07_drug_g

Gabapentin
Important drug interactions
Clinical use
Anti-epileptic – adjunctive treatment of partial • Antidepressants: antagonism of anticonvulsive seizures with or without secondary generalisation Administration
Dose in normal renal function
300 mg on day 1, 300 mg twice daily on day 2, 300 mg three times daily on day 3, then increasedaccording to response to 1.2 g daily (in three divided doses). If necessary may be further increased in steps of 300 mg daily to a maximum2.4 g daily. Usual range 0.9–1.2 g daily; maximum period between doses should not exceed 12 Neuropathic pain: loaded as above but maximum1.8 g daily Pharmacokinetics
Other information
• Can cause false positive readings with some • In patients with moderate to severe renal impairment, start with the lowest possible dose and titrate upwards according to response Dose in renal impairment
GFR (mL/min)
Dose in patients undergoing
renal replacement therapies
Probably dialysed. Dose as in GFR < 15 mL/min Dialysed. Loading dose of300–400 mg in patients who havenever received gabapentin.
Maintenance dose of 200–300 mgafter each HD session Dialysed. Dose as in GFR = 15–30 mL/min Ganciclovir
Important drug interactions
Clinical use
• Increased risk of myelosuppression with other • IV: treatment of life- or sight-threatening • Profound myelosuppression with zidovudine cytomegalovirus (CMV) in immunocompromised • Generalised seizures reported with imipenem- immunosuppressed patients secondary to organtransplantation Administration
• Oral: maintenance treatment of CMV retinitis in AIDS patients (licensed), prophylaxis and • Reconstitute 1 vial (500 mg) with 10 mL water immunosuppressed patients (unlicensed use) Dose in normal renal function
• Then transfer dose to 100 mL sodium chloride 0.9% • IV peripherally in fast-flowing vein or centrally – Induction/Treatment of active CMV disease: Maintenance for CMV retinitis: 6 mg/kg per day for 5 days per week or 5 mg/kg per day 7 days per week Prevention of CMV retinitis: as per treatment • May give 50% dose over 15 minutes after HD in Maintenance for CMV retinitis, or prophylaxis inimmunosuppressed patients: 1000 mg three times Other information
Pharmacokinetics
Creatinine clearance Dose
(mL/min)
1.25mg/kg 24-hourly,given after haemodialysis Dose in renal impairment
GFR (mL/min)
Creatinine clearance Dose
(mL/min)
Dose in patients undergoing
renal replacement therapies
• Monitor patient for myelosuppression, particularly in patients receiving prophylactic • Pre-dialysis therapeutic blood levels in range given post dialysis on dialysis days.
• Not to be infused in concentrations over • Bioavailability of oral ganciclovir is 5%, so this should only be used for maintenance/prophylactic therapy Gemcitabine hydrochloride
Clinical use
Important drug interactions
Palliative treatment, or first-line treatment with cisplatin, of locally advanced or metastatic non- Treatment of bladder cancer in combination with Administration
Dose in normal renal function
• Reconstitute with sodium chloride 0.9%, 5 mL to NSLC: 1000 mg/m2 weekly for 3 weeks, 1 weekrest then repeat • Can be further diluted in sodium chloride 0.9% if Pancreatic:1000 mg/m2 weekly for 7 weeks, restfor 1 week then weekly for 3 weeks out of 4 Pharmacokinetics
Other information
• Gemcitabine causes reversible haematuria with or without proteinuria in about 50% of patients • There is no evidence for cumulative renal Dose in renal impairment
toxicity with repeated dosing of gemcitabine GFR (mL/min)
