Bayer Proviron Mesterolone Tablets

Proviron 25mg Tablets

 

NAME OF THE MEDICINAL PRODUCT

Proviron 25 mg tablets.

 

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 25 mg Mesterolone.

Excipients, see section “List of excipients”

 

PHARMACEUTICAL FORM

White tablets

 

CLINICAL PARTICULARS

Therapeutic indications

> Reduced efficiency in middle and advanced age

Complaints attributable to androgen-deficiency, such as reduced efficiency, easy fatigability, lack of concentration, weak memory, disturbances of libido and potency, irritability, disturbances of sleep, depressive moods, and general vegetative complaints, can be overcome or improved by the use of Proviron tablets.

> Potency disturbances

Potency disorders based on an androgen deficiency are eliminated by administration of Proviron. If other factors are the sole cause or if they contribute to the disorders, Proviron may be administered in support of other therapeutic measures.

> Hypogonadism

Growth, development and function of androgen-dependent target organs are stimulated by Proviron. It promotes development of secondary male sex characteristics in cases of prepuberal androgen-deficiency.

Proviron eliminates deficiency symptoms in cases where a loss of gonadal function has occurred postpuberally.

> Infertility

Oligozoospermia and deficient Leydig-cell secretion may be the cause of infertility. With Proviron sperm count and sperm quality as well as the fructose concentration in the ejaculate can be improved or normalized, thus increasing the chances of procreation.

 

Dosage and method of administration

The tablets are to be swallowed whole with some Liquid.

The following dosages are recommended:

Reduced efficiency and potency disturbances

Commencement of treatment: 1 Proviron tablet 3 times per day.

After satisfactory clinical improvement it can be tried to reduce the dose.

Continuation of treatment: 1 Proviron tablet twice or once per day.

According to type and severity of the complaints, the dose for further treatment is to be adjusted to individual requirements. Continuous treatment over a period of several months is recommended.

> Hypogonadism requires continuous therapy

For development of secondary male sex characteristics 1 – 2 Proviron tablets 3 times per day for several months.

As maintenance dose 1 Proviron tablet 2 – 3 times per day will often be sufficient.

> Infertility – for the improvement of sperm quantity and quality

1 Proviron tablet 2 – 3 times per day for a cycle of spermatogenesis, i. e. for about 90 days.

If necessary, Proviron treatment is to be repeated after an interval of several weeks.

To achieve a higher fructose concentration in the ejaculate in cases of postpuberal Leydig-cell insufficiency: 1 Proviron tablet twice per day over several months.

 

Contraindications

Carcinoma of the prostate, previous or existing liver tumours. Hypersensitivity to the active substances or to any of the excipients see section “List of excipients”.

 

Special warnings and special precautions for use

Androgens are not suitable for enhancing muscular development in healthy individuals or for increasing physical ability.

Proviron is for use in male patients only.

Regular examinations of the prostate should be carried out prophylactically.

In rare cases benign and in even rarer cases malignant liver tumours leading in isolated cases to life-threatening intra-abdominal haemorrhage have been observed after the use of hormonal substances such as the one contained in Proviron. If severe upper abdominal complaints, liver enlargement or signs of intra-abdominal haemorrhage occur, a liver tumour should be included in the differential-diagnostic considerations.

 

Interaction with other medicaments and other forms of interaction

Not applicable.

 

Pregnancy and lactation

Not applicable.

 

Effects on ability to drive and use machines

Not applicable.

 

Undesirable effects

If, in individual cases, frequent or persistent erections occur, the dose should be reduced or the treatment discontinued in order to avoid injury to the penis.

 

Overdose

Acute toxicity studies using single administration showed that Proviron is to be classified as non-toxic. No risk of toxicity is to be expected even after inadvertent single administration of a multiple of the dose required for therapy.

 

Pharmacodynamic properties

Proviron balances a deficiency of androgen formation which begins to fall gradually with increasing age. Therefore, Proviron is suitable for the treatment of all conditions caused by deficient endogenous androgen formation. In the recommended therapeutic dosage, Proviron will not impair spermatogenesis. Proviron is especially well tolerated by the liver.

