Bortezomib Hikma

Package leaflet: Information for the user

Bortezomib Hikma 3.5 mg powder for solution for injection

Bortezomib
Generic medicinal product
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Bortezomib Hikma is and what it is used for

Bortezomib Hikma contains the active substance bortezomib, a so-called "proteasome inhibitor". Proteasomes play an important role in regulating cell functions and cell growth. By interfering with their function, bortezomib can kill tumour cells.

Bortezomib Hikma is used to treat multiple myeloma (a type of cancer of the bone marrow) in patients over 18 years of age:

• alone or in combination with pegylated liposomal doxorubicin or dexamethasone, for patients whose disease is worsening (progressive) after having received at least one prior treatment and for whom blood stem cell transplantation has failed or is not feasible;
• in combination with melphalan and prednisone, for patients whose disease has not been previously treated and who cannot receive high-dose chemotherapy with blood stem cell transplantation;
• in combination with dexamethasone or dexamethasone together with thalidomide, for patients whose disease has not been previously treated and who are to receive high-dose chemotherapy followed by blood stem cell transplantation (induction treatment).

Bortezomib Hikma is also used to treat mantle cell lymphoma (a type of cancer affecting the lymph nodes) in patients aged 18 years and older, in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone, for patients whose disease has not been previously treated and for whom blood stem cell transplantation is not feasible.

2. What you should know before using Bortezomib Hikma

Do not use Bortezomib Hikma

• if you are allergic to bortezomib, to boron, or to any of the other ingredients of this medicine (listed in section 6)
• if you have severe lung or heart problems.

Warnings and precautions
Talk to your doctor if you have any of the following conditions:

• low number of red blood cells or white blood cells,
• bleeding problems and/or low platelet count in the blood,
• diarrhoea, constipation, nausea or vomiting,
• previous episodes of fainting, dizziness or lightheadedness,
• kidney problems,
• moderate to severe liver problems,
• numbness, tingling or pain in the hands or feet (neuropathy) previously experienced,
• heart problems or blood pressure issues,
• shortness of breath or cough,
• seizures,
• shingles (localized, including around the eyes, or widespread on the body),
• symptoms of tumour lysis syndrome such as, for example, muscle cramps, muscle weakness, confusion, vision loss or disturbances, and shortness of breath,
• memory loss, difficulty thinking, difficulty walking or vision loss. These may be signs of a serious brain infection, and your doctor may prescribe further tests and monitoring.

You will need to have regular blood tests before and during treatment with Bortezomib Hikma to continuously monitor your blood cell counts.

If you have mantle cell lymphoma and are being treated with the medicine rituximab together with Bortezomib Hikma, inform your doctor:

• if you think you have hepatitis or have had it in the past. In some cases, patients who have had hepatitis B may experience a reactivation of the disease, which can be fatal. If you have previously had hepatitis B infection, you will be closely monitored by your doctor for signs and symptoms of active hepatitis.

You should read the package leaflets of all the medicines you are taking in combination with Bortezomib Hikma for information about these medicines before starting treatment with Bortezomib Hikma.

When taking thalidomide, particular attention must be paid to the instructions regarding pregnancy testing and the pregnancy prevention programme (see "Pregnancy and breastfeeding" in this section).

Children and adolescents
Bortezomib Hikma must not be used in children and adolescents because the effect of this medicine in this population is unknown.

Other medicines and Bortezomib Hikma
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

In particular, inform your doctor if you are taking medicines containing any of the following active substances:

• ketoconazole, used to treat fungal infections,
• ritonavir, used to treat HIV infection,
• rifampicin, an antibiotic used to treat bacterial infections,
• carbamazepine, phenytoin or phenobarbital, used to treat epilepsy,
• St. John’s wort (Hypericum perforatum), used to treat depression or other conditions,
• oral antidiabetic medicines.

Pregnancy and breastfeeding
Do not use Bortezomib Hikma if you are pregnant unless absolutely necessary. Women of childbearing potential must use effective contraception during treatment and for 8 months after the end of treatment. Consult your doctor if you wish to freeze your eggs before starting treatment.

