TESTOSTERONE UNDECANOATE CAPSULES

NAME OF THE MEDICINAL PRODUCT

Testosterone Undecanoate Capsules IP 40mg,

Testosterone Undecanoate Capsules USP 40mg

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 40 mg of testosterone undecanoate

PHARMACEUTICAL FORM
Soft capsule. (Short term capsule) Soft oval glossy capsule, transparent, orange in colour, with a yellow oily fill, with imprint ‘Org DV3’ in white.

CLINICAL PARTICULARS

Therapeutic indications
In the replacement therapy of male hypogonadism associated with reduced levels of testosterone. In osteoporosis due to androgen deficiency in males.

Posology and method of administration

Posology

Should be used only if hypogonadism (hyper- and hypogonadotrophic) has been demonstrated, and if other aetiology, responsible for the symptoms, has been excluded before treatment is started. Testosterone insufficiency should be clearly demonstrated by clinical features (regression of secondary sexual characteristics, change in body composition, asthenia, reduced libido, erectile dysfunction etc.) and confirmed by 2 separate blood testosterone measurements.

Dosage
 Adults:
The initial dosage required will usually be 120 – 160 mg daily for two to three weeks. Subsequent dosage (40 – 120 mg daily) should be based on the clinical effect obtained during the first weeks of therapy.

Children:
Safety and efficacy have not been adequately determined in children. To ensure absorption, testosterone undecanoate must be taken with a meal, if necessary with a little fluid and swallowed whole without chewing. It is preferable that half of the daily dose be taken in the morning and the other half in the evening. In general, the dose should be adjusted according to the response of the individual patient.

CONTRAINDICATION
o  Use in patients with carcinoma of prostate   or breast.
o  Use in patients with hypercalciuria, hyppercalcaemia, nephrotic syndrome, ischaemic heart disease or untreated congestive heart failure.
o  Hypersensitivity to the active substance or to any of the excipients.

SPECIAL PRECAUTIONS & WARNINGS

Physicians should consider subjects receiving testosterone undecanoate  for monitoring before the start of treatment, at quarterly intervals for the first 12 months and yearly thereafter for the following parameter:
Digital rectal examination (DRE) of the prostate and PSA,
Hematocrit and haemoglobin to exclude polycythemia.
In patients with pre-existing cardiac, renal or hepatic disease androgen treatment may cause complications characterized by edema with or without congestive heart failure.

Testosterone should only be used with great caution in patients with epilepsy, migraine or hypertension (or a history of these conditions), since aggravation or recurrence may occasionally be induced. The metabolic effects of androgens may decrease the blood glucose and therefore, insulin requirements or other antidiabetic requirements. The treatment regimen should avoid undue stimulation on either physical or mental capacity of the patient. Evidence of excessive sexual stimulation requires discontinuance of therapy.

Androgens may reduce thyroxine-binding globulin and PBI levels without inducing clinical hypothyroidism. Treatment of young boys should proceed with extreme care to avoid premature closure of epiphyses or precocious sexual development.

Initiation of testosterone therapy and its overall direction should only be carried out by specialists.

Testosterone therapy should only be used in male hypogonadism in which testosterone levels have been demonstrated to be low.
Testosterone undecanoate  contains Sunset Yellow (E110, FD&C Yellow no. 6) which may cause allergic reactions.

Interaction with other medicinal products and other forms of interaction

Barbiturates and phenylbutazone taken concurrently may stimulate testosterone metabolism, affecting dosage requirements.

Enzyme-inducing agents may decrease and enzyme-inhibiting drugs may increase testosterone levels. Therefore adjustment of the dose of Testosterone undecanoate may be required.
Androgens may improve glucose tolerance and decrease the need for insulin or other anti-diabetic medicines.
Testosterone undecanoate can increase the anticoagulant action of warfarin. This may result in fluctuations in INR. Patients should be carefully monitored especially when starting and stopping testosterone replacement therapy.
Androgens may enhance the anticoagulant action of coumarine type agents allowing a reduction of the dose of these agents. Testosterone undecanoate  must be taken with a meal to establish appropriate plasma

Fertility, pregnancy and lactation
Testosterone undecanoate is not indicated for use in women and must not be used in pregnant or breastfeeding women

Effects on ability to drive and use machines
As far as known Testosterone Undecanoate has no adverse influence on alertness and concentration.

