Phrenilin with Caffeine and Codeine

• Valeant Pharmaceuticals International

• Valeant Pharmaceuticals North America LLC

Phrenilin with Caffeine and Codeine is part of the drug classes:

• Anilides

• Opium alkaloids and derivatives

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

Appropriate studies have not been performed on the relationship of age to the effects of butalbital, acetaminophen, caffeine, and codeine combination in the pediatric population. Safety and efficacy have not been established.

This medicine should not be used to relieve pain after surgery removal of tonsils 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 butalbital, acetaminophen, caffeine, and codeine combination in the elderly. However, elderly patients are more likely to have age-related kidney or lung problems, which may require caution and an adjustment in the dose for patients receiving this medicine.

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.

• Furazolidone
• Iproniazid
• Isocarboxazid
• Linezolid
• Methylene Blue
• Moclobemide
• Nalmefene
• Naltrexone
• Nialamide
• Phenelzine
• Procarbazine
• Rasagiline
• Riociguat
• Safinamide
• Selegiline
• Toloxatone
• Tranylcypromine

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
• Almotriptan
• Alprazolam
• Amineptine
• Amisulpride
• Amitriptyline
• Amitriptylinoxide
• Amobarbital
• Amoxapine
• Amphetamine
• Anileridine
• Anisindione
• Aprobarbital
• Aripiprazole
• Asenapine
• Baclofen
• Benperidol
• Benzphetamine
• Bromazepam
• Bromopride
• Brompheniramine
• Buprenorphine
• Bupropion
• Buspirone
• Butabarbital
• Butalbital
• Butorphanol
• Carbamazepine
• Carbinoxamine
• Carisoprodol
• Carphenazine
• Chloral Hydrate
• Chlordiazepoxide
• Chlorpheniramine
• Chlorpromazine
• Chlorzoxazone
• Citalopram
• Clarithromycin
• Clobazam
• Clomipramine
• Clonazepam
• Clorazepate
• Clozapine
• Cocaine
• Conivaptan
• Cyclobenzaprine
• Dantrolene
• Darunavir
• Desipramine
• Desmopressin
• Dexmedetomidine
• Dextroamphetamine
• Dextromethorphan
• Dezocine
• Diazepam
• Dibenzepin
• Dichloralphenazone
• Dicumarol
• Difenoxin
• Dihydrocodeine
• Diphenhydramine
• Diphenoxylate
• Dolasetron
• Donepezil
• Doxepin
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Doxylamine
• Droperidol
• Duloxetine
• Eletriptan
• Enflurane
• Escitalopram
• Estazolam
• Eszopiclone
• Ethchlorvynol
• Ethopropazine
• Ethylmorphine
• Etonogestrel
• Fentanyl
• Flibanserin
• Flunitrazepam
• Fluoxetine
• Fluphenazine
• Flurazepam
• Fluspirilene
• Fluvoxamine
• Fospropofol
• Frovatriptan
• Granisetron
• Halazepam
• Haloperidol
• Halothane
• Hexobarbital
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Hydroxyzine
• Imatinib
• Imipramine
• Isoflurane
• Isoniazid
• Ketamine
• Ketazolam
• Ketobemidone
• Levomilnacipran
• Levorphanol
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lorazepam
• Lorcaserin
• Lormetazepam
• Loxapine
• Meclizine
• Medazepam
• Melitracen
• Melperone
• Meperidine
• Mephenesin
• Mephobarbital
• Meprobamate
• Meptazinol
• Mesoridazine
• Metaxalone
• Methadone
• Methamphetamine
• Methdilazine
• Methocarbamol
• Methohexital
• Methotrimeprazine
• Midazolam
• Milnacipran
• Mirtazapine
• Molindone
• Moricizine
• Morphine
• Morphine Sulfate Liposome
• Nalbuphine
• Naratriptan
• Nefazodone
• Netupitant
• Nicomorphine
• Nifedipine
• Nitrazepam
• Nitrous Oxide
• Nortriptyline
• Olanzapine
• Ondansetron
• Opipramol
• Opium
• Opium Alkaloids
• Orphenadrine
• Oxazepam
• Oxycodone
• Oxymorphone
• Palonosetron
• Papaveretum
• Paregoric
• Paroxetine
• Peginterferon Alfa-2b
• Pentazocine
• Pentobarbital
• Perampanel
• Perazine
• Periciazine
• Perphenazine
• Phenindione
• Phenobarbital
• Phenprocoumon
• Piperacetazine
• Piperaquine
• Pipotiazine
• Piritramide
• Pixantrone
• Pneumococcal 13-Valent Vaccine, Diphtheria Conjugate
• Prazepam
• Primidone
• Prochlorperazine
• Promazine
• Promethazine
• Propofol
• Protriptyline
• Quazepam
• Quetiapine
• Ramelteon
• Regadenoson
• Remifentanil
• Remoxipride
• Rizatriptan
• Secobarbital
• Sertindole
• Sertraline
• Sibutramine
• Sodium Oxybate
• St John's Wort
• Sufentanil
• Sulpiride
• Sumatriptan
• Suvorexant
• Tapentadol
• Temazepam
• Thiethylperazine
• Thiopental
• Thiopropazate
• Thioridazine
• Tianeptine
• Tilidine
• Tizanidine
• Tolonium Chloride
• Topiramate
• Tramadol
• Trazodone
• Triazolam
• Trifluoperazine
• Trifluperidol
• Triflupromazine
• Trimeprazine
• Trimipramine
• Tryptophan
• Ulipristal
• Venlafaxine
• Vilazodone
• Vortioxetine
• Zaleplon
• Ziprasidone
• Zolmitriptan
• Zolpidem
• Zopiclone
• Zotepine

