sulopenem etzadroxil/probenecid

Sulopenem etzadroxil: Inhibits bacterial cell wall synthesis, resulting in cell death. Probenecid: Inhibits OAT3-mediated renal clearance of sulopenem, resulting in ↑ levels of sulopenem.

Therapeutic effects:

Bactericidal action against susceptible bacteria.

Spectrum:

Active against the following gram-negative organisms:
- Escherichia coli,
- Klebsiella pneumoniae,
- Proteus mirabilis.

Pharmacokinetics ⬆ ⬇

Sulopenem Etzadroxil

Absorption: 40% absorbed in fasting state; food ↑ absorption (64%).

Distribution: Well distributed to tissues.

Metabolism/Excretion: Prodrug that is hydrolyzed by esterases to the active drug, sulopenem, which then undergoes hydrolysis followed by dehydrogenation. 44% excreted in feces (27% as unchanged drug); 41% excreted in urine (3% as unchanged drug).

Half-Life: 1.2 hr.

Probenecid

Absorption: Extent of absorption unknown.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Routes of metabolism and excretion unknown.

Half-Life: 3–4 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–3 hr	12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Serious hypersensitivity to other beta-lactams (cross-sensitivity may occur);
Blood dyscrasias;
Uric acid kidney stones;
Concurrent use with ketorolac;
CCr <15 mL/min or on hemodialysis.

Use Cautiously in:

History of gout (↑ risk of nephrolithiasis);
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

GI: diarrhea, abdominal pain, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), nausea, vomiting

GU: nephrolithiasis, vulvovaginal infection

Metab: gout, hyperuricemia

Neuro: headache

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

May significantly ↑ levels and risk of toxicity of ketorolac; concurrent use contraindicated.
May ↑ levels and risk of toxicity of ketoprofen; concurrent use not recommended.
May ↑ levels and risk of toxicity of indomethacin, lorazepam, naproxen, rifampin, and sulfonylureas.
May ↑ levels and risk of toxicity of methotrexate; avoid concurrent use.
OAT3 inhibitors may ↑ levels and risk of toxicity.

Route/Dosage ⬆ ⬇

PO (Adults ): One tablet (sulopenem etzadroxil 500 mg/probenecid 500 mg) twice daily for 5 days.

Renal Impairment

PO (Adults ): CCr <15 mL/min or hemodialysis: Use not recommended.

Availability ⬆ ⬇

Tablets: sulopenem etzadroxil 500 mg/probenecid 500 mg

Assessment ⬆ ⬇

Monitor for signs/symptoms of urinary tract infection (fever, dysuria, polyuria, hematuria, flank pain, suprapubic pain or pressure).
Monitor for signs/symptoms of CDAD including watery diarrhea with mucus, fever, abdominal pain or cramping, anorexia, nausea, and in severe cases, dehydration, and blood or pus in the stool. May occur >2 mo after therapy.
Monitor for signs/symptoms of hypersensitivity reactions (rash, urticaria, pruritus, flushing, dizziness, vomiting, abdominal pain) and angioedema (swelling of throat, lips, tongue, face, dyspnea, wheezing, hoarseness). If hypersensitivity reaction occurs, discontinue sulopenem etzadroxil/probenecid and provide supportive care.

Lab Test Considerations:

May cause hyperuricemia.

Implementation ⬆ ⬇

PO: Administer twice daily with food.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects. Advise to take twice daily with food as directed. Take missed dose as soon as possible; do not double the dose. Do not share medication with others, even if they have similar symptoms; may be harmful. Advise patient to read Patient Information before starting therapy.
Inform patient of the importance of receiving the full course of therapy even if feeling better. If urinary symptoms worsen or do not resolve, another appointment should be scheduled as soon as possible for re-evaluation.
Instruct patient to notify health care professional immediately if diarrhea, abdominal cramping, fever, or bloody stools occur and not to treat with antidiarrheals without consulting health care professionals.
Advise patients and family to call 911 and seek urgent treatment for signs and symptoms of hypersensitivity reactions such as difficulty breathing, chest tightness, hives, rash, feeling lightheaded, itching, swelling of the face, lips, tongue or throat.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Rep: Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