POTABA 3G POWDER SACHETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Potaba 3g Powder Sachets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each sachet contains 3 g potassium para-aminobenzoate.

3 PHARMACEUTICAL FORM

Powder for oral solution

Each sachet contains 3 g white/off-white powder.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Potaba 3 g powder is indicated for the treatment of Peyronie's disease and scleroderma in adults.

4.2 Posology and method of administration

Posology

One sachet containing 3 g Potaba powder should be taken orally, four times daily.

Paediatric population

The safety of Potaba 3 g powder in children aged 0 to 18 years has not been established. No data are available.

Method of administration

For oral use.

The contents of one sachet should be dissolved in cold water or fruit juice and taken orally with food.

4.3 Contraindications

– Hypersensitivity to the active substance potassium para-aminobenzoate, para-substituted aromatic amines (e. g. benzocaine, procaine, ethyl parahydroxyben­zoate) or to any of the excipients listed in section 6.1.

– Renal insufficiency (GFR < 45 ml/min).

– Hyperkalaemia (each sachet contains 669 mg potassium).

– Potaba 3 g powder should not be given to patients taking sulphonamides as these medicinal products will be inactivated by potassium paraaminobenzoate (see section 4.5 Interaction with other medicinal products and other forms of interaction).

– Severe liver damage.

4.4 Special warnings and precautions for use

Hypersensitivity reactions

Potaba 3 g powder must be discontinued immediately if signs or symptoms of hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by raised liver enzymes, fever, general malaise, fatigue, muscle pain, blisters, oral lesions, oedema and eosinophilia) and must not be restarted.

Severe cutaneous adverse reactions

Severe cutaneous adverse reactions (SCARs) manifesting as drug reactions with eosinophilia and systemic symptoms (DRESS), which can be lifethreatening or fatal, have been reported in association with Potaba 3 g powder treatment. At the time of prescription, patients should be advised of the signs and symptoms and monitored closely for skin reactions.

If signs and symptoms suggestive of this reaction appear, Potaba 3 g powder should be withdrawn immediately.

If the patient has developed DRESS with the use of Potaba 3 g powder, treatment with Potaba 3 g powder must not be restarted in this patient at any time.

Food intake

Treatment with Potaba 3 g powder should be interrupted during periods of low food intake (e.g. during fasting, anorexia, nausea). This is to avoid the possible development of hypoglycaemia. (see section 4.8).

Hyperkalaemia

In patients with impaired renal function or other diseases like diabetes mellitus, cardiovascular diseases, congestive heart failure, hypoaldosteronism and pseudohypoaldos­teronism and/or in case of concomitant treatment with medicinal products that can increase the serum potassium level (see section 4.5), Potaba 3 g powder should be used with caution because of the risk of hyperkalaemia.

Before start of treatment with Potaba 3 g powder, an anamnestic survey of preexisting hyperkalaemia risk factors including an initial serum potassium determination should be performed for all patients. For patients with an increased risk of hyperkalaemia, serum potassium should be measured at least monthly or at closer intervals depending on risk assessment and monitoring requirements due to other risk factors. For patients with an increased initial serum potassium level, the underlying cause should be identified insofar as possible and serum potassium levels should be normalised before start of treatment with Potaba 3 g powder. For these patients, monitoring after start of therapy should also be performed monthly until long-term normal serum potassium levels are established. After that and for all other patients, monitoring is recommended at least quarterly.

Furthermore, serum potassium should be measured promptly for patients who report symptoms possibly indicative of hyperkalaemia such as muscle pain or tightness, flaccid paralysis, weakness, paraesthesia, nausea, vomiting, palpitations, bradycardia or tachypnoea.

Liver dysfunction

Hepatotoxic effects have been observed for Potaba 3 g powder and were reported as hepatitis (various specifications), drug-induced liver injury or (acute) hepatic failure depending on results of diagnostic investigations, time course of drug use and liver disorder and other accompanying symptoms such as nausea, pyrexia, chromaturia or jaundice. For all patients who take Potaba 3 g powder, regular (at least every 4 weeks) liver function tests must be performed (transaminases, gamma-GT, ALP, LDH, bilirubin). If elevated liver function tests or symptoms indicative of a liver disorder are observed, Potaba 3 g powder must be discontinued immediately.

4.5 Interaction with other medicinal products and other forms of interaction Sulfonamides will be inactivated by Potaba 3 g powder since aminobenzoate is preferentially taken up by bacteria.

