Acetaminophen Caffeine Dihydrocodeine

Name: Acetaminophen Caffeine Dihydrocodeine

Acetaminophen Caffeine Dihydrocodeine - Clinical Pharmacology

Acetaminophen, caffeine, and dihydrocodeine bitartrate tablets contain dihydrocodeine which is a semi-synthetic narcotic analgesic related to codeine, with multiple actions qualitatively similar to those of codeine; the most prominent of these involve the central nervous system and organs with smooth muscle components. The principal action of therapeutic value is analgesia.

This combination product also contains acetaminophen, a non-opiate, non-salicylate analgesic and antipyretic. This combination product contains caffeine as an analgesic adjuvant. Caffeine is also a central nervous system and cardiovascular stimulant.

Contraindications

Dihydrocodeine-containing products are contraindicated for postoperative pain management in children who have undergone tonsillectomy and/or adenoidectomy.

This combination product is contraindicated in patients with hypersensitivity to dihydrocodeine, codeine, acetaminophen, caffeine, or any of the inactive components listed above, or any situation where opioids are contraindicated including significant respiratory depression (in unmonitored settings or in the absence of resuscitative equipment), acute or severe bronchial asthma or hypercapnia, and paralytic ileus.

Adverse Reactions

Dihydrocodeine:
The most frequently observed adverse reactions include light-headedness, dizziness, drowsiness, headache, fatigue, sedation, sweating, nausea, vomiting, constipation, pruritus, and skin reactions. With the exception of constipation, tolerance develops to most of these effects. Other reactions that have been observed with dihydrocodeine or other opioids include respiratory depression, orthostatic hypotension, cough suppression, confusion, diarrhea, miosis, abdominal pain, dry mouth, indigestion, anorexia, spasm of biliary tract, and urinary retention. Physical and psychological dependence are possibilities. Hypersensitivity reactions (including anaphylactoid reactions), hallucinations, vivid dreams, granulomatous interstitial nephritis, severe narcosis and acute renal failure have been reported rarely during dihydrocodeine administration.

Acetaminophen:
Acetaminophen in therapeutic doses rarely causes adverse reactions. The most serious adverse reaction is hepatoxicity from overdosage [see Overdosage]. Thrombocytopenia, leukopenia, pancytopenia, neutropenia, thrombocytopenic purpura, and agranulocytosis have been reported in patients receiving acetaminophen or p-aminophenol derivatives. Hypersensitivity reactions including urticarial or erythematous skin reactions, laryngeal edema, angioedema, or anaphylactoid reactions are rare.

Caffeine:
Adverse reactions associated with caffeine use include anxiety, anxiety neurosis, excitement, headaches, insomnia, irritability, lightheadedness, restlessness, tenseness, tremor, extrasystoles, palpitations, tachycardia, diarrhea, nausea, stomach pain, vomiting, diuresis, urticaria, scintillating scotoma, and tinnitus.

Acetaminophen, Caffeine and Dihydrocodeine Bitartrate Tablets 100 Count Bottle

NDC 68047-720-01

Acetaminophen, Caffeine and Dihydrocodeine Bitartrate Tablets CIII

Acetaminophen, Caffeine and Dihydrocodeine Bitartrate Tablets 325 mg/30 mg/16 mg)

Rx ONLY

100 TABLETS

DESCRIPTION
Each tablet contains:
Acetaminophen .................... 325 mg
Caffeine ................................ 30 mg
Dihydrocodeine bitartrate ........ 16 mg

USUAL DOSAGE: See package insert for full prescribing information.

WARNING: Keep this and all medications out of the reach of children.

PHARMACIST: Dispense in a tight, light-resistant container with a child-resistant closure. Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from moisture.

Distributed by:
Larken Laboratories
Canton, MS 39046
www.larkenlabs.com

400746-01
Rev. 04/2016

ACETAMINOPHEN, CAFFEINE AND DIHYDROCODEINE BITARTRATE 
acetaminophen, caffeine and dihydrocodeine bitartrate tablet
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:68047-720
Route of Administration ORAL DEA Schedule CIII    
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ACETAMINOPHEN (ACETAMINOPHEN) ACETAMINOPHEN 325 mg
CAFFEINE (CAFFEINE) CAFFEINE 30 mg
DIHYDROCODEINE BITARTRATE (DIHYDROCODEINE) DIHYDROCODEINE BITARTRATE 16 mg
Inactive Ingredients
Ingredient Name Strength
SILICON DIOXIDE  
CROSPOVIDONE  
MAGNESIUM STEARATE  
CELLULOSE, MICROCRYSTALLINE  
STARCH, PREGELATINIZED CORN  
STEARIC ACID  
POVIDONE K30  
Product Characteristics
Color white Score no score
Shape OVAL Size 16mm
Flavor Imprint Code LL720
Contains     
Packaging
# Item Code Package Description
1 NDC:68047-720-01 100 TABLET in 1 BOTTLE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA204209 10/04/2016
Labeler - Larken Laboratories Inc. (149484540)
Revised: 10/2016   Larken Laboratories Inc.