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.

• Acenocoumarol
• Cannabis
• Carbamazepine
• Fosphenytoin
• Lixisenatide
• Ospemifene
• Phenytoin
• Prednisone
• Warfarin
• Zidovudine

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 is usually not recommended, 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
• Tobacco

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.

• Cabbage
• 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 (an adrenal problem) or
• Alcohol abuse, or history of or
• Brain tumor or
• Breathing or lung problems (eg, COPD, cor pulmonale, hypercapnia, hypoxia, sleep apnea) or
• Depression, or history of or
• Drug abuse or dependence, or history of or
• Enlarged prostate or
• Head injury, history of or
• Hypothyroidism (underactive thyroid) or
• Trouble urinating or
• Weakened physical condition—Use with caution. May increase risk for more serious side effects.

• Gallbladder problems or
• Hypotension (low blood pressure) or
• Pancreatitis (inflammation of the pancreas) or
• Seizures, or history of—Use with caution. May make these conditions worse.

• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• Lung or breathing problems (eg, asthma, respiratory depression), severe or
• Porphyria (enzyme problem) or
• Stomach or bowel blockage (eg, paralytic ileus) or
• Surgery (eg, nasopharyngeal tonsils, tonsils)—Should not be used in patients with these conditions.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Confusion (mild)
• mental depression
• unusual excitement (mild)

• Bleeding or crusting sores on the lips
• chest pain
• convulsions
• fever with or without chills
• hallucinations (seeing, hearing, or feeling things that are not there)
• hive-like swellings on the eyelids, face, lips, or tongue
• hives, itching, or skin rash
• muscle cramps or pain
• red, thickened, or scaly skin
• sores, ulcers, or white spots in the mouth
• sore throat
• swollen or painful glands
• tightness in the chest
• troubled breathing

Get emergency help immediately if any of the following symptoms of overdose occur:

• Anxiety (severe)
• cold and clammy skin
• confusion (severe)
• convulsions (seizures)
• dizziness, lightheadedness, drowsiness, or weakness (severe)
• excitement (severe)
• increased sleepiness in babies (more than usual)
• increased sweating
• irritability (severe)
• limpness (in babies)
• nausea or vomiting
• restlessness (severe)
• slow, fast, or irregular heartbeat
• slurred speech
• stomach cramps or pain
• swelling, pain, or tenderness in the upper abdomen or stomach area
• trembling or shaking of the hands or feet
• trouble sleeping (severe)
• unusually slow or troubled breathing

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bloated or "gassy" feeling
• dizziness or lightheadedness (mild)
• drowsiness (mild)
• nausea
• stomach pain (mild)
• vomiting

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Phrenilin® with Caffeine and Codeine (butalbital, acetaminophen, caffeine and codeine phosphate capsules) are indicated for the relief of the symptom complex of tension (or muscle contraction) headache.

Evidence supporting the efficacy and safety of Phrenilin® with Caffeine and Codeine (butalbital, acetaminophen, caffeine and codeine phosphate capsules) in the treatment of multiple recurrent headaches is unavailable. Caution in this regard is required because codeine and butalbital are habit-forming and potentially abusable.

