Pivmecillinam

Pivmecillinam is a prescription medication indicated for the treatment of female adults with uncomplicated urinary tract infections (UTIs) caused by susceptible isolates of Escherichia coli, Proteus mirabilis, and Staphylococcus saprophyticus.

• Pivmecillinam is available under the following different brand names: Pivya.

Common side effects of Pivmecillinam include:

• nausea 
• diarrhea

Serious side effects of Pivmecillinam include:

• hypersensitivity reactions

Rare side effects of Pivmecillinam include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 185 mg

Urinary Tract Infection

Adult dosage

• 185 mg orally three times a day for 3-7 days as clinically indicated

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Pivmecillinam has severe interactions with no other drugs
• Pivmecillinam has serious interactions with the following drugs:
  • BCG vaccine live
  • demeclocycline
  • doxycycline
  • minocycline
  • mycophenolate
  • oxytetracycline
  • probenecid
  • tetracycline
  • typhoid vaccine live
• Pivmecillinam has moderate interactions with at least 83 other drugs
• Pivmecillinam has minor interactions with the following drugs:
  • azithromycin
  • aztreonam
  • balsalazide
  • biotin
  • clarithromycin
  • colestipol
  • erythromycin base
  • erythromycin ethylsuccinate
  • erythromycin lactobionate
  • erythromycin stearate
  • niacin
  • pantothenic acid
  • pyridoxine
  • pyridoxine (Antidote)
  • roxithromycin
  • thiamine

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• History of serious hypersensitivity (eg, anaphylaxis, Stevens-Johnson syndrome) to Pivmecillinam or another beta-lactam antibiotic (eg, penicillins, cephalosporins)
• Primary or secondary carnitine deficiency resulting from inherited disorders of mitochondrial fatty acid oxidation and carnitine metabolism, and other inborn errors of metabolism (eg, methylmalonic aciduria, or propionic acidemia)
• Acute porphyria

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Pivmecillinam?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Pivmecillinam?”

Cautions

• Hypersensitivity reactions
  • Serious hypersensitivity reactions (anaphylaxis) reported
  • It is more likely to occur in individuals with a history of penicillin, cephalosporin, or carbapenem hypersensitivity or a history of sensitivity to multiple allergens
  • Before initiating, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, carbapenems, and other beta-lactams owing to possible cross-hypersensitivity
  • Pivmecillinam is contraindicated in patients who have experienced a serious hypersensitivity reaction
  • If an allergic reaction occurs, discontinue and institute appropriate therapy
• Severe cutaneous adverse reactions
  • Severe cutaneous adverse reactions (SCAR) including acute generalized exanthematous pustulosis (AGEP), drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) reported
  • Monitor closely and discontinue at first signs or symptoms of SCAR or other signs of hypersensitivity
• Carnitine depletion
  • Clinical manifestations of carnitine depletion may occur with pivalate-containing compounds, including Pivmecillinam
  • Symptoms include hypoglycemia, muscle aches, fatigue, and confusion
  • Pivmecillinam is contraindicated in patients with primary or secondary carnitine deficiency due to inherited metabolic disorders known to cause carnitine depletion
  • No clinical effects of decreased carnitine have been associated with the short-term treatment of Pivmecillinam
  • Clinically significant hypocarnitinemia has been observed in patients receiving long-term treatment with Pivmecillinam
  • Pivmecillinam is not recommended when prolonged antibacterial treatment is necessary
  • Effects on carnitine concentrations of repeated short-term courses are not known
  • Consider alternative antibacterial therapies in patients at risk for reductions in serum carnitine (eg, significant renal impairment or decreased muscle mass)
  • Avoid concurrent treatment with valproic acid, valproate, or other pivalate-generating drugs due to increased risk of carnitine depletion
• Acute porphyria
  • Contraindicated in patients suffering from porphyria as Pivmecillinam has been associated with acute attacks of porphyria
  • These episodes may be life-threatening and include symptoms and signs such as anxiety, confusion, limb or abdominal pain, hyponatremia, seizures, and muscle weakness
• Clostridioides difficile-associated diarrhea
  • C difficile-associated diarrhea (CDAD) reported for nearly all systemic antibacterial agents, including Pivmecillinam
  • CDAD may range in severity from mild diarrhea to fatal colitis
  • Treatment with antibacterial agents alters normal flora of the colon and may permit overgrowth of C difficile
  • If CDAD is suspected or confirmed, consider discontinuing antibacterial drugs not directed against C difficile; manage fluid and electrolyte levels as appropriate, supplement protein intake, monitor antibacterial treatment of C difficile, and institute surgical evaluation as clinically indicated
  • CDAD must be considered in all patients who present with diarrhea following antibacterial use; CDAD may occur 2 months after administering therapy
• Development of drug-resistant bacteria
  • Prescribing in the absence of a proven or strongly suspected bacterial infection or for prophylaxis is unlikely to provide patient benefit and increases risk of developing drug-resistant bacteria
  • Interference with a newborn screening test
  • Use in pregnant women before delivery may cause a false positive test for isovaleric acidemia in the newborn as part of newborn screening
  • Promptly follow up on a positive newborn screening result for isovaleric acidemia
• Drug interaction overview
  • Other pivalate-generating drugs
  • Avoid
    • Avoid concurrent treatment with valproic acid, valproate, or other pivalate-generating drugs due to increased risk of carnitine depletion
    • If coadministration is unavoidable, counsel patients to monitor adverse reactions associated with carnitine depletion (eg, hypoglycemia, muscle aches, fatigue, confusion)
  • Methotrexate
    • Avoid
      • When possible, consider alternative therapy
      • Penicillins decrease methotrexate clearance
  • OAT1/3 inhibitors
    • Monitor
      • Mean mecillinam peak plasma concentration increased by approximately 80% and AUC by approximately 40% following coadministration of oral probenecid (OAT1/3 inhibitor)

Pregnancy and Lactation

• Published observational studies of use during the first trimester do not indicate an increased risk of major birth defects
• There are limited studies regarding use during pregnancy that evaluate the risk of miscarriage and other adverse maternal or fetal outcomes; these studies have methodological limitations hindering the interpretation
• Clinical considerations
  • Interference with newborn screen test: Treatment of pregnant women before delivery may cause a false positive test for isovaleric acidemia
  • Dose adjustments during pregnancy and postpartum: No dosage adjustments required
• Lactation
  • Data are insufficient to exclude the presence of mecillinam in human milk
  • Mecillinam is present in animal milk; when a drug is present in animal milk, it is likely to be present in human milk
  • There are pharmacovigilance reports of adverse reactions with mecillinam exposure in breastfed infants, including rash and diarrhea
  • There are no data on the effects of mecillinam on milk production
  • Consider developmental and health benefits of breastfeeding along with the mother`s clinical need for therapy and potential adverse effects on breastfeeding the child from therapy or underlying maternal condition