Kofeini citrinian Neupharm

LEAFLET INCLUDED IN THE PACKAGING: INFORMATION FOR THE USER

Warning! Keep the leaflet, the information on the immediate packaging is in a foreign language!

Caffeine Citrate Neupharm

20 mg/ml, solution for infusion and oral solution

Caffeine citrate

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the newborn.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult the doctor who is taking care of the child.
• If the newborn experiences any side effects, including any side effects not mentioned in this leaflet, you should inform the doctor who is taking care of the child. See section 4.

Table of contents of the leaflet

• 1. What is Caffeine Citrate Neupharm and what is it used for
• 2. Important information before using Caffeine Citrate Neupharm in newborns
• 3. How to use Caffeine Citrate Neupharm
• 4. Possible side effects
• 5. How to store Caffeine Citrate Neupharm
• 6. Contents of the pack and other information

1. What is Caffeine Citrate Neupharm and what is it used for

Caffeine Citrate Neupharm contains caffeine citrate as the active substance, which is a central nervous system stimulant belonging to the group of medicines called methylxanthines.
Caffeine Citrate Neupharm is used to treat breathing disorders in premature babies (primary apnea of prematurity).
These short periods of breathing arrest in premature babies result from the incomplete development of breathing centers.
It has been shown that this medicine reduces the number of episodes of breathing arrest in premature babies.

2. Important information before using Caffeine Citrate Neupharm in newborns

When not to use Caffeine Citrate Neupharm

• If the newborn is allergic to caffeine citrate or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Before starting treatment with Caffeine Citrate Neupharm in newborns, you should discuss this with the doctor who is taking care of the child.
Before starting treatment for apnea of prematurity with Caffeine Citrate Neupharm, the doctor who is taking care of the child should rule out or treat other causes of apnea.
Caffeine Citrate Neupharm should be used with caution. You should inform the doctor who is treating the baby:

• if the newborn has seizures;
• if the newborn has heart disease;
• if the newborn has liver or kidney disease;
• if the newborn frequently spits up food;
• if the amount of urine excreted by the newborn has increased;
• if the newborn's weight gain or food intake has decreased;
• if the mother of the child consumed large amounts of coffee before birth.

Caffeine Citrate Neupharm and other medicines

You should tell the doctor who is taking care of the child about all medicines that are currently being used or have recently been used for the newborn, as well as any medicines that are planned to be used.
You should tell the doctor who is taking care of the child if the newborn has previously been treated with theophylline.
The following medicines should not be used during treatment with Caffeine Citrate Neupharm without prior consultation with the doctor who is taking care of the child. The doctor may decide to change the dose or replace one of the medicines with another:

• theophylline (used to treat breathing disorders);
• doxapram (used to treat breathing disorders);
• cimetidine (used to treat stomach disease);
• ketokonazole (used to treat fungal infections);
• phenobarbital (used to treat epilepsy);
• phenytoin (used to treat epilepsy);

This medicine may increase the risk of serious intestinal disease with bloody stools (necrotizing enterocolitis) when given together with medicines used to treat stomach disease (such as antihistamine H2 receptor inhibitors and proton pump inhibitors, which reduce stomach acid production).

Pregnancy, breastfeeding, and fertility

If the mother of the newborn is breastfeeding while the baby is being treated with Caffeine Citrate Neupharm, she should not consume coffee or any products containing large amounts of caffeine, as caffeine passes into breast milk.

Caffeine Citrate Neupharm contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per dose, which means that the medicine is considered "sodium-free".

3. How to use Caffeine Citrate Neupharm

Caffeine Citrate Neupharm should only be used in the neonatal intensive care unit, where there are appropriate facilities for monitoring and supervising patients. Treatment should be started under the supervision of a doctor with experience in neonatal intensive care.

in neonatal intensive care.

Dose

The doctor who is taking care of the child will prescribe the appropriate dose of Caffeine Citrate Neupharm based on the child's weight.
The initial dose is 20 mg per kilogram of body weight (which corresponds to 1 ml per kilogram of body weight).
The maintenance dose is 5 mg per kilogram of body weight (which corresponds to 0.25 ml per kilogram of body weight) every 24 hours.

