Bortezomib Accord - patient leaflet, side effects, dosage

Patient leaflet - Bortezomib Accord

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

Bortezomib Accord contains the active substance bortezomib, a so-called ‘proteasome inhibitor’.

Proteasomes play an important role in controlling cell function and growth. By interfering with their function, bortezomib can kill cancer cells.

Bortezomib Accord is used for the treatment of multiple myeloma (a cancer of the bone marrow) in patients older than 18 years:

– alone or together with the medicines pegylated liposomal doxorubicin or dexamethasone, for patients whose disease is worsening (progressive) after receiving at least one prior treatment and for whom blood stem cell transplantation was not successful or is unsuitable.
– in combination with the medicines melphalan and prednisone, for patients whose disease has not been previously treated and are unsuitable for high-dose chemotherapy with blood stem cell transplantation.

– in combination with the medicines dexamethasone or dexamethasone together with thalidomide, for patients whose disease has not been previously treated and before receiving high-dose chemotherapy with blood stem cell transplantation (induction treatment).

Bortezomib Accord is used for the treatment of mantle cell lymphoma (a type of cancer affecting the lymph nodes) in patients 18 years or older in combination with the medicines rituximab, cyclophosphamide, doxorubicin and prednisone, for patients whose disease has not been previously treated and for whom blood stem cell transplantation is unsuitable.

2. What you need to know before you use Bortezomib Accord

Do not use Bortezomib Accord

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

Warnings and precautions

You should tell your doctor if you have any of the following:

low numbers of red or white blood cells
bleeding problems and/or low number of platelets in your blood
diarrhoea, constipation, nausea or vomiting
fainting, dizziness or light-headedness in the past
kidney problems
moderate to severe liver problems
numbness, tingling, or pain in the hands or feet (neuropathy) in the past
heart or blood pressure problems
shortness of breath or cough
seizures
shingles (localised including around the eyes or spread across the body)
symptoms of tumor lysis syndrome such as muscle cramping, muscle weakness, confusion, visual loss or disturbances and shortness of breath
memory loss, trouble thinking, difficulty with walking or loss of vision. These may be signs of a serious brain infection and your doctor may suggest further testing and follow-up.

You will have to take regular blood tests before and during your treatment with Bortezomib Accord, to check your blood cell counts regularly.

If you have mantle cell lymphoma and are given the medicine rituximab with Bortezomib Accord you should tell your doctor:

if you think you have hepatitis infection now or have had it in the past. In a few cases, patients who have had hepatitis B might have a repeated attack of hepatitis, which can be fatal. If you have a history of hepatitis B infection you will be carefully checked by your doctor for signs of active hepatitis B.

You must read the package leaflets of all medicines to be taken in combination with Bortezomib Accord for information related to these medicines before starting treatment with Bortezomib Accord. When thalidomide is used, particular attention to pregnancy testing and prevention requirements is needed (see Pregnancy and breast-feeding in this section).

Children and adolescents

Bortezomib Accord should not be used in children and adolescents because it is not known how the medicine will affect them.

Other medicines and Bortezomib Accord

Please tell your doctor, or pharmacist if you are taking, have recently taken or might take any other medicines.

In particular, tell your doctor if you are using 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 for depression or other conditions
– oral antidiabetics

Pregnancy and breast-feeding

You should not use Bortezomib Accord if you are pregnant, unless clearly necessary.

Both men and women receiving Bortezomib Accord must use effective contraception during and for up to 3 months after treatment. If, despite these measures, pregnancy occurs, tell your doctor immediately.

You should not breast-feed while using Bortezomib Accord. Discuss with your doctor when it is safe to restart breast-feeding after finishing your treatment.

Thalidomide causes birth defects and foetal death. When Bortezomib Accord is given in combination with thalidomide you must follow the pregnancy prevention programme for thalidomide (see package leaflet for thalidomide).

