Drugs in Pregnancy and Breastfeeding latest 2.pdf

Prescribing in pregnancy and breastfeeding. How can we do more good than harm? Katy Harries Reproductive health  NB: Read SAMF prescribing during pregnancy and make notes Influence of the...

Prescribing in pregnancy and breastfeeding. How can we do more good than harm? Katy Harries Reproductive health  NB: Read SAMF prescribing during pregnancy and make notes Influence of the drug on the foetus Characteristics of the medicine Particle size Lipid solubility Free or protein-bound Influence of the drug on the foetus Distribution of drug in the foetal tissue Metabolism of drug in the foetus Stage of foetal development at time of exposure Mary was shocked to discover she was six weeks pregnant, but remembered starting her active tablets a day or two late after her placebo break around six weeks ago. She has made an appointment with her doctor and is anxious to hear how the contraceptive tablets she’s been taking before she realized she was pregnant, might affect the baby. Influence of the drug on the foetus Toxic Teratogenic Therapeutic Influence of the drug on the foetus Toxic High levels of drug in foetus →predictable effects as in adults on high doses, prolonged exposure opiates → respiratory depression benzodiazepine → dependance & withdrawal tetracycline antibiotics → causes staining of deciduous teeth (yellow-grey-brown), enamel hypoplasia, inhibition of bone growth NSAIDS: C/I from 2nd trimester → ↑ risk of premature closure of the ductus arteriosus which can lead to foetal heart failure beta2 Agonists → fetal tachycardia phenytoin → haemorrhagic disease of the newborn Vit K supplementation in late pregnancy chloramphenicol → neonatal grey baby syndrome and cardiovascular collapse  Influence of the drug on the foetus Teratogenic Target certain organs → characteristic malformations Effects depend of stage of foetal development Dose-dependant incidence May cause: - embryonic death - morphological abnormalities - physiological defects - psychomotor, intellectual,behavioural problems Influence of the drug on the foetus Teratogenic Many mechanisms- not all well understood. direct effect on the mother which may result in an indirect effect on the foetus, drugs may act on the placenta, changing the passage of oxygen and nutrients to the foetus, drugs may act directly on the foetus, or they may result in a deficiency of a critical substance eg folic acid. Influence of the drug on the foetus Teratogenic Thalidomide http://www.youtube.com/watch?v=bJSKxUfK3cA&feature=pla yer_embedded (link posted on Moodle) Thalidomide is an example of a drug that may profoundly affect the development of the limbs after only brief exposure, if this exposure occurs at a critical time in the development of the limbs. The risk of phocomelia (congenital absence of the upper arm or leg, the hands or feet being attached to the trunk by a short stump) risk occurs when exposure with thalidomide occurred during the 4th to the 7th weeks of gestation because it is during this time that the arms and legs develop. Thalidomide was used originally as a sedative and then to treat colds, flu, nausea and morning sickness in pregnant women. It was withdrawn when it was linked with this teratogenicity -about 10000 children were born with phocomelia as a result of thalidomide. This drug is relatively safe in humans after birth and is undergoing trials as a drug which regulates the immune system-it is useful in treating some leprosy complications but is only prescribed in limited strictly controlled conditions Influence of the drug on the foetus Teratogenic alcohol: foetal alcohol syndrome. Abstinence considered safest anticonvulsants: - sodium valproate risk regarded as greatest - include ↑risk of neural tube defects and foetal syndrome associated with facial deformities - phenytoin associated with foetal hydantoin syndrome anticonvulsants and trimethoprim (folic acid antagonists) ↑ risk of neural tube and other defects folic acid supplementation before and during pregnancy Vitamin A derivatives e.g. isotretinoin ACE inhibitors and Angiotensin II receptor blockers - include renal damage  Influence of the drug on the foetus Teratogenic fluconazole and other azole antifungals (avoid in HIV positive mothers in first trimester) antineoplastic agents especially alkylating agents eg methotrexate Lithium -including cardiovascular defects especially 1st trimester paroxetine -including cardiovascular defects (ventricular septal defect) statins Stop during pregnancy as this will have a limited effect on long-term lipid control warfarin -including nasal hypoplasia and stippled epiphyses (can lead to shortening of limbs and digits), also CNS and eye defects (mainly 1st trimester) and foetal and neonatal haemorrhage (mainly 3 trimester) can be used between 13 and 36 weeks rd testosterone and danazol -masculinization of female external genitalia Mary was reassured that although hormonal contraception should be stopped in pregnancy, despite many exposures to current hormonal contraceptive types, currently no evidence of harm to the foetus Influence of the drug on the foetus Therapeutic Steroids before preterm birth to stimulate foetal lung maturation Folic acid to decrease risk of neural tube defects ARVs PMTCT Influence of the drug on the foetus Therapeutic Prevention of Mother to Child Transmission of eg HIV Recent guidelines 2019 Guidelines for PMTCT Pg 17  Government advice on this has changed after results of new studies- now this group can also take dolutegravir  Government advice on this has changed after results of new studies as in larger studies this risk only negligibly larger Potential risks of DTG around the time of conception Government advice on this has changed after results of new studies Guidelines have changed- this is no longer necessary  How government advice has changed See Updated guidance for dolutegravir during pregnancy in the PMTCT folder See Updated guidance for dolutegravir during pregnancy in the PMTCT folder Mary is feeling dreadful. She is suffering from severe nausea all day long and has vomited several times in the last week. Even the thought of a cup of tea makes her feel sick and all she feels like eating is a plain baked potato with no seasoning. She phones to ask if there is something she can take for this morning sickness. Nausea and Vomiting of Pregnancy Excerpt from the SAMF Antiemetics and Antinauseants Nausea and Vomiting of pregnancy Mild nausea and vomiting in early pregnancy usually occur soon after rising; management in the first place is by reassurance, attention to emotional factors, and general measures, such as a cup of tea with a biscuit before rising, and light and frequent meals with adequate fibre intake. These approaches are frequently all that is needed. A mixture of sucrose and phosphoric acid (as Emetrol or Emex) may be useful. If moderate nausea occurs, the patient should be investigated. In resistant cases, specific drug therapy may be necessary. Doxylamine (an antihistamine) is the best documented antiemetic for use in pregnancy; its safety and efficacy appear to be acceptable. Other apparently safe antihistamines include cyclizine, while buclizine and diphenhydramine are considered less desirable. The management of hyperemesis gravidarium involves admission to hospital, intravenous hydration, correction of electrolyte abnormalities and parenteral antiemetics, either IM (prochloperazine) or IV (metoclopramide given either as bolus doses or continuous infusion). Ondansetron can be added in pregnancies over 12 weeks if vomiting does not resolve. It is always important to exclude organic causes of hyperemesis such as thyrotoxicosis, urinary tract infection, and gestational trophoblastic disease. Influence of the drug on the foetus Behavioural teratogens Agents which are CNS teratogens (e.g. alcohol) are also likely to cause behavioural abnormalities even when exposure in utero is at doses below which major malformations are produced Possibility for all CNS active drugs Foetus is susceptible to behavioural toxicity is longer than for structural malformations because the CNS grows and develops throughout pregnancy  FDA-assigned Pregnancy categories ▪ A many good studies not shown risk ▪ B ▪ C ▪ D ▪ X evidence of risk greater than any benefit As from June 2015, the Pregnancy and Lactation Labelling Rule (PLLR) came into effect for new drugs (and phased in for old drugs). The pregnancy categories to be removed and risk-benefit information will be required.  Pregnancy categories Old FDA Description Example category A Adequate and well-controlled levothyroxine studies have failed to demonstrate folic acid a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters). B Animal reproduction studies have methyldopa failed to demonstrate a risk to the paracetamol fetus and there are no adequate and well-controlled studies in pregnant women.  