Promethazine VC With Codeine

Follow all directions on your prescription label. Codeine and promethazine can slow or stop your breathing. Never use this medicine in larger amounts, or for longer than prescribed. Cough or cold medicine is usually taken only for a short time until your symptoms clear up.

Codeine may be habit-forming, even at regular doses. Never share this medicine with another person, especially someone with a history of drug abuse or addiction. MISUSE OF NARCOTIC MEDICINE CAN CAUSE ADDICTION, OVERDOSE, OR DEATH, especially in a child or other person using the medicine without a prescription. Selling or giving away codeine is against the law.

You should not use antihistamine medication to make a child sleepy.

Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

Do not take for longer than 7 days in a row. Call your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache or skin rash.

If you need surgery or medical tests, tell the surgeon or doctor ahead of time that you have used a cough or cold medicine in the past few days.

Store at room temperature away from moisture, heat, and light. Do not freeze.

Keep track of your medicine. Codeine is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

Since this medicine is taken when needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Codeine, phenylephrine, and promethazine combination is used to treat for the temporary relief of cough or stuffy nose caused by allergies or the common cold.

Codeine belongs to the group of medicines called narcotic analgesics (pain medicines). It acts on the central nervous system (CNS) to relieve pain. Phenylephrine is a decongestant. It works by narrowing the blood vessels and leads to clearing of the nasal congestion.

Promethazine is an antihistamine. It works by preventing the effects of a substance called histamine, which is produced by the body. Histamine can cause itching, sneezing, runny nose, and watery eyes. It can sometimes close up the bronchial tubes (air passages of the lungs) and make breathing difficult.

When codeine is used for a long time or in large doses, it may become habit-forming, causing mental or physical dependence. Physical dependence may lead to withdrawal side effects when you stop taking the medicine.

This medicine is available only with your doctor's prescription.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Use of codeine, phenylephrine, and promethazine combination in children younger than 6 years of age is not recommended. It should not be used to relieve pain after the surgical removal of tonsils and/or adenoids in any children. Severe breathing problems and deaths have been reported in some children who received codeine after tonsil or adenoid surgery.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of codeine, phenylephrine, and promethazine combination in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving codeine, phenylephrine, and promethazine combination.