Driving and using machines

Bortezomib Accord might cause tiredness, dizziness, fainting, or blurred vision. Do not drive or operate tools or machines if you experience such side effects; even if you do not, you should still be cautious.

3. How to use Bortezomib Accord

Your doctor will work out your dose of Bortezomib Accord according to your height and weight (body surface area). The usual starting dose of Bortezomib Accord is 1.3 mg/m2 body surface area twice a week.

Your doctor may change the dose and total number of treatment cycles, depending on your response to the treatment on the occurrence of certain side effects and on your underlying conditions (e.g. liver problems).

Progressive multiple myeloma

When Bortezomib Accord is given alone, you will receive 4 doses of Bortezomib Accord 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) corresponds to one treatment cycle. You might receive up to 8 cycles (24 weeks).

You may also be given Bortezomib Accord together with the medicines pegylated liposomal doxorubicin or dexamethasone.

When Bortezomib Accord is given together with pegylated liposomal doxorubicin, you will receive Bortezomib Accord intravenously or subcutaneously as a 21-day treatment cycle and pegylated liposomal doxorubicin 30 mg/m2 is given on day 4 of the Bortezomib Accord 21-day treatment cycle as an intravenous infusion after the Bortezomib Accord injection.

You might receive up to 8 cycles (24 weeks).

When Bortezomib Accord is given together with dexamethasone, you will receive Bortezomib Accord intravenously or subcutaneously as a 21-day treatment cycle and dexamethasone 20 mg is given orally on days 1, 2, 4, 5, 8, 9, 11, and 12, of the Bortezomib Accord, 21-day treatment cycle.

You might receive up to 8 cycles (24 weeks).

Previously untreated multiple myeloma

If you have not been treated before for multiple myeloma, and you are not suitable for blood stem cell transplantation you will receive Bortezomib Accord together with two other medicines; melphalan and prednisone.

In this case, the duration of a treatment cycle is 42 days (6 weeks). You will receive 9 cycles (54 weeks).

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

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

If you have not been treated before for multiple myeloma, and you are suitable for blood stem cell transplantation you will receive Bortezomib Accord intravenously or subcutaneously together with the medicines dexamethasone, or dexamethasone and thalidomide, as induction treatment.

When Bortezomib Accord is given together with dexamethasone, you will receive Bortezomib Accord intravenously or subcutaneously as a 21-day treatment cycle and dexamethasone 40 mg is given orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the Bortezomib Accord 21-day treatment cycle.

You will receive 4 cycles (12 weeks).

When Bortezomib Accord is given together with thalidomide and dexamethasone, the duration of a treatment cycle is 28 days (4 weeks).

Dexamethasone 40 mg is given orally on days 1, 2, 3, 4, 8, 9, 10 and 11 of the Bortezomib Accord 28-day treatment cycle and thalidomide is given orally daily at 50 mg up to day 14 of the first cycle, and if tolerated the thalidomide dose is increased to 100 mg on days 15–28 and may be further increased to 200 mg daily from the second cycle onwards.

You might receive up to 6 cycles (24 weeks).

Previously untreated mantle cell lymphoma

If you have not been treated before for mantle cell lymphoma, you will receive Bortezomib Accord intravenously or subcutaneously together with the medicines rituximab, cyclophosphamide, doxorubicin and prednisone.

Bortezomib Accord is given intravenously or subcutaneously on days 1, 4, 8 and 11, followed by a ‘rest period’ without treatment. The duration of a treatment cycle is 21 days (3 weeks). You might receive up to 8 cycles (24 weeks).

The following medicines are given on day 1 of each Bortezomib Accord 21-day treatment cycle as intravenous infusions:

Rituximab at 375 mg/m2, cyclophosphamide at 750 mg/m2 and doxorubicin at 50 mg/m2.

Prednisone is given orally at 100 mg/m2 on days 1, 2, 3, 4 and 5 of the Bortezomib Accord treatment cycle.