Route and method of administration

Caffeine Citrate Neupharm will be administered intravenously using a controlled intravenous infusion with a syringe pump or other device that allows measurement. This method is commonly known as a "drip".
Some doses (maintenance doses) may be given orally.
During treatment, it may be necessary to periodically check the concentration of caffeine in the child's blood to avoid toxicity.

Duration of treatment

The doctor who is taking care of the child will decide how long the treatment with Caffeine Citrate Neupharm should last.
If the child has not had any apnea attacks for 5-7 days, the doctor will stop the use of the medicine.

Use of a higher than recommended dose of Caffeine Citrate Neupharm

In the event that a higher dose of caffeine citrate is given to the child than recommended, the child may experience fever, rapid breathing, seizures, muscle tremors, vomiting, high blood sugar levels (hyperglycemia), low potassium levels in the blood (hypokalemia), high levels of certain chemicals in the blood (urea), increased white blood cell count, and seizures.
In such a situation, treatment with Caffeine Citrate Neupharm should be stopped immediately, and the doctor who is taking care of the child should treat the overdose.
If you have any further doubts about the use of this medicine, you should consult the doctor who is taking care of the child.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
However, it is difficult to distinguish them from common complications in premature babies and complications related to the disease.
During treatment with Caffeine Citrate Neupharm in newborns, the following side effects may occur:

Severe side effects

Side effectswhose frequency cannot be estimated from the available data

• serious intestinal disease with bloody stools (necrotizing enterocolitis).

The doctor who is taking care of the child may also consider the following side effects to be severe, depending on the overall clinical assessment.

Other side effects

Commonside effects (may occur in up to 1 in 10 patients):

• local allergic reactions at the infusion site;
• heart rhythm disorders, such as rapid heartbeat (tachycardia);
• increased blood sugar or serum levels (hyperglycemia).

Uncommonside effects (may occur in up to 1 in 100 patients):

• central nervous system stimulation, manifested as seizures;
• heart rhythm disorders, such as irregular heartbeat (arrhythmia).

Rareside effects (may occur in up to 1 in 1,000 patients):

• allergic reactions.

Side effectswhose frequency cannot be estimated from the available data:

• blood infection (sepsis);
• changes in blood sugar or serum levels (hypoglycemia), lack of proper growth, food intolerance;
• central nervous system stimulation, including irritability, nervousness, anxiety, brain damage;
• deafness;
• vomiting, increased volume of gastric aspirate;
• increased urine output, increased levels of certain urine components (sodium and calcium);
• changes in blood test results (decreased hemoglobin levels after long-term treatment and decreased thyroid hormone levels at the start of treatment).

Reporting side effects

If the newborn experiences any side effects, including any side effects not mentioned in this leaflet, you should inform the doctor who is taking care of the child.
Side effects can also be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products,
Jerozolimskie Avenue 181C, 02-222 Warsaw,
Phone: +48 22 49 21 301,
Fax: +48 22 49 21 309,
Website: https://smz.ezdrowie.gov.pl
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Caffeine Citrate Neupharm

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging.
The expiry date refers to the last day of the month stated.
Do not store in the refrigerator or freeze.
Before administration, all parenteral solutions should be visually inspected for the presence of particulate matter and color change. After opening the ampoule, the medicinal product should be used immediately.

6. Contents of the pack and other information

What Caffeine Citrate Neupharm contains

• The active substance of the medicine is caffeine citrate. One ml contains 20 mg of caffeine citrate (which corresponds to 10 mg/ml of caffeine).
• The other ingredients are citric acid, sodium hydroxide, and water for injections.

What Caffeine Citrate Neupharm looks like and contents of the pack

Caffeine Citrate Neupharm is a solution for infusion and oral solution.
Caffeine Citrate Neupharm is a clear, colorless solution supplied in colorless glass ampoules (type I) in a cardboard box. One cardboard box contains 10 ampoules.
For more detailed information, you should contact the marketing authorization holder or the parallel importer.

