Voriconazole genoptim

Package leaflet: Information for the patient

Voriconazole Genoptim, 200 mg, powder for solution for infusion
Voriconazole
Please read all of this leaflet carefully before starting to take this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm other people, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet
What Voriconazole Genoptim is and what it is used for
What you need to know before taking Voriconazole Genoptim
How to take Voriconazole Genoptim
Possible side effects
How to store Voriconazole Genoptim
Contents of the pack and other information

What Voriconazole Genoptim is and what it is used for
Voriconazole Genoptim contains the active substance voriconazole. Voriconazole Genoptim is an antifungal medicine. It works by killing the fungi causing infections or by inhibiting their growth.
The medicine is used to treat patients (adults and children aged over 2 years) with:
invasive aspergillosis (a type of fungal infection caused by Aspergillus species),
candidaemia (another type of fungal infection caused by Candida species) in patients without concomitant neutropenia (patients who do not have reduced numbers of white blood cells),
serious, invasive fungal infections caused by Candida species resistant to fluconazole (another antifungal medicine),
serious fungal infections caused by Scedosporium and Fusarium species (two different types of fungi).
Voriconazole Genoptim is intended for patients with progressive, potentially life-threatening fungal infections.
The medicine is also indicated for the prevention of fungal infections in high-risk patients following allogeneic hematopoietic stem cell transplantation.
This medicine should only be used under the supervision of a doctor.

Before you take Voriconazole Genoptim

Do not take Voriconazole Genoptim:

• if you are allergic to voriconazole, hydroxypropylbetadex, or any of the other ingredients of this medicine (listed in section 6).

It is very important to inform your doctor or pharmacist about all medicines you are currently taking or have recently taken, including those obtained without a prescription or herbal products.
Do not take Voriconazole Genoptim together with:
terfenadine (used to treat allergies),
astemizole (used to treat allergies),
cisapride (used for gastrointestinal disorders),
pimozide (used in psychiatry),
quinidine (used for heart rhythm disorders),
ivabradine (used to treat symptoms of chronic heart failure),
rifampicin (used to treat tuberculosis),
efavirenz (used to treat HIV infections) at doses of 400 mg or higher once daily,
carbamazepine (used to treat epilepsy),
phenobarbital (used for insomnia and epilepsy),
ergot alkaloids (e.g. ergotamine, dihydroergotamine used for migraine),
sirolimus (used in transplantation),
ritonavir (used to treat HIV infections) at doses of 400 mg or higher twice daily,
St. John’s wort (herbal remedy),
naloxegol (used to treat constipation caused particularly by opioid pain medicines (e.g. morphine, oxycodone, fentanyl, tramadol, codeine)),
tolvaptan (used to treat hyponatremia (low sodium levels in blood) or to slow the worsening of kidney function in patients with autosomal dominant polycystic kidney disease),
lurasidone (used to treat depression),
finerenone (used to treat chronic kidney disease),
venetoclax (used to treat patients with chronic lymphocytic leukemia - CLL).

Warnings and precautions
Before starting treatment with Voriconazole Genoptim, discuss with your doctor or nurse if you:
have had hypersensitivity to other azoles;
have liver disease, even if it occurred in the past. In case of liver disease, your doctor may prescribe a lower dose of Voriconazole Genoptim. Your doctor should also monitor your liver function during treatment with Voriconazole Genoptim by ordering appropriate blood tests;
have been diagnosed with cardiomyopathy, heart rhythm disorders, slow heart rate, or have changes in the electrocardiogram (ECG) known as QTc prolongation.

Avoid any exposure to sunlight during treatment. It is important to wear protective clothing and use sunscreen products with a high sun protection factor (SPF) to protect against ultraviolet (UV) radiation, as photosensitivity reactions may occur. This risk may be further increased by other medicines that make the skin more sensitive to sunlight, such as methotrexate. These precautions also apply to children.
During treatment with Voriconazole Genoptim:

• immediately inform your doctor if you experience severe sunburn, skin rash, blistering, or bone pain.

