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codeine sulfate
generic
Black Box Warnings .
Appropriate Use
should only be prescribed by healthcare professionals knowledgeable about opioid use and how to mitigate assoc. risks; reserve opioid analgesics for pts w/ inadequate tx alternatives; proper dosing and titration essential to decr. resp. depression risk
Addiction, Abuse, and Misuse
opioid agonist Schedule II controlled substance w/ risk of addiction, abuse, and misuse, which can lead to overdose and death; assess opioid abuse or addiction risk prior to prescribing; regularly reassess all pts for misuse, abuse, and addiction
Respiratory Depression
serious, life-threatening, or fatal cases may occur even w/ recommended use, esp. during tx start or after dose incr; to decr. risk, initiate and titrate dose appropriately
Accidental Ingestion
accidental ingestion of even one dose, esp. by children, can result in fatal codeine overdose
Risks from Concomitant Use w/ Benzodiazepines, CNS Depressants
concomitant opioid use w/ benzodiazepines or other CNS depressants, incl. alcohol, may result in profound sedation, resp. depression, coma, and death; avoid use of opioid cough medications in pts taking benzodiazepines, other CNS depressants, or alcohol; reserve concomitant use of opioid analgesics w/ benzodiazepines or other CNS depressants for pts w/ inadequate alternative tx options
Neonatal Opioid Withdrawal Syndrome
extended use in pregnant pts can lead to potentially life-threatening neonatal opioid withdrawal syndrome; advise pregnant pts of risks and ensure tx by neonatology experts avail. at delivery if extended opioid use required
Opioid Analgesic REMS
providers are strongly encouraged to complete risk evaluation and mitigation strategy (REMS)-compliant education program, counsel pts and/or caregivers w/ each Rx on serious risks, safe use, and importance of reading medication guide
Ultra-Rapid Metabolism of Codeine and Other Respiratory Depression Risk in Children
resp. depression and death have occurred in children; most cases occurred in pts post-tonsillectomy and/or adenoidectomy and who were CYP2D6 ultra-rapid metabolizers; contraindicated in pts <12 yo and in pts <18 yo post-tonsillectomy and/or adenoidectomy; avoid use in pts 12-18 yo w/ risk factors that incr. sensitivity to resp. depressant effects of codeine
CYP450 Interactions
concomitant use or D/C of concomitant CYP450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors are complex requiring careful consideration of the effects on codeine and its active metabolite, morphine
Adult Dosing .
Dosage forms: TAB: 15 mg, 30 mg, 60 mg
Special Note
- [prescribing info]
- Info: consider prescribing naloxone if risk of opioid overdose or accidental ingestion
pain, mild-moderate
- [15-60 mg PO q4-6h prn]
- Max: 360 mg/24h; Info: use lowest effective dose, shortest effective tx duration; doses >60 mg rarely more effective or well-tolerated in opioid-naive pts; consider low start dose, titrate slowly in pts 65 yo or older; taper total daily dose by no more than 10-25% q2-4wk to D/C if prolonged or long-term use
cough (off-label)
- [15-30 mg PO q4-6h prn]
- Max: 120 mg/day; Info: use lowest effective dose, shortest effective tx duration; taper dose gradually to D/C if prolonged use
diarrhea (off-label)
- [45-270 mg/day PO divided q4-6h prn]
- Start: 30-60 mg/day PO divided qd-bid, then incr. by 30-60 mg/day prn; Max: 60 mg/dose up to 270 mg/day; Info: use lowest effective dose, shortest effective tx duration; taper dose gradually to D/C if prolonged use
renal dosing
- [see below]
- CrCl 10-50: decr. usual dose by 25%, titrate slowly; CrCl <10: avoid use
- HD/PD: avoid use
hepatic dosing
- [see below]
- hepatic impairment: decr. usual start dose or frequency, amount not defined; Info: titrate slowly
Peds Dosing .
Peds dosing is currently unavailable or not applicable for this drug.
Contraindications / Cautions .
- hypersensitivity to drug or ingredient
- hypersensitivity to morphine
- MAO inhibitor use w/in 14 days
- breastfeeding
- CYP2D6 ultra-rapid metabolizers
- pts <12 yo
- respiratory depression risk (pts 12-18 yo)
- post-tonsillectomy use (pts <18 yo)
- post-adenoidectomy use (pts <18 yo)
- CrCl <10
- respiratory depression, severe
- asthma, acute
- asthma, severe
- GI obstruction, known or suspected
- paralytic ileus
- coma
- consciousness, impaired
- circulatory shock
- abrupt withdrawal (prolonged or long-term use)
- caution: hypersensitivity to opioids
- caution: elderly pts
- caution: debilitated pts
- caution: CrCl 10-50
- caution: hepatic impairment
- caution: pulmonary impairment
- caution: sleep apnea (long-term use)
- caution: CNS depression
- caution: CNS depressant use, concurrent
- caution: alcohol use, concurrent
- caution: alcohol abuse hx
- caution: drug abuse hx
- caution: mental illness hx
- caution: head injury
- caution: ICP incr.
- caution: seizure disorder
- caution: hypovolemia
- caution: GI motility disorder
- caution: pancreatitis, acute
- caution: biliary dz, acute
- caution: GU obstruction
Drug Interactions .
Overview
codeine
opioid
- CYP2D6 substrate
- CYP3A4 substrate
- antidiuretic hormone effects
- CNS depression
- decreases gastrointestinal motility
- hyponatremia
- hypotensive effects
- lowers seizure threshold
- opioid agonist
- potentiates neuromuscular blockade
- serotonergic effects
- urinary retention
- consider prescribing naloxone, esp. w/ concomitant CNS depressant use
- add MAO inhibitor to Interaction Check if recent (14 days) use
Contraindicated
- isocarboxazid
- isoniazid
- linezolid
- methylene blue injection
- methylene blue oral
- naltrexone
- phenelzine
- potassium chloride
- potassium citrate
- procarbazine
- rasagiline
- safinamide
- samidorphan
- selegiline
- selegiline transdermal
- tranylcypromine
- yohimbe
Avoid/Use Alternative
- 5-HTP
- abiraterone acetate
- adagrasib
- aldesleukin
- alfentanil
- allopurinol
- almotriptan
- alprazolam
- amantadine
- amifampridine
- amiodarone
- amitriptyline
- amlodipine
- amoxapine
- amphetamine
- apalutamide
- apomorphine
- apraclonidine ophthalmic
- aprepitant
- aripiprazole bimonthly injection
- aripiprazole lauroxil
- aripiprazole monthly injection
- aripiprazole oral
- artemether/lumefantrine
- asciminib
- asenapine
- atazanavir
- atorvastatin
- avacopan
- baclofen
- baclofen intrathecal
- belumosudil
- berberine
- berotralstat
- bicalutamide
- bosentan
- brexpiprazole
- brimonidine ophthalmic
- brimonidine topical
- brivaracetam
- bromocriptine
- brompheniramine
- buprenorphine
- bupropion
- buspirone
- butalbital
- butorphanol
- cannabidiol
- cannabis
- capivasertib
- carbamazepine
- carbinoxamine
- cariprazine
- carisoprodol
- celecoxib
- cenobamate
- ceritinib
- cetirizine
- chamomile, German
- chlophedianol
- chloramphenicol
- chlordiazepoxide
- chlorpheniramine
- chlorpromazine
- chlorzoxazone
- cilostazol
- cimetidine
- cinacalcet
- ciprofloxacin
- citalopram
- clarithromycin
- clemastine
- clobazam
- clofazimine
- clomipramine
- clonazepam
- clonidine
- clopidogrel
- clorazepate
- clotrimazole oropharyngeal
- clozapine
- cobicistat
- cocaine
- codeine
- conivaptan
- cranberry
- crizotinib
- cyclobenzaprine
- cyclosporine
- cyproheptadine
- dabrafenib
- dacomitinib
- danazol
- danshen
- dantrolene
- daridorexant
- darifenacin
- darunavir
- desflurane
- desipramine
- desvenlafaxine
- deutetrabenazine
- dexbrompheniramine
- dexchlorpheniramine
- dexmedetomidine
- dexmedetomidine injection
- dexmethylphenidate
- dextroamphetamine
- dextromethorphan
- diazepam
- dichlorphenamide
- difelikefalin
- difenoxin
- dihydrocodeine
- dihydroergotamine
- diltiazem
- dimenhydrinate
- diosmin
- diphenhydramine
- diphenoxylate
- domperidone
- doxepin
- doxepin topical
- doxylamine
- dronabinol
- dronedarone
- droperidol
- duloxetine
- duvelisib
- efavirenz
- eletriptan
- eliglustat
- eluxadoline
- enasidenib
- encorafenib
- entacapone
- entrectinib
- enzalutamide
- ergotamine
- erythromycin
- escitalopram
- esketamine
- eslicarbazepine acetate
- estazolam
- eszopiclone
- ethanol
- ethanol (in some formulations)
- ethinyl estradiol (contraceptive)
- ethosuximide
- etomidate
- etravirine
- everolimus
- fedratinib
- felbamate
- felodipine
- fenfluramine
- fentanyl
- fesoterodine
- fexinidazole
- flibanserin
- fluconazole
- fluoxetine
- fluphenazine
- flurazepam
- fluvoxamine
- fosamprenavir
- fosaprepitant
- foslevodopa
- fosphenytoin
- fostamatinib
- frovatriptan
- gabapentin
- gabapentin enacarbil
- ganaxolone
- gefitinib
- gepirone
- ginkgo
- ginseng, Asian
- givinostat
- givosiran
- glecaprevir
- glofitamab
- glycopyrrolate
- goldenseal
- granisetron
- grapefruit
- grazoprevir
- guanfacine
- haloperidol
- hydralazine
- hydrocodone
- hydromorphone
- hydroxychloroquine
- hydroxyzine
- hyoscyamine
- idelalisib
- ifosfamide
- iloperidone
- imatinib
- imipramine
- iohexol
- isavuconazonium
- isoflurane
- istradefylline
- itraconazole
- ivacaftor
- ivosidenib
- kava
- ketamine
- ketoconazole
- kratom
- labetalol
- lacosamide
- lamotrigine
- lapatinib
- larotrectinib
- lasmiditan
- lazertinib
- lefamulin
- lemborexant
- lenacapavir
- letermovir
- levetiracetam
- levocetirizine
- levodopa
- levoketoconazole
- levomilnacipran
- levorphanol
- lisdexamfetamine
- lithium
- lofexidine
- lomitapide
- lonafarnib
- lopinavir/ritonavir
- lorazepam
- lorlatinib
- lovastatin
- loxapine
- lumacaftor/ivacaftor
- lumateperone
- lurasidone
- maribavir
- mavacamten
- mavorixafor
- meclizine
- melatonin
- meperidine
- meprobamate
- metaxalone
- methadone
- methamphetamine
- methocarbamol
- methohexital
- methsuximide
- methyldopa
- methylergonovine
- methylphenidate
- metoclopramide
- metyrapone
- metyrosine
- midazolam
- mifepristone
- milnacipran
- mirabegron
- mirtazapine
- mitapivat
- mitotane
- modafinil
- molindone
- morphine
- mosunetuzumab
- mycophenolate mofetil
- nafcillin
- nalbuphine
- naratriptan
- nefazodone
- nelarabine
- nelfinavir
- netupitant
- nicardipine
- nilotinib
- nirogacestat
- nortriptyline
- olanzapine
- oliceridine
- ondansetron
- opicapone
- opium
- orphenadrine
- osilodrostat
- oxazepam
- oxcarbazepine
- oxybate
- oxybutynin
- oxycodone
- oxymorphone
- pacritinib
- palbociclib
- paliperidone
- palonosetron
- panobinostat
- paroxetine
- passion flower
- pazopanib
- pentazocine
- pentobarbital
- peppermint
- perampanel
- perphenazine
- pexidartinib
- pheniramine
- phenobarbital
- phenytoin
- pibrentasvir
- pimozide
- pirtobrutinib
- posaconazole
- pramipexole
- pramlintide
- prasugrel
- pregabalin
- primidone
- prochlorperazine
- promethazine
- propafenone
- propofol
- propranolol
- protriptyline
- pyrilamine
- quazepam
- quercetin
- quetiapine
- quinidine (antiarrhythmic)
- quinidine (CYP2D6 inhibitor)
- ramelteon
- ranolazine
- remdesivir
- remifentanil
- remimazolam
- repotrectinib
- resveratrol
- revefenacin inhaled
- ribociclib
- rifabutin
- rifampin
- rifapentine
- risperidone
- ritlecitinib
- ritonavir
- rizatriptan
- rolapitant
- ropeginterferon alfa-2b
- ropinirole
- rotigotine transdermal
- rucaparib
- rufinamide
- SAMe
- scopolamine
- selinexor
- selpercatinib
- sertraline
- sevoflurane
- solifenacin
- sotorasib
- spironolactone
- St. John's wort
- stiripentol
- sufentanil
- sumatriptan
- suvorexant
- tapentadol
- tasimelteon
- temazepam
- terbinafine
- tetrabenazine
- thalidomide
- thioridazine
- thiotepa
- thiothixene
- tiagabine
- ticagrelor
- tipranavir
- tizanidine
- tolcapone
- tolterodine
- tolvaptan
- topiramate
- tramadol
- trazodone
- treosulfan
- triazolam
- trifluoperazine
- trihexyphenidyl
- trimethobenzamide
- trimipramine
- triprolidine
- trofinetide
- trospium
- tucatinib
- upadacitinib
- valbenazine
- valerian
- valproic acid
- vemurafenib
- venlafaxine
- verapamil
- vigabatrin
- vilazodone
- viloxazine
- vonoprazan
- voriconazole
- vortioxetine
- voxelotor
- xanomeline
- zaleplon
- ziconotide
- zileuton
- ziprasidone
- zolmitriptan
- zolpidem
- zonisamide
- zuranolone
Monitor/Modify Tx
- acebutolol
- alfuzosin
- aliskiren
- amifostine
- amiloride
- aprocitentan
- articaine
- atenolol
- atracurium
- avanafil
- azilsartan medoxomil
- benazepril
- betaxolol
- betaxolol ophthalmic
- bethanechol
- bexagliflozin
- bisoprolol
- bortezomib
- bumetanide
- bupivacaine
- bupivacaine liposomal
- cabergoline
- canagliflozin
- candesartan cilexetil
- captopril
- carteolol ophthalmic
- carvedilol
- chloroprocaine
- chlorothiazide
- chlorthalidone
- cisatracurium
- clevidipine
- clofarabine
- coenzyme Q-10
- dapagliflozin
- denileukin diftitox
- desmopressin
- dinutuximab
- dipyridamole
- doxazosin
- empagliflozin
- enalapril
- enalaprilat
- eplerenone
- epoprostenol
- ertugliflozin
- esmolol
- ethacrynic acid
- fenoldopam
- ferumoxytol
- flaxseed
- fosinopril
- furosemide
- garlic
- gilteritinib
- hydrochlorothiazide
- iloprost
- iloprost inhaled
- indapamide
- iopamidol
- irbesartan
- iron sucrose
- isosorbide dinitrate
- isosorbide mononitrate
- isradipine
- landiolol
- levobunolol ophthalmic
- lidocaine
- lisinopril
- losartan
- lubiprostone
- magnesium sulfate
- mannitol
- maraviroc
- mepivacaine
- metolazone
- metoprolol
- milrinone
- minoxidil
- moexipril
- nadolol
- nattokinase
- naxitamab
- nebivolol
- niacin (vitamin B3)
- nifedipine
- nimodipine
- nisoldipine
- nitric oxide
- nitrite
- nitroglycerin
- nitroprusside
- olmesartan medoxomil
- palopegteriparatide
- pamabrom
- pancuronium
- pegvisomant
- pentamidine
- perindopril
- phenoxybenzamine
- phentolamine
- pindolol
- prazosin
- quinapril
- ramipril
- riociguat
- rocuronium
- ropivacaine
- sacubitril
- sildenafil
- silodosin
- sodium ferric gluconate complex
- sotagliflozin
- sotalol
- sparsentan
- succinylcholine
- tadalafil
- tagraxofusp
- tamsulosin
- taurine
- telmisartan
- terazosin
- timolol
- timolol ophthalmic
- torsemide
- trandolapril
- treprostinil
- triamterene
- valsartan
- vardenafil
- vasopressin
- vecuronium
- vosoritide
Caution Advised
- acetazolamide
- aclidinium inhaled
- alosetron
- armodafinil
- atropine
- barium
- belladonna alkaloids
- belzutifan
- benztropine
- bexarotene
- botulinum toxin
- brigatinib
- busulfan
- chlorambucil
- cisapride
- clidinium
- darolutamide
- dexamethasone
- dicloxacillin
- dicyclomine
- disopyramide
- echinacea
- elafibranor
- elagolix
- erenumab
- flavoxate
- glycerol phenylbutyrate
- glycopyrrolate inhaled
- glycopyrronium topical
- griseofulvin
- homatropine
- ipratropium inhaled
- lindane topical
- loperamide
- magnesium citrate
- meropenem
- methscopolamine
- mexiletine
- mobocertinib
- nevirapine
- olutasidenib
- omaveloxolone
- pioglitazone
- polyethylene glycol
- polyethylene glycol/electrolytes
- potassium acid phosphate
- potassium gluconate
- potassium phosphate
- prednisone
- pyridostigmine
- sarilumab
- sodium picosulfate
- sofpironium topical
- somatropin
- sulfate bowel prep
- suzetrigine
- tazemetostat
- tecovirimat
- telotristat ethyl
- tiotropium inhaled
- tocilizumab
- tovorafenib
- vaborbactam
- vamorolone
- vinblastine
- vorasidenib
- zanubrutinib
Adverse Reactions .
Serious Reactions
- respiratory depression
- central sleep apnea
- CNS depression
- hypotension, severe
- ICP incr.
- seizures
- bradycardia
- biliary spasm
- hypersensitivity rxn
- anaphylaxis
- anaphylactoid rxn
- adrenal insufficiency
- opioid-induced androgen deficiency (long-term use)
- dependency
- abuse
- withdrawal sx if abrupt D/C (prolonged or long-term use)
- opioid-induced hyperalgesia
- allodynia
Common Reactions
- lightheadedness
- dizziness
- sedation
- nausea
- vomiting
- diaphoresis
- xerostomia
- anorexia
- constipation
- urinary hesitancy
- urinary retention
- weakness
- flushing
- pruritus
- urticaria
- headache
- rash
- visual disturbance
- edema
- disorientation
- euphoria
- dysphoria
- insomnia
- agitation
- biliary spasm
- palpitations
Safety/Monitoring .
Monitoring Parameters
Cr at baseline; s/sx resp. depression; s/sx hypotension incl. BP after tx start if hypotension risk, then after dose incr.
Look/Sound-Alike Drug Names
codeine confused with: Cardene; iodine; Lodine
Pregnancy/Lactation .
Pregnancy
Clinical Summary
weigh risk/benefit during pregnancy, esp. if prolonged use, or immed. before and during labor; risk of teratogenicity low, though risk of neonatal complications, incl. resp. depression and neonatal opioid withdrawal syndrome, based on human data and drug's mechanism of action
Lactation
Clinical Summary
avoid use while breastfeeding; risk of infant CNS and resp. depression, esp. if mother is CYP2D6 ultra-rapid metabolizer, based on limited human data; no human data available to assess effects on milk production
Pharmacology .
Metabolism: liver primarily; CYP450: 2D6 substrate; Info: active metabolite (morphine)
Excretion: urine (5-15% unchanged); Half-life: 2.5-4h
Subclass: Antitussives ; Diarrhea ; Opioids
Mechanism of Action
binds to various opioid receptors, producing analgesia, sedation and antitussive effects (opioid agonist)
Formulary .
No Formulary Selected
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