Review Article

Clinical Pharmacology in Old Persons

Table 9

Adjustment of dosage in renal insufficiency. Calculate the creatinine clearance or GFR (http://nephron.com/cgi-bin/CGSI.cgi). For Crcl < 10 mL/min consult the nephrologist.

Decreased renal function and dose adjustment

ACE Inhibitors
 BenazeprilClcr 10–30 mL/min: start with 2.5–5 mg once daily. Adjust dosage based on effect.
 CaptoprilClcr 10–30 mL/min: start with 12.5–25 mg once daily. Adjust dosage based on effect until 75–100 mg/day
 CilazaprilClcr 10–30 mL/min: start with max. 0.5 mg/day. Adjust dosage based on effect until max. 2.5 mg/day
 EnalaprilClcr 10–30 mL/min: start with max. 5 mg/day. Adjust dosage based on effect until max. 10 mg/day
 LisinoprilClcr 10–30 mL/min: start with max. 5 mg/day. Adjust dosage based on effect until max. 40 mg/day
 PerindoprilClcr 30–50 mL/min: max. 2 mg/day; Clcr 10–30 mL/min: max. 2 mg every two days
 QuinaprilClcr 30–50 mL/min: start with 5 mg/day; Clcr 10–30 mL/min: start with 2.5 mg/day. Adjust dosage based on effect.
 RamiprilClcr 20–50 mL/min: start with max. 1.25 mg/day. Adjust dosage based on effect.
Clcr 10–20 mL/min: insufficient data for sound advise
 TrandolaprilClcr 10–30 mL/min: start with max. 0.5 mg/day. Adjust dosage based on effect until max. 2 mg/day
 ZofenoprilClcr 10–50 mL/min: start with max. 7.5 mg/day. Adjust dosage based on effect until max. 15 mg/day

Antibiotics
 Cephalosporins
  CephalexinClcr 10–50 mL/min: prolong interval to once per every 12 hours.
  CephalothinClcr 50–80 mL/min 2 g every 6 hours; 30–50 mL/min 1.5 g every 6 hours; 10–30 mL/min 1 g every 8 hours.
  CephamandoleClcr 50–80 mL/min 2 g every 6 hours, in case of life-threatening infection 1.5 g every 4 hours;
Clcr 30–50 mL/min 2 g every 8 hours, in case of life-threatening infection 1.5 g every 6 hours;
Clcr 10–30 mL/min 1.25 g every 6 hours, in case of life-threatening infection 1 g every 6 hours.
  CephazolinClcr 30–50 mL/min: 500 mg every 12 hours; 10–30 mL/min: 500 mg every 24 hours.
  CephradineClcr <30 mL/min: contra-indicated
  CephtazidimeClcr 30–50 mL/min: 1 g every 12 hours; 10–30 mL min: 1 g every 24 hours.
  CephtibutenClcr 30–50 mL/min: 200 mg every 24 hours; 10–30 mL/min: 100 mg every 24 hours.
  Cephuroxime parenteralClcr 10–30 mL/min: standard dosage every 12 hours.

 Fluoroquinolones
  CiprofloxacinClcr 10–30 mL/min: 50% of normal dosage
  Levofloxacin; ofloxacinClcr 30–50 mL/min: 50% of normal dosage; Clcr 10–30 mL/min: 25% of normal dosage
  NorfloxacinClcr 10–30 mL/min: prolong interval to once every 24 hours

 Nitrofurantoin
  NitrofurantoinClcr < 50: contra-indicated. Risk of neuropathy and failure of therapy.

 Macrolide
  ClaritromycinClcr 10–30 mL/min: 50% of normal dosage with normal dose frequency

 Penicillins
  Amoxicillin/clavulanateClcr 10–30 mL/min: standard dosage every 12 hours (orally, i.v. of.im.)
  BenzylpenicillinClcr 10–30 mL/min: dosage dependent of indication. Consider intended effect, risks of overdosage and underdosage.
  PiperacillinClcr 30–50 mL/min: max. 12 g per day in 3 or 4 doses; Clcr 10–30 mL/min: max. 8 g per day in 2 doses
  Piperacillin/tazobactamClcr 30–50 mL/min: piperacillin/tazobactam 12 g/1.5 g per day in 3 or 4 doses
Clcr 10–30 mL/min: piperacillin 4 g/0.5 g every 12 hours

 Tetracyclines
  TetracyclineClcr 10–30 mL/min: maintenance dosage 250 mg once daily

Antidiabetics
 MetforminClcr 30–50 mL/min: start with twice daily 500 mg; Clcr 10–<30 mL/min: contraindicated
 Sulfonylurea (e.g., Tolbutamide)Clcr < 50 mL/min start with half the dosage

Antihistaminics
 AcrivastineClcr 10–50 mL/min: 50% of normal dosage OR prolong interval to 1-2x per day
 Cetirizine/Levocetirizine/Hydroxyzine/
  Fexofenadine/Terfenadine
Clcr 10–50 mL/min: 50% of normal dosage