Pregnancy categories Old FDA Description Example category D There is positive evidence of phenytoin, carbamazepine human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. X For this drug, studies in animals or isotretinoin, simvastatin humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits Mary is in her third trimester now and has developed a severe cold. She has a headache and stuffy nose. A front shop lady at the pharmacy has suggested Corenza C® (which contains an antihistamine, a decongestant and aspirin) Mary phones to find out if these are safe in pregnancy and is told that there is a risk of neonatal haemorrhage with the use of aspirin in the third trimester. Mary’s stuffy nose could be managed with non-drug treatment, with steam inhalation and and nasal irrigation with saline for symptomatic relief, Paracetamol could be used for pain (Pregnancy Category B) Food containing vitamin C and maybe a vitamin C supplement would decrease duration of the cold (see Vitamins notes from 2.4) Antihistamines: limit use to true indications, especially in the first trimester  Hypertension in pregnancy Adverse effects in pregnancy with the following antihypertensives: hydrochlorothiazide: category B but D if used in pregnancy-induced hypertension: ineffective and ↓ placental perfusion - may cause foetal and neonatal thrombocytopaenia, hypoglycaemia, electrolyte disturbances, jaundice ACE inhibitors (e.g. enalapril) and ATII receptor antagonists (e.g. valsartan): category C first trimester, category D second and third trimester. -associated with foetal cardiovascular and central nervous system malformations, foetal kidney damage and foetal death - adequate contraception needed for women of childbearing age Beta blockers (e.g. atenolol): category C first trimester, category D second and third - intrauterine growth retardation, neonatal hypoglycaemia, bradycardia, respiratory depression Calcium channel blockers (e.g. amlodipine): category C - Labour may be prolonged The antihypertensive of choice in pregnancy is : methyldopa NB adverse effect of methyldopa: depression Hypertension in pregnancy Read 6.4 ‘Hypertensive Disorders’ in pregnancy in the STG Adult Hospital Guidelines Heart disease in pregnancy Depression in pregnancy  Clotting in pregnancy A clot in the lung is a leading cause of pregnancy-related death Women are 5 x more likely to experience a dangerous clot during pregnancy and 20 x more likely in the three months after giving birth To prevent clots in a pregnant woman who has previously had a clot Non-drug prevention: Compression stockings or compression devices that keep the blood moving in the legs Recommended medication for prevention of clots in pregnancy is unfractionated heparin or low molecular weight heparin (LMWH)e.g. enoxaparin. LMWHs not recommended for therapeutic use e.g. study of use in mothers with prosthetic heart valves stopped due to poor outcomes Other anticoagulants problematic eg warfarin (see earlier slides) and there is no controlled data for use of rivaroxaban (a new oral anticoagulant or NOAC in pregnancy Mary’s waters break in the night 3 days after her due date. She goes into labour and has a healthy baby boy by vaginal delivery. Post- delivery, the doctor prescribes Stopayne, Fybogel Orange and Stilnox® tablets. Influence of drug on breastfed infant Read SAMF prescribing during Post-delivery drugs breastfeeding and make notes Stopayne contains meprobamate (paracetamol, codeine and caffeine.. Problems for mum Codeine causes constipation Problems for baby Caffeine causes irritability Problems for mum and baby Meprobamate an old sedative,largely replaced by benzodiazepines. Mum and baby will be too drowsy to initiate regular feeds and to focus on latching Fybogel Orange contains ispaghula husk (a bulk laxative) helpful to soften and pass stool Stilnox contains zolpidem ( a sleeping tablet) Same issue as meprobamate Five weeks after the baby’s birth, Mary asks for your advice. She is suffering from constipation and plans to buy some Senokot.® What do you advise her? From the SAMF senna monograph: “Senna is excreted in breast milk in sufficient quantities to have an adverse effect on the nursing infant” But from the Prescribing during lactation guidelines: “Senna in usual doses should not affect the infant. So take minimum dose if bulk forming laxatives not helping and monitor infant Mary’s little boy Michael is 10 weeks old and he has a runny nose so she went to her paediatrician for a checkup. The doctor offers reassurance that all is well. bursts into tears and says she’s been feeling weepy, that her breasts do not feel full and that she is convinced she doesn’t have enough milk. The doctor prescribes sulpiride (Eglonyl®). If Mary has a cold and wants an analgesic for headache is aspirin suitable? Check out the SAMF…  Influence of drug on breastfed infant Sulpiride The use of sulpiride and other antipsychotics to enhance breast milk production in breast feeding women is not recommended: Listed as an antipsychotic drug