Men must not father a child during treatment with Bortezomib Hikma and must use an effective contraceptive method during treatment and for 5 months after the end of treatment. Consult your doctor if you wish to preserve sperm before starting treatment.

Do not breastfeed while taking Bortezomib Hikma. Discuss with your doctor when it is appropriate to resume breastfeeding after the end of treatment.

Thalidomide causes congenital malformations and fetal death. When Bortezomib Hikma is administered together with thalidomide, you must follow the pregnancy prevention programme for thalidomide (see the thalidomide package leaflet).

Driving and using machines
Bortezomib Hikma may cause fatigue, dizziness, fainting or blurred vision.
Do not drive or operate tools or machinery if you experience any of these side effects; you should also exercise particular caution even if you do not experience these effects.

3. How to use Bortezomib Hikma

Your doctor will calculate the dose of Bortezomib Hikma based on your height and weight (body surface area). The standard starting dose of Bortezomib Hikma is 1.3 mg/m² body surface area administered twice weekly. Your doctor may adjust the dose and the total number of treatment cycles depending on your response to treatment, the occurrence of certain side effects, and your overall health condition (e.g. liver problems).

Relapsed multiple myeloma
When Bortezomib Hikma is given alone, you will receive 4 doses of Bortezomib Hikma intravenously or subcutaneously on days 1, 4, 8, and 11, followed by a 10-day "rest" period without treatment. This 21-day period (3 weeks) constitutes one treatment cycle. You may receive up to 8 cycles (24 weeks).

You may also receive Bortezomib Hikma in combination with pegylated liposomal doxorubicin or dexamethasone.

When Bortezomib Hikma is administered together with pegylated liposomal doxorubicin, you will receive a 21-day treatment cycle with Bortezomib Hikma given intravenously or subcutaneously, and 30 mg/m² of pegylated liposomal doxorubicin will be administered on day 4 of the Bortezomib Hikma 21-day treatment cycle as an intravenous infusion after the injection of Bortezomib Hikma.
You may receive up to 8 cycles (24 weeks).

When Bortezomib Hikma is administered together with dexamethasone, you will receive a 21-day treatment cycle with Bortezomib Hikma given intravenously or subcutaneously, and oral dexamethasone at a dose of 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of the Bortezomib Hikma 21-day treatment cycle.
You may receive up to 8 cycles (24 weeks).

Previously untreated multiple myeloma
If you have never been treated before for multiple myeloma and are not eligible for stem cell transplantation, you will receive Bortezomib Hikma in combination with two other medicines, melphalan and prednisone.
In this case, the duration of one treatment cycle is 42 days (6 weeks). You will receive 9 cycles (54 weeks).

• In cycles 1 to 4, Bortezomib Hikma is administered twice weekly on days 1, 4, 8, 11, 22, 25, 29, and 32.
• In cycles 5 to 9, Bortezomib Hikma is administered once weekly on days 1, 8, 22, and 29.

Melphalan (9 mg/m²) and prednisone (60 mg/m²) are both administered orally on days 1, 2, 3, and 4 of the first week of each cycle.

If you have never been treated before for multiple myeloma and are eligible for stem cell transplantation, you will receive Bortezomib Hikma intravenously or subcutaneously in combination with dexamethasone, or with dexamethasone and thalidomide, as induction treatment.

When Bortezomib Hikma is administered in combination with dexamethasone, you will receive Bortezomib Hikma intravenously or subcutaneously in 21-day treatment cycles and oral dexamethasone 40 mg on days 1, 2, 3, 4, 8, 9, 10, and 11 of the Bortezomib Hikma 21-day treatment cycle.
You will receive 4 cycles (12 weeks).

