Active ingredients: Testosterone (Testosterone undecanoate)
Andriol 40 mg soft capsules
Why is Andriol used? What is it for?
Andriol contains the active ingredient testosterone undecanoate which belongs to the group of sex hormones called androgens and is responsible for the development of the male sex organs.
Andriol is used to replace testosterone in adult men, for the treatment of various health problems due to testosterone deficiency (male hypogonadism). This condition must be confirmed with two separate blood testosterone measurements and must include clinical symptoms such as:
impotence
infertility
poor sexual desire
tiredness
depressed mood
bone loss due to low hormone levels
Contraindications When Andriol should not be used
Do not take Andriol
- if you are allergic to testosterone undecanoate or any of the other ingredients of this medicine
- if you have, have ever had or are suspected of having breast cancer (see section "Warnings and precautions");
- if you have high blood pressure (hypertension);
- if you suffer from kidney disease (nephrotic syndrome);
- if you have severe liver disease (severe liver dysfunction), or have ever had liver cancer;
- if you suffer from high levels of calcium in the urine and blood (hypercalciuria and hypercalcaemia) (see section "Warnings and precautions").
Andriol is not indicated for use in women and must not be used during pregnancy or breastfeeding (see section 2 "Pregnancy and breastfeeding").
Precautions for use What you need to know before taking Andriol
Talk to your doctor or pharmacist before taking Andriol.
Your doctor will regularly undergo the following tests and visits, before the start of treatment, every three months for the first 12 months and then once a year:
- prostate control;
- blood tests.
Before and during treatment, the doctor must carry out the following blood tests: testosterone levels in the blood, complete blood count. Your doctor will check you carefully, especially if you are elderly:
- if you have high levels of calcium in the blood (hypercalcaemia) and / or diseases that can cause them (kidney disease, prostate cancer, breast cancer, other cancers and skeletal metastases - see section "Do not take Andriol"). If you experience high levels of calcium in your blood (hypercalcaemia) during treatment with androgens, your doctor will ask you to stop taking Andriol. Only after the normal calcium levels have been restored, will you resume therapy with Andriol;
- if you suffer from diabetes mellitus as androgens in general and Andriol can increase the body's ability to metabolise sugars in diabetic patients (see Other medicines and Andriol);
- if you are taking a blood thinning medicine (anticoagulant therapy) as androgens in general and Andriol can increase the blood thinning effect (see Other medicines and Andriol);
- if you have sleep apnea (temporary interruption of breathing during sleep)
- if you are overweight or have chronic lung disease. In this case a careful medical evaluation is necessary.
Treatment must be stopped immediately:
- If you have severe heart, liver or kidney disease, treatment with Andriol can cause serious complications in the form of water accumulation in the body, sometimes accompanied by (congestive) heart failure.
- if you have suffered from myocardial infarction, heart failure, high blood pressure (hypertension) due to the risk of worsening or relapse;
- if you suffer from epilepsy;
- if you suffer from severe and frequent headaches (migraines).
Tell your doctor if you have high blood pressure or are being treated for high blood pressure, as testosterone can cause your blood pressure to rise.
Avoid excessive sexual, mental and physical stimulation if you suffer from heart disease (heart disease). If a "painful and persistent erection (priapism) occurs, therapy must be discontinued (see section" Possible side effects ").
Andriol is not recommended in the treatment of psychic impotence (inability to maintain an erection due to psychological and non-physical problems) since its prolonged use can lead to a reduction in the volume of the testicles (hypotrophy), which are normal and perfectly functional in themselves.
Side effects:
If undesirable effects associated with the use of androgens occur (see section "Possible undesirable effects"), treatment with Andriol should be discontinued and, upon resolution of the disorder, treatment should be resumed at a lower dose.
For those who carry out sporting activities
The use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.
Children and adolescents
Safety and efficacy in children and adolescents have not been established.
The use of androgens in general and Andriol in high doses can accelerate long bone welding and sexual maturation in prepubertal (pre-sexual development) children.
Interactions Which drugs or foods can modify the effect of Andriol
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Your doctor may need to change your Andriol dosage if you are taking any of the following medicines:
- insulin and / or other medicines to control blood sugar levels, in which case the dosage of these medicines may need to be adjusted;
- medicines to reduce blood clotting (anticoagulants). The use of androgens such as Andriol can lead to a reduction in the doses of these medicines;
- ACTH hormone or corticosteroids (used to treat various conditions, such as rheumatism, arthritis, allergic conditions, and asthma). Simultaneous administration of testosterone and ACTH or corticosteroids can increase swelling and fluid retention (edema), especially if you have heart or liver disease.