• Haemolytic uraemic syndrome (HUS) has been reported with a crude incidence rate of 0.015% • A study looking at the use of gemcitabine 500–1000 mg/m2 administered IV on days 1, 8 and 15 every 28 days in patients with renaldysfunction, concluded that this regimen was well Dose in patients undergoing
tolerated in patients with a GFR as low as renal replacement therapies
• Another study in patients with serum creatinines in the range 130–420 micromol/L at doses of 650–800 mg/m2 weekly for 3 weeks out of a 4-week cycle, found dose-limiting toxicities, including neutropenia, fever, raised transaminasesand increased serum creatinine. It was concluded that a reduced dose of gemcitabine may be appropriate in patients with established renalimpairment Gemfibrozil
Important drug interactions
Clinical use
• Enhanced anticoagulant effect seen with Hyperlipidaemias of types IIa, IIb, III, IV and V • Ciclosporin: Parke-Davis have one report on file Dose in normal renal function
of an interaction with ciclosporin where serumciclosporin levels were decreased. No effects on 1.2 g daily, usually in two divided doses; Pharmacokinetics
Administration
Dose in renal impairment
GFR (mL/min)
Initially 900 mg daily. Monitor carefully Initially 900 mg daily. Monitor carefully Other information
Dose in patients undergoing
• Adverse effects have not been reported in patients with renal disease, but such patients renal replacement therapies
should start treatment at 900 mg daily, whichmay be increased after careful assessment of • Rare cases of rhabdomyolysis may be increased • Approximately 60–70% is excreted in the urine • Gemfibrozil alone has caused myalgia and myositis, but the effects appear to occur muchmore frequently and are more severe when anHMG CoA reductase inhibitor is also used.Thecombination is therefore not recommended Gentamicin
• Cholinergics: antagonism of effect of neostigmine • Botulinum toxin: neuromuscular block enhanced Clinical use
Administration
Dose in normal renal function
3–7 mg/kg (ideal body weight) daily (divided into 1–4 doses). CAPD peritonitis – see local policy • Bolus IV injection or short infusion – maximum Pharmacokinetics
• Bolus IV: over not less than 3 minutes. Short Other information
Dose in renal impairment
• Adjustment for renal impairment: Dialysis patients – GFR (mL/min)
See ‘Other information’ for dosage for dialysis andfor single daily dosing regimen Dose in patients undergoing
renal replacement therapies
• Concurrent penicillins may result in • Monitor blood levels. 1 hour post-dose, peak levels must not exceed 10 mg/L. Pre-dose trough • Empirical IP therapy for CAPD peritonitis in vancomycin IP at dose of 1–2 g stat on days 1and 7 of course. Monitoring of blood levels is Important drug interactions
advisable, as absorption is increased by inflamedperitoneum • Potential nephrotoxicity of the drug may worsen • Ciclosporin: increased risk of nephrotoxicity • Long-term concurrent use of gentamicin with • Muscle relaxants: effect of tubocurarine enhanced • Cytotoxics: increased risk of nephrotoxicity with Glibenclamide
Important drug interactions
Clinical use
• Analgesics: azapropazone, phenylbutazone and • Antibacterials: chloramphenicol, co-trimoxazole, Dose in normal renal function
4-quinolones, sulphonamides and trimethoprimenhance effect Initially 5 mg daily (elderly patients – 2.5 mg)adjusted according to response; maximum 15 mg • Antifungals: fluconazole and miconazole increase • Uricosurics: sulfinpyrazone enhances effect of Pharmacokinetics
Administration
Dose in renal impairment
GFR (mL/min)
Initial dose of 1.25–2.5 mg once a day.
Initial dose of 1.25–2.5 mg once a day.
Monitor closely Other information
Initial dose of 1.25–2.5 mg once a day.