When Bortezomib Hikma is administered in combination with thalidomide and dexamethasone, the treatment cycle duration is 28 days (4 weeks).
Dexamethasone 40 mg is administered orally on days 1, 2, 3, 4, 8, 9, 10, and 11 of the 28-day Bortezomib Hikma treatment cycle, and thalidomide is administered daily by mouth at a dose of 50 mg up to day 14 of the first cycle; if tolerated, the thalidomide dose is increased to 100 mg on days 15–28, and may subsequently be increased up to 200 mg per day starting from the second cycle onwards.
You may receive up to 6 cycles (24 weeks).

Previously untreated mantle cell lymphoma
If you have never previously received treatment for mantle cell lymphoma, you will receive Bortezomib Hikma intravenously in combination with the medicines rituximab, cyclophosphamide, doxorubicin, and prednisone.

Bortezomib Hikma is administered intravenously on days 1, 4, 8, and 11, followed by a "rest" period without treatment. The duration of one treatment cycle is 21 days (3 weeks). You may receive up to 8 cycles (24 weeks).

The following medicines are administered on day 1 of each 21-day Bortezomib Hikma treatment cycle as intravenous infusions:
Rituximab at 375 mg/m², cyclophosphamide at 750 mg/m², and doxorubicin at 50 mg/m².

Prednisone is administered orally at a dose of 100 mg/m² on days 1, 2, 3, 4, and 5 of the Bortezomib Hikma treatment cycle.

How Bortezomib Hikma is administered
This medicine is for intravenous or subcutaneous use. Bortezomib Hikma will be administered by a healthcare professional experienced in the use of cytotoxic medicines.

The Bortezomib Hikma powder must be dissolved before administration. This will be done by a healthcare professional. The resulting solution will then be injected into a vein or under the skin. The intravenous injection is rapid, administered over a period of 3 to 5 seconds. The subcutaneous injection can be given either in the thigh or the abdomen.

If you are given more Bortezomib Hikma than you should
Since this medicine is administered by a doctor or nurse, it is unlikely that you will receive more than you should. In the unlikely event of an overdose, your doctor will monitor you for any side effects.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Some of these side effects can be serious.
If you are given Bortezomib Hikma for multiple myeloma or mantle cell lymphoma, inform your doctor immediately if you notice any of the following symptoms:

• muscle cramps, muscle weakness,
• confusion, vision loss or disturbances, blindness, seizures, headache,
• shortness of breath, swelling of the feet or changes in heartbeat, high blood pressure, fatigue, fainting,
• cough and difficulty breathing or chest tightness.

Treatment with Bortezomib Hikma can very commonly cause a decrease in the number of red blood cells, white blood cells, and platelets in the blood. Therefore, you will need regular blood tests before and during treatment with Bortezomib Hikma to monitor your blood cell counts regularly. You may experience a reduction in the number of:

• platelets, which could make you more prone to bruising or bleeding without obvious injury (for example, intestinal, stomach, mouth, or gum bleeding, or cerebral or liver haemorrhage),
• red blood cells, which can cause anaemia, with symptoms such as fatigue and pallor,
• white blood cells, which may increase your susceptibility to infections or flu-like symptoms.

If you are given Bortezomib Hikma for the treatment of multiple myeloma, the side effects that may occur are listed below:

Very common side effects (may affect more than 1 in 10 people)

• Numbness, tingling, burning sensation, or pain in the skin, or pain in the hands or feet due to nerve damage
• reduction in the number of red and/or white blood cells (see above)
• fever
• feeling unwell (nausea) or vomiting, loss of appetite
• constipation with or without bloating (can be severe)

• diarrhoea: if this occurs, it is important that you drink more water than usual. Your doctor may prescribe another medicine to control diarrhoea
• fatigue (tiredness), feeling of weakness
• muscle pain, bone pain

Common side effects (may affect up to 1 in 10 people)

