Abacavir

(ABC)

Ziagen™

Paediatric oral solution:

20 mg/mL;

Tablets:

300 mg In

UK abacavir is used off-label for children under 12 years

Neonatal dose: Not approved for infants less than 3 months of age. In infants between 1 and 3 months of age, a dose of 8 mg/kg of body weight twice daily is under study.

Paediatric/adolescent dose: 8 mg/kg of body weight twice daily, maximum dose 300 mg twice daily. Adult dose: 300 mg twice daily.

Can be given without regard to food. Patients and parents must be cautioned about the risk of serious hypersensitivity reaction. A medication guide and warning card should be provided. Patients in the US experiencing a hypersensitivity reaction should be reported to the Abacavir Hypersensitivity Registry (1-800-270-0425)

Didanosine

(dideoxyinosine)

(ddI),

Videx ®

Paediatric powder for oral solution:

2g, 4g bottle for reconstitution with antacid,

named patient only;

Chewable tablets with buffers:

25, 100 and 150mg;

'Reduced mass' with buffer:

200mg;

Enteric coated formulation

125, 200, 250, 400mg

Neonatal dose (infants aged < 90 days): 200-240 mg per m2 of body surface area every 12 hours. * US guidelines 50mg/m2 every 12 hours. Paediatric dose: In combination with other antiretrovirals, 200-240 mg/m2 of body surface area per day taken either once or twice daily.

(Note: may need higher dose in patients with central nervous system disease.)

Adolescents/Adult dose: Body weight >60kg: 400mg per day, either once or twice daily. Body weight <60kg: 250mg per day, either once or twice daily.

For formulations containing buffering agents or antacids: Food decreases absorption; administer ddI on an empty stomach (at least 30 minutes before and 2 hours after a meal). When administering chewable tablets, at least two tablets should be administered for children over one year of age to ensure adequate buffering capacity (e.g., if the child's dose is 150 mg, administer two 25-mg tablets and one 100mg tablet and not one 150-mg tablet). Children < 1 year should receive a single dose. For oral solution: shake well and keep refrigerated; admixture is stable for 30 days.

For ddI/EC (without buffer): Food decreases absorption; UK HIV Pharmacist Group recommend not eating for two hours either side of the dose until ongoing studies clarify post-dose interaction. ddI/EC not recommended for children under 6 years old.

Lamivudine

(3TC),

Epivir ®

Solution:

10 mg/mL;

Tablets:

150 mg

Neonatal dose (infants aged < 30 days): 2 mg per kg of body weight twice daily.

Paediatric dose: 4 mg per kg of body weight twice daily.

Adolescent/Adult dose (>12 yr): Body weight >50 kg: 150 mg twice daily. Body weight < 50 kg: 2 mg per kg of body weight twice daily.

Can be administered with food.

For oral solution: store at room temperature. á Decrease dosage in patients with impaired renal function.

Stavudine

(d4T),

Zerit ®

Solution

:1 mg/mL;

Capsules:

15, 20, 30, and 40 mg.

Neonatal dose: under evaluation in PACTG 332. As paediatric dose.

Paediatric dose: 1 mg per kg of body weight every 12 hours (up to weight of 30 kg). Over 30kg as adult. Adolescent/Adult dose: Body weight >60 kg:40 mg twice daily. Body weight < 60 kg: 30 mg twice daily.

Can be administered with food.

Need to decrease dose in patients with renal impairment.

For oral solution: shake well and keep refrigerated; solution stable for 30 days.

Zidovudine

(ZDV,

AZT),

Retrovir ®

Syrup:

10 mg/mL;

Capsules:

100 mg;

Tablets:

300 mg;

Concentrate for injection/for intravenous infusion: 10 mg/mL.

Dose for premature infants: (Standard neonatal dose may be excessive in premature infants.) Under study in PACTG protocol 331: 1.5 mg/kg of body weight every 12 hours from birth to 2 weeks of age; then increase to 2 mg/kg of body weight every 8 hours after 2 weeks of age.

