DIPHERELINE 0.1 mg Powder

Contents of the leaflet

1. Leaflet accompanying the packaging: information for the user
2. Diphereline 0.1 mg
3. 1 mg
   1. Read the leaflet carefully before using the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet
4. What is Diphereline 0.1 mg and what is it used for
5. Important information before using Diphereline 0.1 mg
   1. When not to use Diphereline 0.1 mg
   2. Warnings and precautions
   3. Other medicines and Diphereline 0.1 mg
   4. Pregnancy and breastfeeding
   5. Driving and using machines
   6. Diphereline 0.1 mg contains sodium
6. How to use Diphereline 0.1 mg
   1. Using a higher dose of Diphereline 0.1 mg than recommended
7. Possible side effects
   1. Reporting side effects
8. How to store Diphereline 0.1 mg
9. Contents of the packaging and other information
   1. What Diphereline 0.1 mg contains
   2. What Diphereline 0.1 mg looks like and what the pack contains
   3. Marketing authorization holder and manufacturer

Leaflet accompanying the packaging: information for the user

Diphereline 0.1 mg

0.1 mg

powder and solvent for solution for injection
Triptorelinum

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• Ask your doctor or pharmacist if you have any further questions.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, or if any side effects get worse, tell your doctor or pharmacist.

Table of contents of the leaflet

• 1. What is Diphereline 0.1 mg and what is it used for
• 2. Important information 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 packaging and other information

1. What is Diphereline 0.1 mg and what is it 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.
Long-term administration of triptorelin, after initial stimulation, leads to inhibition of gonadotropin secretion, which in turn leads to inhibition of gonadal function (testes or ovaries).
Prostate cancer with metastases
Administration of a single dose of the medicine may initially increase testosterone levels. Continued treatment leads to a decrease in steroid hormone levels within 2-3 weeks to a level equivalent to castration. This condition depends on the duration of treatment.
Infertility in women
Long-term treatment with the preparation leads to inhibition of gonadotropin secretion. This treatment improves the course of folliculogenesis, increasing the number of maturing follicles, which leads to an increased number of pregnancies per cycle.
Indications for use of Diphereline 0.1 mg

• Prostate cancer with metastases Initial treatment before using a prolonged-release form. Patients who have not previously undergone other hormone therapy respond better to triptorelin treatment.
• Infertility in women Adjunctive treatment in combination with gonadotropin administration (hMG, FSH, hCG) to induce ovulation, in preparation for in vitro fertilization and embryo transfer to the uterus.

2. Important information before using Diphereline 0.1 mg

When not to use Diphereline 0.1 mg

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

Warnings and precautions

Before starting treatment with Diphereline 0.1 mg, discuss it with your doctor or pharmacist.
During treatment with Diphereline 0.1 mg, a pituitary tumor (benign tumor) may be revealed, which the patient was not aware of. Symptoms include sudden headache, vomiting, vision disturbances, and eye muscle paralysis.
There have been reports of depression, including severe depression, in patients taking Diphereline 0.1 mg. If depressive moods occur while taking Diphereline 0.1 mg, inform your doctor.
In adults, long-term treatment with triptorelin may cause bone weakness (osteoporosis) associated with an increased risk of bone fractures. Inform your doctor if you have any of the following risk factors, as your doctor may recommend taking bisphosphonates (medicines used to treat osteoporosis) to treat bone loss.
Risk factors may include:

• osteoporosis in the patient or their immediate family;
• alcohol abuse, smoking, malnutrition;
• long-term use of medicines that can cause bone loss, such as those used to treat epilepsy or corticosteroids (such as hydrocortisone, prednisolone).

