DRUGS & SUPPLEMENTS
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Danocrine is a synthetic steroid derived from ethisterone. It is a white to pale yellow crystalline powder, practically insoluble or insoluble in water, and sparingly soluble in alcohol. Chemically, Danocrine is 17α-Pregna-2, 4-dien-20-yno [2, 3-d]-isoxazol-17-ol. The molecular formula is C22H27NO2. It has a molecular weight of 337.46 and the following structural formula:
Danocrine capsules for oral administration contain 50 mg, 100 mg, or 200 mg Danocrine.
Inactive Ingredients: anhydrous lactose, lactose monohydrate, magnesium stearate, pregelatinized starch, sodium lauryl sulfate, talc. Capsule shells for 200 mg Danocrine contain D&C Yellow #10, FD&C Red #40, D&C Red #28, gelatin, and titanium dioxide. Capsule shells for 50 mg and 100 mg Danocrine contain D&C Yellow # 10, FD&C Red # 40, gelatin, and titanium dioxide. The capsule imprinting ink contains: shellac glaze in ethanol, iron oxide black, n-butyl alcohol, propylene glycol, ethanol, methanol, FD&C Blue No. 2 Aluminum Lake, FD&C Red No. 40 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake, and D&C Yellow No. 10 Aluminum Lake.
Danocrine suppresses the pituitary-ovarian axis. This suppression is probably a combination of depressed hypothalamic-pituitary response to lowered estrogen production, the alteration of sex steroid metabolism, and interaction of Danocrine with sex hormone receptors. The only other demonstrable hormonal effect is weak androgenic activity. Danocrine depresses the output of both follicle-stimulating hormone and luteinizing hormone (LH).
Recent evidence suggests a direct inhibitory effect at gonadal sites and a binding of Danocrine to receptors of gonadal steroids at target organs. In addition, Danocrine has been shown to significantly decrease IgG, IgM and IgA levels, as well as phospholipid and IgG isotope autoantibodies in patients with endometriosis and associated elevations of autoantibodies, suggesting this could be another mechanism by which it facilitates regression of the disease.
In the treatment of endometriosis, Danocrine alters the normal and ectopic endometrial tissue so that it becomes inactive and atrophic. Complete resolution of endometrial lesions occurs in the majority of cases.
Changes in vaginal cytology and cervical mucus reflect the suppressive effect of Danocrine on the pituitary-ovarian axis.
In the treatment of fibrocystic breast disease, Danocrine usually produces partial to complete disappearance of nodularity and complete relief of pain and tenderness. Changes in the menstrual pattern may occur.
Generally, the pituitary-suppressive action of Danocrine is reversible. Ovulation and cyclic bleeding usually return within 60 to 90 days when therapy with Danocrine is discontinued.
In the treatment of hereditary angioedema, Danocrine at effective doses prevents attacks of the disease characterized by episodic edema of the abdominal viscera, extremities, face, and airway which may be disabling and, if the airway is involved, fatal. In addition, Danocrine corrects partially or completely the primary biochemical abnormality of hereditary angioedema by increasing the levels of the deficient C1 esterase inhibitor (C1El). As a result of this action the serum levels of the C4 component of the complement system are also increased.
Absorption: After oral administration of a 400 mg dose to healthy male volunteers, peak plasma concentrations of Danocrine are reached between 2 and 8 hours, with a median Tmax value of 4 hours. Steady state conditions are observed following 6 days of twice daily dosing of Danocrine.
The pharmacokinetic parameters for Danocrine after administering a 400 mg oral dose to healthy males are summarized in the following table:
|Parameters||Mean ± SD (n=15)|
|Cmax (ng/mL)||69.6 ± 29.9|
|Tmax (h)||2.47 ± 1.62|
|AUC0-∞ (ng*h/mL)||601 ± 181|
|t1/2 (h)||9.70 ± 3.29|
|Total Body Clearance (L/h)||727 ± 221|
The pharmacokinetic parameters for Danocrine after oral administration of 100, 200 and 400 mg single doses to healthy female volunteers are summarized in the following table:
|Dose (mg)|| |
Mean Cmax ± SD
|Mean Tmax (h)|| |
Mean AUC0-∞ ± SD
|100||45.9 ±23.9||113.8 ± 46.0||1-8||2-6||484 ± 263||741 ± 265|
|200||63.8 ± 27.7||159 ± 57.3||1-6||2-4||681 ± 363||1252 ± 307|
|400||60.4 ± 30.0||253.7 ± 105.5||1-6||2-4||754 ± 443||1851 ± 605|
Dose proportionality: Bioavailability studies indicate that blood levels do not increase proportionally with increases in the administered dose.