Neonatal dose: Oral: 2 mg/kg of body weight every 6 hours. Intravenous: 1.5 mg/kg of body weight every 6 hours.

Paediatric usual dose: Oral: 160 mg/m2 of body surface area every 8 hours. Intravenous (intermittent infusion): 120mg/m2 of body surface area every 6 hours. Intravenous (continuous infusion): 20 mg/m2 of body surface area/per hour.

Paediatric dosage range: 90 mg/m2 of body surface area to 180 mg/m2 of body surface area every 6-8 hours.

Adolescent/Adult dose: 200 mg three times a day or 300 mg twice daily.

Can be administered with food

(although the manufacturer recommends administration 30 minutes before or 1 hour after a meal).

Decrease dosage in patients with severe renal impairment. Substantial granulocytopenia or anemia may necessitate interruption of therapy until marrow recovery is observed; use of erythropoietin, filgrastim, or reduced ZDV dosage may be necessary in some patients. Reduced dosage may be indicated in patients with substantial hepatic dysfunction.

Infuse intravenous loading dose or intermittent infusion dose over 1 hour. For intravenous solution: dilute with 5% dextrose injection solution to concentration <4 mg/mL; refrigerated diluted solution is stable for 24 hours. Some experts in paediatric HIV infection use a dose of 180 mg/m2 of body surface area every 12 hours when using in drug combinations with other antiretroviral compounds, but data on this dosing in children is limited.

Efavirenz

(DMP-266)

Sustiva™

Capsules:

50, 100 and 200 mg. doses

Syrup -

30mg/ml (doses)

Syrup available on named-patient programme.

Neonatal dose: Unknown

Paediatric dose: Indicated for >3 years old and >13kg only. Administered once daily.

There is currently no data available on the appropriate dosage for children under age 3 years.

Adult/adolescent dose: 600 mg once daily

Efavirenz can be taken with and without food although side-effects may be reduced if taken with food.

Relative bioavailability of efavirenz was increased by 50% (range 11-126%) following a high fat meal (1070 kcal, 82 grams fat, 62% of calories from fat - equivalent to 8 Milky Way bars in one sitting). As there is no information on safety of efavirenz when given above the recommended dose, administration with a high fat meal should be avoided.

Capsules may be opened and added to liquids or foods but efavirenz has a peppery taste; grape jelly has been used to disguise the taste.

Bedtime dosing is recommended, particularly during the first 2-4 weeks of therapy, to improve tolerability of central nervous system side effects.

Nevirapine

(NVP)

Viramune®

Suspension:

10 mg/mL;

Tablets:

200 mg.

Neonatal dose (through age 3 months): Under study in Paediatrics AIDS Clinical Trial Group protocol 365: 5 mg/kg of body weight once daily for 14 days, followed by 120 mg/m2 of body surface area every 12 hours for 14 days, followed by 200 mg/m2 of body surface area every 12 hours.

Paediatric dose: 120 to 200 mg/m2 of body surface area every 12 hours. Note: Initiate therapy with 120 mg/m2 of body surface area administered once daily for 14 days. Increase to full dose administered every 12 hours if there are no rash or other untoward effects.

Note: Gt Ormond St recommend 4mg/kg once daily for the first 14 days, then 7mg/kg twice daily for children under 8 years old and 4mg/kg twice daily for children over 8

Adolescent/Adult dose: 200 mg every 12 hours. Note: Initiate therapy at half dose for the first 14 days. Increase to full dose if there is no rash or other untoward effects. .

Can be administered with food.

May be administered concurrently with ddI.

NVP-associated skin rash usually occurs within the first 6 weeks of therapy. If rash occurs during the initial14-day lead-in period, do not increase dose until rash resolves. NVP should be discontinued immediately in patients who develop severe rash or a rash accompanied by constitutional symptoms (i.e., fever, oral lesions, conjunctivitis, or blistering).

Suspension must be shaken well; store at room temperature.

NOTE: EMEA requires fortnightly monitoring including liver fucntion test every two weeks for the first 8 weeks.

