Table 2:
Common drugs and their relation to dialysis [41–47].
| Drug | Dialyzablea | Recommended dose adjustmentb |
|---|---|---|
| Anticholinergic drugs | ||
| Antiepileptics | ||
| Carbamazepine | Controversial (dialyzable or Not) | NDA (75%–100% dose as in normal renal function + supplementary dose as in GFR <15 mL/min |
| Oxcarbazepine | Unknown | NDA + supplementary dose as for GFR <10 mL/min |
| Antiparkinsonians | ||
| Amantadine | Not dialyzable | No additional dose, dose as in GFR <15 mL/min |
| Trihexyphenidyl | Unknown | No known effects but should be used with caution |
| Anxiolytic | ||
| Hydroxyzine | Not dialyzable | NDA, supplement for IHD dose as in GFR <10 mL/min, consider risk of M(+), cetirizine |
| Antidepressants | ||
| Tricyclic | ||
| Amitriptyline | Not dialyzable | NDA, monitor ADRs, especially anticholinergic and QT interval prolonging ones, potentially due to accumulation of glucuronide metabolites |
| Amoxapine | Unknown | No dose recommendations; avoid use, due to risk of overdosage of parent and M(+) with antidopaminergic ADRs |
| Clomipramine | Not dialyzable | NDA, monitor for amitriptyline-like ADRs |
| Doxepin | Not dialyzable | NDA, monitor for amitriptyline-like ADRs |
| Imipramine | Not dialyzable | NDA, monitor for amitriptyline-like ADRs |
| Nortriptyline | Not dialyzable | As for amitriptyline |
| Trimipramine | Not dialyzable | NDA, monitor for amitriptyline-like ADR |
| SSRI | ||
| Citalopram | Not dialyzable | NDA, note high QT-prolonging potential vs lower potential SSRIs |
| Escitalopram | Not dialyzable | As for citalopram |
| Fluoxetine | Not dialyzable | NDA |
| Fluvoxamine | Not dialyzable | NDA |
| Paroxetine | Not dialyzable | NDA |
| Sertraline | Not dialyzable | NDA |
| Other serotonin and norepinephrine acting | ||
| Duloxetine (SNRI) | Not dialyzable | NDA, consider regulatory contraindication if GFR <30 mL/min |
| Mianserine (tetracyclic, NE-MM) | Not dialyzable | NDA, consider risks stemming from variable PK and ADRs from M(+) |
| Mirtazapine (tetracyclic, SN-Ran) | Unlikely to be dialyzable | NDA, based on high PB and large Vd, consider risks of ADRs from M(+) |
| Moclobemide (RIMA—SND-RevEI) | Likely to be dialyzable | Dose as in normal renal function |
| Venlafaxine (SNRI) | Not dialyzable? | NDA, consider risks stemming from variable PK ADRs from M(+) |
| Antihistaminics | ||
| Brompheniramine | Unlikely | Dose as in normal renal function, no supplementary dose required |
| Chlorpheniramine | Not dialyzable | Dose as in normal renal function, no supplementary dose required |
| Cyproheptadine | Unknown | Add 50%–100% dose supplement for IHD, consider overdosage risk |
| Diphenhydramine | Unlikely | Dose as in normal renal function, no supplementary dose required |
| Promethazine | Unlikely | Some experts recommend supplementary dose |
| Drugs related to cardiovascular system | ||
| Alverine | Unknown | Unknown |
| Atropine | Not dialyzable | No specific recommendations are available, but the need for dose adjustment is unlikely |
| Dimenhydrinate | Unknown | NDA + supplementary dose as in GFR <10 mL/min |
| Parasympatholytics | ||
| Scopolamine (hyoscine) | Unknown | Unknown |
| Urinary antispasmodics | ||
| Flavoxate | Unknown | Risk of overdosage due to renal excretion (57%) and presence of M(+), if dose is not adjusted, thus avoid use |
| Oxybutynin | Unlikely | Dose as in normal renal function, consider risk of QT prolongation and M(+) accumulation, transdermal use is less risky |
| Tolterodine | Unlikely | NDA, consider risk of QT prolongation and M(+) accumulation, not recommended use of extended formulations |
| Opioids | ||