UNDESIRABLE EFFECTS
The following adverse reactions have been associated with androgen therapy in general:
System organ class
1.  Neoplasms benign, malignant and unspecified (incl. cysts and polyps) – Prostatic cancer
2.  Blood and lymphatic system disorders- Polycythaemia
3.  Metabolism and nutrition disorders- Fluid retention
4.  Psychiatric disorders- Depression, nervousness, mood disturbances, libido increased, libido decreased
5.  Musculoskeletal and connective tissue disorders -Myalgia
6.  Vascular disorders- Hypertension
7.  Gastrointestinal disorders – Nausea
8. Skin and subcutaneous tissue disorders- Pruritus, acne
9. Reproductive system and breast disorders-Gynecomastia, oligozoospermia, priapism, prostatic disorder 2, ejaculation disorder
10. Investigations – Hepatic function abnormal, lipids abnormal 3, PSA increased

MedDRA version 7.1
1 Progression of a sub-clinical prostatic cancer
2 Prostatic growth (to normogonadal size)
3 Decrease in serum LDL-C, HDL-C and triglycerides
During post marketing use of Testosterone undecanoate, diarrhea and abdominal pain has been reported.

Overdose
The acute oral toxicity of testosterone udecanoate is very low. High dosages of Testosterone undecanoate  may cause gastrointestinal complaints due to the oily solvent contained in the capsule. Treatment may consist of emptying the stomach and supportive measures.

Pharmacological properties

Pharmacodynamic properties

Pharmacotherapeutic group: Androgens. ATC code G03B A03 Treatment of hypogonadal men with Testosterone Undecanoate does-dependently restores serum total and bioavailable testosterone to levels within the normal range. Treatment also results in an increase of serum concentrations of dihydrotestosterone (DHT) and estradiol (E2), as well as in a decrease of sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Treatment dose-dependently decreases serum LDL-C, HDL-C and triglycerides, increases hemoglobin and hematocrit, whereas no clinically relevant changes in liver enzymes and PSA have been reported. Treatment may result in an increase in prostate size, but no adverse effects on prostate symptoms have been observed. In hypogonadal diabetic patients, improvement of insuline sensitivity and/or reduction in blood glucose have been reported.
Testosterone Undecanoatehas effects on the growth and maturation of tha male genital organs and structures (i.e. prostate, seminal vesicles, penis, and scrotum) male secondary sexual characteristics such as the development of male hair distribution, such as facial, pubic, chest, and auxiliary hair and other more general effects such as laryngeal enlargement, vocal chord thickening, and alterations in body musculature, bone mineral density and fat distribution.

Pharmacokinetic properties

Absorption:
Following oral administration of Testosterone Undecanoate, an important part of the active substance testosterone undecanoate is co-absorbed with the lipophilic solvent from the intestine into the lymphatic system, thus partially circumventing the firstpass inactivation by the liver. Testosterone Undecanoate must be taken with a normal meal or breakfast to ensure absorption. The bioavailability is about 7%.

Distribution:
From the lymphatic system testosterone undecanoate is released into the plasma and hydrolyzed to testosterone. Single administration of 80 – 160 mg Testosterone Undecanoate leads to a clinically significant increase of total plasma testosterone with peak-levels of approximately 40 nmol/l (Cmax), reached approximately 4-5h (t max) after administration. Plasma testosterone levels remain elevated for at least 8 hours. Testosterone and testosterone undecanoate display a high (over 97%) non-specific blinding to plasma proteins and sex hormone binding globulin in in vitro tests.

Biotransformation:
In plasma and tissues testosteroneundecanoate is hydrolysed to yield the natural male androgen testosterone. Testosterone is further metabolized to dihydrotestosterone and estradiol.

