Appendix a: summary of pre-clinical and human data on oi drugs in pregnancy

APPENDIX A: SUMMARY OF PRE-CLINICAL AND HUMAN DATA ON OI DRUGS IN
PREGNANCY
FDA PREG-
PLACENTAL
CONCERNS IN HUMAN
RECOMMENDED USE IN
REPRODUCTION
PREGNANCY
PREGNANCY
CATEGORY
(NEWBORN/M
teratogenicity in mice, rats, or rabbits at human levels. mice later in the neonate with use in later pregnancy. reported with streptomycin but not with amikacin. good outcome. Labelled as contra-indicated in pregnancy. Invasive Candida or Aspergillus FDA PREG-
PLACENTAL
CONCERNS IN HUMAN
RECOMMENDED USE IN
REPRODUCTION
PREGNANCY
PREGNANCY
CATEGORY
(NEWBORN/M
recommended. No increase in anomalies with <200 first trimester exposures. limited human experience. prophylaxis if other choices rabbits or monkeys. trimester spontaneous Intrauterine growth anomalies noted but red-brown skin discolouration reported in several infants exposed throughout pregnancy. teratogenicity. May displace bound bilirubin in the neonate, increasing the risk of kernicterus. extremely high doses; no teratogenicity. FDA PREG-
PLACENTAL
CONCERNS IN HUMAN
RECOMMENDED USE IN
REPRODUCTION
PREGNANCY
PREGNANCY
CATEGORY
(NEWBORN/M
acceptable. No evidence of teratogenicity. abnormalities), rats (vertebral abnormalities), and rabbits (monophthalmia, cleft lip, palate). exencephaly, cleft palate) in rats, mice, and rabbits with high doses; not seen with usual human doses. exposures during pregnancy to ARV Registry: (910) 256-0238. during pregnancy. No increase in defects seen in several series after single-dose treatment. fluorouracil, which is teratogenic in animals and possibly in humans. safe in pregnancy as minimal systemic levels. growth retardation in rats depending on when administered. FDA PREG-
PLACENTAL
CONCERNS IN HUMAN
RECOMMENDED USE IN
REPRODUCTION
PREGNANCY
PREGNANCY
CATEGORY
(NEWBORN/M
anophthalmia, aplastic kidney and pancreas, hydrocephalus. human pregnancy without adverse effects. treatment modalities such as cryotherapy or trichloracetic acid recommended for wart treatment during pregnancy. Possible increased risk of intrauterine growth retardation. pregnancy. Prophylactic pyridoxine, 50mg/day, should be given to prevent neurotoxicity. Prophylactic vitamin K recommended at birth to prevent haemorrhagic disease. during pregnancy. No increase in defect rate noted among 156 infants born after first trimester itraconazole exposure. except inner ear changes in multiple species. Case reports of craniofacial, skeletal abnormalities in humans with prolonged fluconazole exposure during pregnancy. FDA PREG-
PLACENTAL
CONCERNS IN HUMAN
RECOMMENDED USE IN
REPRODUCTION
PREGNANCY
PREGNANCY
CATEGORY
(NEWBORN/M
born to 89 women with first trimester exposure. Complete embryolethality in rabbits at doses of 6mg/kg/day. specific pattern of defects noted, several studies did not find increased risk. FDA PREG-
PLACENTAL
CONCERNS IN HUMAN
RECOMMENDED USE IN
REPRODUCTION
PREGNANCY
PREGNANCY
CATEGORY
(NEWBORN/M
use in human pregnancy. Theoretical risk of haemolytic anaemia if foetus has G6PD deficiency. hamsters starting at doses below those used in humans. prevent haemorrhagic disease of the newborn. increased jaundice, kernicterus if used near delivery. at high doses. Decreased foetal weights and increased bone porosity were seen in monkeys with long-term exposure in utero to doses 25x usual human dose. Chronic administration in immature animals of FDA PREG-
PLACENTAL
CONCERNS IN HUMAN
RECOMMENDED USE IN
REPRODUCTION
PREGNANCY
PREGNANCY
CATEGORY
(NEWBORN/M
multiple species at 6-50x human doses have led to dose-specific bone changes ranging from decreased mineral density to severe osteomalacia and fractures. facial clefts with first trimester use. Potential for increased jaundice, kernicterus if used near delivery. embryopathy including "clover-leaf" skull, limb defects, developmental delay sometimes with neural tube defects. Frequency may increase with increasing maternal dose. limited. Prodrug of acyclovir, which is considered safe for use in pregnancy. Teratogenic in rats (cleft palate, hydronephrosis, ossification defects).

Source: http://www.chartcaribbean.org/careofplwa/pdfdcouments/subpdf/Section%20V/Appendix%20A.pdf