Dazidox

Dazidox is part of the drug class:

• Natural opium alkaloids

Serious side effects have been reported. See "Drug Precautions" section.

Common side effects include:

• nausea
• constipation
• vomiting
• headache
• itching

This is not a complete list of oxycodone side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Oxycodone falls into category B. There are no well-done studies that have been done in humans with oxycodone. But in animal studies, pregnant animals were given this medication, and the babies did not show any medical issues related to this medication.

Oxycodone has been detected in human breast milk. Because of the possibility for adverse reactions in nursing infants from oxycodone, a choice should be made whether to stop nursing or to stop use of this medication. The importance of the drug to the mother should be considered.

• Keep oxycodone out of the reach of children. Accidental overdose by a child is dangerous and can lead to death.
• Store oxycodone at 59˚F to 86˚F (15˚C to 30˚C).
• Keep oxycodone in the container it comes in.
• Keep the container tightly closed and away from light.

Oxycodone is a federally controlled substance (CII) because it can be abused or lead to dependence. Keep this medication in a safe place to prevent misuse and abuse. Selling or giving away oxycodone may harm others, and is against the law.

It is very important that your doctor check your progress while you are taking this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it.

Do not use this medicine if you are using or have used an MAO inhibitor within the past 14 days.

This medicine may cause a serious type of allergic reaction called anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth while you are using this medicine.

Do not use more of this medicine or take it more often than your doctor tells you to. This can be life-threatening. Symptoms of an overdose include extreme dizziness or weakness, slow heartbeat or breathing, seizures, trouble breathing, and cold, clammy skin. Call your doctor right away if you notice these symptoms.

This medicine will add to the effects of alcohol and other CNS depressants. CNS depressants are medicines that slow down the nervous system, which may cause drowsiness or make you less alert. Some examples of CNS depressants are antihistamines or medicine for allergies or colds, sedatives, tranquilizers, or sleeping medicine, other prescription pain medicine or narcotics, medicine for seizures or barbiturates, muscle relaxants, or anesthetics (numbing medicines), including some dental anesthetics. This effect may last for a few days after you stop using this medicine. Check with your doctor before taking any of these medicines while you are using this medicine.

This medicine may be habit-forming. If you feel that the medicine is not working as well, do not use more than your prescribed dose. Call your doctor for instructions.

Dizziness, lightheadedness, or fainting may occur when you get up suddenly from a lying or sitting position. Getting up slowly may help lessen this problem. Also, lying down for a while may relieve the dizziness or lightheadedness.

This medicine may make you dizzy, drowsy, or lightheaded. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert.

Using narcotics for a long time can cause severe constipation. To prevent this, your doctor may direct you to take laxatives, drink a lot of fluids, or increase the amount of fiber in your diet. Be sure to follow the directions carefully, because continuing constipation can lead to more serious problems.

If you have been using this medicine regularly for several weeks or longer, do not change your dose or suddenly stop using it without checking with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely. This may help prevent worsening of your condition and reduce the possibility of withdrawal symptoms, such as abdominal or stomach cramps, anxiety, fever, nausea, runny nose, sweating, tremors, or trouble sleeping.

Using this medicine while you are pregnant may cause serious unwanted effects in your newborn baby. Tell your doctor right away if you think you are pregnant or if you plan to become pregnant while using this medicine.

Using too much of this medicine may cause infertility (unable to have children). Talk with your doctor before using this medicine if you plan to have children.

Check with your doctor right away if you have anxiety, restlessness, a fast heartbeat, fever, sweating, muscle spasms, twitching, nausea, vomiting, diarrhea, or see or hear things that are not there. These may be symptoms of a serious condition called serotonin syndrome. Your risk may be higher if you also take certain other medicines that affect serotonin levels in your body.

Make sure any doctor or dentist who treats you knows that you are using this medicine. This medicine may affect the results of certain medical tests.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Applies to oxycodone: compounding powder, oral capsule, oral capsule extended release, oral concentrate, oral solution, oral tablet, oral tablet extended release

General

The most commonly reported adverse reactions in adults included constipation, nausea, somnolence, dizziness, vomiting, pruritus, headache, dry mouth, asthenia, and sweating. In pediatric patients, the most frequently observed adverse reactions included vomiting, nausea, headache, pyrexia, and constipation.[Ref]

Nervous system

Very common (10% or more): Headache (14%, pediatrics)
Common (1% to 10%): Dizziness (pediatrics)
Frequency not reported: Confusion, hypertonia, hypesthesia, nervousness, neuralgia, personality disorder, tremor, migraine
Postmarketing reports: Serotonin syndrome[Ref]