If the above skin disorders occur, your doctor may refer you to a dermatologist, who after consultation may decide on the need for regular follow-up visits. There is a small risk that long-term use of Voriconazole Genoptim may lead to skin cancer.
If you experience symptoms of “adrenal insufficiency”, in which the adrenal glands do not produce sufficient amounts of certain steroid hormones, such as cortisol, including: chronic or prolonged fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain, tell your doctor.
If you experience symptoms of “Cushing’s syndrome”, in which the body produces too much cortisol hormone, leading to symptoms such as: weight gain, fatty hump between the shoulders, rounded face, darkening of the skin on the abdomen, thighs, breasts, and arms, thinning of the skin, easy bruising, high blood sugar levels, excessive hair growth, excessive sweating, tell your doctor.
Your doctor should regularly monitor your liver and kidney function through blood tests.

Children and adolescents
Voriconazole Genoptim must not be given to children under 2 years of age.

Voriconazole Genoptim and other medicines
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, including those available without a prescription.
Some medicines taken together with Voriconazole Genoptim may alter its effect, and Voriconazole Genoptim may also affect the action of other medicines.
Inform your doctor if you are taking the following medicine, as concomitant use with Voriconazole Genoptim should be avoided if possible:

• Ritonavir (used to treat HIV infections) at a dose of 100 mg twice daily
• Glasdegib (used to treat cancer) – if both medicines must be used, your doctor will frequently monitor your heart rhythm.

Inform your doctor if you are taking any of the following medicines, as concomitant use with Voriconazole Genoptim should be avoided if possible (if necessary, the dose of voriconazole may need to be adjusted):

• Rifabutin (used to treat tuberculosis). If you are being treated with rifabutin, blood parameters and adverse effects of rifabutin should be monitored.
• Phenytoin (used to treat epilepsy). If you are being treated with phenytoin during Voriconazole Genoptim treatment, its blood concentration should be monitored and dose adjustment considered.

Inform your doctor if you are taking any of the following medicines, as dose adjustment or monitoring of these medicines and/or Voriconazole Genoptim may be necessary to ensure they remain effective:

• warfarin and other anticoagulants (e.g. phenprocoumon, acenocoumarol) (used to reduce blood clotting),
• cyclosporine (used after organ transplantation),
• tacrolimus (used after organ transplantation),
• sulfonylureas (e.g. tolbutamide, glipizide, glyburide) (used in diabetes),
• statins (e.g. atorvastatin, simvastatin) (used to reduce cholesterol levels),
• benzodiazepines (e.g. midazolam, triazolam) (used for severe insomnia and stress),
• omeprazole (used to treat ulcers),
• oral contraceptives (if Voriconazole Genoptim is taken together with oral contraceptives, adverse effects such as nausea and menstrual irregularities may occur),
• vinca alkaloids (Vinca) (e.g. vincristine, vinblastine) (used in cancer treatment),
• tyrosine kinase inhibitors (e.g. axitinib, bosutinib, cabozantinib, ceritinib, cobimetinib, dabrafenib, dasatinib, nilotinib, sunitinib, ibrutinib, ribociclib) (used in cancer treatment),
• tretinoin (used to treat leukemia),
• indinavir and other HIV protease inhibitors (used to treat HIV infection),
• non-nucleoside reverse transcriptase inhibitors (e.g. efavirenz, delavirdine, nevirapine) (used to treat HIV infection) (some doses of efavirenz must not be used together with Voriconazole Genoptim),
• methadone (used to treat heroin addiction),
• alfentanil, fentanyl, and other short-acting opioids such as sufentanil (pain medicines used during surgical procedures),
• oxycodone and other long-acting opioids such as hydrocodone (used for moderate or severe pain),
• non-steroidal anti-inflammatory drugs (e.g. ibuprofen, diclofenac) (used to treat pain and inflammatory conditions),
• fluconazole (used for fungal infections),
• everolimus (used to treat advanced kidney cancer and in transplant patients),
• letermovir (used to prevent cytomegalovirus (CMV) disease after allogeneic hematopoietic stem cell transplantation),
• ivacaftor (used to treat cystic fibrosis),
• flucloxacillin (an antibiotic used to treat bacterial infections).

Pregnancy and breastfeeding
Do not take Voriconazole Genoptim during pregnancy unless your doctor decides otherwise. Women of childbearing potential must use effective contraception during treatment with Voriconazole Genoptim. If you become pregnant while taking Voriconazole Genoptim, contact your doctor immediately.
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, you should consult your doctor or pharmacist before using this medicine.

