Guidelines for the Prevention and Treatment of ... · PDF fileGuidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV ... (Malarone ) Tablets:

Downloaded from https://aidsinfo.nih.gov/guidelines on 5/22/2018

Guidelines for the Prevention and Treatment of OpportunisticInfections Among HIV-Exposed and HIV-Infected Children


Visit the AIDSinfo website to access the most up-to-date guideline.

Register for e-mail notification of guideline updates at https://aidsinfo.nih.gov/e-news.


Guidelines for the Prevention and Treatment of Opportunistic Infections In HIV-Exposed and HIV-Infected Children HH-1

Table 4. Common Drugs Used for Treatment of Opportunistic Infections inHIV-Infected Children: Preparations and Major Toxicities (Last updatedNovember 6, 2013; last reviewed November 6, 2013) (page 1 of 22)

Drug Preparations Major Toxicitiesa Special Instructions

Indicating Need for MedicalAttention

Indicating Need forMedical Attention if

Persistent or Bothersome

Acyclovir(Zovirax)

OralSuspension: • 40 mg/mL

Capsules: • 200 mg

Tablets: • 400 mg• 800 mg

IV

More Frequent: • Phlebitis (at injection sitewhen given IV)

Less Frequent:• Acute renal failure (parenteraluse, more common with rapidinfusion)

RareParenteral Form Only:• Encephalopathy• Hematologic toxicity(leukopenia, neutropenia,thrombocytopenia, anemia,hemolysis)

• Crystalluria, hematuria• Disseminated intravascularcoagulation

• Hypotension• Neuropsychiatric toxicity(with high doses)

Parenteral and Oral Forms:• Rash (urticarial, exfoliative skindisorders including SJS)

• Anaphylaxis• Seizures• Elevated transaminaseenzymes

• Fever, hallucinations• Leukopenia• Lymphadenopathy• Peripheral edema• Visual abnormalities

More Frequent:• GI disturbances (anorexia,diarrhea, nausea, vomiting)

• Headache, lightheadedness• Malaise

Less Frequent (More Markedin Older Adults):• Agitation• Alopecia• Dizziness• Myalgia, paresthesia• Somnolence

Requires dose adjustment inpatients with renalimpairment.

Avoid other nephrotoxicdrugs.

Administer IV preparation byslow IV infusion over at least1 hour at a final concentrationnot to exceed 7 mg/mL. Thisis to avoid renal tubulardamage related to crystalluria;must be accompanied byadequate hydration.

Albendazole(Albenza)

Tablets:• 200 mg

More Frequent:• Abnormal liver function tests(LFTs)

Less Frequent:• Hypersensitivity (rash,pruritus)

• Neutropenia (with high doses)

Rare: • Pancytopenia

Less frequent:• CNS effects (dizziness,headache)

• GI disturbances (abdominalpain, diarrhea, nausea,vomiting)

Rare:• Alopecia

Should be given with food.

May crush or chew tabletsand give with water.

Monitor CBC and LFTs prior toeach cycle.



Table 4. Common Drugs Used for Treatment of Opportunistic Infections in HIV-Infected Children:

Preparations and Major Toxicities (page 2 of 22)


Indicating Need forMedical Attention



Amikacin IV More Frequent: • Nephrotoxicity• Neurotoxicity (includingmuscle twitching, seizures)

• Ototoxicity, both auditoryand vestibular

Less Frequent:• Hypersensitivity (skin rash,redness, or swelling)

Rare:• Neuromuscular blockade

N/A Must be infused over 30 to 60minutes to avoidneuromuscular blockade.

Requires dose adjustment inpatients with impaired renalfunction.

Should monitor renal functionand hearing periodically (e.g.,monthly) in children onprolonged therapy.

Therapeutic drug monitoring(TDM). indicated

Amphotericin BDeoxycholate(Fungizone)

IV More Frequent: • Infusion-related reactions(fever/chills;nausea/vomiting;hypotension; anaphylaxis)

• Anemia • Hypokalemia• Renal function impairment• Thrombophlebitis (atinjection site)

Less Frequent or Rare:• Blurred or double vision• Cardiac arrhythmias, usuallywith rapid infusions

• Hypersensitivity (rash)• Leukopenia• Polyneuropathy• Seizures• Thrombocytopenia

• GI disturbance (nausea,vomiting, diarrhea,abdominal pain)

• Headache

Monitor BUN, Cr, CBC,electrolytes, LFTs.

Infuse over 1 to 2 hours; inpatients with azotemia,hyperkalemia, or gettingdoses >1 mg/kg, infuse over 3to 6 hours.

Requires dose reduction inpatients with impaired renalfunction.

Avoid other nephrotoxicdrugs, when possible,becausenephrotoxicity is exacerbatedwith concomitant use of othernephrotoxic drugs; permanentnephrotoxicity is related tocumulative dose.

Nephrotoxicity may beameliorated by hydration with0.9% saline IV over 30minutes prior to theamphotericin B infusion.

Infusion-related reactions lessfrequent in children thanadults; the onset is usually 1to 3 hours after infusion,duration <1 hour; frequencydecreases over time.

Pre-treatment withacetaminophen and/ordiphenhydramine mayalleviate febrile reactions.









Amphotericin BLipid Complex(Abelcet)

IV More Frequent: • Infusion-related reactions(fever/chills, nausea/vomiting; headache, nauseaand vomiting)

Less Frequent:• Anemia • Leukopenia• Respiratory distress• Thrombocytopenia• Renal function impairment

• GI disturbance (loss ofappetite, nausea, vomiting,diarrhea, abdominal pain)

Monitor BUN, Cr, CBC,electrolytes, and LFTs.

Infuse diluted solution at rateof 2.5 mg/kg/hour.