Single dose administration of Danocrine in healthy female volunteers found that a 4-fold increase in dose produced only a 1.6 and 2.5-fold increase in AUC and a 1.3 and 2.2-fold increase in Cmax in the fasted and fed state, respectively. A similar degree of non-dose proportionality was observed at steady state.
Food Effect: Single dose administration of 100 mg and 200 mg capsules of Danocrine to female volunteers showed that both the extent of availability and the maximum plasma concentration increased by 3 to 4 fold, respectively, following a meal (> 30 grams of fat), when compared to the fasted state. Further, food also delayed mean time to peak concentration of Danocrine by about 30 minutes. Even after multiple dosing under less extreme food/fasting conditions, there remained approximately a 2 to 2.5 fold difference in bioavailability between the fed and fasted states.
Distribution: Danocrine is lipophilic and can partition into cell membranes, indicating the likelihood of distribution into deep tissue compartments.
Metabolism and Excretion: Danocrine appears to be metabolized and the metabolites are eliminated by renal and fecal pathways. The two primary metabolites excreted in the urine are 2-hydroxymethyl Danocrine and ethisterone. At least ten different products were identified in feces.
The reported elimination half-life of Danocrine is variable across studies. The mean half-life of Danocrine in healthy males is 9.7 h. After 6 months of 200 mg three times a day dosing in endometriosis patients, the half-life of Danocrine was reported as 23.7 hours.
Danocrine capsules are indicated for the treatment of endometriosis amenable to hormonal management.
Fibrocystic Breast Disease
Most cases of symptomatic fibrocystic breast disease may be treated by simple measures (e.g., padded brassieres and analgesics).
In infrequent patients, symptoms of pain and tenderness may be severe enough to warrant treatment by suppression of ovarian function. Danocrine capsules are usually effective in decreasing nodularity, pain, and tenderness. It should be stressed to the patient that this treatment is not innocuous in that it involves considerable alterations of hormone levels and that recurrence of symptoms is very common after cessation of therapy.
Danocrine capsules are indicated for the prevention of attacks of angioedema of all types (cutaneous, abdominal, laryngeal) in males and females.
Danocrine capsules should not be administered to patients with:
Use of Danocrine in pregnancy is contraindicated. A sensitive test (e.g., beta subunit test if available) capable of determining early pregnancy is recommended immediately prior to start of therapy. Additionally a non-hormonal method of contraception should be used during therapy. If a patient becomes pregnant while taking Danocrine, administration of the drug should be discontinued and the patient should be apprised of the potential risk to the fetus. Exposure to Danocrine in utero may result in androgenic effects on the female fetus; reports of clitoral hypertrophy, labial fusion, urogenital sinus defect, vaginal atresia, and ambiguous genitalia have been received.
Thromboembolism, thrombotic and thrombophlebitic events including sagittal sinus thrombosis and life-threatening or fatal strokes have been reported.
Experience with long-term therapy with Danocrine is limited. Peliosis hepatis and benign hepatic adenoma have been observed with long-term use. Peliosis hepatis and hepatic adenoma may be silent until complicated by acute, potentially life-threatening intraabdominal hemorrhage. The physician therefore should be alert to this possibility. Attempts should be made to determine the lowest dose that will provide adequate protection. If the drug was begun at a time of exacerbation of hereditary angioneurotic edema due to trauma, stress or other cause, periodic attempts to decrease or withdraw therapy should be considered.
Danocrine has been associated with several cases of benign intracranial hypertension also known as pseudotumor cerebri. Early signs and symptoms of benign intracranial hypertension include papilledema, headache, nausea and vomiting, and visual disturbances. Patients with these symptoms should be screened for papilledema and, if present, the patients should be advised to discontinue Danocrine immediately and be referred to a neurologist for further diagnosis and care.
A temporary alteration of lipoproteins in the form of decreased high density lipoproteins and possibly increased low density lipoproteins has been reported during Danocrine therapy. These alterations may be marked, and prescribers should consider the potential impact on the risk of atherosclerosis and coronary artery disease in accordance with the potential benefit of the therapy to the patient.
Before initiating therapy of fibrocystic breast disease with Danocrine, carcinoma of the breast should be excluded. However, nodularity, pain, tenderness due to fibrocystic breast disease may prevent recognition of underlying carcinoma before treatment is begun. Therefore, if any nodule persists or enlarges during treatment, carcinoma should be considered and ruled out.