Andriol can change the results of some laboratory tests (e.g. thyroid tests). Tell the doctor or laboratory staff that you are taking Andriol.
Andriol with foods
Andriol must be taken with food, (see section 3 "How to take Andriol").
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
Pregnancy and breastfeeding
Treatment with Andriol is intended for use in men only, therefore it is not indicated in women and should not be used during pregnancy or breastfeeding. This medicine can be harmful to an unborn baby
Fertility
In men, treatment with androgens can lead to impaired fertility by suppressing the formation of semen (see section 4 "Possible side effects").
Driving and using machines
Andriol does not affect the ability to drive or use machines
Andriol contains castor oil, propylene glycol monolaurate, sunset yellow (E110, FD&C Yellow # 6)
Andriol contains castor oil. It can cause stomach upset and diarrhea.
Andriol contains propylene glycol monolaurate. It can cause symptoms similar to those caused by alcohol.
Andriol contains Sunset Yellow (E110, FD&C Yellow No. 6). It can cause allergic reactions.
Dosage and method of use How to use Andriol: Dosage
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
Adults:
The recommended dose is 120-160 mg (3-4 capsules) per day for 2-3 weeks. Subsequently, taking into account the clinical effects obtained during the first weeks of therapy, the dosage can be increased to 40-120 mg (1-3 capsules) per day. Your doctor will decide exactly the dose based on your clinical response.
Swallow the capsules without chewing them, immediately after meals, with a little water; it is preferable to take the daily dose half in the morning and half in the evening.
If the number of capsules to be ingested is odd, take most of them in the morning.
Use in children and adolescents
Safety and efficacy in children and adolescents have not been established.
Overdose What to do if you have taken too much Andriol
If you take more Andriol than you should
In case of accidental ingestion / intake of an excessive dose of Andriol, notify your doctor immediately or go to the nearest hospital.
Symptoms of an overdose of Andriol can be:
- increase in the number of red blood cells in the blood (polycythemia);
- prolonged and painful erection (priapism). If such symptoms occur, treatment should be stopped until they disappear and may possibly be resumed at a lower dose.
Excessive dosage of Andriol can cause gastrointestinal upset caused by castor oil.
If you forget to take Andriol
Do not take a double dose to make up for a forgotten capsule.
If you stop taking Andriol
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Andriol
Like all medicines, this medicine can cause side effects, although not everybody gets them. Side effects that are reported with testosterone therapy include:
Common frequency (may affect up to 1 in 10 people)
- increase in red blood cell count, hematocrit (percentage of red blood cells in the blood) and hemoglobin (the component of red blood cells that carries oxygen), evidenced by periodic blood tests
Frequency not known (frequency cannot be estimated from the available data).
- Itching;
- Acne;
- Nausea;
- Changes in laboratory tests affecting liver function
- Changes in blood lipid levels
- Increased number of red blood cells in the blood (polycythemia)
- Depression, nervousness, mood alteration;
- Muscle pain (myalgia)
- Fluid retention, sodium retention, usually manifested by swelling of the ankles or feet
- Increased blood pressure (hypertension);
- Changes in sexual desire
- Prolonged abnormal and painful erection (priapism);
- Disorders in the formation of sperm;
- Breast enlargement in men (gynecomastia);
- Condition characterized by the enlargement of the prostate (benign prostatic hypertrophy);
- Increase in a value indicative of prostate function (PSA);
- Prostate cancer (man's gland that produces seminal fluid);
Diarrhea and abdominal pain or discomfort have been reported in some patients while using Andriol.
Additional side effects in children and adolescents
The following undesirable effects have been reported in prepubertal children treated with androgens (see section 2 early sexual development, increased frequency of erections, penile enlargement and premature welding of long bones (limited height gain).
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on safety. of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.
Store below 30 ° C.
Do not refrigerate or freeze.
Keep the blister in the outer carton to protect the medicine from light.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What Andriol contains
- The active ingredient is testosterone undecanoate;
- the other components are castor oil and propylene glycol laurate (E477), glycerin, Sunset Yellow (E110, FD&C Yellow No. 6), gelatin, printing ink (Opacode WB, auxiliary substances, medium chain triglycerides and lecithin).
What Andriol looks like and contents of the pack
Andriol is presented as soft, glossy, oval, transparent, orange capsules, with a yellow oily content, with the inscription ORG DV3 imprinted.
