17 replies to this topic

[Dtchgrl]

I have another question for you, does cymbalta affect absorption of medication?

Last year I was pretty hypothyroid, levels dropped significantly after gallbladder surgery.
To support me with this and Ibs doc started me on cymbalta, which did help me get things in place. Because I kept gaining weight, my endo prescribed thyroid meds so I’d be in the upper corner of the range. Now I’ve stopped cymbalta this constant nervous feeling and restlessness is getting worse and worse, some other hyperthyroid symptoms as well. Of course I’m having my lab work done, a month ago I was borderline high, but I’m curious to hear of cymbalta affects medication absorption. Can’t find literature on it...

Thx again

[fishinghat]

Cymbalta would compete with other medicines for access to serotonin and noradrenaline synapses but that would primarily be other antidepressants. Cymbalta is absorbed by both the CYP1A2 and CYP2D6 enzymes in the stomach and as such woulkd compete with any other medicines that are absorbed this way. Drugs like cimetidine (Tagamet) and quinolone antimicrobials such as ciprofloxacin and enoxacin block this enzyme mechanism and would stand in the way of Cymbalta absorption.

 

I would also refer you to this from the ELi Lilley drug insert for Cymbalta.

7.1 Inhibitors of CYP1A2
When duloxetine 60 mg was co-administered with fluvoxamine 100 mg, a potent CYP1A2 inhibitor, to male subjects (n=14) duloxetine AUC was increased approximately 6-fold, the Cmax was increased about 2.5-fold, and duloxetine t1/2 was increased approximately 3-fold. Other drugs that inhibit CYP1A2 metabolism include cimetidine and quinolone antimicrobials such as ciprofloxacin and enoxacin [see Warnings and Precautions (5.12)].

7.2 Inhibitors of CYP2D6
Concomitant use of duloxetine (40 mg once daily) with paroxetine (20 mg once daily) increased the concentration of duloxetine AUC by about 60%, and greater degrees of inhibition are expected with higher doses of paroxetine. Similar effects would be expected with other potent CYP2D6 inhibitors (e.g., fluoxetine, quinidine) [see Warnings and Precautions (5.12)].

7.3 Dual Inhibition of CYP1A2 and CYP2D6
Concomitant administration of duloxetine 40 mg twice daily with fluvoxamine 100 mg, a potent CYP1A2 inhibitor, to CYP2D6 poor metabolizer subjects (n=14) resulted in a 6-fold increase in duloxetine AUC and Cmax.

7.4 Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin, and Warfarin)
Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs or SNRIs are co-administered with warfarin. Concomitant administration of warfarin (2-9 mg once daily) under steady state conditions with duloxetine 60 or 120 mg once daily for up to 14 days in healthy subjects (n=15) did not significantly change INR from baseline (mean INR changes ranged from 0.05 to +0.07). The total warfarin (protein bound plus free drug) pharmacokinetics (AUCτ,ss, Cmax,ss or tmax,ss) for both R- and S-warfarin were not altered by duloxetine. Because of the potential effect of duloxetine on platelets, patients receiving warfarin therapy should be carefully monitored when duloxetine is initiated or discontinued [see Warnings and Precautions (5.5)].

7.5 Lorazepam
Under steady-state conditions for duloxetine (60 mg Q 12 hours) and lorazepam (2 mg Q 12 hours), the pharmacokinetics of duloxetine were not affected by co-administration.

7.6 Temazepam
Under steady-state conditions for duloxetine (20 mg qhs) and temazepam (30 mg qhs), the pharmacokinetics of duloxetine were not affected by co-administration.

7.7 Drugs that Affect Gastric Acidity
CYMBALTA has an enteric coating that resists dissolution until reaching a segment of the gastrointestinal tract where the pH exceeds 5.5. In extremely acidic conditions, CYMBALTA, unprotected by the enteric coating, may undergo hydrolysis to form naphthol. Caution is advised in using CYMBALTA in patients with conditions that may slow gastric emptying (e.g., some diabetics). Drugs that raise the gastrointestinal pH may lead to an earlier release of duloxetine. However, co-administration of CYMBALTA with aluminum- and magnesium-containing antacids (51 mEq) or CYMBALTA with famotidine, had no significant effect on the rate or extent of duloxetine absorption after administration of a 40 mg oral dose. It is unknown whether the concomitant administration of proton pump inhibitors affects duloxetine absorption [see Warnings and Precautions (5.14)].

7.8 Drugs Metabolized by CYP1A2
In vitro drug interaction studies demonstrate that duloxetine does not induce CYP1A2 activity. Therefore, an increase in the metabolism of CYP1A2 substrates (e.g., theophylline, caffeine) resulting from induction is not anticipated, although clinical studies of induction have not been performed. Duloxetine is an inhibitor of the CYP1A2 isoform in in vitro studies, and in two clinical studies the average (90% confidence interval) increase in theophylline AUC was 7% (1%-15%) and 20% (13%-27%) when co-administered with duloxetine (60 mg twice daily).

