Canada-Approved Medicine

This monograph describes a medication approved for use in Canada by the Therapeutic Products Directorate, a division of Health Canada’s Health Products and Food Branch. The medication is not approved by the United States Food and Drug Administration; however, a similar formulation carrying a different generic or brand name might be available in the US.

• Treatment of the following infections due to penicillinase-producing staphylococci: respiratory tract infections, sinusitis, septicemia, endocarditis, osteomyelitis, skin and skin structure infections.

Contraindicated in:

• Previous hypersensitivity to penicillins (cross-sensitivity exists with cephalosporins and other beta-lactam antibiotics).

Use Cautiously in:

• Severe renal or hepatic impairment
• OB: Safety not established
• Pedi: Safety in premature and newborn infants not established.

CNS: SEIZURES.

GI: CLOSTRIDIUM DIFFICILE-ASSOCIATED DIARRHEA (CDAD), diarrhea, epigastric distress, nausea, vomiting.

GU: interstitial nephritis.

Derm: rash, urticaria.

Hemat: eosinophilia, leukopenia.

Misc: ALLERGIC REACTIONS INCLUDING ANAPHYLAXIS AND SERUM SICKNESS, superinfection.

Drug-Drug:

• May ↓ effectiveness of oral contraceptive agents.
• Probenecid↓ renal excretion and ↑ levels (therapy may be combined for this purpose).
• Neomycin may ↓ absorption.
• Concurrent use with methotrexate↓ methotrexate elimination and ↑ risk of serious toxicity.

Drug-Food:

• Food ↓ oral absorption by 50%.

• Capsules: 250 mg; 500 mg;
• Oral solution: 125 mg/5 mL;
• Powder for injection (requires reconstitution/dilution: 250 mg/vial; 500 mg/vial; 1 g/vial; 2 g/vial;

• PO (Adults): 250–500 mg every 6 hr.
• PO (Children >1 mo): 50–100 mg/kg/day divided every 6 hr up to a maximum of 4 g/day.
• IM, IV (Adults): 250–500 mg every 6 hr, maximum dose 6 g/day.
• IM, IV (Children up to 20 kg): 25–50 mg/kg/day in 4 equally divided doses every 6 hr.

• Bind to bacterial cell wall, leading to cell death. Not inactivated by penicillinase enzymes.

• Bactericidal action.

Spectrum:

• Active against most gram-positive aerobic cocci.
• Spectrum is notable for activity against:
  • Penicillinase-producing strains of Staphylococcus aureus and Staphylococcus epidermidis.
• Not active against methicillin-resistant bacteria (MRSA).

Therapeutic Classification: anti-infectives

Pharmacologic Classification: penicillinase resistant penicillins

Absorption: IV administration results in complete bioavailability. Moderately absorbed (50%) following oral administration.

Distribution: Widely distributed; penetration into CSF is minimal but sufficient in the presence of inflamed meninges; crosses the placenta and enters breast milk.

Metabolism/Excretion: Some metabolism by the liver (9–22%) and some renal excretion of unchanged drug (20 %).

Half-life: 0.5–1.1 hr (↑ in severe hepatic impairment, renal impairment, and in neonates).

• Instruct patient to take medication around the clock and to finish the drug completely as directed, even if feeling better. Missed doses should be taken as soon as remembered. Advise patient that sharing of this medication may be dangerous.
• Advise patient to report signs of superinfection (black, furry overgrowth on the tongue; vaginal itching or discharge; loose or foul-smelling stools) and allergy.
• Instruct patient to notify health care professional if fever and diarrhea develop, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional.
• Instruct patient to notify health care professional if symptoms do not improve.

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