Respiratory

Severe adverse effects such as respiratory depression can be treated with the opioid antagonist naloxone.[Ref]

Frequency not reported: Apnea, respiratory arrest, bronchitis, cough increased, dyspnea, epistaxis, laryngismus, lung disorder, pharyngitis, rhinitis, sinusitis[Ref]

Gastrointestinal

Very common (10% or more): Nausea (23% to 27%), constipation (23% to 26%), vomiting (12% to 14%)
Frequency not reported: Abdominal pain, anorexia, diarrhea, dyspepsia, dysphagia, gingivitis, glossitis[Ref]

In pediatric studies with the oral extended release product, gastrointestinal adverse events were reported in 40% of patients 11 to 16 years of age (56 of 140); vomiting, nausea, constipation, and diarrhea were experienced by 21%, 15%, 9%, and 6%, respectively. Abdominal pain and gastroesophageal reflux disease were reported in 1% to less than 5% of patients.[Ref]

Psychiatric

Frequency not reported: Paranoia, psychosis, hallucinations, agitation, anxiety[Ref]

Dermatologic

Common (1% to 10%): Pruritus, hyperhidrosis, rash
Frequency not reported: Herpes simplex, rash, sweating, urticaria[Ref]

Hepatic

Frequency not reported: Increased hepatic enzymes

Cardiovascular

Frequency not reported: QTc prolongation at higher doses, deep thrombophlebitis, heart failure, hemorrhage, hypotension, palpitation, tachycardia, edema, peripheral edema, vasodilation, circulatory collapse[Ref]

Genitourinary

Common (1% to 10%): Dysuria, urinary retention
Frequency not reported: Urinary tract infection[Ref]

Hypersensitivity

Frequency not reported: Allergic reaction
Postmarketing reports: Anaphylaxis[Ref]

Immunologic

Frequency not reported: Flu syndrome, infection, sepsis[Ref]

Metabolic

Common (1% to 10%): Decreased appetite (pediatrics)
Frequency not reported: Gout, hyperglycemia, iron deficiency anemia[Ref]

Musculoskeletal

Frequency not reported: Back pain, neck pain, arthralgia, arthritis, bone pain, myalgia, pathological fracture[Ref]

Ocular

Frequency not reported: Photosensitivity reaction, amblyopia[Ref]

Other

Very common (10% or more): Pyrexia (11%, pediatrics)
Frequency not reported: Chills and fever, accidental injury[Ref]

Endocrine

Opioids:
Postmarketing reports: Adrenal insufficiency, androgen deficiency[Ref]

Some side effects of Dazidox may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Hepatic impairment: Start conservatively with a lower than usual dose; titrate carefully to desired effect

Extended-release tablets/capsules
-Initial dose: One-third to one-half of the usual dose; titrate carefully to desired effect
-Alternative analgesics may be necessary if patient is not a candidate for lowest available dose strength

Data not available

Summary of Use during Lactation

Maternal use of oral narcotics during breastfeeding can cause infant drowsiness, central nervous system depression and even death. Infant sedation is common and well documented with maternal use of oxycodone. Newborn infants seem to be particularly sensitive to the effects of even small dosages of narcotic analgesics. Once the mother's milk comes in, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of oral oxycodone (and combinations) to a few days. A maximum oxycodone dosage of 30 mg daily is suggested, although some sources recommend avoiding oxycodone during breastfeeding.[1] Oxycodone elimination is decreased in young infants with much inter-individual variability. Monitor the infant closely for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants. If the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately. Other agents are preferred over oxycodone during breastfeeding.[2]

Drug Levels

Oxycodone is metabolized to the active metabolites, noroxycodone and oxymorphone. Oxycodone has an oral bioavailability of 60% to 87% in adults.[3] Oxycodone elimination is decreased in young infants and much inter-individual variability exists. Oxycodone can be dangerous when used as an analgesic in newborns.[4]

Maternal Levels. Six breastfeeding mothers who were using 1 to 2 capsules containing a combination of 5 mg oxycodone and 500 mg acetaminophen every 4 to 7 hours for post-cesarean section pain had their milk sampled several times after successive doses. Peak oxycodone milk levels reportedly occurred 1 to 2 hours after the first dose and then at variable times after successive doses. The number of hours after a mother's last dose when oxycodone could still be measured in milk was depended on the number of doses taken. Oxycodone could be measured in milk up to 4, 12, and 36 hours after 4, 9, and 11 doses respectively. In all the mothers, measured oxycodone milk levels ranged from undetectable (<5 mcg/L) to 229 mcg/L. The authors estimated that an exclusively breastfed infant would receive a maximum 8% of the maternal weight-adjusted dosage of oxycodone, but active metabolite levels were not measured.[5]