In-line filters should not beused.

Use with caution with otherdrugs that are bone marrowsuppressants or that arenephrotoxic; renal toxicity isdose-dependent, but lessrenal toxicity than seen withconventional amphotericin B.

Consider dose reduction inpatients with impaired renalfunction.

Amphotericin BLiposome(AmBisome)

IV More Frequent: • Fever, chills• Hypokalemia

Less Frequent:• Back pain• Chest pain• Dark urine• Dyspnea• Infusion-related reaction(fever/chills, headache)

• Jaundice• Renal function impairment

Rare:• Anaphylactic reaction

• GI disturbance (nausea,vomiting, diarrhea,abdominal pain)

• Headache• Skin rash

Monitor BUN, Cr, CBC,electrolytes, and LFTs.

Infuse over 2 hours.

Consider dose reduction inpatients with impaired renalfunction.

Artesunate IV:• Only availablefrom CDCMalaria Hotline;telephone:(770) 488-7788

Rare:• Anaphylactic reaction• Neutropenia• Bradycardia

• GI disturbance (nausea,vomiting)

• Headache• Skin rash

Monitor CBC, LFTs, andelectrolytes.

~40% less mortality than withquinidine use in severemalaria

50% lower incidence ofhypoglycemia than quinidine

Atovaquone(Mepron)

Oral Suspension: • 150 mg/mL

Frequent: • Fever• Skin rash

Frequent:• GI disturbances (nausea,vomiting, diarrhea)

• Headache• Cough

• Insomnia

Should be administered with ameal to enhance absorption;bioavailability increases 3-foldwhen administered with high-fat meal.









Atovaquone/Proguanil(Malarone)

Tablets:• Pediatric tablets;62.5 mg/ 25 mg

• Adult tablets;250 mg/100 mg

Less frequent:• Vomiting• Pruritus

N/A Pediatric tablets are availableto make dosing easier.

Side effects requiringdiscontinuation in ~1%–2% ofpatients

Not recommended forprophylaxis in patients withCrCl <30 mL/min.

Azithromycin(Zithromax)

Oral Suspension: • 20 mg/mL• 40 mg/mL

Tablets:• 250 mg• 500 mg• 600 mg

IV

More Frequent:• Thrombophlebitis (IV form)

Rare:• Acute interstitial nephritis• Allergic reactions/anaphylaxis (dyspnea,hives, rash)

• Pseudomembranous colitis

• GI disturbances (abdominaldiscomfort or pain,diarrhea, nausea, vomiting)

• Dizziness, headache

Administer 1 hour before or 2hours after a meal; do notadminister with aluminum-and magnesium-containingantacids.

IV should be infused atconcentration of 1 mg/mLover a 3-hour period, or 2mg/mL over a 1-hour period;should not be administered asa bolus.

Use with caution in patientswith hepatic functionimpairment; biliary excretionis the main route ofelimination.

Potential drug interactions.

Capreomycin(Capastat)

IM More Frequent:• Nephrotoxicity

Less Frequent:• Hypersensitivity (rash,fever)

• Hypokalemia• Neuromuscular blockade• Ototoxicity, both auditoryand vestibular

• Injection site pain, sterileabscess

N/A Requires dose adjustment inpatients with impaired renalfunction.

Administer only by deep IMinjection into large musclemass (superficial injectionsmay result in sterile abscess).


Monitor LFTs and electrolytes.

Caspofungin(Cancidas)

IV More Frequent:• Histamine-mediatedsymptoms (fever, facialswelling, pruritus,bronchospasm)

Rare:• Hypokalemia• Anaphylactic reaction

• GI disturbances (nausea,vomiting, diarrhea)

• Headache• Skin rash, facial flushing• Elevated livertransaminases

• Thrombophlebitis

Requires dose adjustment inmoderate-to-severe hepaticinsufficiency.

IV infusion over 1 hour innormal saline (do not usediluents containing dextrose)






Indicating Need for MedicalAttention

Indicating Need for MedicalAttention if Persistent or

Bothersome

ChloroquinePhosphate(Aralen)

Tablets:• 500 mg• 250 mg

More Frequent: • Pruritus: Common inindividuals of black race(25%–33%)

Less Frequent, but MoreSevere:• Auditory toxicity• Ocular toxicity• Neuropsychiatric disorders• QT prolongation• Hepatitis• Bone marrow suppression• Peripheral neuropathy

• Psoriasis exacerbations• GI disturbances (nausea,vomiting, diarrhea)

• Visual disturbancesincluding photosensitivity

• Tinnitus• Muscle weakness

Store in child-proof containersand protect from light.

Can be toxic in overdose.

Bitter tasting, so consideradministering with foods thatcan mask the taste.

Solution available worldwide, butnot in United States.

Caution in patients with G6PDdeficiency or seizure disorder.

Monitor CBC; periodic neurologicand ophthalmologic exams inpatients on prolonged therapy.

Cidofovir(Vistide)

IV More Frequent:• Nephrotoxicity• Neutropenia

Less Frequent:• Fever and allergic reactions

Rare:• Vision changes due toocular hypotony

• Metabolic acidosis

• GI disturbances (anorexia,diarrhea, nausea, vomiting)

• Headache• Asthenia• Proteinuria

Infuse over 1 hour.

Should not be used in patientswith severe renal impairment.

Nephrotoxicity risk is decreasedwith pre-hydration with IV normalsaline and probenecid with eachinfusion. Probenecid isadministered prior to each doseand repeated for two additionaldoses after infusion. Additionalhydration after infusion isrecommended if tolerated.

Concurrent use of other nephro-toxic drugs should be avoided.

Monitor renal function, urinalysis,electrolytes, and CBC and performophthalmologic exams.

