- Email: [email protected]
Consumption of teratogenic drugs in pregnant women in the primary care clinic
414
Scientific letters / Med Clin (Barc). 2017;149(9):412–416
References
Williams Hinojosa ∗ , Inés Sayago, Javier López
1. Sayago I, Krsnik I, Gomez-Bueno M, Garcia-Pavia M, Jaramillo N, Salas C, et al. Analysis of diagnostic and therapeutic strategies in advanced cardiac light-chain amyloidosis. J Heart Lung Transpl. 2016;35:995–1002. 2. Dubrey SW, Hawkins PN, Falk RH. Amyloid diseases of the heart: assessment, diagnosis, and referral. Heart. 2011;97:75–84. 3. Sayed RH, Rogers D, Khan F, Wechalekar AD, Lachmann HJ, Fontana M, et al. A study of implanted cardiac rhythm recorders in advanced cardiac AL amyloidosis. Eur Heart J. 2015;36:1098–105. 4. Kristen AV, Dengler TJ, Hegenbart U, Schonland SO, Goldschmidt H, Sack FU, et al. Prophylactic implantation of cardioverter-defibrillator in patients with severe cardiac amyloidosis and high risk for sudden cardiac death. Heart Rhythm. 2008;5:235–40. 5. Gilotra NA, Chow GV, Cingolani OH. Cardiac amyloidosis presenting with prolonged QT interval and recurrent polymorphic ventricular tachycardia. Tex Heart Inst J. 2013;40:193–5.
Instituto de Ciencias del Corazón (ICICOR), Hospital Clínico de Valladolid, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Valladolid, Spain
Consumption of teratogenic drugs in pregnant women in the primary care clinic夽 Consumo de fármacos teratogénicos en gestantes en atención primaria Dear Editor, Congenital malformations affect nearly 5% of new-borns in developed countries, related to exposures to environmental factors (drugs or toxic agents) during pregnancy, mainly in the first trimester. According to the World Health Organisation, 86% of pregnant women take drugs during pregnancy, with an average of 2.9 drugs per pregnant woman. In Spain, this percentage is 92.4% (more than 50% in the first trimester), with 3 drugs on average per pregnant woman. Consultation of a primary care midwife often represents the first contact of the pregnant woman with the health system, making it an appropriate setting to detect the consumption of potentially harmful drugs at this stage, so we propose to estimate the prevalence of this consumption. During 2013, an anonymous and face-to-face survey on consumption of drugs (prescribed or not, and naturopathy) was carried
∗ Corresponding author. E-mail address: williams [email protected] (W. Hinojosa).
2387-0206/ ˜ S.L.U. All rights reserved. © 2017 Elsevier Espana,
out in 2 healthcare sites in Mallorca, during the first visit and during week 16 and 24 of pregnancy control. The teratogenic risk was assessed based on the current Food and Drug Administration1 (FDA) and the Australian Drug Evaluation Committee2 (ADEC) criteria and, if not described in them, on the Spanish Agency of Medicines and Medical Devices (AEMPS).3 A lab test confirmation of the answers was not requested. The results were processed with Excel 972003 and the estimates are presented as means and percentages, together with their 95% confidence intervals (95% CI) calculated using the Epidat 4.1 software. 87 women participated, all of whom completed the 3 visits. The mean age was 28.3 years (95% CI 27.0–29.5). 60.9% (95% CI 49.9–71.2) already had children. Once the drugs usually indicated in gestation were excluded (folic acid, iodine, iron, vitamin B12 ), 13.8% (95% CI 7.3–22.9) did not take any drugs and the rest had a mean of 1.74 (95% CI 1.45–2.01). Analgesics, antibiotics and antiemetics clearly predominated. Drug consumption, when the risk of teratogenicity defined according to the criteria of the FDA and ADEC could be analysed, was (Table 1): 9.3 and 8.5% of groups D and X (in 4 cases they took more than one from these categories), 72 and 39% of group C, and 18.7 and 52.5% of groups A and B combined, respectively. All pregnant women with a risk treatment stopped taking it after this first visit, except one (antiepileptic treatment with oxcarbazepine).
