Indications:
Promethazine is used for the treatment or prevention of hypersensitivity reactions (e.g urticaria, angioedema, rhinitis, conjunctivitis and pruritus), sedation in both children and adults (except babies), as well as relief of anxiety and production of light sleep from which the patient can be easily aroused.
Promethazine is also used as sedatives and antiemetics in surgery and obstetrics.
Promethazine reduces stress, anxiety in preoperative patients, produces a light sleep and reduction of postoperative nausea and vomiting.
Active and prophylactic treatment of motion sickness.
Administration, dosage:
Administration:
Dissolve the granules in a little water just prior to administration.
Promethazine should be taken before meals and at bedtime.
Dosage:
Children:
– From 2 to 6 years of age: ½ sachet once.
– From 7 to 12 years of age: 1 sachet once.
Adults: 2 sachets once.
Promethazine should be taken 3 – 4 times daily.
For prophylactic prevention of motion sickness, the initial dose of promethazine should be taken at least 30 to 60 minutes before departure; a second dose can be taken after 8 – 12 hours, if necessary.
Some special attention on the handling of the medicine before and after use:
There are no special requirements for handling the drug after use.
Contraindications:
Patients in comatose states and taking large doses of central nervous system depressants.
Pregnant women and breast-feeding mothers.
Children under 2 years of age.
Warnings and precautions for use:
Antihistamines should not be administered to newborn or premature infants because they are often very responsive to the the effect of respiratory depression and anticholinergic effect in the CNS of these drugs. Promethazine should not be used in children less than 2 years of age because of the potential for fatal respiratory depression, sleep apnea and reduced consciousness. The use of promethazine should be avoided in pediatric patients whose signs and symptoms may suggest Reye’s syndrome, especially at large doses, because it can cause extrapyramidal symptoms which may easily confused with CNS signs of this syndrome, leading to difficulty in diagnosis.
Promethazine may cause severe drowsiness. Therefore, patients who are taking this drug should not drive or operate machinery.
Due to anticholinergic properties of antihistamines, promethazine should be used cautiously in patients with asthma, narrow angle glaucoma, urinary retention, prostatic hypertrophy, pyloroduodenal obstruction.
Stronger anticholinergic side effects usually occur in elderly patients, especially in those with dementia or brain damage.
Promethazine should be used with caution in patients with epilepsy or severe cardiovascular disease, impaired liver function or bone-marrow depression.
The sedative effect of promethazine is enhanced by CNS depressants such as alcohol, narcotic analgesics, sedatives, hypnotics and tranquilizers. Therefore, concomitant use of these drugs and promethazine should be avoided or the dose should be reduced. The dose of barbiturates should be reduced by at least one-half if they are used concurrently with promethazine; the dose of narcotics (such as morphine, pethidine) should be reduced by one-quarter to one-half. Sedatives or CNS depressants should be avoided in patients with a history of sleep apnea.
This medicine contains lactose monohydrate: Patients with rare hereditary problems of galactose intolerance, complete lactase deficiency or glucose-galactose malabsorption should not take this medicine.
This medicine contains sucrose: Patients with rare hereditary problems such as fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase enzyme deficiency should not take this medicine.
This medicine contains 0.8 mg of benzoic acid per 1.6 g sachet equivalent to 0.5 mg/g.
Pregnancy and lactation:
Pregnancy:
The safety of promethazine during pregnancy has not been established. It is only administered to pregnant women when benefits outweigh the risks to the fetus.
Lactation:
It is not known whether promethazine is distributed into breast milk; therefore, it should be used with caution in breastfeeding mothers because of the risk of unwanted effects (such as irritability and excitement) can occur in children.
Antihistamines may inhibit lactation due to anticholinergic effects.
Fertility:
There are no data on the effect of the drug on human fertility.
Effects on ability to drive, use machines:
Promethazine may cause severe drowsiness. Therefore, patients who are taking promethazin should not drive or operate machinery.
Interactions, incompatibilities of medicine:
Interactions:
CNS depressants: Promethazine synergizes or intensifies the sedative effects of opiates or other analgesics and central-nervous-system depressants (such as barbiturates and other sedatives), antihistamines, tranquillizers and alcohol.
When promethazine is concurrently administered with CNS depressants, caution should be taken to avoid overdose.
Epinephrine: Alpha – adrenergic effect of epinephrine may be blocked if it is given concomitantly with phenothiazine derivatives which possess alpha–adrenergic blocking effects.
MAOIs: When concomitantly taken MAOIs may prolong and intensify anticholinergic and CNS depressant effects of antihistamines.
Concomitant use with antihistamines which are phenothiazine derivatives can increase the risk of hypotension and extrapyramidal reactions.
Beta-adrenergic blocking agents, especially propranolol: Concurrent use with phenothiazine derivatives may result in increased plasma concentration of each medication due to inhibition of metabolism; therefore, this may induce the increase of hypotensive effects, irreversible retinopathy, cardiac arrhythmias, and tardive dyskinesia.