• low blood pressure, sudden drop in blood pressure when standing up, which may lead to fainting
• high blood pressure
• reduced kidney function
• headache
• general feeling of discomfort, pain, dizziness, feeling of emptiness in the head, weakness or loss of consciousness
• chills
• infections, including pneumonia, respiratory infections, bronchitis, fungal infections, cough with phlegm, flu-like illness
• Herpes zoster (localized, including around the eyes, or widespread on the body)
• chest pain or difficulty breathing during physical activity
• various types of skin rash
• skin itching, skin nodules or dry skin
• facial redness or small capillary ruptures
• skin redness
• dehydration
• heartburn, bloating, belching, gas, stomach pain, intestinal or stomach bleeding
• altered liver function
• irritation of the mouth or lips, dry mouth, mouth ulcers or sore throat
• weight loss, loss of taste
• muscle cramps, muscle spasms, muscle weakness, limb pain
• blurred vision
• infection of the outer layer of the eye and the inner surface of the eyelids (conjunctivitis)
• nosebleeds
• sleep difficulties or problems, sweating, anxiety, mood changes, depressed mood, restlessness or agitation, changes in mental state, disorientation
• body swelling, including swelling around the eyes and in other parts of the body

Uncommon side effects (may affect up to 1 in 100 people)

• heart failure, heart attack, chest pain, chest discomfort, increased or decreased heart rate
• kidney failure
• vein inflammation, blood clots in veins and lungs
• blood clotting problems
• circulatory failure
• inflammation of the membrane surrounding the heart or fluid accumulation around the heart
• infections including urinary tract infections, influenza, herpes virus infections, ear infections, and cellulitis
• blood in stools, or mucosal bleeding, for example in the mouth or vagina
• cerebrovascular disorders
• paralysis, seizures, falls, movement disorders, abnormal or altered/reduced sensation (touch, hearing, taste, smell), attention disorders, tremor, spasms
• arthritis, including inflammation of the joints of the fingers, toes, and jaw
• lung disorders, preventing the body from receiving sufficient oxygen. Some of these include difficulty breathing, dyspnoea, dyspnoea without physical activity, shallow, difficult or interrupted breathing, wheezing
• hiccups, speech disorders
• increased or decreased urine production (due to kidney damage), painful urination, or presence of blood/protein in urine, fluid retention
• altered levels of consciousness, confusion, impaired or lost memory
• hypersensitivity
• hearing loss, deafness or ringing in the ears, ear discomfort
• hormonal changes affecting salt and water reabsorption
• overactivity of the thyroid gland
• inability to produce enough insulin or resistance to normal insulin levels
• irritated or inflamed eyes, excessively watery eyes, eye pain, dry eyes, eye infections, eyelid swelling (chalazion), red and swollen eyelids, eye discharge, vision disturbances, eye bleeding
• swollen lymph nodes
• joint or muscle stiffness, feeling of heaviness, groin pain
• hair loss or abnormal hair texture
• allergic reactions
• redness or pain at the injection site
• mouth pain
• infection or inflammation of the mouth, mouth ulcers, oesophagus, stomach, and intestine, sometimes associated with pain or bleeding, reduced intestinal motility (including intestinal blockage), abdominal or oesophageal discomfort, difficulty swallowing, vomiting blood
• skin infections
• bacterial and viral infections
• dental infections
• pancreatitis, bile duct obstruction
• genital pain, erectile problems
• weight gain
• feeling thirsty
• hepatitis
• injection site or infusion device site reactions or disorders
• skin reactions or disorders (which can be severe and life-threatening), skin ulceration
• bruising, falls and injuries
• inflammation or bleeding of blood vessels, which may appear as small red or purple spots (usually on the legs) that may develop into large bruises under the skin or tissues
• benign cysts
• a serious and reversible brain condition including seizures, high blood pressure, headache, fatigue, confusion, blindness or other vision problems

Rare side effects (may affect up to 1 in 1,000 people)