Table 1 Distribution of drug consumption according to the risk of pharmacological teratogenicity of each regulatory agency analysed. Group
Number of active ingredients taken at least once by teratogenic risk groups according to regulatory agencies FDA
ADEC
A B C D X Unclassified
2 12 17 9 3 13
10 11 9 6
Total
56
56
20
Number of times the 87 pregnant women took the active ingredients by teratogenic risk according to the regulatory agencya FDA, total (%) 2 (1.23) 22 (13.5) 93b (57.4) 7 (4.3) 5 (3.1) 33 (20.3) 162
ADEC, total (%) 23 (14.2) 20 (12.3) 32 (19.7) 7 (4.3) – 80b (49.3) 162
AEMPS recommendation
Use
Avoid
Neutral
1
5
1
1
5
1
AEMPS, Spanish Agency of Medicines and Medical Devices; ADEC, Australian Drug Evaluation Committee; FDA, Food and Drug Administration from the USA. a The same woman can take more than one drug belonging to different teratogenic risk categories and the 2 agencies may differ regarding to which category some drugs are assigned. For example, diclofenac is always C according to ADEC, but FDA considers it C in the first and second trimesters and D in the third. b Forty-three corresponding to paracetamol, which is not mentioned by ADEC.
夽 Please cite this article as: Miralles-Corrales S, Campillo-Artero C, PuiguriguerFerrando J. Consumo de fármacos teratogénicos en gestantes en atención primaria. Med Clin (Barc). 2017;149:414–415.
Scientific letters / Med Clin (Barc). 2017;149(9):412–416
Consumption of drugs with a high teratogenic potential was detected in 20.7% of pregnant women, a figure slightly lower than that of other countries (28% in Denmark4 and 60% in France5 ), although the risk of teratogenicity of 12 drugs and other products could not be analysed according to the criteria of the same agencies (15 pregnant women were taking naturopathy or hemopathy products), which could increase the final percentage. In Spain, there are initiatives aimed at promoting information on the risk of teratogenicity during pregnancy (Spanish Collaborative Study of Congenital Malformations or pharmacological prescription in Castilla la Mancha), but the results obtained, although subject to limitations, show an inadequate (but avoidable) control on prescriptions with risk to the health of the foetus. Transferring this experience to other healthcare sites could improve the adequacy of prescription during pregnancy, analysing the specific consumption of these possible teratogens in a standard way during the scheduled routine control interviews. This intervention is simple and, in the case of a midwife’s primary care visit, viable and represents a highly cost-effective opportunity. Note This study has been considered of interest by the Research Commission of the University Hospital Son Espases, with file number CI-041-15. Acknowledgements
415
References 1. Food and Drug Administration. Evaluating the risks of drug exposure in human pregnancies. Rockville, MD: FDA; 2005. 2. Australian Drug Evaluation Committee. Australian categorisation system for prescribing medicines in pregnancy. Canberra: Department of Health, Therapeutics Goods Administration; 2011. ˜ 3. Agencia Espanola de Medicamentos y Productos Sanitarios. Fichas técnicas. Madrid: AEMPS; 2016. Available from: https://www.aemps.gob.es/ medicamentosUsoHumano/portada/home.htm [accessed 01.10.16]. 4. Olesen C, Steffensen FH, Nielsen GL, de Jong-van den Berg L, Olsen J, Sorensen HT. Drug use in the first pregnancy and lactation: a population-based survey among Danish women. The EUROMAP group. Eur J Clin Pharmacol. 1999;55: 139–44. 5. Lacroix I, Damase-Michel C, Lapeyre-Mestre M, Montastruc JL. Prescription of drugs during pregnancy in France. Lancet. 2000;356:1735–6.
