Active ingredients: Paricalcitol
Zemplar 5 micrograms / ml Solution for injection
Zemplar package inserts are available for pack sizes:- Zemplar 1 microgram Soft capsules
- Zemplar 2 micrograms Soft capsules
- Zemplar 5 micrograms / ml Solution for injection
Why is Zemplar used? What is it for?
Zemplar is a synthetic analogue of active vitamin D indicated for the prevention and treatment of high levels of parathyroid hormone in the blood in patients with renal insufficiency undergoing hemodialysis. High levels of parathyroid hormone may be due to low levels of "active" vitamin D in patients with kidney failure.
Vitamin D in its active form ensures the normal function of many tissues in our body, including the kidneys and bones.
Contraindications When Zemplar should not be used
Do not take Zemplar
- If you are allergic (hypersensitive) to paricalcitol or any of the other ingredients of Zemplar (see section 6).
- If you have very high levels of calcium or vitamin D in your blood. Your doctor will monitor your blood levels and will be able to inform you if your case falls within the above conditions.
Precautions for use What you need to know before taking Zemplar
Take special care with Zemplar
- Before starting treatment, it is important that you limit the amount of phosphorus in your diet. Examples of foods with a high phosphorus content include: tea, soda, beer, cheese, milk, cream, fish, chicken or beef liver, beans, peas, cereals, nuts and wheat.
- Phosphate binders, which prevent the absorption of phosphate from food, may be needed to control phosphorus levels.
- If you are taking calcium-based phosphate binders, your doctor may need to adjust your dosage.
- Your doctor will prescribe some blood tests to monitor your treatment.
Interactions Which drugs or foods may change the effect of Zemplar
Tell your doctor, nurse or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
Some medicines can affect the way Zemplar works or make it more likely you will have side effects. It is especially important to tell your doctor if you are taking any of the following medicines:
- medicines to treat fungal infections such as candidiasis or thrush (ketoconazole)
- heart or blood pressure medications (for example, digoxin and diuretics or pills to remove excess water from our body)
- medicines containing magnesium (for example, some digestive medicines called antacids, such as magnesium trisilicate)
- drugs containing aluminum (for example, phosphate binders, such as aluminum hydroxide).
Ask your doctor, nurse or pharmacist for advice before taking any medicine.
Taking Zemplar with food and drink
Zemplar can be taken with or between meals.
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or planning to become pregnant, tell your doctor or nurse before taking Zemplar.
It is not known if Zemplar is safe for pregnant or breastfeeding women. Therefore, do not take it until you have talked to your doctor, who will help you make the best decision for you.
Ask your doctor, nurse or pharmacist for advice before taking any medicine.
Driving and using machines
No studies have been carried out on the effects related to the ability to drive or use machines. Zemplar may affect the ability to drive vehicles safely or operate heavy machinery. Dizziness, fatigue and / or sleepiness are possible side effects of treatment with Zemplar.
Do not drive or use machines if you show these symptoms.
Important information about some of the ingredients of Zemplar
This medicinal product contains 20% v / v ethanol (alcohol). Each dose can contain up to 1.3 g of ethanol. The presence of ethanol in this medicinal product is harmful to people with alcoholism and should be given due consideration when administering it to pregnant or lactating women, children and high-risk groups such as patients with liver disease or epilepsy.
Dosage and method of use How to use Zemplar: Dosage
Based on the results of the laboratory tests, your doctor will decide on the appropriate starting dose for you. Once therapy with Zemplar is started, it is likely that a dose adjustment will be made, depending on the results of routine laboratory tests. Based on the results of the laboratory tests, your doctor will help you determine the appropriate dose of Zemplar.
Zemplar will be given to you by a doctor or nurse during hemodialysis, through the bloodline used to connect you to the machine. You will not need an injection, as Zemplar can be inserted directly into the tube used for your treatment. Zemplar will be given to you every other day, no more than three times a week.