Pregnancy

Breast Feeding

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Amisulpride
• Bepridil
• Bromopride
• Cisapride
• Dronedarone
• Furazolidone
• Iproniazid
• Isocarboxazid
• Linezolid
• Mesoridazine
• Methylene Blue
• Metoclopramide
• Moclobemide
• Nalmefene
• Naltrexone
• Nialamide
• Phenelzine
• Pimozide
• Piperaquine
• Procarbazine
• Rasagiline
• Safinamide
• Saquinavir
• Selegiline
• Sodium Oxybate
• Sparfloxacin
• Terfenadine
• Thioridazine
• Toloxatone
• Tranylcypromine
• Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acepromazine
• Alfentanil
• Alfuzosin
• Almotriptan
• Alprazolam
• Amineptine
• Amiodarone
• Amisulpride
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Anagrelide
• Anileridine
• Apomorphine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Asenapine
• Astemizole
• Azithromycin
• Baclofen
• Benperidol
• Benzphetamine
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Bupropion
• Buserelin
• Buspirone
• Butabarbital
• Butorphanol
• Carbamazepine
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Chloral Hydrate
• Chlordiazepoxide
• Chloroquine
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clobazam
• Clomipramine
• Clonazepam
• Clorazepate
• Clozapine
• Cocaine
• Codeine
• Conivaptan
• Crizotinib
• Cyclobenzaprine
• Dabrafenib
• Darunavir
• Dasatinib
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Desmopressin
• Deutetrabenazine
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Difenoxin
• Dihydrocodeine
• Diphenhydramine
• Diphenoxylate
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Dothiepin
• Doxepin
• Doxylamine
• Droperidol
• Duloxetine
• Efavirenz
• Eletriptan
• Enflurane
• Erythromycin
• Escitalopram
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Fentanyl
• Fingolimod
• Flecainide
• Flibanserin
• Fluconazole
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Foscarnet
• Fospropofol
• Frovatriptan
• Gatifloxacin
• Gemifloxacin
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Halothane
• Hexobarbital
• Histrelin
• Hydrocodone
• Hydromorphone
• Hydroxychloroquine
• Hydroxytryptophan
• Hydroxyzine
• Ibutilide
• Iloperidone
• Imipramine
• Iobenguane I 123
• Isoflurane
• Isradipine
• Ivabradine
• Ketamine
• Ketazolam
• Ketobemidone
• Ketoconazole
• Lapatinib
• Leuprolide
• Levofloxacin
• Levomilnacipran
• Levorphanol
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lopinavir
• Lorazepam
• Lorcaserin
• Loxapine
• Lumefantrine
• Meclizine
• Mefloquine
• Melitracen
• Melperone
• Meperidine
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Metrizamide
• Metronidazole
• Midazolam
• Midodrine
• Mifepristone
• Milnacipran
• Mirtazapine
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Moxifloxacin
• Nafarelin
• Nalbuphine
• Naratriptan
• Nefazodone
• Netupitant
• Nicomorphine
• Nilotinib
• Nitrazepam
• Nitrous Oxide
• Norfloxacin
• Nortriptyline
• Octreotide
• Ofloxacin
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxycodone
• Oxymorphone
• Paliperidone
• Palonosetron
• Panobinostat
• Papaveretum
• Paregoric
• Paroxetine
• Pasireotide
• Pazopanib
• Pentamidine
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenobarbital
• Pimavanserin
• Piperacetazine
• Pipotiazine
• Piritramide
• Pitolisant
• Posaconazole
• Prazepam
• Primidone
• Procainamide
• Procarbazine
• Prochlorperazine
• Promazine
• Promethazine
• Propafenone
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Quinine
• Ramelteon
• Ranolazine
• Remifentanil
• Remoxipride
• Ribociclib
• Rizatriptan
• Salmeterol
• Secobarbital
• Sertindole
• Sertraline
• Sevoflurane
• Sibutramine
• Sodium Oxybate
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sorafenib
• Sotalol
• St John's Wort
• Sufentanil
• Sulpiride
• Sumatriptan
• Sunitinib
• Suvorexant
• Tacrolimus
• Tapentadol
• Telavancin
• Telithromycin
• Temazepam
• Tetrabenazine
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Tilidine
• Tiotropium
• Tizanidine
• Tolonium Chloride
• Topiramate
• Toremifene
• Tramadol
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Triptorelin
• Tryptophan
• Vandetanib
• Vardenafil
• Vemurafenib
• Venlafaxine
• Vilazodone
• Vinflunine
• Voriconazole
• Vortioxetine
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine
• Zuclopenthixol

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aminolevulinic Acid
• Belladonna
• Belladonna Alkaloids
• Betel Nut
• Evening Primrose
• Midodrine
• Phenylalanine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Addison's disease or
• Alcohol abuse, or history of or
• Bladder blockage or
• Brain tumor or
• Breathing problems (eg, COPD, sleep apnea) or
• Depression or
• Drug dependence, especially with narcotics, or history of or
• Enlarged prostate or
• Head injury or
• Thyroid problems or
• Trouble urinating or
• Weakened physical condition—Use with caution. May increase risk for more serious side effects.

• Asthma or
• Hypertension (high blood pressure) or
• Peripheral vascular insufficiency or
• Surgery (eg, nasopharyngeal tonsils, tonsils)—Should not be used in patients with these conditions.

• Bone marrow problems (eg, agranulocytosis, leukopenia) or
• Diabetes or
• Heart or blood vessel problems (eg, arteriosclerosis) or
• Hypotension (low blood pressure) or
• Kidney disease or
• Liver disease (eg, cholestatic jaundice) or
• Narrow-angle glaucoma or
• Seizures, or history of or
• Stomach or bowel problems (eg, bowel blockage, peptic ulcer, ulcerative colitis) or
• Surgery (eg, stomach, urinary tract), recent—Use with caution. May make these conditions worse.

Codeine

Narcotic analgesics, including codeine, exert their primary effects on the central nervous system and gastrointestinal tract. The analgesic effects of codeine are due to its central action; however, the precise sites of action have not been determined, and the mechanisms involved appear to be quite complex. Codeine resembles morphine both structurally and pharmacologically, but its actions at the doses of codeine used therapeutically are milder, with less sedation, respiratory depression and gastrointestinal, urinary, and pupillary effects. Codeine produces an increase in biliary tract pressure, but less than morphine or meperidine. Codeine is less constipating than morphine.

Codeine has good antitussive activity, although less than that of morphine at equal doses. It is used in preference to morphine, because side effects are infrequent at the usual antitussive dose of codeine.