Silvia Miralles-Corrales a,∗ , Carlos Campillo-Artero b , Jordi Puiguriguer-Ferrando c a Gerencia de Atención Primaria de Mallorca, Palma de Mallorca, Spain b Evaluación Clínica y de Servicios de Salud, Servei de Salut de les Illes Balears, Palma de Mallorca, Spain c Unidad de Toxicología Clínica, Servicio de Urgencias, Hospital Universitario Son Espases, Palma de Mallorca, Spain ∗ Corresponding
author. E-mail address: [email protected] (S. Miralles-Corrales). 2387-0206/ ˜ S.L.U. All rights reserved. © 2017 Elsevier Espana,
Mar Crespi, of the Pharmacy Service of the University Hospital Son Espases, and Joan Colom for their collaboration in the review of the teratogenic risk of each of the drugs mentioned.
Lactic acidosis associated (or induced by) metformin夽 Acidosis láctica asociada (o inducida por) metformina Dear Editor, Metformin is the most commonly prescribed oral antidiabetic agent for the treatment of type 2 diabetes1 and lactic acidosis is an adverse event related to it, with estimates of one case per 100,000 patients.2 In fact, 2 types of lactic acidosis have been proposed in this context: metformin-associated lactic acidosis (MALA) and metformin-induced lactic acidosis (MILA). MALA is defined by an arterial lactate >5 mmol/l and an arterial pH < 7.35 and is caused by the accumulation of metformin in the presence of precipitating factors (acute renal failure or dehydration) and risk factors (acute renal injury, hypoxemia, sepsis, alcoholism, hepatic impairment, contrast medium, myocardial infarction, and shock-derived conditions), whereas MILA, less frequent, occurs when metformin is the only cause of lactic acidosis with no apparent associated disease and generally related to acute poisoning.2 Although the pathophysiology is unclear,3 after diagnosis, the treatment involves alkalinization, support of vital functions, treatment of
夽 Please cite this article as: Ortiz-Lasa M, Gonzalez-Castro A, Penasco ˜ Martín Y. Acidosis láctica asociada (o inducida por) metformina. Med Clin (Barc). 2017;149:415–416.
underlying conditions, forced diuresis or haemodialysis for drug clearance.4 The mortality of patients with MALA ranges from 10.8% to 45% in the largest registered case series.5 We report 2 cases. The first patient is a 56-year-old man who was admitted for severe metabolic acidosis. As history of interest, he was a drinker, hypertensive, and presented COPD and type 2 diabetes mellitus on treatment with enalapril, tegretol and metformin (850 mg/8 h). He presented with a 5-day history of COPD exacerbation secondary to a respiratory superinfection before admission. After a decreased level of consciousness associated with abdominal pain, he was transferred to the hospital, showing signs of hypoglycaemia (20 mg/dl), severe metabolic acidosis and acute renal failure, being transferred to the ICU. His vital signs were: Temp 33 ◦ C, BP 140/60 mmHg, HR 80 bpm, RR 18 bpm. Dehydrated, poorly perfused. Lab results: pH 6.91, pCO2 25.3 mmHg, bicarbonate 4.8 mmol/l, base excess −26,500, leucocytes 25,300 (myelocytes 1.0%, band neutrophils 3.0%), lactate 13.84 mmol/l, glucose 19 mg/dl, urea 219 mg/dl, creatinine 11.89 mg/dl, FG 4. He was resuscitated with fluids, measures and correction of acid-base anti-potassium imbalances, with poor response, presenting CPA (asystole); the patient died after 25 min of advanced resuscitation. The levels of metformin collected at admission were 49.30 g/ml (being toxic from 5.00 g/ml). The second case was a 72-year-old man who presented with hypertension, atrial fibrillation and type 2 diabetes mellitus on irbersartan, furosemide, sintrom (warfarin) and metformin (850 mg/8 h). He was found at his home with decreased level of
Scientific letters / Med Clin (Barc). 2017;149(9):412–416
References