How Bortezomib Accord is given

Bortezomib Accord will be administered by a health care professional experienced in the use of cytotoxic medicines.

This medicine is for subcutaneous use (injected under the skin) and, after dilution, also for intravenous use (injected into a vein). Injection into a vein is rapid, taking 3 to 5 seconds. Injection under the skin is in either the thighs or the abdomen.

If you are given too much Bortezomib Accord

As this medicine is being given by your doctor or nurse, it is unlikely that you will be given too much. In the unlikely event of an overdose, your doctor will monitor you for side effects.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Some of these effects may be serious.

If you are given Bortezomib Accord for multiple myeloma or mantle cell lymphoma, tell your doctor straight away if you notice any of the following symptoms:

– muscle cramping, muscle weakness
– confusion, visual loss or disturbances, blindness, seizures, headaches
– shortness of breath, swelling of your feet or changes in your heart beat, high blood pressure, tiredness, fainting
– coughing and breathing difficulties or tightness in the chest.

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

– platelets, which may make you be more prone to bruising, or to bleeding without obvious injury (e.g., bleeding from your bowels, stomach, mouth and gum or bleeding in the brain or bleeding from the liver)
– red blood cells, which can cause anaemia, with symptoms such as tiredness and paleness
– white blood cells may make you more prone to infections or flu-like symptoms.

If you are given Bortezomib Accord for the treatment of multiple myeloma the side effects you may get are listed below:

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

Sensitivity, numbness, tingling or burning sensation of the skin, or pain in the hands or feet, due to nerve damage
Reduction in the number of red blood cells and or white blood cells (see above)
Fever
Feeling sick (nausea) or vomiting, loss of appetite
Constipation with or without bloating (can be severe)
Diarrhoea: if this happens, it is important that you drink more water than usual. Your doctor may give you another medicine to control diarrhoea
Tiredness (fatigue), feeling weak
Muscle pain, bone pain

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

Low blood pressure, sudden fall of blood pressure on standing which may lead to fainting
High blood pressure
Reduced functioning of your kidneys
Headache
General ill feeling, pain, vertigo, light-headedness, a feeling of weakness or loss of

consciousness

Shivering
Infections, including pneumonia, respiratory infections, bronchitis, fungal infections, coughing with phlegm, flu like illness
Shingles (localised including around the eyes or spread across the body)
Chest pains or shortness of breath with exercise
Different types of rash
Itching of the skin, lumps on the skin or dry skin
Facial blushing or tiny broken capillaries
Redness of the skin
Dehydration
Heartburn, bloating, belching, wind, stomach pain, bleeding from your bowels or stomach
Alteration of liver functioning
A sore mouth or lip, dry mouth, mouth ulcers or throat pain
Weight loss, loss of taste
Muscle cramps, muscle spasms, muscle weakness, pain in your limbs
Blurred vision
Infection of the outermost layer of the eye and the inner surface of the eyelids (conjunctivitis)
Nose bleeds
Difficulty or problems in sleeping, sweating, anxiety, mood swings, depressed mood, restlessness or agitation, changes in your mental status, disorientation
Swelling of body, to include around eyes and 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 reduced heart rate
Failing of your kidneys
Inflammation of a vein, blood clots in your veins and lungs
Problems with blood clotting
Insufficient circulation

Inflammation of the lining around your heart or fluid around your heart

Infections including urinary tract infections, the flu, herpes virus infections, ear infection and cellulitis

Bloody stools, or bleeding from mucosal membranes, e.g., mouth, vagina Cerebrovascular disorders

Paralysis, seizures, falling, movement disorders, abnormal or change in, or reduced sensation (feeling, hearing, tasting, smelling), attention disturbance, trembling, twitching

Arthritis, including inflammation of the joints in the fingers, toes, and the jaw

Disorders that affect your lungs, preventing your body from getting enough oxygen. Some of these include difficulty breathing, shortness of breath, shortness of breath without exercise, breathing that becomes shallow, difficult or stops, wheezing