Codeine in oral therapeutic dosage does not usually exert major effects on the cardiovascular system. Narcotic analgesics may cause nausea and vomiting by stimulating the chemoreceptor trigger zone (CTZ); however, they also depress the vomiting center, so that subsequent doses are unlikely to produce vomiting. Nausea is minimal after usual oral doses of codeine.

Narcotic analgesics cause histamine release, which appears to be responsible for wheals or urticaria sometimes seen at the site of injection on parenteral administration. Histamine release may also produce dilation of cutaneous blood vessels, with resultant flushing of the face and neck, pruritus, and sweating.

Codeine and its salts are well absorbed following both oral and parenteral administration. Codeine is about 2/3 as effective orally as parenterally. Codeine is metabolized primarily in the liver by enzymes of the endoplasmic reticulum, where it undergoes O-demethylation, N­-demethylation, and partial conjugation with glucuronic acid. The drug is excreted primarily in the urine, largely as inactive metabolites and small amounts of free and conjugated morphine. Negligible amounts of codeine and its metabolites are found in the feces.

Following oral or subcutaneous administration of codeine, the onset of analgesia occurs within 15 to 30 minutes and lasts for four to six hours.

The cough-depressing action, in animal studies, was observed to occur 15 minutes after oral administration of codeine, peak action at 45 to 60 minutes after ingestion. The duration of action, which is dose-dependent, usually did not exceed 3 hours.

Promethazine

Promethazine is a phenothiazine derivative which differs structurally from the antipsychotic phenothiazines by the presence of a branched side chain and no ring substitution. It is thought that this configuration is responsible for its relative lack (1/10 that of chlorpromazine) of dopamine antagonist properties.

Promethazine is an H1 receptor blocking agent. In addition to its antihistaminic action, it provides clinically useful sedative and antiemetic effects. Promethazine is well absorbed from the gastrointestinal tract. Clinical effects are apparent within 20 minutes after oral administration and generally last four to six hours, although they may persist as long as 12 hours. Promethazine is metabolized by the liver to a variety of compounds; the sulfoxides of promethazine and N-demethylpromethazine are the predominant metabolites appearing in the urine.

Phenylephrine

Phenylephrine is a potent postsynaptic-α-receptor agonist with little effect on β receptors of the heart. Phenylephrine has no effect on β-adrenergic receptors of the bronchi or peripheral blood vessels. A direct action at receptors accounts for the greater part of its effects, only a small part being due to its ability to release norepinephrine.

Therapeutic doses of phenylephrine mainly cause vasoconstriction. Phenylephrine increases resistance and, to a lesser extent, decreases capacitance of blood vessels. Total peripheral resistance is increased, resulting in increased systolic and diastolic blood pressure.

Pulmonary arterial pressure is usually increased, and renal blood flow is usually decreased. Local vasoconstriction and hemostasis occur following topical application or infiltration of phenylephrine into tissues.

The main effect of phenylephrine on the heart is bradycardia; it produces a positive inotropic effect on the myocardium in doses greater than those usually used therapeutically. Rarely, the drug may increase the irritability of the heart, causing arrhythmias. Cardiac output is decreased slightly. Phenylephrine increases the work of the heart by increasing peripheral arterial resistance. Phenylephrine has a mild central stimulant effect.

Following oral administration or topical application of phenylephrine to the mucosa, constriction of blood vessels in the nasal mucosa relieves nasal congestion associated with allergy or head colds. Following oral administration, nasal decongestion may occur within 15 or 20 minutes and may persist for up to 4 hours.

Phenylephrine is irregularly absorbed from and readily metabolized in the gastrointestinal tract. Phenylephrine is metabolized in the liver and intestine by monoamine oxidase. The metabolites and their route and rate of excretion have not been identified. The pharmacologic action of phenylephrine is terminated at least partially by uptake of the drug into tissues.

Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-threatening Respiratory Depression in Children

Life-threatening respiratory depression and death have occurred in children who received codeine. Codeine is subject to variability in metabolism based upon CYP2D6 genotype (described below), which can lead to an increased exposure to the active metabolite morphine. Based upon post-marketing reports, children less than 12 years old appear to be more susceptible to the respiratory depressant effects of codeine, particularly if there are risk factors for respiratory depression. For example, many reported cases of death occurred in the post-­operative period following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being ultra-rapid metabolizers of codeine. Furthermore, children with obstructive sleep apnea who are treated with codeine for post-tonsillectomy and/or adenoidectomy pain may be particularly sensitive to its respiratory depressant effect. Because of the risk of life-threatening respiratory depression and death:

• Promethazine VC with Codeine Oral Solution is contraindicated in all children younger than 12 years of age. (See CONTRAINDICATIONS).