Ciprofloxacin(Cipro)

Oral Suspension:• 50 mg/mL• 100 mg/mL

Tablets:• 100 mg• 250 mg• 500 mg• 750 mg

XR TabletsCipro XR: • 500 mg• 1000 mg

Proquin XR: • 500 mg

IV

Less Frequent:• Phototoxicity

Rare:• CNS stimulation• Hepatotoxicity• Hypersensitivity reactions(rash, pruritus, andexfoliative skin disordersincluding SJS, dyspnea, andvasculitis)

• Interstitial nephritis• Phlebitis (at injection sites)• Pseudomembranous colitis• Tendonitis or tendonrupture

• QT interval prolongation

More Frequent:• GI disturbances (abdominaldiscomfort or pain, diarrhea,nausea, vomiting)

• CNS toxicity (dizziness,headache, insomnia,drowsiness)

Less Frequent:• Change in taste• Photosensitivity

Administer oral formulations atleast 2 hours before, or 6 hoursafter, sucralfate or antacids orother products containingcalcium, zinc, or iron (includingdaily products or calcium-fortified juices). Take with fullglass of water to avoidcrystalluria.

Possible phototoxicity reactionswith sun exposure.

IV infusions should be over 1hour.

Do not split, crush, or chewextended-release tablets.









Clarithromycin(Biaxin)



Rare:• Hepatotoxicity• Hypersensitivity reaction(rash, pruritus, dyspnea)

• Pseudomembranous colitis• Thrombocytopenia• QT interval prolongation

More Frequent:• GI disturbances (abdominaldiscomfort or pain,diarrhea, nausea, vomiting)

Less Frequent:• Abnormal taste sensation• Headache• Rash


Can be administered withoutregard to meals.

Reconstituted suspensionshould not be refrigerated.

Potential drug interactions

Clindamycin(Cleocin)

Oral Solution:• 15 mg/mL

Capsules:• 75 mg, 150mg, 300 mg

IV

More Frequent:• Pseudomembranous colitis

Less Frequent:• Hypersensitivity (skin rash,redness, pruritus)

• Neutropenia• Thrombocytopenia

More Frequent:• GI disturbances (abdominalpain, nausea, vomiting,diarrhea)

Less Frequent:• Fungal overgrowth, rectaland genital areas

IV preparation contains benzylalcohol, not recommended foruse in neonates.

IV preparation must be dilutedprior to administration.

Capsule formulation should betaken with food or a full glassof water to avoid esophagealirritation.

Reconstituted oral solutionshould not be refrigerated.

Cycloserine(Seromycin)

Capsules:• 250 mg

More Frequent:• CNS toxicity (includingconfusion, anxiety)

Less Frequent:• Hypersensitivity (skin rash)• Peripheral neuropathy• Seizures• Psychosis

Rare: • Cardiac arrhythmias

• Headache, dizziness,drowsiness, confusion

Rare: • Photosensitivity

Take with food to minimizegastric irritation.

Neurotoxicity is related toexcessive serumconcentrations; serumconcentrations should bemaintained at 25–30 mcg/mL.


Do not administer to patientswith severe renal impairment(because of increased risk ofneurotoxicity).

Should monitor serum levels,if possible.

Should administer pyridoxineat the same time.

Monitor renal function, LFTs,and CBC.









Dapsone Syrup (availableunderCompassionateUse IND): • 2 mg/mL


More Frequent: • Hemolytic anemia(especially if G6PDdeficiency)

• Methemoglobinemia• Skin rash

Rare: • Blood dyscrasias• Exfoliative skin disorders(including SJS)

• Hepatic toxicity• Mood or other mentalchanges

• Peripheral neuritis• Hypersensitivity reaction(fever, rash, jaundice,anemia)

• CNS toxicity (headache,insomnia, nervousness)

• GI disturbances (anorexia,nausea, vomiting)

• Photosensitivity reactions

Protect from light; dispensesyrup in amber glass bottles.

Monitor CBC and LFTs.

Doxycycline(Vibramycin)

Tablets andCapsules: • 20 mg• 50 mg• 75 mg• 100 mg

Oral Suspensionand Syrup: • 5 mg/mL oralsuspension

• 10 mg/mL oralsyrup

IV

More Frequent:• GI irritation, pill esophagitis• Photosensitivity

Less frequent:• May cause increasedintracranial pressure,photosensitivity, hemolyticanemia, rash, andhypersensitivity reactions.

• Clostridium difficile-associated diarrhea

• Pseudotumor cerebri

• Staining of teeth a concernfor individuals aged <8 years

• Photo-onycholysis• GI disturbances (nausea,vomiting, abdominalcramps)

Swallow with adequateamounts of fluids

Avoid antacids, milk, dairyproducts, and iron for 1 hourbefore or 2 hours afteradministration of doxycycline.

Use with caution in hepaticand renal disease.

IV doses should be infusedover 1 to 4 hours.

Patient should avoidprolonged exposure to directsunlight (skin sensitivity).

Generally not recommendedfor use in children aged <8 years because of risk oftooth enamel hypoplasia anddiscoloration, unless benefitoutweighs risk.

Monitor renal function, CBC,and LFTs if prolonged therapy.









Erythromycin Erythromycin-Base Tablet: • 250 mg• 333 mg• 500 mg

Delayed-ReleaseTablet: • 250 mg• 333 mg• 500 mg

Delayed-ReleaseCapsule: • 250 mg

ErythromycinEthyl SuccinateSuspension:• 200 mg• 400 mg/5 mL

Oral Drops: • 100 mg/2.5 mL

ChewableTablet:• 200 mg

Tablet:• 400 mg

ErythromycinEstolateSuspension: • 125 mg• 250 mg/5 mL

ErythromycinStearateTablet: • 250 mg• 500 mg

ErythromycinGluceptate:• IV

ErythromycinLactobionate:• IV

Less Frequent:• Estolate may causecholestatic jaundice,although hepatotoxicity isuncommon (2% of reportedcases).

