Isoxsuprine Hydrochloride

(BANM, rINNM)
Isoxsuprine Hydrochloride Chemical formula
Synonyms: Caa-40; Hidrocloruro de isoxsuprina; Isoksupriinihydrokloridi; Isoxsuprin hydrochlorid; Isoxsuprine, chlorhydrate d’; Isoxsuprinhydroklorid; Isoxsuprini hydrochloridum; Izokssuprino hidrochloridas; Izoxszuprin-hidroklorid; Phenoxyisopropylnorsuprifen. 1(4-Hydroxyphenyl)-2-(1-methyl-2-phenoxyethylamino)propan1-ol hydrochloride.
Cyrillic synonym: Изоксуприна Гидрохлорид.

💊 Chemical information

Chemical formula: C18H23NO3,HCl = 337.8.
CAS — 395-28-8 (isoxsuprine); 579-56-6 (isoxsuprine hydrochloride).
ATC — C04AA01.
ATC Vet — QC04AA01.

Pharmacopoeias.

In Eur. and US.

Ph. Eur. 6.2

(Isoxsuprine Hydrochloride). A white or almost white crystalline powder. Sparingly soluble in water and in alcohol; practically insoluble in dichloromethane. A 1% solution in water has a pH of 4.5 to 6.0. Protect from light.

USP 31

(Isoxsuprine Hydrochloride). A white, odourless, crystalline powder. Soluble 1 in 500 of water, 1 in 100 of alcohol and of 0.1N sodium hydroxide solution, and 1 in 2500 of 0.1N hydrochloric acid; practically insoluble in chloroform and in ether. pH of a 1% solution in water is between 4.5 and 6.0. Store in airtight containers.

💊 Adverse Effects

Isoxsuprine may cause transient flushing, hypotension, tachycardia, rashes, and gastrointestinal disturbances. Maternal pulmonary oedema and fetal tachycardia have been reported after intravenous use in premature labour.

Pulmonary oedema.

Pulmonary oedema has been reported in mothers given isoxsuprine for premature labour.1,2
1. Nagey DA, Crenshaw MC. Pulmonary complications of isoxsuprine therapy in the gravida. Obstet Gynecol 1982; 59 (suppl): 38S–42S
2. Nimrod C, et al. Pulmonary edema associated with isoxsuprine therapy. Am J Obstet Gynecol 1984; 148: 625–9.

💊 Precautions

Isoxsuprine is contra-indicated after recent arterial haemorrhage. It should not be given immediately post partum, nor should it be used for premature labour if there is infection. In women being treated 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.

Pregnancy.

Ileus was found to be more common in the offspring of mothers who received isoxsuprine than in matched controls.1 The incidence of respiratory distress syndrome also rose as the isoxsuprine concentration in cord blood exceeded 10 nanograms/mL; likewise the incidence of hypocalcaemia and hypotension rose progressively with increasing concentrations. The cord concentrations correlated inversely with the drug-free interval before delivery and it was suggested that with frequent assessment of uterine response it should be possible to avoid delivering infants at a time when they have high plasma-isoxsuprine concentrations.1 In another study2 of the association between ruptured membranes, beta-adrenergic therapy, and respiratory distress syndrome, it was found that both therapy with isoxsuprine and premature rupture of membranes were individually associated with a lowered incidence of respiratory distress syndrome, but when present together they resulted in an increased risk of respiratory distress syndrome. It was suggested that therapy with beta-adrenergic drugs including isoxsuprine should be restricted to patients with intact membranes.1
1. Brazy JE, et al. Isoxsuprine in the perinatal period II: relationships between neonatal symptoms, drug exposure, and drug concentration at the time of birth. J Pediatr 1981; 98: 146–51
2. Curet LB, et al. Association between ruptured membranes, tocolytic therapy, and respiratory distress syndrome. Am J Obstet Gynecol 1984; 148: 263–8.

💊 Pharmacokinetics

Isoxsuprine hydrochloride is well absorbed from the gastrointestinal tract. The peak plasma concentration occurs about 1 hour after an oral dose. A plasma half-life of about 1.5 hours has been reported. Isoxsuprine is excreted in the urine mainly as conjugates.

💊 Uses and Administration

Isoxsuprine is a vasodilator that also stimulates beta-adrenergic receptors. It causes direct relaxation of vascular and uterine smooth muscle and its vasodilating action is greater on the arteries supplying skeletal muscles than on those supplying skin. Isox suprine also produces positive inotropic and chronotropic effects. Isoxsuprine hydrochloride has been used to arrest premature labour, but drugs with a more selective action are now preferred. It has also been given in the treatment of cerebral and peripheral vascular disease. For use as a vasodilator, isoxsuprine hydrochloride is given by mouth in doses of 10 to 20 mg 3 or 4 times daily. To arrest premature labour, isoxsuprine hydrochloride is given initially by intravenous infusion in doses of 200 to 500 micrograms/minute, adjusted according to the patient’s response, until control is achieved. It is now common practice to give beta agonists by syringe pump when using them to delay premature labour. Maternal blood pressure and hydration, and maternal and fetal heart rates should be monitored during the infusion. Once labour has been arrested intramuscular injections of 10 mg are given every 3 to 8 hours for several days. Prophylaxis may be continued by mouth with 30 to 90 mg daily in divided doses. The resinate has also been used similarly.

💊 Preparations

USP 31: Isoxsuprine Hydrochloride Injection; Isoxsuprine Hydrochloride Ta b l e t s .

Proprietary Preparations

Arg.: Duvadilan; Fadaespasmol†; Isodilan; Isotenk; Samaruc; Uterine; Austria: Xuprin; Braz.: Inibina; Gr.: Duvadilan†; India: Duvadilan; Indon.: Duvadilan; Hystolan; Israel: Vasolan†; Ital.: Vasosuprina Ilfi; Mex.: Vadosilan; Philipp.: Duvadilan; Isoxilan; Port.: Dilum; Thai.: Duvadilan†; USA: Vasodilan; Voxsuprine; Venez.: Duvadilan.
Published May 08, 2019.