Marketing authorization holder in Italy, the country of export:

Monico spa
Via Ponte di Pietra 7
30173 Venice Mestre
Italy

Manufacturer:

Monico spa
Via Ponte di Pietra 7
30173 Venice Mestre
Italy

Parallel importer:

Neupharm Sp. z o.o. i wspólnicy Sp. k.
Chełmska Street 30/34
00-725 Warsaw

Repackaged by:

LABOR Pharmaceutical-Chemical Enterprise Sp. z o.o.
Długosza Street 49
51-162 Wrocław
Shiraz Productions Sp. z o. o.
Tymiankowa Street 24/28
95-054 Ksawerów
Marketing authorization number in Italy, the country of export: 048245029

Parallel import authorization number: 287/23

Date of leaflet approval: 15.12.2023 -------------------------------------------------------------------------------------------------------

Information intended only for healthcare professionals:

Treatment with caffeine citrate should be started under the supervision of a doctor with experience in neonatal intensive care. The medicinal product should only be used in the neonatal intensive care unit, where there are appropriate facilities for monitoring and supervising patients.

Dosage

The recommended dosing regimen in previously untreated infants is a loading dose of 20 mg of caffeine citrate per kilogram of body weight, administered during a slow intravenous infusion over 30 minutes using a syringe pump or other device that allows measurement. After a 24-hour interval, a maintenance dose of 5 mg per kilogram of body weight can be administered every 24 hours. Alternatively, maintenance doses of 5 mg per kilogram of body weight can be administered orally every 24 hours, e.g., using a nasogastric tube.
The recommended loading dose and maintenance doses of caffeine citrate are shown in the following table, which reflects the relationship between the volume of injection and the administered doses of caffeine citrate.
The dose of caffeine is half the dose of caffeine citrate (20 mg of caffeine citrate corresponds to 10 mg of caffeine).

*24 hours after the loading dose.
In premature babies who do not respond adequately to the recommended loading dose, a second loading dose of up to 10-20 mg/kg body weight can be administered after 24 hours.
If there is an inadequate response, a higher maintenance dose of 10 mg/kg body weight may be considered, taking into account the possibility of caffeine accumulation and the progressively increasing ability to metabolize caffeine in relation to the age of the newborn, counted from the date of the last menstrual period before conception. The concentration of caffeine in the blood should be monitored.
Diagnosis of apnea of prematurity may need to be reconsidered in the event of an inadequate response to a second loading dose or a maintenance dose of 10 mg/kg/day.
Dose modification and monitoring
It may be necessary to periodically monitor the concentration of caffeine in the blood during treatment in the event of an inadequate clinical response or signs of toxicity.
Additionally, the dose may need to be adjusted according to the doctor's opinion after routine monitoring of caffeine levels in the blood in situations at risk, such as:

• premature babies born significantly before term (gestational age <28 weeks and or birth weight <1000 g), especially if they are receiving parenteral nutrition;< li>
• babies with liver or kidney function disorders;
• babies with seizures;
• babies with diagnosed and clinically significant heart disease;
• babies receiving concomitant medicinal products known to affect caffeine metabolism;
• babies breastfed by mothers consuming caffeine-containing products. It is recommended to determine the initial caffeine concentration in:
• babies whose mothers may have consumed large amounts of caffeine before birth;
• babies who have previously been treated with theophylline, which is metabolized to caffeine.

