Ludasterin
Ludasterin Uses, Dosage, Side Effects, Food Interaction and all others data.
Ludasterin is a dual inhibitor of 5α-reductase. It inhibits both type 1 and type 2, 5α-reductase isoenzymes, which are responsible for the conversion of testosterone to 5α-dihydrotestosterone (DHT). DHT is the androgen primarily responsible for hyperplasia of glandular prostatic tissue.
Ludasterin is a synthetic 4-azasteroid compound that selectively inhibits both the type I and type II isoforms of steroid 5α-reductase, an intracellular enzyme that converts testosterone to 5α-dihydrotestosterone (DHT). Ludasterin works by reducing the levels of circulating DHT. It was also shown to reduce the size of the prostate gland, improve urinary flow, and symptoms of benign prostatic hyperplasia alone or in combination with tamsulosin. The effect of the reduction of DHT by dutasteride is dose-dependent, with the maximum effect observed within 1-2 weeks following initial administration.
After 1 and 2 weeks of daily dosing with dutasteride 0.5 mg, median serum DHT concentrations were reduced by 85% and 90%, respectively. The serum concentrations of DHT were maintained to be decreased by more than 90% in 85% of patients following 1 years' administration of oral dutasteride 0.5 mg/day. As evident from the clinical studies, dutasteride may also cause decreases in serum PSA in the presence of prostate cancer.
Trade Name | Ludasterin |
Availability | Prescription only |
Generic | Dutasteride |
Dutasteride Other Names | Dutasterida, Dutasteride |
Related Drugs | tamsulosin, finasteride, Flomax, prazosin, tadalafil, Cialis |
Type | |
Formula | C27H30F6N2O2 |
Weight | Average: 528.5297 Monoisotopic: 528.221147444 |
Protein binding | Dutasteride is about 99% bound to albumin and 96.6% bound to α-1 acid glycoprotein in the serum. |
Groups | Approved, Investigational |
Therapeutic Class | BPH/ Urinary retention/ Urinary incontinence |
Manufacturer | |
Available Country | Argentina |
Last Updated: | September 19, 2023 at 7:00 am |
![Ludasterin Ludasterin](https://www.medicinesfaq.com/media/png/ludasterin.png)
Uses
Ludasterin is used for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to:
- Improve symptoms
- Reduce the risk of acute urinary retention
- Reduce the risk of the need for BPH-related surgery
Ludasterin is also used to associated treatment for these conditions: Benign Prostatic Hyperplasia (BPH), Symptomatic Benign Prostatic Hyperplasia
How Ludasterin works
The 5α-reductase is a nuclear-bound steroid intracellular enzyme primarily located in the prostatic stromal cell that converts the androgen testosterone into the more active metabolite, 5α-dihydrotestosterone (DHT). DHT is considered to be the primary androgen playing a role in the initial development and subsequent enlargement of the prostate gland. It serves as the hormonal mediator for the hyperplasia upon accumulation within the prostate gland. DHT displays a higher affinity towards androgen receptors in the prostate gland compared to testosterone and by acting on the androgen receptors, DHT modulates genes that are responsible for cell proliferation. Responsible for the synthesis of approximately one-third of circulating DHT, type I 5α-reductase is predominant in the sebaceous glands of most regions of skin, including the scalp, and liver. The type II 5a-reductase isozyme is primarily found in the prostate, seminal vesicles, epididymides, and hair follicles as well as liver, and is responsible for two-thirds of circulating DHT. Due to its dual inhibition of both isoenzymes of 5α-reductase, dutasteride causes a near-complete suppression of DHT. Compared to a 70% reduction of serum DHT levels caused by finasteride, a near-complete suppression of serum DHT-more than 90% is seen with dutasteride.