If seizures occur, inform your doctor immediately. Seizures have been reported in patients taking triptorelin or similar medicines. They occurred in patients with previously diagnosed epilepsy or without it.
Men
At the beginning of treatment, an increase in testosterone levels in the body is observed. This may cause worsening of symptoms related to the tumor. In such a case, contact your doctor. Your doctor may prescribe an additional medicine (anti-androgen) to prevent worsening of these symptoms.
If the patient experiences urinary retention or spinal cord compression due to tumor spread, the doctor will closely monitor the patient during the first few weeks of treatment. In case of difficulty urinating, bone pain, lower limb weakness, or tingling, contact your doctor immediately, who will assess the patient's condition and initiate appropriate treatment.
Triptorelin does not induce further reduction of testosterone levels in patients after orchiectomy (testicle removal).
Results of diagnostic tests of gonadal pituitary and reproductive organ function performed during or after treatment with Diphereline 0.1 mg may be misleading.
Inform your doctor if you have heart or blood vessel disease, including arrhythmias (abnormal heart rhythm) or if you are taking medicines used to treat arrhythmias. The risk of arrhythmias may be increased during treatment with Diphereline 0.1 mg.
Medicines that lower testosterone levels may cause changes in the ECG related to arrhythmias (prolongation of the QT interval).
Inform your doctor if you have diabetes and/or heart disease.
Women
During treatment for infertility, gonadotropins in combination with Diphereline 0.1 mg may cause ovarian enlargement or hyperstimulation, which may cause pelvic and/or abdominal pain and breathing difficulties. In such a case, consult your doctor immediately.

Other medicines and Diphereline 0.1 mg

Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Men:
Diphereline 0.1 mg may affect the action of other medicines used to treat arrhythmias (e.g., quinidine, procainamide, amiodarone, sotalol) or may increase the risk of arrhythmias when taken with other medicines (e.g., methadone used to treat pain and as part of detoxification in case of drug addiction), moxifloxacin (antibiotic), antipsychotic medicines used to treat severe mental illnesses).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor before using this medicine.
It must be confirmed that the patient is not pregnant before prescribing Diphereline 0.1 mg.
Diphereline 0.1 mg must not be used during pregnancy and breastfeeding.

Driving and using machines

During treatment, dizziness, fatigue, or vision problems, such as blurred vision, may occur. These symptoms may be side effects of treatment or the underlying disease. If any of these side effects occur, do not drive or operate any machines.

Diphereline 0.1 mg contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per dose, which means the medicine 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 a day for 7 days before using a prolonged-release form.
Infertility in women
Administer subcutaneously one dose of the medicine (0.1 mg) per day from the second day of the cycle. After achieving decreased pituitary sensitivity (i.e., around the 15th day from the start of treatment), gonadotropin stimulation is started and continued while administering triptorelin until the day before the scheduled day of hCG administration (chorionic gonadotropin).
Method of preparation of the medicine:
Transfer the solvent to the vial containing the powder. Shake until completely dissolved and administer immediately.
Used syringes should be disposed of in a suitable container for sharp objects. Any remaining medicine should be disposed of.

Using a higher dose of Diphereline 0.1 mg than recommended

No side effects have been observed after overdose of the medicine.

4. Possible side effects

Like all medicines, Diphereline 0.1 mg can cause side effects, although not everybody gets 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 occur, inform your doctor immediately.
Men
Many of the side effects are likely to be caused by changes in testosterone levels in the body. These effects include: hot flashes, impotence, and decreased libido.
Very common- side effects that occur in more than 1 in 10 patients

• Hot flashes
• Weakness
• Excessive sweating
• Back pain
• Pins and needles in the lower limbs
• Decreased sexual desire
• Impotence

Common- side effects that occur in no more than 1 in 10 patients

• Nausea, dry mouth
• Pain, bruising, redness, and swelling at the injection site
• Muscle and bone pain, pain in the arms and legs
• Swelling (fluid accumulation in tissues)
• Abdominal pain
• High blood pressure
• Allergic reaction
• Weight gain
• Dizziness, headache
• Loss of sexual desire, depression, mood changes

Uncommon- side effects that occur in no more than 1 in 100 patients

• Increased platelet count
• Palpitations
• Ringing in the ears, dizziness, blurred vision
• Abdominal pain, constipation, diarrhea, vomiting
• Numbness, chills, drowsiness, pain
• Changes in some test results (including increased liver enzyme activity), high blood pressure
• Weight loss
• Loss of appetite, increased appetite, gout (severe pain and swelling of joints, most often affecting the big toe), diabetes, high levels of fats in the blood
• Joint pain, muscle cramps, muscle weakness, muscle pain, swelling of the ankles, feet, or toes, bone pain
• Tingling and numbness
• Sleep disturbances, irritability
• Breast enlargement in men, breast pain (breast tenderness), decreased testicle size, testicle pain
• Shortness of breath
• Acne, hair loss, itching, rash, skin redness, hives
• Frequent urination at night, urinary disorders
• Nosebleeds