Use with caution with continuous • The metabolites of glibenclamide are only weakly hypoglycaemic, this is not clinically relevantwhere renal and hepatic functions are normal. If Dose in patients undergoing
<10 mL/min, accumulation of metabolite renal replacement therapies
and unchanged drug in plasma may causeprolonged hyperglycaemia • Company information states that use is contra- • Compensatory excretion via bile in faeces occurs Unknown dialysability. Dose as inGFR = 10–20 mL/min Gliclazide
Important drug interactions
Clinical use
• Analgesics: azapropazone, phenylbutazone and • Antibacterials: chloramphenicol, co-trimoxazole, Dose in normal renal function
4-quinolones, sulphonamides and trimethoprim Initially: 40–80 mg daily, adjusted according to response up to 160 mg as a single dose, with • Antifungals: fluconazole and miconazole increase breakfast; higher doses divided. Maximum 320 mg • Uricosurics: sulfinpyrazone enhances effect Pharmacokinetics
Administration
Dose in renal impairment
GFR (mL/min)
Initially 20–40 mg daily. Use with cautionand monitor Other information
Initially 20–40 mg daily. Use with cautionand monitor • Care should be exercised in patients with hepatic Initially 20–40 mg daily. Use with great and/or renal impairment and a small starting dose should be used with careful patientmonitoring Dose in patients undergoing
• Company contra-indicates prescribing of renal replacement therapies
Diamicron in severe renal impairment which theydefine as CL Unlikely dialysability. Dose as inGFR = <10 mL/min Unlikely dialysability. Dose as inGFR = <10 mL/min Unknown dialysability. Dose as inGFR = 10–20 mL/min Glimepiride
Important drug interactions
Clinical use
• Azapropazone, phenylbutazone and possibly other NSAIDs enhance effect of sulphonylureas • Antibacterials: chloramphenicol, co-trimoxazole, Dose in normal renal function
4-quinolones, sulphonamides and trimethoprimenhance effect 1–4 mg daily. Maximum 6 mg daily taken shortlybefore or with first main meal • Antifungals: fluconazole and miconazole increase Pharmacokinetics
Administration
% Excreted unchanged in urine 58–60 (as Dose in renal impairment
GFR (mL/min)
Other information
Dose in patients undergoing
renal replacement therapies
Unlikely dialysability. Dose as inGFR = <10 mL/min Unlikely dialysability. Dose as inGFR = <10 mL/min Unlikely dialysability. Dose as inGFR = 10–20 mL/min Glipizide
Important drug interactions
Clinical use
• Azapropazone, phenylbutazone and possibly other NSAIDs enhance effect of sulphonylureas • Antibacterials: chloramphenicol, co-trimoxazole, Dose in normal renal function
4-quinolones, sulphonamides and trimethoprimenhance effect Initially 2.5–5 mg daily, adjusted according toresponse; maximum 20 mg daily; up to 15 mg may • Antifungals: fluconazole and miconazole increase be given as a single dose before breakfast; higher Pharmacokinetics
Administration
Dose in renal impairment
GFR (mL/min)
Other information
• Company does not recommend the use of Dose in patients undergoing
Glibenese in patients with renal insufficiency renal replacement therapies
• Renal or hepatic insufficiency may cause elevated blood levels of glipizide (increased risk of serious Dialysability insignificant, howevercontra-indicated if GFR<10 mL/min Dialysability insignificant. Dose asin GFR = 10–20 mL/min Granisetron
Important drug interactions
Clinical use
Prevention or treatment of nausea and vomitinginduced by cytotoxic chemotherapy, radiotherapy Administration
Dose in normal renal function
PO: 1–2 mg within 1 hour before start of treatment, then 2 mg daily in 1–2 divided dosesduring treatment IV: 3 mg before start of cytotoxic therapy, up to • IV bolus: diluted in 5 mL sodium chloride 0.9% two additional 3 mg doses can be given within • IV infusion: 20–50 mL over 5 minutes Operative procedures: IV: 1 mg before induction of anaesthesia; treatment 1 mg (maximum 2 mg inone day) • Compatible with sodium chloride 0.9%, sodium chloride 0.18% and glucose 4% solution, glucose Pharmacokinetics
5%, Hartmann’s solution, compound sodiumlactate, 10% mannitol • Maximum administered dose over 24 hours Other information
• No special dosing adjustments necessary in Dose in renal impairment
GFR (mL/min)
Dose in patients undergoing
renal replacement therapies
Unknown dialysability. Dose as innormal renal function Unknown dialysability. Dose as innormal renal function. Companyrecommend timing HD for greaterthan 2 hours after granisetrondose Unknown dialysability. Dose as innormal renal function Griseofulvin
Important drug interactions
Clinical use
• Anticoagulants: metabolism of acenocoumarol Antifungal agent: dermatophyte infections of the and warfarin accelerated (reduced anticoagulant • Metabolism of oral contraceptives accelerated Dose in normal renal function
500 mg daily, in divided doses or as a single dose • Ciclosporin: griseofulvin possibly reduces plasma – ciclosporin concentration. (Two reports ofsuch an interaction in literature.) Pharmacokinetics
Administration
Dose in renal impairment
GFR (mL/min)
Other information
Dose in patients undergoing
• Use with extreme caution in patients with SLE renal replacement therapies
Not dialysed. Dose as in normalrenal function Not dialysed. Dose as in normalrenal function Not dialysed. Dose as in normalrenal function

Source: http://www.renalpharmacy.org.uk/pdf/07_Drug_G-2725050rdz.pdf