Ritodrine Hydrochloride

(BANM, USAN, rINNM)
Ritodrine Hydrochloride Chemical formula
Synonyms: (BANM, USAN, rINNM) DU-21220 (ritodrine); Hidrocloruro de ritodrina; Ritodrin Hidroklorür; Ritodrine, Chlorhydrate de; Ritodrini Hydrochloridum. erythro-2-(4-Hydroxyphenethylamino)-1-(4-hydroxyphenyl)propan-1-ol hydrochloride.
Cyrillic synonym: Ритодрина Гидрохлорид.

💊 Chemical information

Chemical formula: C17H21NO3,HCl = 323.8.
CAS — 26652-09-5 (ritodrine); 23239-51-2 (ritodrine hydrochloride).
ATC — G02C A01.
ATC Vet — QG02CA01.

Pharmacopoeias.

In Br., Jpn, and US.

BP 2008

(Ritodrine Hydrochloride). A white or almost white, crystalline powder. Freely soluble in water; soluble in dehydrated alcohol; practically insoluble in acetone and in ether. A 2% solution in water has a pH of 4.5 to 6.0. Store in airtight containers.

USP 31

(Ritodrine Hydrochloride). A white to nearly white, odourless or practically odourless, crystalline powder. Freely soluble in water and in alcohol; practically insoluble in ether; soluble in propyl alcohol. pH of a 2% solution in water is between 4.5 and 6.0. Store in airtight containers at a temperature of 25°, excursions permitted between 15° and 30°.

💊 Adverse Effects and Precautions

As for Salbutamol Sulfate. Leucopenia or agranulocytosis has been reported occasionally with prolonged intravenous use. In women given ritodrine for premature labour, the risk of pulmonary oedema means that extreme caution is required and the precautions and risk factors discussed under Salbutamol Sulfate, apply.

Effects on the eyes.

Ritodrine and to a lesser extent salbutamol have been implicated in retinopathy in the premature infant when used for premature labour.1
1. Michie CA, et al. Do maternal β-sympathomimetics influence the development of retinopathy in the premature infant? Arch Dis Child 1994; 71: F149.

Effects on the heart.

Myocardial ischaemia or signs of myocardial ischaemia have been reported in patients given ritodrine.1-3 Sinus tachycardia and ST-segment depression commonly occur in patients given ritodrine, but the relationship between these changes and ischaemia remains unclear.3
1. Brosset P, et al. Cardiac complications of ritodrine in mother and baby. Lancet 1982; i: 1468
2. Ben-Shlomo I, et al. Myocardial ischaemia during intravenous ritodrine treatment: is it so rare? Lancet 1986; ii: 917–18
3. Verhaert D, Van Acker R. Acute myocardial infarction during pregnancy. Acta Cardiol 2004; 59: 331–9.

Effects on skeletal muscle.

Elevated serum-creatine kinase concentrations have been found in women given ritodrine tocolysis,1 and there have been rare reports of rhabdomyolysis.1,2
1. Matsuda Y, et al. Evaluation of creatine kinase level during longterm tocolysis. J Perinat Med 2002; 30: 476–9
2. Nasu K, et al. Rhabdomyolysis caused by tocolysis with oral ritodrine hydrochloride in a pregnant patient with myotonic dystrophy. Gynecol Obstet Invest 2006; 61: 53–5.

Pulmonary oedema.

Several cases of pulmonary oedema have been reported in patients given a beta2 agonist, including ritodrine, for premature labour.1-4 In 1995 the UK CSM4 commented that it had received 10 reports of pulmonary oedema, fatal in 2 patients. The CSM considered that fluid overload was the most important predisposing factor. Other risk factors included multiple pregnancies, a history of cardiac disease, and maternal infection. For further discussion of the precautions necessary in the use of beta2 agonists to treat premature labour, and the risk factors involved, see Salbutamol.
1. Hawker F. Pulmonary oedema associated with β -sympathomimetic treatment of premature labour. Anaesth Intensive Care 1984; 12: 143–51
2. Pisani RJ, Rosenow EC. Pulmonary edema associated with tocolytic therapy. Ann Intern Med 1989; 110: 714–18
3. Clesham GJ, et al. β Adrenergic agonists and pulmonary oedema in preterm labour. BMJ 1994; 308: 260–2
4. Committee on Safety of Medicines/Medicines Control Agency. Reminder: ritodrine and pulmonary oedema. Current Problems 1995; 21: 7. Also available at: http://www.mhra.gov.uk/home/ idcplg?IdcService=GET_FILE&dDocName=CON2015619& RevisionSelectionMethod=LatestReleased (accessed 30/06/08)

