Selexid Tablets

1. Name Of The Medicinal Product

Selexid^® Tablets.

2. Qualitative And Quantitative Composition

Pivmecillinam hydrochloride 200mg

3. Pharmaceutical Form

Tablets.

4. Clinical Particulars

4.1 Therapeutic Indications

Treatment of infections due to mecillinam sensitive organisms, including:

• urinary tract infections

• salmonellosis

Preliminary experience in a small number of patients suggests that Selexid^® Tablets may be a useful alternative antibiotic in the treatment of acute typhoid fever and in some carriers of salmonellae when antibiotic treatment is considered essential.

4.2 Posology And Method Of Administration

Route of administration is oral. The tablets must be taken with at least half a glass of water and preferably taken with or immediately after a meal.

Adults and children weighing more than 40 kg:

Urinary tract infections:

• acute uncomplicated cystitis: 72 hour course of 2 tablets immediately followed by 1 tablet 3 times daily to a total of 10 tablets.

• Chronic or recurrent bacteriuria: 2 tablets 3 to 4 times daily.

Salmonellosis:

• Enteric fever: 1.2 - 2.4g daily for 14 days.

• Salmonella carriers: 1.2 - 2.4 g daily for 2-4 weeks.

Children weighing less than 40 kg:

• Urinary tract infections: 20-40 mg/kg body weight, daily, in 3 to 4 divided doses.

• Salmonellosis: 30-60 mg/kg body weight, daily, in 3 to 4 divided doses.

Dosage in the elderly:

Renal excretion of mecillinam is delayed in the elderly, but significant accumulation of the drug is not likely at the recommended adult dosage of Selexid^® Tablets.

4.3 Contraindications

Selexid^® Tablets are contra-indicated in patients with:

• Hypersensitivity to the drug substance or any of the other ingredients.

• Hypersensitivity to penicillins and/or cephalosporins

• Oesophageal strictures and/or obstructive changes in the gastrointestinal tract.

• A predisposition to carnitine deficiency.

Selexid^® Tablets are contra-indicated in infants under 3 months.

4.4 Special Warnings And Precautions For Use

During long term use, it is advisable to carry out routine liver and kidney function tests.

Selexid^® Tablets should be used with caution in patients with porphyria since pivmecillinam has been associated with acute attacks of porphyria.

As with other antibiotics which are excreted mainly by the kidneys, raised blood levels of mecillinam may occur if repeated doses are given to patients with impaired renal function.

Selexid^® Tablets should be used with caution for long-term or frequently-repeated treatment, due to the possibility of carnitine depletion.

Concurrent treatment with valproic acid, valproate or other medication liberating pivalic acid should be avoided.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Clearance of methotrexate from the body can be reduced by concurrent use of penicillins. The methotrexate dose may need to be adjusted.

Simultaneous administration of probenecid reduces the excretion of penicillins, and hence increases blood levels of the antibiotic.

Simultaneous administration of other beta-lactam antibiotics with Selexid^® Tablets may produce a synergistic effect.

4.6 Pregnancy And Lactation

The drug, as mecillinam, crosses the placenta. Although tests in two animal species have shown no teratogenic effects, in keeping with current practice, use during pregnancy should be avoided.

4.7 Effects On Ability To Drive And Use Machines

No effects on the ability to drive or use machines have been observed.

4.8 Undesirable Effects

The most frequently reported undesirable effects are gastrointestinal disorders and various skin reactions. Oesophageal and mouth ulceration can occur if Selexid^® Tablets are taken with insufficient amount of fluid. Allergic reactions, changes in blood counts and hepatic function disorders have been reported in isolated cases.

Based on a review of clinical studies in urinary tract infections, undesirable effects have been identified in <10% of patients. Therapy was rarely discontinued due to adverse events.

Blood and lymphatic system disorders

Thrombocytopenia

Granulocytopenia

Leucopenia

Eosinophilia

Immune system disorders

Anaphylactic reaction

Gastrointestinal disorders

Oesophageal ulcer

Oesophagitis

Antibiotic associated colitis

Diarrhoea

Vomiting

Mouth ulceration

Dysphagia

Nausea

Abdominal pain

Hepato-biliary disorders

Hepatic function abnormal

Reversible increase in ASAT, ALAT, alkaline phosphatase and bilirubin

Skin and subcutaneous tissue disorder

Rash (including erythematous or maculo-papular)

Urticaria

Pruritus

Angioneurotic oedema

Investigations

Carnitine decreased

4.9 Overdose

There has been no experience of overdosage with Selexid^® Tablets. However, excessive doses are likely to induce nausea, vomiting and gastritis. Treatment should be restricted to symptomatic and supportive measures.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Selexid^® is an orally active antibiotic. Chemically it is the pivaloyloxymethylester of the amidinopenicillanic acid, mecillinam. On oral administration it is well absorbed and subsequently hydrolysed in the body to mecillinam, the active antibacterial agent, by non-specific esterases present in blood, gastro-intestinal mucosa and other tissues.

Selexid^® is highly active against most enterobacteriaceae, including E. coli, Klebsiella, Proteus, Enterobacter, Serratia, Salmonella, Shigella and Yersina.

Selexid^® is less active against gram positive bacteria and organisms such as Pseudomonas aeruginosa and Streptococcus faecalis are practically resistant to mecillinam.

Whilst Selexid^®, like the penicillins and cephalosporins, interferes with the biosynthesis of the bacterial cell wall, the target of the inhibition is different. This different mode of action is probably responsible for the synergistic action which has been found, both in vitro and in vivo, between Selexid^® and various penicillins and cephalosporins.

5.2 Pharmacokinetic Properties

Peak serum levels of mecillinam averaging 5 microgram/ml are reached after 1 hour following a dose of 10 mg/kg body weight in children and 400 mg in adults.

The serum half-life is 1.2 hours. The protein binding amounts to 5-10%. Approximately 50% of the administered dose is excreted as mecillinam in the urine within the first six hours. Mecillinam is partly excreted with bile, giving rise to biliary concentrations about 3 times the serum levels. Concurrent administration of probenecid delays the renal excretion of mecillinam, producing more sustained serum levels. The absorption of Selexid^® is practically unaffected by taking the tablets with food.

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Cellulose microcrystalline

Hydroxypropyl cellulose

Magnesium stearate

Hypromellose

Simethicone

Paraffin, synthetic

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Store below 25ºC in a dry place.

6.5 Nature And Contents Of Container

Aluminium/Aluminium blister packs containing 10 tablets.

6.6 Special Precautions For Disposal And Other Handling

None.

Administrative Data

7. Marketing Authorisation Holder

LEO Laboratories Limited,

Longwick Road

Princes Risborough

Bucks. HP27 9RR, UK.

8. Marketing Authorisation Number(S)

PL 0043/0048

9. Date Of First Authorisation/Renewal Of The Authorisation

20 May 1977 / 29 October 2004

10. Date Of Revision Of The Text

January 2008

LEGAL CATEGORY

POM