Drug Profile

Pregnancy Warning

Phenothiazines cross the placenta, and there have been reports of prolonged jaundice and nervous system effects in infants of mothers who took these drugs during pregnancy. Tell your doctor if you are pregnant or thinking of becoming pregnant before you take one of these drugs.

Breast-Feeding Warning

Phenothiazines are excreted in human milk. Because of the potential for serious adverse effects in nursing infants, you should not take these drugs while nursing.

FDA BLACK BOX WARNING

Phenergan should not be used in pediatric patients less than 2 years of age because of the potential for fatal respiratory depression. Postmarketing cases of respiratory depression, including fatalities, have been reported with use of phenergan in pediatric patients less than 2 years of age. A wide range of weight-based doses of phenergan have resulted in respiratory depression in these patients.

Caution should be exercised when administering phenergan to pediatric patients 2 years of age and older. It is recommended that the lowest effective dose of phenergan be used in pediatric patients 2 years of age and older and concomitant administration of other drugs with respiratory depressant effects be avoided.

[09/16/2009] FDA is requiring a Boxed Warning for promethazine hydrochloride injection, USP products to better communicate the risks of severe tissue injury associated with administration of this drug.  Perivascular extravasation, unintentional intra-arterial injection and intraneuronal or perineuronal infiltration of the drug may result in irritation and tissue damage, including gangrene. The Boxed Warning will remind practitioners that due to the risks of intravenous injection, the preferred route of administration is deep intramuscular injection and that subcutaneous injection is contraindicated.

This action is based on FDA’s analysis of post-marketing reports of severe tissue injury, including gangrene, requiring amputation following intravenous administration of promethazine as well as FDA’s review of the current prescribing information for these products.  FDA has determined that the presentation, organization, and content of the prescribing information should be revised to more effectively communicate the risk of severe tissue injury following intravenous administration.

In addition to the Boxed Warning, FDA is requiring a revision to the Dosage and Administration section to increase the visibility and accessibility of specific recommendations for the maximum concentration (25 mg per mL) and rate of administration (25 mg per minute) when intravenous administration of promethazine is required.

FDA is requiring the changes to the prescribing information under the authorities granted to FDA by the Food and Drug Administration Amendments Act (FDAAA) of 2007.

Promethazine hydrochloride injection, USP is approved for a variety of uses including allergic reactions, sedation, motion sickness, nausea, and vomiting associated with anesthesia and surgery, and as an adjunct to analgesics for control of postoperative pain.[1]

WARNING

Increased Mortality in Elderly Patients With Dementia-Related Psychosis Seen With Prochlorperazine

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10 week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. COMPAZINE® (prochlorperazine maleate tablets USP) is not approved for the treatment of patients with dementia-related psychosis.

Decreased Sweating

These drugs may make you sweat less, causing your body temperature to increase. Use extra care not to become overheated during exercise or in hot weather while you are taking one of these medications, since overheating may result in heatstroke. Also, hot baths or saunas may make you feel dizzy or faint when you are taking these medications.

Anticholinergic Effects

Warning: Special Mental and Physical Adverse Effects

Older adults are especially sensitive to the harmful anticholinergic effects of these drugs. Drugs in this family should not be used unless absolutely necessary.

Mental Effects: confusion, delirium, short-term memory problems, disorientation and impaired attention

Physical Effects: dry mouth, constipation, difficulty urinating (especially for a man with an enlarged prostate), blurred vision, decreased sweating with increased body temperature, sexual dysfunction and worsening of glaucoma

Dietary Steps to Manage Nausea Induced by Cancer Drugs

Drugs used to treat cancer often cause severe nausea and vomiting, either immediately after the drug is taken or several hours later. You can treat this kind of nausea and vomiting by changing your diet or by taking an antinausea drug. You should always try dietary changes first.

• Eat small, frequent meals so that your stomach is never empty.
• When you get up from sleeping or resting, eat some dry crackers or toast before you start being active.
• Drink carbonated drinks or other clear liquids such as soups and gelatin.
• Eat tart foods such as lemons and pickles.
• Do not eat foods with strong smells.

Sensitivity to Cold

Drugs such as chlorpromazine (THORAZINE), fluphenazine (PROLIXIN), prochlorperazine (COMPAZINE), thioridazine (Mellaril), and trifluoperazine (STELAZINE) may make you more sensitive to cold temperatures. Dress warmly during cold weather. Be careful during prolonged exposure to cold, such as in winter sports or swimming in cold water.

Do not use if you have or have had (if taking prochlorperazine):

• blood pressure that is severely high or low
• coma
• genetic defect in drug metabolism (2D6 enzyme)
• heart or blood vessel disease
• heart rhythm problems
• long QT syndrome that you were born with
• reactions to other antipsychotics (see p. 258)

Tell your doctor if you have or have had:

• alcohol dependence
• allergic reaction to drugs
• angina
• blood disease
• bone marrow depression
• brain damage
• breast cancer
• epilepsy or seizures
• glaucoma
• heart disease
• jaundice
• kidney disease
• liver disease
• lung disease or breathing problems
• Parkinson’s disease
• prostate enlarged or difficulty urinating
• Reye’s syndrome
• stroke or transient ischemic attack
• ulcer of stomach or duodenum

Tell your doctor about any other drugs you take, including aspirin, herbs, vitamins, and other nonprescription products.