Driving and using machines
Voriconazole Genoptim may cause visual disturbances and abnormal reaction to light. In such cases, avoid driving and operating machinery. Contact your doctor if you experience such disturbances.

Voriconazole Genoptim contains sodium
The medicine contains 88.74 mg of sodium (the main component of table salt) in each vial. This corresponds to 4.44% of the maximum recommended daily dietary intake of sodium for adults.

Voriconazole Genoptim contains hydroxypropylbetadex
If you have kidney disease, you should talk to your doctor before starting this medicine.

How to take Voriconazole Genoptim
Always take this medicine exactly as your doctor has told you. If you are unsure, ask your doctor.
Your doctor will decide the dose based on your body weight and type of infection.
Your doctor may change the recommended dose depending on your clinical condition.
The usual recommended dosing for adults (including elderly patients) is shown in the table below:

Intravenous
Loading dose 6 mg/kg body weight every 12 hours for the first 24 hours
Maintenance dose 4 mg/kg body weight twice daily (after the first 24 hours)

Depending on the response to treatment, your doctor may reduce the dose to 3 mg/kg body weight twice daily.
If mild or moderate liver cirrhosis is diagnosed, your doctor may decide to reduce the dose.

Use in children and adolescents
The usual recommended dosing for children and adolescents is shown in the table below:

Intravenous
Children aged 2 to 12 years and adolescents aged 12 to 14 years with body weight below 50 kg
Adolescents aged 12 to 14 years with body weight above 50 kg and adolescents aged over 14 years

Loading dose 9 mg/kg body weight every 12 hours for the first 24 hours
6 mg/kg body weight every 12 hours for the first 24 hours

Maintenance dose 8 mg/kg body weight twice daily
4 mg/kg body weight twice daily

Depending on the response to treatment, your doctor may increase or decrease the daily dose.
Voriconazole Genoptim, powder for solution for infusion, will be prepared by a nurse or pharmacist (see information at the end of the leaflet).
The medicine will be administered as an intravenous infusion at a maximum rate of 3 mg/kg body weight per hour over 1 to 3 hours.
If you are receiving Voriconazole Genoptim for the prevention of fungal infections, your treating doctor may discontinue the medicine if treatment-related adverse effects occur.

If you miss a dose of Voriconazole Genoptim
As the medicine will be administered under strict medical supervision, missing a dose is unlikely. However, if you suspect a dose has been missed, always inform your doctor or nurse.

Stopping Voriconazole Genoptim
Your doctor will decide how long Voriconazole Genoptim will be administered; however, treatment with Voriconazole Genoptim, powder for solution for infusion, should not exceed 6 months.
Patients with impaired immunity or severe infections may require long-term treatment to prevent relapse. Once clinical improvement occurs, the route of administration of Voriconazole Genoptim may be changed from intravenous to oral.
If your doctor decides to stop treatment with Voriconazole Genoptim, you should not be concerned about the consequences of stopping.
If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
If side effects occur, they are mostly mild and temporary.
However, some of them may be serious and may require medical intervention.

Serious side effects – stop taking Voriconazole Genoptim immediately and contact your doctor:

Other adverse reactions
Very common: may occur in more than 1 in 10 people:

• Visual disturbances (vision changes, including blurred vision, changes in colour vision, abnormal light tolerance, loss of colour vision, eye disorders, seeing halos, night blindness, sensation of image vibration, seeing sparks, visual aura, reduced visual acuity, bright vision, loss of part of the normal visual field, floaters in front of the eyes)
  Fever
  Rash
  Nausea, vomiting, diarrhoea
• Headache
• Peripheral oedema
  Abdominal pain
  Difficulty breathing
  Increased liver enzyme activity