Rare- side effects that occur in no more than 1 in 1000 patients

• Red or purple skin discoloration
• Abnormal sensations in the eye, blurred or disturbed vision
• Feeling of fullness in the abdomen, bloating, taste disturbances
• Chest pain
• Difficulty maintaining an upright position
• Flu-like symptoms, fever
• Severe allergic reaction (anaphylactic reaction) that can cause dizziness or difficulty breathing, swelling of the face or throat
• Rhinitis, pharyngitis
• Joint stiffness, joint swelling, musculoskeletal stiffness, osteoarthritis
• Memory loss
• Confusion, decreased activity, excitement
• Shortness of breath when lying down
• Blisters on the skin
• Low blood pressure

Side effects reported after the medicine was placed on the market (frequency not known):

• Severe allergic reaction causing swelling of the face, tongue, and throat, dizziness, or difficulty breathing (Quincke's edema, anaphylactic shock)
• Changes in ECG (prolongation of the QT interval)
• General malaise, anxiety
• Urinary incontinence
• In the case of an existing pituitary tumor, increased risk of bleeding into the pituitary.

As with other GnRH analogues, patients treated with Diphereline 0.1 mg may have an increased white blood cell count.
Women
Many of the side effects are likely to be caused by changes in estrogen levels in the body.
Very common- side effects that occur in more than 1 in 10 patients

• Headache
• Decreased sexual desire, mood swings, sleep disturbances
• Breast tenderness
• Ovarian hyperstimulation syndrome (with ovarian enlargement and fluid accumulation)
• Pain during or after sexual intercourse, vaginal bleeding
• Pelvic pain
• Ovarian cysts, vaginal dryness
• Excessive sweating, acne, seborrhea
• Hot flashes

Common- side effects that occur 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 the ankles, feet, or toes
• Allergic reaction
• Pain in the arms and legs
• Dizziness

Uncommon- side effects that occur in no more than 1 in 100 patients

• Palpitations
• Dizziness
• Dry eyes, blurred vision
• Bloating, vomiting, diarrhea, bloating with gas
• Dry mouth, oral ulcers
• Weight loss, decreased appetite
• Fluid retention
• Back pain, muscle pain
• Taste disturbances
• Numbness
• Temporary loss of consciousness, memory loss, lack of concentration
• Tingling or numbness, involuntary muscle movements
• Mood changes, anxiety, disorientation, depression
• Post-coital bleeding, bladder prolapse, irregular menstrual periods, painful menstrual periods, heavy menstrual bleeding
• Small cysts on the ovaries, which can cause pain, vaginal discharge
• Shortness of breath, nosebleeds
• Hair loss, dry skin, excessive hair growth on the body, brittle nails, itching, rash

Side effects reported after the medicine was placed on the market (frequency not known):

• General malaise, fever
• Seizures
• High blood pressure
• Diarrhea
• Severe allergic reaction causing swelling of the face, tongue, and throat, dizziness, or difficulty breathing (Quincke's edema, anaphylactic shock)
• Changes in some blood test results (including increased activity of some enzymes)
• Muscle weakness
• Confusion, vision disturbances
• Amenorrhea
• In the case of an existing pituitary tumor, increased risk of bleeding into the pituitary

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

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Diphereline 0.1 mg

Store the 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 that month.
Expiry date (EXP)
Batch number (Lot)
Store in a temperature below 25°C.

6. Contents of the packaging and other information

What Diphereline 0.1 mg contains

The active substance of the medicine is triptorelin in the form of triptorelin acetate. One vial contains 0.1 mg of triptorelin.
Other ingredients are:

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

What Diphereline 0.1 mg looks like and what the pack contains

Powder and solvent for solution for injection.
A glass vial containing powder and a glass ampoule containing solvent.
The pack contains 7 vials of powder and 7 ampoules of solvent.

Marketing authorization holder and manufacturer

Marketing authorization holder
Ipsen Pharma
65 Quai Georges Gorse
92100 Boulogne Billancourt
France
Manufacturer
Ipsen Pharma Biotech
Parc d’Activités du Plateau de Signes
Chemin départemental nr 402
83870 Signes
France
To obtain more detailed information about this medicine, contact the local representative of the marketing authorization holder:
Ipsen Poland Sp. z o.o.
ul. Chmielna 73
00-801 Warsaw
phone: 22 653 68 00
fax: 22 653 68 22
Date of last revision of the leaflet:October 2024