Promethazine Vc-Codeine (promethazine/phenylephrine HCl/codeine)

Dosages of promethazine hydrochloride by the various routes of administration are identical.

Because of the risk of potentially fatal respiratory depression, promethazine hydrochloride should not be used in children younger than 2 years of age. The drug should be used cautiously and at the lowest effective dosage in older children (See Cautions: Pediatric Precautions.)

Phenylephrine hydrochloride is administered by IV bolus or continuous IV infusion for the treatment of clinically important hypotension. The drug is available as a 10 mg/mL phenylephrine hydrochloride injection concentrate that must be diluted prior to administration and as a ready-to-use phenylephrine hydrochloride 100 mcg/mL (Immphentiv(R), Biorphen(R)) injection. Ready-to-use phenylephrine hydrochloride 100 mcg/mL (Immphentiv(R), Biorphen(R)) injection should not be further diluted before IV bolus administration.

For treatment of hypotension during anesthesia, the manufacturers recommend administration of phenylephrine hydrochloride as an IV bolus or continuous infusion; when used in the treatment of septic shock, the drug should be administered as a continuous IV infusion with no initial bolus dose. Phenylephrine hydrochloride injection should be stored at 20-25degreesC, but may be exposed to temperatures ranging from 15-30degreesC; single-dose and pharmacy bulk vials should be kept in their original carton until time of use and protected from light.

Commercially available phenylephrine hydrochloride injection concentrate must be diluted with a compatible IV solution prior to administration. Diluted solutions may be stored at room temperature for up to 4 hours or under refrigeration for up to 24 hours; any unused portions should be discarded.

Commercially available phenylephrine hydrochloride bulk vials are intended for use in a pharmacy admixture program for preparation of single doses to be dispensed to multiple patients. Each vial should be penetrated only one time with a suitable sterile transfer device or dispensing set. Dispensing from a pharmacy bulk vial should be completed within 4 hours after the vial is penetrated.

Prior to administration, phenylephrine hydrochloride solutions should be inspected visually for particulate matter and discoloration; the drug should be discarded if the solution is colored, cloudy, or contains any particulate matter.

Care should be taken to avoid extravasation and the infusion site should be checked for free flow.

Promethazine hydrochloride may be administered orally, rectally, or by deep IM injection. Promethazine hydrochloride also is administered by IV injection. However, because IV administration of the drug has been associated with severe tissue injury, including gangrene requiring amputation, the US Food and Drug Administration (FDA) states that deep IM injection is the preferred method for administration of promethazine hydrochloride injections. (See Cautions: Precautions and Contraindications.) If IV administration of promethazine hydrochloride is required, FDA states that the drug should be administered through the tubing of an IV infusion set that is known to be correctly functioning; FDA also states that the maximum rate of IV administration is 25 mg/minute, and the maximum concentration of the injection is 25 mg/mL. If the patient complains of pain at the injection site during presumed IV injection of the drug, the injection should immediately be stopped, and the possibility of intra-arterial placement of the needle or perivascular extravasation should be evaluated. Promethazine hydrochloride injection is commercially available in 2 strengths: 25 mg/mL and 50 mg/mL. FDA states that the preparation containing 50 mg/mL is for IM injection only; the preparation containing 25 mg/mL may be administered by IM or IV injection.

Because of the risk of severe tissue injury and amputations if promethazine hydrochloride is inadvertently administered intra-arterially or if extravasation were to occur, some medication safety experts (e.g., the Institute for Safe Medication Practices (ISMP)) recommend that parenteral administration of the drug be avoided and replaced by safer alternative therapies.

Subcutaneous or intra-arterial injection of promethazine hydrochloride is contraindicated.

Promethazine hydrochloride injection should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. The injection should be discarded if the solution is discolored or contains a precipitate.

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Known hypersensitivity to phenylephrine or to any ingredient in the respective formulation.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

The most commonly reported adverse effects in patients receiving IV phenylephrine hydrochloride were nausea, vomiting, and headache.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

The manufacturers state that safety and efficacy of parenteral preparations of phenylephrine hydrochloride have not been established in pediatric patients.

Data from randomized trials and meta-analyses with phenylephrine injection in pregnant women undergoing Cesarean section have not established a drug-associated risk of major birth defects or miscarriage. Additionally, the data did not identify adverse effects on maternal outcomes or infant Apgar scores. At recommended doses, phenylephrine does not appear to significantly affect fetal heart rate or fetal heart rate variability. Data are not available on phenylephrine use during the first or second trimester.

Untreated hypotension in pregnant women undergoing Cesarean delivery with neuraxial anesthesia has been associated with increased maternal nausea and vomiting. A sustained decrease in uterine blood flow caused by maternal hypotension has also been associated with fetal bradycardia and acidosis.

No data are available on the safety of phenylephrine injection during the period of organogenesis; therefore, conclusions cannot be drawn regarding the risk of birth defects from drug exposure. In addition, no data are available on the risk of miscarriage following fetal exposure to phenylephrine injection.

In animal studies, fetal malformations were observed following phenylephrine infusion over 1 hour during the period of organogenesis at a dosage of 1.2 times the human daily dosage. Decreased pup weight was also observed in offspring of pregnant rats who received 2.9 times the human daily dose of phenylephrine.

If a vasopressor is used in conjunction with oxytocic drugs, the vasopressor effect is potentiated and may result in serious adverse effects.

Safe use of promethazine during pregnancy (except during labor) with respect to possible adverse effects on fetal development has not been established. Although there are no adequate and controlled studies to date in humans, promethazine has not been shown to be teratogenic in rats receiving oral dosages of 6.25-12.5 mg/kg daily (about 2.1-4.2 times the maximum recommended human dosage, depending on the use of the drug). The drug has been shown to produce fetal mortality in rats receiving intraperitoneal dosages of 25 mg/kg daily. Antihistamines, including promethazine, have been fetocidal in rodents, but the pharmacologic effects of histamine in rodents differ from those in humans. Promethazine has been reported to possibly ameliorate the effects of hemolytic disease of the newborn+ (erythroblastosis fetalis) when administered during pregnancy in Rh-sensitized women, but the safety and efficacy of the drug for this use have not been clearly established; other methods of management are preferred. Promethazine should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.

There are no data on whether phenylephrine or its metabolite is distributed into human or animal milk following parenteral administration. The effects on the breast-fed infant and milk production are not known.

The developmental and health benefits of breast-feeding should be weighed along with the mother's clinical need for the drug and any potential adverse effects on the breast-fed infant from phenylephrine or from the underlying maternal condition.

It is not known whether promethazine is distributed into milk. Because many drugs are distributed in human milk and because of the potential for serious adverse reactions to promethazine in nursing infants if it were distributed, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

If phenylephrine is used in geriatric patients, dosage should be selected carefully, usually starting at the low end of the dosage range, since renal, hepatic, and cardiovascular dysfunction and concomitant disease or other drug therapy are more common in this age group.

Clinical studies of phenylephrine hydrochloride did not include sufficient numbers of patients >=65 years of age to determine whether geriatric patients respond differently than younger patients. Clinical experience to date has not identified any differences in response between geriatric and younger patients.

If phenylephrine is used in geriatric patients, dosage should be selected carefully, usually starting at the low end of the dosage range, since renal, hepatic, and cardiovascular dysfunction and concomitant disease or other drug therapy are more common in this age group.