 

Pharmacokinetic properties

Following oral ingestion Mesterolone is rapidly and almost completely absorbed in a dose range of 25 – 100 mg. The intake of Proviron generates maximum serum drug Levels of 3.1 ± 1.1 ng/ml after 1.6 ± 0.6 hours. Thereafter, drug levels in serum decrease with a terminal half-life of 12 – 13 hours. 98% of Mesterolone is bound to serum proteins. Binding to albumin accounts for 40% and binding to SHBG (sex hormone binding globulin) to 58 %.

Mesterolone is rapidly inactivated by metabolism. The metabolic clearance rate from serum accounts for 4.4 ± 1.6 ml.min-1kg-1. There is no renal excretion of unchanged drug. The main metabolite has been identified as lᾳ-methyl-androsterone, which – in conjugated form – accounts for 55 – 70% of renally excreted metabolites. The ratio of main metabolite glucuronide to sulphate was about 12:1. As a further metabolite lᾳ-methyl-5ᾳ-androstane-3ᾳ,17β-diol has been recognized, which accounted for about 3% of renally eliminated metabolites. No metabolic conversion into estrogens or corticoids has been observed. In form of metabolites, Mesterolone is excreted by about 80% of dose with the urine and by about 13% of dose with the feces. Within 7 days 93 % of dose have been recovered in excreta, the half of which had been excreted with urine within 24 hours.

The absolute bioavailability of Mesterolone was determined to about 3% of the oral dose. The daily intake of Proviron 25mg will lead to an about 30 % increase in drug serum levels.

 

Preclinical safety data

In systemic tolerance studies after repeated administration of Proviron no findings were observed which raise objections to its use at the doses required for therapy.

Experimental investigations into possible sensitizing effects of Proviron have not been carried out. Investigations into embryotoxic effects have not been carried out with Proviron, since the preparation is prescribed for the therapeutic use in male patients.

Fertility studies to clarify a possible deleterious effect on sperm cells have not been carried out with Proviron. On the basis of long-term systemic tolerance studies, these results do not indicate a toxic effect on sperm cells, but a central mediated inhibition of spermatogenesis. Although generally known in animal experiments, this effect has not been observed in humans even after years of usage at the recommended therapeutic dose levels.

Investigations into the mutagenic effect have not been carried out. On the basis of the negative results with other steroid hormones in in vitro and in vivo mutagenicity tests, no such potential is to be expected.

Systemic tolerance studies after repeated administration in rats and dogs over a period of 6 and 12 months did not produce any indications of a substance-related tumorigenic effect. Therefore, a further characterization with regard to a possible tumorigenic potential has not been carried out. However, it must be kept in mind that sex steroids can promote the growth of certain hormone dependent tissues and tumours.

On the whole, the results of toxicological investigations do not raise objections to the prescribed use of Proviron in humans for the indications and at the doses given.

 

List of excipients

Lactose monohydrate

Maize starch

Polyvidone 25 000

Methyl parahydroxybenzoate

Propyl parahydroxybenzoate

Magnesium stearate.

 

Incompatibilities

None so far known.

 

Shelf Life

5 years.

 

Special precautions for storage

None.

 

Nature and contents of container

Proviron 25 tablets are contained in blister packs consisting of transparent films made of polyvinyL chloride and metallic foils made of aluminum (mat side hot sealable) or in amber glass bottles (type III) with tamperproof closure made of polyethylene.

Presentations: 10, 15, 20, 50, 100 or 150 tablets.

 

Instructions for use and handling

Do not store above 30°C.

Keep out of reach of children.

Only on prescription.