Elimination:
Testosterone, estradiol and dihydrotestosterone are metabolized via the normal pathways. Excretion mainly takes place via the urine as conjugates of etiocholanolone and androsterone

Linearity:
Dose-linearity has been demonstrated for a dose range of 40-240 mg/day

Preclinical safety data
Toxicological studies with testosterone have only shown effects that can be explained by its hormone profile. Testosterone is not genotoxic. Studies in animals on the relation of testosterone and cancer, indicate on the possibility that high doses may promote the tumor growth in the genital rogans, mammary glands and liver. The clinical relevance of this observation is not known. In view of the oral administration of Andriol Testocaps that the high probability of developing diarrhea when taking large number of capsules due to the Castor oil, it is unlikely that such long lasting, high levels of testosterone can be obtained.

Reproduction studies with rodents and primates demonstrated that testosterone treatment may dose-dependently reduce the fertility by suppression of the spermatogenesis.

Testosterone has virilzing effects in female foetuses when it is administered during the organogenesis to pregnant animals.

Pharmaceutical particulars

List of excipients
Capsule contents:
Propylene Glycol Monolaurate Virgin Castor oil
Capsule shell:
Glycerol Gelatin
Sunset Yellow (E110), FD&C Yellow no. 6

Opacode –WB white (printing ink) containing:
Propylene glycol
Titanium dioxide
Polyvinyl acetate phthalate
Macrogol 400
Ammonium hydroxide

 Incompatibilities

Not applicable.

Shelf life

3 years.

Special precautions for storage
Do not store above 30°C. Store in the original package to protect from moisture.

Nature and contents of container

PVC/aluminium foil blister strips of 10 capsules, packed in an aluminium foil sachet. 3, 6, or 12 sachets are packed in an outer cardboard carton. Not all pack sizes may be marketed.

 Special precautions for disposal and other handling

Any unused product or waste material should be disposed of in accordance with local requirements.

MARKETING AUTHORISATION HOLDER

TAJ PHARMA CIS LTD.
Marksistsky lane 6, office 221, Moscow, 109147, Russia

MANUFACTURER:

Manufactured in India by:
TAJ PHARMACEUTICALS LTD,
220, Mahagujarat Ind. Estate,  Moraiya,

Tal. Sanand , Dist. Ahmedabad,

Gujarat, INDIA.

What is in this leaflet

  1. What Testosterone Undecanoate 40mg is and what is it used for
    2. What do you need to know Before you take testosterone undecanoate 40mg
    3. How to take Testosterone Undecanoate 40mg
    4. Possible side effects
    5. How to store Testosterone Undecanoate 40mg
    6. Contents of the pack and other information

1.What Testosterone Undecanoate 40mg is and what is it used for

These are soft, glossy, oval capsules. The active substance, testosterone undecanoate is turned into testosterone by your body. Testosterone is a natural male hormone known as an androgen. It is produced in the body by both men and women.
It is used in adult men for testosterone replacement to treat various health problems caused by a lack of testosterone (male hypogonadism). This should be confirmed by two separate blood testosterone measurements and also include clinical symptoms such as impotence, infertility, low sex drive, tiredness, depressive moods, bone loss caused by low hormone levels.

These are used if your body does not make enough testosterone of its own, for example:  impotence caused by hormonal disorders
·  after castration or a similar problem called eunuchoidism
·  decreased sex drive and decreased mental and physical activity
·  certain types of infertility because you don’t make enough sperm
· It may also be used to treat a type of bone disease (osteoporosis) caused by having too little testosterone.

  1. What do you need to know Before you take testosterone undecanoate 40mg
  • Do not take testosterone undecanoate:
    If you are allergic (hypersensitive) to testosterone undecanoate or any of the ingredients of this medicine .
    · If you have or have had a tumour of your prostate or breast or are suspected to have one ofthese tumours.
    · If you have ever had liver cancer

Take special care with testosterone undecanoate:
Treatment with male hormones like testosterone may increase the size of the prostate gland, especially in elderly men. Therefore your doctor will examine your prostate gland at regular intervals. In men over the age of 45, the prostate gland will be investigated by digital rectal examination (DRE) and blood tests for prostate-specific antigen (PSA).
Additionally, at regular intervals, blood tests will be done to check the oxygen-carrying substance in your red blood cells (haemoglobin). In very rare cases the number of red blood cells will increase too much leading to complications.
The following blood checks should be carried out by your doctor before and during the treatment: testosterone blood level, full blood count.
Medical check may also be necessary in some other conditions.