Overdose What to do if you have taken too much Zemplar
An overdose of Zemplar can cause an abnormal increase in calcium (in the blood and urine) and phosphate levels in the blood which may require treatment. In addition, an overdose of Zemplar can reduce parathyroid hormone levels. Symptoms that may appear soon after taking an overdose of Zemplar include:
- feeling of weakness and / or numbness
- headache
- nausea or feeling sick
- dry mouth, constipation
- muscle or bone pain
- change in taste.
Symptoms that may occur over a longer period of taking too much Zemplar include:
- loss of appetite
- drowsiness
- weight loss
- eye discomfort
- rhinorrhea
- itchy skin
- feeling of heat and fever
- loss of libido
- severe abdominal pain
- kidney stones
- Blood pressure can change and irregular heartbeat (palpitations) may appear.
Zemplar contains 30% v / v propylene glycol as an excipient. There have been isolated reports of toxic effects associated with the administration of high doses of propylene glycol. Such cases should not occur when administered to hemodialysis patients, as propylene glycol is cleared from the blood during the dialysis process.
If you have elevated blood calcium levels after taking Zemplar, your doctor will ensure that you receive the appropriate treatment to restore normal blood calcium levels. When your blood calcium levels have returned to normal you will probably receive a lower dose of Zemplar.
Your doctor will still check your blood levels and if you notice any of the above symptoms, consult a doctor immediately.
Side Effects What are the side effects of Zemplar
Like all medicines, Zemplar can cause side effects, although not everybody gets them.
Various allergic reactions have been reported with Zemplar.
Important: Tell your doctor or nurse straight away if you notice any of the following side effects:
- wheezing
- difficulty in breathing or swallowing
- dyspnea
- rash, itchy skin or hives
- swelling of the face, lips, mouth, tongue or throat.
Tell your doctor or pharmacist if you notice any of the following side effects:
Most common side effects (at least 1 in 100 patients):
- headache
- change in taste
- itchy skin
- low levels of parathyroid hormone
- high calcium levels (nausea or feeling sick, constipated or confused); blood phosphorus (probably in the absence of symptoms, but with greater susceptibility to fractures)
Less common side effects (at least 1 in 1,000 patients):
- allergic reactions (for example, wheezing, wheezing, rash, itching or swelling of the face and lips); itchy blisters
- blood infections; reduced red blood cell count (anemia - fatigue, shortness of breath, paleness); reduced white blood cell count (increased susceptibility to infections); swollen glands in the neck, armpit and / or groin; prolonged bleeding time (blood does not clot easily)
- heart attack; stroke; chest pain; irregular / rapid heartbeat; low blood pressure (hypotension); high blood pressure (hypertension);
- coma (deep state of unconsciousness during which the person is unable to respond to the environment)
- unusual fatigue, weakness; dizziness fainting
- pain at the injection site
- pneumonia (lung infection); fluid in the lungs; asthma (dyspnoea, cough, difficulty in breathing);
- sore throat; cold; fever; flu-like symptoms; pink eye (itchy / dry eyelids); increased eye pressure; earache; nosebleed
- nerve twitches; confusion, sometimes severe (delirium); agitation (anxiety); nervousness; personality disorders (not feeling like yourself);
- tingling or numbness; reduction of tactile sensations; insomnia; night sweats; muscle spasms in the arms and legs, including during sleep;
- dry mouth; thirst; nausea; difficulty swallowing; He retched; loss of appetite; weight loss; stomach ache; diarrhea and stomach pain; constipation: anal bleeding;
- difficulty with erection; breast cancer; vaginal infections
- breast pain; backache; joint / muscle pain; feeling of heaviness caused by generalized or localized swelling of the ankles, feet and legs (edema); abnormal gait;
- hair loss; excessive hair growth,
- increase in a hepatic enzyme; elevated levels of parathyroid hormone; high levels of potassium in the blood; reduced levels of calcium in the blood.
Frequency not known:
- swelling of the face, lips, mouth, tongue or throat, which may cause difficulty in swallowing or breathing; itchy skin (hives), stomach bleeding. Consult a doctor immediately.