Hiccups, speech disorders

Increased or decreased urine production (due to kidney damage), painful passing of urine or blood/proteins in the urine, fluid retention

Altered levels of consciousness, confusion, memory impairment or loss

Hypersensitivity

Hearing loss, deafness or ringing in the ears, ear discomfort

Hormone abnormality which may affect salt and water absorption

Overactive thyroid gland

Inability to produce enough insulin or resistance to normal levels of insulin

Irritated or inflamed eyes, excessively wet eyes, painful eyes, dry eyes, eye infections, lump in the eyelid (chalazion), red and swollen eyelids, discharge from the eyes, abnormal vision, bleeding of the eye

Swelling of your lymph glands

Joint or muscle stiffness, sense of heaviness, pain in your groin

Hair loss and abnormal hair texture

Allergic reactions

Redness or pain at the injection site

Mouth pain

Infections or inflammation of the mouth, mouth ulcers, oesophagus, stomach and intestines, sometimes associated with pain or bleeding, poor movement of the intestines (including blockage), abdominal or oesophageal discomfort, difficulty swallowing, vomiting of blood Skin infections

Bacterial and viral infections

Tooth infection

Inflammation of the pancreas, obstruction of the bile duct

Genital pain, problem having an erection

Weight increase

Thirst

Hepatitis

Injection site or injection device related disorders

Skin reactions and disorders (which may be severe and life threatening), skin ulcers

Bruises, falls and injuries

Inflammation or haemorrhage of the blood vessels that can appear as small red or purple dots (usually on the legs) to large bruise-like patches under the skin or tissue

Benign cysts

A severe reversible brain condition which includes seizures, high blood pressure, headaches, tiredness, confusion, blindness or other vision problems.

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

Heart problems to include heart attack, angina
Serious nerve inflammation, which may cause paralysis and difficulty breathing (Guillain-Barre syndrome)
Flushing
Discolouration of the veins
Inflammation of the spinal nerve
Problems with your ear, bleeding from your ear
Underactivity of your thyroid gland
Budd-Chiari syndrome (the clinical symptoms caused by blockage of the hepatic veins)
Changes in or abnormal bowel function
Bleeding in the brain
Yellow discolouration of eyes and skin (jaundice)
Serious allergic reaction (anaphylactic shock) signs of which may include difficulty breathing, chest pain or chest tightness, and/or feeling dizzy/faint, severe itching of the skin or raised lumps on the skin, swelling of the face, lips, tongue and /or throat, which may cause difficulty in swallowing, collapse
Breast disorders
Vaginal tears
Genital swelling
Inability to tolerate alcohol consumption
Wasting, or loss of body mass
Increased appetite
Fistula
Joint effusion
Cysts in the lining of joints (synovial cysts)
Fracture
Breakdown of muscle fibers leading to other complications
Swelling of the liver, bleeding from the liver
Cancer of the kidney
Psoriasis like skin condition
Cancer of the skin
Paleness of the skin
Increase of platelets or plasma cells (a type of white cell) in the blood
Blood clot in small blood vessels (thrombotic microangiopathy)
Abnormal reaction to blood transfusions
Partial or total loss of vision
Decreased sex drive
Drooling
Bulging eyes
Sensitivity to light
Rapid breathing
Rectal pain
Gallstones
Hernia
Injuries
Brittle or weak nails
Abnormal protein deposits in your vital organs
Coma
Intestinal ulcers
Multi-organ failure
Death

If you are given Bortezomib Accord together with other medicines for the treatment of mantle cell lymphoma the side effects you may get are listed below:

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

Pneumonia
Loss of appetite
Sensitivity, numbness, tingling or burning sensation of 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
Tiredness, feeling weak
Fever