Methotrexate is displaced from plasma protein binding by aminobenzoate. Subsequently, plasma levels of methotrexate may increase if administered together with Potaba 3 g powder.

The potassium in Potaba 3 g powder can reduce the effect of concomitant cardiac glycosides.

Potassium levels may further increase with concomitant use of aldosterone antagonists, potassium-sparing diuretics, ACE inhibitors, beta blockers, nonsteroidal anti-inflammatory drugs, angiotensin receptor blockers, calcineurin inhibitors, penicillins, pentamidine, ketoconazole, digoxin, heparin, potassium supplements and other medicinal products containing high potassium amounts.

4.6 Fertility, Pregnancy and lactation

Pregnancy

There are no or limited amount of data from the use of potassium para-aminobenzoate in pregnant women.

Potaba 3 g powder is not recommended during pregnancy.

Breastfeeding

It is unknown whether potassium para-aminobenzoate/me­tabolites are excreted in human milk.

A risk to the newborns/infants cannot be excluded.

Fertility

There are no or limited amount of data on the effects of potassium paraaminobenzoate on fertility.

4.7 Effects on ability to drive and use machines

Potaba 3 g powder has no or negligible influence on the ability to drive and use machines. If patients experience confusion, lethargy or weakness they should not drive until such symptoms have fully reversed.

4.8 Undesirable effects

The following convention has been utilised for the classification of undesirable effects:

Very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10000, <1/1000), very rare (<1/10000), not known (cannot be estimated from the available data)

Drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported in association with Potaba 3 g powder treatment.

Not known: hypoglycaemia (see section 4.4)

Immune system disorders

Not known: hypersensitivity reactions, including immunoallergic hepatitis (characterized by fever, rash, oedema, arthralgia/myalgia, elevated liver enzymes) (see section 4.4.)

Common: nausea, vomiting, anorexia, stomach discomfort, diarrhoea

Hepatobiliary disorders

Uncommon: elevated liver enzymes (e.g. transaminases, gamma-GT, ALP, LDH)

Rare: hepatitis

Not known: drug-induced liver injury, hepatic failure

Uncommon: skin rash (exanthema, eczema, dermatitis, urticaria), pruritus

Not known: Drug reaction with eosinophilia and systemic symptoms (DRESS)

Common: pyrexia, chills

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

No particular problems are expected following overdose with Potaba 3 g powder. Symptomatic and supportive therapy should be given as appropriate.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antifibrosis agent

Mechanism of action

Potassium para-aminobenzoate is considered a member of the Vitamin B complex. Small amounts are found in cereal, eggs, milk and meats. Detectable amounts are normally present in human blood, spinal fluid, urine and sweat. The pharmacological action of this chemical has not been clearly established, but it has been suggested that the antifibrosis activity of potassium paraaminobenzoate is brought about by the drug increasing oxygen uptake at the tissue level. Fibrosis is believed to occur from either too much serotonin or too little monoamine oxidase activity over a period of time. The activity of monoamine oxidase is dependent on an adequate oxygen supply. By increasing oxygen supply at tissue level potassium para-aminobenzoate enhances monoamine oxidase activity thereby preventing or bringing about regression of fibrosis.

5.2 Pharmacokinetic properties

Absorption

Aminobenzoate is well absorbed after oral administration.

Oral administration of 3 g Potaba to healthy volunteers resulted in maximum plasma levels of 29–74 pg/mL after 41–90 min. followed by rapid decrease to less than 10 pg/mL after 4 h.

Elimination

Potassium and conjugated aminobenzoate are eliminated by the kidney.

5.3 Preclinical safety data

In-vitro bacterial tests with para-aminobenzoate revealed no mutagenic potential. There are no long-term tests for carcinogenic potential. Adequate reproductive toxicity tests are not available for potassium para-aminobenzoate. In limited studies in pregnant rats, oral administration of 50 mg/kg/day para-aminobenzoate reduced foetal weights. In animal experiments, para-aminobenzoate crosses the placenta.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

None in this presentation.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

5 years.

6.4 Special precautions for storage

Do not store above 25 °C.

Store in the original packaging.

6.5 Nature and contents of container

Cardboard outer containing 40 foil laminate sachets.

6.6 Special precautions for disposal

Any unused product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Neon Healthcare Ltd.

8 The Chase, John Tate Road

Hertford

SG13 7NN

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 45043/0044

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

28/04/1981 / 16/01/2004