You may not be able to tell if you have any of the above side effects unless you tell your doctor about them.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, nurse or pharmacist immediately.
Expiry and Retention
Keep this medicine out of the reach and sight of children.
This medicinal product does not require any special storage conditions.
Once opened, Zemplar should be used immediately.
Do not use Zemplar after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of the month. Do not use Zemplar if you notice any particles or cloudiness.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other information
What Zemplar contains
- The active ingredient is paricalcitol. Each ml of solution contains 5 micrograms of paricalcitol.
- The other ingredients are: ethanol (alcohol), propylene glycol and water for injections.
What Zemplar looks like and contents of the pack
Zemplar solution for injection is a clear, colorless, aqueous solution with no visible particles. It is supplied in packs of 5 glass ampoules of 1ml or 2ml.
The following information is for healthcare professionals only:
Zemplar 5 micrograms / ml solution for injection
Preparation of the solution for injection Zemplar 5 micrograms / ml solution for injection is for single use only. As with all medicinal products administered by injection, the diluted solution should be examined for the presence of particles or cloudiness prior to administration.
Compatibility
Propylene glycol interacts with heparin and neutralizes its effects. Zemplar solution for injection contains propylene glycol as an excipient and must be administered through a route of access other than that through which heparin is administered.
This medicinal product must not be mixed with other medicinal products.
Conservation and validity
Medicinal products administered parenterally must be subjected to a "visual inspection for the presence of corpuscular substances and possible clouding, before proceeding with their administration. The solution is clear and colorless.
This medicinal product does not require any special storage conditions.
This medicine is valid for 2 years.
Dose, method and time of administration
Zemplar solution for injection must be administered through a hemodialysis route.
Adults
- The starting dose should be calculated based on the baseline parathyroid hormone (PTH) levels: The starting dose of paricalcitol should be determined using the following formula:
Initial dose (in micrograms) = basal level of intact PTH expressed in pmol / l: 8; O = basal level of intact PTH expressed in pg / ml: 80
and should be administered intravenously as a bolus dose, every other day, at any time during the hemodialysis session.
In clinical trials, the maximum safe dose administered was 40 micrograms.
- Dosage Titration:
The currently accepted reference range for PTH levels in dialysis patients with end-stage chronic renal failure should not exceed 1.5-3 times the non-uremic upper limit of normal of 15.9-31. 8 pmol / l (150-300 pg / ml) for intact PTH. To obtain physiologically adequate results, patients should be carefully monitored and individual dosage determination made. hypercalcaemia or a corrected, persistently elevated Ca x P product greater than 5.2 mmol2 / l2 (65 mg2 / dl2), the dosage should be reduced or the administration interrupted until these parameters have returned to normal. , paricalcitol will need to be re-administered at a lower dose. The dose of paricalcitol may need to be decreased as PTH levels decrease in response to therapy.
The following table offers an example of a recommended approach for determining the dosage:
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
ZEMPLAR INJECTABLE SOLUTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Zemplar 2 mcg / ml solution for injection:
Each ml of solution for injection contains 2 mcg of paricalcitol.
Each 1 ml vial contains 2 mcg of paricalcitol.
Each 1 ml vial contains 2 mcg of paricalcitol.
Zemplar 5 mcg / ml solution for injection:
Each ml of solution for injection contains 5 mcg of paricalcitol.
Each 1 ml vial contains 5 mcg of paricalcitol.
Each 2 ml vial contains 10 mcg of paricalcitol.
Each 1 ml vial contains 5 mcg of paricalcitol.
Each 2 ml vial contains 10 mcg of paricalcitol.
Excipients: Ethanol (20% v / v) and propylene glycol (30% v / v)
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Injectable solution
Clear and colorless aqueous solution, without visible particles.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Paricalcitol is indicated in adults for the prevention and treatment of secondary hyperparathyroidism in chronic renal failure patients undergoing hemodialysis.
