Paricalcitol Mylan

Package leaflet: Information for the patient

Paracalcitol Mylan 5 micrograms/ml injection solution, 2 micrograms/ml injection solution

paracalcitol
Generic medicine
Please read all of this leaflet carefully before you start taking 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, pharmacist, or nurse.
• If you get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What Paracalcitol Mylan is and what it is used for
2. What you need to know before Paracalcitol Mylan is administered to you
3. How Paracalcitol Mylan will be administered to you
4. Possible side effects
5. How to store Paracalcitol Mylan
6. Contents of the pack and other information

1. What Paracalcitolo Mylan is and what it is used for

Paracalcitolo Mylan contains the active substance paracalcitol, a synthetic form of active vitamin D.
Vitamin D is necessary for the normal function of many tissues in the body, including the parathyroid
glands and bones. In people with normal kidney function, this active form of vitamin D is naturally
produced by the kidneys, but the production of active vitamin D is considerably reduced in the case of
kidney failure. Paracalcitolo Mylan therefore provides a source of active vitamin D when the body does
not produce enough, and helps prevent the consequences of low levels of active vitamin D in patients
with chronic kidney disease, i.e. high levels of parathyroid hormone which can cause bone problems.
Paracalcitolo Mylan is indicated in adult patients with stage 5 kidney disease.

2. What you should know before being administered Paracalcitolo Mylan

Do not be administered Paracalcitolo Mylan if:

• you are allergic to paracalcitol or to any of the other ingredients of this medicine (listed in section 6).
• you have very high levels of calcium or vitamin D in your blood. Your doctor will be able to inform you whether these conditions apply to you.

Warnings and precautions
Talk to your doctor or nurse before you are administered Paracalcitolo Mylan

• Before starting treatment, it is important that you limit the amount of phosphorus you consume in your diet. Examples of foods high in phosphorus include: tea, soda, beer, cheese, milk, cream, fish, chicken or beef liver, beans, peas, cereals, nuts, and wheat.
• Phosphate-binding medications (chelators), which prevent the absorption of phosphorus from food, may be necessary to control phosphorus levels.
• If you are taking calcium-based phosphate chelators, your doctor may need to adjust their dosage.
• Your doctor will prescribe certain blood tests to monitor your treatment.

Other medicines and Paracalcitolo Mylan
Inform your doctor, nurse, or pharmacist if you are taking or have recently taken any other
medicines, including those without a prescription.
Some medicines may affect the action of Paracalcitolo Mylan or increase the likelihood of
side effects. It is particularly important to inform your doctor if you are taking any of the
following medicines:

• medicines for the treatment of fungal infections such as candidiasis or thrush (e.g., ketoconazole)
• medicines to treat heart problems or high blood pressure (e.g., digoxin and diuretics)
• medicines containing a source of phosphate (e.g., medicines to reduce calcium levels in the blood)
• medicines containing calcium or vitamin D, including supplements and multivitamins that can be purchased without a prescription
• medicines containing magnesium or aluminium, for example, certain digestive medicines (antacids) and phosphate chelators

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding,
please consult your doctor, nurse, or pharmacist before taking this medicine.
It is not known whether this medicine is safe for pregnant women; therefore, its use is not
recommended during pregnancy or if pregnancy may occur.
It is not known whether paracalcitol passes into breast milk. Inform your doctor before breastfeeding
while taking Paracalcitolo Mylan.

Driving and using machines
Paracalcitolo Mylan may cause dizziness, which could impair your ability to drive safely or operate heavy machinery. Do not drive or operate machinery if you feel dizzy.

Paracalcitolo Mylan contains ethanol (alcohol)
This medicine contains 157.80 mg of alcohol (ethanol) per ml. The amount in each 1 ml vial of this
medicine is equivalent to less than 4 ml of beer or 1.6 ml of wine, and in each 2 ml vial of this
medicine is equivalent to less than 8 ml of beer or 3 ml of wine.
The amount of alcohol in this medicine does not appear to have an effect on adults and adolescents, and its effects in children are not evident. However, some effects may occur in young children, for example, feeling sleepy.
The alcohol in this medicine may alter the effects of other medicines. Talk to your doctor or pharmacist
if you are taking other medicines.
If you are pregnant or breastfeeding, talk to your doctor or pharmacist before taking this
medicine.
If you have alcohol dependence, talk to your doctor before taking this medicine.