Rare:• QT prolongation• Hypersensitivity reactions(rash, exfoliative skindisorders including SJS)

• GI disturbances (nausea,vomiting, abdominalcramps)

• Rash, urticaria• Increased LFTs

Use with caution in liverdisease.

Oral therapy should replace IVtherapy as soon as possible.

Give oral doses after meals.

Parenteral administrationshould consist of acontinuous drip or slowinfusion over 1 hour or longer.

Adjust dose in renal failure.

Erythromycin should be usedwith caution in neonates;hypertrophic pyloric stenosisand life-threatening episodesof ventricular tachycardiaassociated with prolongedQTc interval have beenreported.

High potential for interactionwith many ARVs and otherdrugs.









Ethambutol(Myambutol)


Less Frequent:• Acute gouty arthritis(secondary tohyperuricemia)

Rare:• Hypersensitivity (rash, fever,joint pain)

• Peripheral neuropathy• Retrobulbar optic neuritis,decreased visual acuity, lossof red-green colordiscrimination

• Bone marrow suppression• Abnormal LFTs,hepatotoxicity

• GI disturbances (abdominalpain, anorexia, nausea,vomiting)

• Confusion• Disorientation• Headache



Monitor visual acuity and red-green color discriminationregularly.

Monitor renal function, LFTs,and CBC.

Avoid concomitant use ofdrugs with neurotoxicity.

Ethionamide(Trecator-SC)

Tablets: • 250 mg

Less Frequent: • Hepatitis, jaundice• Peripheral neuritis• Psychiatric disturbances

Rare:• Goiter or hypothyroidism• Hypoglycemia• Optic neuritis• Skin rash

More Frequent:• GI disturbances (anorexia,metallic taste, nausea,vomiting, stomatitis)

• Orthostatic hypotension

Rare:• Gynecomastia

Avoid use of other neurotoxicdrugs that could increasepotential for peripheralneuropathy and optic neuritis.

Administration of pyridoxinemay alleviate peripheralneuritis.


Monitor LFTs, glucose, andthyroid function. Performperiodic ophthalmologicexams.

Fluconazole(Diflucan)


Tablets: • 50 mg• 100 mg• 150 mg• 200 mg

IV

Less Frequent:• Hypersensitivity (fever,chills, skin rash)

Rare:• Agranulocytosis,eosinophilia, leucopenia,thrombocytopenia

• Exfoliative skin disorders(including SJS)

• Hepatotoxicity • QT prolongation• Thrombocytopenia

More Frequent: • GI disturbances (abdominalpain, constipation,diarrhea, anorexia, nausea,vomiting)

Less Frequent:• CNS effects (dizziness,drowsiness, headache)

• Alopecia

Can be given orally withoutregard to meals.

Shake suspension well beforedosing.


IV administration should beadministered over 1–2 hoursat a rate ≤200 mg/hour.

Daily dose is the same for oraland IV administration.

Multiple potential druginteractions

Monitor periodic LFTs, renalfunction, and CBC.









Flucytosine(Ancobon)

Capsules:• 250 mg• 500 mg

Oral Liquid:• Extempo-raneouspreparation

More Frequent:• Bone marrow suppression(especially leukopenia andthrombocytopenia)

Less Frequent:• Hepatotoxicity • Renal toxicity (includingcrystalluria)

Rare:• Cardiac toxicity (ventriculardysfunction, myocardialtoxicity, cardiac arrest)

• CNS symptoms(hallucinations, seizures,peripheral neuropathy)

• Anaphylaxis• Hearing loss

• GI disturbances (abdominalpain, constipation,diarrhea, anorexia, nausea,vomiting)

• Elevated livertransaminases

• Skin rash

Rare:

• CNS symptoms (headache,drowsiness, confusion,vertigo)

• Crystalluria

Monitor serum concentrationsand adjust dose to maintaintherapeutic levels andminimize risk of bone marrowsuppression.

Requires dose adjustment inpatients with impaired renalfunction; use with extremecaution.

Fatal aplastic anemia andagranulocytosis have beenrarely reported.

Oral preparations should beadministered with food over a15-minute period to minimizeGI side effects

Monitor CBC, LFTs, renalfunction, and electrolytes.

Foscarnet(Foscavir)

IV More Frequent:• Nephrotoxicity• Serum electrolyteabnormalities(hypocalcaemia,hypophosphatemia,hypomagnesemia,hypokalemia)

Less Frequent:• Hematologic toxicity(anemia, granulocytopenia)

• Neurotoxicity (muscletwitching, tremor, seizures,tingling around mouth)

• Cardiac abnormalitiessecondary to electrolytechanges

• Phlebitis (at site ofinjection)

Rare:• Sores or ulcers mouth orthroat

Frequent:


• Anxiety, confusion,dizziness, headache

• Fever


Use adequate hydration todecrease nephrotoxicity. Avoidconcomitant use of otherdrugs with nephrotoxicity.

Monitor serum electrolytes,renal function, and CBC.

Consider monitoring serumconcentrations (TDM)

IV solution of 24 mg/mL canbe administered via centralline but must be diluted to afinal concentration not toexceed 12 mg/mL if given viaperipheral line.

Must be administered at aconstant rate by infusionpump over ≥2 hours (or nofaster than 1 mg/kg/minute).