04.2 Posology and method of administration
Dosage
Adults
1) The starting dose should be calculated based on the basal levels of parathyroid hormone (PTH):
The starting dose of paricalcitol should be determined using the following formula:
OR
and should be administered intravenously as a bolus dose, with a maximum frequency every other day, at any time during the hemodialysis session.
In clinical trials, the maximum safe dose administered was 40 micrograms.
2) Dosage titration:
The currently accepted reference range for PTH levels in dialysis patients with end-stage chronic renal failure should not exceed 1.5-3 times the non-uremic upper limit of normal of 15.9 - 31. 8 pmol / l (150 - 300 pg / ml) for intact PTH.
To obtain physiologically adequate results, patients should be carefully monitored and individual dose titration performed.
If hypercalcaemia or a corrected, persistently elevated Ca x P product greater than 5.2 mmol2 / l2 (65 mg2 / dl2) is noted, the dosage should be reduced or administration discontinued until these parameters will not be included in the standard. Thereafter, paricalcitol will need to be re-administered at a lower dose. Paricalcitol dosage may need to be decreased as PTH levels decline in response to therapy.
The following table offers an example of a recommended approach for dose titration:
Once the paricalcitol dosage has been established, serum calcium and phosphate levels should be measured at least once a month. Monitoring of intact serum PTH every three months is recommended.
During the paricalcitol dosage adjustment phase, laboratory tests may need to be performed more frequently.
Hepatic impairment
Free paricalcitol concentrations in patients with mild to moderate hepatic impairment are similar to those found in healthy subjects and no dosage adjustment is required in this patient population. There is still no experience in patients with severe hepatic impairment.
Pediatric population (0-18 years)
The safety and efficacy of Zemplar have not been established in children. No data are available in children below 5 years of age. Currently available data in pediatric patients are described in section 5.1 but no recommendation on a posology can be made. .
Elderly patients (> 65 years)
Experience with patients 65 years of age and older who received paricalcitol in phase III studies is somewhat limited. During these studies, no substantial differences in the efficacy or safety of the drug were observed between patients 65 years of age and older and younger patients.
Method of administration
Zemplar solution for injection must be administered through a hemodialysis route.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Vitamin D toxicity
Hypercalcemia.
04.4 Special warnings and appropriate precautions for use
An excessive inhibition of the secretion of parathyroid hormone can cause an increase in serum calcium levels and can lead to the onset of osteo-metabolic disease. To obtain adequate physiological reference values, patients should be carefully monitored and individual dose titration performed.
If clinically significant hypercalcaemia occurs and the patient is treated with a calcium-based phosphate ion chelator, the dose of this chelator should be reduced or its administration discontinued.
Chronic hypercalcaemia may be associated with generalized vascular calcifications and other soft tissue calcifications.
Phosphate or vitamin D-related medicinal products should not be taken concomitantly with paricalcitol as there may be an increased risk of hypercalcaemia and an increase in Ca x P product may occur (see section 4.5).
Digitalis toxicity is potentiated by hypercalcaemia of any origin; consequently, extreme caution should be exercised in patients receiving paricalcitol therapy taking concomitant digitalis (see section 4.5).
Caution should be exercised if paricalcitol and ketoconazole are administered concomitantly (see section 4.5).
This medicine contains 20% v / v ethanol (alcohol). Each dose can contain up to 1.3 g of ethanol. The presence of ethanol in this medicinal product can be harmful to subjects suffering from alcoholism and must be taken into due consideration when administering it to pregnant and lactating women, to pediatric subjects and to high-risk groups. such as patients with liver disease or epilepsy.
04.5 Interactions with other medicinal products and other forms of interaction
No interaction studies have been performed with paricalcitol in injectable form. However, a study was performed to evaluate the interaction between ketoconazole and paricalcitol using the capsule formulation.
Phosphate products or vitamin D analogous compounds should not be taken concomitantly with paricalcitol, due to an increased risk of hypercalcaemia and an increase in the CaxP product (see section 4.4).
