Orlynvah

Orlynvah (probenecid and sulopenem etzadroxil) is a combination oral antibiotic used to treat uncomplicated urinary tract infections (uUTI) in adult women who have limited or no alternative antibacterial treatment options.

Orlynvah's active ingredients are sulopenem etzadroxil, a penem antibiotic, and probenecid, which increases blood concentrations of sulopenem. Sulopenem belongs to the penem class of antibacterials, which works against bacterial infections resistant to specific antibiotics.

The recommended dosage of Orlynvah is one tablet orally twice daily with food for 5 days.

Orlynvah is FDA-approved to treat adult women with an uncomplicated urinary tract infection that is:

• caused by the bacteria Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis
• in women who have limited or no alternative oral antibacterial treatment options.

Orlynvah should only be used for the treatment of uncomplicated urinary tract infections (uUTI) that are proven or strongly suspected to be caused by susceptible bacteria. When available, culture and antimicrobial susceptibility should be performed to reduce the development of drug-resistant bacteria and maintain the effectiveness of Orlynvah

Orlynvah should not be used for complicated urinary tract infections (cUTI) or as step-down treatment after intravenous antibacterial treatment of cUTI.

It should not be used for complicated intra-abdominal infections (cIAI) or as step-down treatment after intravenous antibacterial treatment of cIAI.

Orlynvah contains two active ingredients: sulopenem etzadroxil and Probenecid.

• Sulopenem etzadroxil is converted into sulopenem, the active antibacterial that targets bacteria.
• Probenecid reduces kidney clearance, increasing blood concentrations of sulopenem, making it more effective at improving the uUTI.

Uncomplicated urinary tract infections are infections of the bladder or lower urinary tract that occur in women without any structural abnormality of the urinary tract and no other health issues such as diabetes, an immunocompromised state, recent urologic surgery, or pregnancy.

Symptoms of an uUTI are increased urinary frequency, urgency, suprapubic discomfort, and painful urination.

Complicated UTI are any urinary tract infection in males, patients that are immunocompromised, pregnant patients, and patients with fevers, stones, sepsis, urinary obstruction, catheters, or infection that involves the kidneys.

Orlynvah tablets are taken twice daily, with food. Complete the full course to reduce the risk of antibacterial resistance.

Hypersensitivity Reactions: Hypersensitivity reactions have been reported in patients treated with Orlynvah. Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, have been reported with beta-lactam antibacterial drugs. Severe allergic reactions and anaphylaxis have been reported with the use of probenecid (an active ingredient in this medicine). If an allergic reaction occurs, discontinue the drug and immediately start appropriate therapy.

Clostridioides difficile-Associated Diarrhea (CDAD): Advise patients that diarrhea is a common problem caused by antibacterial drugs, including this medicine, and usually resolves when the drug is discontinued. Sometimes, frequent watery or bloody diarrhea may occur, which may be a sign of a more serious intestinal infection. If severe watery or bloody diarrhea develops, patients should contact their healthcare provider.

Exacerbation of Gout: Probenecid (an active ingredient in this medicine) may cause gout flare-up in patients with a known history of gout. These patients should have appropriate gout therapy started.

Also, see the side effects section.

You should not take Orlynvah if you have:

• a history of hypersensitivity to the components of Orlynvah (sulopenem etzadroxil and probenecid) or other beta-lactam antibacterial drugs
• known blood dyscrasias.
• uric acid kidney stones.

You should not take Orlynvah if you are taking ketorolac tromethamine.

Using Orlynvah with ketoprofen is not recommended.

Tell your doctor if you have a history of:

• allergy to Orlynvah, its active ingredients sulopenem etzadroxil and probenecid, other beta-lactam antibacterial medicines, or any inactive ingredients in this medicine.
• gout
• uric acid kidney stones
• known blood dyscrasias

Pregnancy and breastfeeding

Tell your healthcare provider if you are planning a pregnancy, pregnant, or breastfeeding so that you and your healthcare provider can make an informed decision on your treatment options.

Common Orlynvah side effects

Common Orlynvah side effects are diarrhea (10%), nausea (4%), vulvovaginal fungal infection (2%), headache (2%), and vomiting (2%). These side effects occurred in 2% or more of patients in clinical trials.

Serious side effects

Get emergency medical help if you have signs of an allergic reaction: hives, difficult breathing, swelling of your face, lips, tongue, or throat.

Orlynvah may cause other serious side effects. Call your doctor at once if you have:

• severe stomach pain, diarrhea that is watery or bloody (even if it occurs months after your last dose);
• worsening gout symptoms; or
• signs of a kidney stone - pain in your side or lower back, blood in your urine, painful or difficult urination.

Also, see the Warnings section.

The recommended Orlynvah dose is one tablet (500 mg sulopenem etzadroxil and 500 mg probenecid) twice daily.

Dose in renal impairment. Orlynvah is not recommended in patients with creatinine clearance (CrCL) less than 15 mL/min or patients on hemodialysis. No dosage adjustment is required for patients with CrCL greater than or equal to15 mL/min.

If a dose is missed, take the dose as soon as possible. Do not double the dose to make up for the missed dose.

Other drugs may interact with Orlynvah, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

• Taking Orlynvah with ketoprofen is not recommended.
• Do not take Orlynvah with ketorolac tromethamine.
• Probenecid (one of the active ingredients in this medicine) is an inhibitor of organic anion transporters 1 and 3 (OAT1/3) and may increase plasma concentrations of drugs that are dependent on OAT1/3 for elimination.
• Sulopenem is a substrate of OAT3 so drugs that inhibit OAT3 may increase sulopenem plasma concentrations. If using Orylnvah with a drug that inhibits OAT3 is necessary, monitor more frequently for adverse reactions associated with Orlynvah (e.g., diarrhea and nausea).

Store tablets at 20°C to 25°C (68°F to 77°F). Excursions permitted to 15°C to 30°C (59°F to 86°F).

Active ingredients: sulopenem etzadroxil 500 mg and probenecid 500 mg

Inactive tablet ingredients: croscarmellose sodium, hydroxypropylcellulose, lactose monohydrate, magnesium stearate, and microcrystalline cellulose.

Film coating ingredients: carmine, lecithin polyvinyl alcohol, talc, titanium dioxide, and xanthan gum.

Orlynvah manufacturer Iterum Therapeutics U.S. Limited, Chicago, IL 60606 US.