Ganciclovir(Cytovene)

Capsules: • 250 mg• 500 mg

IV

More Frequent:• Granulocytopenia• Thrombocytopenia

Less Frequent:• Anemia• CNS effects (confusion,headache)

• Hypersensitivity (fever,rash)

• Elevated transaminaseenzymes

• Increase in creatinine, BUN• Phlebitis (at injection sites)

Rare:• Retinal detachment• Seizures• Psychosis• Cardiac (hypertension,chest pain)


• Rash



IV infusion over at least 1hour. In-line filter required.

Maintain good hydration.

Undiluted IV solution isalkaline (pH 11); use cautionin handling and preparingsolutions and avoid contactwith skin and mucusmembranes.

Administer oral doses withfood to increase absorption.Do not open or crushcapsules.

Monitor CBC, LFTs, renalfunction; conductophthalmologic examinations.

Interferon-alfa-2B(IFN-α-2B;Intron)

Parenteral (SQor IV use)

More Frequent:• Hematologic toxicity(leukopenia,thrombocytopenia)

• Neurotoxicity (confusion,depression, insomnia,anxiety)

• Injection erythema

Less Frequent:• Cardiovascular effects(chest pain, hypertension,arrhythmias, hypotension)

• Hypoesthesia/paresthesia

Rare: • Abnormality or loss ofvision

• Allergic reaction (rash,hives)

• Hypothyroidism• Development of antinuclearantibodies

More Frequent:• Flu-like syndrome (myalgia,arthralgia, fever, chills,headache, back pain,malaise, fatigue)

• GI disturbances (abdominalpain, anorexia, nausea,vomiting, diarrhea,dyspepsia)

• Pharyngitis, dry mouth

Less Frequent:• Alopecia• Epistaxis• Elevated serumtransaminases, serumcreatinine and BUN,glucose, triglycerides

Severe adverse effects lesscommon in children thanadults.

Toxicity dose-related, withsignificant reduction over thefirst 4 months of therapy.

For non-life-threateningreactions, reduce dose ortemporarily discontinue drugand restart at low doses withstepwise increases.

If patients have visualcomplaints, an ophthalmologicexam should be performed todetect possible retinalhemorrhage or retinal artery orvein obstruction.

Should not be used in childrenwith decompensated hepaticdisease, significant cytopenia,autoimmune disease, orsignificant pre-existing renalor cardiac disease.

If symptoms of hepaticdecompensation occur









Interferon-alfa-2B(IFN-α-2B;Intron),continued

(ascites, coagulopathy,jaundice), IFN-α-2B should bediscontinued.

Reconstituted solution stablefor 24 hours whenrefrigerated.

Monitor CBC, renal function,LFTs, thyroid function, andglucose.

Isoniazid(Nydrazid)

Oral Syrup:• 10 mg/mL


IM

More Frequent:• Hepatitis prodromalsyndrome (anorexia,weakness, vomiting)

• Hepatitis• Peripheral neuritis

Rare:• Blood dyscrasias• Hypersensitivity (fever, rash,joint pain)

• Neurotoxicity (includesseizure)

• Optic neuritis

• GI disturbances (abdominalpain, nausea, vomiting,diarrhea)

• Elevated livertransaminases

• Pyridoxine deficiency


Take ≥1 hour beforealuminum-containingantacids.

Hepatitis less common inchildren.

Use with caution in patientswith hepatic functionimpairment, severe renalfailure, or history of seizures.

Pyridoxine supplementationshould be provided for allHIV-infected children.

Monitor LFTs and periodicophthalmologic examinations.

Itraconazole(Sporanox)

Oral Solution: • 10 mg/mL


IV

Less frequent:• Hypersensitivity (fever,chills, skin rash)

• Hypokalemia (can beassociated with cardiacarrhythmias)

Rare:• Hepatotoxicity• Hematologic abnormalities(thrombocytopenia,leukopenia)

More Frequent: • GI disturbances (abdominalpain, constipation,diarrhea, anorexia, nausea,vomiting)


• Rash

Oral Solution: • Give on an empty stomachbecause gastric acidincreases absorption.

Capsules: • Administer after a full mealto increase absorption.

Itraconazole oral solution has60% greater bioavailabilitycompared with capsules, andthe oral solution and capsulesshould not be usedinterchangeably.

IV infusion over 1 hour.


Monitor LFTs and potassiumlevels.

Monitor serum concentrations(TDM) in severe infections.









Kanamycin IV

IM

More Frequent: • Nephrotoxicity• Neurotoxicity (includingmuscle twitching, seizures)

• Ototoxicity, both auditoryand vestibular

Less Frequent:• Hypersensitivity (skin rash,redness or swelling)


N/A Must be infused over 30 to 60minutes to avoidneuromuscular blockade.



Monitor serum concentrations(TDM).

Monitor renal function;conduct, hearing exams forpatients receiving prolongedtherapy.

Ketoconazole(Nizoral)

Tablets: • 200 mg

Topical:• Shampoo• Cream• Gel• Foam

Suspension:• Extempo-raneouspreparation


Rare:• Hepatotoxicity (includinghepatic failure)

Frequent: • GI disturbances (abdominalpain, constipation,diarrhea, anorexia, nausea,vomiting)


Rare:• Gynecomastia• Impotence• Menstrual irregularities• Photophobia

Adverse GI effects occur lessoften when administered withfood.

Drugs that decrease gastricacidity or sucralfate should beadministered ≥2 hours afterketoconazole.

Disulfiram-like reactions haveoccurred in patients ingestingalcohol.

Hepatotoxicity is anidiosyncratic reaction, usuallyreversible when stopping thedrug, but rare fatalities canoccur any time duringtherapy; more common infemales and adults >40 years,but cases reported in children.

High-dose ketoconazolesuppresses corticosteroidsecretion, lowers serumtestosterone concentration(reversible).

Multiple potential druginteractions.

Monitor LFTs.