Used in new mothers for –mood elevating effect and for increasing breast milk supply. Extrapyramidal side effects associated with all this class of drugs Drug excreted in breastmilk and may be associated with adverse effects in the infant Little data available, use with caution and only if essential *Antipsychotics should only be used in pregnancy for the treatment of psychoses requiring this therapy at the lowest effective doses If an antipsychotic is needed: avoid clozapine due to high drug levels in the breastmilk, excessive sedation and can cause agranulocytosis A friend of ’s warns her that sulpiride brought on a blocked duct problem which was so painful she gave up breastfeeding. When breastfeeding there is a feedback loop between mother and child so that the mother’s milk supply increases in response to nipple stimulation as the baby feeds, in this way, unlike the first few days when there is an oversupply, the body ‘learns’ how much milk to supply so the breasts do not feel full all the time but fill and empty when the baby feeds. Mary might have incorrectly interpreted this lack of fullness together with Michael’s fussiness and inability to stay latched as being caused by an underproductive milk supply. Sulpiride will increase milk supply unrelated to the feedback loop. If Michael’s nasal stuffiness causes less feeding, she will end up with engorgement due to oversupply of milk which may lead to a painful blocked duct which can lead to mastitis, a reason why some give up breastfeeding Mary decided to get a second opinion and checks with her GP who changed the prescription to the antidepressant sertraline. They Postpartum depression sufficient should be taken seriously and while support and non-drug measures may help, for some mothers this may not be enough and a drug may be needed The GP is not sure that breastfeeding is advisable and he suggests weaning. Mary is very disappointed and discusses this with a nursing sister when she visits the well baby clinic for a vaccination. She contacts the La Leche Breastfeeding association who offer specialist advice regarding drugs and lactation. The drug is checked out and is relieved to hear that it can be used as the effect of this drug on breastfeeding has been studied and this drug is excreted into the breastmilk in low levels (compared with many other antidepressants). Armed with the support of the midwife, La Leche and good scientific information, she phones her GP and is able to convince him to agree to her continuing breastfeeding, while carefully monitoring Michael for colic, sedation, irritability and diarrhoea and anything else unusual. Mary meets some other mothers at a breastfeeding support group arranged by La Leche. Relax together with some tea and chat. One mother has had a similar experience and suggests that Michael might be battling to latch or stay latched due to the nasal stuffiness from his cold and therefore his inability to feed and breathe at the same time. She recommends a mucus extractor available at a pharmacy which helped her clear her baby’s nasal passages along with a drop of breastmilk in his nostrils. Mary fllowed this advice and went home to rest with her baby where she could offer him a feed often. As milk production increased with nipple stimulation, this increased her milk supply and her confidence. Mary’s baby is 16 weeks old and she’s really begun to enjoy being a mother. She feels breastfeeding has created a special bond between her and her baby. As the day looms when she will have to return to work, she is grateful that, after time spent apart, she will be able to reconnect with her baby in this special way.  Influence of drug on breastfed infant Post partum depression: (SSRI antidepressant) Consider benefit of drug to mother (and baby) and breastfeeding to mother and baby weighed against risk of drug to mother and baby; weighed against benefit of drug to mother (and baby) and risk of drug to mother and risk of not breastfeeding to baby (and mother) non-pharmacological treatments have been found to be helpful in the treatment of postpartum depression-consider options  Influence of drug on breastfed infant Post partum depression: Tricyclic antidepressants e.g. nortryptiline, imipramine are generally considered safe sertraline, paroxetine, are the most evidence- based medications for use during breastfeeding → low levels excreted in breastmilk serum infant levels of antidepressants do NOT need to be routinely recommended but need to monitor infant for adverse effects e.g. colic, sedation, irritability, diarrhoea, pulmonary hypertension Fluoxetine and citalopram found in high concs in breast milk