Antimycotics
 FluconazoleIn case of >once daily dosing regimen: Clcr 10–50 mL/min: normal starting dosage, decrease maintenance dosage until 50% of normal dosage
 FlucytosineClcr 30–50 mL/min: prolong interval to once every 12 hours, then based on serum plasma concentration
Clcr 10–30 mL/min: prolong interval to once every 24 hours, then based on serum plasma concentration
 TerbinafineClcr 10–50 mL/min: 50% of normal dosage

Antiparkinson drugs
 PramipexoleClcr 30–50 mL/min: start with 0.125 mg (= 0.088 base) twice daily, then based on effect/adverse events
Clcr 10–30 mL/min: start with 0.125 mg (= 0.088 base) once daily, then based on effect/adverse events

Antithrombotics
 DabigatranClcr <30 mL/min: contra-indicated
 Eptifibatide Clcr 10–50 mL/min: normal starting dosage, then 50% of normal dosage
 TirofibanClcr 10–30 mL/min: 50% of normal dosage

Antiviral medication
 Acyclovir orallyDecrease dosage used for herpes zoster treatment: Clcr 10–30 mL/min: 800 mg 3 times a day
 AmantadineStart with 200 mg, maintenance dosage: Clcr 50–80 mL/min: 100 mg once daily;
Clcr 30–50 mL/min: 100 mg every 2 days; Clcr 10–30 mL/min 100 mg every 3 days.
 CidofovirClcr <50 mL/min: preferably do not use
 FamciclovirClcr 30–50 mL/min: normal dosage every 24 hours; 10–30 mL/min: 50% of normal dosage every 24 hours
 FoscarnetClcr 30–80 mL/min: dosage according to schedule manufacturer; <30 mL/min: do not use
 GanciclovirInduction: Clcr 50–80 mL/min: 50% of normal dosage every 12 hours; 30–50 mL/min: 50% of normal dosage every 24 hours; 10–30 mL/min: 25% of normal dosage every 24 hours
Maintenance: Clcr 50–80 mL/min: 50% of normal dosage every 24 hours; 30–50 mL/min: 25% of normal dosage every 24 hours; 10–30 mL/min: 12.5% of normal dosage every 24 hours
 OseltamivirClcr 10–30 mL/min: 50% of normal dosage OR normal dosage but double interval
 RibavirinClcr 10–50 mL/min: dosage based on hemoglobin concentration
 ValaciclovirClcr 10–80 mL/min: adjust dosage according to schedule manufacturer
 ValganciclovirClcr 30–50 mL/min: 50% of normal dosage plus double interval
Clcr 10–30 mL/min: 50% of normal dosage twice a week

Beta-receptor-blocking drugs
 Acebutolol; AtenololClcr 10–30 mL/min: 50% of normal dosage
 BisoprololClcr 10–20 mL/min: start with 50% of normal dosage. Then max. 10 mg/day
 SotalolClcr 30–50 mL/min: max 160 mg/day; Clcr 10–30 mL/min: max. 80 mg/day

Calcium antagonists, dihydropyridine type
 BarnidipineClcr <50 mL/min: contraindicated

Digoxin
 DigoxinClcr 10–50 mL/min: decrease initial dosage by 50%, then go to 0.125 mg/day. Next adjust dosage based on clinical symptoms

DMARDs
 AnakinraClcr < 30 mL/min: contraindicated
 MethotrexateClcr 40–70 mL/min: 50% of normal dosage. Clcr < 40 mL/min: based on serum plasma concentration

Gout medication
 AllopurinolClcr 50–80 mL/min: 300 mg/day; 30–50 mL/min: 200 mg/day; 10–30 mL/min: 100 mg/day
 BenzbromaroneClcr <30 mL/min: contraindicated
 ColchicineClcr 10–50 mL/min: 0.5 mg/day

H2-antagonists
 Nizatidine; cimetidine; famotidine;  ranitidineClcr 10–30 mL/min: 50% of normal dosage, once daily

Hypnotics, sedative agents, anxiolytic drugs, Antipsychotics
 ChloralhydrateClcr <50 mL/min: preferably do not use
 MeprobamateClcr 10–50 mL/min: 50% of normal dosage OR double dosage interval
 RisperidoneClcr 10–50 mL/min: 50% of normal dosage, then based on effect and adverse events

Muscle relaxants
 BaclofenClcr 10–50 mL/min: start with 5 mg once daily, then adjust based on effect and adverse events.
 TizanidineClcr 10–30 mL/min: start with 2 mg once daily, then increase dosage slowly based on effect and adverse events. End with increasing the dose frequency.
 NSAIDsAll NSAID’s: Clcr < 30 mL/min: consider if chronic use is indicated. Check renal function previously to and 1 week after start

OPIOIDs
 MorphineClcr 10–50 mL/min: dosage based on effect and adverse events. Be alert to accumulation of M6G
 TramadolClcr 10–30 mL/min: decrease dose frequency to 2-3 x per day
In case of retard tablet max. 200 mg per day

Tuberculostatics
 EthambutolClcr 10–50 mL/min: 50% of normal dosage

Vertigo medication
 PiracetamClcr 30–50 mL/min: 50% of normal dosage; Clcr 10–30 mL/min: 25% of normal dosage

Xanthine derivates
 PentoxifyllineClcr 30–50 mL/min: 400 mg twice daily; Clcr 10–30 mL/min: 400 mg once daily