Prescription of off-label and unlicensed drugs for preterm infants in a neonatal intensive care unit

Vieira, Verônica Cheles; Costa, Renart Santos; Lima, Raquel Cristina Gomes; Queiroz, Daiane Borges; Medeiros, Danielle Souto de

doi:10.5935/0103-507X.20210034

Acessibilidade / Reportar erro

Brasil

Revista Brasileira de Terapia Intensiva

Español English

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

ORIGINAL ARTICLE • Rev. bras. ter. intensiva 33 (2) • Apr-Jun 2021 • https://doi.org/10.5935/0103-507X.20210034 copy

Prescription of off-label and unlicensed drugs for preterm infants in a neonatal intensive care unit

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective:

To evaluate the use of off-label and unlicensed medications in preterm infants hospitalized in a neonatal intensive care unit.

Methods:

This nonconcurrent cohort study included preterm infants admitted to 3 neonatal intensive care units in 2016 and 2017 who were followed up during the neonatal period. The type and number of medications used were recorded for the entire period and classified based on the Anatomical Therapeutic Chemical. Descriptive and bivariate data analyses were performed to assess associations between the number of drugs used (total, off-label and unlicensed) and the explanatory variables of interest.

Results:

Four hundred preterm infants received 16,143 prescriptions for 86 different pharmaceuticals; 51.9% of these medications were classified as off-label and 23.5% as unlicensed. The most prescribed drugs were gentamicin and ampicillin (17.5% and 15.5% among off-label, respectively) and caffeine (75.5% among unlicensed). The results indicated significant associations between the use of off-label drugs and lower gestational age, low birth weight, lower 5-minute Apgar score, advanced resuscitation maneuver in the delivery room and death. The prescription of unlicensed drugs was associated with lower gestational age, low birth weight and 5-minute Apgar score below 7.

Conclusion:

Neonates admitted to neonatal intensive care units are highly exposed to off-label and unlicensed medications. Further studies are needed to achieve greater safety and quality of drug therapy used in neonatology.

Keywords:
Infant, preterm; Infant, newborn; Intensive care units, neonatal; Drug prescription; Off-label use

Variables	n (%)
Gestational age
Moderate/late preterm	237 (59.3)
Very preterm	117 (29.2)
Extremely preterm	46 (11.5)
Birth weight (g)
≥ 2,500	48 (12.0)
≥ 1,500 and < 2,500	178 (45.0)
≥ 1,000 and < 1,500	122 (30.0)
< 1,000	52 (13.0)
5-minute Apgar score
≥ 7	335 (86.0)
< 7	54 (14.0)
Resuscitation maneuver in the delivery room
No	217 (54.3)
Only PPV	156 (39.0)
Advanced maneuvers	27 (6.7)
Death
Yes	64 (16.0)
No	336 (84.0)

Anatomical and therapeutic group	Total	Off-label	Unlicensed
Digestive system and metabolism	3,961 (24.5)	975 (11.6)
Medicines for acidogastric disorders	380 (2.3)	380 (4.5)
Medicines for gastrointestinal disorders	442 (2.8)	442 (5.3)
Medicines for biliary tract and liver	39 (0.2)	39 (0.4)
Vitamins	2,959 (18.3)	114 (1.4)
Blood and hematopoietic organs	327 (2.0)		212 (5.6)
Antianemic drugs	212 (1.3)		212 (5.6)
Cardiovascular system	953 (5.9)	731 (8.7)	83 (2.2)
Medications for cardiac disorders	650 (4.0)	509 (6.1)	2 (0.1)
Diuretic drugs	219 (1.3)	138 (1.6)	81 (2.1)
Vasoprotective drugs	79 (0.5)	79 (0.9)
Drugs that act on the renin-angiotensin system	5 (0.1)	5 (0.1)
Dermatological	38 (0.2)
Genitourinary system and sex hormones	75 (0.5)	75 (0.9)
Medicines for urological disorders	75 (0.5)	75 (0.9)
Anti-infectives for systemic use	5,954 (36.9)	5,345 (63.8)	14 (0.4)
Antibacterials for systemic use	5,253 (32.5)	4,691 (56.0)	14 (0.4)
Antimycotics for systemic use	684 (4.2)	646 (7.7)
Immunological sera and immunoglobulins	17 (0.1)	8 (0.1)
Antineoplastic and immunomodulatory agents	11 (0.1)	11 (0.1)
Antineoplastic agents	11 (0.1)	11 (0.1)
Musculoskeletal system	30 (0.2)	23 (0.3)
Anti-inflammatory and antirheumatic drugs	23 (0.1)	23 (0.3)
Nervous system	4,451 (27.6)	983 (11.7)	3,468 (91.5)
Anesthetics	663 (4.1)	663 (7.9)
Analgesics	68 (0.4)	55 (0.6)	13 (0.3)
Antiepileptics	634 (3.9)	41 (0.5)	593 (15.5)
Psychological	115 (0.7)	115 (1.4)
Psychoanalytic	2,862 (17.7)		2,862 (75.4)
Other	109 (0.7)	109 (1.3)
Antiparasitic products, insecticides and repellents	13 (0.1)		13 (0.3)
Antiprotozoa	13 (0.1)		13 (0.3)
Respiratory system	329 (2.0)	229 (2.7)
Nasal preparations	69 (0.4)	69 (0.8)
Medicines for obstructive diseases	161 (0.9)	160 (1.9)
Sensory organs	1 (0.01)
Total	16,143 (100.0)	8,372 (100.0)	3,790 (100.0)