• Promethazine VC with Codeine Oral Solution is contraindicated for post-operative management in pediatric patients younger than 18 years of age following tonsillectomy and/or adenoidectomy. (See CONTRAINDICATIONS).

• Avoid the use of Promethazine VC with Codeine Oral Solution in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine. Risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression.

• When prescribing codeine for adolescents, healthcare providers should choose the lowest effective dose for the shortest period of time and inform patients and caregivers about these risks and the signs of morphine overdose. (See OVERDOSAGE).

Nursing Mothers

At least one death was reported in a nursing infant who was exposed to high levels of morphine in breast milk because the mother was an ultra-rapid metabolizer of codeine. Breastfeeding is not recommended during treatment with Promethazine VC with Codeine Oral Solution. (See PRECAUTIONS -Nursing Mothers).

CYP2D6 Genetic Variability: Ultra-rapid metabolizer

Some individuals may be ultra-rapid metabolizers because of a specific CYP2D6 genotype (e.g., gene duplications denoted as *1/*1xN or *1/*2xN). The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 1 to 10% for Whites (European, North American), 3-4% for Blacks (African Americans), 1-2% for East Asians (Chinese, Japanese, Korean), and may be greater than 10% in certain ethnic groups (i.e., Oceanian, Northern African, Middle Eastern, Ashkenazi Jews, Puerto Rican). These individuals convert codeine into its active metabolite, morphine, more rapidly and completely than other people. This rapid conversion results in higher than expected serum morphine levels. Even at labeled dosage regimens, individuals who are ultra-rapid metabolizers may have life-threatening or fatal respiratory depression or experience signs of overdose (such as extreme sleepiness, confusion, or shallow breathing). (See OVERDOSAGE). Therefore, individuals who are ultra-rapid metabolizers should not use codeine.

Promethazine and Respiratory Depression in Children

Postmarketing cases of respiratory depression, including fatalities have been reported with use of promethazine in pediatric patients. Concomitant administration with other respiratory depressants may increase the risk of respiratory depression. Children may be particularly sensitive to the additive respiratory depressant effects when promethazine is combined with other respiratory depressants, including codeine. See WARNINGS -Ultra-Rapid Metabolism of Codeine and Respiratory Depression for limitations on the use of Promethazine VC with Codeine Oral Solution in children.

• Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of opioids, including Promethazine VC with Codeine Oral Solution, with benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Because of these risks, avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol. (See PRECAUTIONS - Drug Interactions).

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. Because of similar pharmacologic properties, it is reasonable to expect similar risk with concomitant use of opioid cough medications and benzodiazepines, other CNS depressants, or alcohol.

Advise both patients and caregivers about the risks of respiratory depression and sedation if Promethazine VC with Codeine Oral Solution is used with benzodiazepines, alcohol, or other CNS depressants. (See PRECAUTIONS -Information for Patients).

• Dosage of codeine SHOULD NOT BE INCREASED if cough fails to respond; an unresponsive cough should be re-evaluated in 5 days or sooner for possible underlying pathology, such as a foreign body or lower respiratory tract disease.

• Codeine may cause or aggravate constipation.

• Administration of codeine may be accomplished by histamine release and should be used with caution in atopic children.

• Head Injury and Increased Intracranial Pressure

  The respiratory-depressant effects of narcotic analgesics and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, intracranial lesions, or a pre-existing increase in intracranial pressure. Narcotics may produce adverse reactions which may obscure the clinical course of patients with head injuries.

• Asthma and Other Respiratory Conditions

  Narcotic analgesics or cough suppressants, including codeine, should not be used in asthmatic patients (see CONTRAINDICATIONS). Nor should they be used in acute febrile illness associated with productive cough or in chronic respiratory disease where interference with ability to clear the tracheobronchial tree of secretions would have a deleterious effect on the patient's respiratory function.

• Hypotensive Effect

Codeine may produce orthostatic hypotension in ambulatory patients.

Promethazine

• CNS Depression
Promethazine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. The impairment may be amplified by concomitant use of other central nervous system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore avoid use of Promethazine VC with Codeine Oral Solution in patients on these medications. (See PRECAUTIONS - Information for Patients and Drug Interactions).

• Respiratory Depression
Promethazine may lead to potentially fatal respiratory depression. Use of promethazine in patients with compromised respiratory function (e.g. COPD, sleep apnea) should be avoided.

