Bonzol

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Bonzol uses


DESCRIPTION

Bonzol 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, Bonzol 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:

Bonzol capsules for oral administration contain 50 mg, 100 mg, or 200 mg Bonzol.

Inactive Ingredients: anhydrous lactose, lactose monohydrate, magnesium stearate, pregelatinized starch, sodium lauryl sulfate, talc. Capsule shells for 200 mg Bonzol 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 Bonzol 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.

Bonzol Molecular Structure

CLINICAL PHARMACOLOGY

Bonzol 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 Bonzol with sex hormone receptors. The only other demonstrable hormonal effect is weak androgenic activity. Bonzol 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 Bonzol to receptors of gonadal steroids at target organs. In addition, Bonzol 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, Bonzol 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 Bonzol on the pituitary-ovarian axis.

In the treatment of fibrocystic breast disease, Bonzol 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 Bonzol is reversible. Ovulation and cyclic bleeding usually return within 60 to 90 days when therapy with Bonzol is discontinued.

In the treatment of hereditary angioedema, Bonzol 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, Bonzol 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.

Pharmacokinetics

Absorption: After oral administration of a 400 mg dose to healthy male volunteers, peak plasma concentrations of Bonzol 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 Bonzol.

The pharmacokinetic parameters for Bonzol 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 Bonzol 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

( ng/mL)

Mean Tmax (h)

Mean AUC0-∞ ± SD

( ng*h/mL)

Fasting Fed Fasting Fed Fasting Fed
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 Bonzol 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 Bonzol 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 Bonzol 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: Bonzol is lipophilic and can partition into cell membranes, indicating the likelihood of distribution into deep tissue compartments.

Metabolism and Excretion: Bonzol 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 Bonzol and ethisterone. At least ten different products were identified in feces.

The reported elimination half-life of Bonzol is variable across studies. The mean half-life of Bonzol 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 Bonzol was reported as 23.7 hours.

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INDICATIONS AND USAGE

Endometriosis

Bonzol 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. Bonzol 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.

Hereditary Angioedema

Bonzol capsules are indicated for the prevention of attacks of angioedema of all types (cutaneous, abdominal, laryngeal) in males and females.

CONTRAINDICATIONS

Bonzol capsules should not be administered to patients with:

  • Undiagnosed abnormal genital bleeding.
  • Markedly impaired hepatic, renal, or cardiac function.
  • Pregnancy (see WARNINGS ).
  • Breast feeding.
  • Porphyria - Bonzol can induce ALA synthetase activity and hence porphyrin metabolism.
  • Androgen-dependent tumor.
  • Active thrombosis or thromboembolic disease and history of such events.
  • Hypersensitivity to Bonzol.
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WARNINGS

Use of Bonzol 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 Bonzol, administration of the drug should be discontinued and the patient should be apprised of the potential risk to the fetus. Exposure to Bonzol 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 Bonzol 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.

Bonzol 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 Bonzol 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 Bonzol 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 Bonzol, 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.

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PRECAUTIONS

Because Bonzol 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 Bonzol, periodic liver function tests should be performed.

Administration of Bonzol has been reported to cause exacerbation of the manifestations of acute intermittent porphyria (see CONTRAINDICATIONS ).

Laboratory monitoring of the hematologic state should be considered.

Drug Interactions

Prolongation of prothrombin time occurs in patients stabilized on warfarin.

Therapy with Bonzol may cause an increase in carbamazepine levels in patients taking both drugs.

Bonzol can cause insulin resistance. Caution should be exercised when used with antidiabetic drugs.

Bonzol 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 Bonzol.

Bonzol 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 Bonzol 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 Bonzol.

Laboratory Tests

Bonzol 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Current data are insufficient to assess the carcinogenicity of Bonzol.

Pregnancy

Teratogenic Effects

Pregnancy Category X

Bonzol 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 Bonzol 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.

Nursing Mothers

(See CONTRAINDICATIONS .)

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of Bonzol did not include sufficient numbers of subjects aged 65 and over to determine the safety and effectiveness of Bonzol in elderly patients.

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ADVERSE REACTIONS

The following events have been reported in association with the use of Bonzol:

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 Bonzol, 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 Bonzol of 400 mg or more. It is recommended that patients receiving Bonzol 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 Bonzol 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 Bonzol 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.

DOSAGE AND ADMINISTRATION

Endometriosis

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 Bonzol. 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 Bonzol 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 Bonzol. A nonhormonal method of contraception is recommended when Bonzol 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 Bonzol. 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.

Hereditary Angioedema

The dosage requirements for continuous treatment of hereditary angioedema with Bonzol 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.

HOW SUPPLIED

Bonzol 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)

Bonzol 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)

Bonzol 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.

Distributed by:

Lannett Company, Inc.

Philadelphia, PA 19154

CIB70495B

Rev. 08/17

Bonzol pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Bonzol available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Bonzol destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Bonzol Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Bonzol pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."DANAZOL CAPSULE [LANNETT COMPANY, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."DANAZOL: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "danazol". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Bonzol?

Depending on the reaction of the Bonzol after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Bonzol 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 Bonzol 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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Review

sdrugs.com conducted a study on Bonzol, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Bonzol consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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