| Buprenorphine | Yes | NDA; transdermal: dose as in normal renal function |
| Codeine | Not dialyzed | Avoid its use in ESKD and dialysis |
| Dihydrocodeine | Unknown | ND |
| Fentanyl | Not dialyzed | NDA |
| Hydrocodone | Unknown | Use alternative medicines |
| Meperidine/pethidine | Not dialyzed | NDA, risk for CNS and respiratory depression due to M(+) ADRs |
| Methadone | Poorly dialyzed | NDA |
| Hydromorphone | Unknown | NDA, metabolites may cause neuroexcitation and cognitive impairment |
| Morphine | Yes | NDA, some centres avoid use slow release preparations due to M(+) |
| Oxycodone | Unknown | NDA, limited accumulation of metabolites in renal failure compared with morphine |
| Oxymorphone | Unknown | Use alternative medicines |
| Propoxyphene | Poorly dialyzed | NDA |
| Tapentadol | Unknown | Not recommended in ESKD |
| Tramadol | Yes | NDA |
| Benzodiazepines and similar agents | ||
| Alprazolam | Not dialyzable | NDA |
| Bromazepam | Unlikely | NDA, risk of overdosage should be considered during long-term use due to several M(+) |
| Clobazam | Not dialyzable | NDA, effect is less predictable due to M(+) |
| Diazepam | Not dialyzable | NDA, effect is less predictable due to presence of several M(+)—nordazepam, oxazepam and temazepam |
| Estazolam | Not dialyzable | NDA |
| Lorazepam | Not dialyzable | NDA, caution should be exercised for repeated i.v. formulation use due to risk of propylene glycol toxicity; monitor osmol gap closely |
| Lormetazepam | Not dialyzable | NDA |
| Midazolam | Not dialyzable | NDA (oral), use with caution and monitor closely for excessive sedation; consider longer dosing intervals for intermittent dosing and slower titration of continuous infusions |
| Nitrazepam | Not dialyzable | NDA |
| Nordazepam | Unknown | Unknown |
| Oxazepam | Not dialyzable | NDA, risk of overdosage should be monitored |
| Prazepam | Not dialyzable | NDA, effect is less predictable due to presence of several M(+)—nordazepam and oxazepam |
| Z-Drugs | ||
| Zolpidem | Not dialyzable | NDA: option of dosage reductions is advised by some experts due to increased protein binding |
| Zopiclone | Controversial data | NDA, despite moderate PB (45%) |
| Psycholeptics (neuroleptics) | ||
| Aripiprazole | Unlikely | NDA, based on high PB of parent and M(+) |
| Clozapine | Not dialyzable | NDA, based on high PB and complete metabolism with limited or no activity metabolites, but consider regulatory contraindication to use in case of severe renal disorder |
| Chlorpromazine | Not dialyzable | NDA, caution should be exercised due to unknown level of M(+) |
| Levomepromazine (methotrimeprazine) | Unknown | NDA, although caution should be exercised due to unknown presence or absence of activity of metabolites |
| Loxapine | Controversial data | NDA, based on high PB and complete metabolism with limited or no activity metabolites |
| Olanzapine | Not dialyzable | NDA, based on high PB, large Vd and complete metabolism to M(–) |
| Perphenazine | Unknown | Unknown, caution should be exercised due to M(+) |
| Pimozide | Unknown | NDA, although caution should be exercised due to unknown presence or absence of M(+) and its PK |
| Quetiapine | Unlikely | NDA, based on relatively high PB (83%) and large Vd, although caution should be exercised due to M(+) and non-negligible renal elimination |
| Risperidone | Not significantly dialyzed | Oral: use with caution, doses up to 2 mg have been tolerated, i.m. or s.c.: avoid use; risk due to extensive hepatic metabolism to M(+); both risperidone and M(+) are mainly excreted by the kidney and may increase risk of ADRs (e.g. orthostatic hypotension, QT prolongation) |