Administration of high doses of calcium-containing medicines or thiazide diuretics could increase the risk of hypercalcaemia.
Medicinal products containing aluminum (e.g. antacids or phosphate ion chelators) should not be administered in long-term therapy in combination with medicinal products containing vitamin D, as this may result in increased blood levels of aluminum and bone toxicity from aluminum.
Medicines containing magnesium (e.g. antacids) should not be taken concomitantly with medicines containing vitamin D, as hypermagnesaemia may occur.
Ketoconazole is known to be a non-specific inhibitor of several cytochrome P450 enzymes.
Data available both in vivo and in vitro suggest that ketoconazole may interact with enzymes that are responsible for the metabolism of paricalcitol and other Vitamin D analogues.
Particular care should be taken when paricalcitol is co-administered with ketoconazole (see section 4.4). The effect of multiple doses of ketoconazole administered at a dose of 200 mg, twice daily (BID) for 5 days, on the pharmacokinetics of paricalcitol capsules was studied in healthy subjects. In the presence of ketoconazole the Cmax of paricalcitol was affected in The mean half-life of paricalcitol was 17.0 hours in the presence of ketoconazole compared to 9.8 hours when paricalcitol was administered alone. The results of this study indicate that following oral administration of paricalcitol the maximum increase in AUCo-? Of paricalcitol due to drug interaction with ketoconazole should not be greater than two fold.
Digitalis toxicity is enhanced by the presence of hypercalcemia of any origin; consequently, extreme caution should be exercised if digitalis is prescribed concomitantly with paricalcitol (see section 4.4).
04.6 Pregnancy and lactation
Pregnancy
There are insufficient data on the use of paricalcitol in pregnant women. Animal studies have shown reproductive toxicity (see section 5.3). The potential risk in humans is unknown. Zemplar should not be used during pregnancy unless clearly necessary.
Breastfeeding
Animal studies have shown that paricalcitol or its metabolites are excreted in breast milk in small quantities. A decision must be made whether to discontinue breast-feeding or to discontinue paricalcitol therapy taking into account the benefit of breast-feeding for the child and the benefit of paricalcitol therapy for the woman.
04.7 Effects on ability to drive and use machines
Paricalcitol negligibly affects the ability to drive or use machines. Dizziness may occur after administration of paricalcitol (see section 4.8).
04.8 Undesirable effects
In Phase II / III / IV clinical trials, approximately 600 patients were treated with Zemplar. Overall, 6% of patients treated with Zemplar reported adverse reactions.
The most common adverse reaction associated with Zemplar therapy was hypercalcaemia, which occurred in 4.7% of patients. Hypercalcaemia is dependent on the level of parathyroid hormone over-suppression and can be minimized by adequate dose titration.
Possible adverse reactions related to paricalcitol, both clinical and laboratory, are listed in the following table according to the MedDRA convention by system organ classification, and frequency. As regards frequency, the following categories were used: Very common (≥ 1 / 1O); common (≥ 1/100,
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicine is important, as it allows for continuous monitoring of the benefit / risk balance of the medicine. Healthcare professionals are asked to report any adverse reactions via the national reporting system. address www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
No cases of overdose have been reported.
Paricalcitol overdose can lead to hypercalcaemia, hypercalcinuria, hyperphosphataemia and excessive PHT suppression (see section 4.4).
In the event of an overdose, the signs and symptoms of hypercalcaemia (serum calcium levels) should be monitored and reported to the physician. Treatment must be initiated appropriately.
Paricalcitol is not significantly eliminated by dialysis. Treatment of patients with "clinically significant hypercalcaemia is" immediate dose reduction or immediate discontinuation of paricalcitol therapy and a low diet. of calcium, the suspension of calcium supplements, patient mobilization, control of electrolyte and fluid imbalances, an assessment of changes in the electrocardiographic trace (of fundamental importance in patients who are treated with digitalis), and "hemodialysis or dialysis peritoneal with calcium-free dialysate, as permitted.
