Dihydrocodeine with Other Central Nervous System Depressants
Patients receiving other opioid analgesics, sedatives or hypnotics, muscle relaxants, general anesthetics, centrally acting anti-emetics, phenothiazines or other tranquilizers, or alcohol concomitantly with this combination product may exhibit additive depressant effects on the central nervous system. When such combined therapy is contemplated, the dosage of one or both agents should be reduced.
Following an acute overdosage with Acetaminophen, Caffeine and Dihydrocodeine Bitartrate Tablets, toxicity may result from the dihydrocodeine, acetaminophen, or, less likely, caffeine component. An overdose is a potentially lethal polydrug overdose situation, and consultation with a regional poison control center is recommended. A listing of the poison control centers can be found in standard references such as the Physician’s Desk Reference®.
Signs and Symptoms and Laboratory Findings
Toxicity from dihydrocodeine is typical of opioids and includes pinpoint pupils, respiratory depression, and loss of consciousness. Convulsions, cardiovascular collapse, and death may occur. A single case of acute rhabdomyolysis associated with an overdose of dihydrocodeine has been reported. With acetaminophen, dose-dependent potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and thrombocytopenia may occur. Early symptoms of hepatotoxicity include nausea, vomiting, diaphoresis, and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours after ingestion. Acute caffeine poisoning may cause insomnia, restlessness, tremor, delirium, tachycardia, extrasystoles, and seizures.
Because overdose information on this combination product is limited, it is unclear which of the signs and symptoms of toxicity would manifest in any particular overdose situation.
Immediate treatment of an overdosage of Acetaminophen, Caffeine and Dihydrocodeine Bitartrate Tablets includes support of cardiorespiratory function and measures to reduce drug absorption. Vomiting should be induced with syrup of ipecac, if the patient is alert and has adequate laryngeal reflexes. Oral activated charcoal should follow. The first dose of charcoal should be accompanied by an appropriate cathartic. Gastric lavage may be necessary. Hypotension is usually hypovolemic and should be treated with fluids. Endotracheal intubation and artificial respiration may be necessary. Peritoneal or hemodialysis may be necessary. If hypoprothrombinemia occurs, Vitamin K should be administered.
A pure opioid antagonist, such as naloxone or nalmefene, is a specific antidote against respiratory depression which results from opioid overdose. Opioid antagonists should not be given in the absence of clinically significant respiratory or circulatory depression secondary to opioid overdose. They should be administered cautiously to persons who are known, or suspected to be, physically dependent on any opioid agonist including Acetaminophen, Caffeine and Dihydrocodeine Bitartrate Tablets. In such cases, an abrupt or complete reversal of opioid effects may precipitate an acute abstinence syndrome. The prescribing information for the specific opioid antagonist should be consulted for details of their proper use.
In adults and adolescents, regardless of the quantity of acetaminophen reported to have been ingested, acetylcysteine should be administered immediately if 24 hours or less have elapsed from the reported time of ingestion. It is not advisable to await the plasma concentration determination of acetaminophen before administering acetylcysteine. Serum liver enzyme levels should be measured. Therapy in children involves a similar treatment scheme; however, a regional Poison Control Center should be contacted.
No specific antidote is available for caffeine. In addition to the supportive measures above, administration of demulcents such as aluminum hydroxide gel may diminish gastrointestinal irritation. Seizures may be treated with intravenous diazepam or a barbiturate.
This combination product is contraindicated in patients with hypersensitivity to dihydrocodeine, codeine, acetaminophen, caffeine, or any of the inactive components listed above, or in 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.
DRUG ABUSE AND DEPENDENCE
This combination product is subject to the provisions of the Controlled Substance Act, and has been placed in Schedule III.
Dihydrocodeine can produce drug dependence of the codeine type and therefore has the potential of being abused. Like other opioid analgesics, dihydrocodeine may produce subjective effects other than analgesia (e.g., euphoria, relaxation), which may contribute to abuse by some patients. Psychological dependence, physical dependence, and tolerance may develop upon repeated administration of dihydrocodeine, and it should be prescribed and administered with the same degree of caution appropriate to the use of other oral opioid analgesic medications. Symptoms of dihydrocodeine withdrawal consist of irritability, restlessness, insomnia, diaphoresis, anxiety and palpitations.
Prolonged, high intake of caffeine may produce tolerance and habituation. Physical signs of withdrawal, such as headaches, irritation, nervousness, anxiety, and dizziness may occur upon abrupt discontinuation.