7.9 Drugs Metabolized by CYP2D6
Duloxetine is a moderate inhibitor of CYP2D6. When duloxetine was administered (at a dose of 60 mg twice daily) in conjunction with a single 50 mg dose of desipramine, a CYP2D6 substrate, the AUC of desipramine increased 3-fold [see Warnings and Precautions (5.12)].

7.10 Drugs Metabolized by CYP2C9
Results of in vitro studies demonstrate that duloxetine does not inhibit activity. In a clinical study, the pharmacokinetics of S-warfarin, a CYP2C9 substrate, were not significantly affected by duloxetine [see Drug Interactions (7.4)].

7.11 Drugs Metabolized by CYP3A
Results of in vitro studies demonstrate that duloxetine does not inhibit or induce CYP3A activity. Therefore, an increase or decrease in the metabolism of CYP3A substrates (e.g., oral contraceptives and other steroidal agents) resulting from induction or inhibition is not anticipated, although clinical studies have not been performed.

7.12 Drugs Metabolized by CYP2C19
Results of in vitro studies demonstrate that duloxetine does not inhibit CYP2C19 activity at therapeutic concentrations. Inhibition of the metabolism of CYP2C19 substrates is therefore not anticipated, although clinical studies have not been performed.

7.13 Monoamine Oxidase Inhibitors (MAOIs)
[See Dosage and Administration (2.8, 2.9), Contraindications (4), and Warnings and Precautions (5.4)].

7.14 Serotonergic Drugs
[See Dosage and Administration (2.8, 2.9), Contraindications (4), and Warnings and Precautions (5.4)].

7.15 Alcohol
When CYMBALTA and ethanol were administered several hours apart so that peak concentrations of each would coincide, CYMBALTA did not increase the impairment of mental and motor skills caused by alcohol.
In the CYMBALTA clinical trials database, three CYMBALTA-treated patients had liver injury as manifested by ALT and total bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, and this may have contributed to the abnormalities seen [see Warnings and Precautions (5.2, 5.12)].

7.16 CNS Drugs
[See Warnings and Precautions (5.12)].

7.17 Drugs Highly Bound to Plasma Protein
Because duloxetine is highly bound to plasma protein, administration of CYMBALTA to a patient taking another drug that is highly protein bound may cause increased free concentrations of the other drug, potentially resulting in adverse reactions. However, co-administration of duloxetine (60 or 120 mg) with warfarin (2-9 mg), a highly protein-bound drug, did not result in significant changes in INR and in the pharmacokinetics of either total S-or total R-warfarin (protein bound plus free drug) [see Drug Interactions (7.4)].

[fishinghat]

Sorry about the typos. I only type with 2 fingers and sometimes they get very confused.  lol

[fishinghat]

I also found this...

https://www.ncbi.nlm...pubmed/21366359
Clin Pharmacokinet. 2011 May;50(5):281-94. doi: 10.2165/11539240-000000000-00000.
Duloxetine: clinical pharmacokinetics and drug interactions.
Knadler MP1, Lobo E, Chappell J, Bergstrom R.

Abstract
Duloxetine, a potent reuptake inhibitor of serotonin (5-HT) and norepinephrine, is effective for the treatment of major depressive disorder, diabetic neuropathic pain, stress urinary incontinence, generalized anxiety disorder and fibromyalgia. Duloxetine achieves a maximum plasma concentration (C(max)) of approximately 47 ng/mL (40 mg twice-daily dosing) to 110 ng/mL (80 mg twice-daily dosing) approximately 6 hours after dosing. The elimination half-life of duloxetine is approximately 10-12 hours and the volume of distribution is approximately 1640 L. The goal of this paper is to provide a review of the literature on intrinsic and extrinsic factors that may impact the pharmacokinetics of duloxetine with a focus on concomitant medications and their clinical implications. Patient demographic characteristics found to influence the pharmacokinetics of duloxetine include sex, smoking status, age, ethnicity, cytochrome P450 (CYP) 2D6 genotype, hepatic function and renal function. Of these, only impaired hepatic function or severely impaired renal function warrant specific warnings or dose recommendations. Pharmacokinetic results from drug interaction studies show that activated charcoal decreases duloxetine exposure, and that CYP1A2 inhibition increases duloxetine exposure to a clinically significant degree. Specifically, following oral administration in the presence of fluvoxamine, the area under the plasma concentration-time curve and C(max) of duloxetine significantly increased by 460% (90% CI 359, 584) and 141% (90% CI 93, 200), respectively. In addition, smoking is associated with a 30% decrease in duloxetine concentration. The exposure of duloxetine with CYP2D6 inhibitors or in CYP2D6 poor metabolizers is increased to a lesser extent than that observed with CYP1A2 inhibition and does not require a dose adjustment. In addition, duloxetine increases the exposure of drugs that are metabolized by CYP2D6, but not CYP1A2. Pharmacodynamic study results indicate that duloxetine may enhance the effects of benzodiazepines, but not alcohol or warfarin. An increase in gastric pH produced by histamine H(2)-receptor antagonists or antacids did not impact the absorption of duloxetine. While duloxetine is generally well tolerated, it is important to be knowledgeable about the potential for pharmacokinetic interactions between duloxetine and drugs that inhibit CYP1A2 or drugs that are metabolized by CYP2D6 enzymes.