Medications	ATC Code	Off-label	Unlicensed
Caffeine	N06BC01		2,862 (75.5)
Gentamicin	J01GB03	1,467 (17.5)
Ampicillin	J01CA01	1,295 (15.5)
Amikacin	J01GB06	741 (8.9)
Fentanyl	N01AH01	656 (7.8)
Fluconazole	J02AC01	642 (7.7)
Phenobarbital	N03AA02		593 (15.6)
Cefepime	J01DE01	566 (6.8)
Domperidone	A03FA03	412 (4.9)
Meropenem	J01DH02	373 (4.5)
Ranitidine	A02BA02	359 (4.3)
Ferrous sulfate	B03AA07		212 (5.6)
Aminophylline	R03DA05	150 (1.8)
Furosemide	C03CA01	138 (1.6)
Vancomycin	J01XA01	125 (1.5)
Methadone	N07BC02	109 (1.3)
Piperacillin and tazobactam	J01CR05	102 (1.2)
Midazolam	N05CD08	97 (1.2)
Hydrochlorothiazide	C03AA03		53 (1.4)
Spironolactone	C03DA01		28 (0.7)
Pyrimethamine	P01BD01		13 (0.3)
Sulfadiazine	J01EC02		13 (0.3)
Dipyrone	N02BB02		8 (0.2)
Other		1,140 (13.6)	8 (0.2)
Total		8,372 (100.0)	3,790 (100.0)

	n	Median	Minimum value - maximum value	p value
Variables per total drug use
Gestational age				< 0.001^* * p value estimated by the Kruskal-Wallis test;
Moderate/late preterm	237	18.0	0 - 177
Very preterm	117	58.0	4 - 217
Extremely preterm	46	44.0	0 - 155
Birth weight (g)				< 0.001^* * p value estimated by the Kruskal-Wallis test;
≥ 2,500	48	7.5	0 - 173
≥ 1,500 and < 2,500	178	20.5	0 - 138
≥ 1,000 and < 1,500	122	51.0	0 - 217
< 1,000	52	49.0	0 - 155
5-minute Apgar score				0.003^† † p value estimated by the Mann-Whitney test.
≥ 7	335	28.0	0 - 217
< 7	54	47.0	0 - 155
Resuscitation maneuvers in the delivery room				0.004^* * p value estimated by the Kruskal-Wallis test;
No	217	26.0	0 - 154
Only PPV §	156	33.0	0 - 177
Advanced maneuver	27	51.0	5 - 217
Death				0.030^† † p value estimated by the Mann-Whitney test.
Yes	64	36.5	0 - 217
No	336	29.0	0 - 173
Variables by off-label drugs
Gestational age				< 0.001^* * p value estimated by the Kruskal-Wallis test;
Moderate/late preterm	237	8.0	0 - 139
Very preterm	117	23.0	0 - 161
Extremely preterm	46	23.0	0 - 95
Birth weight (g)				< 0.001^* * p value estimated by the Kruskal-Wallis test;
≥ 2,500	48	6.0	0 - 139
≥ 1,500 and < 2,500	178	8.5	0 - 119
≥ 1,000 and < 1,500	122	21.0	0 - 161
< 1,000	52	26.0	0 - 115
5-minute Apgar score				< 0.001^† † p value estimated by the Mann-Whitney test.
≥ 7	335	12.0	0 - 161
< 7	54	23.5	0 - 107
Resuscitation maneuvers in the delivery room				< 0.001^* * p value estimated by the Kruskal-Wallis test;
No	217	12.0	0 - 119
Only PPV	156	14.0	0 - 139
Advanced maneuvers	27	29.0	0 - 161
Death				< 0.001^† † p value estimated by the Mann-Whitney test.
Yes	64	27.5	0 - 161
No	336	11.5	0 - 139
Variables for unlicensed drugs
Gestational age				< 0.001^* * p value estimated by the Kruskal-Wallis test;
Moderate/late preterm	237	0	0 - 34
Very preterm	117	19.0	0 - 52
Extremely preterm	46	5.0	0 - 56
Birth weight (g)				< 0.001^* * p value estimated by the Kruskal-Wallis test;
≥ 2,500	48	0	0 - 26
≥ 1,500 and < 2,500	178	0	0 - 52
≥ 1,000 and < 1,500	122	18.0	0 - 49
< 1,000	52	5.0	0 - 56
5-minute Apgar score				0.020^† † p value estimated by the Mann-Whitney test.
≥ 7	335	2.0	0 - 52
< 7	54	7.5	0 - 56
Resuscitation maneuvers in the delivery room				0.050^* * p value estimated by the Kruskal-Wallis test;
No	217	0	0 - 52
Only PPV	156	5.0	0 - 50
Advanced maneuvers	27	9.0	0 - 56
Death				0.820^† † p value estimated by the Mann-Whitney test.
Yes	64	3.0	0 - 37
No	336	4.0	0 - 56

Associação de Medicina Intensiva Brasileira - AMIB Rua Arminda, 93 - Vila Olímpia, CEP 04545-100 - São Paulo - SP - Brasil, Tel.: (11) 5089-2642 - São Paulo - SP - Brazil
E-mail: rbti.artigos@amib.com.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] Corresponding author: Verônica Cheles Vieira, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Rua Hormindo Barros, 58 - Candeias, Zip code: 45029-094 - Vitória da Conquista (BA), Brazil. E-mail: veronicacheles@gmail.com