| Other antipsychotics | ||
| Lithium | Dialyzable (80%) | Avoid use when possible, consider risk of lithium induced kidney damage in patients with significant residual kidney function; if necessary, initiate therapy at 300 mg 3 times weekly after dialysis; gradually titrate based on clinical response, tolerability, and serum lithium levels |
| Antibiotics | ||
| Penicillins | ||
| Amoxicillin and amoxicillin/clavulanate | Dialyzable | NDA, dose after IHD |
| Ampicillin and ampicillin/sulbactam | Dialyzable | NDA, dose after IHD |
| Benzylpenicillin | Dialyzable | NDA, dose after IHD |
| Cloxacillin | Not dialyzable | NDA |
| Oxacillin | Poorly dialyzable | Due to risk of neurotoxicity, the maximum daily dose of 8 g/day may be considered, otherwise—NDA |
| Phenoxymethylpenicillin | Dialyzable | NDA |
| Piperacillin | Dialyzable | 2 g every 8 h + 1 g after IHD |
| Piperacillin and tazobactam | Dialyzable | 2.25 g less frequently (every 8–12 h) + 0.75 g after IHD |
| Sultamicillin | Dialyzable | NDA, dose after IHD |
| Temocillin | Dialyzable | NDA, dose after IHD |
| Ticarcillin | Dialyzable | NDA, dose after IHD |
| Cephalosporines | ||
| Cefadroxil | Dialyzable | 1 g first dose; 500–1000 mg 3 times a week, or every 36 h, dose after IHD |
| Cefalexin | Dialyzable | NDA, dose after IHD |
| Cefazolin | Dialyzable | NDA, dose after IHD |
| Cefepime | Dialyzed | 1 g on day 1 followed by 0.5–1 g every 24 h, dose after IHD |
| Cefixime | Not dialyzable | NDA |
| Cefotaxime | Dialyzable | NDA, dose after IHD |
| Cefoxitin | Dialyzable | NDA, dose after IHD |
| Cefuroxime | Dialyzable | NDA, dose after IHD |
| Cefpodoxime | Dialyzable | 100–200 mg every 24 h, dose after IHD |
| Ceftazidime | Dialyzable | NDA, dose after IHD |
| Ceftazidime/avibactam | Dialyzable | 0.94 g every 24 h, dose after IHD |
| Ceftozolane/tazobactam | Dialyzable | 0.75–2.25 g loading dose, followed by 1250–450 mg every 8 h, dose after IHD |
| Ceftriaxone | Poorly dialyzable | NDA |
| Astreonam | Dialyzable | NDA, dose after IHD |
| Carbapenem | ||
| Ertapenem | Dialyzable | NDA, dose after IHD |
| Imipenem/cilastatin | Dialyzable | Due to neurotoxicity, consider alternative therapy; otherwise—NDA, dose after IHD |
| Meropenem | Dialyzable | NDA, dose after IHD |
| Fluoroquinolones | ||
| Ciprofloxacin | Minimally dialyzable (<10%) | NDA, dose after IHD |
| Levofloxacin | Dialyzable (up to 21% in HF) | NDA, dose after IHD |
| Moxifloxacin | Poorly dialyzable | NDA, dose after IHD |
| Norfloxacin | Not dialyzable | NDA, dose after IHD |
| Ofloxacin | Dialyzable | NDA, dose after IHD |
| Sulfonamides | ||
| Sulfadiazine | Dialyzable | In some countries the administration is contraindicated in case of severe renal insufficiency; if used NDA, dose after IHD |
| Sulfamethoxazole | Dialyzable | In some countries the administration is contraindicated in case of severe renal insufficiency where repeated plasma measurements cannot be performed; if used NDA, dose after IHD |
| Trimethoprim | Dialyzable | NDA, dose after IHD |
| Macrolides | ||
| Azithromycin | Not dialyzable | NDA |
| Clarithromycin | Not dialyzable | In ESKD: for IR formulation—prolong interval for the same single dose (from twice daily to once daily), for ER formulation—50% dose |
| Erythromycin | Not dialyzable | NDA, consider limiting dose to 2 g/day due to risk of ototoxicity |
| Josamycin (rovamycin) | Unlikely to be dialyzable | Consider use alternative macrolide |
| Spiramycin | Unlikely to be dialyzable | Consider use alternative macrolide |
| Roxithromycin | Unlikely to be dialyzable | Consider use alternative macrolide |
| Aminoglycosides | ||