• Do not stop taking this drug suddenly. Your doctor must give you a schedule to lower your dose gradually, to prevent withdrawal symptoms such as nausea, vomiting, stomach upset, trembling, dizziness, and symptoms of Parkinson’s disease.
• Do not use over-the-counter drugs for colds or allergies.
• Do not take over-the-counter antacids or antidiarrheals within two hours of taking promethazine.
• It may take two or three weeks before you can tell that this drug is working.
• Until you know how you react to this drug, do not drive or perform other activities requiring alertness. Prochlorperazine can cause blurred vision, drowsiness, and fainting.
• To avoid heatstroke, use caution when exercising, when the weather is hot, and when taking hot baths.
• Wear protective clothing and use sunblock when outdoors and avoid use of sunlamps, tanning beds, or tanning booths. Check with your doctor if you get a severe reaction.
• Wear sunglasses to protect your eyes from ultraviolet light.
• If you have dry mouth, use sugarless gum or candy, ice, or saliva substitute and check with your doctor or dentist if this condition lasts more than two weeks.
• Do not drink alcohol or use other drugs that can cause drowsiness.
• You may feel dizzy when rising from a lying or sitting position. When getting out of bed, hang your legs over the side of the bed for a few minutes, then get up slowly. When getting up from a chair, stay by the chair until you are sure that you are not dizzy.
• If you plan to have any surgery, including dental, tell your doctor that you take this drug.

• If you miss a dose, take it as soon as you remember, but skip it if it is almost time for the next dose. Do not take double doses.
• Do not share your medication with others.
• Take the drug at the same time(s) each day.
• Take with food or a full glass (eight ounces) of milk or water to prevent stomach upset.
• Swallow extended-release capsules whole.
• Store at room temperature with lid on tightly. Do not store in the bathroom. Do not expose to heat, moisture, or strong light. Do not let the liquid form freeze. Keep out of reach of children.

The following drugs, biologics (e.g., vaccines, therapeutic antibodies), or foods are listed in Evaluations of Drug Interactions 2003 as causing “highly clinically significant” or “clinically significant” interactions when used together with any of the drugs in this section. In some sections with multiple drugs, the interaction may have been reported for one but not all drugs in this section, but we include the interaction because the drugs in this section are similar to one another. We have also included potentially serious interactions listed in the drug’s FDA-approved professional package insert or in published medical journal articles. There may be other drugs, especially those in the families of drugs listed below, that also will react with this drug to cause severe adverse effects. Make sure to tell your doctor and pharmacist the drugs you are taking and tell them if you are taking any of these interacting drugs:

barbiturates (e.g., phenobarbital), cabergoline, DOSTINEX, epinephrine, EPIPEN, ESIMIL, GLUCOPHAGE, guanethidine, HALFAN, halofantrine, INDERAL, INDERAL LA, ISMELIN, monoamine oxidase (MAO) inhibitors (e.g., phenelzine), metformin, NEOSPORIN, NORPRAMIN, ORAP, PARLODEL, pergolide, PERMAX, pimozide, polymyxin B, propranolol, tramadol, ULTRAM, zotepine.

Call your doctor immediately if you experience:

• signs of tardive dyskinesia: lip smacking, chewing movements, puffing of cheeks, rapid, darting tongue movements, uncontrolled movements of arms or legs
• signs of parkinsonism: difficulty speaking or swallowing, loss of balance, masklike face, muscle spasms, stiffness of arms or legs, trembling and shaking, unusual twisting movements of body, shuffling walk
• signs of neuroleptic malignant syndrome: troubled or fast breathing, high or low blood pressure, increased sweating, loss of bladder control, muscle stiffness, seizures, unusual tiredness or weakness, fast heartbeat, irregular pulse, pale skin
• abdominal or stomach pain
• arms, legs, or muscles weak
• bleeding or bruising that is unusual
• breathing difficulty
• changed or blurred vision; difficulty seeing at night
• confusion
• difficulty urinating
• erections that are prolonged, painful, or inappropriate
• eyes or skin yellow
• eyes unable to move
• fainting
• fatigue
• fever
• mouth, gums, or throat sore
• muscles and joints aching
• nausea, vomiting, diarrhea
• nightmares
• restlessness or need to keep moving
• skin hot or dry
• skin rash, itching, or sunburn
• skin tanned or blue/gray discoloration
• sweating decreased

Call your doctor if these symptoms continue:

• breast swelling or pain
• constipation
• dizziness, lightheadedness
• drowsiness
• ears ringing or buzzing
• menstrual period changes
• milk, unusual secretion
• mouth dry
• mouth watering
• nasal congestion
• sexual ability decreased
• skin rash
• skin sensitivity to sun
• sweating decreased
• tongue rough or “fuzzy”
• weight gain that is unusual

Signs of overdose:

• agitation
• breathing difficulty
• confusion
• convulsions
• drowsiness, stupor, or coma
• fever
• heart rhythm disturbance
• mouth dry
• muscle weakness
• pupils dilated
• reflexes increased or decreased
• vision blurred
• vomiting

If you suspect an overdose, call this number to contact your poison control center: (800) 222-1222.

Call your doctor if these symptoms continue after you stop taking this drug:

• dizziness
• eyes unable to move
• muscle spasms of face, neck, body, arms, or legs
• nausea and vomiting
• stomach pain
• tardive dyskinesia
• ticlike or twitching movements
• sticking out of tongue
• trembling of fingers and hands
• trouble breathing, speaking, or swallowing
• twisting movements of body

Ask your doctor which of these tests should be done periodically while you are taking this drug:

• complete blood count if you develop a sore throat
• glaucoma tests
• blood potassium levels
• monitoring of heart function (ECG or EKG)
• liver function tests
• urine tests for bile and bilirubin
• observation for early signs of tardive dyskinesia
• evaluation of continued need for drug
• blood pressure
• eye examinations