Mefloquine(Lariam)

Tablets:• 250 mg

More Frequent:• CNS (psychosis,depression, hallucinations,paranoia, seizures)

Rare:• Blood dyscrasias• Cholestasis, elevatedbilirubin

• Rash• GI disturbances (abdominalpain, constipation,diarrhea, anorexia, nausea,vomiting)

• CNS (dizziness, vividdreams, insomnia)

• Tinnitus, blurred vision

Side effects less prominent inchildren.

Administer with food andplenty of water.

Tablets can be crushed andadded to food; bitter tastingso administer with foods thatcan mask the taste

Monitor LFTs.

Nitazoxanide(Alinia)

Oral Suspension: • 20 mg/mL

Tablets: • 500 mg

N/A More Frequent:• GI disturbances (abdominalpain, nausea, vomiting)

• Headache

Rare:• Scleral icterus• Rash

Should be given with food.

Shake suspension well priorto dosing.

P-AminosalicyclicAcid(Paser)

Delayed ReleaseGranules: • 4 g per packet

Rare:• Hypersensitivity (fever, skinrash, exfoliative dermatitis,mono-like or lymphoma-likesyndrome, jaundice,hepatitis, pericarditis,vasculitis, hematologicabnormalities includinghemolytic anemia,hypoglycemia, opticneuritis, encephalopathy,reduction in prothrombin)

• Crystalluria• Hemolytic anemia

• GI disturbances (abdominalpain, nausea, vomiting,diarrhea)

Should not be administered topatients with severe renaldisease.

Drug should be discontinuedat first sign of hypersensitivityreaction (rash, fever, and GIsymptoms typically precedejaundice).

Vitamin B12 therapy shouldbe considered in patientsreceiving for >1 month.

Administer granules bysprinkling on acidic foodssuch as applesauce or yogurtor a fruit drink like tomato ororange juice.

Maintain urine at neutral oralkaline pH to avoidcrystalluria.

The granule soft “skeleton”may be seen in the stool.










PegylatedInterferon Alfa-2A(Pegasys)

Injection:• Vials andprefilledsyringes






Rare: • Vision abnormalities or lossof vision






Less Frequent:• Alopecia• Epistaxis• Elevated serumtransaminases, serumcreatinine and BUN,glucose, triglycerides

Toxicity dose-related. Dosemodifications based on typeand degree of toxicity.

For non-life threateningreactions, reduce dose ortemporarily discontinue drugand restart at low doses withstepwise increases.

If patients have visualcomplaints, anophthalmologic exam shouldbe performed to detectpossible retinal hemorrhageor retinal artery or veinobstruction.


If symptoms of hepaticdecompensation occur(ascites, coagulopathy,jaundice),Peg- IFN-α-2Ashould be discontinued.


Store vials and syringes inrefrigerator. Protect from light.

Administer SQ in abdomen orthigh. Rotate injection sites.

PegylatedInterferon Alfa-2B(Pegintron)

Injection:• Vials andprefilledsyringes









Less Frequent:• Alopecia• Epistaxis• Elevated serum

Toxicity dose-related. Dosemodifications based on typeand degree of toxicity.

For non-life threateningreactions, reduce dose ortemporarily discontinue drugand restart at low doses withstepwise increases.

If patients have visualcomplaints, anophthalmologic exam shouldbe performed to detectpossible retinal hemorrhageor retinal artery or veinobstruction.









PegylatedInterferon Alfa-2B(Pegintron),continued

Rare: • Abnormality or loss ofvision



transaminases, serumcreatinine and BUN,glucose, triglycerides


If symptoms of hepaticdecompensation occur(ascites, coagulopathy,jaundice),Peg- IFN-α-2Ashould be discontinued.


Store vials and syringes inrefrigerator. Protect from light.

Administer SQ in abdomen orthigh. Rotate injection sites.

Pentamidine(Pentam)

IV

Aerosol

IVMore Frequent:• Nephrotoxicity • Hypoglycemia• Hyperglycemia or diabetesmellitus

• Elevated liver transaminases• Hypotension• Leukopenia or neutropenia• Thrombocytopenia

Less Frequent:• Anemia• Cardiac arrhythmias• Hypersensitivity (skin rash,fever)

• Pancreatitis• Phlebitis• Sterile abscess (at siteinjection)

AresolMore Frequent:• Sneezing• Cough

IVMore Frequent:• GI disturbances (anorexia,nausea, vomiting, diarrhea)

Less Frequent:• Unpleasant metallic taste

AresolMore Frequent:• Bronchospasm

Rapid infusion may result inprecipitous hypotension; IVinfusion should beadministered over ≥1 hour(preferably 2 hours).

Cytolytic effect on pancreaticbeta islet cells, leading toinsulin release, can result inprolonged severehypoglycemia (usually occursafter 5–7 days of therapy, butcan also occur after the drugis discontinued); riskincreased with higher dose,longer duration of therapy,and re-treatment within 3months of prior treatment.

Hyperglycemia and diabetesmellitus can occur up toseveral months after drugdiscontinued.

Monitor LFTs, renal function,glucose, electrolytes, BP.

Inhalation: • A special nebulizer isrequired for aerosoladministration. Medicalpersonnel should be trainedin the proper administrationof aerosolized pentamidine.









Posaconazole(Noxafil)


Less frequent:• Hypersensitivity (fever,chills, skin rash)

• Anaphylactoid reaction withIV infusion



• Renal dysfunction• Cardiac arrhythmias (QTinterval prolongation,torsades de pointes,hypertension)

• Hemolytic uremic syndrome• Pulmonary embolism• Neutropenia

• Bone marrow suppression• Muscular pain• CNS: headache, dizziness,fatigue

• Elevated serumtransaminases

Must be given with meals.Adequate absorption isdependent on food forefficacy.

Monitor LFTs, renal functionand electrolytes.

