Leaflet: information for the user

Pentacarinat 300 mg powder for injectable solution

Pentamidine isethionate

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

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

1. What is Pentacarinat and what it is used for

2. What you need to know before starting to use Pentacarinat

3. How to use Pentacarinat

4. Possible side effects

5. Storage of Pentacarinat

6. Contents of the pack and additional information

Pentacarinat 300 mg powder for injectable solution is a powder for administration via intramuscular or intravenous routes.

The active ingredient of Pentacarinat is pentamidine isethionate, which is an antiprotozoal agent that acts lethally against microorganismsPneumocystis jirovecii(previously known asPneumocystis carinii),Trypanosoma gambienseandLeishmania, possibly inhibiting protein synthesis.

It is indicated for the treatment of:

• pneumonia caused byPneumocystis jirovecii(previously known asPneumocystis carinii),
• cutaneous leishmaniasis,
• early stage of African sleeping sickness caused byTrypanosoma gambiense.

No use Pentacarinat

• If you are allergic to pentamidine isethionate or any of the other components of this medication (listed in section 6).

Warnings and Precautions

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

• If your liver and/or kidney function is impaired, you have high or low blood pressure, elevated or low blood sugar levels, or a decreased number of white blood cells, red blood cells, or platelets in your blood.
• Due to the possibility of severe adverse reactions, sometimes with fatal outcome, such as low blood pressure (hypotension), low blood sugar (hypoglycemia), acute pancreatitis, and cardiac arrhythmias.
• After a dose of Pentacarinat, your blood pressure may drop to very low levels suddenly. Therefore, your doctor will monitor your blood pressure before and during administration, as well as at regular intervals during treatment. The medication will be administered in a lying down position, face up.
• Due to the possibility of QT interval prolongation. Cases of severe cardiac arrhythmias (sometimes with fatal outcome) caused by this effect, such as "Torsades de pointes", have been reported. Therefore, your doctor will consider the possibility of performing an electrocardiogram before starting treatment. Therefore, special care should be taken when administering Pentacarinat if you have conditions that increase the risk of arrhythmias, including patients with long QT syndrome, heart disease, a history of arrhythmias, low potassium and/or low magnesium levels in the blood, bradycardia (slow heart rate), or during concomitant administration with medications that prolong the QT interval (see "Pentacarinat use with other medications").
• Due to the possible alteration of certain parameters in blood, urine, or liver function. Laboratory tests should be performed, before, during, and after treatment:

• Daily during treatment: blood urea, nitrogen, and creatinine, complete blood count and platelet count, urine analysis, and serum electrolyte levels.
• Fasting blood sugar levels, daily during treatment, and at regular intervals after treatment. Hyperglycemia and diabetes mellitus, with or without previous hypoglycemia, may appear even several months after treatment is completed.
• Calcium levels, weekly, and magnesium levels, twice a week.
• Electrocardiogram 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, controls will be performed weekly.

If baseline liver function test values are elevated, or become elevated during treatment, you will be monitored weekly, unless you are being treated with medications that can damage the liver, in which case you will be monitored every 3-5 days.

Pentacarinat use with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Caution is advised if you are using Pentacarinat at the same time as:

• Medications known to prolong the QT interval, including:

• Certain medications for arrhythmia treatment (such as quinidine, disopyramide, and procainamide or amiodarone and sotalol).
• Medications for depression (tricyclic antidepressants or certain tetracyclic antidepressants such as maprotiline).
• Certain medications for psychosis treatment (such as phenothiazines and pimozide).
• Certain medications for allergy treatment (such as astemizol and terfenadine).
• Antibiotics (such as quinolones, intravenous erythromycin).
• Medications for malaria treatment (such as halofantrine, mefloquine).
• Bepridil (for angina pectoris treatment).
• Cisapride (medication to improve gastric motility).

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

Pregnancy and lactation

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy:

Do not use Pentacarinat if you are pregnant, as the safety of Pentacarinat use during pregnancy has not been studied.

Lactation:

Do not recommend using Pentacarinat if you are breastfeeding.

Driving and operating machinery

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

Cases of dizziness have been reported, so you should be aware when driving or operating machinery.

Follow exactly the administration instructions of this medication as indicated by your doctor.

In case of doubt, consult your doctor or pharmacist again.

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

The recommended dose for:

• Pneumocystis jiroveci pneumonia: 4 mg/kg of body weight of pentamidine isethionate, once a day, for at least 14 days, preferably by slow intravenous infusion. Intramuscular administration is not recommended in these cases. IV 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, by intramuscular or intravenous injection.
• Trypanosomiasis: 4 mg/kg of body weight of pentamidine isethionate, once a day, or every two days, until a total of 7-10 doses. Either intramuscular or intravenous administration can be used.

