(British Approved Name Modified, rINNM)
INNs in main languages (French, Latin, Russian, and Spanish):
Pharmacopoeias. In China, and US.
The United States Pharmacopeia 31, 2008 (Hydroxyprogesterone Caproate). A white or creamy-white, crystalline powder. Odourless or having a slight odour. Insoluble in water soluble in ether slightly soluble in benzene. Protect from light. Store at a temperature of 25°, excursions permitted between 15° and 30°.
Adverse Effects and Precautions
As for progestogens in general (see Progesterone). There may be local reactions at the site of injection. Rarely, coughing, dyspnoea, and circulatory disturbances may occur during or immediately after injection of hydroxyprogesterone caproate but can be avoided by injecting the drug very slowly.
Abnormalities reported in infants born to mothers who had received hydroxyprogesterone during pregnancy have included tetralogy of Fallot in one infant, genito-urinary abnormalities in 2 infants, and adrenocortical carcinoma in one infant.
As for progestogens in general (see Progesterone).
Uses and Administration
Hydroxyprogesterone caproate is a progestogen structurally related to progesterone that has been used for recurrent miscarriage and various menstrual disorders. In recurrent miscarriage associated with proven progesterone deficiency, doses of 250 to 500 mg weekly by intramuscular injection have been given during the first half of pregnancy. Hydroxyprogesterone caproate has also been used to prevent premature labour (see below). The acetate and the enantate have also been used.
In women who have a history of spontaneous premature delivery, there is some evidence to suggest that prophylactic progesterone, may reduce the risk for premature delivery in subsequent pregnancies. A placebo-controlled study has used intramuscular injections of hydroxyprogesterone caproate, starting in weeks 16 to 20 of gestation and continuing until delivery or week 36. The risk of delivery at less than 37 weeks was reduced in women given hydroxyprogesterone, but the rate was still high at 36.3% of 306 women compared with 54.9% of 153 given placebo.
Vaginal progesterone has been found to reduce the frequency of uterine contractions and the rate of preterm delivery in women at high risk, and to reduce preterm delivery in women with a short cervix at mid-gestation. The best timing of therapy is unclear, although two retrospective analyses found that rates of preterm delivery were similar for two groups of women started on hydroxyprogesterone prophylaxis at either 16 to 20.9 weeks of gestation or 21 to 26.9 weeks. Another retrospective study suggested that early cessation of hydroxyprogesterone was associated with an increased risk of spontaneous recurrent preterm delivery and that treatment should continue until 36 weeks of gestation.
Systematic reviews of studies using progestogens (mainly hydroxyprogesterone) have concluded that prophylaxis does reduce the risk of preterm delivery and low birth-weight (less than 2.5 kg). However, further study is required, particularly to identify the optimal timing, route, and dose of treatment, and long-term effects on infant health. Based on limited data, an expert committee in the USA has recommended that the use of progesterone and hydroxyprogesterone should be restricted to women with a history of previous spontaneous delivery at less than 37 weeks.
In Canada, a history of preterm labour is considered an indication for intramuscular hydroxyprogesterone caproate 250 mg weekly, or vaginal progesterone 100 mg daily, given from 20 weeks of gestation until the risk of prematurity is low. For women with a short cervix (less than 15 mm at 22 to 26 weeks of gestation), vaginal progesterone 200 mg daily may be used.
There is an increased risk of preterm delivery in twin gestations, but the use of hydroxyprogesterone does not appear to be of benefit.
The United States Pharmacopeia 31, 2008: Hydroxyprogesterone Caproate Injection
Argentina: Gestageno Proluton Depot
Austria: Proluton Depot
Chile: Primolut Depot
Czech Republic: Neolutin Forte
France: Progesterone-retard Pharlon
Germany: Progesteron-Depot Proluton Depot
Greece: Proluton Depot
India: Maintane NT-Natal Proluton Depot
Israel: Depolut Proluton Depot
Italy: Lentogest Proluton
Mexico: Caposten Primolut Depot
The Netherlands: Proluton Depot
Philippines: Proluton Depot
Singapore: Proluton Depot
Thailand: Proluton Depot
Turkey: Proluton Depo
Argentina: Dos Dias N Primosiston
Brazil: Gestadinona Trinestril
Germany: Gravibinon Syngynonl
Mexico: Gravidinona Primosiston