| Amikacin | Dialyzable | I.v. (administered after IHD): 5–12.5 mg/kg/dose 3 times weekly; according to levels; postdialysis concentrations should be drawn ≥2 and up to 4 h after hemodialysis to allow for redistribution |
| Gentamicin | Dialyzable | I.v. (administered after IHD): after reduced loading dose (e.g. 2–3 mg/kg), in case of conventional dosage regimen—1 mg/kg/dose 3 times weekly; in case of consolidated dosage regimen—2–3 mg/kg/dose 3 times weekly; according to levels; postdialysis concentrations should be drawn ≥2 and up to 4 h after hemodialysis to allow for redistribution |
| Tobramycin | Dialyzable | I.v. (administered after IHD): after loading dose (e.g. 2–3 mg/kg), 1–2 mg/kg/dose 3 times weekly; according to levels; postdialysis concentrations should be drawn ≥2 and up to 4 h after hemodialysis to allow for redistribution |
| Other antibiotics | ||
| Metronidazole | Dialyzable in IHD, 10% removal in PD | Metabolized in the liver; M(+) have long half-life in renal impairment; NDA, dose after IHD |
| Vancomycin | Not dialyzable, but adsorbable in case of high-flux membrane | Oral: NDA; i.v. (administered after IHD): after normal loading dose (e.g. 25 mg/kg), in case of low-flux membrane—7.5 mg/kg after 48 h and every 48 h; in case of high-flux membrane—10 mg/kg after 48 h and every 48 h |
| Linezolid | Dialyzable | NDA, dose after dialysis |
| Polymyxins (Colistin) | Dialyzable | Increased dose: after normal loading dose (e.g. 9 MIU), 4.3 MIU per day in 2 divided doses on nondialysis days, adding 1.2 MIU after 3 h of IHD or 1.6 MIU after 4 h IHD |
| Isoniazid | Dialyzable | Dose as in normal renal function, dose after dialysis |
| Antivirals | ||
| Acyclovir | Dialyzable | NDA, dose after dialysis |
| Darunavir | Unlikely | Dose as in normal renal function |
| Famciclovir | Dialyzable | NDA, dose after dialysis |
| Foscarnet | Dialyzable | NDA, dose after dialysis |
| Ganciclovir | Dialyzable | Oral: 500 mg 3 weekly post IHD; i.v.: NDA, dose after dialysis; for IHD, the fraction of ganciclovir removed in a single dialysis session varied from 50% to 63% |
| Indinavir | Not dialyzable | Dose as in normal renal function |
| Ritonavir | Not dialyzable | Dose as in normal renal function |
| Nirmatrelvir | NA | Nirmatrelvir is contraindicated in case of severe renal impairment |
| Tenofovir | Dialyzable | Avoid use; if no alternative therapy is available—NDA, dose after dialysis |
| Valaciclovir | Dialyzable | NDA, dose after dialysis |
a
Based on intermittent haemodialysis; not dialyzable category includes limited (0% to 5%) dialyzability.
b
The dosing recommendations are based upon the dosage level of CKD 5 (not on dialysis) with CrCL <10 mL/min (if not otherwise stated), best available evidence and clinical expertise, but not considering obesity, cachexia and/or other risk factors for PK.
ER: extended release (formulation); HF: high-flux (dialyzer); ID: insufficient data; IHD: intermittent haemodialysis; i.m.: intramuscular; IR: immediate release (formulation); i.v.: intravenous; NA: not applicable; NDA: no dose adjustments in case of IHD of CKD patients, dose as in case of GFR <10 mL/min; MIU: million international units; M(+): active metabolites; M(–): inactive metabolites; NE-MM: norepinephrine multimodal; PB: protein binding; PD: peritoneal dialysis; PK: pharmacokinetic; RIMA: reversible inhibitor of monamino oxidase A; s.c.: subcutaneous; SN-Ran: serotonin, norepinephrine receptor antagonist; SND-RevEI: serotonin, norepinephrine, dopamine reversible enzyme inhibitor; SNRI: serotonin norepinephrine reuptake inhibitor; SSRI: selective serotonin reuptake inhibitor; Vd: volume of distribution.