Williams Hinojosa ∗ , Inés Sayago, Javier López
1. Sayago I, Krsnik I, Gomez-Bueno M, Garcia-Pavia M, Jaramillo N, Salas C, et al. Analysis of diagnostic and therapeutic strategies in advanced cardiac light-chain amyloidosis. J Heart Lung Transpl. 2016;35:995–1002. 2. Dubrey SW, Hawkins PN, Falk RH. Amyloid diseases of the heart: assessment, diagnosis, and referral. Heart. 2011;97:75–84. 3. Sayed RH, Rogers D, Khan F, Wechalekar AD, Lachmann HJ, Fontana M, et al. A study of implanted cardiac rhythm recorders in advanced cardiac AL amyloidosis. Eur Heart J. 2015;36:1098–105. 4. Kristen AV, Dengler TJ, Hegenbart U, Schonland SO, Goldschmidt H, Sack FU, et al. Prophylactic implantation of cardioverter-defibrillator in patients with severe cardiac amyloidosis and high risk for sudden cardiac death. Heart Rhythm. 2008;5:235–40. 5. Gilotra NA, Chow GV, Cingolani OH. Cardiac amyloidosis presenting with prolonged QT interval and recurrent polymorphic ventricular tachycardia. Tex Heart Inst J. 2013;40:193–5.
Instituto de Ciencias del Corazón (ICICOR), Hospital Clínico de Valladolid, Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Valladolid, Spain
Consumption of teratogenic drugs in pregnant women in the primary care clinic夽 Consumo de fármacos teratogénicos en gestantes en atención primaria Dear Editor, Congenital malformations affect nearly 5% of new-borns in developed countries, related to exposures to environmental factors (drugs or toxic agents) during pregnancy, mainly in the first trimester. According to the World Health Organisation, 86% of pregnant women take drugs during pregnancy, with an average of 2.9 drugs per pregnant woman. In Spain, this percentage is 92.4% (more than 50% in the first trimester), with 3 drugs on average per pregnant woman. Consultation of a primary care midwife often represents the first contact of the pregnant woman with the health system, making it an appropriate setting to detect the consumption of potentially harmful drugs at this stage, so we propose to estimate the prevalence of this consumption. During 2013, an anonymous and face-to-face survey on consumption of drugs (prescribed or not, and naturopathy) was carried
∗ Corresponding author. E-mail address: williams [email protected] (W. Hinojosa).
2387-0206/ ˜ S.L.U. All rights reserved. © 2017 Elsevier Espana,
out in 2 healthcare sites in Mallorca, during the first visit and during week 16 and 24 of pregnancy control. The teratogenic risk was assessed based on the current Food and Drug Administration1 (FDA) and the Australian Drug Evaluation Committee2 (ADEC) criteria and, if not described in them, on the Spanish Agency of Medicines and Medical Devices (AEMPS).3 A lab test confirmation of the answers was not requested. The results were processed with Excel 972003 and the estimates are presented as means and percentages, together with their 95% confidence intervals (95% CI) calculated using the Epidat 4.1 software. 87 women participated, all of whom completed the 3 visits. The mean age was 28.3 years (95% CI 27.0–29.5). 60.9% (95% CI 49.9–71.2) already had children. Once the drugs usually indicated in gestation were excluded (folic acid, iodine, iron, vitamin B12 ), 13.8% (95% CI 7.3–22.9) did not take any drugs and the rest had a mean of 1.74 (95% CI 1.45–2.01). Analgesics, antibiotics and antiemetics clearly predominated. Drug consumption, when the risk of teratogenicity defined according to the criteria of the FDA and ADEC could be analysed, was (Table 1): 9.3 and 8.5% of groups D and X (in 4 cases they took more than one from these categories), 72 and 39% of group C, and 18.7 and 52.5% of groups A and B combined, respectively. All pregnant women with a risk treatment stopped taking it after this first visit, except one (antiepileptic treatment with oxcarbazepine).