[Dtchgrl]

I’ll definitely look up if thyroid medication is anyway related to those enzymes. It can’t be a coincidence that my levels have gone up since tapering off cymbalta
Thx again :-)

[Dtchgrl]

https://hypothyroidm...y-are-you-sure/ “Antidepressants: Many selective serotonin reuptake inhibitors (SSRI) like Prozac, Zoloft, and Paxil decrease the effectiveness of thyroid medication” wish she had a resource. She has very good info on the thyroid though

[Dtchgrl]

Ah she’s has some articles at the bottom, now to find the right article

[fishinghat]

Post the links if you would and I will add them to my library. I would appreciate it.

[Dtchgrl]

Scanned through the articles and couldn’t find ad’s specifically yet.
Here’s one article https://www.ncbi.nlm...les/PMC1070767/

[Dtchgrl]

The other articles refe to coffee impairing absorption etc. but I assume you’d be more interested in the relation between ad’s and medication absorption....

I’ve only found non scientific sources and careful with those. I can let you know how my thyroid results turn out. I’m pretty sure they have changed since stopping cymbalta

[fishinghat]

This is from my library. You may find it interesting.

 

DG - It is only logical that if antidepressants lower thyroid enzymes then coming of that antidepressant will raise them.

reboxetine - TSH reduced and T4 increased.
sertraline - TSH increased and T4 reduced.
https://www.ncbi.nlm.../?term=18262705

sertraline and fluoxetine showed reductions in TSH,T3 and T4 levels.
https://www.ncbi.nlm.../?term=15486607

Fluoxetine decreased T3 and T4, increased TSH
https://www.ncbi.nlm...d/?term=6413229

ssri/snri replacement is a viable option.

Do not treat with thyroid hormones if hypothyroidism present while on an antidepressant unless hypothyroid symptoms are present.

These are often accompanied by findings such as low blood pressure, low blood glucose, low sodium, high potassium, and high calcium.

https://www.ncbi.nlm...pubmed/22450350
Escitalopram-induced subclinical hypothyroidism. A case report.

https://www.ncbi.nlm...pubmed/20851281
Reversible escitalopram-induced hypothyroidism.

https://www.ncbi.nlm...pubmed/17874352
Reversible paroxetine-induced symptomatic hypothyroidism.

https://www.ncbi.nlm...pubmed/11054982
Depressed patients should be screened for hypothyroidism. In hypothyroid patients, depression may be more responsive to a replacement regimen that includes T3 rather than T4 alone. Therefore, inclusion of T3 in the treatment regimen may be warranted after adequate trial with T4 alone.

https://www.ncbi.nlm.../pubmed/7779834
Effects of long term treatment with sertraline (Zoloft) simulating hypothyroidism in an adolescent.


https://www.drugs.com/pro/effexor.html
Side effects
"Endocrine system—Rare: goiter, hyperthyroidism, hypothyroidism, thyroid nodule, thyroiditis."

https://dailymed.nlm...54-00144ff88e88
The same is mentioned in the section on 'adverse reactions' in the drug insert for Effexor.


http://www.ehealthme...hypothyroidism/
65,121 people reported to have side effects when taking Effexor.
Among them, 420 people (0.64%) have Hypothyroidism

http://www.ehealthme...hypothyroidism/
An FDA supported website.
84,701 people reported to have side effects when taking Cymbalta.
Among them, 292 people (0.34%) have Hypothyroidism

https://dailymed.nlm...f2-c185fbad64ba
Drug insert. (Cymbalta)
Endocrine Disorders — Infrequent: hypothyroidism.

 

 

[Dtchgrl]

Oh awesome! I thought I was scientifica article savvy, but you are amazing

[Dtchgrl]

And t3 replacement definitely helped me get rid of depressive symptoms. Now it’s just anxiety...

[Dtchgrl]

Scanning through the articles, my assumption is, that in my case, it as to do with the pituitary, since I don’t have a thyroid anymore.

[fishinghat]

If your thyroid hormones are now normal it would be logical to think pituitary. Did you have a TSH done with your t3 and t4 test?

[fishinghat]

By the way don't feel bad. I have been doing this kind of work for over 30 years.


file:///C:/Users/Neil/AppData/Local/Microsoft/Windows/INetCache/IE/K78IEYPO/hh-article-January-2016%20(1).pdf
http://www.hanstenan...anuary-2016.htm
The first link talks about what drugs interfer with levothyroxine and the second link is their references.


file:///C:/Users/Neil/AppData/Local/Microsoft/Windows/INetCache/IE/LWZGUZ3K/Pharmacogenomic_Associations_Tables.pdf
Levothyroxine not metabolized by either CYP1A2 or CYP2D6 enzymes.

I found no information on Liothyronine absorption.

[Dtchgrl]

They always test tsh but because I’m taking armour, which has t3, it interferes with the tsh levels.

And I don’t think it’s as direct as same enzymes but pretty much every change seems to influence thyroid/ endocrine balances...

[fishinghat]

I agree.