• In Pneumocystis jiroveci pneumonia:

• In cases with vital risk, administer 4 mg/kg of body weight once a day for 7-10 days, and then 4 mg/kg of body weight on alternate days until completing the cycle of at least 14 doses.
• In less severe cases: administer 4 mg/kg of body weight on alternate days until completing the cycle of at least 14 doses.

Intramuscular administration is not recommended in these cases. IV is the route of administration for the treatment of Pneumocystis jiroveci pneumonia.

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

No special dose recommendations exist for elderly patients and those with altered liver function.

Pentacarinat is administered by deep intramuscular injection or slow intravenous infusion (see "Instructions for correct administration of the preparation by healthcare professionals").

It must be administered always with the patient in a horizontal position, both for deep intramuscular injection and for slow intravenous infusion.

The dose to be administered must be reconstituted in water for injectable preparations (see "Instructions for correct administration of the preparation by healthcare professionals").

Your doctor will indicate the duration of your treatment with Pentacarinat. Do not discontinue your treatment before, as it must continue until he considers it necessary.

If you use more Pentacarinat than you should

Consult your doctor immediately. Cardiac rhythm alterations, including the so-called "Torsade de Pointes", have been reported after pentamidine isethionate overdose.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount administered or ingested.

If you forgot to use Pentacarinat

No double dose will be administered to compensate for the missed doses.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

The following side 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:decreased white blood cell count (leucopenia), decreased red blood cell count (anemia), decreased platelet count (thrombocytopenia)

Immune system disorders

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

Metabolism and nutrition disorders

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

Common:decreased blood sugar (hypoglycemia), increased blood sugar (hyperglycemia), diabetes mellitus with or without previous decreased blood sugar (hypoglycemia) (cases have been reported up to several months after treatment completion), increased potassium levels in the blood (hyperkalemia), decreased calcium levels (hypocalcemia), decreased magnesium levels (hypomagnesemia)

Nervous system disorders

Common: fainting (syncope), dizziness

Frequency not known: cases of tingling, numbness (paresthesia) in the extremities and decreased sensation (hypoesthesia) in the face or around the mouth, in children and adults, with intravenous administration of pentamidine. These effects occurred during or shortly after the intravenous infusion and disappeared when the infusion was completed or interrupted

Cardiac disorders

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

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

Vascular disorders

Common: decreased 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 liver function test results (hepatic function)

Skin and subcutaneous tissue disorders

Common:skin rash

Frequency not known: a set of symptoms called Stevens-Johnson syndrome may appear, characterized by redness of the skin (rubefaction) along with severe vesicular skin and mucous membrane reactions

Renal and urinary disorders

Very common: blood in the urine (macroscopic hematuria), decreased kidney filtration capacity (acute renal insufficiency)

General disorders and administration site conditions

Very common: local reactions from mild discomfort and pain to pus accumulation (abscesses), tissue hardening (induration), and muscle tissue death (rhabdomyolysis)

Frequency not known: after intramuscular administration, cases of muscle fiber destruction accompanied by urinary excretion of myoglobin (rhabdomyolysis) have been reported.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Store below 25°C.

Once reconstituted, store the solution in the refrigerator between 2°C and 8°C.

Discard any unused quantity if 24 hours have passed after reconstitution.

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

Expiration Date

Do not use this medication after the expiration date that appears on the packaging. The expiration date is the last day of the month indicated.

Medicines should not be thrown down the drain or in the trash. Ask your pharmacist how to dispose of the packaging and unused medications. In this way, you will help protect the environment.

Composition of Pentacarinat 300 mg powder for injectable solution

- The active ingredient is pentamidine isethionate. Each vial contains 300 mg of pentamidine isethionate.

Appearance of the product and contents of the packaging

The vial contains a white to off-white powder.

It is presented in packaging containing 1 vial.

Holder of the marketing authorization and responsible for manufacturing

Holder

The Simple Pharma Company Limited

Ground Floor, 71 Lower Baggot Street

Dublin, D02 P593

Ireland

Responsible for manufacturing

SANOFI S.r.l.

Via Valcanello, 4

03012 Anagni (FR)

Italy

Last review date of this leaflet: February 2021

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

INSTRUCTIONS FOR THE CORRECT ADMINISTRATION OF THE PREPARATION BY HEALTH PROFESSIONALS

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

For the initial reconstitution of the pentamidine isethionate solution, saline solutions should not be used as they may cause precipitation of the medication. The resulting solution from reconstitution should not be mixed with other injectable solutions except glucose solution (intravenous infusion) or sodium chloride 0.9 %.