Selexid^® Tablets.

Pivmecillinam hydrochloride 200mg.

Tablets

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.

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.

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.

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.

The tablets must be taken with at least half a glass of water due to risk of oesophageal ulceration.

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.

Concurrent treatment with valproic acid, valproate or other medication liberating pivalic acid should be avoided due to increased risk of carnitine depletion (see section 4.4)

Pregnancy

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.

Lactation

Selexid^® can be used during breast-feeding and no effects on the infant are anticipated. However, as for other penicillins, trace quantities of mecillinam is excreted into breast milk with the possible risk of sensitisation and subsequent allergic reactions in a sensitised infant.

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

Based on pooled data from clinical studies including more than 2500 patients receiving treatment courses of Selexid^® tablets of 3-7 days duration, undesirable effects occurred in less than 10% of patients.

The most frequently reported undesirable effects are gastrointestinal disorders and various skin reactions. Upper gastrointestinal reactions occurred in 5% of the patients, diarrhoea in 2% of the patients and rash in 1% of the patients.

Anaphylactic reactions, changes in blood counts and hepatic function disorders have been reported in isolated cases.

Treatment was withdrawn in less than 1% of patients due to undesirable effects.

Undesirable effects are listed by MedDRA SOC and the individual undesirable effects are listed starting with the most frequently reported.

Very common 1/10

Common 1/100 and < 1/10

Uncommon 1/1,000 and < 1/100

Rare 1/10,000 and < 1/1,000

Very Rare < 1/10,000

Not Known (Cannot be estimated from the clinical data)

Blood and lymphatic system disorders

Not Known

Thrombocytopenia

Granulocytopenia

Leucopenia

Eosinophilia

Immune system disorders

Not Known

Anaphylactic reaction

Nervous system disorders

Uncommon

Headache

Dizziness

Vertigo

Gastrointestinal disorders

Common

Diarrhoea

Vomiting

Abdominal discomfort

Nausea

Abdominal pain

Not Known

Antibiotic associated colitis

Mouth ulceration

Oesophageal ulcer

Oesophagitis

Hepato-biliary disorders

Not known

Hepatic function abnormal

Slight reversible increase in ASAT, ALAT, alkaline phosphatase and bilirubin

Skin and subcutaneous tissue disorder

Uncommon

Rash (including erythematous, macular or maculo-papular)

Not known

Urticaria

Pruritus

Angioneurotic oedema

General disorders and administration site conditions

Uncommon

Fatigue

Investigations

Not known

Carnitine decreased

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.

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.

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.

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

Cellulose microcrystalline

Hydroxypropyl cellulose

Magnesium stearate

Hypromellose

Simethicone

Paraffin, synthetic

Not applicable.

3 years

Store below 25ºC in a dry place.

Amber glass bottles containing 2, 10 or 100 tablets or

Blister strip packs containing 2, 10 or 100 tablets or

PVC/AL blisters with polyamide-coated aluminium cover containing 10 tablets or

Aluminium/Aluminium blister packs containing 10 tablets

None.

LEO Laboratories Limited,

Longwick Road

Princes Risborough

Bucks. HP27 9RR, UK.

PL 0043/0048

Date of First Authorisation: 20 May 1977

Date of last Renewal: 29 October 2004

25 May 2011