It is available in packs of 3 or 6 aluminum sachets, each containing a blister of 10 capsules.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
ANDRIOL 40 MG SOFT CAPSULES
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Andriol contains testosterone undecanoate, a fatty acid ester of the natural hormone testosterone.
Each capsule contains
Active ingredient: 40 mg of testosterone undecanoate dissolved in a mixture of castor oil and propylene glycol laurate which is equivalent to 25.3 mg of testosterone.
Excipients with known effects: castor oil and propylene glycol monolaurate (E477), sunset yellow (E110, FD&C yellow No. 6).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Soft capsules.
Soft, glossy, oval, transparent, orange colored capsules with a yellow oily content, imprinted with ORG DV3.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Testosterone replacement therapy for male hypogonadism, when testosterone deficiency has been confirmed by the clinical picture and biochemical analyzes.
Andriol is indicated in particular:
- after castration;
- in "eunuchoidism;
- in the "impotence of endocrine origin;
- in male climacteric syndrome with decreased libido;
- in some types of infertility due to the action of testosterone on spermatogenesis.
Testosterone therapy may also be indicated in forms of osteoporosis due to androgenic insufficiency.
04.2 Posology and method of administration
Dosage:
In general, the dose should be adjusted according to each patient's response.
Adults
Normally it starts with a dosage of 120-160 mg per day for 2-3 weeks.
Subsequently, taking into account the clinical effects obtained during the first weeks of therapy, the dosage can be reduced to 40-120 mg per day.
Pediatric population
Safety and efficacy in children have not yet been established.
Method of administration:
The capsules should be swallowed without being chewed, with a little water.
To ensure its absorption, Andriol should be taken with a meal; it is preferable to take the daily dose half in the morning and half in the evening.
If the number of capsules to be ingested is odd, most of them should be taken in the morning.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Known or suspected prostate or breast cancer (see section 4.4).
Hypertension, nephrotic syndrome, severe hepatic dysfunction, history of primary liver cancer, established hypercalciuria and hypercalcaemia (see section 4.4).
Pregnancy and lactation (see section 4.6).
04.4 Special warnings and appropriate precautions for use
Medical examination:
In patients receiving Andriol, physicians should consider monitoring the following parameters, prior to initiation of treatment, at quarterly intervals, for the first 12 months, and annually thereafter:
• Digital rectal examination (EDR) of the prostate and determination of the PSA value to exclude the possible presence of benign prostatic hypertrophy and subclinical prostate cancer (see section 4.3)
• Hematocrit and hemoglobin to rule out polycythemia.
Testosterone levels should be monitored at baseline and at regular intervals during treatment. Physicians should adjust the dose on an individual basis from patient to patient to ensure maintenance of eugonadal testosterone levels.
In patients receiving long-term androgen therapy, the following laboratory parameters should also be monitored at regular intervals: hemoglobin and hematocrit, liver function parameters and lipid profile.
Conditions that need supervision:
Patients, especially the elderly, with the following conditions should be monitored for:
• hypercalcaemia and / or conditions leading to hypercalcaemia such as nephropathies, prostate and breast cancer, other cancers and skeletal metastases (see section 4.3). Hypercalcemia can also occur during treatment with androgens. Hypercalcemia must first be treated appropriately and, after normal calcium levels are restored, hormone therapy can be resumed.
• Comorbid conditions - In patients with severe heart, liver or kidney failure or ischemic heart disease, testosterone treatment can induce severe complications characterized by edema with or without congestive heart failure. In this case, the treatment must be stopped immediately.
Patients who have had myocardial infarction, heart, liver or kidney failure, hypertension, epilepsy or migraine should be monitored for the risk of worsening or recurrence. In such cases, treatment should be stopped immediately.
Testosterone can cause an increase in blood pressure and Andriol should be used with caution in hypertensive individuals.
• Diabetes mellitus - Androgens in general and Andriol can improve glucose tolerance in diabetic patients (see section 4.5).
• Anticoagulant therapy - Androgens in general and Andriol may enhance the anticoagulant action of coumarin-type agents (see section 4.5).
• Sleep apnea - There is insufficient evidence for a recommendation regarding the safety of treatment with testosterone esters in men with sleep apnea. Careful medical evaluation and caution are required in patients with risk factors such as overweight or chronic lung disease.
Stimulation that increases nervous, mental and physical activity beyond the patient's cardiovascular capacity should be avoided.