• heart problems including heart attack, angina
• severe nerve inflammation, which can cause paralysis and breathing difficulties (Guillain-Barré syndrome)
• hot flushes
• change in the colour of veins
• inflammation of the spinal nerve
• ear problems, ear bleeding
• reduced activity of the thyroid gland
• Budd-Chiari syndrome (clinical signs caused by blockage of the liver veins)
• altered or abnormal intestinal function
• cerebral haemorrhage
• yellowing of the eyes and skin (jaundice)
• severe allergic reaction (anaphylactic shock), signs include breathing difficulties, chest pain or tightness, and/or dizziness/fainting, severe skin itching or appearance of swellings on the skin, swelling of the face, lips, tongue and/or throat causing difficulty swallowing, collapse
• breast disorders
• vaginal discharge
• genital swelling
• inability to tolerate alcohol consumption
• wasting or loss of body mass
• increased appetite
• fistulas
• joint effusion
• cysts in the membrane covering the joints (synovial cysts)
• fractures
• muscle fibre rupture leading to further complications
• enlarged liver, liver haemorrhage
• kidney cancer
• skin condition similar to psoriasis
• skin tumour
• pale skin
• increased platelets or plasma cells (a type of white blood cell) in the blood
• blood clot in small blood vessels (thrombotic microangiopathy)
• abnormal reaction to blood transfusion
• partial or complete loss of vision
• decreased sexual desire
• loss of saliva
• protruding eyes
• light sensitivity
• rapid breathing
• rectal pain
• gallstones
• hernia
• injuries
• brittle or weak nails
• abnormal protein deposition in vital organs
• coma
• intestinal ulcers
• multi-organ failure
• death
• severe nerve inflammation, which can cause paralysis and breathing difficulties (Guillain-Barré syndrome)

If you are given Bortezomib Hikma in combination with other medicines for the treatment of mantle cell lymphoma, the side effects you may experience are listed below:

Very common side effects (may affect more than 1 in 10 people)

• pneumonia
• loss of appetite
• numbness, tingling, burning sensation, or pain in the skin, or pain in the hands or feet due to nerve damage
• nausea and vomiting
• diarrhoea
• mouth ulcers
• constipation
• muscle pain, bone pain
• hair loss and abnormal hair texture
• fatigue, feeling of weakness
• fever

Common side effects (may affect up to 1 in 10 people)

• Herpes zoster (localized, including around the eyes, or widespread on the body)
• herpes virus infection
• bacterial and viral infections
• respiratory infections, bronchitis, cough with phlegm, flu-like illness
• fungal infections
• hypersensitivity (allergic reaction)
• inability to produce enough insulin or resistance to normal insulin levels
• fluid retention
• difficulty or problems sleeping
• loss of consciousness
• altered levels of consciousness, confusion
• dizziness
• increased heart rate, high blood pressure, sweating
• abnormal vision, blurred vision
• heart failure, heart attack, chest pain, chest discomfort, increased or decreased heart rate
• high or low blood pressure
• sudden drop in blood pressure when standing up, which may lead to fainting
• shortness of breath during physical activity
• cough
• hiccups
• ringing in the ears, ear discomfort
• intestinal or stomach bleeding
• heartburn
• stomach pain, bloating
• difficulty swallowing
• infection or inflammation of the stomach and intestine
• stomach pain
• irritation of the mouth or lips, sore throat
• altered liver function
• skin itching
• skin redness
• skin rash
• muscle spasms
• urinary tract infection
• limb pain
• body swelling, including swelling around the eyes and in other parts of the body
• chills
• redness and pain at the injection site
• general feeling of discomfort
• loss of body weight
• increase in body weight

Uncommon side effects (may affect up to 1 in 100 people)

• hepatitis
• severe allergic reaction (anaphylactic reaction), signs may include breathing difficulties, chest pain or tightness, and/or dizziness/fainting, severe skin itching or appearance of swellings on the skin, swelling of the face, lips, tongue and/or throat causing difficulty swallowing, collapse
• movement disorders, paralysis, contractions
• dizziness
• hearing loss, deafness
• lung disorders, preventing the body from receiving sufficient oxygen. Some of these include difficulty breathing, shortness of breath even without physical activity, shallow, difficult or interrupted breathing, wheezing
• blood clots in the lungs
• yellowing of the eyes and skin (jaundice)
• eyelid swelling (chalazion), red and swollen eyelids