Paediatric oral solution

15mg/mL;

Capsules:

50 and 150mg.

Neonatal Dose: No pharmacokinetic data on dosing in children less than 4 years old.

Paediatric/Adolescent Dose (<50kg): Oral Solution: 22.5 mg/kg bid or 17mg/kg tid (maximum daily dose 2,800 mg).

Capsules: 20 mg/kg bid or 15 mg/kg tid (maximum daily dose 2,400 mg)

Adults Dose: 1,200 mg (eight 150 mg capsules) bid

NOTE: Adult dosing of amprenavir is now largely in BID combinations with ritonavir at 100mg RTV/600mg APV BID. These doses have not been approved by either the FDA or EMEA and confirming drug levels with TDM in dual PI combinations is recommended in paediatric care.

Amprenavir should not be used in children less than 3 years of age because of the lack of data in children < 3 years of age, the paucity of data in children in general, the uncertain impact of extremely high doses of vitamin E, and the propylene glycol content of the oral liquid preparation (the serum half-life of propylene glycol in neonates is prolonged at 16.9 hours compared to 5 hours in adults).

The oral solution and capsule formulation are not interchangeable on a mg per mg basis. The oral bioavailability of the oral solution is 14% less than that of the capsule. Amprenavir may be taken with or without food, but should not be given with a high fat meal (about seven Milky Way bars) as there is a 21% decrease in the AUC when amprenavir is administered after a high fat meal of 67 grams of fat compared with the fasting state. Patients taking antacids (or ddI) should take amprenavir at least 1 hour before or after antacid (or ddI) use.

Indinavir

IDV

Crixivan¨

Capsules:

200, 333 and 400 mg.

100mg capsules expected July 2001

Paediatric formulation (solution) only available in Netherlands.

Neonatal Dose: Unknown. Due to side effect of hyperbilirubinemia, should not be given to neonates until further information is available.

Children and Adolescents (4-17yo): 500 mg/m2 (dose adjusted from body surface area (BSA) based on height and weight every 8 hours (see below). Equivalent adult dose of 800mg every 8 hours should not be exceeded.

Adult dose: 800mg every 8 hours.

NOTE: Adult dosing of indinavir is now largely in BID combinations with ritonavir at 400mg/400mg BID, 100mg RTV/800mg IDV BID, or 200mg RTV/600mg IDV BID. These doses have not been approved by either the FDA or EMEA and confirming drug levels with TDM in dual PI combinations is recommended in paediatric care.

Administer on an empty stomach 1 hour before and 2 hours after a meal (or can take with a light meal).

Adequate hydration required to minimise risk of nephrolithiasis (at least 48 oz of fluid daily in adult patients).

If co-administered with ddI, give at least 1 hour apart on an empty stomach.

Decrease dose in patients with hepatic insufficiency.

Capsules are sensitive to moisture and should be stored in original container with desiccant. Blister packs of 400mg now available.

Indinavir capsules should only be given to children who are able to swallow hard capsules. Indinavir has not been studied in children under 4 years old.

Lopinavir/r

Kaletra

ABT-378

Available in UK on named patient basis only.

Paediatric dosing based on limited data.

Capsules:

50, 100 and 200 mg. doses

Syrup -

30mg/ml (doses)

Syrup available on named-patient programme.

Capsules: >2 years with body surface area >1.3m2 is 3 capsules taken twice daily with food.

Adolescent/Adult dose: 3 capsules twice daily.

Oral solution: 230/57.5mg/m2 up to a maximum of 400/100mg twice daily. A higher dose of 300/75mg/m2 should be considered when co-administered with efavirenz or nevirapine. Some clinicians prefer this higher dose to be used for all children - as in the M98-940 paediatric study - see this report.

Adolescent/Adult dose: 5ml (400/100mg) twice daily.

Doses of both formulations should be administered with food.

Oral solution dose should be administered using a claibrated syringe.

Both formulations can be stored at room temperature for up to six weeks, and refridgerated otherwise.

