Diphereline 0.1 mg

Package leaflet: Information for the user

Diphereline 0,1 mg
0.1 mg, powder and solvent for solution for injection
Triptorelinum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• Please consult your doctor or pharmacist if you have any further questions.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them even if their symptoms are the same as yours.
• If any of the side effects worsens, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.

Contents of the leaflet

1. What Diphereline 0,1 mg is and what it is used for
2. What you need to know before using Diphereline 0,1 mg
3. How to use Diphereline 0,1 mg
4. Possible side effects
5. How to store Diphereline 0,1 mg
6. Contents of the pack and other information

1. What Diphereline 0,1 mg is and what it is used for

This medicine contains triptorelin. Triptorelin belongs to a group of medicines known as gonadotropin-releasing hormone (GnRH) analogues. One of its actions is to reduce the production of sex hormones in the body.
Prolonged administration of triptorelin, after an initial stimulation phase, leads to suppression of gonadotropin hormone secretion, resulting in inhibition of gonadal function (testes or ovaries).

Metastatic prostate cancer
Administration of a single dose of the medicine may initially cause an increase in testosterone levels. Continued treatment leads to a reduction in steroid hormone levels within 2–3 weeks to levels comparable to those after castration. This condition depends on the duration of treatment.

Female infertility
Long-term treatment with this medicine suppresses the secretion of gonadotropin hormones. This treatment improves folliculogenesis, increasing the number of maturing follicles, thereby increasing the number of pregnancies per cycle.

Indications for Diphereline 0,1 mg

• Metastatic prostate cancer
  Initial treatment prior to administration of the prolonged-release formulation. Patients who have not previously received other hormonal therapy generally respond better to triptorelin treatment.

• Female infertility
  Adjunctive treatment in combination with gonadotropins (hMG, FSH, hCG) to induce ovulation, in preparation for in vitro fertilization and embryo transfer.

2. Important information before using Diphereline 0.1 mg

When not to use Diphereline 0.1 mg

• In case of allergy (hypersensitivity) to triptorelin, gonadoliberin (GnRH), other GnRH analogues, or any of the other ingredients of Diphereline 0.1 mg
• During pregnancy or breastfeeding

Warnings and precautions
Before starting treatment with Diphereline 0.1 mg, discuss this with your doctor or pharmacist.
During treatment with Diphereline 0.1 mg, a previously unknown enlargement (benign tumour) of the pituitary gland may become apparent. Symptoms include sudden headache, vomiting, visual disturbances, and eye muscle paralysis.
There have been reports of depression, including severe depression, in patients receiving Diphereline 0.1 mg. If depressive moods occur during treatment with Diphereline 0.1 mg, inform your doctor immediately.
In adults, long-term treatment with triptorelin may cause bone weakening (osteoporosis) associated with an increased risk of bone fractures. Inform your doctor if the patient has any of the following risk factors, as the doctor may recommend bisphosphonates (medicines used to treat osteoporosis) to manage bone loss.
Risk factors may include:

• Presence of osteoporosis in the patient or in their immediate family;
• Alcohol abuse, smoking, malnutrition;
• Long-term use of medicines that may cause bone loss, such as antiepileptic drugs or corticosteroids (e.g. hydrocortisone, prednisolone).