💊 Interactions

💊 Pharmacokinetics

Ritodrine is rapidly absorbed from the gastrointestinal tract but is subject to fairly extensive first-pass metabolism; about 30% of an oral dose is bioavailable. It is metabolised in the liver primarily by conjugation with glucuronic acid or sulfate and excreted in urine as unchanged drug and metabolites. About 70 to 90% of a dose is reported to be excreted in the urine within 10 to 12 hours. It crosses the placenta.
1. Gandar R, et al. Serum level of ritodrine in man. Eur J Clin Pharmacol 1980; 17: 117–22
2. Gross AS, Brown KF. Plasma protein binding of ritodrine at parturition and in nonpregnant women. Eur J Clin Pharmacol 1985; 28: 479–81
3. Kuhnert BR, et al. Ritodrine pharmacokinetics. Clin Pharmacol Ther 1986; 40: 656–64
4. Caritis SN, et al. Pharmacokinetics of orally administered ritodrine. Am J Obstet Gynecol 1989; 161: 32–5
5. Caritis SN, et al. Pharmacokinetics of ritodrine administered intravenously: recommendations for changes in the current regimen. Am J Obstet Gynecol 1990; 162: 429–37
6. Caritis SN, et al. Pharmacokinetics and pharmacodynamics of ritodrine after intramuscular administration to pregnant women. Am J Obstet Gynecol 1990; 162: 1215–19
7. Pacifici GM, et al. Sulphation and glucuronidation of ritodrine in human foetal and adult tissues. Eur J Clin Pharmacol 1993; 44: 259–64
8. Pacifici GM, et al. Ritodrine sulphation in the human liver and duodenal mucosa: interindividual variability. Eur J Drug Metab Pharmacokinet 1998; 23: 67–74.

💊 Uses and Administration

Ritodrine hydrochloride is a direct-acting sympathomimetic with mainly beta-adrenergic activity and a selective action on beta 2 receptors (a beta 2 agonist). It has general properties similar to those of salbutamol. It decreases uterine contractility and is used to arrest premature labour. Ritodrine hydrochloride is usually given by intravenous infusion. Where possible this should be with the aid of a syringe pump, when the concentration should be 3 mg/mL, using glucose 5% as the diluent. A recommended initial rate of infusion is 50 micrograms/minute increased at intervals of 10 minutes by increments of 50 micrograms/minute until there is evidence of patient response, which is usually at a rate of 150 to 350 micrograms/minute, the latter figure being the maximum recommended rate. If no syringe pump is available then the infusion may be made using a controlled infusion device to deliver a more dilute solution of 300 micrograms/mL, with glucose 5% being used once again as the diluent. The same dose is used as with the syringe pump. The maternal pulse should be monitored throughout the infusion and the rate adjusted to avoid a maternal heart rate of more than 140 beats/minute. A close watch should also be kept on the patient’s state of hydration since fluid overload is considered to be a key risk factor for pulmonary oedema. The infusion should be continued for 12 to 48 hours after the contractions have stopped. Ritodrine hydrochloride may subsequently be given by mouth in an initial dose of 10 mg every 2 hours for 24 hours, starting 30 minutes before the end of the intravenous infusion. Thereafter, 10 to 20 mg may be given every 4 to 6 hours according to the patient’s response. The total daily oral dose should not exceed 120 mg. If intravenous infusion is inappropriate, 10 mg may be given intramuscularly every 3 to 8 hours and continued for 12 to 48 hours after the contractions have stopped.
1. Yaju Y, Nakayama T. Effectiveness and safety of ritodrine hydrochloride for the treatment of preterm labour: a systematic review. Pharmacoepidemiol Drug Safety 2006; 15: 813–22.

💊 Preparations

BP 2008: Ritodrine Injection; Ritodrine Tablets; USP 31: Ritodrine Hydrochloride Injection; Ritodrine Hydrochloride Tablets.

Proprietary Preparations

Arg.: Ritopar; Belg.: Pre-Par; Braz.: Miodrina; Chile: Materlac†; Cz.: PrePar†; Gr.: Pre-Par†; Yutopar; Hong Kong: Yutopar†; India: Yutopar ; Indon.: Yutopar ; Israel: Ritopar; Ital.: Miolene; Port.: Pre-Par†; Spain: Pre-Par; Tu rk.: Pre-Par; UK: Yutopa r.
Published November 11, 2018.