The half-life of caffeine in premature babies is prolonged, and accumulation is possible, which may require monitoring in babies treated for a longer period.
Samples for control should be taken immediately before the administration of the next dose in the event of treatment failure and 2 to 4 hours after the administration of the previous dose in the event of suspected toxicity.
Although a therapeutic range of caffeine concentrations in the blood has not been established in the literature, clinical benefits have been observed in studies at concentrations ranging from 8 to 30 mg/l, and the safety margin is usually not reduced at blood concentrations below 50 mg/l.
Duration of treatment
The optimal duration of treatment has not been established. In a recent large, multicenter study in premature babies, the average treatment duration was 37 days.
In clinical practice, treatment is usually continued until the premature baby reaches a gestational age of 37 weeks, counted from the date of the last menstrual period, at which time apnea of prematurity usually resolves spontaneously. However, this limit can be changed according to the clinical assessment of individual cases, depending on the response to treatment, the continued occurrence of apnea episodes despite treatment, or other clinical factors. It is recommended to discontinue caffeine citrate administration if there are no significant apnea attacks for 5-7 days.
If apnea recurs in the patient, caffeine citrate administration can be resumed using a maintenance dose or half of the loading dose, depending on the duration of the interval between the discontinuation of caffeine and the recurrence of apnea.
Due to the slow elimination of caffeine in this patient population, there is no need to reduce the dose during discontinuation of treatment.
Because there is a risk of apnea recurrence after discontinuation of caffeine citrate treatment, the patient should be monitored for approximately one week.
Impaired liver or kidney function
Experience with the use of the medicinal product in patients with impaired renal or liver function is limited. In a post-marketing safety study, the frequency of adverse reactions in a small group of premature babies born significantly before term with impaired liver or kidney function appears to be higher than in premature babies without impaired organ function.
In the event of impaired kidney function, there is a higher risk of accumulation. The daily maintenance dose of caffeine citrate should be reduced, and the dose should be adjusted according to the concentration of caffeine in the blood.
In premature babies born significantly before term, the clearance of caffeine is not dependent on liver function. The metabolism of caffeine in the liver develops gradually in the weeks after birth, and in older babies, liver disease may require monitoring of caffeine concentrations in the blood and dose adjustment.
Method of administration
Caffeine citrate can be administered intravenously or orally. The medicinal product should not be administered by intramuscular, subcutaneous, intrathecal, or intraperitoneal injection.
In the event of intravenous administration, caffeine citrate should be administered using a controlled intravenous infusion, exclusively using a syringe pump or other device that allows measurement. Caffeine citrate can be used undiluted or diluted in sterile solutions for infusion, such as glucose 50 mg/ml (5%) or sodium chloride 9 mg/ml (0.9%) or calcium gluconate 100 mg/ml (10%) immediately after withdrawal from the ampoule.

Preparation of the infusion solution

During the preparation of the medicinal product, aseptic technique should be strictly followed, as the product does not contain preservatives.
Before administration of the medicinal product Caffeine Citrate Neupharm, it should be visually inspected for the presence of particulate matter and color change. Ampoules containing discoloration or visible particulate matter should be discarded.
Caffeine Citrate Neupharm can be used undiluted or diluted in sterile solutions for infusion, such as glucose 5% (50 mg/ml) or 0.9% sodium chloride solution (9 mg/ml) or 10% calcium gluconate solution (100 mg/ml) immediately after withdrawal from the ampoule.
The diluted solution must be clear and colorless. Before administration, all undiluted and diluted solutions for parenteral administration should be visually inspected for the presence of particulate matter and color change. The solution should not be used if discoloration or particulate matter is present.
For single use only. Any unused portion remaining in the ampoule should be discarded.
Do not leave unused residues for later administration.
No special requirements for disposal.

Stability and storage conditions of the diluted medicinal product

After opening the ampoule, the medicinal product should be used immediately. Dilute using aseptic technique.

Overdose

Published caffeine concentrations in the blood after overdose range from 50 mg/l to 350 mg/l.
Symptoms
Objective and subjective symptoms reported in the literature after caffeine overdose in premature babies include hyperglycemia, hypokalemia, muscle tremors, anxiety, hypertension, opistotonus, tonic-clonic movements, seizures, rapid breathing, tachycardia, vomiting, gastrointestinal irritation, gastrointestinal bleeding, fever, tremors, increased urea levels in the blood, and increased white blood cell count, as well as aimless movements of the jaws and lips.
A single case of caffeine overdose with complications in the form of intraventricular hemorrhage and long-term neurological consequences has been reported. No deaths related to caffeine overdose have been observed in premature babies.
Procedure
Treatment of caffeine overdose is mainly symptomatic and supportive. Potassium and glucose levels in the blood should be monitored, and hypokalemia and hyperglycemia should be corrected. It has been shown that the concentration of caffeine in the blood decreases after blood transfusion. Muscle tremors can be treated by administering intravenous anticonvulsant drugs (diazepam or barbiturates, such as sodium pentobarbital or phenobarbital).

Incompatibilities

This medicinal product should not be mixed or administered in the same intravenous line with other medicinal products, except for those mentioned in the section "Preparation of the infusion solution".