If priapism or other signs of sexual over-stimulation occur, therapy should be discontinued (see section 4.8).
A reduction in PBI (Protein Bound Iodine) may occur during therapy; however, this data has no clinical significance.
It is not recommended in psychic impotence since its prolonged use can lead to hypotrophy of the testicles which are in themselves normal and perfectly functional.
Adverse events:
If adverse reactions associated with the use of androgens occur (see section 4.8), treatment with Andriol should be discontinued and, upon resolution of the disorder, restarted at a lower dose.
(Improper) use in sport:
Patients participating in competitions regulated by the World Anti-Doping Agency (WADA) must consult the WADA code before using this medicine as Andriol can interfere with doping tests. The misuse of androgens to improve ability in sport carries serious risks for health and should be discouraged.
Pediatric population:
In children of prepubertal age, statural growth and sexual development must be monitored as androgens in general and Andriol in high doses can accelerate the sealing of the epiphyses and sexual development.
Senior citizens
There is limited experience on the safety and efficacy of the use of Andriol in patients over the age of 65. There is currently no agreement on age-specific testosterone reference values. However, it must be considered that serum testosterone levels decrease physiologically with increasing age.
Important information about some of the ingredients
Andriol contains castor oil. It can cause stomach upset and diarrhea. Andriol contains propylene glycol monolaurate. It can cause symptoms similar to those caused by alcohol.
Andriol contains Sunset Yellow (E110, FD&C Yellow No. 6). It can cause allergic reactions.
04.5 Interactions with other medicinal products and other forms of interaction
Testosterone levels can be decreased by enzyme inducers and increased by enzyme inhibitors. Therefore, a dose adjustment of Andriol may be needed.
Insulin and other antidiabetic medicines:
Androgens may increase glucose tolerance and reduce the need for insulin or other antidiabetic medicinal products in diabetic patients (see section 4.4). Patients with diabetes mellitus should therefore be monitored especially at the start or end of treatment and at periodic intervals during treatment with Andriol.
Anticoagulant therapy:
High doses of androgens may potentiate the anticoagulant action of coumarin-type agents (see section 4.4). Therefore close monitoring of prothrombin time and, if necessary, dose reduction of anticoagulants is required during therapy.
ACTH or corticosteroids:
Concomitant administration of testosterone and ACTH or corticosteroids can increase edema formation; therefore the combination of these active substances should be done with caution, especially in patients with cardiac or hepatic disease or in patients predisposed to edema (see section 4.4).
Interactions with laboratory tests:
Androgens can reduce thyroxine-binding globulin levels resulting in a reduction in total serum T4 levels and an increase in resin uptake of T3 and T4. However, free thyroid hormone levels remain unchanged and there is no clinical evidence of thyroid dysfunction.
Andriol should be taken with a meal to ensure absorption (see section 4.2).
04.6 Pregnancy and lactation
Fertility
In men, androgen treatment can lead to impaired fertility by suppressing sperm formation (see section 4.8).
Pregnancy and breastfeeding:
Treatment with Andriol is intended for use in men only, therefore it should not be used by pregnant or breastfeeding women (see section 4.3). If used during pregnancy Andriol exposes the fetus to risk of virilization (see section 5.3). ).
04.7 Effects on ability to drive and use machines
Andriol does not affect the ability to drive or use machines.
04.8 Undesirable effects
The following adverse reactions have been associated with androgen therapy in general. The most appropriate MedDRA term to describe a given adverse event is given.
All adverse reactions are listed by system organ class and by frequency: common (≥1 / 100,
1 Progression of a subclinical prostate cancer
2 Enlarged prostate (compared to normal size)
3 Decrease in serum LDL-C, HDL-C and triglyceride levels
Diarrhea and abdominal pain or discomfort have been reported in some patients while using Andriol.
Pediatric population:
The following undesirable effects have been reported in prepubertal children using androgens (see section 4.4): early sexual development, increased frequency of erections, penile enlargement and premature sealing of the epiphyses.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
04.9 Overdose
Acute toxicity of testosterone is low.
Reversible priapism may be observed in the event of an overdose.
In the event of the onset of symptoms and signs of overdose (eg polycythemia, priapism), treatment should be interrupted until the symptoms disappear, and may possibly be resumed at a lower dose.
An overdose of Andriol can cause gastrointestinal upset caused by castor oil, treatment consists of supportive measures.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: sex hormones and modulators of the genital system, androgens, 3-oxoandrostene derivatives.
ATC code: G03BA03.
