A new CDC guideline for prescribing opioids for pain recently became available. Nonopioid drugs for pain were reviewed in a previous issue.

View the Comparison Table: Some Oral/Transdermal Opioid Analgesics

Acute cough (<3 weeks in duration) generally does not require pharmacologic treatment, especially in children. Suppression of productive cough may be harmful. Management of patients with cough should include elimination of any precipitating factor (e.g., cigarette smoking) and treatment of any underlying cause such as upper airway cough syndrome, gastroesophageal reflux disease, asthma, or other pulmonary disease.

Use of nonopioid drugs for pain was reviewed in a previous issue. For many types of moderate to severe acute pain, acetaminophen and/or an NSAID may be as effective as an opioid. Immediate-release formulations of full opioid agonists should generally be used for acute pain that is severe enough to require treatment with an opioid. Use of extended-release or long-acting opioid formulations initially and treatment durations >1 week have been associated with an increased risk of unintended long-term use.

View the Comparison Table: Some Oral/Topical Opioid Analgesics

View the Comparison Table: Some Nonopioid Analgesics for Pain

The FDA has issued new warnings about the use of the opioid analgesics codeine and tramadol in children, particularly those <12 years old, and in breastfeeding women due to concerns about the risk of respiratory depression and death. The FDA previously issued warnings about these drugs in 2013 and 2015.

The Drug Enforcement Administration (DEA) has reclassified all hydrocodone combination products as schedule II controlled substances; they were previously classified as schedule III. Hydrocodone alone (Zohydro ER) is already a schedule II controlled substance.

Pain can be acute or chronic. The two major types of chronic pain are nociceptive pain and neuropathic pain. Nociceptive pain can be treated with nonopioid analgesics or opioids. Neuropathic pain is less responsive to opioids and is often treated with adjuvant drugs such as antidepressants and antiepileptics. Combining different types of analgesics may provide an additive analgesic effect without increasing adverse effects.

Breaking drug tablets in half is a common practice. Since our last article on this subject, some new data have become available.

The FDA recently warned that accidental ingestion of the antitussive benzonatate (Tessalon Perles, and others) by children less than 10 years old can be fatal.1 This widely prescribed oral agent, which has been available in the US since 1958, can also cause severe morbidity and death in older children and adults, and not only in overdosage.

Benzonatate is a polyglycol derivative structurally related to procaine and tetracaine. It acts peripherally on stretch receptors in the lower respiratory tract to suppress the cough reflex. If the patient chews or sucks the liquid-filled capsules or "softgels", the drug can cause laryngospasm, bronchospasm and circulatory collapse. Adverse effects that can occur after swallowing an intact capsule include a feeling of numbness in the chest, mental confusion, a sensation of burning in the eyes, and visual hallucinations.

Taken in overdose, benzonatate can rapidly cause seizures, cardiac arrhythmias and death. Serious adverse outcomes reported to the National Poison Center between 2000 and 2006 occurred in 116 patients (41 in children <6 years old), with 4 deaths.2 The 5 children known to the FDA who died from benzonatate ingestion were ≤2 years old and some apparently took only one or two capsules. In one well-documented case report, a 17-year-old girl who intentionally took 10 or more 200-mg capsules developed seizures, cardiac arrest from which she was resuscitated, and then blindness, which persisted.3 When a cough suppressant is truly necessary, dextromethorphan or even codeine might be a safer choice.

1. FDA. FDA Drug Safety Communication: Death resulting from overdose after accidental ingestion of Tessalon (benzonatate) by children under 10 years of age. Available at www.fda.gov/Drugs/DrugSafety/ucm236651.htm. Accessed January 27, 2011.

2. ML Winter et al. Benzonatate ingestion reported to the National Poison Center Database System (NPDS). J Med Toxicol 2010; 6:398.

3. V Cohen et al. Cardiac arrest with residual blindness after overdose of Tessalon (benzonatate) Perles. J Emerg Med 2009 Nov 4 (epub).

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The FDA has required manufacturers of propoxyphene-containing products (Darvon, and others) to strengthen boxed warnings to include the potential for overdose.1 This action followed disclosure of fatal overdoses linked to propoxyphene-containing products taken alone or concurrently with other CNS depressants, including alcohol. Many of the overdoses occurred in patients with a history of emotional instability or suicide attempts. Accumulation of metabolites of propoxyphene can lead to central nervous system, cardiac and respiratory depression; convulsions and cardiotoxicity have occurred.

