Table 2.
Summary of reports of overexposure in immunosuppressant due to a drug-drug interaction with nirmatrelvir/ritonavir (Paxlovid®) recorded in the French Pharmacovigilance database over the period from 01/20/2022 to 12/03/2022.
| Patient number | Sex | Age group | Seriousness? (Y/N) | Drug (speciality) | IS current daily dose (mg) | Posology adaptation? (Y/N) | ADRs related to the DDI | Paxlovid® duration (days) | Overdosage discovery time since initiation (D) | Main clinical context |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | F | 50–60 | Y | Tacrolimus (Advagraf®) | 12 mg | Yes | Acute renal insufficiency (+ hyperkalemia + metabolic acidosis) | 5 | 6 | Liver transplantation on alcoholic hepatitis Hypertension Psoriasis IgA mesangial deposition nephropathy Chronic kidney disease |
| 2 | F | 30–40 | N | Tacrolimus (Advagraf®) | ND | Yes | None | 5 | 8 | Lupus nephritis Kidney transplant |
| 3 | M | 60–70 | N | Tacrolimus (Envarsus®) | 2.75 mg | Yes | None | 5 | 7 | Organ transplant (no other details) |
| 4 | F | 50–60 | N | Tacrolimus (Advagraf®) | 3 mg | Y | Acute renal insufficiency + encephalopathy (tremor + +) | 4 | 7 | Organ transplant (no other details) |
| 5 | F | 40–50 | Y | Tacrolimus (Prograf®) | 9 mg | Y | None | 5 | 8 | Heporenal polykystosis with preemptive graft Hypertension Nephritic colic |
| 6 | F | 30–40 | Y | Ciclosporin (Neoral®)/prednison | 270 mg | Y | None (suspected hyperglycemia) | 5 | 3 | COVID-19 Organ transplant (no other details) Cystic fibrosis Renal insufficiency Diabetes |
| 7 | M | 50–60 | Y | Tacrolimus (Advagraf®) | 3.5 mg | Y | Acute renal insufficiency | 6 | 9 | Liver transplantation for primary sclerosing cholangitis Benign prostatic hyperplasia |
| 8 | F | 60–70 | N | Tacrolimus (Adoport®) | 5 mg | N | None | 5 | 3 | Organ transplant (no other details) |
| 9 | M | 40–50 | Y | Tacrolimus (ND) | 4 mg | ND | Acute renal insufficiency | 5 | 10 | Organ transplant (no other details) |
| 10 | M | 60–70 | Y | Ciclosporin (Neoral®) | 240 mg | ND | Encephalopathy (coma) | 3 | 5 | Organ transplant (no other details) |
| 11 | M | 30–40 | Y | Tacrolimus (Envarsus®) | 2 mg | Y | None | 5 | 10 | Autoimmune hepatitis Cirrhosis IgG4-related sclerosing disease Ulcerative colitis |
| 12 | F | 60–70 | Y | Tacrolimus (Advagraf®) | ND | ND | Vomiting Diarrhea Lethargy Weight loss |
1 | 6 | COVID-19 Liver transplantation |
| 13 | M | 50–60 | N | Tacrolimus (Advagraf®) | 8 mg | ND | None | 5 | 11 | Kidney transplant |
| 14 | M | 10–20 | Y | Tacrolimus (Prograf®) | 12 mg | Y | Acute renal insufficiency (aggraved) | 5 | 1 | Kidney transplant |
| 15 | F | 40–50 | Y | Tacrolimus (Advagraf®) | 9 mg | Y | Acute renal insufficiency | 2 | 2 | Kidney transplant |
| Pravastatine | 10 mg | Yes (but not applicated by the patient) | Rhabdomyolysis | – | – | |||||
| 16 | F | 30–40 | Y | Tacrolimus (ND) | 15 mg | Yes (but not applicated by the patient) | Acute renal insufficiency | 4 | 2 | Kidney transplant |
ADR: adverse drug reaction; COVID-19: coronavirus disease 2019; D: day; F: female; N: no; Y: yes.