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

Shingles (localized including around the eyes or spread across the body)
Herpes virus infections
Bacterial and viral infections
Respiratory infections, bronchitis, coughing with phlegm, flu like illness
Fungal infections
Hypersensitivity (allergic reaction)
Inability to produce enough insulin or resistance to normal levels of insulin
Fluid retention
Difficulty or problems in sleeping
Loss of consciousness
Altered level of consciousness, confusion
Feeling dizzy
Increased heartbeat, high blood pressure, sweating,
Abnormal vision, blurred vision
Heart failure, heart attack, chest pain, chest discomfort, increased or reduced heart rate
High or low blood pressure
Sudden fall of blood pressure upon standing which may lead to fainting
Shortness of breath with exercise
Cough
Hiccups
Ringing in the ears, ear discomfort
Bleeding from your bowels or stomach
Heartburn
Stomach pain, bloating
Difficulty swallowing
Infection or inflammation of the stomach and intestines
Stomach pain
Sore mouth or lip, throat pain
Alteration of liver function
Itching of skin
Redness of skin
Rash
Muscle spasms
Infection of the urinary tract
Pain in limbs
Swelling of body, to include eyes and other parts of the body
Shivering
Redness and pain at injection site
General ill feeling
Weight loss
Weight increase

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

Hepatitis
Severe allergic reaction (anaphylactic reaction) signs of which may include difficulty breathing, chest pain or chest tightness, and/or feeling dizzy/faint, severe itching of the skin or raised lumps on the skin, swelling of the face, lips, tongue and /or throat, which may cause difficulty in swallowing, collapse
Movement disorders, paralysis, twitching
Vertigo
Hearing loss, deafness
Disorders that affect your lungs, preventing your body from getting enough oxygen. Some of these include difficulty breathing, shortness of breath, shortness of breath without exercise, breathing that becomes shallow, difficult or stops, wheezing
Blood clots in your lungs
Yellow discoloration of the eyes and skin (jaundice)
Lump in the eyelid (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)
Serious nerve inflammation, which may cause paralysis and difficulty breathing (Guillain-Barre syndrome)

Reporting of side effects

If any of the side effects, gets serious, or if you notice , any side effects not listed in this leaflet, please tell your doctor or pharmacist immediately. You can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Bortezomib Accord

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 carton after EXP.

Store in a refrigerator (2°C to 8 °C).

Keep the vial in the outer carton in order to protect from light.

Diluted solution

The chemical and physical in-use stability of the diluted solution at a concentration of 1 mg/mL has been demonstrated for 24 hours at 20°C-25°C. From a microbiological point of view, unless the method of opening/ dilution precludes the risk of microbial contamination, the diluted solution should be used immediately after preparation. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

Bortezomib Accord is for single use only. Any unused product or waste material should be disposed of in accordance with local requirements.

6. Contents of the pack and other information

What Bortezomib Accord contains

the active substance is bortezomib. Each vial contains 1 mL or 1.4 mL solution for injection which contains 2.5 mg per mL of bortezomib (as a mannitol boronic ester).
the other ingredients are mannitol (E421) and water for injections.

Intravenous use:

after dilution, 1 mL of solution for intravenous injection contains 1 mg bortezomib.

Subcutaneous use:

1 mL of solution for subcutaneous injection contains 2.5 mg bortezomib.

What Bortezomib Accord looks like and contents of the pack

Bortezomib Accord solution for injection is a clear colourless solution.

Clear glass vial with grey rubber stopper and an aluminium seal, with orange cap, containing 1 mL of solution.

Clear glass vial with grey rubber stopper and an aluminium seal, with red cap, containing 1.4 mL of solution.

Pack sizes

1 × 1 mL vial

4 × 1 mL vials

1 × 1.4 mL vial

4 × 1.4 mL vials

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona

s/n, Edifici Est 6a planta

08039 Barcelona

Spain

Manufacturer

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50,95–200 Pabianice

Poland

Accord Healthcare B.V.