Patients should be watched closely for signs of androgenic effects some of which may not be reversible even when drug administration is stopped.
Because Danocrine may cause some degree of fluid retention, conditions that might be influenced by this factor, such as epilepsy, migraine, or cardiac or renal dysfunction, polycythemia and hypertension require careful observation. Use with caution in patients with diabetes mellitus.
Since hepatic dysfunction manifested by modest increases in serum transaminases levels has been reported in patients treated with Danocrine, periodic liver function tests should be performed.
Administration of Danocrine has been reported to cause exacerbation of the manifestations of acute intermittent porphyria (see CONTRAINDICATIONS ).
Laboratory monitoring of the hematologic state should be considered.
Prolongation of prothrombin time occurs in patients stabilized on warfarin.
Therapy with Danocrine may cause an increase in carbamazepine levels in patients taking both drugs.
Danocrine can cause insulin resistance. Caution should be exercised when used with antidiabetic drugs.
Danocrine may raise the plasma levels of cyclosporin and tacrolimus, leading to an increase of the renal toxicity of these drugs. Monitoring of systemic concentrations of these drugs and appropriate dose adjustments may be needed when used concomitantly with Danocrine.
Danocrine can increase the calcemic response to synthetic vitamin D analogs in primary hypoparathyroidism.
The risk of myopathy and rhabdomyolysis is increased by concomitant administration of Danocrine with statins such as simvastatin, atorvastatin and lovastatin. Caution should be exercised if used concomitantly. Consult the product labeling for statin drugs for specific information on dose restrictions in presence of Danocrine.
Danocrine treatment may interfere with laboratory determinations of testosterone, androstenedione and dehydroepiandrosterone. Other metabolic events include a reduction in thyroid binding globulin and T4 with increased uptake of T3, but without disturbance of thyroid stimulating hormone or of free thyroxin index.
Current data are insufficient to assess the carcinogenicity of Danocrine.
Pregnancy Category X
Danocrine administered orally to pregnant rats from the 6th through the 15th day of gestation at doses up to 250 mg/kg/day (7-15 times the human dose) did not result in drug-induced embryotoxicity or teratogenicity, nor difference in litter size, viability or weight of offspring compared to controls. In rabbits, the administration of Danocrine on days 6-18 of gestation at doses of 60 mg/kg/day and above (2-4 times the human dose) resulted in inhibition of fetal development.
(See CONTRAINDICATIONS .)
Safety and effectiveness in pediatric patients have not been established.
Clinical studies of Danocrine did not include sufficient numbers of subjects aged 65 and over to determine the safety and effectiveness of Danocrine in elderly patients.
The following events have been reported in association with the use of Danocrine:
Androgen like effects include weight gain, acne and seborrhea. Mild hirsutism, edema, hair loss, voice change, which may take the form of hoarseness, sore throat or of instability or deepening of pitch, may occur and may persist after cessation of therapy. Hypertrophy of the clitoris is rare.
Other possible endocrine effects are menstrual disturbances including spotting, alteration of the timing of the cycle and amenorrhea. Although cyclical bleeding and ovulation usually return within 60-90 days after discontinuation of therapy with Danocrine, persistent amenorrhea has occasionally been reported.
Flushing, sweating, vaginal dryness and irritation and reduction in breast size, may reflect lowering of estrogen. Nervousness and emotional lability have been reported. In the male a modest reduction in spermatogenesis may be evident during treatment. Abnormalities in semen volume, viscosity, sperm count, and motility may occur in patients receiving long-term therapy.
Hepatic dysfunction, as evidenced by reversible elevated serum enzymes and/or jaundice, has been reported in patients receiving a daily dosage of Danocrine of 400 mg or more. It is recommended that patients receiving Danocrine be monitored for hepatic dysfunction by laboratory tests and clinical observation. Serious hepatic toxicity including cholestatic jaundice, peliosis hepatis, and hepatic adenoma have been reported (see WARNINGS and PRECAUTIONS ).
Abnormalities in laboratory tests may occur during therapy with Danocrine including CPK, glucose tolerance, glucagon, thyroid binding globulin, sex hormone binding globulin, other plasma proteins, lipids and lipoproteins.
