Pentamidine isetionate Tillomed 300 mg powder for solution for injection/infusion

pentamidine isetionate

Pentamidine isetionate Tillomed contains the active substance pentamidine isetionate and is an antiparasitic medicine used in adults and children:

• for the prevention and treatment of pneumonia caused by the pathogen Pneumocystis jirovecii (formerly known as Pneumocystis carinii),
• for the treatment of Kala-Azar (visceral leishmaniasis) and cutaneous leishmaniasis,
• for the treatment of the early stage of sleeping sickness (human African trypanosomiasis with Trypanosoma brucei gambiense as pathogen).

The name of your medicine is Pentamidine isetionate Tillomed Powder for Solution for Injection or Infusion, but will be referred to as Pentamidine isetionate throughout this leaflet.

Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Unless otherwise prescribed by the doctor, the following information applies to adults, adolescents, children and infants.

Pneumocystis jirovecii pneumonia:

Prophylaxis

Inhalation (see also "Method of administration"): For prophylactic administration,

The dosage in adults is 300 mg pentamidine isetionate administered as a single inhalation every 4 weeks or 150 mg every 2 weeks.

Therapy

Infusion (see also "Method of administration"): 4 mg pentamidine per kg body weight once daily, are preferably administered by slow intravenous infusion over 60 minutes. The duration of the treatment of 14 days is generally sufficient. In some severe cases, prolonging the treatment may be necessary. The total duration of treatment should not exceed 21 days.

Kala-Azar (visceral leishmaniasis):

Every 2 days, 3 to 4 mg of pentamidine isetionate per kg of body weight by intramuscular injection. The number of applications should not exceed 10. However, it is also possible to administer a second therapy cycle, if necessary.

Skin leishmaniasis:

About 3 to 4 mg pentamidine isetionate per kg body weight every other day for 3-4 doses by intramuscular injection or intravenous infusion.

Sleeping sickness (human African trypanosomiasis):

Once daily or every other day (up to a total of 7 to 10 applications) 4 mg pentamidine isetionate per kg body weight by intramuscular injection or intravenous infusion (see also " Method of administration").

Patients with impaired kidney function

In case of severely impaired kidney function (creatinine clearance <10 ml/min) a dose adjustment is required:

• For life-threatening Pneumocystis jirovecii pneumonia, 4 mg pentamidine isetionate per kg body weight should be given once daily for 7 to 10 days. Thereafter, the dose is given every 2 days to a total of 14 doses.
• In less severe cases of Pneumocystis jirovecii pneumonia, 4 mg pentamidine isetionate per kg body weight should be given every 2 days.
• For sleeping sickness and leishmaniasis, the dosing interval should not be less than 48 hours.

In mild cases of kidney impairment, at least 36 hours should have elapsed between doses of the product.

Patients with impaired liver function

In patients with a decrease in hepatic function, the benefits of continuation of therapy should outweigh the potential risk.

Elderly patients

There are no specific dosage recommendations.

If you have any further questions on the use of the medicine, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Possible side-effects after intravenous or intramuscular administration

Very common: (may affect more than 1 in 10 people)

• increase of nitrogenous metabolic products of protein in the blood
• reversible renal diseases: primarily acute renal failure, potentially life-threatening; blood in the urine;
• reactions at the injection site: swelling, inflammation and pain until hardening, abscess formation and death of muscle tissue.

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

• diseases of the blood (sometimes life-threatening): reduction in the number of white blood cells and platelets; reduction in the number of red blood cells (anaemia)
• metabolic disorders (potentially life-threatening): reduction in blood sugar, blood sugar increase, diabetes mellitus (persistent), reduction in serum magnesium levels, increase in serum potassium levels and reduction in serum calcium levels,
• sudden, short-term unconsciousness, dizziness,
• circulatory disorders (potentially life-threatening): too high or too low blood pressure, circulatory problems, feeling hot,
• nausea, vomiting, taste disorders,
• changes in liver function / liver function tests,
• rashes.

Rare: (may affect up to 1 in 1,000 people)

• QT interval prolongation, cardiac arrhythmia, potentially life-threatening
• pancreatitis, potentially life threatening

Not known: frequency cannot be estimated from the available data

• hypersensitivity reactions including anaphylactic reaction, angioedema and anaphylactic shock, potentially life threatening,
• Torsades de pointes (a special form of cardiac arrhythmia),
• slowed heartbeat,
• severe inflammation of the skin and mucous membrane (Stevens-Johnson syndrome),
• rhabdomyolysis (disintegration of muscle fibers) after intramuscular administration,
• discomfort such as tingling and / or prickling (paresthesia) in the arms and legs, reduced sensitivity around the mouth and in other areas of the face (hypesthesia). These occurred during or shortly after the infusion and
• regressed after cessation or discontinuation of the infusion.

Possible side effects of inhalation therapy:

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

• coughing, shortness of breath, rales, spasms of the bronchial musculature,
• taste disorders, nausea.

Rare: (may affect up to 1 in 1,000 people)

• inflammation of the lung due to allergic reactions (eosinophilic pneumonia).

Not known: frequency cannot be estimated from the available data

• hypersensitivity reactions, including anaphylactic reaction, angioedema and anaphylactic shock, potentially life threatening,
• very low blood sugar,
• dizziness,
• slowed heartbeat,
• conjunctivitis (after accidental aerosol contact with the eyes),
• too low blood pressure,
• air accumulation in the chest (after previous Pneumocystis jirovecii pneumonia), hemoptysis,
• salivation, retrosternal burning sensationum, vomiting, pancreatitis, potentially life-threatening,
• rash, hives, blotchy rash with nodule formation (maculopapular rash),
• impaired renal function,
• fever, fatigue, decreased appetite.

Note:

Because inhalation therapy of pentamidine can cause severe, sometimes life-threatening side effects (see above) too, patients should be closely monitored for the development of severe side effects.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor straight away.

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

Do not use this medicine after the expiry date, which is stated on the outer carton and the vial after‘EXP’. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

After first opening:

The medicinal product must be used immediately.

After reconstitution/dilution:

The chemical and physical in-use stability of the solution diluted in glucose 50mg/ml (5%) solution or sodium chloride 9 mg/ml (0.9%) solution has been demonstrated for 24 hours at a temperature (20-25°C).

From a microbiological point of view, the medicinal product should be used immediately, if not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not longer than 24 hours at (2 to 8°C) unless reconstitution/ dilution has taken place in controlled and validated aseptic conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.