TOCOLYSIS: NIFEDIPINE ADMINISTRATION FOR PRETERM LABOUR

POLICY The physician directs the treatment of women with preterm labour (PTL).

Applicability: Treatment for PTL occurs in the Birthing area of the Acute Perinatal Program.

PROCEDURE

Definition of true preterm . Gestational age is between 23+6 and 34 +0 weeks labour: . Regular contractions - at least 4 in 20 minutes . Including one of the following: - cervix greater than or equal to (≥) 2 centimetres (cm) dilated - cervix ≥ 80% effaced - progressive cervical change - positive fetal fibronectin - cervical endovaginal scan with less than (<) 2.5 cm length

1.1 Contraindications

Contraindications to tocolytic therapy including: . Abnormal fetal health surveillance by electronic fetal monitoring (EFM) . Cervical dilatation ≥ 4 cm for a woman who is actively labouring . Chorioamnionitis or suspected intrauterine infection . Fetal demise or lethal congenital anomaly . Gestational age less than or equal to (≤) 23 +6 weeks (in exceptional circumstances tocolytic treatment may be used under 24 weeks gestational age) . Gestational age ≥ 34 +0 weeks . Significant vaginal bleeding (relative contraindication, assess each case) . Other obstetrical or medical conditions that contraindicate the prolongation of pregnancy

Contraindications to nifedipine therapy including: . Allergy to nifedipine . Any contraindications to tocolysis (listed above) . Concurrent use of maternal nitroglycerin, beta-blockers, beta-agonists, digoxin . Conditions of relatively enhanced maternal vasodilatation: i.e. sepsis . Maternal cardiac disease: coronary artery disease, acute coronary syndrome, previous myocardial infarction, dilated cardiomyopathy, IHSS, congestive heart failure, SA node or AV node conduction disturbances, pre-excitation syndromes (i.e. WPW), severe aortic stenosis . Maternal hypotension (defined as 100/60) . Maternal liver disease where metabolizing function is impaired . Maternal risk for undiagnosed coronary artery disease and ECG status unknown (e.g. any woman with type 1 or type 2 diabetes for ≥ 15 years, chronic hypertension, maternal age ≥ 45 years)

1.2 Side Effects Side effects of nifedipine are dose related and include the following: . Dizziness (10-27%) . Peripheral edema (7-30%) . Flushing & headache (10-25%) . Tachycardia, rarely associated with palpitations (1-7%) . Nausea & heartburn (10%) . Transient hypotension (5%) . Weakness (10-12%) Symptoms are fainting and hypotension If the blood pressure is < 100/60 mmHg and/or the woman has a sustained pulse > 110 bpm: WW 05.16 Fetal Maternal Newborn and Family Health Policy & Procedure Manual Effective Date: 18-OCT-2011 Page 1 of 4 Refer to online version – Print copy may not be current – Discard after use

TOCOLYSIS: NIFEDIPINE ADMINISTRATION FOR PRETERM LABOUR

 Hold the nifedipine and call the physician.

If significant hypotension occurs during loading or maintenance administration, initiate the following interventions:  Place the woman in the left lateral recumbent position  Notify the physician immediately  Continue electronic fetal monitoring (EFM)  Monitor vital signs and oxygen saturation  Consider need for urinary catheterization to monitor urinary output

Rare side effect to watch for: . Chest pain (< 1%) . Pulmonary edema with resulting dyspnea (2%) . Severe hypotension (< 5%)

Discontinue nifedipine under the following circumstances: . 48 hours after the first dose of corticosteroids has been administered, and the woman has arrived in an appropriate level of care facility . If significant side effects occur . When delivery is imminent consider Magnesium Sulfate Administration for Neonatal Neuroprotection

1.3 Assessment Physician/ Obstetrician/ Assess for: Obstetrical Resident . True PTL, assess contractions by palpation and frequency . Contraindications to tocolytic therapy . Contraindications to nifedipine therapy. Review possible drug interactions, see drug information data, Appendix B

Prior to the administration of nifedipine discuss the treatment plan, including anticipated benefits and effects of nifedipine tocolysis with the woman: . Confirm fetal presentation with ultrasound (if unclear clinically) . Complete Physician’s Orders - PTL Nifedipine for Tocolysis

See Physician’s Orders. Note: With nifedipine capsule do not give grapefruit juice concurrently as it has been shown to increase plasma levels of nifedipine.

