Pentacarinat 300 mg powder for injection solution

Patient Information Leaflet

Introduction

Patient Information Leaflet

Pentacarinat 300 mg powder for injectable solution

Pentamidine isethionate

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, since it could harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if these effects are not listed in this leaflet. See section 4.

Leaflet contents:

1. What Pentacarinat is and what it is used for
2. What you need to know before using Pentacarinat
3. How to use Pentacarinat
4. Possible side effects
5. How to store Pentacarinat
6. Contents of the pack and other information

1. What Pentacarinat is and what it is used for

Pentacarinat 300 mg powder for injectable solution is a powder for administration by intramuscular or intravenous route.

The active substance of Pentacarinat is pentamidine isethionate, which is an antiprotozoal agent that acts lethally against the microorganisms Pneumocystis jirovecii (previously known as Pneumocystis carinii), Trypanosoma gambiense, and Leishmania, possibly by inhibiting protein synthesis.

It is indicated for the treatment of:

• pneumonia due to Pneumocystis jirovecii (previously known as Pneumocystis carinii),
• cutaneous leishmaniasis,
• early stage of African sleeping sickness caused by Trypanosoma gambiense.

2. What you need to know before using Pentacarinat

Do not use Pentacarinat

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

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to use Pentacarinat:

• If you have impaired liver and/or kidney function, high or low blood pressure, high or low blood sugar levels, or a reduced number of white blood cells, red blood cells, or platelets in your blood.

• Due to the possibility of serious adverse reactions, sometimes fatal, such as low blood pressure (hypotension), decreased blood sugar levels (hypoglycemia), inflammation of the pancreas (acute pancreatitis), and disturbances in heart rhythm (cardiac arrhythmias).

• After a dose of Pentacarinat, your blood pressure may suddenly drop to very low levels. Therefore, your doctor will monitor your blood pressure before and during administration, and at regular intervals throughout treatment. The medicine will be administered while you are lying down on your back.

• Due to the possibility of QT interval prolongation. Serious (and sometimes fatal) cardiac arrhythmias (disturbances in heart rhythm), such as "Torsades de pointes," have been reported due to this effect. Therefore, your doctor may consider performing an electrocardiogram (ECG) before starting treatment. Special caution should be taken when administering Pentacarinat if you have conditions that increase the risk of arrhythmias, including patients with long QT syndrome, heart disease, history of arrhythmias, low potassium and/or low magnesium levels in the blood, bradycardia (slow heart rate), or if you are taking other medications that prolong the QT interval (see "Use of Pentacarinat with other medicines").

• Due to possible changes in certain blood, urine, or liver function parameters. Laboratory tests should be performed before, during, and after treatment to monitor:

• blood urea, serum nitrogen, and creatinine, complete blood and platelet count, urine analysis, and serum electrolyte levels – daily during treatment,

• fasting blood glucose levels – daily during treatment and at regular intervals after treatment ends. Increased blood glucose and diabetes mellitus, with or without prior hypoglycemia, may occur even several months after treatment has ended,

• calcium levels – weekly, and magnesium levels – twice weekly,

• electrocardiograms at regular intervals,

• liver function tests, including bilirubin, alkaline phosphatase, aspartate aminotransferase (AST/SGOT), and alanine aminotransferase (ALT/SGPT). If baseline values are normal and remain normal during treatment, monitoring will be performed weekly.

If baseline liver function test results are elevated, or become elevated during treatment, monitoring will be performed weekly, unless you are taking other medications that may harm the liver, in which case monitoring will be performed every 3–5 days.

Use of Pentacarinat with other medicines

Inform your doctor or pharmacist if you are currently using, have recently used, or might need to use any other medicines.