Once serum calcium levels have returned to normal limits, paricalcitol can be re-administered at a lower dose. If a persistent and marked increase in serum calcium levels occurs, the variety of therapeutic alternatives available should be considered. These include the use of drugs such as phosphates and corticosteroids as well as measures to induce diuresis.
Zemplar solution for injection contains 30% v / v propylene glycol as an excipient. Isolated cases of central nervous system depression, haemolysis and lactic acidosis have been reported as a toxic effect associated with the administration of high doses of propylene glycol. Although such toxic effects are not expected to occur following administration of Zemplar as propylene glycol is eliminated during the dialysis process, the risk of toxic effects in the event of an overdose must still be considered.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antiparathyroid agents, ATC code: H05BX02
Mechanism of action
Paricalcitol is a synthetic analogue of calcitriol, the biologically active form of vitamin D, with modifications on the side chain (D2) and on the A (19-nor) ring. Unlike calcitriol, paricalcitol is a selective activator of the Vitamin D (VDR). Paricalcitol selectively stimulates vitamin D receptors in the parathyroid glands without causing an increase in vitamin D receptors in the intestine and is less active on bone resorption. Furthermore, paricalcitol stimulates the calcium-sensitive receptors (CaSR) present in the parathyroid glands. Consequently, paricalcitol reduces parathyroid hormone (PTH) levels by inhibiting parathyroid proliferation and decreasing PTH synthesis and secretion, with minimal impact on calcium and phosphorus levels; paricalcitol can act directly on osteoblasts to preserve bone volume and improve mineralization surfaces. Correction of altered levels of parathyroid hormone, together with normalization of calcium and phosphorus homeostasis, can prevent or cure metabolic bone disease associated with chronic renal failure.
Pediatric population
The safety and efficacy of Zemplar were evaluated in a 12-week, randomized, double-blind, placebo-controlled study of 29 hemodialysis pediatric end stage chronic renal failure patients aged 5 to 19 years. In the study, the six youngest patients treated with Zemplar ranged in age from 5 to 12 years. The starting dose of Zemplar was 0.04 mcg / kg 3 times per week, respectively, if baseline iPTH levels were below 500 pg / mL, or 0.08 mcg / kg 3 times per week if baseline levels were of iPTH were ≥ 500 pg / mL. The dose of Zemplar was adjusted in 0.04 mcg / kg increments based on serum levels of iPTH, calcium and Ca x P product. 67% of patients treated with Zemplar and 14% of patients treated completed the study. with placebo. 60% of subjects in the Zemplar group had 2 consecutive 30% decreases in iPTH levels from baseline compared to 21% of patients in the placebo group. Due to excessive increases in iPTH levels, 71% of patients in the placebo group had to drop out of the study. Neither in the Zemplar group nor in the placebo group developed hypercalcemia.There are no data available for patients less than 5 years of age.
05.2 Pharmacokinetic properties
Distribution
The pharmacokinetics of paricalcitol have been studied in patients with chronic renal failure (CRF) who required hemodialysis. Paricalcitol is administered as an intravenous bolus injection. Within two hours of administration of doses ranging from 0.04 and 0.24 mcg / kg, paricalcitol concentrations decreased rapidly; subsequently, paricalcitol concentrations decreased in a logarithmically linear fashion, with a mean half-life of approximately 15 hours. In addition, no accumulation of paricalcitol was observed in the presence of multiple dosing. The plasma protein binding of paricalcitol in vitro it was found to be extensive (> 99.9%) and non-saturable throughout the concentration range between 1 ng / mL and 100 ng / mL.
Biotransformation
In both urine and faeces, several unknown metabolites were identified and no detectable paricalcitol was found in the urine. These metabolites have not been characterized or identified. Overall, these metabolites contributed 51% of urinary radioactivity and 59% of faecal radioactivity.
Elimination
In healthy subjects, a study was conducted in which a single bolus dose of 0.16 mcg / kg of 3H-paricalcitol (n = 4) was administered intravenously, the radioactivity observed in plasma was Paricalcitol was eliminated essentially by hepatobiliary excretion, as 74% of the radioactive dose was recovered in the faeces and only 16% was recovered in the urine.