A Schedule IV controlled substance, propoxyphene is a weak full agonist opioid indicated for relief of mild to moderate pain.2 It is often prescribed in combination with acetaminophen (Darvocet, and others). One reasonable alternative would be codeine with acetaminophen; 32 mg of codeine has an analgesic effect similar to that of 65 mg of propoxyphene. Another would be 400 mg of ibuprofen, which may be more effective than either propoxyphene or codeine combined with acetaminophen.

1. FDA News Release. FDA takes actions on Darvon, other pain medications containing propoxyphene. Available at www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm170769.html. Accessed August 23, 2010.

2. Drugs for pain. Treat Guidel Med Lett 2010; 92:25.

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Pain can be acute or chronic. Chronic pain has been broadly classified into two types: nociceptive and neuropathic. Nociceptive pain can be treated with nonopioid analgesics or opioids. Neuropathic pain is less responsive to opioids; adjuvant medicines such as antidepressants and anticonvulsants are often used to treat neuropathic pain. Combining different types of analgesics may provide an additive analgesic effect without increasing adverse effects.

Pain can be acute or chronic. Chronic pain has been broadly classified into two types: nociceptive and neuropathic. Nociceptive pain is generally treated with nonopioid analgesics and opioids. Antidepressants and anticonvulsants have been used to treat neuropathic pain. Combining two different types of analgesics may nprovide an additive analgesic effect without increasing adverse effects.

A fixed-dose combination of oxycodone 5 mg and ibuprofen 400 mg (Combunox - Forest Laboratories) is now available and is being heavily advertised for short-term treatment of moderate to severe acute pain.

The FDA recently cleared the AmpliChip CYP450 Test (Roche), which analyzes blood-derived DNA to detect genetic variations in the activity of cytochrome P450 (CYP) enzymes CYP2D6 and CYP2C19 and determines the metabolizer status of the patient. The test is intended to help guide clinicians in prescribing individualized drug therapy. About 25% of all drugs, including many antidepressants and antipsychotics, are substrates of either CYP2D6 or CYP2C19. The test is being promoted initially to psychiatrists.

Three types of analgesic drugs are available: non-opioids, including aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; opioids; and adjuvant drugs that are not usually thought of as analgesics, such as antidepressants, which can act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain. Combining two different types of analgesics may provide an additive analgesic effect without necessarily increasing adverse effects.

Changes caused by one drug in the absorption, distribution, metabolism or excretion of another may lead to a pharmacokinetic adverse drug interaction (DN Juurlink et al, JAMA 2003; 289:1652). Additive drug interactions, such as vasodilation caused by both sildenafil (Viagra) and nitrates, can also have adverse effects.

The number of cough remedies available in the USA continues to multiply, but most products contain the same or similar ingredients in varying combinations. Most acute coughs do not require treatment with drugs, especially in children, and suppression of a productive cough may be harmful.

Three types of analgesic drugs are available: first, non-opioids, including aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; second, opioids; and third, drugs not usually thought of as analgesics, which act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain. Non-opioids can be given concurrently with opioids for an additive analgesic effect.

Reports of adverse interactions between drugs continue to accumulate. Recently, the FDA has expanded the recommendations on drug interactions found in the package inserts of new drugs.

Three types of analgesic drugs are available: first, non-opioids, including aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; second, opioids; and third, some drugs not usually thought of as analgesics, which act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain.

Tramadol hydrochloride (Ultram - Ortho-McNeil), a centrally-acting analgesic marketed in Germany since 1977, was recently approved by the US Food and Drug Administration for oral treatment of moderate to moderately severe pain. Despite some opioid activity, tramadol has not been scheduled as a controlled substance.

Three types of analgesic drugs are available in the USA: first, aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen; second, opioids; and third, drugs not usually thought of as analgesics, which act as adjuvants when given with NSAIDs or opioids, or have analgesic activity of their own in some types of pain. (American Pain Society, Principles of analgesic Use, 3rd ed, Skokie, illinois: American pain society, 1992).

Since the implication of aspirin in Reye's syndrome, acetaminophen (Tylenol; and others) has become the standard drug for symptomatic treatment of fever and pain in children. Ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID) available for many years in tables (Mortin; Advil; and others), has now become available in a suspension. The suspension will be sold by presecription for treatment of fever or arthritis in children.