Caution is advised if you are taking, concurrently with Pentacarinat:

• Medicines known to prolong the QT interval, including:

• certain antiarrhythmic drugs (such as quinidine, disopyramide, procainamide, amiodarone, or sotalol),

• medicines for depression (tricyclic antidepressants or certain tetracyclic antidepressants such as maprotiline),

• certain medicines for the treatment of psychosis (such as phenothiazines and pimozide),

• certain antihistamines (such as astemizole and terfenadine),

• antibiotics (such as quinolones, intravenous erythromycin),

• antimalarial drugs (such as halofantrine, mefloquine),

• bepridil (used to treat angina pectoris),

• cisapride (a medicine to improve gastric motility).

• Foscarnet (a medicine used to treat certain viral infections), due to the risk of decreased calcium levels.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy:

If you are pregnant or think you might be pregnant, do not use Pentacarinat, as the safety of Pentacarinat during pregnancy has not been studied.

Breastfeeding:

If you are breastfeeding, Pentacarinat is not recommended.

Driving and using machines

The effect of Pentacarinat on the ability to drive or operate machinery is unknown.

Dizziness has been reported; therefore, caution should be exercised when driving or operating machinery.

3. How to use Pentacarinat

Follow exactly the instructions for administration of this medicine as given by your doctor.

If in doubt, consult your doctor or pharmacist again.

If you think that the effect of Pentacarinat is too strong or too weak, inform your doctor, pharmacist, or nurse.

The recommended dose for:

• Adults, children, and infants:

• Pneumocystis jiroveci pneumonia: 4 mg/kg of body weight of pentamidine isethionate, once daily for at least 14 days, preferably by slow intravenous infusion. Intramuscular administration is not recommended in these cases. The IV route is the preferred route of administration for the treatment of Pneumocystis jiroveci pneumonia.

• Cutaneous leishmaniasis: 4 mg/kg of body weight of pentamidine isethionate, three doses on alternate days, administered by intramuscular or intravenous injection.

• Trypanosomiasis: 4 mg/kg of body weight of pentamidine isethionate, once daily or every other day, up to a total of 7–10 doses. The intramuscular or intravenous route may be used.

• Patients with impaired renal function:

• In Pneumocystis jiroveci pneumonia:

• in life-threatening cases: administer 4 mg/kg of body weight once daily for 7 to 10 days, followed by 4 mg/kg of body weight on alternate days until completing a cycle of at least 14 doses.

• in less severe cases: administer 4 mg/kg of body weight on alternate days until completing a cycle of at least 14 doses.

In these cases, intramuscular administration is not recommended. The IV route is the route of administration for the treatment of Pneumocystis jiroveci pneumonia.

• In cases of leishmaniasis and trypanosomiasis, dose reduction is not necessary.

• Elderly patients and patients with impaired hepatic function:

There are no special dosage recommendations for elderly patients or those with impaired liver function.

Pentacarinat is administered by deep intramuscular injection or by slow intravenous infusion (see “Instructions for correct preparation and administration by healthcare professionals”).

It must always be administered with the patient in a supine position, whether for deep intramuscular injection or for slow intravenous infusion.

The dose to be administered must be reconstituted in water for injections (see “Instructions for correct preparation and administration by healthcare professionals”).

Your doctor will advise you on the duration of your treatment with Pentacarinat. Do not stop your treatment prematurely, as it should continue until your doctor considers it necessary.

If you use more Pentacarinat than you should

Contact your doctor immediately. Cardiac rhythm disturbances, including “Torsade de Pointes,” have been reported following overdose of pentamidine isethionate.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number 91 562 04 20, indicating the medicine and the amount administered or ingested.

If you forget to use Pentacarinat

Do not administer a double dose to make up for missed doses.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

The following adverse effects have been reported according to the frequencies detailed below:

Very common: may affect more than 1 in 10 patients

Common: may affect up to 1 in 10 patients

Uncommon: may affect up to 1 in 100 patients

Rare: may affect up to 1 in 1,000 patients

Very rare: may affect up to 1 in 10,000 patients

Frequency not known: cannot be estimated from available data.