The following reactions have been reported, a causal relationship to the administration of Danocrine has neither been confirmed nor refuted; allergic: urticaria, pruritus and rarely, nasal congestion; CNS effects: headache, nervousness and emotional lability, dizziness and fainting, depression, fatigue, sleep disorders, tremor, paresthesias, weakness, visual disturbances, and rarely, benign intracranial hypertension, anxiety, changes in appetite, chills, and rarely convulsions, Guillain-Barre syndrome; gastrointestinal: gastroenteritis, nausea, vomiting, constipation, and rarely, pancreatitis and splenic peliosis; musculoskeletal: muscle cramps or spasms, or pains, joint pain, joint lockup, joint swelling, pain in back, neck, or extremities, and rarely, carpal tunnel syndrome which may be secondary to fluid retention; genitourinary: hematuria, prolonged posttherapy amenorrhea; hematologic: an increase in red cell and platelet count. Reversible erythrocytosis, leukocytosis or polycythemia may be provoked. Eosinophilia, leukopenia and thrombocytopenia have also been noted. Skin: rashes (maculopapular, vesicular, papular, purpuric, petechial), and rarely, sun sensitivity, Stevens-Johnson syndrome and erythema multiforme; other: increased insulin requirements in diabetic patients, change in libido, myocardial infarction, palpitation, tachycardia, elevation in blood pressure,interstitial pneumonitis, and rarely, cataracts, bleeding gums, fever, pelvic pain, nipple discharge. Malignant liver tumors have been reported in rare instances, after long-term use.
In moderate to severe disease, or in patients infertile due to endometriosis, a starting dose of 800 mg given in two divided doses is recommended. Amenorrhea and rapid response to painful symptoms is best achieved at this dosage level. Gradual downward titration to a dose sufficient to maintain amenorrhea may be considered depending upon patient response. For mild cases, an initial daily dose of 200 mg to 400 mg given in two divided doses is recommended and may be adjusted depending on patient response. Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with Danocrine. It is essential that therapy continue uninterrupted for 3 to 6 months but may be extended to 9 months if necessary. After termination of therapy, if symptoms recur, treatment can be reinstituted.
Fibrocystic Breast Disease
The total daily dosage of Danocrine for fibrocystic breast disease ranges from 100 mg to 400 mg given in two divided doses depending upon patient response. Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with Danocrine. A nonhormonal method of contraception is recommended when Danocrine is administered at this dose, since ovulation may not be suppressed.
In most instances, breast pain and tenderness are significantly relieved by the first month and eliminated in 2 to 3 months. Usually elimination of nodularity requires 4 to 6 months of uninterrupted therapy. Regular menstrual patterns, irregular menstrual patterns, and amenorrhea each occur in approximately one-third of patients treated with 100 mg of Danocrine. Irregular menstrual patterns and amenorrhea are observed more frequently with higher doses. Clinical studies have demonstrated that 50% of patients may show evidence of recurrence of symptoms within one year. In this event, treatment may be reinstated.
The dosage requirements for continuous treatment of hereditary angioedema with Danocrine should be individualized on the basis of the clinical response of the patient. It is recommended that the patient be started on 200 mg, two or three times a day. After a favorable initial response is obtained in terms of prevention of episodes of edematous attacks, the proper continuing dosage should be determined by decreasing the dosage by 50% or less at intervals of one to three months or longer if frequency of attacks prior to treatment dictates. If an attack occurs, the daily dosage may be increased by up to 200 mg. During the dose adjusting phase, close monitoring of the patient's response is indicated, particularly if the patient has a history of airway involvement.
Danocrine Capsules USP, 50 mg are available as maize opaque/white opaque capsules imprinted with logo "LANNETT" on the cap and "1392" on the body and are supplied in:
Bottles of 100 (NDC 0527-1392-01)
Danocrine Capsules USP, 100 mg are available as maize opaque/maize opaque capsules imprinted with logo "LANNETT" on the cap and "1368" on the body and are supplied in:
Bottles of 100 (NDC 0527-1368-01)
Danocrine Capsules USP, 200 mg are available as orange opaque/orange opaque capsules imprinted with logo "LANNETT" on the cap and "1369" on the body and are supplied in:
Bottles of 60 (NDC 0527-1369-06)
Bottles of 100 (NDC 0527-1369-01)
Store at 20° to 25°C (68° to 77°F).
Dispense in a well-closed container with a child-resistant closure as defined in the USP.
Lannett Company, Inc.
Philadelphia, PA 19154
Depending on the reaction of the Danocrine after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Danocrine not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Danocrine addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
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The information was verified by Dr. Rachana Salvi, MD Pharmacology