CODEINE

 

DESCRIPTION / DEFINITIONS: Codeine is an opiate painkiller use to treat moderate to severe pain. It is also used in cough medicines and as a treatment for diarrhea. In many countries, and in some States in the U.S., codeine is still available in over-the-counter preparations such as cough syrup and pain relievers.

ABUSE: Codeine is frequently abused. The FDA put a black box warning on the label because the risk of abuse is so high. See more information below.
ADDICTION / DEPENDENCE: As with other opiates and opioids, the label for codeine contains a black box warning about the dangers of dependence and addiction. See more information below.
SIDE EFFECTS: The side effects of codeine include abdominal pain, very low blood pressure, infertility, loss of sexual desire, impotence, anxiety, chest pain, and feeling faint. See more complete information below.

WITHDRAWAL SYMPTOMS: Codeine withdrawal symptoms can include abdominal cramps, anxiety, increased blood pressure, heart and respiratory rates, insomnia, muscle pain, and vomiting. See more complete list below.

TREATMENT: A medically-supervised detox program is the safest and most comfortable way to stop taking codeine. Call us to talk to a Detox Advisor.

DESCRIPTION / DEFINITIONS

Codeine is an opiate painkiller use to treat moderate to severe pain. It is also used in prescription cough medicines, and as a treatment for diarrhea. However, unlike most other opiate painkillers, codeine has no analgesic effects on its own. It is a prodrug – meaning that when metabolized in the body, it turns into the active drug. In the case of codeine, it is metabolized by the liver and turns into morphine. The morphine then acts on the pain.

Because codeine needs to be metabolized to relieve pain, and everyone’s metabolism is different, it is not effective for all people.

Codeine is available by itself, but is often combined in tablets or solutions with drugs or substances. These include acetaminophen (such as Tylenol), caffeine, butalbital (a barbiturate), carisoprodol (a muscle relaxant), guaifenesin (an expectorant that works by thinning and loosening mucus in the airways), promethazine (an antihistamine), triprolidine (an antihistamine), pseudoephedrine hydrochloride (a decongestant), pseudodine (a decongestant and antihistamine), acetylsalicylic acid (Aspirin), chlorpheniramine maleate (an antihistamine), brompheniramine maleate (an antihistamine), pyrilamine maleate (an antihistamine and diuretic), and dihydrocodeine bitartrate (a synthetic opioid analgesic, twice as potent as codeine, one third of the potency of morphine).

Codeine, and the various drugs that are in combination with codeine, is available in tablets and syrups under hundreds of different brand names, manufacturers, and distributors.

Taking codeine can be dangerous in a number of ways. These are summarized on the label warning:

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE- THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; ULTRA-RAPID METABOLISM OF CODEINE AND OTHER RISK FACTORS FOR LIFE-TREATENING RESPIRATORY DEPRESSION IN CHILDREN; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES; AND RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS

Addiction, Abuse, and Misuse
Codeine sulfate tablets expose patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing codeine sulfate tablets, and monitor all patients regularly for the development of these behaviors and conditions.

Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of codeine sulfate tablets. Monitor for respiratory depression, especially during initiation of codeine sulfate tablets or following a dose increase.

Accidental Ingestion
Accidental ingestion of even one dose of codeine sulfate tablets, especially by children, can result in a fatal overdose of codeine.

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. Most of the reported cases occurred following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being an ultra-rapid metabolizer of codeine due to a CYP2D6 polymorphism. Codeine sulfate tablets are contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Avoid the use of codeine sulfate tablets 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.

Neonatal Opioid Withdrawal Syndrome
Prolonged use of codeine sulfate tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes
The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine sulfate tablets requires careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine.

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants
Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.

  • Reserve concomitant prescribing of codeine sulfate tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
  • Limit dosages and durations to the minimum required.
  • Follow patients for signs and symptoms of respiratory depression and sedation.

ABUSE

Like any opiate or opioid, codeine is subject to abuse. However, because it is available over the counter in many countries, and in some U.S. States, codeine is even more susceptible to abuse than similar drugs. It is not unusual for people to buy cough syrup, painkillers and other over-the-counter formulations simply to get high. Codeine is less potent than other opiates, but it is easier to get than other opiates and produces effects similar to morphine.

ADDICTION / DEPENDENCE

Most people start using codeine for legitimate reasons – usually because they are in pain.
However, two things can lead to dependence and addiction:
First, the body develops a tolerance to the drug making it necessary to take more to relieve the pain. While this is happening, one is also developing a dependence on the drug.
Second, codeine, as with other opiates or opioids, has a euphoric effect and tends to make you forget your troubles. For some people, that can lead to the psychological addiction of getting relief from emotional distress

HALF LIFE AND METABOLISM

The biological half-life of a substance is the time it takes for a drug to lose half of its pharmacologic activity. This is significant because it affects how soon withdrawal symptoms may appear.
The half life of codeine is about three hours.
Codeine is metabolized to morphine in the liver primarily by the CYP2D6 enzyme.
The CYP enzymes are the major enzymes involved in drug metabolism, and since many drugs may increase or decrease the activity of various CYP isozymes, this is a major source of adverse drug interactions, since changes in CYP enzyme activity may affect the metabolism and clearance of various drugs. For example, if one drug inhibits the CYP-mediated metabolism of another drug, the second drug may accumulate within the body to toxic levels, possibly causing an overdose.