By forming a stable complex with both type II and type II 5α-reductase, dutasteride inhibits its enzymatic action of converting testosterone to 5α-dihydrotestosterone (DHT), which is the androgen primarily responsible for the initial development and subsequent enlargement of the prostate gland. It is proposed that DHT is the principal androgen responsible for prostatic growth in later life-normal masculinization of the external genitalia and maturation of the prostate gland during development-thus reducing the serum DHT levels results in reduced prostatic volume and increased epithelial apoptosis. Ludasterin is a competitive and specific inhibitor of both Type I and Type II 5α-reductase isoenzymes and when evaluated under in vitro and in vivo conditions, the dissociation of the drug from the drug-enzyme complex is reported to be extremely slow. Ludasterin does not bind to the human androgen receptor.
Dosage
Ludasterin dosage
The recommended dose is Ludasterin 0.5 mgorally once daily. The capsules should be swallowed whole. Ludasterin may be administered with or without food.
Side Effects
- Sexual problems (such as decreased sexual interest/ ability, decrease in the amount of semen/ sperm released during sex)
- Impotence (trouble getting or keeping an erection)
- Testicle pain or swelling
- Increased breast size
- Breast tenderness.
Toxicity
LD50 values
The estimated dermal LD50 of dutasteride in rabbits is > 2,000 mg/kg.
Overdose
In studies of volunteers receiving single doses of dutasteride up to 40 mg (which is 80 times the therapeutic dose) for 7 days, there were no reports of clinically significant adverse events. Low incidences of impotence, reduced libido, gynecomastia, and ejaculation disorder occurred significantly more often in dutasteride than placebo recipients. There are no known antidotes for dutasteride. In case of overdose, appropriate symptomatic and supportive treatment should be given.
Nonclinical Toxicology
In a 2-year carcinogenicity mouse study, there was an increased incidence of benign hepatocellular adenomas in female mice receiving 250 mg/kg/day. An increased incidence of Leydig cell hyperplasia was observed in male rats receiving doses of 7.5 mg/kg/day and greater. At tumorogenic doses, the luteinizing hormone (LH) levels in rats were increased by 167%. There was no demonstrated a genotoxic potential of dutasteride or its metabolites in a bacterial mutagenesis assay, a chromosomal aberration assay in CHO cells, and a micronucleus assay in rats. At much higher doses than the maximum recommended human dose (MRHD) in sexually mature male rats, dutasteride caused a dose- and time-dependent decrease in fertility, reduced cauda epididymal (absolute) sperm counts but not sperm concentration (at 50 and 500 mg/kg/day), reduced weights of the epididymis, prostate, and seminal vesicles, and microscopic changes in the male reproductive organs. At exposures 425- and 315-fold the expected clinical exposure of dutasteride in rats and dogs, respectively, there were some signs of non-specific, reversible, centrally-mediated toxicity without associated histopathological changes.
Pregnancy and Lactation
As DHT is a necessary hormone for the development of male genitalia, exposure to dutasteride in pregnant women bearing male fetuses may cause fetal harm. In animal reproduction and developmental toxicity studies, dutasteride inhibited normal development of external genitalia in male fetuses. Although it is not known whether dutasteride is excreted in human milk, the use of dutasteride in women of childbearing potential, including nursing women. In elderly patients, the half-life of dutasteride may increase. As the renal elimination of dutasteride is very minimal, the use of dutasteride in patients renal insufficiency is reported to be safe. There are no specific dosage adjustment recommendations for use in elderly patients or patients with renal impairment.
Precaution
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 Ludasterin. Patients with a large residual urinary volume and/or severely diminished urinary flow may not be good candidates for 5 a-reductase inhibitor therapy and should be carefully monitored for obstructive uropathy. Blood Donation: Men being treated with Ludasterin should not donate blood until at least 6 months have passed following their last dose. The purpose of this deferred period is to prevent administration of Ludasterin to a pregnant female transfusion recipient.
Interaction
Care should be taken when administering Ludasterin to patients taking potent, chronic CYP3A4 inhibitors. Ludasterin does not inhibit the in vitro metabolism of model substrates for the major human cytochrome P450 isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) at a concentration of 1,000 ng/ml, 25 times greater than steady-state serum concentrations in humans. In vitro studies demonstrate that Ludasterin does not displace Warfarin, Diazepam, or Phenytoin from plasma protein binding sites, nor do these model compounds displace Ludasterin.