• Lower Seizure Threshold
Promethazine may lower seizure threshold. It should be used with caution in persons with seizure disorders or in persons who are using concomitant medications, such as narcotics or local anesthetics, which may also affect seizure threshold.

• Bone-Marrow Depression
Promethazine should be used with caution in patients with bone marrow depression. Leukopenia and agranulocytosis have been reported, usually when promethazine HCl has been used in association with other known marrow toxic agents.

• Neuroleptic Malignant Syndrome
A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with promethazine HCl alone or in combination with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmias).

The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology.

The management of NMS should include 1) immediate discontinuation of promethazine HCl, antipsychotic drugs, if any, and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.

Since recurrences of NMS have been reported with phenothiazines, the reintroduction of promethazine HCl should be carefully considered.

Use in Pediatric Patients

Life-threatening respiratory depression and death have occurred in children who received codeine. (See WARNINGS - Ultra-Rapid Metabolism of Codeine and Respiratory Depression). In most of the reported cases, these events followed tonsillectomy and/or adenoidectomy, and many of the children had evidence of being ultra-rapid metabolizers of codeine (i.e., multiple copies of the gene for cytochrome P450 isoenzyme 2D6 or high morphine concentrations). Children with sleep apnea may be particularly sensitive to the respiratory depressant effects of codeine. Postmarketing cases of respiratory depression, including fatalities have been reported with use of promethazine in pediatric patients. (See WARNINGS ­- Promethazine and Respiratory Depression in Children). Because of the risk of life­-threatening respiratory depression and death:

• Promethazine VC with Codeine Oral Solution is contraindicated in all children younger than 12 years of age. (See CONTRAINDICATIONS).

•  Promethazine VC with Codeine Oral Solution is contraindicated for post-operative pain management in pediatric patients of any age undergoing tonsillectomy and/or adenoidectomy. (See CONTRAINDICATIONS).

Avoid the use of Promethazine VC with Codeine Oral Solution in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine. Risk factors include postoperative status, obstructive sleep apnea, obesity and other conditions associated with hypoventilation syndromes (e.g. neuromuscular disease), concomitant use of other medications that cause respiratory depression, and severe pulmonary disease. (See WARNINGS - Ultra-Rapid Metabolism of Codeine and Respiratory Depression).

Excessively large dosages of antihistamines, including promethazine hydrochloride, in pediatric patients may cause sudden death (see OVERDOSAGE). Hallucinations and convulsions have occurred with therapeutic doses and overdoses of promethazine hydrochloride in pediatric patients. In pediatric patients who are acutely ill associated with dehydration, there is an increased susceptibility to dystonias with the use of promethazine HCl.

Other Considerations

Administration of promethazine has been associated with reported cholestatic jaundice.

Phenylephrine

Because phenylephrine is an adrenergic agent, it should be given with caution to patients with thyroid diseases, diabetes mellitus and heart diseases or those receiving tricyclic antidepressants.

Men with symptomatic, benign prostatic hypertrophy can experience urinary retention when given oral nasal decongestants.

Phenylephrine can cause a decrease in cardiac output, and extreme caution should be used when administering the drug parenterally or orally to patients with arteriosclerosis, to elderly individuals, and/or to patients with initially poor cerebral or coronary circulation.

Phenylephrine should be used with caution in patients taking diet preparations, such as amphetamines or phenylpropanolamine, because synergistic adrenergic effects could result in serious hypertensive response and possible stroke.

Controlled Substance

Promethazine VC with Codeine Oral Solution is a Schedule V Controlled Substance.

Abuse

Codeine is known to be subject to abuse; however, the abuse potential of oral codeine appears to be quite low. Even parenteral codeine does not appear to offer the psychic effects sought by addicts to the same degree as heroin or morphine. However, codeine must be administered only under close supervision to patients with a history of drug abuse or dependence.

Dependence

Psychological dependence, physical dependence and tolerance are known to occur with codeine.

Each 5 mL of reddish-clear solution with odor of strawberry menthol contains promethazine hydrochloride 6.25 mg, phenylephrine hydrochloride 5 mg, codeine phosphate 10 mg; and alcohol 7% and is available as follows:

NDC 0603-1588-54               4 fluid ounce (118 mL)
NDC 0603-1588-58                1 pint (473 mL).

Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature].

Dispense in a tight, light-resistant container with a child-resistant closure as defined in the USP.

DEA Order Form Required

Distributed by:
Par Pharmaceutical
Chestnut Ridge, NY 10977

8181659
Revised: 07/17
R10