Special populations
Gender, race and age: In adult patients studied, no age- or gender-related pharmacokinetic differences were observed. No pharmacokinetic differences due to race were identified.
Hepatic impairment: Free paricalcitol concentrations in patients with mild to moderate hepatic impairment are similar to those reported in healthy subjects and no dosage adjustment is required in this patient population. There is no experience in patients with severe hepatic impairment.
05.3 Preclinical safety data
The salient data from repeated dose toxicity studies in rodents and dogs were generally ascribed to the calcemic activity of paricalcitol. Effects that were not clearly related to hypercalcaemia included a decrease in white blood cell count in dogs. , the occurrence of thymic atrophy in dogs and the presence of altered values of activated partial thromboplastin time (increased in dogs and decreased in rats). No changes in white blood cell count were observed in clinical studies.
Paricalcitol did not cause negative effects on the fertility of rats and it was shown that it does not possess any teratogenic activity in either rats or rabbits. High doses of other vitamin D preparations administered to pregnant animals induced teratogenesis.
Paricalcitol has been shown to affect fetal viability and may promote a significant increase in peri-natal and post-natal mortality in newborn rats when administered at maternally toxic doses.
During a series of genetic toxicity tests in vitro and in vivo, it has been shown that paricalcitol does not possess any potential genotoxic activity.
Studies on carcinogenicity in rodents do not indicate the presence of any particular risk when paricalcitol is used in humans.
Doses administered and / or systemic exposures to paricalcitol are slightly higher than therapeutic doses / systemic exposures.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Ethanol (20% v / v)
Propylene glycol
Water for injections
06.2 Incompatibility
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Propylene glycol interacts with heparin and neutralizes its effects. Zemplar solution for injection contains propylene glycol as an excipient and must be administered through a route of access other than that through which heparin is administered.
06.3 Period of validity
2 years.
Use immediately after opening.
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Zemplar 2 mcg / ml solution for injection:
Each type 1 glass vial contains 1 ml of solution for injection.
Each type 1 glass vial contains 1 ml of solution for injection.
Zemplar presentations are:
One pack containing 5 ampoules of 1 ml of solution for injection.
One pack containing 5 vials of 1 ml solution for injection.
Zemplar 5 mcg / ml solution for injection:
Each type 1 glass vial contains 1 ml or 2 ml of solution for injection.
Each type 1 glass vial contains 1 ml or 2 ml of solution for injection.
Zemplar presentations are:
One pack containing 5 ampoules of 1 ml of solution for injection.
A pack containing 5 ampoules of 2 ml of solution for injection.
One pack containing 5 vials of 1 ml solution for injection.
One pack containing 5 vials of 2 ml solution for injection.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
Medicinal products administered parenterally must be subjected to a "visual inspection for the presence of corpuscular substances and possible clouding, before proceeding with their administration. The solution is clear and colorless.
For single use only. Unused medicine and wastes derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
AbbVie S.r.l.
S.R. 148 Pontina km 52 snc
04011 Campoverde di Aprilia (LT)
08.0 MARKETING AUTHORIZATION NUMBER
Zemplar 2 mcg / ml solution for injection "5 ampoules of 1 ml - AIC n. 036374128
Zemplar 2 mcg / ml solution for injection "5 glass vials of 1 ml - AIC n. 036374155
Zemplar 5 mcg / ml solution for injection "5 ampoules of 1 ml - AIC n. 036374015
Zemplar 5 mcg / ml solution for injection "5 ampoules of 2 ml - AIC n. 036374027
Zemplar 5 mcg / ml solution for injection "5 glass vials of 1 ml - AIC n. 036374130
Zemplar 5 mcg / ml solution for injection "5 glass vials of 2 ml - AIC n. 036374142
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 22 January 2005
Date of most recent renewal: November 22, 2010
10.0 DATE OF REVISION OF THE TEXT
09/2016