Winthontlaan 200, 3526KV Utrecht

Netherlands

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

The following information is intended for healthcare professionals only:

Note: Bortezomib Accord is a cytotoxic agent. Therefore, caution should be used during handling and preparation. Use of gloves and other protective clothing to prevent skin contact is recommended. Pregnant personnel should not handle this medicine.

ASEPTIC TECHNIQUE MUST BE STRICTLY OBSERVED THROUGHOUT HANDLING OF BORTEZOMIB ACCORD SINCE NO PRESERVATIVE IS PRESENT.

Bortezomib 2.5 mg/mL solution for injection IS FOR SUBCUTANEOUS OR INTRAVENOUS USE. Do not give by other routes. Intrathecal administration has resulted in death.

1. PREPARATION FOR INTRAVENOUS INJECTION
- 1.1 Preparation of the 2.5 mg/1 mL vial: add 1.6 mL of 9 mg/mL (0.9%) sodium chloride solution for injection to the vial containing the Bortezomib.

Preparation of the 3.5 mg/1.4 mL vial: add 2.2 mL of 9 mg/mL (0.9%) sodium chloride solution for injection to the vial containing the Bortezomib.

Each vial contains an additional overfill of 0.1 mL. Consequently each 1 mL and 1.4 mL vials contain 2.75 mg and 3.75 mg of bortezomib respectively.

The concentration of the resulting solution will be 1 mg/mL. The solution will be clear colourless.

1.2 Before administration, visually inspect the solution for particulate matter and discolouration. If any discolouration or particulate matter is observed, the solution should be discarded. Be sure that the correct dose is being given for the intravenous route of administration (1 mg/mL).

The diluted solution is preservative-free and should be used immediately after preparation. However, the chemical and physical in-use stability of the diluted solution has been demonstrated for 24 hours at 20°C-25°C. The total storage time for the diluted medicine should not exceed 24 hours prior to administration. If the diluted solution is not used immediately, inuse storage times and conditions prior to use are the responsibility of the user. It is not necessary to protect the diluted medicine from light.

2. ADMINISTRATION FOR INTRAVENOUS INJECTION
- 2.1 Once diluted, withdraw the appropriate amount of the diluted solution according to calculated dose based upon the patient’s body surface area.
- 2.2 Confirm the dose and concentration in the syringe prior to use (check that the syringe is marked as intravenous administration).
- 2.3 Inject the solution as a 3–5 second bolus intravenous injection through a peripheral or central intravenous catheter into a vein.
- 2.4 Flush the peripheral or intravenous catheter with 9 mg/mL (0.9 %) sodium chloride solution.
3. PREPARATION FOR SUBCUTANEOUS INJECTION
- 3.1 Bortezomib solution for injection is ready to use when administered subcutaneously.

The concentration of the solution is 2.5 mg/mL. The solution is clear colourless.

3.2 Before administration, visually inspect the solution for particulate matter and discolouration. If any discolouration or particulate matter is observed, the solution should be discarded. Be sure that the correct dose is being given for the subcutaneous route of administration (2.5 mg/mL).
3.3 The product is preservative free and should be used immediately after withdrawal of the appropriate amount of solution.
3.4 During preparation for administration and during administration itself it is not necessary to protect the medicine from light.

4. ADMINISTRATION FOR SUBCUTANEOUS INJECTION
- 4.1 Withdraw the appropriate amount of the solution according to calculated dose based upon the patient’s body surface area.
- 4.2 Confirm the dose and concentration in the syringe prior to use (check that the syringe is marked as subcutaneous administration).
- 4.3 Inject the solution subcutaneously, under a 45°-90°angle.
- 4.4 The solution is administered subcutaneously through the thighs (right or left) or abdomen (right or left).
- 4.5 Injection sites should be rotated for successive injections.
- 4.6 If local injection site reactions occur following bortezomib injection subcutaneously, either a less concentrated bortezomib solution (1 mg/mL instead of 2.5 mg/mL) may be administered subcutaneously or a switch to intravenous injection is recommended.
5. DISPOSAL