The pharmacological action, typical of androgens, was studied in animals with the Hershberger test.
Mechanism of action
Treatment with Andriol in men with hypogonadism restores total and bioavailable serum testosterone to levels within the normal range in a dose-dependent manner.
Pharmacodynamic effects
Treatment also involves an increase in serum concentrations of dihydrotestosterone (DHT) and estradiol (E2), as well as a decrease in sex hormone binding globulin (SHBG), luteinizing hormone (LH) and follicle stimulating hormone (FSH). .
Clinical efficacy and safety
Treatment with Andriol results in an improvement in testosterone deficiency symptoms in both young and adult men with hypogonadism. In addition, the treatment increases bone mineral density. The treatment also improves sexual function, including libido and erectile function. Treatment dose-dependently reduces serum LDL-C, HDL-C and triglyceride levels and increases hemoglobin and hematocrit, while no clinically relevant changes in liver enzymes and PSA have been observed. Treatment may result in an increase in prostate size, however no adverse effects on prostatic symptoms have been observed.
Pediatric population
In adolescents with constitutional retardation of growth and puberty, treatment with Andriol primarily accelerates growth and induces the development of secondary sexual characteristics.
05.2 Pharmacokinetic properties
Absorption:
After oral administration of Andriol, an important part of the active ingredient testosterone undecanoate is co-absorbed with the lipophilic solvent from the intestine into the lymphatic system, thus partially bypassing the first pass inactivation by the liver. Andriol should be taken with a normal meal or breakfast to ensure its absorption. Bioavailability is approximately 7%.
Distribution:
Testosterone undecanoate is released from the lymphatic system into plasma and hydrolyzed to testosterone.
Multiple oral administrations of Andriol 80 mg in male hypogonadism resulted in a clinically significant increase in total testosterone, with a mean concentration of 12 nmol / L (Cavg) and peak levels of 11-60 nmol / L (Cmax), which they occur after 2-6 hours (tmax). Plasma testosterone levels remain elevated for at least 8 hours. In in vitro tests, testosterone and testosterone undecanoate show high (over 97%) non-specific binding to plasma proteins and sex hormone binding globulin.
Biotransformation:
Testosterone undecanoate is hydrolyzed, in plasma and tissues, to natural male androgen testosterone. Testosterone is subsequently metabolised to dihydrotestosterone and estradiol, which are further metabolised via the normal pathways.
Elimination:
Excretion occurs mainly through the urine in the form of conjugates of ethiocholanolone and androsterone.
Elimination: fecal for 54-78%; urinary for 10-39% of which about half in the first 24 hours.
Linearity:
Dose linearity has been demonstrated over a dose range of 40-160 mg / day.
05.3 Preclinical safety data
The LD50 of testosterone undecanoate is greater than 4,000 mg / kg p.o. Repeated administration is well tolerated in dogs and rats: during the chronic experimentation no lethal cases were observed, nor were any effects other than those attributable to hormonal activity observed. In particular, unlike what happens with derivatives. of testosterone alkylated in C17, no undesirable effects on liver function were observed Reproductive toxicology studies did not reveal any abnormalities, except for a reduction in fertility, due to the suppression of spermatogenesis, which was completely reversible.
No abnormalities were observed in rats born to parents treated with testosterone undecanoate. Mutagenesis: Ames and micronucleus tests did not show any mutagenic activity of the product.
Preclinical data with androgens generally reveal no risk for humans. The use of androgens in different species has been shown to cause virilization of the external genitalia of female fetuses.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Capsule contents
Each soft capsule contains approximately 293 mg of a mixture of castor oil and propylene glycol monolaurate (E477).
Capsule shell ingredients
Glycerin, sunset yellow (E110, FD&C yellow # 6) and gelatin.
Printing ink
Opacode WB
Auxiliary substances
Medium-chain triglycerides and lecithin.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Store below 30 ° C.
Do not refrigerate or freeze.
Store in the original package and keep the container in the outer carton.
06.5 Nature of the immediate packaging and contents of the package
One box of Andriol contains 3 or 6 aluminum sachets, each containing a blister of 10 capsules.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
MSD Italia S.r.l.
Via Vitorchiano, 151
00189 Rome
08.0 MARKETING AUTHORIZATION NUMBER
40 mg soft capsules, 30 capsules No. 024585010
40 mg soft capsules, 60 capsules No. 024585034
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
April 1982
Last renewal date 31 May 2010
10.0 DATE OF REVISION OF THE TEXT
AIFA Determination of July 2015