Common: may occur in fewer than 1 in 10 people:
Sinusitis, gingivitis, chills, fatigue
Low number of certain types of blood cells, including severe cases of red blood cells (sometimes immune-mediated) and (or) white blood cells (sometimes associated with fever), low number of blood cells called platelets, which help in blood clotting
Low blood sugar levels, low blood potassium levels, low blood sodium levels
Anxiety, depression, confusion, agitation, insomnia, hallucinations
Seizures, tremor or uncontrolled muscle movements, tingling or unusual skin sensations, increased muscle tone, somnolence, dizziness
Retinal haemorrhage
Heart rhythm disorders, including very fast heartbeat, very slow heartbeat, fainting
Low blood pressure, phlebitis (which may be associated with blood clot formation)
Acute breathing difficulties, chest pain, facial swelling (oral cavity, lips, and around eyes), fluid accumulation in the lungs
Constipation, dyspepsia, cheilitis
Jaundice, hepatitis and liver damage
Rashes that may lead to severe blistering and skin peeling characterised by flat, red areas on the skin covered with small merging papules, skin redness
Itching
Alopecia
Back pain
Kidney failure, blood in urine, changes in kidney function tests
Sunburn or severe skin reaction after exposure to light or sunlight
Skin cancer

Uncommon: may occur in fewer than 1 in 100 people:
Influenza-like symptoms, irritation and inflammation of the gastrointestinal tract, gastrointestinal inflammation causing antibiotic-associated diarrhoea, lymphangitis

• Inflammation of the thin tissue lining the inner wall of the abdominal cavity and covering abdominal organs (peritonitis)
  Lymph node enlargement (sometimes painful), bone marrow failure, increased number of eosinophils
  Adrenal gland dysfunction, hypothyroidism
  Brain dysfunction, Parkinson-like symptoms, nerve damage causing numbness, pain, tingling or burning sensations in hands or feet
  Balance or coordination disorders
  Brain oedema
  Double vision, severe eye disorders, including: eye pain and inflammation of eyes and eyelids, abnormal eye movements, optic nerve damage leading to vision disturbances, optic disc oedema
  Reduced sensitivity to touch
  Taste disturbances
  Hearing loss, tinnitus, vertigo
  Inflammation of certain internal organs – pancreas and duodenum, swelling and inflammation of the tongue
  Liver enlargement, liver failure, gallbladder disorders, gallstones
  Arthritis, subcutaneous phlebitis (which may be associated with blood clot formation)
  Kidney inflammation, proteinuria, kidney damage
• Very fast heartbeat or skipped heartbeats, sometimes with abnormal electrical impulses
• Abnormal electrocardiogram (ECG) findings
• Increased blood cholesterol levels, increased blood urea levels
• Skin allergic reactions (sometimes severe), including life-threatening skin disease characterised by development of painful blisters with accompanying skin and mucous membrane pain, particularly in the oral cavity, skin inflammation, urticaria, redness and skin irritation, red or purpuric skin discolourations which may be caused by low platelet count, rash
• Infusion site reaction
• Allergic reaction or excessive immune response
• Inflammation of the tissue surrounding the bone (periostitis)

Rare: may occur in fewer than 1 in 1,000 people:
Hyperthyroidism
Worsening of brain function, which is a severe complication of liver disease
Loss of most optic nerve fibres, corneal opacity, involuntary eye movements
Blistering skin rash due to photosensitivity
Disorders in which the immune system attacks part of the peripheral nervous system
Heart rhythm or conduction disorders (sometimes life-threatening)

• Life-threatening allergic reaction
• Blood coagulation disorders
• Severe skin allergic reactions, including sudden swelling (acute oedema) of the dermis, subcutaneous tissue, mucous membranes and submucosal tissues, itchy or painful thickened red skin patches with silvery scales, skin and mucous membrane irritation, life-threatening skin disease characterised by detachment of large sheets of the epidermis (outer skin layer) from deeper skin layers
• Small, dry, scaling skin lesions, sometimes thickened with sharp projections or "horns"

Frequency not known:
Freckles and pigmented spots
Other significant adverse reactions whose frequency is unknown, but which should be reported to a doctor immediately:
Red, peeling skin patches or ring-shaped skin lesions, which may be symptoms of an autoimmune disease called cutaneous lupus erythematosus.

During intravenous infusion of Voriconazole Genoptim, infusion-related adverse reactions (flushing, fever, sweating, increased heart rate, and sensation of breathlessness) have occurred uncommonly. If these symptoms occur, the doctor may decide to discontinue the infusion.

