promethazine

Promethazine is a phenothiazine in the same drug class as chlorpromazine (Thorazine) and trifluoperazine (Stelazine). However, unlike the other drugs in this class, promethazine is not used as an antipsychotic. It used as an antihistamine, sedative, and antiemetic (anti-nausea).

The body releases histamine during several types of allergic reactions. When histamine binds to its receptors on cells, it stimulates changes within the cells that lead to sneezing, itching, and increased mucus production. Antihistamines such as promethazine compete with histamine for one of the receptors for histamine (the H1 receptor) in cells.

However, when the antihistamines bind to the receptors they do not stimulate the cells. Instead, they prevent histamine from binding and stimulating the cells. Promethazine also blocks the action of acetylcholine (anticholinergic effect), and this may explain its benefit in reducing the nausea of motion sickness. It is used as a sedative because it causes drowsiness as a side effect.

The FDA approved promethazine in 1951.

Promethazine causes sedation, confusion, and disorientation. In children less than two it can depress respiration and lead to death. Therefore, it should not be used in children less than two years old. Dizziness may also occur. Ironically, promethazine sometimes stimulates patients, particularly children. Such stimulation may be manifest by restlessness, inability to sleep, heart palpitations or even seizures.

Other side effects include anticholinergic side effects such as:

• blurred vision,
• dry mouth,
• dilated pupils,
• nausea,
• urinary retention (inability to urinate),
• impotence, and
• constipation.

Extrapyramidal symptoms (EPS) may occur. EPS are categorized as dystonic reactions (alterations in muscle tone), sharp, involuntary muscle movements (often limited to one muscle or muscle group), akathisia (subjective restlessness), and Parkinsonism. Parkinsonian symptoms are more common in older persons whereas children more often develop involuntary muscle movement reactions. Dystonic reactions are most commonly seen during the first week of treatment. Restlessness and Parkinsonian symptoms usually develop days to weeks after starting therapy.

A serious complex called neuroleptic malignant syndrome (NMS) can occur in patients receiving phenothiazines. NMS consists of high body temperature, severe EPS, changes in consciousness and mental status, and increased heart rate with low or high blood pressure. NMS occurs more frequently in young men and in persons who are dehydrated.

Rarely, blood cell disorders can occur; low white cell counts can lead to infections.

Phenothiazines such as promethazine can cause skin hyperpigmentation (darkening) but usually only after prolonged use. The effect usually is restricted to areas of the body exposed to sunlight. Thus, people who need long-term treatment with promethazine should either keep out of the sun or use effective sunscreens.

Phenothiazines can cause blurred vision, difficulty with nighttime vision, or changes in color vision.

Liver damage has been reported rarely with phenothiazines. Jaundice is possible. Jaundice also may occur in newborns of mothers who receive phenothiazines during pregnancy.

Phenothiazines such as promethazine block dopamine receptors. This effect can lead to increases in blood levels of prolactin, a hormone involved in lactation (formation of breast milk). As a result, phenothiazines can cause the breast to produce fluid ("milk") even when a woman is not pregnant.

Additionally, phenothiazines can cause:

• missed menstrual periods,
• breast enlargement or tenderness,
• loss of sexual drive,
• impotence,
• inability to ejaculate, and
• priapism, and
• Weight gain.

• Allergic reactions are treated with 6.25-25 mg orally 3 times daily. A single 25 mg dose administered at bedtime also may suffice. A 25 mg injection is also used.
• Nausea and vomiting may be managed with 12.5-25 mg administered orally by injection every 4-6 hours as needed.
• Doses of 25-50 mg by injection are used for sedation before or after surgery.
• For prevention of motion sickness, 25 mg is used 30 to 60 minutes before the motion begins and then every 8 to 12 hours as needed. Oral, rectal and injectable doses are similar.
• Promethazine injections are used when the oral route is not possible (for example, with severe vomiting).
• Tablets may be taken with or without food.
• Suppositories are unwrapped and moistened with water before insertion into the rectum. If the suppository is too soft from being stored in a warm place, it may be chilled in the refrigerator for 20 to 30 minutes or placed in cold water before the wrapper is removed.

• There are no adequate studies of promethazine in pregnant women. Administration of promethazine within two weeks of delivery may affect platelet function in the newborn.
• It is not known whether promethazine is excreted in breast milk.

What preparations of promethazine are available?

• Tablets: 12.5, 25 and 50 mg;
• Suppositories: 12.5, 25 and 50 mg;
• Syrup: 6.25 mg/5 ml;
• Injection: 25 and 50 mg/ml.

How should I keep promethazine stored?

Tablets, syrup and injection should be stored at room temperature, between 15 C to 25 C (68 F to 77 F). Suppositories should be stored at 2 C to 8 C (36 F to 46 F).