Usual Adult Dose for Pain

Initial dose: 2 capsules orally every 4 hours as needed
Maximum dose: 5 doses or 10 capsules in 24 hours; no more than 2 capsules should be taken within any 4-hour period.

Comment:
-Individualize therapy taking into account patients pain severity, prior analgesic treatment experiences, and risk factors for addiction, abuse, and misuse.

Use: For the management of moderate to moderately severe pain that is severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Precautions

US BOXED WARNING(S):
-DEATH RELATED TO ULTRA-RAPID METABOLISM OF CODEINE TO MORPHINE:
Respiratory depression and death have occurred in children who received codeine following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine due to a CYP2D6 polymorphism.
-HEPATOTOXICITY: Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the case of liver injury are associated with the use of acetaminophen at doses that exceed 4000 mg/day, and often involve more than 1 acetaminophen containing product.
-ADDICTION, ABUSE, AND MISUSE: This drug exposes patients and other users to the risk of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions.
-LIFE-THREATENING RESPIRATORY DEPRESSION: Serious life-threatening or fatal respiratory depression may occur, especially during initiation or following a dose increase.
-ACCIDENTAL INGESTION: May result in fatal overdose, especially in children.
-NEONATAL OPOID WITHDRAWAL SYNDROME: Prolonged use during pregnancy can result in neonatal withdrawal syndrome, which may be life-threatening if not recognized and treated; treatment should be according to protocols developed by neonatology experts. Pregnant women should be advised of the risk and ensure that appropriate treatment will be available.
-CYTOCHROME P450 3A4 INTERACTION: Concomitant use with CYP450 3A4 inhibitors may result in increased concentrations which could increase or prolong adverse reactions and cause potentially fatal respiratory depression. Additionally, discontinuation of a concomitantly used CYP450 3A4 inducer may increase plasma concentrations. Monitor patients receiving CYP450 3A4 inhibitors and inducers.
-RISK FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS: Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients in whom alternative treatment options are inadequate; limit dose and duration to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule III

Acetaminophen / caffeine / dihydrocodeine Pregnancy Warnings

Use is not recommended unless clearly needed US FDA pregnancy category: C Comment: -Prolonged use of opioids during pregnancy can result in physical dependence in the neonate; women should be advised of the risk of neonatal abstinence syndrome and ensure that appropriate treatment will be available.

Animal reproduction studies have not been conducted. Epidemiologic data for acetaminophen including a population based case-control study from the National Birth Defects Prevention Study (n= 11,610) and data from 26,424 live singleton births have shown no increased risk of major birth defects in children with first trimester prenatal exposure. In 2015, the US Food and Drug Administration released results of their evaluation on published research studies looking at mothers who took acetaminophen (either over the counter or as a prescription product) at any time during their pregnancy and the risk of attention deficit hyperactivity (ADHD) in their babies. They found all studies reviewed had potential limitations in their designs that prevented drawing reliable conclusions. Dihydrocodeine use in pregnant women may lead to neonatal abstinence syndrome. There are no controlled data on this combination product in human pregnancy. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Acetaminophen / caffeine / dihydrocodeine Breastfeeding Warnings

Dihydrocodeine is a semi-synthetic narcotic analgesic related to codeine; it is secreted into human milk in low, dose-dependent quantities in women with normal metabolism (normal CYP450 2D6 activity). However, in women who are ultra-rapid metabolizers (those with multiple copies of the gene for CYP450 2D6), higher-than-expected levels of dihydromorphine may be excreted in breast milk and result in dangerously high serum dihydromorphine levels in breastfed infants. In most cases, a person's specific CYP2D6 genotype is unknown. Several small series and 1 small retrospective study suggest that codeine may have been causative in episodes of apnea, bradycardia, and cyanosis in the first weeks of life. A death of a breastfeed infant due to respiratory depression has been reported; the mother was found to be a CYP450 2D6 ultrarapid metabolizer. Due to the potential for serious adverse reactions in nursing infants, other agents are preferred.

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Yes (acetaminophen); Yes (caffeine); Yes (dihydrocodeine) Comments: -The American Academy of Pediatrics recommends against use of codeine during breastfeeding as other agents are preferred. -Monitor breastfed infants for signs of morphine toxicity including increase sleepiness, difficulty breastfeeding, breathing difficulties, or limpness; seek medical attention promptly if these signs occur.

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