Due to the known effects of Voriconazole Genoptim on the liver and kidneys, the function of these organs should be monitored with appropriate blood tests. Patients should also inform their doctor if they experience abdominal pain or changes in stool consistency.
Cases of skin cancer have been reported in patients treated with Voriconazole Genoptim for prolonged periods.
Sunburn or severe skin reactions after exposure to light or sunlight occurred more frequently in children. If skin disorders occur, the doctor may refer the patient to a dermatologist, who may decide after consultation that regular dermatological check-ups are necessary. Increased liver enzyme activity has also been observed more frequently in children.

If any of these adverse reactions persist or become troublesome, the patient should inform their doctor.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, the patient should inform their doctor, pharmacist, or nurse.
Adverse reactions 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 reactions can also be reported to the Marketing Authorisation Holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

How to store Voriconazole Genoptim
Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the label. The expiry date refers to the last day of the stated month.
This medicine does not require special storage conditions prior to opening.
Chemical and physical stability has been demonstrated for 72 hours at 25°C and at 2°C–8°C.
From a microbiological standpoint, once reconstituted, the product should be used immediately. If not used immediately, the storage time of the concentrate should not exceed 24 hours at 2°C–8°C (in a refrigerator), provided reconstitution was performed under controlled and validated aseptic conditions.
Reconstituted Voriconazole Genoptim should be diluted in a compatible infusion fluid immediately before infusion. (See information provided at the end of the leaflet.)
Medicines must not be disposed of via the sewage system or household waste. Ask a pharmacist how to dispose of medicines no longer required. This will help protect the environment.

Contents of the pack and other information

What Voriconazole Genoptim contains
The active substance is voriconazole.
Each vial contains 200 mg of voriconazole. After reconstitution, each ml of solution contains 10 mg of voriconazole.
Other components of the medicine are hydroxypropylbetadex, sodium chloride, hydrochloric acid concentrated (for pH adjustment).

What Voriconazole Genoptim looks like and contents of the pack
Each pack contains one vial. Voriconazole Genoptim is a white or almost white lyophilised powder for solution for infusion in a 25 ml colourless glass type I vial with a grey chlorobutyl rubber stopper, aluminium seal, and plastic red flip-off cap, packed in a cardboard box.

Marketing Authorisation Holder
Synoptis Pharma Sp. z o.o.
ul. Krakowiaków 65
02-255 Warsaw
Tel: 22 32 16 240

Manufacturer
Pharmathen S.A.
6, Dervenakion str.
153 51, Pallini, Attiki
Greece
Anfarm Hellas S.A.
320 09, Schimatari Viotias
Greece
Pharmathen International S.A.
Sapes Industrial Park Block 5
69300 Rodopi
Greece

This medicinal product is authorised for sale in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:

Information intended exclusively for healthcare professionals:

Reconstitution (preparation of concentrate) and dilution instructions

• Voriconazole Genoptim, powder for solution for infusion, must be dissolved in 19 mL of water for injections or 19 mL of 9 mg/mL (0.9%) sodium chloride for injections to obtain a 20 mL clear concentrate containing 10 mg/mL of voriconazole.
• The Voriconazole Genoptim vial should be discarded if, during the introduction of the solvent, the solvent is not automatically drawn into the vial by the vacuum present inside.
• To ensure accurate measurement of the volume (19 mL) of water for injections or 9 mg/mL (0.9%) sodium chloride for injections, it is recommended to use standard 20 mL (non-automated) syringes.
• To obtain an infusion solution containing 0.5 mg/mL to 5 mg/mL of voriconazole, the required volume of prepared concentrate should be added to the recommended compatible infusion solution (see below).
• This solution is for single use only. Any unused solution must be discarded. Do not use solutions that are not clear or that contain any cloudiness or particulate matter.
• The solution is not intended for rapid intravenous injection (bolus).
• Information on storage conditions is provided in section 5 "How to store Voriconazole Genoptim".

Voriconazole Genoptim is a non-preserved, sterile lyophilisate intended for single use. Therefore, from a microbiological point of view, the reconstituted concentrate should be used immediately. If the concentrate is not used immediately, the user is responsible for the storage time and conditions prior to use. The storage time of the concentrate should not exceed 24 hours at 2°C–8°C, provided that reconstitution was performed under controlled and validated sterile conditions.