If seizures occur, inform your doctor immediately. Seizures have been reported in patients receiving triptorelin or similar medicines, both in patients with and without a prior history of epilepsy.
Men
At the beginning of treatment, increased testosterone levels may be observed. This may worsen tumour-related symptoms. In such cases, contact your doctor. The doctor may prescribe an additional medicine (antiandrogen) to prevent worsening of these symptoms.
If the patient develops urinary obstruction or spinal cord compression due to tumour spread, the doctor will closely monitor the patient during the first few weeks of treatment. In case of difficulty urinating, bone pain, weakness in the lower limbs, or tingling sensations, contact your doctor immediately. The doctor will assess the patient's condition and initiate appropriate treatment.
Tryptorelin does not further reduce testosterone levels in patients who have undergone orchidectomy (removal of the testes).
Diagnostic test results for gonadal function of the pituitary gland and reproductive organs, performed during or after discontinuation of Diphereline 0.1 mg therapy, may be misleading.
Inform your doctor if the patient has heart or blood vessel disease, including heart rhythm disorders (arrhythmia), or if the patient is taking medicines used to treat heart rhythm disorders. The risk of heart rhythm disturbances may be increased when using Diphereline 0.1 mg.
Medicines that lower testosterone levels may cause ECG changes related to heart rhythm disturbances (prolongation of the QT interval).
Inform your doctor if the patient has diabetes and/or heart disease.
Treatment with GnRH analogues, including Diphereline 0.1 mg, may increase the risk of anaemia (defined as a reduced number of red blood cells).
Women
During infertility treatment with gonadotropins (ovarian-stimulating hormones) in combination with Diphereline 0.1 mg, ovarian enlargement or ovarian hyperstimulation may occur, causing pelvic and/or abdominal pain and/or breathing difficulties. In such cases, consult your doctor immediately.
If you have concerns regarding the situations described above, speak with your doctor.
Other medicines and Diphereline 0.1 mg
Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken, or plan to take.
Men:
Diphereline 0.1 mg may affect the action of other medicines used to treat heart rhythm disorders (e.g. quinidine, procainamide, amiodarone, sotalol) or may increase the risk of heart rhythm disturbances when taken together with other medicines (e.g. methadone used for pain relief or as part of detoxification in drug addiction), moxifloxacin (an antibiotic), or antipsychotic medicines used to treat severe mental illnesses.
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, suspect you may be pregnant, or are planning to have a child, consult your doctor before using this medicine.
Pregnancy must be excluded before prescribing Diphereline 0.1 mg.
Diphereline 0.1 mg must not be used during pregnancy or breastfeeding.
Driving and operating machinery
Dizziness, fatigue, or visual disturbances such as blurred vision may occur during treatment. These symptoms may be side effects of the treatment or related to the underlying disease. If any of these side effects occur, do not drive or operate machinery.
Diphereline 0.1 mg contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, meaning it is considered "sodium-free".

3. How to use Diphereline 0.1 mg

The medicine is administered subcutaneously.
Prostate cancer with metastases
One subcutaneous injection of Diphereline 0.1 mg once daily for 7 days before initiating treatment with the prolonged-release formulation.
Infertility in women
Administer one dose of the medicine (0.1 mg) subcutaneously daily, starting on the second day of the cycle. After achieving pituitary desensitization (approximately on day 15 of treatment initiation), gonadotropin stimulation should be started and continued concurrently with triptorelin until the day before the scheduled administration of hCG (human chorionic gonadotropin).
Preparation of the medicine:
Transfer the solvent into the vial containing the powder. Shake until complete dissolution is achieved and administer immediately.
Used syringes should be disposed of in an appropriate sharps container. Any remaining medicine should be discarded.
Use of a higher than recommended dose of Diphereline 0.1 mg
No adverse effects have been observed following overdose of the medicine.

4. Possible side effects
Like all medicines, Diphereline 0.1 mg can cause side effects, although not everybody will experience them.
In rare cases, a severe allergic reaction may occur. If symptoms such as difficulty swallowing or breathing, swelling of the lips, face, throat or tongue, rash or dizziness develop, contact a doctor immediately.

Men
Many of the adverse effects may be expected due to changes in testosterone levels in the body. These effects include hot flushes, impotence and decreased libido.
Very common – adverse effects occurring in more than 1 in 10 patients

• Hot flushes
• Weakness
• Excessive sweating
• Back pain
• Tingling sensation in the lower limbs
• Decreased sexual drive
• Impotence

Common – adverse effects occurring in no more than 1 in 10 patients

• Nausea, dryness of the mouth
• Pain, bruising, redness and swelling at the injection site
• Muscle and bone pain, pain in arms and legs
• Edema (fluid accumulation in tissues)
• Lower abdominal pain
• High blood pressure
• Allergic reaction
• Increase in body weight
• Dizziness, headache
• Loss of sexual drive, depression, mood changes

Uncommon – adverse effects occurring in no more than 1 in 100 patients

• Increased platelet count
• Palpitations
• Tinnitus, dizziness, blurred vision
• Abdominal pain, constipation, diarrhea, vomiting
• Somnolence, chills, drowsiness, pain
• Changes in results of certain laboratory tests (including increased values of parameters indicating liver function), elevated blood pressure
• Decrease in body weight
• Loss of appetite, increased appetite, gout (severe pain and swelling of joints, most commonly affecting the big toe), diabetes, high blood lipid levels
• Joint pain, muscle cramps, muscle weakness, muscle pain, swelling of ankles, feet or fingers, bone pain
• Tingling and numbness
• Sleep disturbances, irritability
• Breast enlargement in men, breast pain (tenderness), testicular atrophy, testicular pain
• Dyspnea
• Acne, hair loss, itching, rash, skin redness, urticaria