Levodopa: When used concurrently with phenothiazine derivatives, antiparkinsonian effects of levodopa may be inhibited because of blockade of dopamine receptors in the brain by phenothiazines.
Interaction with diagnostic tests:
- Pregnancy test: Diagnostic pregnancy tests based on immunological reactions between HCG and anti-HCG may result in false-negative or false-positive interpretations.
- Glucose tolerance test: An increase in blood glucosecan occur in patients receiving promethazine.
Incompatibilities: Because there are no studies of drug incompatibility, do not mix this drug with other drugs.
Undesirable effects:
Undesirable effects are classified according to frequency: Very common (ADR ≥ 1/10), common (1/100 ≤ ADR < 1/10), uncommon (1/1,000 ≤ ADR < 1/100), rare (1/10,000 ≤ ADR < 1/1,000), very rare (ADR < 1/10,000); cannot be estimated from the available data “Not known”.
Undesirable effects of promethazine can vary in frequency and severity, depending on individual patient.
These effects are generally expressed in the central nervous system.
Common
- Nervous: Drowsiness, blurred vision.
- Skin: Rash.
- Others: Thick mucus.
Uncommon
- Nervous: Dizziness, fatigue, tinnitus, loss of coordination, double vision, insomnia, tremors, convulsive seizures, irritability, hysteria.
- Gastrointestinal: Dry mouth or throat (more common in the elderly). Nausea, vomiting (commonly seen in surgical procedures or combination drug therapy).
Rare
- Nervous: Disorientation, lossof movement control, confusion, painful urination (more common in the elderly), nightmares, hyperexcitability, restlessness (more common in children and the elderly). Extrapyramidal reactions such as oculogyric crises, torticollis and tongue protrusion (often occurring with high doses).
- Hematologic: Leukopenia, thrombocytopenia, agranulocytosis.
- Skin: Photosensitivity, allergic dermatitis, jaundice.
- Teeth: Long term use may lead to risk of tooth decay due to dry mouth.
Guidelines for ADR management
If serious side effects occur, you should stop taking promethazin.
Contact your doctor if you experience these side effects.
Pharmacodynamics:
Pharmacological group: Antihistamine (H1 receptor); sedative, hypnotic; antiemetic.
ATC code: R06AD02.
Promethazine is an antihistamine with strong sedative effect. However, it may also stimulate or inhibit paradoxically central nervous system. Sedative effect is the manifestation of CNS inhibition resulting from doses that provide antihistamine effect. Promethazine also produces antiemetic, anticholinergic and anti-motion sickness effects. In addition, the drug is effective in the treatment of mild cough that reflects the potential respiratory depression.
Promethazine is a histamine H1–receptor antagonist competing with histamine for binding at H1–receptor sites on effector cells. However, promethazine does not prevent the release of histamine. Therefore, this medicine only prevents histamine-induced allergic reactions. Promethazine antagonizes, most, but not all, of the pharmacological effects of histamine at different levels, including urticaria, pruritus. Therefore, promethazine is used in preanesthesia and before the procedure which may cause histamine release. In addition, the anticholinergic actions of most antihistamines provide a drying effect on the nasal and oral mucosa.
Promethazine and most antihistamines cross the blood – brain barrier, induce sedative effects by inhibiting histamine N-methyltransferase, and blocking central histamine receptors. This is a particular risk for young children because fatal sleep apnea caused by antihistamines has been proven.
Pharmacokinetics:
Absorption: Promethazine is well absorbed from the gastrointestinal tract. Plasma levels to obtain effective antihistaminic and sedative effects have not been known. After oral administration, antihistaminic and sedative effects are apparent within 20 minutes. Antihistaminic effects may last up to 12 hours or more, sedative effects may persist from 2 to 8 hours depending on doses and route of administration.
Distribution: Plasma protein binding varies from 76 to 93%. The drug is widely distributed to all tissues of the body. Although the concentration in the brain is lower than in other parts, but it is still higher than the concentration in plasma.
Elimination: Promethazine readily crosses the placenta. It is unknown if this medication passes into breast milk.
Promethazine is extensively metabolized by the liver, excreted in the urine and feces.
Overdose and management:
Overdose:
The casualties due to high doses of promethazine have not been recorded; however when overdosing, the following symptoms may occur: Low blood pressure, mild depression of the central nervous system, respiratory depression, convulsions, perceptual disturbances, coma. Other reactions including hyperreflexia, hypertonia, loss of movement coordination, tremors, extrapyramidal signs, dry mouth, dilated pupils, facial flushing, digestive disorders.
Management:
In case of overdose or accidentally taking very high dose, patient should be immediately transferred to the nearest medical facility and inform the doctor about the information of promethazine overdose to get treatment in time.
Storage conditions, shelf life, quality specification of the medicine:
Storage conditions: Protect from humidity and light, below 300C.
Shelf life: 36 months from the manufacture date.
Quality specification: In house.