Rare side effects (may affect up to 1 in 1,000 people)

• Blood clot in small blood vessels (thrombotic microangiopathy)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at
http://www.aifa.gov.it/content/segnalazione-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Bortezomib Hikma

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial and the outer carton after Exp.
The expiry date refers to the last day of that month.
Store the vial in the outer packaging to protect the medicine from light.
The reconstituted solution should be used immediately after preparation. If the reconstituted
solution is not used immediately, the times and conditions of storage prior to use are the
responsibility of the user.
However, the reconstituted solution is stable for 8 hours at 25 °C in the vial and/or in a syringe,
with a total storage time not exceeding 8 hours before administration.
Do not use this medicine if you notice the presence of particles or discoloration before
administration.
Bortezomib Hikma is for single use only. Any unused product and waste materials derived from it
must be disposed of in accordance with local regulations.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. These measures will help protect the environment.

6. Package contents and other information

What Bortezomib Hikma contains

• The active substance is bortezomib. Each vial contains 3.5 mg of bortezomib (as mannitol boronic ester).
• The other excipients are mannitol (E 421) and nitrogen. Reconstitution for intravenous use: after reconstitution, 1 ml of injectable solution for intravenous use contains 1 mg of bortezomib. Reconstitution for subcutaneous use: after reconstitution, 1 ml of injectable solution for subcutaneous use contains 2.5 mg of bortezomib. Description of the appearance of Bortezomib Hikma and contents of the pack Bortezomib Hikma is a white to off-white powder. Each pack of Bortezomib Hikma contains 1 clear glass vial of 8 ml with a grey bromobutyl rubber stopper and an aluminium flip-off cap with white plastic coating.

Marketing Authorisation Holder
Hikma Pharma GmbH
Lochhamer Str. 13
82152 Martinsried
Germany
Manufacturer
PHARMIDEA SIA
4 Rupnica Street,
Olaine LV-2114
Latvia
For any information about this medicinal product, please contact the marketing authorisation holder.
Marketing Authorisation Holder in Italy
Hikma Italia SpA
Viale Certosa 10
27100 Pavia
This medicinal product is authorised in the European Economic Area Member States under the following names:
Austria Bortezomib Ribosepharm 3.5 mg Powder for solution for injection
Germany Bortezomib Ribosepharm 3.5 mg Powder for solution for injection
Italy Bortezomib Hikma 3.5 mg powder for injectable solution
Portugal Bortezomib Hikma
Spain Bortezomib Hikma 3.5 mg powder for injectable solution EFG
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The following information is intended for healthcare professionals only:

1. RECONSTITUTION FOR INTRAVENOUS INJECTION

Note: Bortezomib Hikma is a cytotoxic agent. Therefore, particular care must be taken during handling and preparation. It is recommended to wear gloves and other protective clothing to prevent skin contact.
DUE TO THE ABSENCE OF ANY TYPE OF PRESERVATIVE, ASEPTIC TECHNIQUE MUST BE OBSERVED DURING THE HANDLING OF BORTEZOMIB HIKMA.
1.1 Preparation of the 3.5 mg vial:
Carefully add 3.5 ml of sterile sodium chloride 9 mg/ml (0.9%) solution for injection to the vial containing Bortezomib Hikma lyophilized powder using an appropriate syringe, without removing the vial stopper. The lyophilized powder dissolves completely within less than 2 minutes.
The concentration of the resulting solution will be 1 mg/ml. The solution will be clear and colourless, with a final pH between 4 and 7. It is not necessary to check the pH of the solution.
1.2 Prior to administration, the solution should be visually inspected for the presence of particles or discoloration. If particles or discoloration are observed, the solution must be discarded. Ensure that the correct dose is administered by intravenous route (1 mg/ml).
1.3 The reconstituted solution contains no preservatives and should be used immediately after preparation. However, its chemical and physical in-use stability has been demonstrated for 8 hours at 25 °C when stored in the original vial and/or in a syringe. The total storage time of the reconstituted medicinal product must not exceed 8 hours before administration. If the reconstituted solution is not used immediately, it is the responsibility of the user to ensure appropriate storage conditions and storage times prior to use.
It is not necessary to protect the reconstituted medicinal product from light.