Compatible solutions for preparing the infusion solution:
The concentrate may be diluted in:

• 9 mg/mL (0.9%) sodium chloride solution for injections
• Sodium lactate infusion solution
• 5% glucose solution and Ringer's lactate solution for intravenous infusion
• 5% glucose and 0.45% sodium chloride solution for intravenous infusion
• 5% glucose solution for intravenous infusion
• 5% glucose with 20 mEq potassium chloride solution for intravenous infusion
• 0.45% sodium chloride solution for intravenous infusion
• 5% glucose and 0.9% sodium chloride solution for intravenous infusion

Compatibility of Voriconazole Genoptim with solutions other than those listed above (or mentioned under "Incompatibilities" below) has not been established.

Incompatibilities:
Voriconazole Genoptim must not be co-administered with other medicinal products in the same infusion line or intravenous access, including parenteral nutrition (e.g., Aminofusin 10% Plus).
Concomitant administration of blood products with Voriconazole Genoptim is not permitted.
Administration of intravenous infusions for parenteral nutrition may occur simultaneously with Voriconazole Genoptim, but not through the same intravenous access or cannula.
4.2% sodium bicarbonate solution for intravenous infusion must not be used to dilute Voriconazole Genoptim.

Required volumes of Voriconazole Genoptim concentrate 10 mg/mL

| Body weight (kg) | Volume of Voriconazole Genoptim concentrate (10 mg/mL) required for: |
|----------------------|------------------------------------------------------------------------|
| | 3 mg/kg dose | 4 mg/kg dose | 6 mg/kg dose | 8 mg/kg dose | 9 mg/kg dose |
| | (mL) (number of vials) | (mL) (number of vials) | (mL) (number of vials) | (mL) (number of vials) | (mL) (number of vials) |
| 10 | – 4.0 mL (1) | – | – 8.0 mL (1) | – | 9.0 mL (1) |
| 15 | – 6.0 mL (1) | – | – 12.0 mL (1) | – | 13.5 mL (1) |
| 20 | – 8.0 mL (1) | – | – 16.0 mL (1) | – | 18.0 mL (1) |
| 25 | – 10.0 mL (1) | – | – 20.0 mL (1) | – | 22.5 mL (2) |
| 30 | 9.0 mL (1) | 12.0 mL (1) | 18.0 mL (1) | 24.0 mL (2) | 27.0 mL (2) |
| 35 | 10.5 mL (1) | 14.0 mL (1) | 21.0 mL (2) | 28.0 mL (2) | 31.5 mL (2) |
| 40 | 12.0 mL (1) | 16.0 mL (1) | 24.0 mL (2) | 32.0 mL (2) | 36.0 mL (2) |
| 45 | 13.5 mL (1) | 18.0 mL (1) | 27.0 mL (2) | 36.0 mL (2) | 40.5 mL (3) |
| 50 | 15.0 mL (1) | 20.0 mL (1) | 30.0 mL (2) | 40.0 mL (2) | 45.0 mL (3) |
| 55 | 16.5 mL (1) | 22.0 mL (2) | 33.0 mL (2) | 44.0 mL (3) | 49.5 mL (3) |
| 60 | 18.0 mL (1) | 24.0 mL (2) | 36.0 mL (2) | 48.0 mL (3) | 54.0 mL (3) |
| 65 | 19.5 mL (1) | 26.0 mL (2) | 39.0 mL (2) | 52.0 mL (3) | 58.5 mL (3) |
| 70 | 21.0 mL (2) | 28.0 mL (2) | 42.0 mL (3) | – | – |
| 75 | 22.5 mL (2) | 30.0 mL (2) | 45.0 mL (3) | – | – |
| 80 | 24.0 mL (2) | 32.0 mL (2) | 48.0 mL (3) | – | – |
| 85 | 25.5 mL (2) | 34.0 mL (2) | 51.0 mL (3) | – | – |
| 90 | 27.0 mL (2) | 36.0 mL (2) | 54.0 mL (3) | – | – |
| 95 | 28.5 mL (2) | 38.0 mL (2) | 57.0 mL (3) | – | – |
| 100 | 30.0 mL (2) | 40.0 mL (2) | 60.0 mL (3) | – | – |