 

Manufactured by

Bayer Weimar GmbH und Co. KG

Döbereinerstrasse 20

99427 Weimar

Germany

 

DATE OF REVISION OF THE TEXT

13.07.13

NCI 100 Sildenafil Citrate Tablets

NCI 100

Rx SILDENAFIL CITRATE TABLETS

 

NCI Sildenafil Tablets 100 mg phosphodiesterase-5 (PDE5) inhibitor indicated for the treatment of erectile dysfunction (ED)

 

COMPOSITION

Each film-coated tablet contains:

Sildenafil citrate equivalent to Sildenafil 100mg

Colour: Indigo Carmine

 

PHARMACOLOGY

Sildenafil tablets 100mg is a selective inhibitor of cyclic guanosine monophosphate specific-phosphodiesterase type 5 (PDE-5) enzyme. The physiologic mechanism of erection of the penis involves the release of nitric oxide “NO” in the human corpus cavernosum during sexual stimulation. “NO” activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (c-gmp) producing smooth muscle relaxation and increased blood flow. In the absence of sexual stimulation, Sildenafil is not effective when administered at its therapeutic doses.

 

INDICATIONS

Sildenafil tablets 100 mg is mainly indicated for patients with a failure to achieve erection during sexual intercourse.

 

PHARMACOKINETICS

Following the oral administration in healthy male volunteers, Sildenafil is rapidly absorbed with an absolute bioavailability of about 40% Peak plasma concentrations are attained within 30 to 120 minutes of oral dosing in the fasting state. Both sildenafil and its metabolites are actively bound to the proteins (96%) and have terminal half lives (T1/2) of about 4 hours. The elimination is mainly in the form of faeces and to a lesser extent in the urine.

 

CONTRAINDICATIONS

NCI Sildenafil tablets 100 mg is contraindicated in patients with a known hypersensitivity on sildenafil or any one of the tablet components. There are no adequate and well controlled studies of sildenafil pregnant and lactating women and in paediatric patients.

– Administration of NCI Sildenafil Tablets 100 mg to patients using Nitric oxide donors; such as organic nitrates or organic nitrites in any form. Sildenafil was shown to potentiate the hypotensive effect of nitrates.

– Known hypersensitivity to sildenafil or any component of the tablet.

– NCI Sildenafil Tablets 100 mg is not indicated for use in women. There are no adequate and well controlled studies of sildenafil in pregnant women.

– NCI Sildenafil Tablets 100 mg is not indicated for use in paediatric patients. Safety and effectiveness have not been established in paediatric patients.

 

WARNINGS

NCI Sildenafil should be administered with caution in patients with pre-existing cardiovascular diseases such as myocardial infarction, stroke or life-threatening arrhythmias, patients with a brief history of blood pressure complications, patients with unstable angina, cardiac failure and patients with retinitis pigmentosa.

In the event of an erection that persists longer than 4 hours, the patient should seek immediate medical assistance. If priapism (Painful erection greater than 6 hours in duration) is not treated immediately, penile tissue damage and permanent loss of potency could result.

Patients should stop using NCI Sildenafil tablets 100 mg and seek medical care if a sudden loss of vision occurs in one or both eyes which could be sign of non arteretic anterior ischemic optic neuropathy (NAION). NCI Sildenafil Tablets 100 mg should be used with caution and only when anticipated benefits outweigh the risks in patients with a history of NAION, Patients with a “crowded” optic disc may also be at an increased risk of NAION. Patients should stop NCI Sildenafil Tablets 100 mg and seek prompt medical attention in the event of sudden decrease or loss of hearing. Decreased blood pressure, syncope and prolonged erection may occur at higher sildenafil exposures. In patients taking strong CYP Inhibitors such as ritonavir, Sildenafil exposure is increased. Decrease in Sildenafil is recommended. Recommended dose for ritonavir – treated patients is 25mg prior to sexual activity and the recommended maximum dose is 25 mg within 48 hrs period because concomitant administration increased the blood levels of sildenafil by 11-fold. Consider starting dose of 25mg in patients treated with Erythromycin or strong CYP3A4 Inhibitors (e.g. Ketoconazole itracorrazole, saquinavir) Clinical data have shown that co-administration with saquinavir or erythromycin increased pIasma level of Sildenafil by about 3-fold.
 

