chapter
Antivirals – other
Pages 5

Care with co-administering probenecid with high-dose antivirals

ACICLOVIR/ VALACICLOVIR

BRONCHODILATORS – THEOPHYLLINES

≠ theophylline levels Uncertain Monitor for signs of toxicity and check levels

ACICLOVIR/ VALACICLOVIR

H2 RECEPTOR BLOCKERS – CIMETIDINE

≠ efficacy and adverse effects of antivirals

Competition for renal excretion Use doses 4 g/day valaciclovir with caution or consider alternative acid suppression. For doses 1 g/day, interaction is not thought to be clinically significant. Studies available only for valaciclovir

GANCICLOVIR, VALGANCICLOVIR

GANCICLOVIR/ VALGANCICLOVIR

ANTIBIOTICS – 1. IMIPENEM WITH CILASTATIN 2. TRIMETHOPRIM

1. ≠ adverse effects (e.g. seizures) 2. Possibly ≠ adverse effects (e.g. myelosuppression) when trimethoprim is co-administered with ganciclovir or valganciclovir

1. Additive side-effects; these drugs can cause seizure activity 2. Small ≠ bioavailability; possible additive toxicity

1. Avoid combination if possible; use only if benefit outweighs risk 2. Well tolerated in one study. For patients at risk of additive toxicities, use only if benefits outweigh risks and monitor FBC closely

GANCICLOVIR/ VALGANCICLOVIR

ANTICANCER AND IMMUNOMODULATING DRUGS –1. CICLOSPORIN 2. MYCOPHENOLATE 3. TACROLIMUS

1. ≠ risk of nephrotoxicity 2. Possible ≠ efficacy 3. Possible ≠ nephrotoxicity/neurotoxicity

1. Additive nephrotoxic effects 2. Competition for renal excretion 3. Additive side-effects

1.Monitor renal function 2. Monitor renal function particularly if on 4 g valaciclovir; ↓ dose of aciclovir if there is a background of renal failure 3. Monitor more closely; check tacrolimus levels

D R

U G

STO TR

EA TIN

FEC TIO

N S

A N

TIV IR

A LS-O

TH ER

Mechanism Precautions

Competitive inhibition of renal excretion

Care with co-administering probenecid with high-dose antivirals

GANCICLOVIR/ VALGANCICLOVIR

ANTIVIRALS – NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

1. ≠ adverse effects with tenofovir, zidovudine and possibly didanosine, lamivudine and zalcitabine 2. Possibly ↓ efficacy of ganciclovir

1. Uncertain; possibly additive toxicity. Lamivudine may compete for active tubular secretion in the kidneys 2. Uncertain; ↓ bioavailability

1. Avoid if possible, otherwise monitor FBC and renal function weekly. It has been suggested that the dose of zidovudine should be halved from 600 mg to 300 mg daily. Monitor for peripheral neuropathy, particularly with zalcitabine 2. Uncertain clinical significance; if in doubt, consider alternative cytomegalovirus prophylaxis

ADEFOVIR DIPIVOXIL

ADEFOVIR DIPIVOXIL 1. ANTIBIOTICS – aminoglycosides, vancomycin 2. ANTICANCER AND IMMUNOMODULATING DRUGS – ciclosporin, tacrolimus 3. ANTIFUNGALS – amphotericin, 4. ANTIPROTOZOALS – pentamidine 5. ANTIVIRALS – cidofovir, foscarnet sodium, tenofovir

Possible ≠ efficacy and side-effects Competition for renal excretion Monitor renal function weekly

D R

U G

STO TR

EA TIN

FEC TIO

N S

A N

TIV IR

A LS-O

TH ER631

DRUGS TO TREAT INFECTIONS ANTIVIRALS – OTHER Foscarnet

↓ renal excretion of metformin Watch for lactic acidosis. The onset of lactic acidosis is often subtle, with symptoms of malaise, myalgia, respiratory distress and ≠ nonspecific abdominal distress. There may be hypothermia and resistant bradyarrhythmias

CIDOFOVIR ANTIVIRALS

CIDOFOVIR ADEFOVIR DIPIVOXIL Possible ≠ efficacy and side-effects Competition for renal excretion Monitor renal function weekly CIDOFOVIR TENOFOVIR ≠ adverse effects ≠ plasma levels; competition for

renal excretion via organic anion transporter

Monitor renal function weekly

FOSCARNET SODIUM

FOSCARNET SODIUM ANTIBIOTICS

FOSCARNET SODIUM AMINOGLYCOSIDES Possible ≠ nephrotoxicity Additive side-effect Monitor renal function closely FOSCARNET SODIUM QUINOLONES Risk of seizures Unknown; possibly additive

side-effect Avoid combination in patients with past medical history of epilepsy. Consider an alternative antibiotic

FOSCARNET SODIUM ANTICANCER AND IMMUNOMODULATING DRUGS – CICLOSPORIN

≠ risk of renal failure Additive nephrotoxic effects Monitor renal function

FOSCARNET SODIUM ANTIFUNGALS – AMPHOTERICIN

Possible ≠ nephrotoxicity Additive side-effect Monitor renal function closely

D R

U G

STO TR

EA TIN

FEC TIO

N S

A N

TIV IR

A LS-O

TH ER

Mechanism Precautions

(INTRAVENOUS)

Unclear; possibly additive hypocalcaemic effects

Use extreme caution with intravenous pentamidine; monitor serum calcium (correct before the start of treatment), renal function and for signs of tetany closely. Stop one drug if necessary

FOSCARNET SODIUM ANTIVIRALS

FOSCARNET SODIUM ADEFOVIR DIPIVOXIL Possible ≠ efficacy and side-effects Competition for renal excretion Monitor renal function weekly FOSCARNET SODIUM NUCLEOSIDE REVERSE

TRANSCRIPTASE INHIBITORS – LAMIVUDINE, TENOFOVIR, ZALCITABINE

≠ adverse effects with tenofovir and possibly lamivudine and zalcitabine

Uncertain; possibly additive toxicity via competition for renal excretion

Avoid if possible; otherwise monitor FBC and renal function weekly

FOSCARNET SODIUM PROTEASE INHIBITORS ↓ renal function when co-administered with ritonavir or saquinavir

Uncertain; possibly ↓ renal excretion of foscarnet

Monitor renal function closely

OSELTAMIVIR METHOTREXATE Possible ≠ efficacy/toxicity Competition for renal excretion Monitor more closely for signs of immunosupression. Predicted interaction

RIBAVIRIN

RIBAVIRIN ANTIVIRALS – NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

1. ≠ side-effects; risk of lactic acidosis, peripheral neuropathy, pancreatitis, hepatic decompensation, mitochondrial toxicity and anaemia with didanosine and stavudine 2. ↓ efficacy of lamivudine

1. Additive side-effects; ≠ intracellular activation of didanosine and stavudine. 2. ↓ intracellular activation of lamivudine

1. Not recommended; use with extreme caution. Monitor lactate, LFTs and amylase closely. Stop co-administration if peripheral neuropathy occurs. Stavudine and didanosine carry a higher risk 2. Monitor HIV RNA levels; if they ≠, review treatment combination

TELBIVUDINE INTERFERON Peripheral neuropathy Unclear Use with caution