Monitor serum drugconcentrations (TDM).

Shake suspension prior todosing.

Primaquine Tablets:• 15 mg (base) =26.3 mgprimaquinephosphate

More Frequent:• Hemolytic anemia (withG6PD deficiency)

Less Frequent:• Methemoglobinemia

Rare:• Leukopenia

• GI disturbances (nausea,vomiting)

Take with meals or antacids tominimize gastric irritation.

Store in a light-resistantcontainer.

Bitter taste.

Monitor CBC.

Pyrazinamide Tablets:• 500 mg

Oral Suspension:• Extempo-raneouspreparation

More Frequent:• Arthralgia

Less Frequent:• Hepatotoxicity (dose-related)

Rare:• Acute gouty arthritissecondary to hyperuricemia

• Thrombocytopenia, anemia• Interstitial nephritis• Porphyria

• Skin rash, pruritus• Photosensitivity• Malaise• GI disturbances (nausea,vomiting)

• Arthralgia• Hyperuricemia

Avoid in patients with severehepatic impairment.

Reduce dose in patients withrenal or hepatic impairment.

Monitor LFTs and uric acid.

Pyrimethamine(Daraprim)

Tablet: • 25 mg


Less Frequent:• Neutropenia• Thrombocytopenia• Megaloblastic anemia

Rare:• SJS• Seizure

• Skin rash• Photosensitivity• Dry mouth• GI disturbances (nausea,vomiting)

• CNS (depression, insomnia

To prevent hematologictoxicity, administer withleucovorin.

Monitor CBC.









Quinidine IV Serious:• Cardiac arrhythmias• QT interval prolongation• Hypoglycemia• Hemolytic anemia (withG6PD deficiency)

• Hepatotoxicity

Very Frequent:• Cinchonism—syndrome oftinnitus, reversible high-frequency hearing loss,deafness, vertigo, blurredvision, diplopia,photophobia, headache,confusion, and delirium;dose dependent

EKG monitoring is standard ofcare.

Do not give by bolus infusion.

If EKG changes observed,slow infusion rate.


Ribavirin

Virazole Powder forsolution fornebulization

RebetolOral capsulesand oralsolution

Copegus,Ribasphere,RibapakOral tablets andcapsules

Powder forSolution forNebulization: • Reconstitutedproductcontains 20 mg/mL


Capsules:• 200 mg

Tablets:• 200 mg• 400 mg• 600 mg

• Hemolytic anemia (withassociated potential forincrease in unconjugatedbilirubin and uric acid)

Less Frequent:• Neutropenia,thrombocytopenia, anemia

• Pancreatitis

• CNS effects (fatigue,headache, insomnia,depression)

• GI disturbances (abdominalpain, nausea, vomiting)

• Skin rash• Myalgia, arthralgia,weakness

Should not be used in patientswith severe renal impairment.

Should not be used asmonotherapy for treatment ofhepatitis C, but used incombination with IFN-α.

Intracellular phosphorylationof pyrimidine nucleosideanalogues (zidovudine,stavudine, zalcitabine)decreased by ribavirin, mayhave antagonism; use withcaution.

Enhances phosphorylation ofdidanosine; use with cautionbecause of increased risk ofpancreatitis/mitochondrialtoxicity.

Oral solution containspropylene glycol.

Teratogenic/embryocidal.Contraindicated in pregnantwomen and their malepartners. Avoid pregnancy foradditional 6 months aftertreatment.

Monitor CBC, renal function,LFTs, and thyroid function.Perform pregnancy testsregularly while on therapy.









Rifabutin(Mycobutin)



More Frequent:• Allergic reaction (rash,pruritus)

• Neutropenia

Less Frequent:• Asthenia

Rare:• Arthralgia, myalgia• Change in taste • Pseudojaundice • Thrombocytopenia• Uveitis

• Headache• Insomnia• Rash, staining of skin• GI disturbances (abdominalpain, diarrhea, nausea,vomiting, anorexia)

Preferably take on emptystomach, but may beadministered with food inpatients with GI intolerance.

The contents of capsules maybe mixed with applesauce ifpatient is unable to swallowcapsule.

May cause reddish to brown-orange color urine, feces,saliva, sweat, skin, or tears (candiscolor soft contact lenses).

Uveitis seen with high-doserifabutin (i.e., adults >300 mg/day), especially when combinedwith clarithromycin.


Use with caution in patientswith renal or hepaticimpairment.

Monitor CBC, LFTs; conductophthalmologic examinations.

Reduce dose in patients withrenal impairment.

Rifampin(Rifadin)


Capsules:• 150 mg• 300 mg

IV

Less Frequent:• Flu-like syndrome

Rare:• Blood dyscrasias• Hepatitis prodromalsyndrome (anorexia,nausea, vomiting,weakness)

• Hepatitis • Interstitial nephritis • Exfoliative skin disorders(including SJS)

• GI disturbances (abdominalpain, diarrhea)

• CNS effects (fatigue,headache, insomnia,depression)

• Rash• Discoloration of body fluids• Elevated serumtransaminases

• Visual changes

Preferably take on emptystomach, but can beadministered with food inpatients with GI intolerance;take with full glass of water.

Suspension formulation stablefor 30 days. Shake well prior todosing.

May cause reddish to brown-orange color urine, feces, saliva,sweat, skin, or tears (candiscolor soft contact lenses).


Use with caution in patientswith hepatic impairment.

Administer IV by slow infusion.Extravasation may cause localirritation and inflammation.










Streptomycin IM More Frequent: • Nephrotoxicity• Neurotoxicity (includingmuscle twitching, seizures)

• Peripheral neuritis• Ototoxicity, both auditoryand vestibular

Less Frequent:• Hypersensitivity (skin rash,redness, or swelling)

• Optic neuritis• Bone marrow suppression


• CNS effects (headache,ataxia, dizziness )

Usual route of administration is deepIM injection into large muscle mass.

