Practical Scenarios Calculating doses for newborns. Karen Buckberry

Transcription

1 Practical Scenarios Calculating doses for newborns Karen Buckberry

2 Real Life Midwife phones you HIV+ mother in labour Needs you to tell Dr what meds to prescribe for baby What info do you need?

3 Info needed Mum s last viral load Mum s current ARVs Mum s ARV/resistance history if has undetectable VL? Gestation Baby s weight BHIVA Pregnancy guidelines

4 Case One Mum s last viral load = undetectable Mum s current ARVs = Combivir/Saquinavir/ritonavir This is first regimen, started at 20/40 Full term baby (>34 weeks) Baby s weight = 3.5kg

5 Meds for baby Case One zidovudine monotherapy for 4/52 Dose for term baby? 4mg/kg BD orally Dose for 3.5kg baby? 4mg x 3.5kg = 14mg BD Zidovudine liquid 10mg/ml What volume should be given? 1.4ml BD

6 Case Two Mum s last viral load = unknown Mum s current ARVs = none No history of ARVs new diagnosis Term baby Baby s weight = 3.10kg

7 Case Two Meds for baby (high risk of MTCT) Zidovudine Lamivudine Nevirapine Doses?

8 Case Two Meds for baby (high risk of MTCT) Zidovudine 4mg/kg bd 4/52 Lamivudine 2mg/kg bd 4/52 Nevirapine 2mg/kg od 1/52 then 4mg/kg od 1/52 then STOP

9 Case Two Meds for baby (3.1kg) Zidovudine 12.4mg bd 4/52 Lamivudine 6.2mg bd 4/52 Nevirapine 6.2mg od 1/52 then 12.4mg od 1/52 then STOP What volumes are required? Round up to the nearest 0.1ml - think practical (measuring in syringe)

10 Case Two Would the doses be different if Mum had received ARVs for 1 week predelivery? depends if Mum had received Nevirapine

11 Case Three Mum s last viral load 150 copies/ml Mum s current ARVs TENOFOVIR 245mg OD RALTEGRAVIR 400mg BD ETRAVIRINE 200mg BD Mum s previous ARVs long history, many resistance mutations, low adherence, social issues, 1 positive child Currently 20/40

12 Case Three Long MDT discussion Benefits vs risks Decision to give baby ETRAVIRINE DARUNAVIR RITONAVIR ENFUVIRTIDE (T-20) What doses do you use?

13 Case Three - difficulties NO evidence for neonates Neonates are NOT small children Absorption Distribution Metabolism Excretion Extrapolating from paed dosing data for children (6yrs +) Drug Formulation

14 Case Three - considerations Mum MDR HIV If child +ve will be very difficult to treat Risk of seroconverting > risk of overdosing Paed data does not show dose related safety concerns Tablet formulations aliquots not accurate, may underdose Kaletra TDM in younger children tends to show low levels

15 Case Three - considerations Paed dose ranges Decision to use higher end of range?gestation of adequate gut absorption d/w neonate gastroenterologist Little data on drug absorption Decided try orals from 24/40

16 Case Three paed dosing data Darunavir/ritonavir Pharmacokinetic, and safety data supports a dose of 11-19mg/kg bd Boosted with mg/kg RTV bd Pts 6-17yrs, wt 20-50kg 19mg/kg DRV + 2.5mg/kg RTV

17 Case Three - paed dosing data Etravirine Safety data supports a dose of 4mg/kg (stage 1 of a paed study) Study now stage 2, using 5.2mg/kg - results not available Drug interaction between darunavir and etravirine [ETR] + [DRV] - No dose adjustment in adults Consider [ETR] seen in paeds at 4mg/kg in ETR plasma levels due to drug interaction with DRV lack of dose related side effects seen increase the dose by 30% to 5.2mg/kg bd

18 Case Three - paed dosing data Enfuvirtide Paed dose >6yrs 2mg/kg bd Licensed Subcutaneous injection Neonates little/no subcut tissue Administer IV - limited data in adults and paeds 90mg in 1ml - dilute down

19 Case Three - Monitoring Therapeutic Drug Levels (weekly) DRV + ETR Must state that sample is for a neonate on PEP - ensure if sample is haemolysed it will still get processed. Must state that sample is requested urgently - help result be prioritised. LFTs (deranged LFTs seen with darunavir and etravirine) U+Es (increased bicarbonate seen in paeds) FBC (decreased platelet count and neutropaenia seen in paeds) INR (increased INR seen in paeds)

20 Case Three ETRAVIRINE 5.2mg/kg ORALLY every 12 hours DARUNAVIR 19mg/kg ORALLY every 12 hours RITONAVIR 2.5mg/kg ORALLY every 12 hours ENFUVIRTIDE 2mg/kg by INTRAVENOUS INJECTION every 12 hours? emetogenic, suggest co-prescribe ONDANSETRON LIQUID 100mcg/kg TWICE a DAY, 30 minutes before Antiretroviral drugs.

21 Case Three Example for 3.5kg neonate ETRAVIRINE 18.2mg ORALLY every 12 hours DARUNAVIR 66.5mg ORALLY every 12 hours RITONAVIR 8.75mg ORALLY every 12 hours ENFUVIRTIDE 7mg by INTRAVENOUS INJECTION every 12 hours

22 Case Three - administration Darunavir and Etravirine only available in tablet formulation Tabs dissolve fairly well, but not completely in small volumes of water volume of water to disperse the tablet = volume to administer to neonate. Volumes of water chosen to disperse the tablets - balance between adequate dissolution and volumes to be administered.

23 Case Three - administration Darunavir - disperse 1 x 300mg tablet in 60ml water 5mg/ml 66mg = 13.2ml Etravirine - disperse 1 x 100mg tablet in 50ml water 2mg/ml 18mg = 9.0ml Ritonavir - 400mg/5ml 8.75mg = 0.1ml Enfuvirtide - 90mg/ml Remove 0.1ml (9mg), make up to 0.5ml with WFI (18mg/ml) 7mg =0.4ml

24 Case Three Birth plan agreed & prepared Communicated to Leicester Dr, CNS, Pharm Gestation >24/40 - orals Pharmacy obtained supply of drugs Mum weekly viral loads

25 Case Three Born (Saturday!!) Mum s VL = 54copies/ml Cloacal exstrophy Rare birth defect (affects 1 in 250,000) Imperforate anus HIV results 2 negatives so far

26 Etravirine TDM Case Three Trough level = 457ng/ml Minimum Effective Concentration for NNRTI resistant virus est. 52ng/ml Dose not subtherapeutic

27 Questions???