Tell your doctor if you have ever had, still have, or are suspected to have:
·  breast cancer which has spread to the bones
·  kidney or lung cancer
·  heart disease
·  kidney disease
·  liver disease
·  high blood pressure
·  diabetes mellitus
·  epilepsy
·  migraine, headaches
·  prostatic complaints, such as problems passing urine
·  blood clotting problems – thrombophilia (an abnormality of blood coagulation that increases the risk of thrombosis – blood clots in blood vessels)

If you are suffering from severe heart, liver or kidney disease, treatment with testosterone undecanoate may cause severe complications in the form of water retention in your body sometimes accompanied by (congestive) heart failure.
Tell your doctor if you have high blood pressure or if you are treated for high blood pressure as testosterone may cause a raise in blood pressure.

If you have sleep apnea (temporarily stopping breathing during your sleep), this may get worse if you are using testosterone-containing products. Let your doctor know if you are worried about this. Extra supervision by your doctor may be necessary in case you are overweight or suffer from chronic lung disease.

Also tell your doctor
if you are taking anticoagulants (drugs to treat blood clots)
Your medication may need to be monitored more closely.

Children and adolescents
The safety and efficacy of this medicine has not been adequately determined in children and adolescents.
Extra supervision by the doctor is necessary in the treatment of children and adolescents since testosterone administration in general may cause early sexual development and limits growth.

Other medicines and testosterone undecanoate
➞ Please tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines-even those not prescribed.

Other medicines may affect how testosterone undecanoate works or testosterone undecanoate may affect how they work. Therefore you must tell your doctor or pharmacist if you are using or are about to use:  · insulin and/or other medicines to control your blood sugar levels;
·  medicines to reduce the clotting of your blood (anti-coagulants);
The following medicines may decrease the effect of testosterone undecanoate:
·antibiotics such as rifampicin
·anti-epileptic drugs such as barbiturates, carbamazepine, dichloralphenazone, phenylbutazone, phenytoin and primidone.
The use of androgens like testosterone undecanoate may lead to a reduction of the doses of these medicines

➞Also tell your doctor or pharmacist if you are using or about to use the hormone ACTH or corticosteroids (used to treat various conditions such as rheumatism, arthritis, allergic conditions and asthma). The use of androgens like testosterone undecanoate may increase the risk of water retention, especially if your heart and liver are not working properly.
Laboratory tests:
Androgens may also affect the results of some laboratory tests (e.g. thyroid gland). Therefore you must tell your doctor or the laboratory staff performing the tests that you are using this medicine.

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Using testosterone undecanoate with food and drink
Food allows testosterone undecanoate, the active substance of this medicine to be absorbed by your body.
➞Therefore, testosterone undecanoate  40mg capsule must be taken with a normal meal.

Pregnancy, breast-feeding and fertility testosterone undecanoate are not for use in women, therefore this medicine must not be taken by women who are pregnant or think that they are pregnant, or by women who are breast-feeding.
In men, treatment with testosterone undecanoate can lead to fertility disorders by repressing sperm formation.
If you are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines
As far as is known this medicine has no influence on driving or using machines.

Important information about some of the ingredients of testosterone undecanoate
This medicine contains :

Sunset yellow (E110) which can cause allergic type reactions including asthma. Allergy is more common in those people who are allergic to aspirin.

Improper use
If you are a patient who participates in competitions governed by the World Anti-Doping Agency (WADA), then you should consult the WADA-code before using this medicine as testosterone undecanoate can interfere with anti-doping testing.
The misuse of this medicine to enhance ability in sports carries serious health risks and is to be discouraged.

  1. How to take Testosterone Undecanoate 40mg

Always take this medicine exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Adults
The recommended dose is 3–4 capsules daily during the first 2–3 weeks, followed by a gradual decrease to 1–3 capsules daily. Look at the label on the pack to see how many capsules your doctor would like you to take each day.

You must take this medicine with a normal meal.
Swallow the capsules whole without chewing, using some water or other fluid.
Depending on the dose prescribed for you, take the capsules as shown below.