Phrenilin® with Caffeine and Codeine (butalbital, acetaminophen, caffeine and codeine phosphate capsules) are contraindicated under the following conditions:

• Hypersensitivity or intolerance to acetaminophen, caffeine, butalbital, or codeine.

• Patients with porphyria.

Following an acute overdosage of Phrenilin® with Caffeine and Codeine (butalbital, acetaminophen, caffeine and codeine phosphate), toxicity may result from the barbiturate, the codeine, or the acetaminophen. Toxicity due to caffeine is less likely, due to the relatively small amounts in this formulation.

Signs and Symptoms: Toxicity from barbiturate poisoning include drowsiness, confusion, and coma; respiratory depression; hypotension; and hypovolemic shock. Toxicity from codeine poisoning includes the opioid triad of: pinpoint pupils, depression of respiration, and loss of consciousness. Convulsions may occur. In acetaminophen overdosage: dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and thrombocytopenia may also occur. Early symptoms, following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis, and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 -72 hours post-ingestion. In adults hepatic toxicity has rarely been reported with acute overdoses of less than 10 grams, or fatalities with less than 15 grams. Acute caffeine poisoning may cause insomnia, restlessness, tremor, and delirium, tachycardia, and extrasystoles.

Treatment: A single or multiple overdose with Phrenilin® with Caffeine and Codeine (butalbital, acetaminophen, caffeine and codeine phosphate) is a potentially lethal polydrug overdose, and consultation with a regional poison control center is recommended. Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption. Vomiting should be induced mechanically, or with syrup of ipecac, if the patient is alert (adequate pharyngeal and laryngeal reflexes). Oral activated charcoal (1 g/kg) should follow gastric emptying. The first dose should be accompanied by an appropriate cathartic. If repeated doses are used, the cathartic might be included with alternate doses as required. Hypotension is usually hypovolemic and should respond to fluids. The value of vasopressor agents such as norepinephrine or phenylephrine hydrochloride in treating hypotension is questionable since they increase vasoconstriction and decrease blood flow. However, if prolonged support of blood pressure is required, norepinephrine bitartrate may be given I.V. with the usual precautions and serial blood pressure monitoring. A cuffed endotracheal tube should be inserted before gastric lavage of the unconscious patient and, when necessary, to provide assisted respiration. If renal function is normal, forced diuresis may aid in the elimination of the barbiturate. Alkalinization of the urine increases renal excretion of some barbiturates, especially phenobarbital.

Meticulous attention should be given to maintaining adequate pulmonary ventilation. In severe cases of intoxication, peritoneal dialysis, or preferably hemodialysis may be considered. If hypoprothrombinemia occurs due to acetaminophen overdose, vitamin K should be administered intravenously.

Naloxone, a narcotic antagonist, can reverse respiratory depression and coma associated with opioid overdose. Naloxone 0.4 to 2 mg is given parenterally. Since the duration of action of codeine may exceed that of the naloxone, the patient should be kept under continuous surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration. A narcotic antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression.

If the dose of acetaminophen may have exceeded 140 mg/kg, N-acetylcysteine should be administered as early as possible. Serum acetaminophen levels should be obtained, since levels 4 or more hours following ingestion help predict acetaminophen toxicity. Do not await acetaminophen assay results before initiating treatment. Hepatic enzymes should be obtained initially, and repeated at 24-hour intervals.

Methemoglobinemia over 30% should be treated with methylene blue by slow intravenous administration.

Toxic doses (for adults)

One or two capsules every four hours. Total daily dosage should not exceed 6 capsules.

Extended and repeated use of this product is not recommended because of the potential for physical dependence.

Phrenilin® with Caffeine and Codeine (butalbital, acetaminophen, caffeine and codeine phosphate capsules, 50 mg/325 mg/40 mg/30 mg).

Opaque lavender and opaque white capsules imprinted in black with PCC 0843 and VALEANT.

Bottle of 100 (NDC 0187-0843-01).

Store at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F), tight container.

Distributed by:
Valeant Pharmaceuticals North America
One Enterprise
Aliso Viejo, CA 92656 USA

Manufactured by:
Mallinckrodt Inc.
Hobart, NY 13788

Printed with food grade ink.

MG #21839

Rev. 9/07
L2PP12