Rare – adverse effects occurring in no more than 1 in 1000 patients

• Red or purple skin discoloration
• Unusual sensations in the eye, blurred or disturbed vision
• Feeling of fullness in the abdomen, bloating, taste disturbances
• Chest pain
• Difficulty maintaining a standing position
• Influenza-like symptoms, fever
• Severe allergic reaction (anaphylactic reaction), which may cause dizziness or breathing difficulties, facial or throat swelling
• Nasal mucositis, pharyngitis
• Joint stiffness, joint swelling, musculoskeletal stiffness, osteoarthritis
• Memory loss
• Confusion, decreased activity, excitement
• Dyspnea in lying position
• Skin blisters
• Low blood pressure

Adverse effects reported after marketing authorization (frequency unknown):

• Severe allergic reaction causing swelling of the face, tongue and neck, dizziness or breathing difficulties (Quincke's edema, anaphylactic shock)
• Changes in ECG (prolongation of QT interval)
• General malaise, anxiety
• Urinary incontinence
• In patients with existing pituitary tumor, increased risk of pituitary hemorrhage
• Anemia (decreased number of red blood cells)

As with other GnRH analogs, patients treated with Diphereline 0.1 mg may experience an increase in white blood cell count.

Women
Many of the adverse effects may be expected due to changes in estrogen levels in the body.
Very common – adverse effects occurring in more than 1 in 10 patients

• Headache
• Decreased sexual drive, mood swings, sleep disturbances
• Breast discomfort
• Ovarian hyperstimulation syndrome (with ovarian enlargement and fluid retention)
• Pain during or after sexual intercourse, vaginal bleeding
• Pelvic pain
• Ovarian hypertrophy, vaginal dryness
• Excessive sweating, acne, seborrhea
• Hot flushes

Common – adverse effects occurring in no more than 1 in 10 patients

• Breast pain
• Muscle cramps, joint pain
• Weight gain, nausea, abdominal pain or discomfort
• Depression (with long-term treatment), nervousness
• Pain, bruising, redness and swelling at the injection site
• Swelling of ankles, feet or fingers
• Allergic reaction
• Pain in hands and legs
• Dizziness

Uncommon – adverse effects occurring in no more than 1 in 100 patients

• Palpitations
• Dizziness
• Dry eyes, blurred vision
• Bloating, vomiting, diarrhea, flatulence
• Dry mouth, oral ulcers
• Decreased body weight, decreased appetite
• Fluid retention
• Back pain, muscle pain
• Taste disturbances
• Loss of sensation
• Transient loss of consciousness, memory loss, lack of concentration
• Tingling or numbness, involuntary muscle movements
• Mood changes, anxiety, disorientation, depression
• Bleeding after intercourse, bladder prolapse, irregular menstruation, painful menstruation, heavy menstrual bleeding
• Small ovarian cysts, which may cause pain, vaginal discharge
• Breathing difficulties, epistaxis

Adverse effects reported after marketing authorization (frequency unknown):

• General malaise, fever
• Seizures
• Increased arterial blood pressure
• Diarrhea
• Severe allergic reaction causing swelling of the face, tongue and neck, dizziness or breathing difficulties (Quincke's edema, anaphylactic shock)
• Changes in certain blood test parameters (including increased activity of certain enzymes)
• Muscle weakness
• Confusion, visual disturbances
• Absence of menstruation
• In patients with existing pituitary tumor, increased risk of pituitary hemorrhage

During infertility treatment, gonadotropins in combination with Diphereline 0.1 mg may cause pelvic and/or abdominal pain and dyspnea. If such symptoms occur, inform your doctor immediately.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the responsible entity.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Diphereline 0,1 mg

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton. The expiry date refers to the last day of the stated month. Expiry date (EXP). Batch number (Lot).
Store below 25°C.

6. Contents of the pack and other information

What Diphereline 0,1 mg contains
The active substance is triptorelin, in the form of triptorelin acetate. One vial contains 0.1 mg of triptorelin.
Other components are:

• the powder vial contains mannitol
• the solvent ampoule contains sodium chloride and water for injections.

What Diphereline 0,1 mg looks like and contents of the pack
Powder and solvent for solution for injection.
One glass vial containing powder and one glass ampoule containing solvent.
The pack contains 7 vials of powder and 7 ampoules of solvent.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Ipsen Pharma
70 rue Balard
75015 Paris
France

Manufacturer
Ipsen Pharma Biotech
Parc d’Activités du Plateau de Signes
Chemin départemental no 402
83870 Signes
France

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Ipsen Poland Sp. z o.o.
Chmielna 73 Street
00-801 Warsaw
Phone: +48 22 653 68 00
Fax: +48 22 653 68 22