Table 1 Distribution of drug consumption according to the risk of pharmacological teratogenicity of each regulatory agency analysed. Group
Number of active ingredients taken at least once by teratogenic risk groups according to regulatory agencies FDA
ADEC
A B C D X Unclassified
2 12 17 9 3 13
10 11 9 6
Total
56
56
20
Number of times the 87 pregnant women took the active ingredients by teratogenic risk according to the regulatory agencya FDA, total (%) 2 (1.23) 22 (13.5) 93b (57.4) 7 (4.3) 5 (3.1) 33 (20.3) 162
ADEC, total (%) 23 (14.2) 20 (12.3) 32 (19.7) 7 (4.3) – 80b (49.3) 162
AEMPS recommendation
Use
Avoid
Neutral
1
5
1
1
5
1
AEMPS, Spanish Agency of Medicines and Medical Devices; ADEC, Australian Drug Evaluation Committee; FDA, Food and Drug Administration from the USA. a The same woman can take more than one drug belonging to different teratogenic risk categories and the 2 agencies may differ regarding to which category some drugs are assigned. For example, diclofenac is always C according to ADEC, but FDA considers it C in the first and second trimesters and D in the third. b Forty-three corresponding to paracetamol, which is not mentioned by ADEC.
夽 Please cite this article as: Miralles-Corrales S, Campillo-Artero C, PuiguriguerFerrando J. Consumo de fármacos teratogénicos en gestantes en atención primaria. Med Clin (Barc). 2017;149:414–415.
Scientific letters / Med Clin (Barc). 2017;149(9):412–416
Consumption of drugs with a high teratogenic potential was detected in 20.7% of pregnant women, a figure slightly lower than that of other countries (28% in Denmark4 and 60% in France5 ), although the risk of teratogenicity of 12 drugs and other products could not be analysed according to the criteria of the same agencies (15 pregnant women were taking naturopathy or hemopathy products), which could increase the final percentage. In Spain, there are initiatives aimed at promoting information on the risk of teratogenicity during pregnancy (Spanish Collaborative Study of Congenital Malformations or pharmacological prescription in Castilla la Mancha), but the results obtained, although subject to limitations, show an inadequate (but avoidable) control on prescriptions with risk to the health of the foetus. Transferring this experience to other healthcare sites could improve the adequacy of prescription during pregnancy, analysing the specific consumption of these possible teratogens in a standard way during the scheduled routine control interviews. This intervention is simple and, in the case of a midwife’s primary care visit, viable and represents a highly cost-effective opportunity. Note This study has been considered of interest by the Research Commission of the University Hospital Son Espases, with file number CI-041-15. Acknowledgements
415
References 1. Food and Drug Administration. Evaluating the risks of drug exposure in human pregnancies. Rockville, MD: FDA; 2005. 2. Australian Drug Evaluation Committee. Australian categorisation system for prescribing medicines in pregnancy. Canberra: Department of Health, Therapeutics Goods Administration; 2011. ˜ 3. Agencia Espanola de Medicamentos y Productos Sanitarios. Fichas técnicas. Madrid: AEMPS; 2016. Available from: https://www.aemps.gob.es/ medicamentosUsoHumano/portada/home.htm [accessed 01.10.16]. 4. Olesen C, Steffensen FH, Nielsen GL, de Jong-van den Berg L, Olsen J, Sorensen HT. Drug use in the first pregnancy and lactation: a population-based survey among Danish women. The EUROMAP group. Eur J Clin Pharmacol. 1999;55: 139–44. 5. Lacroix I, Damase-Michel C, Lapeyre-Mestre M, Montastruc JL. Prescription of drugs during pregnancy in France. Lancet. 2000;356:1735–6.