OPIOID INDUCED HYPERALGESIA

Although all opioids carry the risk of developing Opioid-Induced Hyperalgesia – a condition where the opioids actually make the pain receptors more sensitive and, therefore, make the pain greater – studies have shown that you may be more likely to develop it with codeine than with other opioids.
When one has Opioid-Induced Hyperalgesia, and the pain seems to be getting worse, some people may think they need more codeine and increase the dose. Of course, the pain does not go away. This can easily lead to overdose.

SIDE EFFECTS

The severity of the side effects of codeine depends on how high a dosage you’ve been taking and how long you’ve been taking it, as well as how you react to the drug based on your body. Side effects include:

  • abdominal cramps
  • abdominal pain
  • adrenal insufficiency – a potentially life-threatening condition that may be indicated if nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure occur
  • agitation
  • allergic reactions
  • anaphylaxis – an acute allergic reaction that prompts the immune system to respond. The symptoms can include: fainting, lightheadedness, low blood pressure, dizziness, flushing, difficulty breathing, rapid breathing, shortness of breath,  wheezing, hives, swelling under the skin, blue skin from poor circulation, rashes, nausea,  vomiting, fast heart rate, feeling of impending doom, itching, tongue swelling, difficulty swallowing, facial swelling, mental confusion, nasal congestion, or impaired voice.
  • androgen deficiency – with chronic use, lower levels of male sex hormones, particularly testosterone, than is needed for health. This may cause hot flashes, sweating, insomnia, nervousness, irritability, tiredness, loss of motivation, short-term memory problems, declining self-esteem, depression, decreased energy levels, diminished muscle strength, decline or loss of libido or sexual desire, poor erections, reduced orgasmic quality, reduced volume of semen, diminished muscle mass, hair loss, abdominal obesity, reduction in high-density lipoprotein (HDL) cholesterol, an increase in total body fat, and osteoporosis that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility.
  • anorexia
  • anxiety
  • breast-feeding mother taking codeine sulfate tablets could cause your baby to experience increased sleepiness, confusion, difficulty breathing, shallow breathing, limpness, or difficulty breastfeeding.
  • cardiac arrest

  • chest pain
  • circulatory depression
  • constipation
  • diarrhea
  • dizziness
  • drowsiness
  • dry mouth
  • dysphoria
  • euphoria
  • extreme drowsiness
  • faintness
  • fast heartbeat
  • fatigue
  • feeling faint
  • flushing
  • gastrointestinal distress
  • headache
  • high body temperature
  • hypotension
  • immunosuppressive
  • inability to safely perform potentially hazardous activities such as driving a car or operating heavy machinery
  • infertility – possibly permanent
  • insomnia
  • lightheadedness
  • light-headedness when changing positions
  • low blood pressure
  • mental changes such as confusion.
  • nausea
  • neonatal opioid withdrawal syndrome – prolonged use of codeine sulfate tablets during pregnancy can result in, which may be life-threatening if not recognized and treated
  • nervousness
  • orthostatic hypotension
  • palpitations
  • pancreatitis

  • pruritis – itching
  • rash
  • respiratory arrest
  • respiratory depression – which could be serious, life-threatening, or fatal
  • sedation
  • serotonin syndrome – (when taken in combination with serotonergic drugs) – serotonin syndrome is a group of potentially life-threatening symptoms that include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea, associated with serotonergic drugs. Serotonergic drugs are used to treat migraine, depression, and other mood disorders.
  • shakiness
  • shock – a critical condition brought on by a sudden drop in blood flow through the body
  • shortness of breath
  • sleepiness
  • stiff muscles
  • sweating
  • swelling of the throat
  • swelling of the tongue
  • swelling of your face
  • syncope – temporary loss of consciousness caused by a fall in blood pressure
  • tiredness
  • trouble breathing
  • trouble walking
  • urticaria – a rash of very itchy round, red welts on the skin. It is sometimes accompanied by dangerous swelling and is generally an allergic reaction
  • vertigo – a sensation of spinning dizziness
  • visual disturbances
  • vomiting
  • weakness

Overdose symptoms for Codeine include:

  • airway obstruction, partial or complete
  • arrhythmias
  • bradycardia – very slow heart rate
  • cardiac arrest
  • cold and clammy skin
  • constricted pupils – pupils are smaller
  • hypotension – low blood pressure
  • marked mydriasis (dilation of the pupil of the eye )

  • pulmonary edema – excess fluid in the lungs, which makes it difficult to breathe
  • respiratory depression
  • skeletal muscle flaccidity
  • snoring – when the person doesn’t usually snore or unusual snoring
  • somnolence progressing to stupor or coma


WITHDRAWAL SYMPTOMS

Codeine withdrawal symptoms can be mild or severe, depending on how long you’ve been taking it, and at what dosage. Codeine withdrawal symptoms include:

(The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered.)

  • abdominal cramps
  • anorexia
  • anxiety
  • backache
  • chills
  • diarrhea
  • increased blood pressure
  • increased heart rate

  • increased respiratory rate
  • insomnia
  • irritability
  • joint pain
  • lacrimation – shedding tears, more than usual, like you have something in your eye
  • myalgia – pain in a muscle or group of muscles
  • mydriasis – dilation of the pupil of the eye

  • nausea
  • perspiration
  • restlessness
  • rhinorrhea – runny nose
  • vomiting
  • weakness
  • yawning

Note: If a breast-feeding mother uses codeine, the baby can experience withdrawal symptoms when the mother stops taking codeine or stops breastfeeding.

TREATMENT

Withdrawing from codeine suddenly can bring about severe, painful, uncomfortable and possibly medically dangerous symptoms. Treatment should always been done under medical supervision. For the safest and most comfortable treatment, call us to talk to a Detox Advisor.