2. ADMINISTRATION

• After reconstitution, withdraw the appropriate volume of the reconstituted solution according to the dose calculated based on the patient's body surface area.
• Confirm the dose and concentration in the syringe before use (check that the syringe is labeled for intravenous administration).
• Administer the solution as an intravenous bolus injection over 3–5 seconds through a peripheral or central intravenous catheter.
• Flush the peripheral or intravenous catheter with sterile sodium chloride solution 9 mg/ml (0.9%). Bortezomib Hikma is FOR SUBCUTANEOUS OR INTRAVENOUS USE. Do not administer by other routes. Intrathecal administration has resulted in deaths.

3. DISPOSAL

The vial is for single use only and any remaining solution must be discarded. Unused medicine and waste material derived from this medicine must be disposed of in accordance with local applicable regulations.

The following information is intended for healthcare professionals only:
Only the 3.5 mg vial can be administered subcutaneously, as described below.

1. RECONSTITUTION FOR SUBCUTANEOUS INJECTION

Note: Bortezomib Hikma is a cytotoxic agent. Therefore, particular care must be taken during handling and preparation. It is recommended to wear gloves and other protective clothing to prevent skin contact.
DUE TO THE ABSENCE OF ANY TYPE OF PRESERVATIVE, ASEPTIC TECHNIQUE MUST BE OBSERVED DURING THE HANDLING OF BORTEZOMIB HIKMA.
1.1 Preparation of the 3.5 mg vial:
Add 1.4 ml of sterile water for injections or sterile 9 mg/ml (0.9%) sodium chloride solution to the vial containing Bortezomib Hikma lyophilized powder using an appropriate syringe, without removing the vial stopper. The lyophilized powder dissolves completely within less than 2 minutes.
The concentration of the resulting solution will be 2.5 mg/ml. The solution will be clear and colourless, with a final pH between 4 and 7. It is not necessary to check the pH of the solution.
1.2 Prior to administration, the solution should be visually inspected for the presence of particulate matter or discoloration. If particulate matter or discoloration is observed, the solution must be discarded. Check the concentration on the vial label to ensure that the correct dose is administered subcutaneously (2.5 mg/ml).
1.3 The reconstituted solution contains no preservatives and should be used immediately after preparation. However, its chemical and physical in-use stability has been demonstrated for 8 hours at 25 °C when stored in the original vial and/or in a syringe. The total storage time of the reconstituted medicinal product must not exceed 8 hours prior to administration. If the reconstituted solution is not used immediately, it is the responsibility of the user to ensure appropriate storage conditions and storage times prior to use.
It is not necessary to protect the reconstituted medicinal product from light.

2. ADMINISTRATION

• After reconstitution, withdraw the appropriate volume of the reconstituted solution according to the dose calculated based on the patient's body surface area.
• Verify the dose and concentration in the syringe before use (ensure the syringe is labeled for subcutaneous administration).
• Inject the solution subcutaneously at an angle of 45–90°.
• The reconstituted solution is administered subcutaneously in the thighs (right or left) or abdomen (right or left side).
• For subsequent administrations, the injection site must be rotated.
• If local reactions at the injection site occur after subcutaneous administration of Bortezomib Hikma, a lower concentration of Bortezomib Hikma solution may be administered (1 mg/ml instead of 2.5 mg/ml), or administration via the intravenous route is recommended. Bortezomib Hikma is FOR SUBCUTANEOUS OR INTRAVENOUS USE ONLY. Do not administer by other routes. Intrathecal administration has resulted in deaths.

3. DISPOSAL

The vial is for single use only, and any remaining solution must be discarded. Unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.