    b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).
    5) MILD CASES
    a) DIPHENHYDRAMINE
    1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
    2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    6) MODERATE CASES
    a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).
    7) SEVERE CASES
    a) EPINEPHRINE
    1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
    2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TL,et al).
    8) AIRWAY MANAGEMENT
    a) OXYGEN: 5 to 10 liters/minute via high flow mask.
    b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
    c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
    d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
    e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
    f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    9) MONITORING
    a) CARDIAC MONITOR: All complicated cases.
    b) IV ACCESS: Routine in all complicated cases.
    10) HYPOTENSION
    a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.
    1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
    2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).
    11) H1 and H2 ANTIHISTAMINES
    a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
    1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).
    b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
    c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).
    12) DYSRHYTHMIAS
    a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.
    13) OTHER THERAPIES
    a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).
    E) DRUG-INDUCED GYNECOMASTIA
    1) GYNECOMASTIA has been reported following finasteride therapy.
    2) CASE STUDY: One study describes treating male gynecomastia with tamoxifen. In a small study, 5 of 6 men with advanced prostate carcinoma experiencing painful gynecomastia had a decrease in symptoms following low dose tamoxifen (10 mg/day for 1 month); the remaining patient was treated with 30 mg/day for 1 additional month with resolution of the pain (Staiman & Lowe, 1997).

Enhanced Elimination

    A) LACK OF EFFECT
    1) Hemodialysis and hemoperfusion are UNLIKELY to be effective because of the high degree of protein binding (90%).

Range Of Toxicity

Summary

    A) TOXICITY: No cases of significant toxicity from isolated finasteride ingestion have been reported. Single doses up to 400 mg and multiple doses of finasteride up to 80 mg/day for 3 months have resulted in NO adverse effects.
    B) THERAPEUTIC DOSE: Recommended dose is 5 mg orally once daily for benign prostatic hyperplasia and 1 mg daily for male pattern alopecia.

Therapeutic Dose

    7.2.1) ADULT
    A) BENIGN PROSTATIC HYPERPLASIA: The recommended dose for the treatment of benign prostatic hyperplasia is 5 mg orally once daily; administered alone or in combination with doxazosin (Prod Info PROSCAR(R) oral tablets, 2013).
    B) MALE PATTERN ALOPECIA: The recommended dose for the treatment of male pattern alopecia is 1 mg orally once daily (Prod Info PROPECIA(R) oral tablets, 2012).
    7.2.2) PEDIATRIC
    A) Finasteride is not indicated for use in pediatric patients. The safety and effectiveness of finasteride in children have not been established (Prod Info PROSCAR(R) oral tablets, 2013).

Minimum Lethal Exposure

    A) ANIMAL DATA
    1) MICE: Significant lethality occurred in male and female MICE at single oral doses of 1500 mg/square meter (500 mg/kg) (Prod Info PROSCAR(R) oral tablets, 2013).
    2) RATS: Oral doses of 2360 mg/square meter (400 mg/kg) and 5900 mg/square meter (1000 mg/kg), caused significant lethality in female and male rats, respectively (Prod Info PROSCAR(R) oral tablets, 2013).

Maximum Tolerated Exposure

    A) Single doses up to 400 mg and multiple doses of finasteride up to 80 mg/day for 3 months have been well tolerated with NO adverse effects (Prod Info PROSCAR(R) oral tablets, 2013).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (INTRAPERITONEAL)MOUSE:
    a) 372 mg/kg (RTECS , 2001)
    2) LD50- (ORAL)MOUSE:
    a) 486 mg/kg (RTECS , 2001)
    3) LD50- (SUBCUTANEOUS)MOUSE:
    a) >2 g/kg (RTECS , 2001)
    4) LD50- (INTRAPERITONEAL)RAT:
    a) 885 mg/kg (RTECS , 2001)
    5) LD50- (ORAL)RAT:
    a) 418 mg/kg (RTECS , 2001)
    6) LD50- (SUBCUTANEOUS)RAT:
    a) >2 g/kg (RTECS , 2001)

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Finasteride is a synthetic 4-azasteroid compound that competitively and specifically inhibits 5 alpha-reductase (type 2), an isoenzyme that metabolizes testosterone to dihydrotestosterone (DHT) in the prostate gland, liver, and skin. This inhibition blocks the peripheral conversion of testosterone to DHT, leading to a reduction in serum and tissue DHT (Prod Info PROSCAR(R) oral tablets, 2013).

Toxicologic Mechanism

    A) Excessive doses of finasteride can lead to decreased systemic dihydrotestosterone (DHT) concentrations (Prod Info PROSCAR(R) oral tablets, 2013).

References

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