Fifty mothers who delivered by cesarean section and received oxycodone had milk (colostrum) and serum samples measured for oxycodone at 24, 48 and 72 hours postpartum without respect to the time of the previous oxycodone dose. The most common doses received by the mothers during the previous 24 hours (including one 30 mg dose rectally immediately postoperatively in some cases) were 60 mg (range 30 to 90 mg), 40 mg (range 0 to 90 mg), and 20 mg (range 0 to 50 mg), respectively. Mean colostrum concentrations at the 3 collection times were 58 mcg/L (range 7 to 130 mcg/L), 49 mcg/L (range 0 to 168 mcg/L), and 35 mcg/L (range 0 to 31 mcg/L), respectively. Little correlation was found between maternal dosage and colostrum concentrations, although colostrum levels correlated well with maternal serum levels, with a colostrum concentrations 3.2 to 3.4 higher than serum. Ten mothers had colostrum oxycodone concentrations over 100 mcg/L and 5 had detectable oxycodone in milk 37 hours after the last dose.[6]

Infant Levels. In a study of 50 mothers taking oxycodone post-cesarean section, 45 blood samples were taken from 41 breastfed infants at 24, 48 or 72 hours postpartum. Only 1 of the samples had a detectable (>2 mcg/L) oxycodone level of 7.4 mcg/L. Because these infants were in the first 3 days postpartum, their dose was probably limited by the small volumes of colostrum they were ingesting.[6]

A woman who was exclusively breastfeeding her infant was taking 5 to 10 mg of oxycodone every 4 to 6 hours for episiotomy pain. Her 45-day-old infant's urine drug screen showed a concentration of >2000 mcg/L (positive cutoff for opioid metabolites was 5 mcg/L).[7]

Effects in Breastfed Infants

A 10-month-old, 7.7 kg infant of a prescription drug-dependant mother died of cardiac arrest after a 12- to 24-hour period of lethargy, hypersomnolence and dyspnea. The infant also had a recent history of fever. The mother had reportedly been breastfeeding the infant 3 times a day for several weeks and had taken 180 mg of oxycodone, as well as muscle relaxants, the day prior to her infant's death. A blood oxycodone level of 600 mcg/L was measured on autopsy. The medical examiner considered it unlikely that such a high level of oxycodone in the infant's blood could be due to breastfeeding exposure as reported by the mother and thus considered the death a homicide resulting from either the intentional administration of oxycodone directly to the infant or from a higher dose of oxycodone in breastmilk than that reported by the mother.[8]

In a study of 50 mothers taking oxycodone post-cesarean section, 50 neonates were evaluated for sedation over 48 hours after birth. None was severely sedated and less than 4% had sedation of 3 on a 1 (fully alert) to 5 (difficult to rouse) scale and none more sedated than 3 on the scale. Because these infants were in the first 3 days postpartum, their oxycodone dose was probably limited by the small volumes of colostrum they were ingesting.[6]

An infant was born to a mother taking oxycodone 20 mg 3 times daily, fluoxetine 40 mg daily and quetiapine 400 mg daily. The infant was breastfed 6 to 7 times daily and was receiving 120 mcg of oral morphine 3 times daily for opiate withdrawal. Upon examination at 3 months of age, the infant's weight was at the 25th percentile for age, having been at the 50th percentile at birth. The authors attributed the weight loss to opiate withdrawal. The infant's Denver developmental score was equal to his chronological age.[9]

A woman who was exclusively breastfeeding her infant was taking 5 to 10 mg of oxycodone every 4 to 6 hours for episiotomy pain. Her 45-day-old infant was brought to the emergency department with a temperature of 98.4 degrees F, a heart rate of 154 per minute, 20 breaths per minute, a blood pressure of 71/52, and an oxygen saturation of 60% to 69% on room air. The infant had been constipated since birth, passing one stool every 5 to 8 days. The infant had sluggish movements slow, shallow, and irregular breathing. Her pupils were small, but reactive. Hydromorphone levels in urine were elevated. The patient was intubated and given opiates around the clock for two days before being extubated and discharged. The infant's constipation, CNS and respiratory depression were probably caused by oxycodone in breastmilk.[7]

In a retrospective study, nursing mothers who were taking either oxycodone, codeine or acetaminophen for pain while breastfeeding were contacted by telephone to ascertain the degree of maternally perceived central nervous system (CNS) depression. Mothers taking oxycodone reported signs of CNS depression in 20% (28/139) of their infants, while those taking acetaminophen reported infant CNS depression in only 0.5% (1/184) of their infants. Women who reported infant sedation were taking 0.4 mg/kg daily of oxycodone, and unaffected were taking 0.15 mg/kg daily. Affected infants had more hours of daily uninterrupted sleep than unaffected infants, and 4 of the affected infants reportedly had "irregular breathing". Thirty-eight of 39 mothers reported that infant sedation ceased with maternal oxycodone discontinuation. Mothers of affected infants were also more likely to experience lethargy and other side effects than mothers of unaffected infants. Mothers who took codeine reported a similar rate of infant sedation (17%) compared to oxycodone, but the groups were statistically different in parity and postmenstrual age (PMA), with the codeine group having a slightly higher PMA.[10]

A newborn infant was exclusively breastfed and found to be well by his physician at 2 days of age. At 3 days postpartum, the infant began to be sedated and became difficult to arouse and did not feed from either breast. At 4 days of age, the infant was brought to the emergency department where the infant was found to have lethargy, hypothermia, pinpoint pupils, and a poor sucking reflex. The mother reported that her milk had come in the previous evening. She had taken 10 mg of oxycodone that evening and another 5 mg the next morning in the form of Percocet (oxycodone 5 mg plus acetaminophen 325 mg). The infant was given naloxone 0.34 mg intramuscularly and within 2 minutes, the baby's eyes opened and he drank 45 mL of formula. No further sedation was seen over the next 24 hours.[11] The infant's sedation was probably caused by oxycodone in breastmilk.

Effects on Lactation and Breastmilk

Oxycodone can increase serum prolactin.[12] However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed.

Alternate Drugs to Consider

Acetaminophen, Butorphanol, Hydromorphone, Ibuprofen, Morphine

References

1. Lamvu G, Feranec J, Blanton E. Perioperative pain management: An update for obstetrician-gynecologists. Am J Obstet Gynecol. 2017. PMID: 28666699

2. Sachs HC and the American Academy of Pediatrics committee on Drugs. The transfer of drugs and therapeutics into human breast milk: An update on selected topics. Pediatrics. 2013;132:e796-809. PMID: 23979084

3. Baselt RC. Disposition of toxic drugs and chemicals in man. 6th ed. Foster City: Biomedical Publications, 2002:787-9.

4. Pokela ML, Anttila E, Seppala T et al. Marked variation in oxycodone pharmacokinetics in infants. Paediatr Anaesth. 2005;15:560-5. PMID: 15960639

5. Marx CM, Pucino F, Carlson JD et al. Oxycodone excretion in human milk in the puerperium. Drug Intell Clin Pharm. 1986;20:474. Abstract.

6. Seaton S, Reeves M, McLean S. Oxycodone as a component of multimodal analgesia for lactating mothers after Caesarean section: Relationships between maternal plasma, breast milk and neonatal plasma levels. Aust N Z J Obstet Gynaecol. 2007;47:181-5. PMID: 17550483

7. Sulton-Villavasso C, Austin CA, Patra KP et al. Index of suspicion. Case 1: Infant who has respiratory distress. Case 2: Abnormal behavior, seizures, and altered sensorium in a 7-year-old boy. Case 3: Fever and dysphagia in a 4-year-old girl. Pediatr Rev. 2012;33:279-84. PMID: 22659261

8. Levine B, Moore KA, Aronica-Pollak P et al. Oxycodone intoxication in an infant: accidental or intentional exposure? J Forensic Sci. 2004;49:1358-60. PMID: 15568714

9. Rampono J, Kristensen JH, Ilett KF, Hackett LP, Kohan R. Quetiapine and breast feeding. Ann Pharmacother. 2007;41:711-4. PMID: 17374621

10. Lam J, Kelly L, Ciszkowski C et al. Central nervous system depression of neonates breastfed by mothers receiving oxycodone for postpartum analgesia. J Pediatr. 2012;160:33-37.e2. PMID: 21880331

11. Timm NL. Maternal use of oxycodone resulting in opioid intoxication in her breastfed neonate. J Pediatr. 2013;162:421-2. PMID: 23063265

12. Saarialho-Kere U, Mattila MJ, Seppala T. Psychomotor, respiratory and neuroendocrinological effects of a mu-opioid receptor agonist (oxycodone) in healthy volunteers. Pharmacol Toxicol. 1989;65:252-7. PMID: 2555803