Blood and lymphatic system disorders

Common: decrease in white blood cells (leucopenia), decrease in red blood cells (anaemia), decrease in platelet count (thrombocytopenia)

Immune system disorders

Frequency not known: hypersensitivity reactions, including anaphylactic reactions and severe allergic reaction (anaphylactic shock), generalized urticaria accompanied by swelling of feet, hands, throat, lips and respiratory tract (angioedema)

Metabolism and nutrition disorders

Very common: presence of urea or other nitrogenous substances in blood (azotemia)

Common: low blood sugar (hypoglycaemia), high blood sugar (hyperglycaemia), diabetes mellitus with or without previous low blood sugar (hypoglycaemia) (cases have occurred up to several months after treatment ended), increased potassium levels in blood (hyperkalaemia), decreased calcium levels (hypocalcaemia), decreased magnesium levels (hypomagnesaemia)

Nervous system disorders

Common: fainting (syncope), dizziness

Frequency not known: cases of tingling sensation, numbness (paraesthesia) in the limbs, and decreased sensation (hypoesthesia) in the face or around the mouth have been reported in children and adults following intravenous administration of pentamidine. These effects occurred during or shortly after intravenous infusion and resolved upon completion or interruption of the infusion.

Cardiac disorders

Rare: prolongation of the cardiac QT interval, disturbance in heart rhythm (cardiac arrhythmia)

Frequency not known: type of tachycardia (“Torsade de Pointes”), slow heart rate (bradycardia)

Vascular disorders

Common: low blood pressure (hypotension), redness of the skin (rubefaction)

Gastrointestinal disorders

Common: nausea and vomiting, altered taste

Rare: inflammation of the pancreas (pancreatitis)

Hepatobiliary disorders

Common: abnormal results in liver function tests (hepatic function)

Skin and subcutaneous tissue disorders

Common: skin rash

Frequency not known: a group of symptoms known as Stevens-Johnson syndrome may occur, characterized by redness of the skin (rubefaction) together with severe blistering skin reactions and mucosal membrane involvement

Renal and urinary disorders

Very common: blood in urine (macroscopic haematuria), reduced kidney filtration capacity (acute renal failure)

General disorders and administration site conditions

Very common: local reactions ranging from mild discomfort and pain to pus accumulation (abscesses), hardening of the area (induration), and muscle tissue death (muscular necrosis)

Frequency not known: following intramuscular administration, cases of muscle fibre destruction accompanied by excretion of myoglobin in urine (rhabdomyolysis) have occurred.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Pentacarinat

Store below 25°C.

After reconstitution, store the solution in the refrigerator between 2°C and 8°C.

Discard any unused amount if more than 24 hours have passed after reconstitution.

Keep this medicine out of the sight and reach of children.

Expiry

Do not use this medicine after the expiry date stated on the container. The expiry date refers to the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to properly dispose of unused medicines and their packaging. This will help protect the environment.

6. Contents of the container and other information

Composition of Pentacarinat 300 mg powder for injectable solution

• The active substance is pentamidine isethionate. Each vial contains 300 mg of pentamidine isethionate.

Appearance of the product and contents of the container

The vial contains a white to off-white powder.

It is presented in packs containing 1 vial.

Marketing Authorization Holder and Manufacturer

Holder

The Simple Pharma Company Limited

Ground Floor, 71 Lower Baggot Street

Dublin, D02 P593

Ireland

Manufacturer

SANOFI S.r.l.

Via Valcanello, 4

03012 Anagni (FR)

Italy

Date of the most recent review of this summary: February 2021

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

INSTRUCTIONS FOR THE CORRECT ADMINISTRATION OF THE PREPARATION BY HEALTHCARE PROFESSIONALS

Pentamidine isethionate powder must be reconstituted with water for injections (3 ml of water for injections). For intravenous administration, the required dose of pentamidine isethionate should be diluted, after reconstitution, in 50–250 ml of glucose 5% solution for infusion or in 150–300 ml of 0.9% sodium chloride solution.

Saline solutions must not be used for the initial reconstitution of pentamidine isethionate solution, as they may cause precipitation of the drug. The reconstituted solution must not be mixed with other injectable solutions except glucose solution (for intravenous infusion) or 0.9% sodium chloride.