Debilitating side effects of commonly prescribed drugs

It's well established that most medications cause some sort of adverse effects. But, what do you do when the drugs that are meant to treat you have side effects so strong they make it almost impossible for you to go about your daily life?

Tamoxifen is a non-steroidal antiestrogen drug commonly used as adjuvant treatment for breast cancer and for the treatment of metastatic breast cancer as well as for breast cancer prevention. According to the American College of Obstetricians and Gynecologists (ACOG), the drug may be used for up to 10 years based on the data

But this drug has a dark side for some patients, according to a Committee Opinion issued by ACOG. 

“Women taking tamoxifen should be informed about the risks of endometrial proliferation, endometrial hyperplasia, endometrial cancer, and uterine sarcomas, and any abnormal vaginal bleeding, bloody vaginal discharge, staining, or spotting should be investigated,” they wrote.

“Postmenopausal women taking tamoxifen should be closely monitored for symptoms of endometrial hyperplasia or cancer. Premenopausal women treated with tamoxifen have no known increased risk of uterine cancer and require no additional monitoring beyond routine gynecologic care,” they continued.

Taking a drug meant to treat cancer only to develop another type of cancer attributable to its use makes for a tragic turn. Endometrial cancer is debilitating and deadly. Unfortunately, several other commonly prescribed, effective drugs also pose debilitating health threats, including the following five.

Venlafaxine

Ironically, venlafaxine use can exacerbate a condition it is intended to treat: depression. 

In addition to depression, this commonly prescribed antidepressant is indicated to treat social anxiety disorder and cataplexy. Off-label, it is prescribed for obsessive-compulsive disorder, post-traumatic stress disorder, fibromyalgia, attention deficit disorder, complex pain syndromes, diabetic neuropathy, hot flashes, premenstrual dysphoric disorder, and migraine prevention. One benefit is that venlafaxine is relatively fast acting, improving symptoms in as little as 1 or 2 weeks. This drug can be taken alone or in combination with other psychotropics.

Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI), which at lower dosages (ie, 75 mg/day) basically acts as a selective serotonin reuptake inhibitor (SSRI), whereas at higher dosages (ie, 225 mg/day) inhibits norepinephrine reuptake, along with serotonin reuptake. 

A black-box warning has been issued for venlafaxine. In addition to exacerbating depression, it can also cause hypomania/mania, serotonin syndrome, and suicidality. Venlafaxine can also result in blood dyscrasias and anaphylaxis, among many other serious adverse effects.

This drug is contraindicated in patients aged 18 years old or less.

Levodopa/carbidopa

“Orthostatic hypotension is a chronic, debilitating illness that is difficult to treat,” wrote the authors of a review article published in the Cleveland Clinic Journal of Medicine.

“The therapeutic goal is to improve postural symptoms, standing time, and function rather than to achieve upright normotension, which can lead to supine hypertension. Drug therapy alone is never adequate. Because orthostatic stress varies with circumstances during the day, a patient-oriented approach that emphasizes education and nonpharmacologic strategies is critical,” they added.

Even at treatment initiation, levodopa and carbidopa often cause orthostatic hypotension via the dopaminergic activation of cutaneous, mesenteric, and renal vasodilation, as well as lower central sympathetic tone, decreased renin/aldosterone release, a slight drop in heart rate, and so forth. When combined with selegiline, another antiparkinsonian agent, levodopa administration can lead to severe hypotension—even after long-term therapy.

Predictably, other drugs that cause orthostatic hypotension include antihypertensives, diuretics, alpha-adrenoceptor blockers for prostatic hypertrophy, and calcium channel blockers.

Antibiotics

Various antibiotics cause nausea, including penicillins, clindamycin, metronidazole, tetracycline, and carbapenem. Antivirals such as acyclovir can also lead to nausea. 

The pathophysiologic underpinnings of nausea are complex and include the autonomic nervous system, the central nervous system, the endocrine system, and gastric dysrhythmias, as well as psychological stressors.

Nausea and vomiting often co-occur and their financial burden in the US is in the billions. Moreover, the psychological burden is incalculable. In epidemiological studies, more than 50% of adults noted at least one episode of nausea during the past year, with more than 30% also reporting vomiting. Race has also been tied to nausea, with Asians and Asian Americans reporting higher rates than Whites and Blacks.

Metformin

Besides being a staple in many low-cost pharmaceutical formularies, metformin is highly effective at treating type 2 diabetes. But the downside is that the drug can cause debilitating gastrointestinal distress in some patients. More so than any other antidiabetic agent, metformin is a principal cause of diarrhea, nausea, and vomiting, with between 2% and 63% of those taking it experiencing these symptoms.

With metformin administration, gastrointestinal adverse effects usually abate over time. Nevertheless, 5% of those taking the drug end up discontinuing due to such complaints, which impairs adherence. Possible workarounds include taking the drug at mealtimes, dose adjustment, and use of extended-release formulations. Alternatively, patients can take a more expensive diabetes medication such as sitaliptin. 

Results from one prospective interventional study (n=75) suggested that switching patients from metformin tablets to capsules decreased the number of those experiencing gastrointestinal symptoms from 53.3% to 21.3% (P = 0.001).

Of note, it’s unclear why patients experience gastrointestinal discomfort with metformin, and it could be due to genotype, comorbidities, or the administration of other medications.

Tenofovir

This antiretroviral drug, which is commonly used to treat HIV and hepatitis B, has been linked to increased risk of kidney damage and chronic kidney disease, according to the results of a longitudinal study by San Francisco VA Medical Center (SFVAMC) and the University of California, San Francisco (UCSF) researchers, published in the journal AIDS.

The researchers followed 105 women with HIV for 7 years, and found that those exposed to the highest concentrations, or those in the highest tertile, had a significantly decreased glomerular filtrations rates compared with those in the lowest tertile of exposure. The correlation was particularly pronounced at 7 years and remained after multivariable regression for covariates including hypertension, age, race, BMI, ritonavir use, duration of tenofovir exposure, current CD4+ cell count, and HIV viral load.

More specifically, the difference in annual risk between users of the drug and non-users of the drug with an average risk for kidney disease was 13% vs. 8%, respectively, for proteinuria; 9% vs. 5%, for rapidly declining kidney function; and 2% vs. 1%, for chronic kidney disease.

The authors wrote, “The longitudinal association of higher TFV AUC with a more rapid subsequent decline in kidney function provides strong evidence that greater exposure to TFV can injure the kidney over time. These data indicate that the extent of TFV exposure may influence the occurrence of kidney injury, which may have implications for dosing and prescribing strategies.”

“We need a better understanding of the factors that determine the pharmacokinetics and pharmacodynamics of TFV and the extent to which these are modified by changes in dosing. Modification to dosing must be evaluated while also ensuring that control of HIV replication is maintained,” they continued.