Pentacarinat Ready-to-Use solution

In terms of the active ingredient

Pentamidine Isetionate 300mg

(Equivalent to 172.4mg Pentamidine base)

Nebuliser Solution

Pentacarinat Ready-to-Use Solution is indicated in the treatment of Pneumocystis carinii pneumonia (PCP) in patients infected by the human immunodeficiency virus

(HIV).

Pentacarinat Ready-to-Use Solution is also indicated for the prevention of Pneumocystis carinii pneumonia in patients infected by the human immunodeficiency virus who have experienced a previous episode of PCP.

Adults

Treatment of Pneumocystis carinii pneumonia

600mg, (two bottles) given once daily for 3 weeks, administered by a suitable nebuliser.

Prevention of Pneumocystis carinii pneumonia

300mg given once a month or 150mg given every two weeks, administered using a suitable nebuliser.

There are no specific dosage recommendations for the elderly.

Hepatic failure

No information is available.

The drug should not be administered to patients with a known hypersensitivity to pentamidine.

Fatalities due to severe hypotension, hypoglycaemia, acute pancreatitis and cardiac arrhythmias have been reported in patients treated with pentamidine isetionate, by both the intramuscular and intravenous routes. Therefore patients receiving pentamidine by inhalation should be closely monitored for the development of severe adverse reactions.

Pentamidine isetionate should be used with particular caution in patients with hepatic and/or renal dysfunction, hypertension, hyperglycaemia, hypoglycaemia, leucopenia, thrombocytopenia or anaemia. Bronchospasm has been reported to occur following the use of the nebuliser. This has been particularly noted in patients who have a history of smoking or asthma. This can be controlled by prior use of bronchodilators.

The benefit of aerosolised pentamidine therapy in patients at high risk of a pneumothorax should be weighed against the clinical consequences of such a manifestation.

Pentamidine isetionate may prolong the QT interval. Cardiac arrhythmias indicative of QT prolongation, such as Torsades de Pointes, have been reported in isolated cases with administration of pentamidine isetionate. Therefore, pentamidine isetionate should be used with care in patients with coronary heart disease, a history of ventricular arrhythmias, uncorrected hypokalaemia and or hypomagnesaemia, bradycardia (<50 bpm), or during concomitant administration of pentamidine isetionate with QT prolonging agents.

Particular caution is necessary if the QTc exceeds 500 msec whilst receiving pentamidine isetionate therapy, continuous cardiac monitoring should be considered in this case.

Should the QTc-interval exceed 550 msec then an alternative regimen should be considered.

Caution is advised when pentamidine isetionate is concomitantly used with drugs that are known to prolong the QT interval such as phenothiazines, tricyclic antidepressants, terfenadine and astemizole, IV erythromycin, halofantrine, and quinolene antibiotics (see Warnings section).

There is no evidence on the safety of aerosolised pentamidine in human pregnancy. A miscarriage within the first trimester of pregnancy has been reported following aerosolised prophylactic administration. Pentamidine isetionate should not be administered to pregnant patients unless considered essential. The use of pentamidine isetionate is contraindicated in breast feeding mothers unless considered essential by the physician.

Pentamidine has no known effect on the ability to drive and use machines.

Cases of pneumothorax have been reported in patients with a history of PCP. Although the aetiology of the pneumothorax was not linked primarily to the aerosolised administration of pentamidine in the majority of cases, a causal relationship cannot be ruled out. Local reactions involving the respiratory tract can occur, ranging in severity from cough, shortness of breath and wheezing, bronchospasms to eosinophilic pneumonia. Other adverse effects reported with the use of aerosolised pentamidine are rash, hypotension, hypoglycaemia, acute pancreatitis, renal insufficiency, fever, decrease in appetite, taste disturbances, fatigue, lightheadedness and nausea.

Pentamidine isetionate may prolong the QT interval. Isolated cases of Torsades de Pointes have been reported with the administration of pentamidine isetionate.

Should overdosage occur, treatment is symptomatic.

Cardiac rhythm disorders, including Torsades de Pointes, have been reported following overdose of pentamidine isetionate.

Pentamidine isetionate is an aromatic diamine. It is an antiprotozoal agent which acts by interfering with DNA and folate transformation, and by the inhibition of RNA and protein synthesis.

When administered by the use of a nebuliser, human kinetic studies revealed significant differences when compared to parenteral administration. Aerosol administration resulted in a 10-fold increase in bronchial alveolar lavage (BAL) supernatant fluid and an 80-fold increase in BAL sediment concentrations in comparison with those seen with equivalent parenteral doses.

Limited data suggests that the half life of pentamidine in BAL fluid is greater than 10-14 days.

Long term pulmonary parenchymal effects of aerosolised pentamidine are not known. Lung volume and alveolar capillary diffusion, however, have not been shown to be affected by high doses of pentamidine administered by inhalation to AIDS patients.

No additional data of relevance to the prescriber.

Pentamidine nebuliser solution should not be mixed with any other solution.

12 months.

Store below 25°C. Do not refrigerate. See 6.6 (lnstructions for Use/Handling)

Low density polyethylene bottles and plug with yellow high density polyethylene tamper evident caps

Any solid material evident in the polyethylene bottle should be re-dissolved by gentle warming in the hand before use. The solution placed in the nebuliser reservoir should be visually inspected prior to use. Any solution containing particulate matter should be discarded and the nebuliser reservoir rinsed with sterile water prior to re-use.

The optimal particle size for alveolar deposition is between 1 and 2 microns.

The solution containing the required dosage should be administered by inhalation using a suitable nebuliser such as a Respirgard II (trade mark of Marquest Medical Products inc.), modified Acorn system 22 (trade mark of Medic-Aid) or an equivalent device with either a compressor or piped oxygen at a flow rate of 6 to 10 litres/minute.

The nebuliser should be used in a vacated well ventilated room. Only staff wearing adequate protective clothing (mask, goggles, gloves) should be in the room when nebulisers are being used.

A suitable well fitted one way system should be employed such that the nebuliser stores the aerosolised drug during exhalations and disperses exhaled pentamidine into a reservoir. A filter should be fitted to the exhaust line to reduce atmospheric pollution. It is advisable to use a suitable exhaust tube which vents directly through a window to the external atmosphere. Care should be taken to ensure that passers-by will not be exposed to the exhaust. All bystanders including medical personnel, women of child bearing potential, pregnant women, children and people with a history of asthma should avoid exposure to atmospheric pentamidine resulting from nebuliser usage.

Dosage equivalence: 4 mg pentamidine isetionate contain 2.3 mg pentamidine base. 1 mg pentamidine base is equivalent to 1.74 mg pentamidine isetionate.

Sanofi-aventis

One Onslow Street

Guildford

Surrey

GU1 4YS

UK

PL 04425/0571

1^st September 1997

21^st December 2006

Legal Category: POM