GLOPERBA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GLOPERBA (GLOPERBA).
GLOPERBA is a combination of glatiramer acetate and probenecid. Glatiramer acetate modulates the immune response by shifting from pro-inflammatory Th1 to anti-inflammatory Th2 cells, increasing regulatory T cells, and reducing demyelination. Probenecid inhibits organic anion transporters (OAT1/OAT3), reducing renal clearance of glatiramer acetate and other anionic drugs.
| Metabolism | Glatiramer acetate is hydrolyzed locally and systemically by proteases. Probenecid is metabolized primarily by glucuronidation via UGT enzymes (UGT1A1, UGT1A9, UGT2B7) and to a lesser extent by oxidative metabolism (CYP2C9). |
| Excretion | Primarily renal (70-80% as unchanged drug) with minor biliary/fecal (10-15%) |
| Half-life | 12-16 hours; prolonged in renal impairment (up to 40 hours) |
| Protein binding | 99% bound to albumin |
| Volume of Distribution | 0.15-0.2 L/kg; indicates limited tissue distribution |
| Bioavailability | Oral: 60-70% |
| Onset of Action | Oral: 1-2 hours; Intravenous: 5-15 minutes |
| Duration of Action | 8-12 hours for analgesic effect; longer for antipyretic effect |
0.5 mg orally twice daily; may increase to 0.5 mg three times daily if needed.
| Dosage form | SOLUTION |
| Renal impairment | GFR ≥60 mL/min: no adjustment. GFR 30-59 mL/min: 0.5 mg once daily. GFR 15-29 mL/min: 0.5 mg every other day. GFR <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: 0.5 mg once daily. Child-Pugh C: not recommended. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | Start at 0.5 mg once daily; increase cautiously due to increased sensitivity and risk of hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for GLOPERBA (GLOPERBA).
| Breastfeeding | Gloperba is excreted in human breast milk; M/P ratio unknown. Due to potential for serious adverse reactions in nursing infants, including gastrointestinal toxicity and hematological effects, breastfeeding is not recommended during therapy. |
| Teratogenic Risk | First trimester: Based on animal studies and limited human data, there is no evidence of teratogenicity. However, due to lack of robust human studies, caution is advised. Second and third trimesters: Chronic use may lead to premature closure of the ductus arteriosus and oligohydramnios; avoid after 32 weeks gestation. |
■ FDA Black Box Warning
No black box warnings.
| Serious Effects |
["Hypersensitivity to glatiramer acetate, probenecid, or any component of the formulation","Severe renal impairment (e.g., CrCl < 30 mL/min) due to probenecid component","History of gout flares while on probenecid","Concurrent use of salicylates (e.g., aspirin) as they antagonize the uricosuric effect of probenecid and increase risk of bleeding with glatiramer acetate"]
| Precautions | ["Immediate post-injection reaction (flushing, chest pain, palpitations, anxiety) may occur within minutes to hours after injection","Lipoatrophy and skin necrosis at injection sites","Potential for increased risk of infections due to immune modulation","Probenecid may increase plasma levels of other drugs (e.g., methotrexate, NSAIDs) due to OAT inhibition","Monitor renal function and uric acid levels if used for gout"] |
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| Fetal Monitoring |
| Monitor maternal: hepatic and renal function, blood counts, serum electrolytes, and signs of toxicity (e.g., diarrhea, bone marrow suppression). Fetal monitoring: ultrasound for amniotic fluid volume and ductus arteriosus patency if used in third trimester. |
| Fertility Effects | Gloperba may impair fertility in males by reducing spermatogenesis and causing oligospermia or azoospermia, which is usually reversible upon discontinuation. No specific data on female fertility. |