1.4 Preparation for therapy Registered Nurse (RN)  Start intravenous (IV) with normal saline  Limit woman’s activity, with bathroom privileges only  Restrict oral intake to nothing by mouth until after the loading dose of nifedipine has been administered and contractions have ceased

Prior to the administration of the nifedipine capsule (loading dose):  Assess vital signs - blood pressure, heart rate, respiratory rate, oxygen saturation  Initiate continuous EFM

1.5 Administration of Nifedipine Monitor the woman during the first/loading dose of nifedipine

WW 05.16 Fetal Maternal Newborn and Family Health Policy & Procedure Manual Effective Date: 18-OCT-2011 Page 2 of 4 Refer to online version – Print copy may not be current – Discard after use

TOCOLYSIS: NIFEDIPINE ADMINISTRATION FOR PRETERM LABOUR

 Assess BP every 15 minutes for 2 hours following the medication loading dose  Assess vital signs (heart rate, respiratory rate, oxygen saturation) every hour  Continuous EFM during the administration of the nifedipine capsule loading dose and for 2 hours following the administration of the last loading dose  Observe for drug side effects, see 2.2

Maintenance therapy During maintenance doses of nifedipine (Adalat XL)  Assess maternal vital signs and fetal heart rate before each dose and  Repeat in 4 hours following each dose  Evaluate response to nifedipine therapy  Assess frequency and strength of contractions on an ongoing basis as warranted by the woman’s condition. Observe for: . Absence or decreased uterine activity by palpation (RN or physician) . Absence or decreased abdominal cramping as perceived by the woman . No further cervical dilatation or effacement

Key bpm = beats per minute IHSS = Idiopathic hypertrophic subaortic stenosis > = greater than cm = centimetres mmHg = millimetres mercury < = less than ECG = electrocardiogram SA = sinoatrial ≤ = less than or equal to e.g. = for example SaO2 = oxygen saturation ≥ = greater than or equal to GBS = Group B Strep WPW = Wolff-Parkinson-White syndrome AV = atrioventricular HR = heart rate

DOCUMENTATION  Fetal Heart Tracing and Label  Interprofessional Progress Notes  Labour Partogram or Special Clinical Record  Physician’s Orders - PTL Nifedipine for Tocolysis  Triage and Assessment Record

REFERENCES Al-Omari, W et al. Atosiban and nifedipine in acute tocolysis: a comparative study. EurJOGRB. (2006). Cararach, V et al. Nifedipine versus Ritodrine for suppression of preterm labor. Comparison of their efficacy and secondary effects. EurJOGRB. (2006). Conde-Agudelo, et al. Nifedipine in the management of preterm labour: a systematic review and metaanalysis. ACOG:134e (2011, Feb.) Coomarasamy, A et al. Effectiveness of Nifedipine versus Atosiban for tocolysis in preterm labor a meta- analysis with an indirect comparison of randomized trials. BJOG. (2003). De Heus, R et al. Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study. BMJ. (2009). De Heus, R et al. The effects of the tocolytics Atosiban and nifedipine on fetal movements, heart rate and blood flow. JMatFetNNMed. (2009). Laohapoianart, N et al. Safety and efficacy of oral nifedipine versus terbutaline injection in preterm labor. JMedAssThai. (2007).

WW 05.16 Fetal Maternal Newborn and Family Health Policy & Procedure Manual Effective Date: 18-OCT-2011 Page 3 of 4 Refer to online version – Print copy may not be current – Discard after use

TOCOLYSIS: NIFEDIPINE ADMINISTRATION FOR PRETERM LABOUR

Lyell, J et al. MgSO4 compared with nifedipine for acute tocolysis of preterm labor. ObsGyne. (2007). Magnesium Sulfate Administration for Seizure Prevention/ for Neonatal Neuroprotection (2011). Maitra, N et al. Tocolytic efficacy of nifedipine versus ritodrine in preterm labor. IntJOGO. (2007). Marin, T et al. Nifedipine serum levels in pregnant women undergoing tocolysis with nifedipine. JObsGyn. (2007). Mawaldi, L et al. Terbutaline versus nifedipine for prolongation of pregnancy in patients with preterm labor. IntJGynObs. (2008). Nassar, A et al. Nifedipine-associated pulmonary complications in pregnancy. IntJGynObs. (2007). Oie, SG. Calcium channel blockers for tocolysis: a review of their role and safety following reports of serious adverse events. EurJOGRB. (2006). Preterm Labour. Obstetric Guideline 2A. BCRCP. (2005). Simhan, H et al. Prevention of preterm delivery. NEJM. (2007). Tsatsaris, V et al. Tocolysis with Nifedipine or beta-adrenergic agonists: a meta-analysis. ObsGyne. (2001). Van de Water, M et al. Tocolytic effectiveness of nifedipine versus ritodrine and follow-up of newborns: a randomized controlled trial. ActaObsGynScand. (2008). van Geijn, H et al. Nifedipine trials: effectiveness and safety aspects. BJOG. (2005). Waterman, B. BCWH Protocol Nifedipine for Tocolysis. (2007, October).

APPENDIX Appendix A Physician’s Orders – Preterm Labour Nifedipine for Tocolysis Appendix B Nifedipine: Drug Information

WW 05.16 Fetal Maternal Newborn and Family Health Policy & Procedure Manual Effective Date: 18-OCT-2011 Page 4 of 4 Refer to online version – Print copy may not be current – Discard after use