3. How to take Paracalcitolo Mylan

Your doctor will determine the appropriate starting dose for you based on laboratory test results.
Once treatment with Paracalcitolo Mylan has begun, the dose will likely be adjusted according to the results of routine laboratory tests. Based on these test results, your doctor will help you establish the correct dose of Paracalcitolo Mylan for you.
Paracalcitolo Mylan will be administered by a doctor or nurse during haemodialysis. It will be given through the tube (bloodline) used to connect you to the machine. No injection is required, as Paracalcitolo Mylan can be directly introduced into the tubing used for your treatment. Paracalcitolo Mylan will be administered on alternate days and no more than three times per week.

If you take more Paracalcitolo Mylan than you should
An overdose of Paracalcitolo Mylan may lead to excessively high levels of calcium in the blood, which can be harmful. Symptoms that may occur soon after taking an excessive dose of Paracalcitolo Mylan include:

• feeling weak and/or numb
• headache
• nausea (feeling unwell) or vomiting (sickness)
• dry mouth, constipation
• muscle and bone pain
• metallic taste in the mouth.

If you develop high levels of calcium in the blood after taking Paracalcitolo Mylan, your doctor will ensure you receive appropriate treatment to restore normal blood calcium levels. Once blood calcium levels return to normal, you will likely be given a lower dose of Paracalcitolo Mylan. Your doctor will continue to monitor your blood levels. If you notice any of the above symptoms, consult a doctor immediately.

Symptoms that may develop over a longer period of excessive Paracalcitolo Mylan intake include:

• loss of appetite
• drowsiness
• weight loss
• eye pain
• runny nose
• skin itching
• feeling warm and feverish
• loss of libido
• severe abdominal pain (due to inflamed pancreas)
• kidney stones

Blood pressure may change and irregular heartbeat (palpitations) may occur. Blood and urine tests may show elevated levels of cholesterol, urea, nitrogen, and increased liver enzymes. Paracalcitolo Mylan may rarely cause mental changes including confusion, drowsiness, insomnia, and nervousness. If you receive too high a dose of Paracalcitolo Mylan or notice any of the symptoms listed above, consult a doctor immediately.

If you have any doubts about how to use this medicine, contact your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Allergic reactions of various types have been reported with Paracalcitol Mylan.

Important: Immediately inform your doctor or nurse if you notice any of the following side effects:

Uncommon (may affect up to 1 in 100 people):

• shortness of breath
• difficulty breathing or swallowing
• dyspnea
• skin rash, skin itching including urticaria
• swelling of the face, lips, mouth, tongue or throat

Inform your doctor or pharmacist if you notice any of the following side effects:

Common (may affect up to 1 in 10 people):

• low levels of parathyroid hormone
• high levels of calcium in the blood (nausea or vomiting, constipation or confusion); phosphorus in the blood (likely without symptoms, but with increased risk of fractures)
• headache
• altered taste
• skin itching

Uncommon (may affect up to 1 in 100 people):

• blood infections, pneumonia (lung infection), sore throat, vaginal infections, influenza
• breast tumour
• reduced red blood cell count (anaemia - fatigue, shortness of breath, pallor); reduced white blood cell count (increased susceptibility to infections); enlarged glands in the neck, armpit and/or groin
• high levels of parathyroid hormone
• high levels of potassium in the blood
• low levels of calcium in the blood, loss of appetite
• confusion, which may sometimes be severe (delirium), personality disorders (feeling unlike oneself), agitation (feeling nervous, anxious), sleep disorders, restlessness
• coma (deep unconscious state during which the person is unable to respond to surroundings), heart attack, fainting, muscle spasms in arms and legs, even during sleep, reduced tactile sensations, tingling or numbness, dizziness
• increased eye pressure, pink eye (itchy/dry eyelids)
• earache
• heart attack, irregular/rapid heartbeat
• low blood pressure (hypotension), high blood pressure (hypertension)
• fluid in the lungs, asthma, shortness of breath, difficulty breathing, nosebleeds, cough
• rectal bleeding, inflammation of the colon, diarrhoea, stomach ache, difficulty swallowing, constipation, nausea, vomiting, dry mouth
• skin rash with itchy blisters, hair loss, excessive hair growth, unpredictable and excessive sweating
• joint pain, joint stiffness, back pain, muscle cramps, muscle pain
• breast pain, erectile dysfunction
• abnormal gait, generalised or localised swelling of ankles, feet and legs, injection site pain, fever, chest pain, unusual tiredness or weakness, malaise or general discomfort, thirst
• prolonged bleeding time (blood does not clot quickly), increased liver enzyme, changes in laboratory test results, weight loss

Not known (frequency cannot be estimated from the available data):

• swelling of the face, lips, mouth, tongue or throat, possibly causing difficulty in swallowing or breathing; skin itching (urticaria), gastrointestinal bleeding

If you experience these symptoms, consult a doctor immediately.
You may not be able to tell whether you are experiencing any of the side effects listed above unless your doctor informs you.
If any of the side effects worsen, inform your doctor or nurse immediately. If you notice any side effect not listed in this leaflet, inform your doctor, nurse or pharmacist immediately.

