Vontrol

‘Vontrol’ may cause hallucinations, disorientation, or confusion. For this reason, its use is limited to patients who are hospitalized or under comparable, continuous, close, professional supervision. Even then, the physician should carefully weigh the benefits against the possible risks and give due consideration to alternate therapeutic measures.

‘Vontrol’ (diphenidol, SK&F) apparently exerts a specific antivertigo effect on the vestibular apparatus to control vertigo and inhibits the chemoreceptor trigger zone to control nausea and vomiting.

‘Vontrol’ (diphenidol, SK&F) may cause hallucinations, disorientation or confusion. For this reason, its use is limited to patients who are hospitalized or under comparable, continuous, close, professional supervision. Even then, the physician should carefully weigh the benefits against the possible risks and give due consideration to alternate therapeutic measures.

The incidence of auditory and visual hallucinations, disorientation and confusion appears to be less than ½% or approximately one in 350 patients. The reaction has usually occurred within three days of starting the drug in recommended dosage and has subsided spontaneously usually within three days after discontinuation of the drug. Patients on ‘Vontrol’ should be observed closely and in the event of such a reaction the drug should be stopped.

Usage in Pregnancy

Use of any drug in pregnancy, lactation or in women of childbearing age requires that the potential benefits of the drug be weighed against its possible hazards to the mother and child.

In animal teratogenesis and reproduction studies of ‘Vontrol’ (diphenidol, SK&F), there were no significant differences between drug-treated groups and untreated control groups, except as noted under animal Reproduction Studies (see “Pharmacology [animal],” column 4).

In 936 patients who received ‘Vontrol’ during pregnancy, the incidences of normal and abnormal birth were comparable to those reported in the literature for the average population of pregnant patients. And in no instance was there any evidence that ‘Vontrol’ played a part in birth abnormality (see “In Pregnancy,” column 5).

‘Vontrol’ is not indicated for use in nausea and vomiting of pregnancy, since the therapeutic value and safety in this indication have not yet been determined.

Auditory and visual hallucinations, disorientation and confusion have been reported. Drowsiness, overstimulation, depression, sleep disturbance, dry mouth, g.i. irritation (nausea and indigestion), or blurred vision may occur.

Rarely, slight dizziness, skin rash, malaise, headache, or heartburn may occur. Mild jaundice of questionable relationship to the use of ‘Vontrol’ (diphenidol, SK&F) has been reported. Slight, transient lowering of blood pressure has been reported in a few patients.

(See laboratory studies under “Pharmacology [human],” Column 4.)

In the event of overdosage, the patient should be managed according to his symptoms. Treatment is essentially supportive, with maintenance of blood pressure and respiration, plus careful observation. Early gastric lavage may be indicated depending on the amount of overdose and nature of symptoms.

‘Vontrol’ (diphenidol, SK&F) exerts its antiemetic effect primarily by inhibiting the chemoreceptor trigger zone, as evidenced by its activity in blocking emesis induced by apomorphine in dogs. In this regard ‘Vontrol’, as the hydrochloride salt, has a potency equal to the potent phenothiazine antiemetic, chlorpromazine hydrochloride. In animals ‘Vontrol’ has only weak parasympatholytic activity and no significant sedative, tranquilizing or antihistaminic action or effects on blood pressure, heart rate, respiration or the electrocardiogram.

Subacute and chronic toxicity studies in rats and dogs, in which large doses of ‘Vontrol’, as the hydrochloride salt, were administered orally and intramuscularly for periods up to one year, revealed no significant effects on hematology, liver function, kidney function or blood glucose determinations. Histological examination of the animals’ tissues did not reveal any significant lesions attributable to administration of ‘Vontrol’.

Reproduction Studies

Teratogenesis and reproduction studies were carried out in rats and rabbits. In rats, ‘Vontrol’ (diphenidol, SK&F), as the hydrochloride salt, was fed daily to male and female animals in doses of 20 mg./kg. and 40 mg./kg. (approximately three and six times the maximum recommended daily dose in adult humans) for 60 days before mating, and during mating, gestation and lactation for each of two litters. There were no significant differences between drug-treated and untreated control groups with regard to conception rate, litter size, live birth or viability in either of the two litters. There was no congenital anomaly among the offspring. In rabbits, ‘Vontrol’, as the hydrochloride salt, was fed in the diets in doses of 5 mg./kg. or 75 mg./kg. (approximately equal to, and 12 times as much as, the maximum recommended daily dose in adult humans) from the first day of gestation through the 26th or 27th day of gestation, when the young were delivered by Cesarean section. There were no significant differences between drug-treated and control groups with regard to number and weight of fetuses, numbers of resorption sites or viable fetuses. There was also no statistically significant difference between drug-treated and control groups with regard to the total percentage of underdeveloped fetuses. However, when data were calculated on the basis of a ratio between underdeveloped fetuses and number of pregnant does, an adverse dose-related effect was observed in the high-dose test group.