PRECAUTIONS

In geriatic patients (age group 65 years and above) with a history of hepatic and renal impairment. Oral administration resulted in reduced clearance of sildenafil. In such subjects, starting dose of 25 mg is recommended as higher plasma levels may increase both the efficacy and incidence of adverse effects.

 

ADVERSE EFFECTS

The following adverse effects were reported on oral administration: headache, flushing, respiratory tract infection, angina pectoris, AV block, syncope, tachycardia, paresthesia, tremor, depression, oesophagitis, rectal hemorrhage, liver function tests, hypoglycemia, retinal vascular disease, photosensitivity, temporary vision loss/decreased vision, ocular, redness, swelling, vitreous detachment/traction, increased intraocular pressure.

 

DRUG INTERACTIONS

Concurrent administration with cytochrome P450 inhibitors resulted in reduced sildenafil clearance in hypertensive subjects, concurrent administration of Sildenafil and calcium channel blocker such as amlodipine (5mg and 10mg) resulted in as additional blood pressure reduction of both systolic and diastolic types. Oral administration of HIV protease inhibitor-ritonavir caused a significant 11-fold increase in Sildenafil plasma AUC (Area Under Curve)

 

DOSAGE

The recommended dose should be taken one hour prior to sexual activity. The maximum frequency of dosing is once per day. The oral recommended dose is 50mg for most patients. Or as directed by the physician.

Based on effectiveness and toleration, the dose may be increased to a maximum recommended dose of 100mg or decreased to 25mg. NCI Sildenafil tabs may be taken with or without food.

Dosage Adjustment In Special Population

Geriatric use: Consider starting dose of 25 mg

Severe renal impairment: Consider starting dose of 25 mg

Hepatic impairment: Consider starting dose of 25mg.

 


OVERDOSAGE

For management of a suspected drug overdose, contact your regional Poison Control centre.

In studies with healthy volunteers of single doses of up to 800 mg, adverse events were similar to those seen at lower doses but incidence rates and severities were increased in cases of overdose standard-supportive be adopted as required. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and not eliminated in the urine.

Treatment of Priapism

Patients should be instructed to report any erections persisting for more than 4 hours to physician. The treatment of priapism/prolonged erection should be according to established medical practice. Physicians may refer to two suggested protocols for detumescence presented below .

Detumescence Protocols

1) Aspirate 40 to 60 ml blood from either left or right corpora using vacutainer and holder for drawing blood. Patient will often detumesce while aspirating. Apply ice for 20 minutes post aspiration if erection remains.
If procedure 1) is unsuccessful then try procedure 2).

2) Put patient in supine position. Dilute 10 mg phenylephrine into 20 ml distilled water for injection (0.05%) with an insulin syringe inject 0.1 to 0.2 ml (50-100 ug) into the corpora every 2 to 5 minutes, until the detumescence occurs. The occasional patient may experience transient bradycardia and hypertension when given phenylephrine injections, therefore monitor patient’s blood pressure and pulse every 10 minutes. Patients at risk include those with cardiac arrhythmias and diabetes. Refer to the prescribing information for phenylephrine before use.

Do not give phenylephrine to patients on MAO inhibitors. When phenylephrine is used within the first 12 hours of erection, the majority of patients will respond.
If procedure 2) is unsuccessful, then try procedure 3).

3) If the above measures fail to detumesce the patient, a urologist should be consulted as soon as possible, especially if the erection has been present for many hours. If priapism is not treated immediately, penile tissue damage and/or permanent loss of potency may result.

 

STORAGE

Store in a cool, dry and dark place.
KEEP ALL MEDICINE OUT IF REACH OF CHILDREN

 

PRESENTATION

Blister of 4 tablets.

 

Marketed in Nigeria by

NCI Pharm Chem Ind. Ltd.

29,Igbehinadun Street,

Oshodi, Lagos, NIGERIA.

 

Manufactured in India by

Syncom Formulations (I) Ltd.

256-257, Sector-I

Pithampur (Dhar) 454-775, India

http://www.sfil.in