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 https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Paracalcitolo Mylan

Keep this medicine out of the sight and reach of children.
Keep the vials in the outer packaging to protect the medicine from light.
For single use only.
Once opened, Paracalcitolo Mylan must be used immediately.
Do not use this medicine after the expiry date stated on the carton after “Exp.”. The expiry date refers to the last day of that month.
Do not use this medicine if you notice the presence of particles or discoloration.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Paracalcitolo Mylan contains
The active substance is paricalcitol. Each millilitre contains 2 micrograms or 5 micrograms of
paricalcitol.
The other components are: ethanol (alcohol), macrogol 15-hydroxystearate and water for injectable
preparations.

Description of the appearance of Paracalcitolo Mylan and contents of the pack
Paracalcitolo Mylan injectable solution is an aqueous, clear, colourless solution free from visible particles.

Paracalcitolo Mylan 2 micrograms/ml injectable solution
Supplied in packs of 5 type I glass vials of 1 ml (2 micrograms/1 ml).
Supplied in packs of 5 type I glass vials of 2 ml (4 micrograms/2 ml).

Paracalcitolo Mylan 5 micrograms/ml injectable solution
Supplied in packs of 5 type I glass vials of 1 ml (5 micrograms/1 ml).
Supplied in packs of 5 type I glass vials of 2 ml (10 micrograms/2 ml).

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Mylan S.p.A.
Via Vittor Pisani, 20
20124 Milano
Italy

Manufacturer
Pharmathen S.A.
6, Dervenakion str.
15351 Pallini, Attiki
Greece
VIATRIS SANTE
1 Rue de Turin
69007 Lyon
France

The following information is intended exclusively for physicians or healthcare professionals:

Paracalcitolo Mylan 2 and 5 micrograms/ml injectable solution
Preparation of the injectable solution
Paracalcitolo Mylan 2 micrograms/ml injectable solution and 5 micrograms/ml injectable solution is for single use only. As with all injectable medicines, the diluted solution should be inspected visually prior to administration for the presence of particles or discoloration.

Compatibility
This medicinal product must not be mixed with other medicinal products.

Storage and shelf life
Parenterally administered medicinal products should be inspected visually for the presence of particulate matter and discoloration before administration. The solution is clear and colourless.
Keep the vials in the outer packaging to protect the medicinal product from light.
This medicinal product has a shelf life of 2 years.
Paracalcitolo Mylan must be used immediately after opening.

Dosage, method and timing of administration
Paracalcitolo Mylan injectable solution must be administered via a haemodialysis access route.

Adults

1. The initial dose should be calculated based on baseline parathyroid hormone (PTH) levels:
   The initial dose of paricalcitol should be determined according to the following formula:
   Initial dose (in micrograms) = baseline level of intact PTH expressed in pmol/l
   Or
   = baseline level of intact PTH expressed in pg/ml
   and should be administered intravenously as a bolus dose, on alternate days, at any time during the haemodialysis session.
   In clinical studies conducted, the highest safe dose administered was 40 micrograms.

2. Dose titration:
   The currently accepted reference range for PTH levels in dialysed patients with end-stage chronic renal failure should not exceed 1.5–3 times the upper non-uraemic normal limit of 15.9–31.8 pmol/l (150–300 pg/ml) for intact PTH. To achieve physiologically appropriate results, patients must be carefully monitored and individual dose adjustments made. If hypercalcaemia or a persistently elevated corrected Ca x P product exceeding 5.2 mmol/l (65 mg/dl) is observed, the dosage should be reduced or administration interrupted until these parameters return to normal.
   Paricalcitol should then be restarted at a lower dose.
   It may be necessary to reduce the paricalcitol dose progressively as PTH levels decrease in response to therapy.

The following table provides an example of a recommended approach for dose determination:

Recommended Dosing Guidelines
(Dose adjustments every 2–4 weeks)

Adjustment of paricalcitol dose
Baseline iPTH level
Increase by 2–4 micrograms
Remains unchanged or increased
Decreased by < 30%
Decreased by ≥ 30%, ≤ 60%
Unchanged
Decreased by > 60%
Decrease by 2–4 micrograms
iPTH level < 15.9 pmol/l (150 pg/ml)