Ampicillin / sulbactam (Unasyn)

How Medicare covers it

Usual path Part B (injections and infusions given by a clinician — J0295, see the Part B basis in this package). The Part D aggregation in this package is carried exactly as computed. Part A during a covered inpatient stay.

What it treats

Treats infections caused by susceptible bacteria: skin and skin-structure infections, intra-abdominal (belly) infections, and gynecological infections (Unasyn label). It should be used only for infections proven or strongly suspected to be bacterial, to limit drug-resistant bacteria.

What it is for, in depth

Ampicillin-sulbactam is a combination antibiotic used to treat serious bacterial infections. It pairs ampicillin with sulbactam, which protects ampicillin from bacteria that would otherwise break it down. The label lists infections caused by susceptible bacteria: skin and skin-structure infections, intra-abdominal infections, meaning infections inside the belly, and gynecological infections. It should be used only for infections proven or strongly suspected to be bacterial, to help limit drug-resistant bacteria. It is not a pill taken at home. A clinician gives it as an IV infusion or as a deep injection into a muscle, usually every 6 hours, in a clinic or hospital. It comes as an injectable solution and as injections of 1000 mg ampicillin with 500 mg sulbactam, and 2000 mg ampicillin with 1000 mg sulbactam.

How it works

Ampicillin is a penicillin-family antibiotic that kills bacteria by blocking cell-wall building. Many bacteria resist ampicillin by making beta-lactamase enzymes that destroy it; sulbactam blocks those enzymes, which restores ampicillin's activity against them.

How it is taken

Given by a clinician as an IV infusion or deep intramuscular injection, usually every 6 hours. The usual adult dose is 1.5 g (1 g ampicillin plus 0.5 g sulbactam) to 3 g (2 g ampicillin plus 1 g sulbactam) every 6 hours, with lower and less frequent doses in kidney impairment. It is a hospital/clinic drug and is not taken at home by mouth.

Common side effects

Pain at the injection site (especially after intramuscular injection), diarrhea, nausea, vomiting, rash, itching, and headache. Mild temporary rises in liver enzymes occur in some patients.

Serious warnings

Serious and occasionally fatal allergic reactions (anaphylaxis) can occur, including in people with penicillin or cephalosporin allergy, and severe skin reactions such as Stevens-Johnson syndrome and DRESS have been reported — stop the drug and seek care if a rash progresses. Clostridioides difficile diarrhea can occur during or after treatment and can be severe. Other serious risks include seizures at high doses (mainly in kidney impairment), liver injury including cholestatic hepatitis, blood cell problems, and superinfection with resistant organisms during prolonged use.

Who should be careful

Do not use it after a serious allergic reaction to ampicillin, sulbactam, or any beta-lactam antibiotic (penicillins and cephalosporins) — tell the care team about any drug allergy before the first dose. People with kidney impairment need dose adjustment, people with liver problems need monitoring, and people with infectious mononucleosis often develop a rash on ampicillin. Safety data in pregnancy and breastfeeding are limited, so risks and benefits need discussion.

Major interactions

Probenecid slows the kidney removal of ampicillin and sulbactam and raises their blood levels, so the combination is not recommended. Bacteriostatic antibiotics such as tetracyclines can interfere with penicillin killing. Ampicillin can raise rash risk when taken with allopurinol, can reduce the effect of oral contraceptives in rare reports on the label, and can cause false-positive urine glucose tests with copper-based test methods.

Why it is in its tier

Ampicillin-sulbactam is most often placed on Tier 4. In Medicare Part D, Tier 1 is the lowest-cost tier, often $0-$15, and each higher tier usually means a higher copay or coinsurance. Tier 5, the specialty tier, carries the highest percentage coinsurance, so Tier 4 sits toward the higher-cost end. In the CMS formulary data, 5495 plans list this drug, a listing share of 100.0%. Of those listing plans, 77.31% place it on Tier 4, a clear majority, and the tier counts show 4248 plans at that tier. What is visible in the data is a generic combination antibiotic given by injection or IV infusion, with a higher cost level than a basic pill: the CMS dashboard average spending was $663.62942623 per beneficiary in 2024. That is a CMS program average, not a patient's copay.

Sources

• UNASYN- ampicillin sodium and sulbactam sodium injection, powder, for solution — DailyMed
• MedlinePlus — Ampicillin and Sulbactam Injection

What official patient guides say

Ampicillin and sulbactam injection, as described on this MedlinePlus page, comes as a powder to be mixed with liquid and injected into a vein or into a muscle every 6 hours, 4 times daily. The length of treatment depends on the type of infection you have, and your doctor will tell you how long to use it. You may receive it in a hospital, or you may use it at home; if you will be using it at home, your healthcare provider will show you how to use the medication. You should begin to feel better during the first few days of treatment; if your symptoms do not improve or get worse, call your doctor, and tell your doctor if you still have symptoms of infection after you finish. Use it until you finish the prescription, even if you feel better: the page warns that stopping too soon or skipping doses may leave the infection incompletely treated and allow the bacteria to become resistant to antibiotics, and it gives no separate take-when-you-remember missed-dose rule. For storage, your healthcare provider will tell you how to store your medication, so store it only as directed and make sure you understand how to store it properly. Keep all medication out of the sight and reach of children, and dispose of unneeded medication through a medicine take-back program rather than flushing it.

Source: MedlinePlus — Ampicillin and Sulbactam Injection

Part D formulary coverage

Source: CMS Prescription Drug Plan Formulary, Pharmacy Network, and Pricing Information Files — Monthly file 2026-10-15 (plan year 2027), file 2027_20261008.zip (data.cms.gov dataset ed1496ea-23e7-41f1-9292-172fa842ccfb): basic drugs formulary file + plan information file, both dated 20261031 inside the zip; downloaded and aggregated 2026-10-30. Medication RxCUI sets resolved through the NLM RxNav (RxNorm) API.

What you pay

A tier is not a price; what you pay depends on your plan, pharmacy, and benefit stage; Extra Help or Medicaid can lower it further.

Sources: CMS Plan Benefit Package + formulary data; CMS NADAC · Checked 2026-11-07

Coverage by plan and tier

Of the 5,495 Medicare drug plans we track for 2027, 5,495 list Ampicillin / sulbactam (Unasyn) — 100% of plans. Most of those plans put it on Tier 4: 4,248 plans, 77.3% of the plans that list it. Other plans place it on Tier 2 (581 plans), Tier 1 (365 plans) or Tier 3 (278 plans). For example: Aetna Medicare Dual Extra (HMO D-SNP) puts it on Tier 4; Aetna Medicare Dual Extra Care (PPO D-SNP) puts it on Tier 4; Aetna Medicare Value Plus (PPO) puts it on Tier 4. You can compare these plans side by side on our Medicare Advantage hub. A tier is not a price. What you pay also depends on whether you have met your plan';s deductible, whether the drug costs a flat copay or a share of the price, and whether you get Extra Help or Medicaid.

Read next

• Part D in 2027: The $700 Deductible, the $2,400 Cap, and the $35 Insulin Rule
• Extra Help in 2027: Lower Drug Copays and Who Qualifies
• Checking Medicare Savings Programs and Extra Help

Part D spending averages (2024)

Source: CMS Medicare Part D Spending by Drug (Drug Spending Dashboard), release RY26 P04 V10, data through 2024 (DSD_PTD_RY26_P04_V10_DY24_BGM.csv), downloaded 2026-10-30

Companies covering this drug

Part D and Medicare Advantage plan sponsors that list this drug on a formulary, 50 at a time.