Food Interaction
- Take with or without food. The absorption is unaffected by food.
Ludasterin Drug Interaction
Unknown: aspirin, aspirin, aspirin, aspirin, apixaban, apixaban, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, tamsulosin, tamsulosin, metoprolol, metoprolol, metoprolol, metoprolol, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol
Ludasterin Disease Interaction
Volume of Distribution
Ludasterin displays a large volume of distribution ranging from 300 to 500 L. Following daily oral administration of 0.5 mg dutasteride healthy subjects for 12 months, the semen dutasteride concentrations averaged 3.4 ng/mL (range: 0.4 to 14 ng/mL) with 11.5% of serum dutasteride concentrations being partitioned into semen.
Elimination Route
Following oral administration of a single dose of 0.5 mg dutasteride, the peak serum concentrations were reached within 2 to 3 hours. Following daily oral administration of 0.5 mg dutasteride, the steady-state concentration of 40 ng/mL is expected to be achieved at 6 months following initial administration. In healthy subjects, the absolute bioavailability was 60%, ranging from 40% to 94%. While food intake reduced the maximum serum concentrations by 10 to 15%, food intake is reported to have a negligible effect on the bioavailability of the drug.
Half Life
The terminal elimination half-life of dutasteride is approximately 5 weeks at steady state. This long half-life accounts for the serum concentrations remaining detectable for up to 4 to 6 months after discontinuation of treatment.
Clearance
In a study of healthy volunteers receiving single oral doses of dutasteride ranging from 0.01 to 40 mg, dutasteride displayed a low linear clearance of 0.58 L/h. The estimated inter-individual variability for the linear clearance was high.
Elimination Route
Ludasterin and its metabolites mainly undergo fecal excretion. About 1-15% of the dose is excreted as the unchanged parent compound, while 2-90% of the total dose is excreted in the form of dutasteride-related metabolites in the feces. Trace amounts of unchanged dutasteride, with less than 1%, can also be detected in the urine. Therefore, on average, the dose unaccounted for approximated 55%, with a range between 5% and 97%.
Pregnancy & Breastfeeding use
Pregnancy Category X. Ludasterin is contraindicated for use in women.
Contraindication
Ludasterin is contra-indicated for use in women and children and for patients with known hypersensitivity to Ludasterin, and other 5 a-reductase inhibitors. Warnings: Exposure of women-risk to male fetus: Ludasterin is absorbed through the skin. Therefore, women who are pregnant or may be pregnant should not handle Ludasterin capsules because of the possibility of absorption of Ludasterin and the potential risk of a fetal anomaly to a male fetus. If contact is made with leaking capsules, the contact area should be washed immediately with soap and water.
Special Warning
Pediatric use: Ludasterin is not indicated for use in the pediatric population. Safety and effectiveness in the pediatric population have not been established.
Geriatric use: No overall differences in safety or efficacy were observed between elderly and adult subjects.
Elderly use: No dosage adjustment is necessary for subjects with renal impairment or for the elderly.
Hepatic impairment: Due to the absence of data in patients with hepatic impairment, no dosage recommendation can be made.
Acute Overdose
In volunteer studies, single doses of Ludasterin up to 40 mg (80 times the therapeutic dose) for 7 days have been administered without significant safety concerns. In a clinical study, daily doses of 5 mg (10 times the therapeutic dose) were administered to 60 subjects for 6 months with no additional adverse effects to those seen at therapeutic doses of 0.5 mg. There is no specific antidote for Ludasterin. Therefore, in cases of suspected overdosage symptomatic and supportive treatment should be given as appropriate, taking the long half-life of Ludasterin into consideration.
Storage Condition
Store in a cool and dry place, protected from light
Innovators Monograph
You find simplified version here Ludasterin
Ludasterin contains Dutasteride see full prescribing information from innovator Ludasterin Monograph, Ludasterin MSDS, Ludasterin FDA label