Silvia Miralles-Corrales a,∗ , Carlos Campillo-Artero b , Jordi Puiguriguer-Ferrando c a Gerencia de Atención Primaria de Mallorca, Palma de Mallorca, Spain b Evaluación Clínica y de Servicios de Salud, Servei de Salut de les Illes Balears, Palma de Mallorca, Spain c Unidad de Toxicología Clínica, Servicio de Urgencias, Hospital Universitario Son Espases, Palma de Mallorca, Spain ∗ Corresponding
author. E-mail address: [email protected] (S. Miralles-Corrales). 2387-0206/ ˜ S.L.U. All rights reserved. © 2017 Elsevier Espana,
Mar Crespi, of the Pharmacy Service of the University Hospital Son Espases, and Joan Colom for their collaboration in the review of the teratogenic risk of each of the drugs mentioned.
Lactic acidosis associated (or induced by) metformin夽 Acidosis láctica asociada (o inducida por) metformina Dear Editor, Metformin is the most commonly prescribed oral antidiabetic agent for the treatment of type 2 diabetes1 and lactic acidosis is an adverse event related to it, with estimates of one case per 100,000 patients.2 In fact, 2 types of lactic acidosis have been proposed in this context: metformin-associated lactic acidosis (MALA) and metformin-induced lactic acidosis (MILA). MALA is defined by an arterial lactate >5 mmol/l and an arterial pH < 7.35 and is caused by the accumulation of metformin in the presence of precipitating factors (acute renal failure or dehydration) and risk factors (acute renal injury, hypoxemia, sepsis, alcoholism, hepatic impairment, contrast medium, myocardial infarction, and shock-derived conditions), whereas MILA, less frequent, occurs when metformin is the only cause of lactic acidosis with no apparent associated disease and generally related to acute poisoning.2 Although the pathophysiology is unclear,3 after diagnosis, the treatment involves alkalinization, support of vital functions, treatment of
夽 Please cite this article as: Ortiz-Lasa M, Gonzalez-Castro A, Penasco ˜ Martín Y. Acidosis láctica asociada (o inducida por) metformina. Med Clin (Barc). 2017;149:415–416.
underlying conditions, forced diuresis or haemodialysis for drug clearance.4 The mortality of patients with MALA ranges from 10.8% to 45% in the largest registered case series.5 We report 2 cases. The first patient is a 56-year-old man who was admitted for severe metabolic acidosis. As history of interest, he was a drinker, hypertensive, and presented COPD and type 2 diabetes mellitus on treatment with enalapril, tegretol and metformin (850 mg/8 h). He presented with a 5-day history of COPD exacerbation secondary to a respiratory superinfection before admission. After a decreased level of consciousness associated with abdominal pain, he was transferred to the hospital, showing signs of hypoglycaemia (20 mg/dl), severe metabolic acidosis and acute renal failure, being transferred to the ICU. His vital signs were: Temp 33 ◦ C, BP 140/60 mmHg, HR 80 bpm, RR 18 bpm. Dehydrated, poorly perfused. Lab results: pH 6.91, pCO2 25.3 mmHg, bicarbonate 4.8 mmol/l, base excess −26,500, leucocytes 25,300 (myelocytes 1.0%, band neutrophils 3.0%), lactate 13.84 mmol/l, glucose 19 mg/dl, urea 219 mg/dl, creatinine 11.89 mg/dl, FG 4. He was resuscitated with fluids, measures and correction of acid-base anti-potassium imbalances, with poor response, presenting CPA (asystole); the patient died after 25 min of advanced resuscitation. The levels of metformin collected at admission were 49.30 g/ml (being toxic from 5.00 g/ml). The second case was a 72-year-old man who presented with hypertension, atrial fibrillation and type 2 diabetes mellitus on irbersartan, furosemide, sintrom (warfarin) and metformin (850 mg/8 h). He was found at his home with decreased level of