Nelfinavir

Viracept ®

Suspension:

10 mg/mL;

Tablets:

200 mg.

Neonatal dose: Recent PK subsudies including PENTA 7 (see Treatment for newly born babies page of this report) suggested dosing up to 170 mg/kg/day of body weight, split into twice daily doses.

< 12 months old: 150kg/mg/day split into twice daily doses.

Paediatric dose: 50 to 60mg/kg of body weight twice daily. Not to exceed 1250g maximum dose.

Adolescent/Adult dose: 1250 mg twice daily.

Administer with meal or light snack.

If coadministered with ddI, nelfinavir should be administered 2 hours before or 1 hour after ddI.

For oral solution: powder may be mixed with water, milk, pudding, ice cream, or formula (for up to 6 hours). Do not mix with any acidic food or juice because of resulting poor taste. Do not add water to bottles of oral powder; a special scoop is provided with oral powder for measuring purposes.

Tablets can be dispersed in water and are used more frequently than the powder. The dispersion can be mixed with milk or chocolate milk; tablets also can be crushed and administered with pudding.

Ritonavir

Norvir ®

Paediatric oral solution

15mg/mL;

Capsules:

50 and 150mg.

Neonatal dose: Under study in Paediatric AIDS Clinical Trial Group protocol 354 (single dose pharmacokinetics).

Paediatric usual dose(> 2years): 350 mg/m2 of body surface area every 12 hours. [US guidelines suggest this dose should be 400mg/m2]. To minimize nausea/vomiting, initiate therapy starting at 250 mg/m2 of body surface area every 12 hours and increase stepwise to full dose over 5 days as tolerated.

Paediatric dosage: 350 to 400mg/m2 of body surface area every 12 hours. Not to exceed 600mg BID.

Adolescent/Adult dose: 600 mg twice daily. To minimize nausea/vomiting, initiate therapy starting at 300mg twice daily and increase stepwise to full dose over 5 days as tolerated.

NOTE: Adult use of ritonavir is now largely as a PK enhancer for a second PI (indinavir, saquinavir, amprenavir). Recommendations for doses these combinations have not been made by either the FDA or EMEA and confirming drug levels with TDM in dual PI combinations is recommended in paediatric care.

Administration with food increases absorption.

If ritonavir is prescribed with ddI, there should be 2 hours between taking each of the drugs.

Oral solution must be kept refrigerated and stored in original container; can be kept at room temperature if used within 30 days.

To minimize nausea, therapy should be initiated at a low dose and increased to full dose over 5 days as tolerated.

Techniques to increase tolerance in children: a) mixing oral solution with milk, chocolate milk, or vanilla or chocolate pudding or ice cream; b) dulling the taste buds before administration by chewing ice, giving popsicles or spoonfuls of partially frozen orange or grape juice concentrates; c) coating the mouth by giving peanut butter to eat before the dose; or d) administration of strong-tasting foods such as maple syrup, cheese, or strong-flavored chewing gum immediately after dose.

Saquinavir

Fortovase™

(soft gel capsule)

Invirase™

(hard gel capsule - old formulation)

Soft gel capsules: 200 mg

Hard gel capsules: 200 mg;

Neonatal dose: Unknown.

Paediatric dose:

Soft Gel Capsule: 33mg/kg three times daily. (Currently being studied in PACTG protocol 397).

[In children >7 years there is some experience of dual combination with Invirase (hard gel capsule) and ritonavir dosed at 200mg/200/mg BID.]

Adolescent/Adult dose: Soft gel capsules: 1200 mg three times a day or 1600mg twice daily. Hard gel capsules: 600 mg three times a day;

NOTE: Adult dosing of saquinavir is now largely in BID combinations of Fortovase with ritonavir at 400mg/400mg BID. This dose has not been approved by either the FDA or EMEA and confirming drug levels with TDM in dual PI combinations is recommended in paediatric care.

Administer within 2 hours of a full meal to increase absorption.

Concurrent administration of grapefruit juice increases saquinavir concentration.