For patients who cannot tolerate IMinjections, dilute to 12–15 mg in 100mL of 0.9% sodium chloride; mustbe infused over 30 to 60 minutes toavoid neuromuscular blockade.


Monitor renal function and hearingperiodically (e.g., monthly) inchildren on prolonged therapy.

Monitor serum concentrations(TDM).

Sulfadiazine Tablet:• 500 mg


Rare: • Crystalluria, renal failure• Bone marrow suppression/blood dyscrasias

• Severe hypersensitivitysyndrome

• Hemolytic anemia (withG6PD deficiency)

• GI disturbances (abdominalpain, diarrhea, nausea)

• CNS effects (headache,dizziness)

• Rash• Photosensitivity

Ensure adequate fluid intake toavoid crystalluria.

Monitor CBC, renal function, andurinalysis.

Monitor serum concentrations(TDM) if serious infection.

Trimethoprim-Sulfameth-oxazole(TMP-SMX)(Bactrim,Septra)

Oral Suspension: • TMP 8 mg/mLand SMX 40 mg/mL

TabletsSingle Strength:• TMP 80 mgand SMX 400 mg

DoubleStrength: • TMP 160 mgand SMX 800 mg

IV

More Frequent:• Skin rash

Less Frequent:• Hypersensitivity reactions(skin rash, fever)

• Hematologic toxicity(leukopenia, neutropenia,thrombocytopenia, anemia)

Rare:• Exfoliative skin disorders(including SJS)

• Hemolytic anemia (withG6PD deficiency)

• Methemoglobinemia• Renal toxicity (crystalluria,nephritis, tubular necrosis)

• CNS toxicity (asepticmeningitis)

• Pseudomembranous colitis• Cholestatic hepatitis• Thyroid functiondisturbance

• GI disturbances (anorexia,nausea, vomiting, diarrhea)

• Photosensitivity• Rash


Maintain adequate fluid intake toprevent crystalluria and stoneformation (take with full glass ofwater).

Potential for photosensitivity skinreaction with sun exposure.

IV infusion over 60 to 90 minutes

Monitor CBC, renal function.









Valacyclovir(Valtrex)

Tablets: • 500 mg• 1 g

Note: An oralsuspensionformulation 50 mg/mL canbe prepared inOra-Sweet orSyrpalta syrups)

Rare:• Renal failure• Bone marrow suppression• Thromboticmicroangiopathy/hemolyticuremic syndrome

• CNS (psychosis, seizures,delirium)

More Frequent:• Headache, nausea

Less Frequent:• Arthralagia• Dizziness, fatigue• GI disturbances (diarrheaor constipation, anorexia,abdominal pain, vomiting)

• Dysmenorrhea

Thrombotic thrombocytopeniapurpura/hemolytic uremicsyndrome has been reportedin HIV-infected adults withadvanced disease receivinghigh (i.e., 8 g/day) but not lowdoses.

Monitor CBC and renalfunction.

Valganciclovir(Valcyte)

Tablets:• 450 mg


More Frequent:• Granulocytopenia• Thrombocytopenia

Less Frequent:• Anemia• CNS effects (seizures,psychosis, hallucinations

• Hypersensitivity (fever,rash)

• Elevated transaminaseenzymes

• Increase in creatinine, BUN• Retinal detachment


• CNS effects (headache,insomnia)



Tablets should not be brokenor crushed.

Monitor CBC and renalfunction.

Potentially teratogenic andcarcinogenic.









Voriconazole(VFEND)

Tablet:• 50 mg• 200 mg

Oral Suspension:• 40 mg/mL

IV


• Anaphylactoid reaction withIV infusion



• Renal dysfunction• Cardiac arrhythmias• Pancreatitis• QT prolongation• Electrolyte abnormalities• Optic neuritis, papilledema

More Frequent:• Visual changes, dose-related (photophobia,blurry vision)

• CNS effects (dizziness,drowsiness, headache)

• GI disturbances (abdominalpain, constipation,diarrhea, anorexia, nausea,vomiting)

• Photosensitivity

Rare:• Gynecomastia• Elevated serumtransaminases

Oral tablets should be taken 1hour before or after a meal.

Shake oral suspension wellprior to dosing.

Maximum IV infusion rate 3 mg/kg/hour over 1 to 2hours.

Oral administration to patientswith impaired renal function ifpossible (accumulation of IVvehicle occurs in patients withrenal insufficiency)

Dose adjustment needed ifhepatic insufficiency.

Visual disturbances common(>30%) but transient andreversible when drug isdiscontinued.


Monitor renal function,electrolytes, and LFTs

Consider monitoring serumconcentrations (TDM).

a The toxicities listed in the table have been selected based on their potential clinical significance and are not inclusive of all side effectsreported for a particular drug.

Key to Acronyms: ARV = antiretroviral; BP = blood pressure; BUN = blood urea nitrogen; CBC = complete blood count; CDC = Centers forDisease Control and Prevention; CNS = central nervous system; Cr = creatinine; CrCl = creatinine clearance; EKG = electrocardiogram;G6PD = Glucose-6-phosphate dehydrogenase; GI = gastrointestinal; IFN-� = interferon alfa; IM = intramuscular; IND = investigational newdrug; IV = intravenous; LFT = liver function test; SJS = Stevens-Johnson Syndrome; SMX = sulfamethoxazole; SQ = subcutaneous; TDM = therapeutic drug monitoring; TMP = trimethoprim

Documents

Guidelines for the Prevention and Treatment of ... · PDF fileGuidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV ... (Malarone ) Tablets: