cyproheptadine

First Generation Antihistamines

Oral Administration

May be administered without regard to meals.

Severe

seizures / Delayed / Incidence not known
anaphylactic shock / Rapid / Incidence not known
agranulocytosis / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known

Moderate

euphoria / Early / Incidence not known
neuritis / Delayed / Incidence not known
impaired cognition / Early / Incidence not known
excitability / Early / Incidence not known
confusion / Early / Incidence not known
urinary retention / Early / Incidence not known
constipation / Delayed / Incidence not known
hypotension / Rapid / Incidence not known
sinus tachycardia / Rapid / Incidence not known
leukopenia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
edema / Delayed / Incidence not known
blurred vision / Early / Incidence not known
wheezing / Rapid / Incidence not known

Mild

dizziness / Early / Incidence not known
paresthesias / Delayed / Incidence not known
insomnia / Early / Incidence not known
tremor / Early / Incidence not known
drowsiness / Early / Incidence not known
restlessness / Early / Incidence not known
irritability / Delayed / Incidence not known
increased urinary frequency / Early / Incidence not known
nausea / Early / Incidence not known
xerostomia / Early / Incidence not known
dyspepsia / Early / Incidence not known
vomiting / Early / Incidence not known
anorexia / Delayed / Incidence not known
diarrhea / Early / Incidence not known
weight gain / Delayed / Incidence not known
appetite stimulation / Delayed / Incidence not known
chills / Rapid / Incidence not known
fatigue / Early / Incidence not known
rash / Early / Incidence not known
hyperhidrosis / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
photosensitivity / Delayed / Incidence not known
vertigo / Early / Incidence not known
diplopia / Early / Incidence not known
tinnitus / Delayed / Incidence not known
bronchial secretions / Early / Incidence not known
nasal congestion / Early / Incidence not known

Periactin

Rx

Oral piperidine antihistamine (H1-blocker) that also antagonizes serotonin receptors
Has sedative and anticholinergic effects
Primarily used to treat perennial and seasonal allergic rhinitis, vasomotor rhinitis, urticaria, and allergic conditions in adults and children as young as 2 years

For relief of symptoms of seasonal or perennial allergic rhinitis (e.g., rhinorrhea, sneezing), allergic conjunctivitis, vasomotor rhinitis, allergic reactions to blood or plasma, dermatographism, pruritus or mild/uncomplicated allergic skin manifestations of urticaria or angioedema; used adjunctively to epinephrine for severe allergic reactions, including anaphylaxis, after the acute manifestations have been controlled. Oral dosage Adults

4 mg PO 3 times per day. May increase if needed. Usual range is 4 to 20 mg/day, in divided doses. Max: 0.5 mg/kg/day or 32 mg/day PO, whichever is less.

Adolescents 15 to 17 years

4 mg PO 3 times per day. May increase if needed. Usual range is 4 to 20 mg/day, in divided doses. Max: 0.5 mg/kg/day or 32 mg/day PO, whichever is less.

Children and Adolescents 7 to 14 years

4 mg PO 2 to 3 times per day. May increase if needed. Max: 16 mg/day.

Children 2 to 6 years

2 mg PO 2 to 3 times per day or 0.25 mg/kg/day in 2 or 3 divided doses. Max: 12 mg/day.

For the adjunct treatment of anorexia nervosa† or non-psychogenic anorexia† for stimulation of appetite. Oral dosage Adults

Initially, 2 mg PO 2 or 3 times daily with meals. Usual maintenance dose: 4 mg PO 2 to 3 times per day with meals. Max: 32 mg/day. Varied evidence of efficacy in literature. If weight gain or appetite stimulation does not occur within the first few weeks, discontinue.

Children and Adolescents 7 years and older

Initially, 2 mg PO 2 or 3 times daily with meals. Usual maintenance dose: 4 mg PO 2 to 3 times per day with meals. Max: 16 mg/day. Varied evidence of efficacy in literature. If weight gain or appetite stimulation does not occur within the first few weeks, discontinue.

For the treatment of male or female anorgasmy† secondary to antidepressant therapy. Oral dosage Adults

4 to 12 mg PO given 1 to 2 hours before anticipated sexual activity or up to 16 mg/day in divided doses.

For the treatment of spasticity† associated with spinal cord injury. Oral dosage Adults

4 mg PO at bedtime. May increase by 4 mg every 3 to 4 days to clinical response and tolerance. Usual dosage: 16 mg/day PO, given in divided doses. Max: 36 mg/day.

For migraine prophylaxis†. Oral dosage Adults

2 to 4 mg PO twice daily. Clinical practice guidelines classify cyproheptadine as possibly effective for migraine prophylaxis.

†Indicates off-label use

Hepatic Impairment

Dosage should be reduced for patients with hepatic impairment; however, specific guidelines for dosage adjustments are not available.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Codeine: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Additive CNS depression may occur if dichloralphenazone is used concomitantly with any of the sedating H1 blockers. Use caution with this combination. Dosage reduction of one or both agents may be necessary.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Acetaminophen; Oxycodone: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Alfentanil: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Alosetron: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Amantadine: (Moderate) Medications with significant anticholinergic activity may potentiate the anticholinergic effects of amantadine, and may increase the risk of antimuscarinic-related side effects. Additive drowsiness may also occur.
Amobarbital: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with cyproheptadine.
Amoxapine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Amphetamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers (i.e., diphenhydramine). This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine.
Amphetamine; Dextroamphetamine Salts: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers (i.e., diphenhydramine). This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine.
Amphetamine; Dextroamphetamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers (i.e., diphenhydramine). This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine.
Apomorphine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and cyproheptadine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted.
Aripiprazole: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Asenapine: (Moderate) Using drugs that can cause CNS depression, such as sedating H1-blockers, concomitantly with asenapine may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with cyproheptadine.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Aspirin, ASA; Carisoprodol: (Moderate) Carisoprodol is metabolized to meprobamate, a significant CNS depressant. Carisoprodol can cause additive CNS depression if used concomitantly with other CNS depressants. Additive effects of sedation and dizziness, which can impair the ability to undertake tasks requiring mental alertness, may occur if carisoprodol is taken with sedating H1-blockers. Utilize appropriate caution if carisoprodol is coadministered with another CNS depressant.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Carisoprodol is metabolized to meprobamate, a significant CNS depressant. Carisoprodol can cause additive CNS depression if used concomitantly with other CNS depressants. Additive effects of sedation and dizziness, which can impair the ability to undertake tasks requiring mental alertness, may occur if carisoprodol is taken with sedating H1-blockers. Utilize appropriate caution if carisoprodol is coadministered with another CNS depressant. (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Atropine: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Atropine; Difenoxin: (Moderate) An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Azelastine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Azelastine; Fluticasone: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression.
Baclofen: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including skeletal muscle relaxants, such as baclofen.
Barbiturates: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with cyproheptadine.
Belladonna; Opium: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and belladonna use. Concomitant use may result in additive anticholinergic adverse effects.
Benzhydrocodone; Acetaminophen: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Benzodiazepines: (Moderate) Coadministration can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent. Use caution with this combination.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects.
Benzphetamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine.
Benztropine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Buprenorphine: (Moderate) If concurrent use of sedating H1-blockers and buprenorphine is necessary, consider a dose reduction of one or both drugs because of the potential for additive pharmacological effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Buprenorphine; Naloxone: (Moderate) If concurrent use of sedating H1-blockers and buprenorphine is necessary, consider a dose reduction of one or both drugs because of the potential for additive pharmacological effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Butabarbital: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with cyproheptadine.
Butalbital; Acetaminophen: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with cyproheptadine.
Butalbital; Acetaminophen; Caffeine: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with cyproheptadine.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with cyproheptadine. (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with cyproheptadine. (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Butorphanol: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol.
Capsaicin; Metaxalone: (Moderate) Concomitant administration of metaxalone with other CNS depressants can potentiate the sedative effects of either agent.
Carbidopa; Levodopa; Entacapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including sedating H1-blockers, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Carisoprodol: (Moderate) Carisoprodol is metabolized to meprobamate, a significant CNS depressant. Carisoprodol can cause additive CNS depression if used concomitantly with other CNS depressants. Additive effects of sedation and dizziness, which can impair the ability to undertake tasks requiring mental alertness, may occur if carisoprodol is taken with sedating H1-blockers. Utilize appropriate caution if carisoprodol is coadministered with another CNS depressant.
Celecoxib; Tramadol: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Cetirizine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cetirizine and sedating H1-blockers. Concomitant use may result in additive CNS depression or anticholinergic effects.
Cetirizine; Pseudoephedrine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cetirizine and sedating H1-blockers. Concomitant use may result in additive CNS depression or anticholinergic effects.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Chlorzoxazone: (Moderate) Additive CNS depression is possible if chlorzoxazone is used concomitantly with other CNS depressants including sedating H1-blockers. Additive effects of sedation and dizziness can occur, which can impair the ability to undertake tasks requiring mental alertness. Dosage adjustments of one or both medications may be necessary.
Citalopram: (Moderate) Cyproheptadine is a serotonin antagonist in the CNS and can oppose the pharmacologic actions of selective serotonin reuptake inhibitors (SSRIs) such as citalopram. Cyproheptadine has been used for the management of orgasm dysfunction caused by the SSRIs and for the adjunctive treatment of SSRI overdose (i.e., serotonin syndrome) in emergency situations; however, a reversal of antidepressant effects may occur.
Clobazam: (Moderate) Clobazam, a benzodiazepine, may cause drowsiness or other CNS effects. Additive drowsiness may occur when clobazam is combined with CNS depressants such as sedating H1-blockers. In addition, caution is recommended when administering clobazam with medications extensively metabolized by CYP2D6 such as diphenhydramine because clobazam has been shown to inhibit CYP2D6 in vivo and may increase concentrations of drugs metabolized by this enzyme.
Clozapine: (Moderate) Clozapine exhibits clinically significant anticholinergic effects and sedation that may be additive with other medications that may cause anticholinergic effects and sedation, including antihistamines such as cyproheptadine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines and to avoid tasks requiring mental alertness until they are aware of the effects of the combination.
Codeine: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Codeine; Guaifenesin: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Codeine; Promethazine: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
COMT inhibitors: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including sedating H1-blockers, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Cyclobenzaprine: (Moderate) Cyclobenzaprine and cyproheptadine exhibit additive anticholinergic activity. Monitor for anticholinergic-related effects such as constipation and urinary retention. Additive CNS depression causing sedation and/or dizziness is also possible. Dosage adjustments of either or both drugs may be necessary.
Dantrolene: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect (e.g., drowsiness) may occur when dantrolene is combined with other CNS depressants.
Daratumumab; Hyaluronidase: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Desloratadine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Desloratadine; Pseudoephedrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers.
Deutetrabenazine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as cyproheptadine, may have additive effects and worsen drowsiness or sedation.
Dexmedetomidine: (Moderate) Consider a dosage reduction for dexmedetomidine or the sedating antihistamine during concomitant use due to the risk of additive CNS effects.
Dextroamphetamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers (i.e., diphenhydramine). This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine.
Dicyclomine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and dicyclomine use. Concomitant use may result in additive anticholinergic adverse effects.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Diphenoxylate; Atropine: (Moderate) An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Disopyramide: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Donepezil: (Moderate) Concurrent use of sedating H1-blockers and donepezil should be avoided if possible. Donepezil inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of donepezil.
Donepezil; Memantine: (Moderate) Concurrent use of sedating H1-blockers and donepezil should be avoided if possible. Donepezil inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of donepezil.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with antihistamines is necessary. Concurrent use of dronabinol, THC with antihistamines may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Droperidol: (Moderate) Sedating H1-blockers have additive or potentiating sedative and other CNS effects with droperidol. Following administration of droperidol, lower doses of the other CNS depressant may need to be used.
Efgartigimod Alfa; Hyaluronidase: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Entacapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including sedating H1-blockers, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Escitalopram: (Moderate) Cyproheptadine is a serotonin antagonist in the CNS and can oppose the pharmacologic actions of selective serotonin reuptake inhibitors (SSRIs) such as escitalopram. Cyproheptadine has been used for the management of orgasm dysfunction caused by the SSRIs and for the adjunctive treatment of SSRI overdose (i.e., serotonin syndrome) in emergency situations; however, a reversal of antidepressant effects may occur when cyproheptadine is given in a routine manner along with the SSRIs due to the serotonin antagonistic effects of cyproheptadine.
Esketamine: (Moderate) Closely monitor patients receiving esketamine and cyproheptadine for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Eszopiclone: (Moderate) A reduction in the dose of eszopiclone and concomitantly administered CNS depressants, such as sedating H1-blockers, should be considered to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Etomidate: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Fenfluramine: (Moderate) Monitor for decreased efficacy of fenfluramine if coadministered with cyproheptadine. Concurrent use may decrease the activity of fenfluramine.
Fentanyl: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Flavoxate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and flavoxate use. Concomitant use may result in additive anticholinergic adverse effects.
Flibanserin: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them.
Fluoxetine: (Moderate) Cyproheptadine is a serotonin antagonist in the CNS and can oppose the pharmacologic actions of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine. Cyproheptadine has been used for the management of orgasm dysfunction caused by the SSRIs and for the adjunctive treatment of SSRI overdose (i.e., serotonin syndrome) in emergency situations; however, a reversal of antidepressant effects may occur when cyproheptadine is given in a routine manner along with the SSRIs due to the serotonin antagonistic effects of cyproheptadine. Cyproheptadine reportedly has interfered with the antidepressant and anti-bulimia actions of fluoxetine but more data are needed to confirm a direct drug-drug interaction.
Fluvoxamine: (Moderate) Cyproheptadine is a serotonin antagonist in the CNS and can oppose the pharmacologic actions of selective serotonin reuptake inhibitors (SSRIs) such as fluvoxamine. Cyproheptadine has been used for the management of orgasm dysfunction caused by the SSRIs and for the adjunctive treatment of SSRI overdose (i.e., serotonin syndrome) in emergency situations; however, a reversal of antidepressant effects may occur when cyproheptadine is given in a routine manner along with the SSRIs due to the serotonin antagonistic effects of cyproheptadine.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cyproheptadine and gabapentin. Concurrent use may result in additive CNS depression.
Galantamine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of galantamine.
Glycopyrrolate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Glycopyrrolate; Formoterol: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Halogenated Anesthetics: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Haloperidol: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur.
Heparin: (Minor) Antihistamines may partially counteract the anticoagulant actions of heparin, according to the product labels. However, this interaction is not likely of clinical significance since heparin therapy is adjusted to the partial thromboplastin time (aPTT) and other clinical parameters of the patient.
Homatropine; Hydrocodone: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and homatropine use. Concomitant use may result in additive anticholinergic adverse effects.
Hyaluronidase, Recombinant; Immune Globulin: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Hyaluronidase: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Hydrocodone: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hydromorphone: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Hyoscyamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects.
Ibuprofen; Oxycodone: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Iloperidone: (Moderate) Drugs that can cause CNS depression, if used concomitantly with iloperidone, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when iloperidone is given in combination with other centrally-acting medications, such as sedating H1-blockers.
Indacaterol; Glycopyrrolate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Isocarboxazid: (Contraindicated) Concomitant use of monoamine oxidase inhibitors and sedating H1-blockers is contraindicated due to increased anticholinergic effects.
Ketamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant.
Levocetirizine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cetirizine and sedating H1-blockers. Concomitant use may result in additive CNS depression or anticholinergic effects.
Levorphanol: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Lofexidine: (Moderate) Monitor for excessive hypotension and sedation during coadministration of lofexidine and cyproheptadine. Lofexidine can potentiate the effects of CNS depressants.
Loratadine: (Minor) Although loratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of loratadine with CNS depressants such as other H1-blockers.
Loratadine; Pseudoephedrine: (Minor) Although loratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of loratadine with CNS depressants such as other H1-blockers.
Loxapine: (Moderate) Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with other drugs having anticholinergic activity and CNS depressant properties such as traditional antipsychotic agents, including loxapine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other CNS effects may also occur.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and cyproheptadine. Concurrent use may result in additive CNS depression.
Lurasidone: (Moderate) Due to the CNS effects of lurasidone, caution should be used when lurasidone is given in combination with other centrally acting medications. Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur.
Maprotiline: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers.
Meclizine: (Major) Meclizine is an H1-blocker which exhibits significant anticholinergic effects. The anticholinergic effects of meclizine may be enhanced when combined with other drugs with antimuscarinic activity, including other sedating H1-blockers. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive sedation may also occur.
Melatonin: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of melatonin and sedating H1-blockers due to the risk for additive CNS depression.
Meperidine: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Meprobamate: (Moderate) The CNS-depressant effects of meprobamate can be potentiated with concomitant administration of other drugs known to cause CNS depression including sedating H1-blockers.
Metaxalone: (Moderate) Concomitant administration of metaxalone with other CNS depressants can potentiate the sedative effects of either agent.
Methadone: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Methamphetamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of sedating H1-blockers. This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine. Coadminister with caution and monitor for altered response to drug therapy.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects.
Methocarbamol: (Moderate) Methocarbamol may cause additive CNS depression if used concomitantly with other CNS depressants such as sedating H1-blockers. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient's ability to undertake tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary.
Methohexital: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with cyproheptadine.
Methscopolamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and methscopolamine use. Concomitant use may result in additive anticholinergic adverse effects.
Metoclopramide: (Minor) Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation.
Metyrosine: (Moderate) The concomitant administration of metyrosine with sedating H1-blockers can result in additive sedative effects.
Minocycline: (Minor) Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants, such as sedating H1-blockers. Caution should be exercised when using these agents concurrently.
Mirtazapine: (Moderate) Consistent with the CNS depressant effects of mirtazapine, additive effects may occur with other CNS depressants such as cyproheptadine. Mirtazapine should be administered cautiously with such agents because the CNS effects on cognitive performance and motor skills can be additive.
Mitotane: (Moderate) Mitotane can cause sedation, lethargy, vertigo, and other CNS side effects. Concomitant administration of mitotane and CNS depressants, including sedating h1-blockers, may cause additive CNS effects.
Molindone: (Moderate) An enhanced CNS depressant effect may occur when sedating h1-blockers are combined with other CNS depressants including molindone.
Monoamine oxidase inhibitors: (Contraindicated) Concomitant use of monoamine oxidase inhibitors and sedating H1-blockers is contraindicated due to increased anticholinergic effects.
Morphine: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Morphine; Naltrexone: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Nabilone: (Moderate) Concomitant use of nabilone with other CNS depressants, such as sedating H1-blockers, can potentiate the effects of nabilone on respiratory depression.
Nalbuphine: (Moderate) Concomitant use of nalbuphine with other CNS depressants, such as sedating H1-blockers, can potentiate the effects of nalbuphine on respiratory depression, CNS depression, and sedation.
Nefazodone: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including nefazodone.
Neostigmine; Glycopyrrolate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Olanzapine: (Moderate) Olanzapine exhibits anticholinergic effects that may be clinically significant. Clinicians should keep this in mind when using antimuscarinics and other medications with anticholinergic activity in combination with olanzapine. Some medications exhibit additive anticholinergic effects include sedating H1-blockers. Olanzapine may also cause additive sedation with many of these drugs.
Olanzapine; Fluoxetine: (Moderate) Cyproheptadine is a serotonin antagonist in the CNS and can oppose the pharmacologic actions of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine. Cyproheptadine has been used for the management of orgasm dysfunction caused by the SSRIs and for the adjunctive treatment of SSRI overdose (i.e., serotonin syndrome) in emergency situations; however, a reversal of antidepressant effects may occur when cyproheptadine is given in a routine manner along with the SSRIs due to the serotonin antagonistic effects of cyproheptadine. Cyproheptadine reportedly has interfered with the antidepressant and anti-bulimia actions of fluoxetine but more data are needed to confirm a direct drug-drug interaction. (Moderate) Olanzapine exhibits anticholinergic effects that may be clinically significant. Clinicians should keep this in mind when using antimuscarinics and other medications with anticholinergic activity in combination with olanzapine. Some medications exhibit additive anticholinergic effects include sedating H1-blockers. Olanzapine may also cause additive sedation with many of these drugs.
Olanzapine; Samidorphan: (Moderate) Olanzapine exhibits anticholinergic effects that may be clinically significant. Clinicians should keep this in mind when using antimuscarinics and other medications with anticholinergic activity in combination with olanzapine. Some medications exhibit additive anticholinergic effects include sedating H1-blockers. Olanzapine may also cause additive sedation with many of these drugs.
Oliceridine: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Opiate Agonists: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Opicapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including sedating H1-blockers, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Oxybutynin: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and oxybutynin use. Concomitant use may result in additive anticholinergic adverse effects.
Oxycodone: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Oxymorphone: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Paliperidone: (Moderate) Coadministration of drugs with CNS depressant effects, including paliperidone and cyproheptadine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Monitor for signs and symptoms of CNS depression and advise patients to avoid driving or engaging in other activities requiring mental alertness until they know how this combination affects them.
Paroxetine: (Moderate) Cyproheptadine is a serotonin antagonist in the CNS and can oppose the pharmacologic actions of selective serotonin reuptake inhibitors (SSRIs) such as paroxetine. Cyproheptadine has been used for the management of orgasm dysfunction caused by the SSRIs and for the adjunctive treatment of SSRI overdose (i.e., serotonin syndrome) in emergency situations; however, a reversal of antidepressant effects may occur when cyproheptadine is given in a routine manner along with the SSRIs due to the serotonin antagonistic effects of cyproheptadine. In addition, additive anticholinergic effects may be seen when paroxetine is used with antihistamines having anticholinergic properties such as cyproheptadine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines.
Pentazocine: (Moderate) Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity. Coadministration of pentazocine with sedating H1-blockers may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation.
Pentazocine; Naloxone: (Moderate) Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity. Coadministration of pentazocine with sedating H1-blockers may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation.
Pentobarbital: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with cyproheptadine.
Perampanel: (Moderate) Co-administration of perampanel with CNS depressants, including ethanol, may increase CNS depression. The combination of perampanel (particularly at high doses) with ethanol has led to decreased mental alertness and ability to perform complex tasks (such as driving), as well as increased levels of anger, confusion, and depression; similar reactions should be expected with concomitant use of other CNS depressants, such as sedating H1-blockers.
Pertuzumab; Trastuzumab; Hyaluronidase: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Phenelzine: (Contraindicated) Concomitant use of monoamine oxidase inhibitors and sedating H1-blockers is contraindicated due to increased anticholinergic effects.
Phenobarbital: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with cyproheptadine.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with cyproheptadine. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects. (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects. (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and scopolamine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Pimozide: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur.
Pitolisant: (Major) Avoid coadministration of pitolisant with cyproheptadine as the effect of pitolisant may be decreased. Pitolisant increases histamine concentrations in the brain; therefore, H1-receptor antagonists like cyproheptadine, may reduce pitolisant efficacy.
Pramipexole: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cyproheptadine and pregabalin. Concurrent use may result in additive CNS depression.
Primidone: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with cyproheptadine.
Procarbazine: (Moderate) Use procarbazine and sedating H1-blockers together with caution; additive central nervous system depression may occur.
Propantheline: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and propantheline use. Concomitant use may result in additive anticholinergic adverse e

ffects.
Propofol: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics.
Quetiapine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Ramelteon: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as ramelteon.
Rasagiline: (Moderate) Concurrent use of monoamine oxidase inhibitors (MAOIs) and sedating H1-blockers (sedating antihistamines) may result in additive sedation, anticholinergic effects, or hypotensive reactions. Rasagiline may be less likely to produce these interactions than other MAOIs, due to MAO-B selectivity. However, consider alternatives therapy to antihistamines where possible. If alternative combinations are not available, these medications may be used together with close monitoring. Many non-prescription products for coughs, colds, allergy, hay fever or insomnia contain sedating antihistamines. Patients receiving rasagiline should be counseled that it is essential to consult their healthcare provider or pharmacist prior to the use of any non-prescription products. Patients should also be advised against driving or engaging in other activities requiring mental alertness until they know how this combination affects them.
Remifentanil: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Risperidone: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur.
Rituximab; Hyaluronidase: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Rivastigmine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Ropinirole: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Safinamide: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers.
Scopolamine: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and scopolamine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Secobarbital: (Moderate) Additive CNS depression may occur if barbiturates are used concomitantly with cyproheptadine.
Selegiline: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and cyproheptadine. Concurrent use may result in additive CNS depression.
Sertraline: (Moderate) Cyproheptadine is a serotonin antagonist in the CNS and can oppose the pharmacologic actions of selective serotonin reuptake inhibitors (SSRIs) such as sertraline. Cyproheptadine has been used for the management of orgasm dysfunction caused by the SSRIs and for the adjunctive treatment of SSRI overdose (i.e., serotonin syndrome) in emergency situations; however, a reversal of antidepressant effects may occur when cyproheptadine is given in a routine manner along with the SSRIs due to the serotonin antagonistic effects of cyproheptadine.
Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by concurrent medications, including H1-blockers. False study results are possible; thorough patient history is important in the interpretation of procedure results.
Sodium Iodide: (Moderate) Antihistamines may alter sodium iodide I-131 pharmacokinetics and dynamics for up to 1 week after administration. In addition, medications that decrease salivation increase the time of radiation exposure to salivary glands. Consider discontinuing sedating H1-blockers prior to sodium iodide I-131 administration.
Solifenacin: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as sedating H1 blockers.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and cyproheptadine. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Suvorexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of suvorexant and sedating antihistamines (H1-blockers). Dosage adjustments of suvorexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with suvorexant.
Tapentadol: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Tasimelteon: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Thalidomide: (Major) Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects.
Thiothixene: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur.
Tizanidine: (Moderate) Concurrent use of tizanidine and CNS depressants like sedating h1-blockers can cause additive CNS depression.
Tolcapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including sedating H1-blockers, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Tramadol: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Tramadol; Acetaminophen: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Tranylcypromine: (Contraindicated) Concomitant use of monoamine oxidase inhibitors and sedating H1-blockers is contraindicated due to increased anticholinergic effects.
Trastuzumab; Hyaluronidase: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect.
Trazodone: (Moderate) CNS depressants should be used cautiously in patients receiving trazodone because of additive CNS-depressant effects, including possible respiratory depression or hypotension.
Tricyclic antidepressants: (Moderate) Additive anticholinergic and CNS effects may be seen when tricyclic antidepressants are used concomitantly with sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Trihexyphenidyl: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and trihexyphenidyl use. Concomitant use may result in additive anticholinergic adverse effects.
Trimethobenzamide: (Moderate) The concurrent use of trimethobenzamide with other medications that cause CNS depression, like the sedating h1-blockers, may potentiate the effects of either trimethobenzamide or the sedating h1-blocker.
Trospium: (Moderate) Additive anticholinergic effects may be seen when trospium is used concomitantly with drugs that are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function and temperature regulation. While CNS-related side effects such as drowsiness and blurred vision are not typically noted with trospium, they may occur in some patients.
Venlafaxine: (Moderate) Cyproheptadine is a serotonin and histamine antagonist. Cyproheptadine may interfere with serotonin-enhancing antidepressants, including the selective serotonin reuptake inhibitors (SSRIs) and drugs with similar activity, such as venlafaxine. Cyproheptadine has been used for the management of orgasm dysfunction caused by the SSRIs and for the adjunctive treatment of SSRI or venlafaxine overdose (i.e., serotonin syndrome) in emergency situations; however, a reversal of antidepressant effects may occur when cyproheptadine is given in a routine manner along with the SSRIs due to the serotonin antagonistic effects of cyproheptadine.
Vigabatrin: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Vilazodone: (Moderate) Due to the CNS effects of vilazodone, caution should be used when vilazodone is given in combination with other centrally acting medications such as anxiolytics, sedatives, and hypnotics. Also, Cyproheptadine is an antagonist of serotonin in the CNS, a property which may oppose some of the pharmacologic effects of vilazodone. Cyproheptadine has been used for the management of orgasm dysfunction caused by the serotonergic antidepressants and for the adjunctive treatment of serotonin syndrome; however, a reversal of antidepressant effects may occur when cyproheptadine is given in a routine manner along with the antidepressant. Clinically, cyproheptadine reportedly has interfered with the antidepressant and anti-bulimia actions of fluoxetine, but more data are needed to confirm a direct drug-drug interaction.
Zaleplon: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of sedating H1-blockers and zaleplon due to the risk for additive CNS depression and next-day psychomotor impairment; dose adjustments may be necessary.
Ziconotide: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Ziprasidone: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone.
Zolpidem: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of sedating H1-blockers and zolpidem due to the risk for additive CNS depression and next-day psychomotor impairment; dose adjustments may be necessary. Limit the dose of Intermezzo sublingual tablets to 1.75 mg/day.

Cyproheptadine/Cyproheptadine Hydrochloride Oral Sol: 2mg, 5mL
Cyproheptadine/Cyproheptadine Hydrochloride/Periactin Oral Tab: 4mg

Adults

0.5 mg/kg/day PO or 32 mg/day PO, whichever is less.

Geriatric

0.5 mg/kg/day PO or 32 mg/day PO, whichever is less.

Adolescents

15 to 17 years: 0.5 mg/kg/day PO or 32 mg/day PO, whichever is less.
13 to 14 years: 16 mg/day PO.

Children

7 to 12 years: 16 mg/day PO.
2 to 6 years: 12 mg/day PO.
Less than 2 years: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Use is contraindicated.

Cyproheptadine does not prevent the release of histamine, as do cromolyn and nedocromil, but rather competes with free histamine for binding at H1-receptor sites. Cyproheptadine competitively antagonizes the effects of histamine on H1-receptors in the GI tract, uterus, large blood vessels, and bronchial smooth muscle. Blockade of H1-receptors also suppresses the formation of edema, flare, and pruritus that result from histaminic activity. H1-antagonists also possess anticholinergic properties in varying degrees. The anticholinergic activity of piperidine derivatives such as cyproheptadine is moderate.
 
Sedative effects from cyproheptadine are a result of antagonism at central histaminergic receptors, although sedation is not as pronounced as with other H1-antagonists such as diphenhydramine. Following prolonged administration, tolerance may occur, but this may be beneficial because sedative effects may be reduced. Cyproheptadine also competes with serotonin at receptor sites in smooth muscle in the intestines and other locations. Antagonism of serotonin on the appetite center of the hypothalamus may account for cyproheptadine's ability to stimulate appetite. Cyproheptadine also has been used to counter vascular headaches, which many believe are caused by changes in serotonin activity. It is unclear how cyproheptadine, a serotonin-receptor antagonist, exerts a beneficial effect on this condition, since sumatriptan, an agent specifically indicated for treating migraine, acts as an agonist at serotonin receptors.

Cyproheptadine is administered orally. Distribution of cyproheptadine has not been elucidated and it is unknown if the drug is distributed into milk. The parent compound is extensively metabolized in the liver to a number of conjugated metabolites. Plasma half-life ranges from 1—4 hours. Excretion is mainly renal, with no apparent excretion of unchanged drug. Some unchanged drug and metabolites are excreted in feces.

Oral Route

In general, H1-blockers are well absorbed from the GI tract, but they vary in solubility, which ultimately affects the onset of action. Less soluble H1-antagonists have a slower onset of action and are less likely to cause toxicity; cyproheptadine has moderate solubility. Peak concentration of cyproheptadine occurs in about 6—9 hours, and the duration of action is about 8 hours.

Pregnancy

While cyproheptadine is recommended to be used in a pregnant individual only when clearly needed, 2 studies of cyproheptadine use during human pregnancy have not shown an increased risk of fetal abnormalities when administered during the first, second and third trimesters. No teratogenic effects were observed in any of the newborns. Reproduction studies have been performed in rabbits, mice and rats at oral or subcutaneous doses up to 32 times the maximum recommended human oral dose and have revealed no evidence of impaired fertility or harm to the fetus due to cyproheptadine. Cyproheptadine has been shown to be fetotoxic in rats when given by intraperitoneal injection in doses 4 times the maximum recommended human oral dose.

Cyproheptadine is contraindicated in individuals who are breast-feeding. Per experts, unless it is being used to intentionally lower prolactin concentrations, cyproheptadine should be avoided because it may interfere with lactation. Non-sedating second-generation antihistamines, such as loratadine, are preferred alternatives when an antihistamine is needed during breast-feeding.