Daily dose= 1 then 1 capsule in morning
If Daily dose = 2 then 1 capsule in morning and 1 in evening
if Daily dose= 3 then 2 capsule in morning and 1 in evening
if daily dose = 4 then 2 capsule in morning and 2 in evening

Elderly
Smaller doses, taken less often, may be given if you are elderly.
Your doctor will have chosen the correct dose for you.

 Use in children and adolescents
The safety and efficacy of this medicine have not been adequately determined in children and adolescents. Pre-pubertal children using this medicine will be monitored by your doctor. If you take more testosterone undeacnoate than you should:
If you have taken several capsules at once, there is no need for great concern, however you should tell your doctor. The castor oil in the capsule may cause diarrhoea.

If you forgot to take testosterone undecanoate:
 Don’t worry. If you miss the morning dose and it is more than 2 hours after breakfast, wait until lunch-time and then take the dose.
If you miss the evening dose, and its more than 2 hours after dinner, don’t take the missed dose. Take the next morning dose as normal.

Remember to always take testosterone undecanoate  with food.

If you stop taking testosterone undecanoate: When treatment with this medicine is stopped, complaints such as those experienced before treatment may re-occur within a few weeks.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

  1. Possible side effects

Like all medicines, testosterone undecanoate can have side effects, although not everybody gets them.

Common (may affect up to 1 in 10 people)  increase in red blood cell count (the cells which carry the oxygen in your blood); hematocrit (percentage of red blood cells in blood) and haemoglobin (the component of red blood cells that carries oxygen), identified by periodic blood tests.

Not known (cannot be estimated from available data)
· itching (pruritus)
·  acne
·  nausea (feeling sick)
·  problems with your liver including liver tumours, though this is rare
·  changes in the way your body processes fats
·  depression
·  nervousness
·  mood alterations
·  muscle pain
·  fluid retention in the tissues, usually marked by the swelling of ankles or feet
·  high blood pressure
·  increased or decreased sex drive
·  prolonged painful erection
·  decreased amounts of ejaculation fluid and sperm
·  enlargement of the breasts
·  growth of the prostate gland
·  increased levels of a blood marker which is associated with prostate cancer (PSA)
·  worsening of the early stage of prostate cancer
·  yellowing of the skin or eyes
·  difficulty passing urine
·  allergy to sunset yellow, a colour used in the capsules.
·  electrolyte changes (sodium, potassium, calcium, inorganic phosphate and water retention)
·  no sperm count
· In a few patients diarrhoea, stomach pain or discomfort have been reported during the use of this medicine.

Children and adolescents:
The following side effects have been reported in pre-pubertal children using androgens:
· early sexual development;
·  penis enlargement;
·  an increased frequency of erections;
·  growth limitation (limited body height)

 Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

  1. How to store Testosterone Undecanoate 40mg

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the package, sachet and blister, after the term “exp” (expiry date). The expiry date refers to the last day of that month. Do not store above 30 °C.
Do not refrigerate or freeze.
Store in the original package and keep the blister in the outer carton.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

  1. Contents of the pack and other information


What Testosterone Undecanoate contain

The active substance is: Testosterone undecanoate, 40 mg which is equivalent to 25.3 mg testosterone.
The other ingredients are:
Capsule contents:
· Castor oil and propylene glycol laurate (E477)
Capsule shell ingredients:· Glycerin, Sunset Yellow (E110) and gelatin
Printing ink:
· Opacode WB® white
Auxiliary substances:
· Medium-chain triglycerides and Lecithin

What Testosterone Undecanoate looks like and contents of the pack
Testosterone Undecanoate are soft oval glossy capsules, transparent, orange in colour containing a yellow oily fill.
A box of Testosterone Undecanoate contains either 3 or 6 sachets.
Each sachet contains a blister strip with 10 capsules.
If you have any further questions or require the full prescribing information for this medicine, please consult your doctor or pharmacist.

Manufactured by:
Taj Pharmaceuticals Limited
220, Mahagujarat Ind. Estate, Moraiya, Tal. Sanand, Dist. Ahmedabad, Gujarat, INDIA

Marketing Authorization Holder:
Regal sun co., Ltd.Myanmar

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